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  • 1
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Posttransplant lymphoproliferative disease ; Epstein-Barr virus ; Humans ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epstein-Barr virus (EBV) infection can induce uncontrolled lymphocyte B proliferation in immunosuppressed transplant patients. Monitoring circulating EBV-infected lymphocytes can help in identifying patients at risk of posttransplant lymphoproliferative disease (PTLD). Circulating EBV genome levels were determined in 54 liver transplant pediatric recipients. Ten patients had more than 500 EBV genome/105 peripheral blood lymphocytes (PBL) and exhibited clinical manifestations of EBV infection; three developed PTLD. To treat EBV infection, the level of immunosuppression was reduced and acute rejection developed in 4 patients. Three were treated with steroid and one had to be switched from cyclosporine to tacrolimus. Treatment of acute rejection was associated with increases in circulating EBV genome. None of the patients with less than 500 EBV genome/105 PBL developed PTLD or EBV infection. Monitoring of EBV DNA is useful in the management of EBV infection and PTLD following pediatric liver transplantation. EBV infection should be treated in ways which do not expose patients to the risk of rejection.
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  • 2
    ISSN: 1432-2161
    Keywords: Key words Bone mineral density ; Dual energy X-ray absorptiometry ; Children ; Rickets ; X-linked hypophosphatemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Objective. To evaluate the bone mineral status of children being treated for X-linked hypophosphatemia, including potential differences between cortical bone in the radial diaphysis and combined cortical and trabecular bone in the lumbar spine. Design and patients. Forty-four bone mineral evaluations were performed in 11 children and adolescents with X-linked hypophosphatemia. Bone mineral density (BMD) of the lumbar spine and the radial diaphysis were measured by dual X-ray absorptiometry (DXA), second metacarpal cortical thickness was measured on hand radiographs, and these results were expressed as Z-scores (standard deviations from the mean). Results. For the 11 initial examinations, Z-scores (mean±SD) were: radial BMD, –2.73±1.15, lumbar BMD, +1.28±1.53; and cortical thickness, –2.21±0.95. Lumbar BMD Z-scores were significantly greater than those for radial BMD and cortical thickness. On follow-up examinations there was a mild increase in radial BMD and decrease in lumbar BMD. Although these changes were statistically significant, they were quite small and the discordance between radial and lumbar BMD was not corrected. Conclusions. Children and adolescents who are being treated for X-linked hypophosphatemia manifest a bone mineral disorder characterized by decreased BMD in the appendicular skeleton and increased BMD in the lumbar spine. Although current therapy is successful in its anti-rachitic effects, it does not correct this bone mineral disorder and additional therapeutic trials should be considered.
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  • 3
    ISSN: 1432-2129
    Keywords: Schlüsselwörter ; Kopfschmerz ; Kinder ; Akuttherapie ; Flupirtin ; Paracetamol ; Keywords ; Children ; Acute treatment ; Tension-type headache ; Flupirtine ; Paracetamol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: About 10% of all schoolchil- dren are suffering from migraine and 50% from tension-type headache. Headache of acute onset usually will be treated with analgesic substances like paracetamol, acetylsalicylic acid or ibuprofen, the first one being the reference drug for tension-type headache in childhood. In case of lacking improvement or side-effects there is demand for an alternative safe substance for the acute analgesic therapy. Methods: In a double-blind randomised investigation flupirtine and paracetamol were given in two consecutive attacks of episodic tension-type headache. 30 children, 6–12 years old, were included. Dosage was determined according to age and weight. The children documented the acute headache intensity and duration in a special diary. Results: Headache intensity was reduced during 2 h after intake in 89% of the 19 children treated. The reduction was 6,5 to 3,1 for flupirtine and 6,9 to 3,3/10 for paracetamol. There was no statistically significant difference between the two substances. Relevant side-effects could not be observed. Conclusion: Flupirtine has shown a convincing clinical effect treating acute episodic tension-type headache for children. The substance was well tolerated by the patients. In addition, flupirtine provides a high degree of safety.
    Notes: Zusammenfassung Hintergrund: Etwa 10% aller Schulkinder leiden nach neueren deutschen epidemiologischen Untersuchungen zumindest gelegentlich an Migräne und etwa 50% an Kopfschmerzen vom Spannungstyp. Häufig nehmen sie bei Spannungskopfschmerzen analgetische Monosubstanzen wie Paracetamol, Azetylsalizylsäure oder Ibuprofen ein. Bei nicht ausreichender Wirkung bzw. Unverträglichkeit besteht Bedarf nach weiteren Substanzen für die Akutanwendung. Methode: In einer doppelblindrandomisierten und gekreuzten Anordnung wurden Paracetamol bzw. das analgetisch und muskelrelaxierend wirksame Flupirtin 30 6- bis 12jährigen Kindern für 2 episodische Spannungskopfschmerzattacken angeboten. 10 Kinder benötigten nach dem Erstkontakt keine Medikation mehr, 1 Kind lehnte die Einnahme grundsätzlich ab. Ergebnisse: Die Kopfschmerzstärke verringerte sich laut Kopfschmerztagebuch innerhalb von 2 h nach der Einnahme auf einer numerischen Schmerzskala (0–10) von 6,5 auf 3,1 unter Flupirtin und von 6,9 auf 3,3 unter Paracetamol bei 89% der verbliebenen 19 Kinder. Statistisch signifikante Unterschiede zwischen beiden Substanzen bestanden nicht. Als Nebenwirkung trat 1-mal Erbrechen unter Paracetamol auf. Schlussfolgerung: Flupirtin hat sich in der Akutphase von episodischen Spannungskopfschmerzen beim Kind bewährt. Es verfügt über eine gute Verträglichkeit. Im Vergleich zu Paracetamol scheint v.a. bei akzidenteller Überdosierung eine größere Sicherheit zu bestehen.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 14 (2000), S. 302-308 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Schmerzmessung ; Diagnostik ; Instrumente ; Neugeborene ; Kinder ; Keywords Pain ; Measurement ; Assessment ; Instruments ; Neonates ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background. The assessment and measurement of pain is essential in the implementation and control of pain relieving strategies. The measurement of pain in infants and children should be based on the consideration of age, cognitive level, psychological status, intercurrent diseases and the social context in order to register the child's individual situation and to avoid misinterpretation. Diagnosis. In the preverbal infant, behavioral and physiological cues have to be interpreted by the caregivers. For the assessment of pain in children of four and older who have at least a basic understanding of the pain concept self assessment methods (as rating scales, specific pain interviews, diaries and questionnaires) can be used. In any case the instruments used should be age appropriate. The instruments used for the different age groups are presented with comments on quality and clinical applicability.
    Notes: Zusammenfassung Hintergrund. Voraussetzung zur Durchführung und Kontrolle einer adäquaten und effektiven Schmerztherapie sind die Erfassung und Quantifizierung des Schmerzes in seinen verschiedenen Dimensionen. Bei der Diagnostik des Schmerzes im Kindesalter müssen Alter, kognitiver Entwicklungsstand, psychologischer Status, interkurrierende Erkrankungen und der soziale Kontext berücksichtigt werden, um das Kind in seiner individuellen Situation erfassen zu können und Fehleinschätzungen zu vermeiden. Schmerzdiagnostik im Kindesalter. Im präverbalen Alter werden die physiologischen und verhaltensbezogenen Schmerzäußerungen von Neugeborenen, Säuglingen und Kleinkindern durch eine Fremdbeurteilung erfasst. Bei Kindern ab etwa 4 Jahren, die über ein einfaches Verständnis von Schmerz verfügen, sind Verfahren der Selbsteinschätzung wie einfache Ratingskalen, spezifische Schmerzinterviews, Tagebücher und Fragebögen die primär einzusetzenden Instrumente. In jedem Fall sollten die Instrumente altersgerecht gestaltet sein. Für die verschiedenen Altersgruppen werden Instrumente der Schmerzerfassung mit qualitativen Hinweisen auf deren Güte und klinische Anwendbarkeit vorgestellt.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 14 (2000), S. 319-323 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Schmerz ; Kinder ; Impfung ; Verbrennung ; Injektion ; Keywords Pain ; Children ; Vaccination ; Burn ; Injection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Phenomenon pain. While pain is one of the main reasons for an unscheduled visit to the paediatrician, pain due to painful procedures is of major importance in scheduled visits. Actual pain therapy is illustrated in the treatment of burns. Incomplete analgesia may have an unfavourable impact on morbidity and mortality. The pain score does not correlate with the extent of the burned area, and is regularly underestimated. General anaesthesia or analgo-sedation are warranted during the care of the burned patient. Unsufficient analgesia. Consequence of insufficient analgesia during primary care is an increased need of analgesics, and an increased pain treatment failure rate during subsequent procedures. Pain is interfering with anxiety, sleep disturbancies and post-tramatic psychologic alterations. All those symptoms must be treated adequately. Acute illness and injections. This article covers pain from otitis media, pharyngitis, Guillain-Barré syndrome, purpura fulminans, Toxic Epidermal Nekrolysis, as well as the usage of local anaesthesia during injections, not to forget the application of non-pharmacologic methods for pain therapy and prophylaxis.
    Notes: Zusammenfassung Phänomen Schmerz. Das Phänomen “Schmerz” begleitet fast alltäglich den Kontakt zwischen Arzt und krankem Kind. Auf der einen Seite sind Schmerzen der häufigste Grund für eine ungeplante Kinderarztkonsultation, auf der anderen Seite sind bei geplanten Kinderarztbesuchen häufig schmerzhafte Prozeduren durchzuführen. Anhand der starken Schmerzen bei den im Kleinkindalter häufigen Verbrennungen werden schmerztherapeutische Prinzipien konkretisiert: Schmerztherapeutische Prinzipien. Unzureichende Analgesie kann Morbidität und Mortalität ungünstig beeinflussen. Das Schmerzmaß korreliert nicht mit der Ausdehnung der Verbrennung und wird vom Behandler regelmäßig unterschätzt. In vielen Fällen der Erstversorgung sind Allgemeinanästhesie oder Analgosedierung gerechtfertigt, ähnliches gilt für den Verbandwechsel. Ungenügende Analgesie bei der Erstversorgung führt zu erhöhtem Analgetikaverbrauch und schmerztherapeutischen Misserfolgen bei Folgeeingriffen. Wechselwirkungen zwischen Schmerzen und anderen Symptomen wie Angst, Schlafstörungen oder postraumatischen psychischen Veränderungen sind zu beachten und adäquat zu therapieren. Akute Erkrankungen + Injektionen. Weiter wird auf Schmerzen bei Otitis media, Pharyngitis, Guillain-Barré-Syndrom, Purpura Fulminans und Toxischer Epidermaler Nekrolyse sowie den Einsatz von Lokalanästhetika bei Injektionen eingegangen. Schließlich haben auch nicht pharmakologische Methoden ihren Platz in Schmerztherapie und Prophylaxe.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Schmerz 14 (2000), S. 333-339 
    ISSN: 1432-2129
    Keywords: Schlüsselwörter Postoperative Schmerztherapie ; Schmerz ; Kinder ; Jugendliche ; Analgetika ; Keywords Postoperative pain therapy ; Pain ; Children ; Adolescents ; Analgesics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Treatment of pain. Undertreatment of postoperative pain in children is a problem in clinical practice. This is due to a lack of both knowledge about age-specific aspects of physiology and pharmacology, and routine pain assessment. For example, the fear of side-effects prevents the adequate usage of opioids. It is of major importance to select a route of drug administration where the child feels comfortable with (avoid intramuscular injections). Non-opioid analgesics. Non-opioid analgesics are recommended for basic pain treatment after minor surgical procedures. Instead of using the whole multitude of drugs available, the doctor should stick to those drugs he is familiar with (acetaminophen, ibuprofen, diclofenac, dipyrone). Opioids. Opioid usage requires individual dose titration and careful monitoring of side-effects (respiratory monitoring, sedation score). The strong opioids piritramide and morphine may advantageously be administered as either continuous, or patient-controlled iv- infusion (PCA). Forms of therapy. In addition to infiltration anesthesia, intraoperatively applied nerve blocks provide excellent pain relief. Epidural analgesia with local anesthetics and/or opioids via a thoracic or lumbar epidural catheter is a therapeutic option after thoracic or abdominal surgery, or after extensive orthopedic or urological interventions. Adjuvant analgesics and nonpharmacologic interventions, i. e. transcutaneous electrical nerve stimulation (TENS), are primarily indicated in patients suffering from neuropathic pain. Conclusion. The establishment of pain services and the comprehensive education of both the nursing and the medical staff should help to improve postoperative pediatric pain therapy.
    Notes: Zusammenfassung Schmerztherapie bei Kindern. Postoperative Schmerzen bei Kindern werden häufig wegen mangelnder physiologischer und pharmakologischer Kenntnisse und des Fehlens einer regelmäßigen standardisierten Schmerzmessung noch immer unzureichend behandelt. Die Angst vor Nebenwirkungen verhindert eine adäquate Opioidtherapie. Bei der Verwendung von Analgetika ist auf eine kindgerechte Applikationsweise (keine i.-m.-Injektionen!) zu achten. Nichtopioidhaltige Analgetika. Nichtopioidhaltige Analgetika (Parazetamol, Ibuprofen, Diclofenac, Metamizol) sind zur Basisschmerztherapie bei kleineren schmerzhaften Eingriffen geeignet. Opioide. Opioide müssen nach Wirkung titriert werden; Nebenwirkungen können nur bei sorgfältigem Monitoring von Atmung und Sedierungsgrad frühzeitig erkannt werden. Opioide (Tramadol, Piritramid, Morphin) können entweder kontinuierlich i. v. oder mittels PCA-Pumpe verabreicht werden. Therapieformen. Neben der Oberflächenanästhesie sind intraoperativ angelegte Nervenblockaden effektive therapeutische Möglichkeiten. Eine lumbale und thorakale Periduralanästhesie mittels Lokalanästhetika und/oder Opioiden bietet sich bei thorakoabdominalen Eingriffen an. Koanalgetika werden vornehmlich bei Nervenschmerzen verwendet und richten sich gegen die schmerzverursachende Pathophysiologie. Optimierung der Schmerztherapie. Die postoperative Schmerztherapie bei Kindern kann durch Einrichtung eines Akutschmerzdiensts und kontinuierliche Weiterbildung von Pflegepersonal und Ärzten optimiert werden.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 14 (2000), S. 1016-1021 
    ISSN: 1432-198X
    Keywords: Key words Nephrocalcinosis ; Sonography ; Renal function ; Body growth ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We carried out a retrospective survey on 152 children and adolescents with nephrocalcinosis (NC) in 22 German centers of pediatric nephrology. Etiology, clinical manifestations, growth and development, sonographic appearance of NC and renal function were analyzed. The median age at the time of diagnosis was 3.3 (range 0.1–21) years and the median duration of follow-up was 4.1 years. In 34% of children NC was associated with idiopathic hypercalciuria (IHC) and in 32% with various hereditary tubular disorders. In 9% NC was observed subsequent to prophylactic bolus administration of vitamin D in infancy. A positive family history was found in 36%. Clinical manifestations were mainly failure to thrive during the 1st year of life (46%), psychomotor/mental retardation (28%) and urinary tract infection (34%). In 14% nephrolithiasis was associated. During the follow-up the proportion of patients with the most severe degree of NC (stages 2b or 3) increased from 40% to 55% and that of hypercalciuria decreased from 79% to 52%. Body height was 〈2 standard deviation scores (SDS) of normal in 41% at the time of diagnosis and in 32% at the last observation; the increase in relative height was significant only for IHC. Glomerular filtration rate (GFR) and urinary concentration capacity changed only slightly with time. At the last investigation GFR was 〈50 ml/min/1.73 m2 in 6% and concentration capacity 〈800 mosmol/kg in 48% of patients. The degree of NC was negatively correlated with GFR and concentration capacity.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 15 (2000), S. 302-316 
    ISSN: 1432-198X
    Keywords: Key words Calcium channel blockers ; Children ; Pharmacokinetics ; Hypertension
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The calcium channel blockers (CCBs) are a diverse group of antihypertensive medications with variable pharmacokinetics and clinical effects. Although CCBs have been widely applied to the treatment of hypertensive children, data regarding the pharmacokinetics, efficacy and safety of these agents in children are extremely limited. In this review we briefly summarize the mechanism of action of CCBs and then summarize pertinent pharmacokinetic information on each of the CCBs commonly used in children, including amlodipine, diltiazem, felodipine, isradipine, intravenous nicardipine, nifedipine and verapamil. Clinically important drug interactions and adverse effects are discussed, as well as the potential role of CCBs in renal protection. Available pediatric efficacy and safety data are summarized, and recommendations made regarding the rational use of CCBs in the management of pediatric hypertension.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 15 (2000), S. 57-59 
    ISSN: 1432-198X
    Keywords: Keywords X-linked hypophosphatemia ; Dipyridamole ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  X-linked hypophosphatemia (XLH) is characterized clinically by rickets, hypophosphatemia and hyperphosphaturia. Conventional treatment of XLH with oral phosphate and vitamin D is associated with hypercalcuria and nephrocalcinosis. Recently, intravenous and oral dipyridamole has been reported to decrease fractional excretion of phosphate in adults with idiopathic hyperphosphaturia. Our objective was to determine whether oral dipyridamole therapy reduces urinary phosphate excretion and increases serum phosphate concentration in children with XLH. A prospective study was performed in six children with XLH. The average age of the patients at the start of the study was 12.5±1.0 years. The effects of 12 weeks of oral dipyridamole therapy, at 4.4±0.4 mg/kg body weight per day, on serum phosphorous, parathyroid hormone (PTH), 1,25 (OH)2 vitamin D, osteocalcin, tubular maximum for phosphate reabsorption (TmP/GFR), urinary calcium excretion, and cyclic adenosine 3’,5’-monophosphate (cAMP) excretion, were compared to baseline levels. Our results show that there was no change in serum phosphorous concentration or TmP/GFR after 12 weeks of dipyridamole therapy. Dipyridamole therapy also had no effect on serum PTH, serum 1,25 (OH)2 vitamin D, alkaline phosphatase, osteocalcin levels, urinary calcium or cAMP excretion. We therefore concluded that in children with XLH, a 12-week course of dipyridamole had no effect on serum phosphorous or its urinary excretion. Dipyridamole therapy is unlikely to improve the bone disease in children with XLH.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric nephrology 15 (2000), S. 248-251 
    ISSN: 1432-198X
    Keywords: Key words Nephrotic syndrome ; Acute renal failure ; Children ; Peritonitis ; Ischemic tubular necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Idiopathic acute renal failure (IARF) is an uncommon but severe complication in children with relapsing nephrotic syndrome and may require long-term dialytic support until recovery of renal function takes place. Due to limited understanding of the pathophysiology of IARF, specific guidelines for its prevention and therapy have not been developed. Among triggering factors, peritonitis was present in half of all pediatric patients with this complication described in the English literature over the past 15 years. We report an additional nephrotic child who developed IARF following spontaneous bacterial peritonitis. The renal biopsy showed tubular epithelial changes consistent with acute tubular necrosis. A discussion of related literature and possible pathogenesis of this association is presented.
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  • 11
    ISSN: 1433-0350
    Keywords: Key words Child abuse ; Shaken baby syndrome ; Brain injury ; Infants ; Children ; Neuroimaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Acute CT/MRI findings were examined in a prospective, longitudinal study of 60 children 0–6 years of age hospitalized for moderate to severe traumatic brain injury (TBI). TBI was categorized as either inflicted (n=31) or noninflicted (n=29). Glasgow Coma Scale scores and perinatal history were comparable in both groups. Acute CT/MRI studies were visually inspected by a radiologist blind to group membership. Compared with the noninflicted TBI group, the inflicted TBI group had significantly elevated rates of subdural interhemispheric and convexity hemorrhages as well as signs of pre-existing brain abnormality, including cerebral atrophy, subdural hygroma, and ex vacuo ventriculomegaly. Intraparenchymal hemorrhage, shear injury, and skull fractures were more frequent after noninflicted TBI. Subarachnoid hemorrhage and infarct/edema occurred with comparable frequency in both groups. Characteristic acute neuroimaging findings of inflicted TBI included multiple extraaxial hemorrhages in addition to the mild atrophy, subdural hygromas, and ventriculomegaly that suggest prior brain abnormality.
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  • 12
    ISSN: 1433-0350
    Keywords: Key words Brain death ; Children ; Electroencephalogram ; Etiology ; Evoked potentials ; Radioisotopic angiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The objective of this study was to determine the main clinical, neurophysiological and angiographic findings in brain death (BD) in children seen at the Instituto Nacional de Pediatría, a third-level facility in Mexico City, between 1991 and 1996. The following variables were retrospectively analyzed: sex, age, etiology, associated morbidity, duration of stay in hospital, and the results of two of three confirmatory studies (electroencephalogram, evoked potentials, radioisotopic angiography). In all, 125 patients were studied [78 male; median age 2 years (range: 18 days to 17 years)]. The most frequent etiology was infection (34%); 57% of the children developed associated morbidity. In 111 of 122 patients electrocerebral silence was observed; 100 of 107 had brain stem and somatosensory evoked potentials affording conclusive evidence of BD; and 83 of 90 patients had a positive radioisotopic angiography indicating BD. In 76 patients all three confirmatory studies were performed: for 15 there was at least one false-negative test result. Our age cohort showed a predominance of children less than 2 years old. BD etiologies in developing countries differ from those reported in developed countries.
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Child's nervous system 16 (2000), S. 755-759 
    ISSN: 1433-0350
    Keywords: Keywords Head trauma ; Children ; CT scan ; MRI scan ; Follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  CT scanning is the current first imaging technique to be used after head injury, in those settings where a CT scan is available. The first scan is usually done without contrast enhancement. The value of CT is the demonstration of scalp, bone, extra-axial hematomas and parenchymal injury. It is rapid and easily done in the presence of the multiple monitors that many trauma patients have in place. It can be used to demonstrate the bony anatomy of the spine and is good for evaluation of abdominal and chest trauma also. MRI is more sensitive for all post-traumatic lesions other than skull fracture and subarachnoid hemorrhage, and can demonstrate parenchymal spinal cord injury. The cons are a longer scanning time, interference of the imaging by certain ICP monitors and problems with the positions of the monitoring equipment and ventilators outside the MRI magnetic field. MRI will be used increasingly to study early head injury because of its ability to measure cerebral blood flow, cerebral blood volume and the location and extent of cerebral edema. If the CT does not demonstrate pathology adequate to account for the clinical state, MRI is warranted. Follow up is best done with MRI as it is more sensitive to parenchymal change than is CT.
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  • 14
    ISSN: 1433-044X
    Keywords: Schlüsselwörter Thoraxtrauma ; Atelektasen ; Pädiatrie ; Bauchlage ; Keywords Thoracic trauma ; Atelectasis ; Children ; Prone position
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract We report on the ventilation in prone position in a 5-year-old traumatized child with severe thoracic and abdominal injuries (lung contusion, rib fractures, rupture of liver and spleen). Under continuous analgosedation, the young patient was ventilated in prone position for 6 h, since acute lung injury and atelectasis persisted despite various therapeutic measures (artifical ventilation in the pressure controlled mode, fiberoptic bronchoscopy, reexpansion maneuver). After initiation of the prone position, we observed a rapid increase i narterial oxygenation, which persisted in the following period. The hemodynamic situation remained stable. The complete disappearance of atelectasis was demonstrated radiologically after supine repositioning. After cessation of analgosedation, the extubation was performed 2 days later. Furthermore, we found no side effects of the prone position on the injured abdomen, and the liver function improved rapidly. Although there is a lack of experience with ventilation in prone position in pediatric intensive care, our report might be a recommendation for the indication of this technique in children.
    Notes: Zusammenfassung In dieser Kasuistik wird über die erfolgreiche Anwendung der Beatmung in Bauchlage bei einem 5-jährigen Mädchen berichtet, welches von einem Pkw überrollt worden war und sich Thorax- und Abdominalverletzungen (Rippenserienfraktur, Lungenkontusion, Leber- und Milzeinrisse) zugezogen hatte. Wegen des akuten Lungenversagens mit persistierenden Atelektasen, die durch wiederholte fiberoptische Bronchiallavagen und durch Reexpansionsmanöver nicht zu beheben waren, wurde der Entschluss zur 6-stündigen Lagerung auf den Bauch gefasst, obwohl über den Effekt dieser Lagerungsmaßnahme bei traumatisierten Kindern wenig bekannt ist und zu möglichen negativen Auswirkungen auf das schwerverletzte Abdomen eine Informationen vorliegen. Die Beatmung in Bauchlage führte zur raschen Verbesserung des pulmonalen Gesaustausches, die hämodynamische Situation wurde nicht beeinflusst. Die radiologische Kontrolle nach Rücklagerung zeigte eine vollständigen Rückgang der Atelektasen; die kleine Patientin konnte bald darauf extubiert werden. Weder laborchemisch noch klinisch wurde ein schädigender Einfluss auf das verletzte Abdomen gefunden. Die Beatmung in Bauchlage hat sich als Routineverfahren bei der Behandlung des Lungenversagens des Erwachsenen etabliert; nach der hier beschriebenen Erfahrung ist diese Maßnahme auch bei traumatisierten Kindern in Betracht zu ziehen, insbesondere wenn andere Maßnahmen nicht ausreichend sind.
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  • 15
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Cochlear Implant ; Ambulante Rehabilitation ; Kinder ; Erwachsene ; Ergebnisse ; Keywords Cochlear implant ; Outpatient rehabilitation ; Cost effectiveness ; Results ; Children ; Adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and objective. This study compares the results of the outpatient-based program of the Cochlear Implant Center Ruhr with inpatient-based rehabilitation, which is almost exclusively performed in Germany. Patients/methods. The Department of Otorhinolaryngology at the University of Essen in Germany provided 52 patients with either 22- or 24-channel Nucleus cochlear implants from March 1996 to July 1999. Almost all patients (n=49) were rehabilitated on an outpatient basis, which is the standard in many cochlear implant centers outside Germany. Results. The longest follow-up period at the University of Essen Department of Otorhinolaryngology was 36 months. Minor complications occurred in 10% of the patients. After 24 months, the first three implanted patients were able to discriminate 100% of numbers and over 60% of syllables in the Freiburg speech discrimination test. The patients who developed an understanding of open speech were able to discriminate 31 words per minute with cochlear implant and without lipreading after 24 months. Children were seen to double their Schmid-Giovannini scores at 6 months postimplantation. Conclusions. The Essen outpatient-based cochlear implant program demonstrates results in speech development and speech understanding equal to those of centers providing inpatient rehabilitation. A special advantage is continuous rehabilitation with professionals known to the child for several years. In children especially, exhaustive commuting reduces school attendance and is a burden on the accompanying guardians. As an inpatient, however, the child is torn from his familiar environment. Parents with several children have particular difficulties in accompanying their child and indeed this may not always be possible.
    Notes: Zusammenfassung Hintergrund und Fragestellung. In dieser Arbeit werden die Ergebnisse der ambulanten Rehabilitation nach Cochlear-Implant-Versorgung mit denen der stationären Rehabilitation verglichen, die bisher in Deutschland fast ausschließlich durchgeführt wird. Von März 1996 bis Juli 1999 wurden an der Universitäts-Hals-Nasen-Ohren-Klinik Essen 52 taube oder an Taubheit grenzende Patienten mit einem 22-kanaligen bzw. 24-kanaligen Nucleuscochlear-Implant versorgt. Fast alle Patienten (n=49) konnten wohnortnah ambulant rehabilitiert werden, wie dies dem internationalen Standard entspricht. Ergebnisse. Der längste bisherige Nachbeobachtungszeitraum an der Universitäts-Hals-Nasen-Ohren-Klinik Essen sind 36 Monate. Nach 2 Jahren wurden von den 3 am längsten nachbeobachteten Patienten 100% der Zahlen und über 60% der Einsilber im Freiburger Sprachtest verstanden. Im “speech tracking” erreichten Patienten mit CI und ohne Lippenabsehen nach 24 Monaten 31 Wörter/min. Die Kinder zeigten 6 Monate nach Implantation eine Verdopplung des Scores im Test nach Schmid-Giovannini. Schlussfolgerungen. Das Essener Modell zeigt, dass eine ambulante Rehabilitation nach CI zu vergleichbaren Ergebnissen in der Sprachentwicklung und im Sprachverstehen führt, wie sie von anderen Zentren vorgelegt wurden, in denen fast ausschließlich stationär rehabilitiert wird. Besonders bei Kindern bedeuten lange Anfahrtswege mit einwöchigem stätionärem Aufenthalt Schulausfälle und eine Belastung für die begleitenden Eltern und Familienangehörigen zu Hause, sowie erhebliche Fahrtkosten. Stationäre Aufenthalte zur Rehabilitation reißen zudem das Kind aus seiner gewohnten Umgebung und sind für Eltern mit mehreren Kindern oft unmöglich.
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  • 16
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Hörstörung ; Prävalenz ; Konnatale Hörstörungen ; Erworbene Hörstörungen ; Progredienz ; Infektionen ; Kinder ; Keywords Hearing loss ; Prevalence ; Connatal hearing loss ; Acquired hearing loss ; Progressive hearing loss ; Infections ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract The results of international investigations on connatally acquired hearing loss are compared with the data of the German Registry on Childhood Hearing Loss (4058 cases). The connatal hearing disorders have shown a notable change in the last years regarding to aetiology and prevalence. In contrast to countries of the third world in developed nations the prevalence of permanent childhood hearing loss has been reduced down to 1 in 1.000 births. The results let assume a prevalence of approximately 1:1.200 births in Germany. For instance the number of rubella embryopathia decreased effectively. In contrast CMV infections and alcohol fetopathia are playing an increasing role. In the patients of the German Registry on Childhood Hearing Loss the percentage of certainly progressive hearing loss is 10.3 within the 4058 children with permanent hearing impairment. Diagnostic procedures first of all for the early diagnosis of CMV but also of toxoplasmosis are considerable because these infections may result in treatable hearing loss. Also consequent hearing tests are demanded in children with alcohol fetopathia.
    Notes: Zusammenfassung Im vorliegenden Beitrag werden die Daten internationaler Studien zu angeborenen erworbenen Hörstörungen mit den Ergebnissen aus 4058 Fällen im Deutschen Zentralregister für kindliche Hörstörungen (DZH) verglichen und ausgewertet. Die angeborenen Erkrankungen des Hörvermögens haben innerhalb der letzten Jahre bezüglich Ätiologie und Prävalenz einen deutlichen Wandel erlebt. Im Gegensatz zu Ländern der 3. Welt ist die Prävalenz permanenter kindlicher Hörstörungen in den westlichen Industrienationen auf ca. 1:1.000 gesunken. In Deutschland liegt die Prävalenz nach ersten Ergebnissen des DZH bei ca. 1,2:1.000. So ist beispielsweise der Anteil der Rötelnembryopathien stark zurückgegangen. Dagegen spielen heute die Zytomegalievirus-(CMV)-Infektion und die Alkoholfetopathie eine größere Rolle. Im Patientenkollektiv des DZH mit 4058 permanent hörgestörten Kindern beträgt der Anteil gesichert progredienter Verläufe 10,3%. Diagnostische Verfahren, vor allem zur Früherkennung von CMV und Toxoplasmose, gewinnen zunehmend an Bedeutung. Ebenso ist eine konsequente Hördiagnostik auch bei Kindern mit Alkoholfetopathie zu fordern.
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  • 17
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    Der Anaesthesist 49 (2000), S. 275-278 
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Tropisetron ; postoperatives Erbrechen ; Adenotonsillektomie ; Antiemetika ; Kinder ; Key words Tropisetron ; PONV ; Adenotonsillectomy ; Antiemetics ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background: Postoperative nausea and vomiting (PONV) after tonsillectomy is a common problem in children. Tropisetron is a new 5HT3 receptor antagonist and is successfully used in paediatric patients receiving cancer therapy. The aim of the study was to assess efficacy and safety of a single intravenous dose of tropisetron for prevention of PONV in paediatric patients at risk for postoperative vomiting. Methods: In a randomised, double-blind, placebo-controlled trial, we studied 98 children aged 2–12 years undergoing tonsillectomy or adenotonsillectomy. Patients received placebo or tropisetron 0.1 mg (=0.1 ml)/kg body weight immediately after induction of anesthesia. A standard general anesthetic technique (Sevoflurane/N2O/O2 without neuromuscular blockers or opioids) was used. Perioperative vital signs, grade of sedation and episodes of postoperative nausea and vomiting were recorded. Results: No vomiting episodes occurred in 65.3% of the tropisetron treated patients compared to 34.7% of the placebo group (p=0.0024). Only 10.2% of the tropisetron treated patients vomited more than 3 times compared to 22.4% of the control patients (p=0.0004). The need for antiemetic rescue medication was significantly lower in the study group (10.4%) compared to 28.6% (p=0.025). No significant adverse effects of the study medication were shown. Conclusion: A single intravenous prophylactic dose of tropisetron effectively reduces the incidence of PONV during the first 24 postoperative hours after tonsillectomy and/or adenoidectomy. Because of the low incidence of adverse effects, the prophylactic use of tropisetron seems to be safe and justified in paediatric surgical patients at high risk for postoperative vomiting.
    Notes: Zusammenfassung Fragestellung: Erbrechen und Übelkeit nach Tonsillektomien bei Kindern sind ein häufiges Problem. Aufgrund der positiven Erfahrungen mit Tropisetron, einem neueren 5HT3 Rezeptor-Antagonisten bei Chemotherapien in der pädiatrischen Onkologie und mit anderen 5HT3 Rezeptor-Antagonisten in der Kinderchirurgie, prüften wir die Wirksamkeit und Sicherheit einer Einzeldosis Tropisetron zur Prävention von postoperativem Erbrechen bei chirurgischen Kindern mit erhöhtem Risiko für postoperatives Erbrechen. Methodik: Bei 98 Kindern im Alter von 2– 12 Jahren, die eine Tonsillektomie oder Adenotonsillektomie benötigten, führten wir eine randomisierte, doppelblinde, plazebokontrollierte Studie durch. Die Patienten erhielten Tropisetron oder Plazebo in einer Dosis von 0,1 mg (=0,1 ml)/kg KG i.v. unmittelbar nach der Narkoseeinleitung. Die Narkose erfolgte standardisiert mit Sevofluran/N2O/O2 ohne Einsatz von Opioiden und Muskelrelaxanzien. Vitalparameter, Sedationstiefe, das Auftreten von postoperativem Erbrechen und unerwünschte Wirkungen wurden aufgezeichnet. Ergebnisse: In der Tropisetrongruppe zeigten 65,3% der Kinder kein postoperatives Erbrechen, im Gegensatz zu nur 34,7% der Kinder in der Plazebogruppe (P=0,0024). Mehr als 3 Episoden von postoperativem Erbrechen zeigten nur 10,2% der Patienten in der Tropisetrongruppe im Vergleich zu 22,4% der Patienten der Kontrollgruppe (P=0,0004). Auch der Bedarf an antiemetischer Zusatzmedikation war in der Tropisetrongruppe mit 10,4% signifikant niedriger als in der Kontrollgruppe mit 28,6% (P=0,025). Bedeutsame Nebenwirkungen der Studienmedikation konnten nicht dokumentiert werden. Schlussfolgerungen: Eine prophylaktische intravenöse Einzelgabe von Tropisetron reduziert bei Kindern wirksam das Auftreten von postoperativem Erbrechen während der ersten 24 h nach einer Tonsillektomie oder Adenotonsillektomie. Die geringe Inzidenz von Nebenwirkungen rechtfertigt unserer Ansicht nach die prophylaktische Anwendung von Tropisetron bei Kindern nach Tonsillektomien.
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  • 18
    ISSN: 1432-1076
    Keywords: Key words Coeliac disease ; Children ; Iron deficiency anaemia ; Occult blood ; AbbreviationsCD coeliac disease ; ID iron deficiency ; GFD gluten-free diet
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has recently been suggested that in adults with coeliac disease, faecal blood loss may play a role in the development of iron deficiency. A group of 45 children diagnosed with coeliac disease during 1996 and 1997 were therefore prospectively evaluated for the presence of gluten in their diet, iron deficiency anaemia, and faecal occult blood. Sixty children admitted for elective surgery or asthma served as controls. Faecal occult blood was found in four iron deficient children on normal diet, of whom three were newly diagnosed. Occult blood loss disappeared in three of the four children when gluten was removed from their diet. Faecal occult blood was found in 26.7% of children on gluten-containing diet, but not in children on gluten-free diet (P=0.01), or in control children (P=0.001). Conclusion Our data suggest that the incidence of occult blood loss in coeliac disease occurs mainly in newly diagnosed cases and responds to a gluten-free diet. Occult blood testing may not be warranted in the absence of iron deficiency anaemia nor in children with iron deficiency anaemia who are on a gluten-free diet.
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  • 19
    ISSN: 1432-1076
    Keywords: Key words Gentamicin ; Once daily ; Children ; Saliva
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gentamicin is widely used in paediatric medicine and therapeutic monitoring is mandatory due to the narrow margin of safety. Saliva sampling may be of potential interest, especially in children in whom blood sampling is often difficult. Experience with once daily intravenous administration of aminoglycosides has grown in recent years. Gentamicin levels were measured in serum and saliva of 55 children treated with the drug (5 mg/kg per day), administered intravenously in three different regimens: thrice (n=19), twice (n=18), and once daily (n=18). No correlation was found between serum gentamicin concentrations and saliva levels when the drug was administered twice or thrice daily, however, there was good correlation when the drug was administered once daily (r 2=0.96, P 〈 0.0001). Conclusion In children with uncomplicated infections treated with once daily gentamicin, trough concentrations of the drug can be monitored in saliva.
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  • 20
    ISSN: 1432-1076
    Keywords: Key words Sodium cromoglycate ; Children ; Exercise-induced asthma ; Urinary eosinophil protein X excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This double-blind, randomised and cross-over study was designed to compare the preventive effect against exercise-induced bronchoconstriction (EIB), defined as the percentage decrease in FEV1≥15% after 6 min of exercise, of 2 mg and 10 mg of sodium cromoglycate (SCG), administered through a metered dose inhaler via spacer, in asthmatic children. Each of the 30 subject (age 11.6 ± 3.2 years) was tested on five occasions. For inclusion, EIB in test1 was required. In tests 2 to 5, all subjects inhaled 2 mg or 10 mg of SCG 20 min and 120 min before exercise in a randomised order. In order to assess excretion of eosinophil protein X (EPX) accompanying EIB, urine samples were collected before and after exercise. The mean percentage fall in FEV1 (±SD) in test 1 was 26.8 ± 9.8%. Inhalation of 2 mg and 10 mg of SCG 20 min before exercise provided a significant preventive effect in 83% and 77% and inhalation 120 min before exercise provided a preventive effect in 63% and 70%, respectively (n=30). Variance analysis did not reveal a statistically different absolute fall in FEV1 after exercise when both doses (120 min before exercise) were compared (P=0.356). In an unselected subgroup of 12 children, urinary EPX increased after the challenge without SCG premedication (test 1) (mean change: +48.7 μg/mmol creatinine, P=0.034), whereas no significant increase was found in case of SCG premedication (mean change in μg/mmol creatinine): 2 mg/20 min: +12.1; 2 mg/120 min: +8.5; 10 mg/20 min: −10.4 and 10 mg/120 min: −23.5; P 〉 0.1). Conclusion Administration of 10 mg of sodium cromoglycate is no more effective in preventing exercise-induced bronchoconstriction than 2 mg regardless of whether the medication is given 20 or 120 min before exercise. The preventive effect of sodium cromoglycate on exercise-induced bronchoconstriction in asthmatic children is associated with the inhibition of urinary eosinophil protein X excretion.
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  • 21
    ISSN: 1432-1076
    Keywords: Key words Health-related quality of life ; Health status ; Cross-cultural adaptation ; Children ; Health Utilities Index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Steady progress in developing effective treatments for childhood cancer and other severe pediatric diseases has established the need to consider the nature and frequency of late physical and psychological effects. The Health Utilities Index Mark 2 and Mark 3 (HUI2/3) systems were developed by Feeny, Furlong, Torrance et al. in Canada. These systems are generic multi-attribute measures of a person's health status and health-related quality of life. The first German version of the Canadian HUI2/3 questionnaire was created in our clinic, following recommended guidelines for cross-cultural adaptation of health-related quality of life measures. The usefulness of the resultant version was investigated using a sample of 142 patients who presented to our oncological outpatients' department for a routine health care visit after completion of treatment. The 15 items of the HUI2/3-questionnaire were answered independently by three groups of assessors – nurses, physicians, and parents or patients. Two additional questions covered ratings of the severity of treatment effects and the specification of these effects. The questionnaire was both easy to use and acceptable to the assessors. Percentage agreement between observers about levels for individual attributes ranged from 56% to 100%, with the lowest agreement on the subjective attributes of emotion, pain and cognition. These results are in accordance with previous studies using the original instrument. HUI2 global utility scores were significantly related to ratings of treatment sequelae, giving support to the discriminant validity of the measure. Conclusion The German version of HUI2/3 is a useful instrument with generally high inter-observer agreement and good suitability for outcome measurement in childhood cancer patients. Further research is needed to assess the usefulness of the instrument in other clinical populations and its sensitivity in longitudinal studies.
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  • 22
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    European journal of pediatrics 159 (2000), S. 515-519 
    ISSN: 1432-1076
    Keywords: Key words Osteogenesis imperfecta ; Hearing loss ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue. Progressive hearing loss is one of the principal symptoms of OI, affecting about 50% of adult patients. Hearing loss may also occur in childhood and results in additional disability in education and psychosocial adaptation and aggravates the physical handicap. This can be avoided by appropriate otological and audiological treatment. In a nationwide search, 254 Finnish patients with OI were identified indicating a prevalence of 4.9/100 000. Of the 60 children, 45 aged between 4 and 16 years accepting to participate the study on hearing, were evaluated by a questionnaire and clinical audiometry. Hearing loss was defined as pure tone average (PTA0.5–2 kHz) more than 20 dB hearing level (HL). A clinical geneticist determined the type of OI among the 45 patients. Two sporadic OI cases with conductive hearing loss were ascertained (4.4%): An 11-year-old girl with type IV OI with a PTA0.5–2 kHz of 35/40 dB HL and a 15-year-old boy with type IV OI with a PTA0.5–2 kHz of 27/18 dB HL. In addition, a 6-year-old girl with familial OI type I had either a congenital sensorineural deafness or early progressive deafness with PTA0.5–2 kHz of 97/103 dB HL, probably of unrelated aetiology. Conclusion Hearing loss in children with osteogenesis imperfecta is less frequent than generally suspected. Nevertheless, it is recommended that audiometry is performed in children with osteogenesis imperfecta even without symptoms of hearing loss at the age of 10 years, and repeated every 3 years thereafter.
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  • 23
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    European journal of pediatrics 159 (2000), S. 430-433 
    ISSN: 1432-1076
    Keywords: Key words Alport syndrome ; Angiotensin-converting enzyme inhibitors ; Proteinuria ; Children ; AbbreviationACEi angiotensin-converting enzyme inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Enalapril, a long-acting inhibitor of angiotensin-converting enzyme, was given for 2 years to seven children with Alport syndrome. Five patients had a classical X-linked form of the disease; two siblings had the autosomal recessive variant. Their age was between 5.15 and 13.75 years when enalapril was started. All patients had haematuria and proteinuria, creatinine clearance was 〉80 ml/min per 1.73 m2 in all, and only one patient was hypertensive. The starting dose of enalapril (0.1 mg/kg body weight per day) was increased progressively according to individual clinical tolerance. The median doses were 0.13, 0.12, 0.21 and 0.29 mg/kg at 6, 12, 18 and 24 months, respectively. Median values of mean blood pressure were 95 mmHg at the start and 84 mmHg after 24 months. Median daily proteinuria decreased from 52 mg/kg to 18 mg/kg at 6 months, 21 mg/kg at 12 months, 12 mg/kg at 18 months and 30 mg/kg at 24 months. Serum creatinine increased over time from a median of 0.64 mg/dl at baseline to 0.77 mg/dl at 24 months. Concomitantly, there was a decrease in GFR from 104 to 83 ml/min per 1.73 m2 at 18 months and an increase again to 95 ml/min per 1.73 m2 at 24 months. Analysis of the individual data showed three patterns: no response (n=2), temporary response (n=2) and sustained response (n=3). Conclusion When given enalapril at the dosages mentioned, Alport patients as a group display a marked reduction in urinary protein excretion with a nadir of 23% of the baseline figure at 18 months, a decrease that cannot be accounted for by the slight decrease in glomerular filtration rate. Although these are preliminary data, it is recommended to try an angiotensin-converting enzyme inhibitor in every paediatric Alport patient with proteinuria.
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  • 24
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    European journal of pediatrics 159 (2000), S. 575-578 
    ISSN: 1432-1076
    Keywords: Key words Haemophilia ; HIV-negative patients ; Children ; Growth ; Body mass index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown that HIV-positive haemophilic children develop growth retardation. As not only the HIV infection but also other disease-related factors might compromise growth in these children, growth data were analysed in a longitudinal cross-sectional manner in 84 HIV-negative haemophilic patients from two university clinics. A total of 2–24 height and weight measurements (median 6) were recorded in each patient resulting in 683 single values collected between 1977–1995. Height SDS of all haemophilic boys was −0.31 ± 2.13 (mean ± SD, NS versus 0) and body mass index SDS was 0.21 ± 3.49 (mean SD, NS versus 0) at first measurement and remained unchanged throughout the observation period. Neither height nor body mass index differed with respect to the severity of haemophilia (mild/moderate/severe) or the study centre (Vienna/Prague). Conclusion Growth in HIV-negative patients with haemophilia is not affected in spite of the immunological abnormalities attributed to the substitution therapy or the bleeding episodes in the joints with the potential effect on the growth plate.
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  • 25
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    European journal of pediatrics 159 (2000), S. 649-656 
    ISSN: 1432-1076
    Keywords: Key words Antiretroviral therapy ; Children ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The introduction of combination antiretroviral therapy has been associated with a dramatic clinical improvement in children with human immunodeficiency virus infection. However, the uptake of antiretroviral therapy has been variable across Europe. The Paediatric European Network for the Treatment of AIDS Steering Committee has performed a systematic literature review of paediatric antiretroviral therapy trials. An analysis of the evidence base for the commencement and maintenance of antiretroviral therapy was produced. Suggestions for when to commence antiretroviral therapy, which drugs to start with and how to monitor and sequence drug regimens are given. Conclusion The aim of these guidelines is to help in obtaining equity of access to a uniformly high standard of care for children with human immunodeficiency virus infection in all European countries.
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  • 26
    ISSN: 1432-1076
    Keywords: Key words Insulin aspart ; Insulin analogue ; Type 1 diabetes ; Pharmacokinetics ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6–12 years) and nine adolescents (aged 13–17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (Cmax ins), 881 ± 321 (SD) pmol/l versus 422 ± 193 pmol/l for human insulin (P 〈 0.001); and with a shorter median serum insulin t max ins, 40.0 min (interquartile range: 40–50 min) versus 75.0 min (interquartile range: 60–120 min) for human insulin, (P 〈 0.001). An age-related effect on Cmax ins and area under the curve (AUC0–5h ins) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted ΔCmax glu being lower for insulin aspart compared with human insulin (increase of 7.6 ± 5.1 versus 9.4 ± 4.4 mmol/l respectively, P 〈 0.05). The incidence of adverse events was similar for the two insulin types. Conclusion The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes.
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  • 27
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    European journal of pediatrics 159 (2000), S. 507-508 
    ISSN: 1432-1076
    Keywords: Key words Behçet disease ; Children ; Myositis ; Pustulosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 12-year-old boy presented with a limp and findings suggesting localised myositis of his right calf and a working diagnosis of Behçet disease was made. During 3 years of follow-up, he had another three episodes of calf myositis, all responsive to corticosteroids within days. Conclusion A case of recurrent localised myositis as a main manifestation of Behçet disease is reported. The evolution of incomplete Behçet disease, which is common in children, to the full blown form, with the emphasis on muscle involvement and the importance of early diagnosis of Behçet disease, is discussed.
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  • 28
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    European journal of pediatrics 159 (2000), S. 530-534 
    ISSN: 1432-1076
    Keywords: Key words Schistosomiasis ; Children ; Travellers ; Ultrasonography ; Immunodiagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reports on schistosomiasis in children growing up in Europe are rare despite increased travel activity. We report on eight male and three female German children aged 50 months to 15 years with schistosomiasis. Six children were asymptomatic, whereas two presented with typical signs of Katayama fever. Persisting haematuria, headache with eosinophilia and pyelonephritis were observed in one child each. An exposure was reported for six of the children. Two were examined solely because schistosomiasis was diagnosed in a family member. All had antibodies against schistosomal antigens in at least two of three screening tests. However, schistosomal ova (Schistosoma haematobium) were detected in urine and faecal specimens from only three children. A tumour-like lesion of the bladder was found by ultrasound in only one of the children who also exhibited haematuria. Neither eosinophilia nor elevated IgE levels were constant findings. Six to 12 months after praziquantel treatment, parasitological and ultrasound checks were negative and levels of specific antibodies decreased. However, 2 years later, elevated antibody levels were detected in one girl without evidence of any new exposure. She became antibody-negative 1 year after a second course of treatment. Conclusion In contrast to residents of endemic areas, parasitological and ultrasound examinations seem to be inferior to immunodiagnostics in children from non-endemic areas at temporary risk for schistosomiasis.
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  • 29
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    Der Hautarzt 51 (2000), S. 95-100 
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Dubowitz-Syndrom ; Atopisches Ekzem ; Monozygote Zwillinge ; Kinder ; Keywords Dubowitz syndrome ; Atopic eczema ; Monozygotic twins ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Autosomal recessive inheritance, intrauterine growth retardation, short stature, microcephaly, distinct facial dysmorphism, psychomotoric retardation, and often uncharacterized eczematous skin lesions distinguish the rare Dubowitz syndrome. Here a pair of monozygotic twins with Dubowitz syndrome and clear-cut atopic eczema is presented.
    Notes: Zusammenfassung Autosomal rezessiver Erbgang, intrauterine Wachstumsretardierung, Kleinwüchsigkeit, Mikrozephalie, charakteristische Gesichtsdysmorphie, psychomotorischer Entwicklungsrückstand sowie häufig nicht näher charakterisierte ekzematöse Hautveränderungen kennzeichnen das seltene Dubowitz-Syndrom. Wir berichten über monozygote Zwillinge mit Dubowitz-Syndrom und eindeutigem atopischen Ekzem.
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  • 30
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Atopisches Ekzem ; Kinder ; Elternschulung ; Video ; Mütter ; Key words Atopic eczema ; Parental education ; Video ; Children ; Mothers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and Objective. Psychological problems in children and parents related to children's atopic eczema (AE) may impede the success of treatment. We studied the question, if behavior-based parental education in groups (DPE) or standardized video-education (VPE) could enhance dermatological treatment effects and reduce skin-damaging behaviors in children and stress in their mothers. Patients/Methods. 47 mothers attending the university outpatient-clinic for dermatology and their AE-children (mean age 4 years) participated in the study. 18 mothers underwent the DPE (10 sessions), 15 mothers worked with VPE at home. Dermatological standard treatment (CG; N=14) served as control for a 16-weeks-evaluation-period. Results. AE-symptoms improved overall, but the effectiveness of the treatments differed significantly, improval with parent education and was best with VPE. Psychological problems of mothers were equally reduced with DPE and VPE. Conclusions. It is suggested that VPE is a cost effective and less time consuming method for supporting dermatological therapy of AE in children.
    Notes: Zusammenfassung Hintergrund und Fragestellung. Das atopische Ekzem (AE) im Kindesalter kann psychologische Probleme bei Kind und Eltern zur Folge haben, die den Behandlungserfolg erschweren. Die Effektivität direkter verhaltensorientierter Elterngruppenschulungen (DES) bzw. standardisierter Videoschulungen (VES) gegenüber der dermatologischen Standardbehandlung (KG) zur Besserung des AE, des Kratzverhaltens der Kinder und krankheitsbedingter Belastungen der Mütter wurde überprüft. Patienten/Methodik. An der Studie nahmen 47 Mütter und deren AE-Kinder (Durchschnittsalter 4 Jahre) aus der Neurodermitisambulanz der Universitätshautklinik teil, 18 Mütter besuchten die DES (10 Gruppensitzungen), 15 Mütter arbeiteten mit der VES zu Hause. Die Behandlung der KG (n=14) erfolgte im vergleichbaren 4-Monats-Zeitraum. Ergebnisse. Das AE war über alle Behandlungsbedingungen gebessert, ihre Effekstärken unterschieden sich jedoch signifikant: Elternschulungen waren effektiver als Standardbehandlung, den stärksten Effekt hatte die VES. Belastungen der Mütter reduzierten sich nach beiden Schulungsformen. Schlussfolgerungen. Die Ergebnisse verweisen auf eine Zeit und Kosten sparende Möglichkeit, Videoschulungen für die Unterstützung der Therapie des AE im Kindesalter zu nutzen.
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  • 31
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Dermatologie ; Primary Health Care ; Langzeitergebnisse ; Kinder ; Kenia ; Keywords Dermatology ; Primary health care ; Long-term effects ; Children ; Kenya
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Background and Objective. In spite of the importance of skin diseases in Africa south of the Sahara, dermatology is insufficiently represented within the established primary health care systems. Aim of this study was to find out whether an integrated dermatology project could reduce the prevalence of dermatoses. Patients/Methods. Since 1994 trained community health workers have carried out regular weekly visits to schools and nurseries in 10 communities in rural western Kenya. Epidemiological studies were done in 13 schools in 4 communities involving 5780 and 4961 pupils one year before (1993) and 5 years (1999) following the introduction of the dermatology project. Results. Within this period the prevalence of bacterial skin infections fell from 12.7% to 11.3% (n.s.). Mycoses rose from 10.1% to 13.9% (p〈0.05), while arthropod infections (mainly scabies) remained unchanged with a prevalence of 8.3% in 1993 and 8.0% in 1999 (n.s.). Dermatitis also showed no changes (1.7% in both years). Conclusions. The prevalence of infective dermatoses depends not only on medical treatment but also far more on socio-economic factors.
    Notes: Zusammenfassung Hintergrund und Fragestellung. Trotz der großen Bedeutung der Dermatosen in Schwarzafrika ist die Dermatologie in den dort etablierten Basisgesundheitsdiensten völlig unzureichend repräsentiert. Untersucht werden sollten die Langzeitauswirkungen eines in das Primary Health Care-System integrierten Dermatologieprojekts in Bezug auf die Prävalenz von Hauterkrankungen. Patienten/Methodik. Seit 1994 besuchen ausgebildete Community Health Workers einmal wöchentlich Schulen und Vorschulkindergärten in 10 Gemeinden im ländlichen Westkenia. In 13 Schulen von 4 Gemeinden wurden 1 Jahr vor (1993) und 5 Jahre nach (1999) Projektinitiierung Reihenuntersuchungen an 5780 bzw. 4961 Kindern durchgeführt. Ergebnisse. Innerhalb dieses Zeitraums sank die Prävalenz bakteriell bedingter Dermatosen von 12,7% auf 11,3% (n.s.). Bei den Mykosen fand sich ein Anstieg von 10,1 auf 13,9% (p〈0,05). Arthropodenbedingte Infektionen (vorwiegend Skabies) blieben mit 8,3% 1993 und 8,0% 1999 (n.s.) im Wesentlichen gleich. Ekzeme wiesen zu beiden Zeitpunkten eine Prävalenz von 1,7% auf. Schlussfolgerungen. Die Prävalenz infektiöser Dermatosen hängt nur zu einem geringen Teil von der medizinischen Versorgung, sondern überwiegend von sozioökonomischen Faktoren ab.
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  • 32
    ISSN: 1129-2377
    Keywords: Key words Coeliac disease ; Headache ; Children ; HLA antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The linkage between HLA antigens and disease susceptibility has been investigated in several diseases. Two different mechanisms are known to act in the relation between the HLA system and headache: linkage and association of alleles. Among neurological disorders associated with coeliac disease (CD) we focused on headache in 1997. From a group of 70 coeliac children, we studied 10 children with headache (3 boys and 7 girls). For each subject we evaluated clinical history and HLA antigens. The incidence of headache was not different with respect to the prevalence of headache in the general population. The HLA setting is not different between the 2 groups examined. However, we highlight 2 cases for the particular HLA setting.
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  • 33
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    The journal of headache and pain 1 (2000), S. 169-172 
    ISSN: 1129-2377
    Keywords: Key words Migraine ; Sleep ; Sleep apnea ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In our previous study we found a high prevalence of disordered sleep breathing in migraine children vs. controls. Since no quantitative studies about sleep respiratory disorders have been carried out in migraine children, we performed a polysomnographic (PSG) study in 10 migraine patients (7 boys, 3 girls; mean age 8.11 years, range, 5.8–14.5) attending the Headache Center of our department, to evaluate the presence of sleep apnea. Mothers completed a headache diary and a sleep diary for at least 1 month and filled out a sleep questionnaire. PSG data showed a normal sleep architecture in 3 cases, an insomnia pattern in 2, a reduction of slow wave sleep in 3 and a reduction of REM sleep in 2. Respiratory analysis revealed that 2 of 10 patients had obstructive sleep apnea. These 2 patients presented habitual snoring and associated sleep disturbances such as restless sleep and hypnic jerks. Sleep apnea may be a subtle and often undiagnosed symptom in several migraine patients. The report of habitual snoring associated with other sleep disturbances such as restless sleep and other parasomnias may be a sign of sleep apnea in migraine children.
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  • 34
    ISSN: 1432-2013
    Keywords: Key words vitamin C (L-ascorbic acid) ; apoptosis ; human articular chondrocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chondrocytes present in articular cartilage survive as a resident cell population throughout the lifespan of the individual organism. However, articular chondrocytes as other cells also undergo apoptosis and there is an ever increasing list of diverse stimuli that can induce this phenomenon in vitro. Our main interest was to investigate potential cytotoxic effects of vitamin C (L-ascorbic acid) on human articular chondrocytes. The present study suggests that vitamin C can induce apoptosis in a cell culture of chondrocytes after 18 h of cultivation. Apoptosis-inducing activity of L-ascorbic acid is dose dependent and significantly affected by the presence of serum. The increased number of vitamin C induced apoptotic cells was associated with DNA fragmentation and morphological changes of the cells.
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  • 35
    ISSN: 1468-2869
    Keywords: Asthma ; Children ; Chronic illnesses ; Diabetes ; Self-help ; Training
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Abstract A randomized field trial of a child-centered model of training for self-management of chronic illnesses was conducted of 355 Spanish-speaking school-aged children, between 6 and 15 years old, with moderate to severe asthma and epilepsy, in Buenos Aires, Argentina. The model, based on play techniques, consists of five weekly meetings of 8–10 families, with children's and parents' groups held simultaneously, coordinated by specially trained teachers and outside the hospital environment. Children are trained to assume a leading role in the management of their health; parents learn to be facilitators; and physicians provide guidance, acting as counselors. Group activities include games, drawings, stories, videos, and role-playing. Children and parents were interviewed at home before the program and 6 and 12 months after the program, and medical and school records were monitored for emergency and routine visits, hospitalizations, and school absenteeism. In asthma and epilepsy, children in the experiment showed significant improvements in knowledge, beliefs, attitudes, and behaviors compared to controls (probability of experimental gain over controls=.69 for epilepsy and .56 for asthma, with σ2= .007 and .016, respectively). Parent participants in the experiment had improved knowledge of asthma (39% before vs. 58% after) and epilepsy (22% before vs. 56% after), with a probability of gain=.62 (σ2=.0026) with respect to the control group. Similar positive outcomes were found in fears of child death (experimental 39% before vs. 4% after for asthma, 69% before vs. 30% after for epilepsy), as well as in disruption of family life and patient-physician relationship, while controls showed no change. Regarding clinical variables, for both asthma and epilepsy, children in the experimental group had significantly fewer crises than the controls after the groups (P=.036 andP=.026). Visits to physicians showed a significant decrease for those with asthma (P=.048), and emergency visits decreased for those with epilepsy (P=.046). An 18-item Children Health Locus of Control Scale (CHLCS) showed a significant increase in internality in experimental group children with asthma and epilepsy (P〈.01), while controls did not change or performed worse 12 months after the program. School absenteeism was reduced significantly for those with asthma and epilepsy (for the group with asthma, fall/winterP=.006, and springP=.029; for the group with epilepsy,P=.011). Conclusion The program was successful in improving the health, activity, and quality of life of children with asthma and epilepsy. The data suggested that an autonomous (Piagetian) model of training is a key to this success, reinforcing children's autonomous decision making.
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  • 36
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; antifolates ; apoptosis ; DNA repair ; p53 ; thymidylate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymidylate synthase (TS) is an essential enzyme for the de novo synthesis of thymidylate and subsequently DNA synthesis. TS has been usedas a target for cancer chemotherapy in the development of fluoropyrimidinessuch as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novelfolate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331,LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331.Although TS has been considered as a target for chemotherapy, the precisemechanism by which TS inhibition leads to cell death is still not completelyresolved. TS inhibition results in depletion of dTTP, an essential precursorfor DNA, and an increase in dUTP. This results in the so-called thymine-lessdeath due to misincorporation of dUTP into DNA; its excision, catalysed byuracil-DNA glycosylase, results in DNA damage. Both this imbalance indTTP/dUTP and DNA damage can result in induction of downstream events, leadingto apoptosis. On the other hand a specific interaction exists betweenoncogenes and TS, by binding of TS protein to the p53and c-mycRNA, while wt p53can also inhibit TS promotor activity. TSinhibition by either 5-FU or antifolates can also result in a depression ofTS protein mediated inhibition of TS mRNA translation leading to induction ofmore TS protein synthesis, and p53protein may further deregulatethis process. These complex indirect and direct interactions between oncogenesand TS may have as yet unclear clinical implications, since most data arebased on in vitroor in vivo studies and some results arecontradictive. In some preliminary clinical studies evidence was postulatedfor a combined prognostic role for TS and p53.This knowledge shouldbe used to design clinical studies with the aim to deliver effective treatmentto potentially sensitive patients both in the adjuvant setting and in advancedstage disease.
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  • 37
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    Virus genes 20 (2000), S. 143-147 
    ISSN: 1572-994X
    Keywords: equine arteritis virus ; cell infection ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Equine arteritis virus (EAV) is the etiological agent of equine viral arteritis, a contagious viral disease of equids. EAV is the prototype virus of the arteriviruses, a group of small enveloped viruses with positive single-stranded RNA genomes. Because apoptosis or programmed cell death is believed to play an important role in the biogenesis of several cytopathogenic viruses, we examined whether EAV was able to induce cell apoptosis in vitro. To do this, Vero cells were infected with EAV at a multiplicity of infection of 0.1 tissue culture infectious dose (TCID50) per cell, and analyzed at various time intervals for the appearance of apoptotic signs. Fragmentation of chromosomal DNA into nucleosomal oligomers and caspase activation were observed in the infected cells at the time (e.g. 24 h postinfection) where a noticeable cytopathic effect was observed. The kinetics of the DNA fragmentation correlated with that of the production of progeny virus, so that viral multiplication was not interrupted by the apoptotic cell damage. All these data provide evidence that EAV is able to induce apoptotic cell death in vitro.
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  • 38
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    Virus genes 21 (2000), S. 13-25 
    ISSN: 1572-994X
    Keywords: adenovirus E3 proteins ; E3 protein sequence comparison ; immune evasion ; interference with antigen presentation ; CD95 (Fas/APO-1) ; apoptosis ; receptor down-regulation ; TNF mediated lysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Persistent viruses have evolved multiple strategies to escape the host immune system. One important prerequisite for efficient viral reproduction in the face of an ongoing immune response is prevention of premature lysis of infected cells. A number of viruses achieve this goal by interfering with antigen presentation and recognition of infected cells by cytotoxic T cells (CTL). Another viral strategy aims to block apoptosis triggered by host defense mechanisms. Both types of strategies seem to be realized by human adenoviruses (Ads). The early transcription unit E3 of Ads encodes proteins that inhibit antigen presentation by MHC class I molecules as well as apoptosis induced by tumor necrosis factor α (TNF-α) and Fas ligand (FasL). Here, we will describe the organization of the E3 regions of different Ad subgroups and compare the structure and functions of the known immunomodulatory E3 proteins.
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  • 39
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    Virus genes 21 (2000), S. 97-109 
    ISSN: 1572-994X
    Keywords: myxoma virus ; immuno-modulator ; viroceptor ; TNF receptor ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Myxoma virus, a member of the poxvirus family of DNA viruses, encodes many virulence factors to combat and evade the host immune responses. Among the virus-encoded immuno-modulators is M-T2, a tumor necrosis factor receptor (TNF-R) homologue. M-T2 is secreted as monomeric and dimeric species that bind and inhibit rabbit TNF in a species-specific manner. Deletion analysis indicates that the anti-TNF function is mediated by the first three of four cysteine rich domains (CRDs) of M-T2. In addition, the intracellular form of M-T2 has the ability to block virus-induced apoptosis in lymphocytes, and the first two CRDs appear to be sufficient for this function. Although the mechanisms for the anti-TNF and anti-apoptotic functions of M-T2 are not yet fully defined, we postulate that these dual activities of M-T2 are mediated through different functional motifs and abrogate distinct cellular responses to virus infection.
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  • 40
    ISSN: 1572-994X
    Keywords: apoptosis ; bZIP ; coiled body ; herpesvirus ; Jun ; nucleolus ; oncogene ; transactivation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to adapt to and to cope with an often hostile host environment, many viruses have evolved to encode products that are homologous to cellular proteins. These proteins exploit the existing host machinery and allow viruses to readily integrate into the host functional network. As a result, viruses are able to maneuver their journey seemingly effortlessly inside the host cell to achieve ultimate survival. Such molecular mimicries sometime go overboard, allowing viruses to overtake the cellular pathways or evade the immune system as do many of the retroviral oncogenes. Retroviral oncogenes are derived directly from host genes, and they are virtually identical to host genes in sequences except those mutations that make them unregulatable by host. Oncogenic herpesviruses also encode oncogenes, or transforming genes, which have independently evolved and are distantly related to host genes. However, these genes do share consensus structural motifs with cellular genes involved in cell growth and apoptosis and are functional analogues to host genes. The Marek's disease virus oncoprotein, MEQ, is one such example. MEQ is a basic region-leucine zipper (bZIP) transactivator which shares extensive homology with the Jun/Fos family of transcription factors within the bZIP domain, but not in other regions. Like all other bZIP proteins, MEQ is capable of dimerizing with itself and with a variety of bZIP partners including c-Jun, B-Jun, c-Fos, CREB, ATF-1, ATF-2, and SNF. MEQ-Jun heterodimers bind to a TRE/CRE-like sequence in the meq promoter region and have been shown to up-regulate MEQ expression in both chicken embryo fibroblasts and F9 cells. In addition, the bZIP and transactivation domains are interchangeable between MEQ and c-Jun in terms of transforming potential; i.e. MEQ can functionally substitute for c-Jun. These properties enable MEQ to engage in host cell processes by disguising itself as c-Jun. On the other hand, there are properties of MEQ notably different from c-Jun, which include its capability to bind RNA, to bind a CACAC-bent DNA structure as a homodimer, to inhibit apoptosis, and to interact with CDK2. MEQ’s subcellular localization in the nucleolus and coiled body, is also different from Jun/Fos family of transactivators. These unique features may provide the MEQ with additional facility in regulating MDV replication, establishing latency, and cellular transformation. In this review, we will attempt to summarize the past research progress on MDV meq, with a focused on the similarities and differences between MEQ and cellular proteins, and between MEQ and other viral oncoproteins.
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  • 41
    ISSN: 1436-3771
    Keywords: Key words Age ; Children ; Dental fluorosis ; Severity ; Tooth eruption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this study was to investigate the influence of age on the severity of dental fluorosis in children exposed to drinking water with either low or high fluoride concentrations. The children selected for this study were aged 10–14 years, with 28 permanent teeth and at least 1 tooth pair with fluorosis. The children were permanent residents of districts in western Uganda with either 0.5 mg (n=33) or 2.5 mg fluoride/l in drinking water (n=186). All vestibular tooth surfaces were examined for fluorosis using the modified Thylstrup and Fejerskov (TF) index. In the high fluoride community, the proportion of teeth per child with TF scores ≥4, and ≥5 was significantly higher among children aged 13–14 years compared to those aged 10–12 years. Children’s chronological age correlated positively and significantly with the median TF scores for all teeth, including early erupting (first molars and incisors) and late erupting teeth (canines, premolars and second molars). In linear regression analyses, the median TF score for all teeth, as well as for early erupting and late erupting teeth, increased significantly with age. On the other hand, in the low fluoride community there was no significant association between age and the severity of fluorosis. This study showed a significant increase in the severity of fluorosis with increasing age in a high fluoride community, whereas no change in severity with age was observed in a low fluoride community.
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  • 42
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    Trauma und Berufskrankheit 2 (2000), S. S138 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Vorderes Kreuzband ; Kind ; Wachstumsfuge ; Fehlwachstum ; Key words ; Anterior cruciate ligament ; Children ; Growth plate ; Growth disturbance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Lesions of the anterior and posterior cruciate ligaments are relatively rare in childhood and adolescence; in this age group they need even more consistent and aggressive treatment than in adults as far as conservation of the menisci and definitive stabilization are concerned. Virtually no cases in which serious growth disturbance has arisen following transepiphyseal drilling are known from the literature. Thus, cruciate ligament suturing should also not be done in children, because the long-term efficacy has not been confirmed. The operative procedure is presented in detail and is related to bone age. Early transepiphyseal drilling is permissible.
    Notes: Zusammenfassung Ligamentäre Kreuzbandverletzung beim Kind und im Adoleszentenalter sind relativ selten, sie bedürfen im Vergleich zum Erwachsenen ¶einer noch konsequenteren und aggressiven Behandlung bezüglich Meniskuserhalt und definitiver Stabilisierung. In der Literatur sind praktisch keine Fälle bekannt, bei denen es tatsächlich zu einem gravierenden Fehlwachstum nach transepiphysärer Bohrung gekommen ist. Insofern sollte auch die Kreuzbandnaht beim Kind wegen der nicht bewiesenen Langzeiteffizienz unterlassen werden. Das Vorgehen im Einzelnen in Bezug zum Skelettalter wird dargestellt. Frühzeitige transepiphysäre Bohrungen sind erlaubt.
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  • 43
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Children ; Risk factors for survival ; Primary non-function ; Hepatic artery thrombosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several recipient, donor and operation factors as well as postoperative complications related to patient survival after liver transplantation (LT) in children were studied by univariate and multivariate analyses . In a 13-year period, 103 patients under 15 years of age underwent 120 LT; the mean age was 63 months and 36 % were under 2 years of age. Indications for LT were cholestatic disease in 68 (56 %), metabolic diseases in 18 (14 %), fulminant hepatic failure in 8 (7.5 %), cirrhosis in 7 (5.8 %), and retransplants in 17 (14 %). Whole liver was transplanted in 79 % of cases and partial liver in 21 %. Actuarial survival at 1, 5, and 10 years was 70 %, 61 %, and 57 %, respectively. United Network of Organ Sharing (UNOS) I recipients (RR = 2.7), primary non-function (PNF) (RR = 13.9), and hepatic artery thombosis (HAT) (RR = 3.8) were independent factors for lower patient survival in multivariate analysis. Thus, in our experience, postoperative mortality as a consequence of the patient's condition before transplantation, or complications such as PNF or HAT, are the major causes of decreased survival in pediatric LT.
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  • 44
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    Bulletin of experimental biology and medicine 130 (2000), S. 957-960 
    ISSN: 1573-8221
    Keywords: human T lymphocytes ; staphylococcal enterotoxin B ; nitric oxide ; proliferation ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The involvement of nitric oxide (NO) in the regulation of human T cell response to bacterial superantigen (staphylococcal enterotoxin B) was studied. It was shown that stimulated T lymphocytes are the main source of NO. This superantigen markedly increased NO production and triggered the proliferative response of mononuclear cells from healthy individuals; the degree of apoptosis was low. In patients with purulent surgical diseases with high spontaneous and induced NO production, superantigen enhanced apoptosis of lymphocytes and induced anergy of T cells to enterotoxins. Increasing the concentration of NO in cultured cells from healthy individuals in the presence of NO donors also stimulated apoptosis and inhibited proliferative activity. These data suggest that NO regulates T lymphocyte response to superantigens. The increased production of NO probably contributes to the development of immunosuppression during bacterial infection.
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  • 45
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    Bulletin of experimental biology and medicine 130 (2000), S. 892-894 
    ISSN: 1573-8221
    Keywords: immune deficiency ; apoptosis ; lymphocytes ; neoplasms and autoimmune diseases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract CD95 expression on peripheral blood lymphocytes in patients with neoplasms was higher than in patients with autoimmune disorders. Apoptosis of T cells increased during tumor growth. The data suggest that neoplasms are accompanied by more severe immune dysfunction than autoimmune disorders.
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  • 46
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    Bulletin of experimental biology and medicine 130 (2000), S. 912-916 
    ISSN: 1573-8221
    Keywords: whole-body hyperthermia ; hepatocytes ; alkaline dissociation of tissues ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract hyperthermia caused hemodynamic disorders in the liver and degenerative and necrobiotic changes in hepatocytes of CBA mice. Total hepatocyte count decreased during restitution, this decrease being most pronounced 30 min after exposure. The number of binucleated cells also markedly decreased. The absence of necrotic changes in hepatocytes during the entire restitution period indicated their apoptotic death and elimination by macrophagal resorption. Under these conditions liver regeneration at the cellular level occured mainly via division of binucleated hepatocytes. On the other hand, proliferation of oval cells in the portal zones and their differentiation into hepatocytes were observed at certain stages of reparative regeneration of the liver.
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  • 47
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    Intensive care medicine 26 (2000), S. 942-949 
    ISSN: 1432-1238
    Keywords: Key words Ventilator-associated pneumonia ; Cardiac surgery ; Children ; Pediatric intensive care ; Complications ; Extubation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: This study was undertaken to determine the delay of extubation attributable to ventilator-associated pneumonia (VAP) in comparison to other complications and complexity of surgery after repair of congenital heart lesions in neonates and children.¶Methods: Cohort study in a pediatric intensive care unit of a tertiary referral center. All patients who had cardiac operations during a 22-month period and who survived surgery were eligible (n = 272, median age 1.3 years). Primary outcome was time to successful extubation. Primary variable of interest was VAP. Surgical procedures were classified according to complexity. Cox proportional hazards models were calculated to adjust for confounding. Potential confounders comprised other known risk factors for delayed extubation.¶Results: Median time to extubation was 3 days. VAP occurred in 26 patients (9.6 %). The rate of VAP was not associated with complexity of surgery (P = 0.22), or cardiopulmonary bypass (P = 0.23). The adjusted analysis revealed as further factors associated with delayed extubation: other respiratory complications (n = 28, chylothorax, airway stenosis, diaphragm paresis), prolonged inotropic support (n = 48, 17.6 %), and the need for secondary surgery (n = 51, 18.8 %; e. g., re-operation, secondary closure of thorax). Older age promoted early extubation. The median delay of extubation attributable to VAP was 3.7 days (hazards ratio HR = 0.29, 95 % CI 0.18–0.49), exceeding the effect size of secondary surgery (HR = 0.48) and other respiratory complications (HR = 0.50).¶Conclusion: VAP accounts for a major delay of extubation in pediatric cardiac surgery.
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  • 48
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    Trauma und Berufskrankheit 2 (2000), S. S136 
    ISSN: 1436-6274
    Keywords: Schlüsselwörter ; Vordere Kreuzbandverletzung ; Kinder ; Rekonstruktion ; Indikation ; Key words ; ACL lesion ; Children ; Reconstruction ; Indications
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract For ACL lesions in children near to the end of the growth phase the treatment can be treated identical to that in adults. For younger children (8–12 years) the treatment must be conservative, combined with controls at short intervals. Behaviour during sport should be modified. If instability is experienced in activities of daily life or during sport a reconstruction of the ACL should be done using a central tibial transepiphyseal hamstring reconstruction with a femoral over-the-top position to avoid possible growth disturbances.
    Notes: Zusammenfassung Kreuzbandverletzungen bei Kindern, die nahe ihres Wachstumsabschlusses sind (14. bis 17. Lebensjahr) können wie Kreuzbandverletzungen von Erwachsenen behandelt werden. Kreuzbandverletzungen bei Kindern, die 13 Jahre und jünger sind, sollten zunächst abwartend behandelt werden (Kniebandage, Koordinationstraining, Belastungsreduzierung). Stellt sich im täglichen Leben oder bei sportlicher Belastung eine Instabilität im Sinne eines Giving way heraus, so sollte das Kreuzband rekonstruiert werden. Dabei ist es nach allen vorliegenden Daten unbedenklich, die Tibia zentral mit einem 8-mm-Bohrloch zu durchbohren und ein ligamentäres Transplantat durchzuziehen. Femoral ist es aus Sicherheitsgründen eher sinnvoll, statt einer transossären Bohrung die Over-the-top-Position zu wählen. Auch andere, rein epiphysäre Verankerungsmethoden (Semitendinosusplastik mit transossärer Drahtfixation) sind möglich.
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  • 49
    ISSN: 1439-0973
    Keywords: Key Words Ritonavir ; Nelfinavir ; Children ; Antiretroviral agents ; HIV-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Background: Knowledge concerning the long-term antiretriviral and immunological efficacy of protease inhibitors in children is limited. Patients and Methods: An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3–16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the durrent treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed. Results: Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log10 copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/μl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean plasma HIV-1 RNA levels than non-naive (5.18 vs 4.64 log10 copies/ml; p = 0.02). The decline in plasma HIV-1 RNA levels 72 weeks after treatment with ritonavir and nelfinavir was −2.17 and −1.30 log10 copies/ml, respectively (p = 0.006) and in ART-naive vs non-naive patietns −2.70 vs − 1.39 log10 copies/ml (p ≤ 0.01). 69% of ART-naive patients and 32% of non-naive patients achieved sustained plasma HIV-1 RNA levels 〈 400 copies/ml. Increases in CD4 cells were higher in ART naive compared to non-naive patients (p 〈 0.04). Conclusion: The antiretroviral and immunologic benefits of protease inhibitors are more profound in ART-naive than in non-naive children.
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  • 50
    ISSN: 1439-0973
    Keywords: Key words Tick-borne encephalitis ; Children ; Adults
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this prospective study was to compare epidemiological data and clinical features in children and adults with tick-borne encephalitis (TBE). Patients with aseptic meningitis diagnosed at the University Medical Centre, Department of Infectious Diseases, Ljubljana, Slovenia, from June to August 1997, in whom the diagnosis of TBE was ascertained by the presence of serum IgM antibodies against TBE virus, who were serologically negative for Borrelia burgdorferi sensu lato and had a negative PCR CSF result on enteroviral infection, were included in the study. Out of 213 patients with aseptic meningitis, 80 (37–56%) fulfilled inclusion criteria. There were 20 children and 60 adults. In both groups males predominated. Virtually all patients had headache and fever, and more than 50% suffered from vomiting. The majority of patients in both groups recalled a tick bite, had a biphasic course of the illness, and was found to have obviously expressed meningeal signs. In both groups the median CSF leukocyte count was somewhat lower than 100 × 106/l with a predominance of lymphocytes. Children were more often given antibiotics during the initial phase of TBE than adults (p = 0.0095). Several other statistically significant distinctions (p 〈 0.05) were found including the frequency of fatigue, malaise, vertigo, photophobia, myalgias, arthralgias, as well as elevated CSF albumin and protein concentration, elevated albumin quotient and IgG quotients; all these findings were more often present in adults. In addition a longer duration of fever, more frequent need for anti-edematous treatment and longer hospitalization were found in adults. Direct comparison of clinical and epidemiological characteristics of TBE in children and adults revealed differences in several clinical and laboratory features and corroborates the previous conclusion that TBE in childhood is a milder illness than TBE in adults.
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  • 51
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    Journal of urban health 77 (2000), S. 723-734 
    ISSN: 1468-2869
    Keywords: Child welfare ; Children ; Disclosure ; HIV ; Mothers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this investigation was to ascertain the reasons given by mothers diagnosed with AIDS (acquired immunodeficiency syndrome) for disclosing or not disclosing their HIV (human immunodeficiency virus) status to their children, a dilemma faced by most HIV-infected parents and those who counsel them. We interviewed 29 mothers residing in one of two New York City facilities that provide housing and medical treatment for adults with AIDS. The majority of these mothers do not live with their children, but all had recent face-to-face contact with them. The two reasons most frequently considered important for disclosing to children were that disclosure was the “right thing to do” and the need to make arrangements for children's future in case of maternal death or incapacity. The reason most frequently considered important for not disclosing was maternal concern about discussing death and dying with children. These findings have significant implications for counseling of HIV-positive parents.
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  • 52
    ISSN: 1439-0973
    Keywords: Key words Pertussis ; Bordetella pertussis ; Hospitalization ; Complications ; Vaccine ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We prospectively followed 725 children under 2 years of age with laboratory-diagnosed Bordetella pertussis infection to investigate the hospitalization rate and complications. Diagnosis was made by culture and polymerase chain reaction (PCR) from nasopharyngeal swabs in 11,016 children who presented with ≥ 7 days of cough at 63 pediatric practices in Germany. Of these children, 33 (4.5%) were hospitalized at a mean age of 4.8 months (range, 17 days to 19.5 months). Complications occurred in 16 (48%) of the 33 patients. Pneumonia developed in two (6%) children and a convulsion was observed in one (3%). Intensive care monitoring was required for 23 (70%) children. Further complications were bradycardia (21%), apnea (12%), conjunctivitis (12%), loss of weight (12%), otitis media (6%), atelectasis (3%) and dehydration (3%). Children aged 6–24 months who had not received any dose of pertussis vaccine had a ten-fold increased risk of hospitalization compared to those who had been partially or fully immunized (p 〈 0.05). Pertussis immunization should be given at an early point in time and completely in order to prevent severe courses of pertussis and hospitalization in young children.
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  • 53
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    Infection 28 (2000), S. 282-286 
    ISSN: 1439-0973
    Keywords: Key Words Chronic ; Osteomyelitis ; Therapy ; Children ; Ewing's sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Background: Presently, most children with chronic osteomyelitis undergo surgery with the inherent risk of damage to their growth plate. We demonstrate a treatment regimen based on imaging procedures focussing on antibiotics in order to reduce the rate of surgical interventions. Patients and Methods: We retrospectively evaluated all 11 patients with clinically suspected chronic osteomyelitis who were treated at our institution from 1989 to 1995. Patients underwent open biopsy and surgical treatment only if imaging procedures showed signs indistinguishable from malignancy, or if they were highly suggestive for the presence of pus, joint infection or osteonecrosis. The patients were followed up for a minimum of 3 years. Results: All five patients treated solely with antibiotics recovered completely. Three patients were subjected to open biopsy and surgical treatment since they showed radiological signs indistinguishable from malignancy, and two patients due to pus or osteonecrosis. In follow-up, there was one relapse of chronic osteomyelitis 11 months after the first treatment course with surgery and antibiotics. One patient suffering from Ewing's sarcoma as detected by open biopsy was excluded. Conclusion: Our diagnostic procedure was useful to reduce the rate of surgery. Surgical treatment of chronic osteomyelitis is not always neccessary especially in cases of missing necrosis, joint infection and abscess as demonstrated by the complete recovery of our patients treated solely with antibiotics.
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  • 54
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    Journal of clinical immunology 20 (2000), S. 229-239 
    ISSN: 1573-2592
    Keywords: Aging ; apoptosis ; TNF receptor ; Fas ; Fas ligand ; mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cellular and molecular basis of immune senescence is unclear. A number of mechanisms have been proposed. In this issue of the Journal of Clinical Immunology, some of the mechanisms for various immunologic abnormalities in aging are presented. In this article, various molecular steps of both death receptor and mitochondrial pathways of apoptosis in general are reviewed. In particular, the role of apoptosis in T-cell immune senescence is discussed.
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  • 55
    ISSN: 1573-4919
    Keywords: tumour necrosis factor ; receptors ; subtypes ; calcium ; apoptosis ; cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Tumour necrosis factor-α (TNF) receptors mediate a variety of effects dependent on cell type. A role for Ca2+ in TNF-induced death remains uncertain. Here we investigated restricting intracellular/extracellular Ca2+ in HeLa epithelial carcinoma cells expressing low and high levels of p75TNFR receptor subtype and KYM-1 rhabdomyosarcoma cells, models of rapid TNF-induced apoptosis. Ca2+-chelators EGTA and BAPTA-AM as well as microsomal Ca2+-ATPase inhibitor thapsigargin, did not alter TNF-induced death. TNF was also unable to alter resting [Ca2+]i levels which remained 〈 200 nM even during times when these cells were undergoing apoptotic cell death. These findings indicate no role for modulated Ca2+ concentrations in TNF-induced apoptotic cell death.
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  • 56
    ISSN: 1573-4919
    Keywords: phosphatidylserine ; base exchange ; apoptosis ; thymocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The exposure of phosphatidylserine toward the external surface of the membrane is a well-established event of programmed cell death. The possibility that an apoptotic stimulus influences the metabolism of this phospholipid could be relevant not only in relation to the previously mentioned event but also in relation to the capability of membrane phosphatidylserine to influence PKC activity. The present investigation demonstrates that treatment of mouse thymocytes with the apoptotic stimulus dexamethasone, enhances the incorporation of [3H]serine into phosphatidylserine. Cell treatment with dexamethasone also enhanced the activity of serine base exchange enzyme, assayed in thymocyte lysate. Both the effects were observed at periods of treatment preceding DNA fragmentation. The addition of unlabelled ethanolamine, together with [3H]serine to the medium containing dexamethasone-treated thymocytes lowered the radioactivity into phosphatidylserine. Serine base exchange enzyme activity was influenced by the procedure used to prepare thymocyte lysate and was lowered by the addition of fluoroaluminate, that is widely used as a G-protein activator. The increase of serine base exchange enzyme activity induced by dexamethasone treatment was observed independently by the procedure used to prepare cell lysate and by the presence or absence of fluoroaluminate.
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  • 57
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    Molecular and cellular biochemistry 212 (2000), S. 35-43 
    ISSN: 1573-4919
    Keywords: cAMP ; CRE ; Cox-2 ; NO ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous studies revealed that expression and activation of cyclooxygenase-2 (Cox-2) conveyed a protective principle in murine macrophages, thus attenuating pro-apoptotic actions of chemotherapeutic agents or programmed cell death as a result of massive nitric oxide (NO) generation. Expression of Cox-2 was achieved by treatment of cells with lipopolysaccharide/interferon-γ or nontoxic doses of NO releasing agents. We reasoned E-type prostanoid formation, and in turn an intracellular cAMP increase as the underlying protective mechanism. To prove our hypothesis, we analyzed the effects of lipophilic cAMP-analogs on NO, cisplatin, or etoposide induced apoptosis in RAW 264.7 macrophages. Selected apoptotic parameters comprised DNA fragmentation (diphenylamine assay), annexin V staining of phosphatidylserine, caspase activity (quantitated by the cleavage of a fluorogenic caspase-3-like substrate Ac-DEVD-AMC), and mitochondrial membrane depolarisation (ΔΨ). Western blots detected accumulation of the tumor suppressor protein p53, relocation of cytochrome c to the cytosol, and expression of the anti-apoptotic protein Bcl-xL. Prestimulation with lipophilic cAMP-analogs attenuated apoptosis with the notion that cell death parameters were basically absent. To verify gene induction by cAMP in association with protection we established activation of cAMP response element binding protein (CREB) by gel-shift analysis and moreover, treated macrophages with oligonucleotides containing a cAMP-responsive element (CRE) in order to scavenge CREB. Decoy oligonucleotides, but not control oligonucleotides, attenuated cAMP-evoked protection and reestablished pro-apoptotic parameters. We conclude that gene induction by cAMP protects macrophages towards apoptosis that occurs as a result of excessive NO formation or addition of chemotherapeutica. Attenuating programmed cell death by the cAMP-signaling system may be found in association with Cox-2 expression and tumor formation.
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  • 58
    ISSN: 1573-4919
    Keywords: T-type Ca2+ channel ; polyglutamine-expanded androgen receptor ; CAG trinucleotide repeats ; spinobulbar muscular atrophy ; apoptosis ; motorneuron ; cell lines ; neuroblastoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have analyzed Ca2+ currents in two neuroblastoma-motor neuron hybrid cell lines that expressed normal or glutamine-expanded human androgen receptors (polyGln-expanded AR) either transiently or stably. The cell lines express a unique, low-threshold, transient type of Ca2+ current that is not affected by L-type Ca2+ channel blocker (PN 200-110), N-type Ca2+ channel blocker (ω-conotoxin GVIA) or P-type Ca2+ channel blocker (Agatoxin IVA) but is blocked by either Cd2+ or Ni2+. This pharmacological profile most closely resembles that of T-type Ca2+ channels [1-3]. Exposure to androgen had no effect on control cell lines or cells transfected with normal AR but significantly changed the steady-state activation in cells transfected with expanded AR. The observed negative shift in steady-state activation results in a large increase in the T-type Ca2+ channel window current. We suggest that Ca2+ overload due to abnormal voltage-dependence of transient Ca2+ channel activation may contribute to motor neuron toxicity in spinobulbar muscular atrophy (SBMA). This hypothesis is supported by the additional finding that, at concentrations that selectively block T-type Ca2+ channel currents, Ni2+ significantly reduced cell death in cell lines transfected with polyGln-expanded AR.
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  • 59
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    Molecular and cellular biochemistry 203 (2000), S. 59-71 
    ISSN: 1573-4919
    Keywords: PTEN tumor suppressor ; cyclin-dependent kinase inhibitors ; apoptosis ; chemosensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The recently discovered tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, PTEN was able to suppress the growth of these cells. Here, we have analyzed how PTEN might alter cell cycle-regulatory controls to achieve this growth-inhibitory effect. We found that overexpression of PTEN stimulates the synthesis of three inhibitors of cyclin-dependent kinases, p21WAF1, p27KIP1, and p57,KIP2. This effect is very specific, as the expression of other components of the cell cycle engine, various cyclins and cyclin-dependent kinases, is not affected. For p21WAF1 we show that this induction is due to the p53-independent transcriptional activation of its promoter. In addition, increased expression of PTEN rendered the cells more sensitive to apoptotic cell death. Therefore, our data suggest a two-fold mechanism of growth inhibition by PTEN: one that acts via the increased expression of CKIs such as p21WAF1, and another that augments the cellular propensity for apoptotic cell death.
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  • 60
    ISSN: 1573-4919
    Keywords: retinoic acid ; RARβ ; protein kinase A ; apoptosis ; caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor β (RARβ) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARβ promoter resulted in loss of both transcriptional activation of RARβ and synergy between RA and 8-Cl-cAMP. RARβ expression appears to be associated with induction of apoptosis. Introduction of the RARβ gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARβ expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARβ expression leading to apoptosis in ovarian cancer cells.
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  • 61
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    Molecular and cellular biochemistry 204 (2000), S. 83-88 
    ISSN: 1573-4919
    Keywords: FHIT ; cell cycle ; ecdysone ; tumor suppressor ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The mechanism of tumor suppressor action of the fragile histidine triad (FHIT) gene is unknown. Disruption of cell cycle regulation leads to the tumor formation and many tumor suppressor genes suppress tumorigenesis through their effect on cell cycle regulation. We examined the expression of FHIT during the cell cycle, and determined whether overexpression of FHIT affects cell cycle kinetics and apoptosis. The FHIT cDNA was cloned into the ecdysone-inducible expression vector in both the sense and antisense orientations. Overexpression of the sense or antisense construct did not affect cell proliferation, cell cycle distribution or apoptosis in human 293T cells. Analysis of the FHIT expression in 293T cells collected at various cell cycle phases showed that the expression of FHIT is not under cell cycle regulation. These results indicate that the tumor suppressor activity of the FHIT gene may be independent of an effect on the cell cycle and apoptosis mechanisms.
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  • 62
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    Molecular and cellular biochemistry 207 (2000), S. 19-27 
    ISSN: 1573-4919
    Keywords: PKC ; apoptosis ; bile acid ; hepatocyte
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of GCDC-induced apoptosis on PKC activity and PKC's role in GCDC-induced hepatocyte apoptosis is unclear. The specific aims of this study were to determine if GCDC-induced apoptosis changed intracellular PKC activity and if modulation of PKC activity affected GCDC-induced hepatocyte apoptosis. Apoptosis was induced in isolated hepatocytes using GCDC. PKC activity was measured and specific PKC and calpain inhibitors were used to study the effects of PKC and calpain modulation on GCDC-induced apoptosis. After 4 h exposure, 50 μM GCDC induced apoptosis in 42% of hepatocytes. Intracellular PKC activity decreased to 44% of controls 2 h after exposure of hepatocytes to GCDC (p 〈 0.001). Pre-incubation of hepatocytes with the calpain protease inhibitor restored PKC activity in GCDC exposed hepatocytes to 91± 5% of control cells. Pre-incubation of hepatocytes with a calpain inhibitor decreased GCDC-induced apoptosis as did pre-incubation with the PKC activating phorbol ester, PMA. The combination of calpain inhibition and PMA further reduced GCDC-induced apoptosis but caused low level hepatic apoptosis. Inhibition of PKC with chelerythrine also substantially reduced GCDC-induced hepatocyte apoptosis. GCDC-induced apoptosis is associated with decreases in total cellular PKC activity, which appear to be dependent on intracellular calpain-like protease activity. The combination of protease inhibition and phorbol ester pretreatment preserved total cellular PKC activity and decreased GCDC-induced apoptosis but induced low level apoptosis in the absence of GCDC exposure. PKC inhibition also decreased GCDC-induced hepatocyte apoptosis highlighting the complex interactions of PKC and proteases during GCDC-induced apoptosis.
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  • 63
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    Molecular and cellular biochemistry 212 (2000), S. 19-28 
    ISSN: 1573-4919
    Keywords: melanoma ; transcription factors ; CREB ; invasion ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The purpose of this study was to determine the role of CREB and its associated proteins in melanoma progression. We used MeWo human melanoma cells transfected with a dominant negative construct of CREB, KCREB. KCREB has a mutation in its DNA-binding domain and can not bind the CRE element. Expression of KCREB yields proper heterodimerization with CREB and its associated proteins, but the proteins associated with KCREB do not confer the same degree of transcriptional activity as they would in the case of wild-type CREB. Here, we demonstrate that expression of KCREB in MeWo melanoma cells leads to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain at least partially this effect of KCREB. The first, is one in which CREB and its associated proteins play an essential role in invasion. We showed that the invasive properties of KCREB-transfected MeWo cells were reduced due to the downregulation of the CRE-dependent expression of the type IV collagenase MMP-2 and the adhesion molecule MCAM/MUC18. In the second mechanism, CREB and its associated proteins act as survival factors for human melanoma cells. Here we demonstrated that expression of KCREB in MeWo cells rendered them susceptible to apoptosis induced by thapsigargin, which in turn increased the intracellular level of Ca2+. Thapsigargin induced CREB and ATF-1 phosphorylation and activated CRE-dependent transcription in MeWo cells. Collectively, our data demonstrate that CREB and its associated proteins play an important role in tumor growth and metastasis of human melanoma.
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  • 64
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    Cancer and metastasis reviews 19 (2000), S. 87-92 
    ISSN: 1573-7233
    Keywords: angiogenesis ; endothelial cell survival ; apoptosis ; thrombospondin-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Angiogenesis is a process of capillary formation from pre-existing blood vessels. It is tightly controlled by the balance between positive and negative environmental signals – inducers and inhibitors of angiogenesis in such a way that predominance of inducers results in angiogenesis and predominance of inhibitors – in vascular quiescence. Here we discuss the ability of the angiogenic stimuli to promote survival and the pathways they may utilize. We also summarize information available on the signaling events elicited in the endothelial cells by a naturally occurring inhibitor of angiogenesis Thrombospondin-1 (TSP-1), that result in the endothelial cell apoptosis and inhibition of angiogenesis in vivo. This ability to cause programmed cell death in vascular endothelium is not unique to TSP-1. A substantial number of known angiogenesis inhibitors can also trigger apoptosis in the activated endothelial cells. This fact argues for the possibility of apoptosis to be a common denominator for a major fraction of anti-angiogenic molecules. If this is the case, it is equally possible that the ratio between environmental factors that control angiogenesis is interpreted within individual endothelial cell as a balance between pro-apoptotic and survival signals. Thus the relative strength of the death and survival signal or signals determines the fate of endothelial cell and therefore the fate of remodeling vessel.
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  • 65
    ISSN: 1573-7039
    Keywords: estrous cycle ; mammary gland ; rat ; proliferation ; differentiation ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Sprague-Dawley rat is highly regarded for studies designed to investigate the effects of endocrine modulation on mammary carcinogenesis. In this study, we further evaluate the validity of the Sprague-Dawley rat model for the study of human breast cancer by evaluating the effects of normal 4-day estrous cycling on mammary epithelial cell proliferation, differentiation, and apoptotic death. Trends in mammary gland development with stage of 4-day estrous cycle were evident. Mammary glands isolated from follicular and early luteal stages had predominantly ductal histoarchitecture, whereas glands isolated from mid-late luteal were predominantly lobuloalveolar. Quantitation of BrdU incorporation revealed that epithelial cell proliferation was eight-fold higher in metestrus and diestrus-1 than in proestrus. Expression of β-casein and whey acidic protein (WAP)4 mRNA was also highly dependent on stage of estrous, with detection restricted to midcycle. Apoptotic cell death of mammary epithelium was found to be suppressed during the peak in cell proliferation. TRPM-2/clusterin mRNA was elevated when apoptosis was low and milk protein mRNA levels were high, consistent with putative roles for TRPM-2/clusterin in inhibiting cell death in regressing tissues and inducing mammary epithelial cell differentiation. Cell proliferation, differentiation, and death occurred only in a subset of epithelial cells per estrous cycle, and these cells appeared randomly distributed throughout multiple ductules and alveoli. These observations suggest that cellular response(s) to ovarian hormone-dependent signals is asynchronous. Cumulatively, these observations demonstrate that rat mammary epithelial cell proliferation, differentiation, and death are under the control of cycling ovarian hormones, similarly to the human mammary epithelium during the menstrual cycle.
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  • 66
    ISSN: 1573-7276
    Keywords: apoptosis ; butyrate ; cell cycle ; cholesteryl butyrate ; drug delivery ; melanoma ; solid lipid nanospheres
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Literature data show that butyric acid derivatives bear a dose-dependent differentiative anti-proliferative activity on cancer cell lines and that apoptosis induction may play a major role. Although it was recently shown that solid lipid nanospheres (SLNs) are a suitable tool for several in vivo drug administration routes, there is little available information on melanoma cell lines. This study was aimed at evaluating the anti-proliferative and apoptotic in vitro effects of cholesteryl butyrate (chol-but) SLNs on melanoma cells. Increasing concentrations of chol-but SLNs were used to test two melanoma cell lines. Both cell lines were treated with Na-butyrate (Na-but) and chol-but SLNs for viability. Those tested with chol-but SLNs were more effective than Na-butirate (3 to 72 h). The apoptotic effects of chol-but SLNs were evaluated between 3 and 72 h by annexin-V (ANX-V)/propidium iodide (PI) staining and the antiproliferative effect by PI staining. Apoptosis anti-proliferative-regulatory proteins as bcl-2, Fas/APO1 (CD95) and PCNA (PC10) were also investigated. Flow cytometric analyses evidenced a G0/1-S transition block and a `sub-G0/1' apoptotic peak from 0.5 to 1.0 mM butyric acid. In ANX-V/PI flow cytometric staining, a dose- and time-dependent increase in the apoptotic cell percentage (ANX-V+) coupled with a down-regulation of PC10 and bcl-2 and a parallel up-regulation of Fas/APO1 (CD95) were found in both lines started after 3 to 24 h of chol-but SLNs treatment. Results show that chol-but SLNs exerts a dose/time-dependent effect in melanoma cell apoptosis induction between 3 and 24 h and a dose but not time-dependent effect after 24 h of treatment.
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  • 67
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    Journal of assisted reproduction and genetics 17 (2000), S. 168-173 
    ISSN: 1573-7330
    Keywords: Aging ; apoptosis ; granulosa cells ; in vitro fertilization ; oocyte quality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The objective was to determine the effects of women'sage on the ovarian fecundity as assessed by the incidenceof apoptotic granulosa cells. Methods: Twenty-eight normo-ovulatory women underwentovulation induction for standard IVF. The husbands of thesewomen showed severe male infertility factors. The womenwere divided into four groups according to their ages. Womenunderwent follicle aspiration after the administration ofhuman menopausal gonadotropin plus human chorionicgonadotropin. The nuclei of granulosa cells were examinedby using fluorescence microscopy, and the incidence of apoptotic granulosa cells was tabulated. Results: Granulosa cells in the older women revealed asignificant increase in the number of apoptotic cells. Thenumber of total oocytes and the number of mature oocytesobtained significantly decreased with age. However, endometrial thickness and follicular estradiol, progesterone, andfree testosterone levels were not significantly different amongfour different age groups. Conclusions: Age increases apoptotic changes in granulosacells and consequently decreases the ovarian fecundity.
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    Journal of bioenergetics and biomembranes 32 (2000), S. 15-25 
    ISSN: 1573-6881
    Keywords: Mitochondria ; endoplasmic reticulum ; Ca2+ ; IP3 ; local signaling ; energy metabolism ; apoptosis ; necrosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Many agonists bring about their effects on cellular functions through a rise incytosolic [Ca2+]([Ca2+]c) mediated by the second messenger inositol 1,4,5-trisphosphate (IP3). Imaging studiesof single cells have demonstrated that [Ca2+]c signals display cell specific spatiotemporalorganization that is established by coordinated activation of IP3 receptor Ca2+ channels.Evidence emerges that cytosolic calcium signals elicited by activation of the IP3 receptors areefficiently transmitted to the mitochondria. An important function of mitochondrial calciumsignals is to activate the Ca2+-sensitive mitochondrial dehydrogenases, and thereby to meetdemands for increased energy in stimulated cells. Activation of the permeability transitionpore (PTP) by mitochondrial calcium signals may also be involved in the control of cell death.Furthermore, mitochondrial Ca2+ transport appears to modulate the spatiotemporal organizationof [Ca2+]c responses evoked by IP3 and so mitochondria may be important in cytosolic calciumsignaling as well. This paper summarizes recent research to elucidate the mechanisms andsignificance of IP3-dependent mitochondrial calcium signaling.
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  • 69
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    Journal of bioenergetics and biomembranes 32 (2000), S. 35-46 
    ISSN: 1573-6881
    Keywords: Ca2+ signaling ; inositol 1,4,5-trisphosphate receptor ; mitochondrial Ca2+ uptake ; mitochondrial Ca2+ efflux ; permeability transition ; apoptosis ; Bcl-2 family
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Cellular Ca2+ signals are crucial in the control of most physiological processes, cell injuryand programmed cell death; mitochondria play a pivotal role in the regulation of such cytosolicCa2+ ([Ca2+]c) signals. Mitochondria are endowed with multiple Ca2+ transport mechanismsby which they take up and release Ca2+ across their inner membrane. These transport processesfunction to regulate local and global [Ca2+]c, thereby regulating a number of Ca2+-sensitivecellular mechanisms. The permeability transition pore (PTP) forms the major Ca2+ effluxpathway from mitochondria. In addition, Ca2+ efflux from the mitochondrial matrix occursby the reversal of the uniporter and through the inner membrane Na+/Ca2+ exchanger. Duringcellular Ca2+ overload, mitochondria take up [Ca2+]c, which, in turn, induces opening of PTP,disruption of mitochondrial membrane potential (ΔΨm) and cell death. In apoptosis signaling,collapse of ΔΨ;m and cytochrome c release from mitochondria occur followed by activationof caspases, DNA fragmentation, and cell death. Translocation of Bax, an apoptotic signalingprotein from the cytosol to the mitochondrial membrane, is another step during thisapoptosis-signaling pathway. The role of permeability transition in the context of cell death in relationto Bcl-2 family of proteins is discussed.
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  • 70
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    Neurochemical research 25 (2000), S. 71-76 
    ISSN: 1573-6903
    Keywords: Arginylation ; post-translational modification ; apoptosis ; PC12 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of this study was to analyze the N-terminal post-translational incorporation of arginine into cytosolic proteins from cultured cells and the in vitro incorporation of arginine into soluble proteins of PC12 cells after serum deprivation. Arginine incorporation was measured in the presence of protein synthesis inhibitors. None of the inhibitors used affected significantly the arginylation reaction while the novo synthesis of protein was reduced by 98%. Under these conditions, we found that of the total [14C]arginine incorporated into the proteins, around 20% to 40% was incorporated into the N-terminal position of soluble proteins by a post-translational mechanism. These results suggest that this post-translational aminoacylation may be a widespread reaction in neuronal and non-neuronal cells. We also found that in PC12 cells, the in vitro post-translational arginylation was 60% higher in apoptotic cells with respect to control cells. These findings suggest that the post-translational arginylation of proteins may be involved in programmed cell death.
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  • 71
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    Neurochemical research 25 (2000), S. 341-347 
    ISSN: 1573-6903
    Keywords: Neuronal survival ; apoptosis ; Heat-Shock Proteins ; HSP-70 ; NMDA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cerebellar granule cells (CGC) die apoptotically after five days in culture (DIV) at physiological concentrations of potassium (5 mM; K5). When CGC are depolarized (K25) or treated with NMDA (150 μM) cell survival is increased. CGC changed from K25 to K5 die after 24–48 h. It is known that heat shock protein (HSP) may protect from cell death. Here, we found that cells in K5 showed an increase in HSP-70 levels after 3 DIV. Similarly, in cells changed from K25 to K5, HSP-70 levels were increased after 6 h. Neither NMDA nor K25 treatment affected HSP-70 levels from 2–7 DIV. Ethanol or thermal stress induced HSP-70, but cell survival was not affected in K5 medium. These results suggest that HSP, particularly HSP-70, are not involved in the mechanisms by which NMDA and KCl promote cell survival.
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  • 72
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    Breast cancer research and treatment 62 (2000), S. 223-235 
    ISSN: 1573-7217
    Keywords: adriamycin ; apoptosis ; DNA damage ; growth arrest ; ionizing radiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Breast tumor cells are relatively refractory to apoptosis in response to modalities which induce DNA damage such as ionizing radiation and the topoisomerase II inhibitor, adriamycin. Various factors which may modulate the apoptotic response to DNA damage include the p53 status of the cell, levels and activity of the Bax and Bcl-2 families of proteins, activation of NF-kappa B, relative levels of insulin like growth factor and insulin-like growth factor binding proteins, activation of MAP kinases and PI3/Akt kinases, (the absence of) ceramide generation and the CD95 (APO1/Fas) signaling pathway. Prolonged growth arrest associated with replicative senescence may represent an alternative and reciprocal response to DNA-damage induced apoptosis that is p53 and/or p21waf1/cip1 dependent while delayed apoptosis may occur in p53 mutant breast tumor cells which fail to maintain the growth-arrested state. Clearly, the absence of animmediate apoptotic response to DNA damage does not eliminate other avenues leading to cell death and loss of self-renewal capacity in the breast tumor cell. Nevertheless, prolonged growth arrest (even if ultimately succeeded by apoptotic or necrotic cell death) could provide an opportunity for subpopulations of breast tumor cells to recover proliferative capacity and to develop resistance to subsequent clinical intervention.
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  • 73
    ISSN: 1573-7217
    Keywords: adriamycin ; apoptosis ; breast tumor cells ; EB 1089 ; vitamin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure of MCF-7 breast tumor cells to the vitamin D3 analog, EB 1089 enhances the response to adriamycin. Clonogenic survival studies indicate that EB 1089 shifts the dose-response curve for sensitivity to adriamycin by approximately six-fold in p53 wild-type MCF-7 cells; comparative studies in MCF-7 cells with a temperature-sensitive dominant negative p53 mutation show less than a two-fold shift in adriamycin sensitivity in the presence of EB 1089. The combination of EB 1089 with adriamycin also promotes apoptotic cell death in the p53 wild-type MCF-7 cells but not in the MCF-7 cells expressing mutant p53. EB 1089 treatment blocks the increase in p21waf1/cip1 levels induced by adriamycin and interferes with induction of MAP kinase activity by ionizing radiation, effects which could be related to the capacity of EB 1089 to promote secretion of insulin-like growth factor binding protein. Taken together with our previous findings that EB 1089 enhances breast tumor cell sensitivity to ionizing radiation, there studies further support the concept that vitamin D3 analogs could have utility in combination with conventional chemotherapy and/or radiotherapy in the treatment of breast cancer.
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  • 74
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; melatonin ; retinoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been established that melatonin (Mlt) and retinoic acid, individually, inhibit the proliferation of the estrogen receptor-alpha (ERα)-positive MCF-7 breast cancer cell line. Our laboratory has previously demonstrated that Mlt and all-trans-retinoic acid (atRA) not only inhibit the proliferation, but also induce apoptosis of MCF-7 cells when used in a sequential regimen of Mlt followed 24 h later by atRA. Using this same MCF-7 breast cancer cell line, we investigated the potential pathways through which apoptosis is being induced. We found that treatment of MCF-7 cells with Mlt for 24 h before the addition of atRA decreased the protein levels of the death suppressor, Bcl-2, and increased, although with different time courses, the levels of the death promoters, Bax and Bak; however, there was no change in the levels of the tumor suppressor gene, p53. MCF-7 cells treated sequentially with Mlt and atRA also demonstrated an enhanced sensitivity to the apoptotic effects of atRA, which did not appear to be due to increased expression of the retinoic acid receptors, RARα or RXRα, but rather to enhanced transcriptional activity of the RARα. These data suggest that the sequential treatment regimen of Mlt and atRA may induce apoptosis by modulation of members of the Bcl-2 family of proteins. Thus, this combinatorial regimen, which reduces the concentration of atRA needed for clinical efficacy while enhancing its anti-tumorigenic activity, could be of great therapeutic benefit, and may, in fact, specifically induce the regression of established breast tumors due to its apoptosis-promoting effects.
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  • 75
    ISSN: 1573-7217
    Keywords: antisense oligodeoxynucleotides ; antineoplastic agents ; apoptosis ; Bcl-2 ; breast cancer ; chemosensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have investigated the effects of transient Bcl-2 down-regulation induced by the Bcl-2 antisense oligodeoxynucleotide (ODN) G3139 (Genta Incorporated) in high Bcl-2 protein expressing, estrogen receptor (ER) positive MCF-7 and low Bcl-2 expressing, ER negative MDA435/LCC6 human breast cancer cells. Treatment with Bcl-2 antisense ODN in vitro caused 〉 80% reduction of Bcl-2 protein levels in a sequence specific manner for both cell lines. Maximum mRNA reduction was achieved within 24 h of the first antisense ODN exposure whereas full protein down-regulation required antisense exposure over 48 h. This Bcl-2 reduction was associated with 80–95% loss of viable cells compared to untreated cells. Similar cytotoxic effects were observed in both cell lines despite a nine-fold intrinsic difference in Bcl-2 protein expression suggesting that the relative degree of down-regulation of Bcl-2 is more important than the absolute reduction. Cell death associated with G3139 exposure exhibited properties indicative of apoptosis such as mitochondrial membrane depolarization and caspase activation. Combined treatment with G3139 and cytotoxic agents resulted in additive cytotoxicity in both cell lines. However, under most conditions studied, the direct cytotoxic activity of G3139 antisense was not synergistic with the cytotoxic agents. These results suggest that while Bcl-2 clearly constitutes an attractive therapeutic target due to its role in regulating apoptosis in breast cancer cells, additional mechanisms are important in the control of apoptosis arising from exposure to anticancer agents in vitro.
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  • 76
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; caspases ; NF-κB ; TRAIL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Most breast cancer cell lines are resistant to TNF-related apoptosis inducing ligand (TRAIL) induced apoptosis. In sensitive breast cancer cell lines TRAIL rapidly induces the cleavage and activation of caspases leading to the subsequent cleavage of downstream caspase substrates. In contrast, there is no caspase activation in the resistant cell lines. The transcription factor NF-κB can inhibit apoptosis induced by a variety of stimuli including activation of death receptors. We investigated whether NF-κB contributes to the resistance of breast cancer cells to TRAIL induced apoptosis. All of the resistant breast cancer cell lines expressed NF-κB and had detectable NF-κB activity in nuclear extracts prior to treatment with TRAIL. Upon TRAIL treatment, a significant increase in NF-κB activity was seen in most of the cell lines. To directly test if NF-κB activity contributes to the resistance of these cell lines to TRAIL, we transiently transfected the resistant cell lines with an inhibitor of NF-κB (IκBΔN) and measured TRAIL induced apoptosis in control and transfected cells. All of the resistant cell lines tested showed an increase in TRAIL induced apoptosis when transfected with the IκBΔN. These results demonstrate that TRAIL resistant breast cancer cells fail to rapidly activate the apoptotic machinery but they do activate NF-κB. Inhibition of NF-κB activity increases the sensitivity to TRAIL mediated apoptosis in resistant cells. These results suggest that agents which inhibit NF-κB should increase the clinical efficacy of TRAIL in breast cancer cells.
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  • 77
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; continuous variables statistical analysis ; cytokeratins ; multiple correspondence analysis ; prognosis ; tissue cytosol ; tissue polypeptide antigen (TPA)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Apoptosis is associated with caspase-mediated proteolysis of Type I (K18 and K19) cytokeratins. We previously showed a positive association between the levels of tissue polypeptide antigen (TPA), that recognizes cytokeratins K8, K18, and K19 fragments, and induced apoptosis in breast cancer cell lines. The aim of the present study was to evaluate the interrelationships between TPA, steroid receptors, and p53, and their joint prognostic role in node-negative breast cancer patients not treated with adjuvant therapies. Age and pT were also considered since they are known prognostic factors. Five hundred and ninety-nine cases with N- breast cancer were evaluated (median follow-up: 60 months). TPA was measured by an immunoradiometric assay and p53 by an immuno-chemiluminescent assay in tumor cytosol. Multiple correspondence analysis was used to study the associations among variables. Their prognostic role (univariate analysis) and their joint effect (multivariate analysis) on RFS were investigated with Cox regression models. TPA showed a direct association with ER and PgR. Higher p53 values were weakly associated to low values of ER, PgR, and TPA. Younger age was related to low and intermediate values of ER and PgR and to low p53 values, while older age was related to high values of ER. Multivariate analysis showed a significant prognostic impact for pT, age, ER, and TPA. Among the interactions considered clinically relevant, only that between ER and age was found. RFS estimated values were poorer in cases with lower than in those with higher TPA values, both in patients expected to have a poor (pT2, young age, low ER) and a better prognosis (pT1, older age, high ER). From the findings of the present study we can draw the following conclusions: The relationship of TPA with prognosis gives an additional contribution to pT, age, and steroid receptors in N- breast cancer; TPA may be considered the first marker of apoptosis measured with a fully standardized quantitative method in tumor cytosol and could be evaluated in prognostic indexes including markers related to different biological mechanisms.
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  • 78
    ISSN: 1573-7217
    Keywords: reversal ; paclitaxel ; resistance ; P-glycoprotein ; breast cancer ; valspodar ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paclitaxel (Taxol®) kills tumor cells by inducing both cellular necrosis and apoptosis. A major impediment to paclitaxel cytotoxicity is the establishment of multidrug resistance whereby exposure to one chemotherapeutic agent results in cross-resistance to a wide variety of other drugs. For example, selection of MCF-7 breast cancer cells for resistance to doxorubicin (MCF-7ADR cells) results in cross-resistance to paclitaxel. This appears to involve the overexpression of the drug transporter P-glycoprotein which can efflux both drugs from tumor cells. However, MCF-7ADR cells possess a deletion mutation in p53 and have considerably reduced levels of the Fas receptor, Fas ligand, caspase-2, caspase-6, and caspase-8, suggesting that paclitaxel resistance may also stem from a bona fide block in paclitaxel-induced apoptosis in these cells. To address this issue, we examined the ability of the P-glycoprotein inhibitor valspodar to restore paclitaxel accumulation, paclitaxel cytotoxicity, and paclitaxel-induced apoptosis. Compared to drug sensitive MCF-7 cells, MCF-7ADR cells accumulated 〉6-fold less paclitaxel, were approximately 100-fold more resistant to killing by the drug, and were highly resistant to paclitaxel-induced apoptosis. In contrast, MCF-7ADR cells pretreated with valspodar were indistinguishable from drug-sensitive cells in their ability to accumulate paclitaxel, in their chemosensitivity to the drug, and in their ability to undergo paclitaxel-induced apoptosis. Valspodar, by itself, did not affect these parameters. This suggests that the enhancement of paclitaxel toxicity in MCF-7ADR cells involves a restoration of apoptosis and not solely through enhanced drug-induced necrosis. Morever, it appears that changes in the levels/activity of p53, the Fas receptor, Fas ligand, caspase-2, caspase-6, or caspase-8 activity have little effect on paclitaxel-induced cytotoxicity and apoptosis in human breast cancer cells.
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  • 79
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    Pharmaceutical research 17 (2000), S. 515-520 
    ISSN: 1573-904X
    Keywords: apoptosis ; cationic liposome ; B cell ; WEHI 231 ; reactive oxygen species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Liposomes are of considerable interest as drug carriers andimmunoadjuvants. However, few investigators have studied thechanges exerted by liposomes in the cells with which they interact.The purpose of this study was to investigate whether liposomes induceapoptosis in B cells. Methods. The mouse immature B cell line WEHI 231 cells and mousesplenic B cells were treated with liposomes, and the induction ofapoptosis was evaluated by monitoring changes in DNA content, DNAfragmentation and chromatin condensation by flow cytometry, agarosegel electrophoresis and by morphological investigation. Results. Cationic liposomes induced apoptosis in WEHI 231 cells, butneutral and anionic liposomes did not. A contact time of 30 minbetween WEHI 231 cells and cationic liposomes was sufficient toinduce apoptosis, and 80% of the cells showed hypodiploid DNAcontent. Apoptosis induced by cationic liposomes composed ofstearylamine was inhibited by addition of the oxidant scavenger,N-acetyl-cysteine. Conclusions. Cationic liposomes induced apoptosis in WEHI 231 cells,and the production of reactive oxygen species is important in theregulation of apoptosis induced by cationic liposomes. It is well knownthat cationic liposomes show cytotoxicity, and apoptosis may be oneof the causes of this toxicity.
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  • 80
    ISSN: 1573-8469
    Keywords: apoptosis ; bacteria ; chromatin condensation ; DNA degradation analysis ; plant ; programmed cell death
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Ultrastructural details of the hypersensitive reaction induced by infiltration with avirulent race 2 Xanthomonas campestris pv. vesicatoria in pepper ‘Early Calwonder-10R’ leaves (incompatible interaction) are reported. Affected cells displayed plasmalemma undulations and disruption, lysis of the chloroplast membrane, degeneration of other organelles, general cytoplasm disorganisation and, often, protoplast shrinkage. The nuclei contained large masses of electron-dense material, apparently formed by chromatin aggregation. In many cases a single chromatin-like layer was deposited on the inner side of the nuclear envelope leaving a finely granular matrix in the centre of the nucleus; the nucleolus usually disappeared. The nuclear envelope was sometimes ruptured and the internal matrix leaked into the cytoplasm. The content of many affected cells eventually coagulated and became very electron-dense. The walls often collapsed. All these alterations were especially visible in spongy mesophyll cells at sites where bacteria occurred in the intercellular spaces. Although some of the nuclear and cytoplasmic alterations recall certain aspects of apoptotic cell death, molecular determinations did not reveal any DNA degradation in hypersensitively reacting tissues. The first cell alterations in leaves infected with the virulent bacterial race 1 (compatible interaction) were observed only 27 h after inoculation, when the cytoplasm of some cells showed limited internal disorganisation and plasmolysis at sites where bacterial colonies developed.
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  • 81
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    Reading and writing 12 (2000), S. 191-218 
    ISSN: 1573-0905
    Keywords: Morphological awareness ; Sensitivity to word relations ; Reading ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Education
    Notes: Abstract The morpho-phonological nature of English orthography is examined in this study of the relation between morphological sensitivity and decoding ability in the latter elementary grades. Children in grades three to six were required to distinguish derivationally-related word pairs (e.g., nature-natural) from foil pairs that are related in spelling but not in morphology (e.g., ear-earth). The materials included both transparently-related (i.e., the second word incorporated the pronunciation of the first, as in person-personal) and complexly-related word pairs (i.e., the second word involved some change in pronunciation, as in atom-atomic). Across two experiments, these items were presented in either oral or written form along with various tests of reading ability, intelligence and phonological awareness. The results indicate that children's recognition of derivational relationships improved with grade-level. As anticipated, there was also a significant association between sensitivity to derivational relatedness and decoding ability which remains significant even when the word pairs were orally presented and even when phonological awareness in taken into account. Both phonological awareness and sensitivity to morphological structure emerge as important factors in decoding skill in the later elementary grades.
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  • 82
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    Plant molecular biology 44 (2000), S. 255-266 
    ISSN: 1573-5028
    Keywords: abscisic acid ; apoptosis ; gibberellic acid ; nuclease ; programmed cell death ; protease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Progress in understanding programmed cell death (PCD) in the cereal aleurone is described. Cereal aleurone cells are specialized endosperm cells that function to synthesize and secrete hydrolytic enzymes that break down reserves in the starchy endosperm. Unlike the cells of the starchy endosperm, aleurone cells are viable in mature grain but undergo PCD when germination is triggered or when isolated aleurone layers or protoplasts are incubated in gibberellic acid (GA). Abscisic acid (ABA) slows down the process of aleurone cell death and isolated aleurone protoplasts can be kept alive in media containing ABA for up to 6 months. Cell death in barley aleurone occurs only after cells become highly vacuolated and is manifested in an abrupt loss of plasma membrane integrity. Aleurone cell death does not follow the apoptotic pathway found in many animal cells. The hallmarks of apoptosis, including internucleosomal DNA cleavage, plasma membrane and nuclear blebbing and formation of apoptotic bodies, are not observed in dying aleurone cells. PCD in barley aleurone cells is accompanied by the accumulation of a spectrum of nuclease and protease activities and the loss of organelles as a result of cellular autolysis.
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  • 83
    ISSN: 1573-4919
    Keywords: endosulfan ; cytotoxicity ; mitochondria ; apoptosis ; Jurkat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Several organochlorinated pesticides including DDT, PCBs and dieldrin have been reported to cause immune suppression and increase susceptibility to infection in animals. Often this manifestation is accompanied by atrophy of major lymphoid organs. It has been suggested that increased apoptotic cell death leading to altered T-B cell ratios, and loss of regulatory cells in critical numbers leads to perturbations in immune function. The major objective of our study was to define the mechanism by which endosulfan, an organochlorinated pesticide, induces human T-cell death using Jurkat, a human T-cell leukemic cell line, as an in vitro model. We exposed Jurkat cells to varying concentrations of endosulfan for 0-48 h and analyzed biochemical and molecular features characteristic of T-cell apoptosis. Endosulfan lowered cell viability and inhibited cell growth in a dose- and time-dependent manner. DAPI staining was used to enumerate apoptotic cells and we observed that endosulfan at 10-200 μM induced a significant percentage of cells to undergo apoptotic cell death. At 48 h, more than 90% cells were apoptotic with 50 μM of endosulfan. We confirmed these observations using both DNA fragmentation and annexin-V binding assays. It is now widely being accepted that mitochondria undergo major changes early during the apoptotic process. We examined mitochondrial transmembrane potential (ΔΨm) in endosulfan treated cells to understand the role of the mitochondria in T-cell apoptosis. Within 30 min of chemical exposure, a significant percentage of cells exhibited a decreased incorporation of DiOC6(3), a cationic lipophilic dye into mitochondria indicating the disruption of ΔΨm. This drop in ΔΨm was both dose- and time-dependent and correlated well with other parameters of apoptosis. We also examined whether this occurred by the down regulation of bcl-2 protein expression that is likely to increase the susceptibility of Jurkat cells to endosulfan toxicity. Paradoxically, the intracellular expression of bcl-2 protein was elevated in a dose dependent manner suggesting endosulfan-induced apoptosis occurred by a non-bcl-2 pathway. Based on these data, as well as those reported elsewhere, we propose the following sequence of events to account for T-cell apoptosis induced by endosulfan: uncoupling of oxidative phosphorylation → excess ROS production → GSH depletion → oxidative stress → disruption of ΔΨm → release of cytochrome C and other apoptosis related proteins to cytosol → apoptosis. This study reports for the first time that endosulfan can induce apoptosis in a human T-cell leukemic cell line which may have direct relevance to loss of T cells and thymocytes in vivo. Furthermore, our data strongly support a role of mitochondrial dysfunction and oxidative stress in endosulfan toxicity.
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  • 84
    ISSN: 1573-4919
    Keywords: etoposide ; Bcl-XL ; Bax ; apoptosis ; K562 cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Etoposide is a potent anticancer agent that is used to treat various tumors. We have investigated the dose-dependent effect of etoposide on apoptosis using chronic myeloid leukemia K562 cells treated with low (5 μM) or high (100 μM) concentrations of the drug. At a low concentration, etoposide induced little apoptosis at 24 h, while about 20% of the cells showed apoptosis morphologically at a high concentration. Processing of caspase-3 was slightly detected from 12 h and became obvious at 24 h with 100 μM etoposide. Caspase-3-like protease activity was detected at 24 h with a high concentration. Moreover, these changes were accompanied by cleavage of poly ADP ribose polymerase (PARP). Changes of the mRNA levels of most apoptosis-regulating genes were not prominent at both concentrations, except for the rapid induction of c-IAP-2/HIAP-1 and the down-regulation of Bcl-XL by 100 μM etoposide. The downregulation of Bcl-XL protein occurred from 6 h, while Bax protein conversely showed a slight increase from 6 h. Taken together, the present findings show that the dose-dependent apoptotic effect of etoposide is based on a change in the balance between Bcl-XL and Bax, which precedes the activation of caspase-3.
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  • 85
    ISSN: 1573-4978
    Keywords: apoptosis ; CD95 ; human hepatoma cell ; hydrogen peroxide ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Reactive oxygen species (ROS) play an important role in cell death induced by many different stimuli. Direct exposure of human hepatoma cell line SMMC-7221 to hydrogen peroxide (H2O2) can induce apoptosis characterized by morphological evidence and fragmentation of DNA assayed by terminal deoxynucleotidyl transferase assay (TUNEL assay). Analysis of flow cytometry indicated that H2O2 can decrease the level of CD95(APO-1/Fas), and it is confirmed that H2O2 can also activate the differential expression of some specific gene such as p53 by means of RT-PCR technique. The results indicated that CD95 signal transduction system may be involved in the H2O2-induced apoptosis, and can regulate some specific genes associated with apoptosis in transcription and translation levels such as p53.
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  • 86
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    Archives of orthopaedic and trauma surgery 120 (2000), S. 336-337 
    ISSN: 1434-3916
    Keywords: Key words Pulled elbow ; Children ; Trauma ; Immobilization ; Nursemaid’s elbow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the effectiveness in decreasing recurrence of cast application after manual reduction of pulled elbow. Sixty-four children with pulled elbow were randomized into two treatment groups: Group A underwent manipulative reduction followed by splinting the elbow in a flexed and supinated position for 2 days; group B underwent manipulative reduction only. Both groups were examined 2, 5, and 10 days later. None of the 33 patients in group A had a pulled elbow at follow-up. Four (13%) of 31 patients in group B had a pulled elbow 2–5 days later. Immobilizing the elbow for 2 days after manipulative reduction improves the success of treatment of a pulled elbow.
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  • 87
    ISSN: 1433-0350
    Keywords: Keywords Syringomyelia ; Chiari I malformation ; Foramen magnum decompression ; Children ; Scoliosis ; MRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The authors studied the role of the sole posterior fossa bony decompression in the management of symptomatic children affected by Chiari type I anomalies. The series in the pediatric literature on this subject were reviewed and compared with that presented in this article. From May 1994 to December 1998, 53 patients (3 months to 26 years) were observed. They were divided into: asymptomatic patients (27), who received no surgical treatment and were only subject to clinical observation; symptomatic patients (brain stem compression 16, syringomyelia 10, including 7 with holocord). All the symptomatic patients were treated with the same surgical approach: bony decompression of posterior fossa with removal of the posterior arch of C-1 and the outer layer of the dura without dural opening. In all 16 (100%) of the 16 patients with brain stem compression the symptoms resolved or improved; in patients with syringomyelia the symptoms were resolved or improved in 94.4% of cases. Two children required further surgery after 13 and 24 months, respectively.This series seems to demonstrate that even a simple extradural surgical approach, with a lower rate of postoperative complications and short stay in hospital, is sufficient to arrest the disease and to improve the symptomatology in a high percentage of cases (97.2%), which is comparable to that achieved with other, more aggressive, procedures.
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  • 88
    ISSN: 1433-0350
    Keywords: Key words Botulism ; Electrophysiology ; Blink reflex ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Electrophysiological studies of a child with presumed botulism showed that the amplitude of the serially and electrically elicited blink reflexes Rl, R2 and R2’ was reduced during recovery. These findings suggest a conduction block of the facial nerves. Other nerve conduction studies and an incremental response to repetitive stimulation demonstrated a block of the presynaptic neuromuscular transmission. Results of the biological tests were negative, but those of electrodiagnosis and clinical examination favored a diagnosis of botulism. A combination of electrically elicited blink reflexes and rapid repetitive stimulation of the peripheral nerves was found to be a sensitive method of assessing the integrity of neuromuscular junctions and the subclinical impairment of muscle nerves.
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  • 89
    ISSN: 1433-0350
    Keywords: Key words Hydrocephalus ; Endoscopic III ventriculostomy ; Outcome ; MRI ; Cine-MRI ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to analyze the surgical outcome according to clinical characteristics and to evaluate the correlation between clinical improvement and neuroimaging changes, we retrospectively reviewed 32 children who had undergone endoscopic III ventriculostomy (ETV) from February 1994 to May 1998. There were 15 boys and 17 girls, with a mean age of 5.2 years (range: 1 month to 13 years). The etiology of the hydrocephalus was primary aqueductal stenosis in 18 patients, secondary aqueductal stenosis caused by tumors in 5, IV ventricle outlet obstruction in 5, and hydrocephalus associated with meningomyelocele in 4. The mean duration of follow-up was 19.4 months (range 1–50 months). Overall, surgical outcome was regarded as good in 21 of 29 patients. Surgical outcome was poor in patients younger than 1 year (P〈0.05). Neuroimaging 1 month after ETV showed a decrease in ventricular size in 11 of the 16 patients with good surgical outcomes. Five showed minimal changes only. In patients with good outcomes, ventricular size tended to decrease as time passed. Resolution of periventricular edema, flow void in the III ventricle on T2-weighted axial images, and cine-MR imaging were sensitive indicators of good outcome. We suggest that ETV be considered as a primary treatment option in patients older than 1 year of age with noncommunicating hydrocephalus. In addition, time factors should be taken into consideration when surgical outcome is judged. Changes in ventricular size could not predict surgical outcome completely in themselves. Therefore, a comprehensive postoperative assessment should be made with the help of T2-weighted MRI and cine-MRI.
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  • 90
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    Digestive diseases and sciences 45 (2000), S. 291-297 
    ISSN: 1573-2568
    Keywords: apoptosis ; pit cell lineage ; caspase ; gastric mucosal cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to elucidate the mechanism of spontaneous and rapid cell death of cultured gastric pit cells. Gastric pit cells have a rapid cell turnover rate in vivo. We here show that guinea pig gastric pit cells in culture undergo spontaneous and rapid apoptotic DNA fragmentation, which may represent the rapid cell turnover cycle of gastric pit cells in vivo. This spontaneous apoptotic DNA fragmentation required the presence of fetal calf serum in the culture media. Furthermore, the spontaneous apoptotic DNA fragmentation was prevented by protein synthesis and caspase inhibitors.
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  • 91
    ISSN: 1573-2568
    Keywords: Helicobacter pylori ; chronic gastritis ; Fas receptor ; Fas ligand ; immune privilege ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract H. pylori infection almost invariably results in chronic gastritis, but only a proportion of patients develops severe destruction of epithelial glandular structure or peptic ulcer. To confirm the recent data obtained in testis and eye, showing that Fas ligand is involved in the phenomenon of “immune privilege,” expression of Fas receptor and its ligand of the stomach was investigated in a panel of gastric biopsies obtained from patients H. pylori-positive (N = 42) and with H. pylori-negative (N = 18) by two-color flow cytometry. The results show that membrane-bound Fas ligand protein is constitutively expressed on freshly isolated human gastric mucosal epithelium coupled with infiltrating lymphocytes. There was significant overexpression of Fas receptor and its ligand, and a higher frequency of apoptotic cell death detected by TUNEL in epithelium and infiltrating lymphocytes in H. pylori-infected patients. These findings suggest that involvement of Fas receptor and its ligand system contributes to some extent to mucosal damage in H. pylori-associated gastritis. However, the more specific findings are apoptotic depletion of invading mucosal lymphocytes associated with Fas ligand expression by gastric epithelium. These provide the first direct quantitative evidence to support Fas receptor counterattack and/or paracrine fratricide as a mechanism of immune privilege in vivo in the H. pylori-infected glandular stomach.
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  • 92
    ISSN: 1573-2649
    Keywords: Children ; Population sample ; Quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed to assess the quality of life of a population sample of schoolchildren. The Generic Children's Quality of Life Measure (GCQ) has been developed to allow comparison between chronically ill children and the general child population. The measure assesses how the child views his or her life and also how they would like it to be. Quality of life is measured as the discrepancy between the two viewpoints. This large community-based survey aimed to establish GCQ norm values for children aged 6–14 years. The children were from a sample of schools stratified by geographical location and social need: rural affluent, rural low affluence, urban affluent and urban low affluence. 720 completed questionnaires were analysed. The scores were normally distributed with a wide range. The GCQ showed an acceptable reliability with a Cronbach's α of 0.75. The quality of life score was not correlated with age (r = −0.02, p = 0.64) nor with the deprivation score of the area in which the children lived (r = −0.026, p = 0.49). There were no significant differences between the scores by gender (p = 0.22) nor by rural/urban location (p = 0.60). Normative values were established. The GCQ is suitable for using with children over a large age range (6–14 years) without the scores being confounded by the age, gender, affluence or geographical location.
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  • 93
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    Reviews in endocrine & metabolic disorders 1 (2000), S. 183-196 
    ISSN: 1573-2606
    Keywords: thyroid cancer ; gene mutations ; oncogenes ; tumor suppressor genes ; cell cycle control ; apoptosis ; growth factors ; differentiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 94
    ISSN: 1573-2568
    Keywords: cholangiocellular carcinoma ; p53 ; proliferation markers ; apoptosis ; histopathological parameters ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was performed to examine the correlation between mutations of the p53 tumor suppressor gene, the occurrence of apoptosis, and proliferation in cholangiocellular carcinoma of the liver. The results obtained were compared with pathohistological stage (according to UICC) and grade and with disease related survival rate. In 41 curatively (R0−) resected intrahepatic cholangiocellular carcinomas, the status of the p53 gene was determined by direct sequencing of exons 4–9 and immunohistochemically. Apoptosis was assessed using the in situ end labeling (ISEL) technique in combination with morphological criteria. Proliferation was analyzed by immunohistochemistry of MIB-1 (Ki-67), Proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), grade, several other histopathological factors, and survival rate. Mutations of p53 were detected in 15/41 carcinomas examined (37%). The most common change was a G→C and C→T transition, changing the hot spot amino acid determined by exons 4–8. Of these 15 tumors, 14 were also p53-positive by immunohistochemistry. In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots and also apoptotic cells in variable proportions. The proliferation markers showed a significant correlation among themselves. In univariate survival analysis, the extent of the primary tumor, lymph node status, grade, and p53 were significant factors influencing patient survival. Performing multivariate Cox regression survival analysis, however, only the extent of primary tumor and lymph node status had an independent prognostic impact. Apoptosis was not related to patient prognosis or to other parameters examined. In conclusion, these results indicated that p53 could serve as an additional prognostic parameter that could provide auxiliary information for patient outcome. However, tumor stage and lymph node involvement were the strongest prognostic factors. We failed to establish apoptosis or other pathological parameters as factors predicting the prognosis of patients with cholangiocellular carcinoma.
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  • 95
    ISSN: 1573-2568
    Keywords: burns ; starvation ; gut ; apoptosis ; proliferation ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Maintenance of gut mucosal homeostasis depends on a balance between cell proliferation and cell death. Gut mucosal integrity is impaired after severe burn and during starvation. We determined the effect of burn, starvation, and the combination of both on small bowel epithelial apoptosis and proliferation. Fifty adult male Fischer 344 rats (260–300 g) received a 60% full-thickness scald burn and were randomly divided into fed and starved groups. Small intestine was taken at 12, 24, and 48 hr after injury. All animals in the 12-hr group were starved while recovering from anesthesia. Apoptosis was quantified by immunohistochemical staining (TUNEL) and mucosal proliferation was determined by bromodeoxyuridine (BrdU) incorporation. The apoptotic index was higher in burned rats compared to controls at 12 hr after burn; both these groups were starved (P 〈 0.05). At 24 and 48 hr after burn, apoptosis was highest in the starved groups, with no additional effects of burn (P 〈 0.05). Mucosal epithelial cell proliferation was not different between groups at any time point. In conclusion, burn and starvation both increase apoptosis in the small bowel mucosa; however, these effects are not additive. Apoptosis could be attenuated by enteral feeding, which delineates the importance of early enteral feeding initiation after injury to maintain mucosal integrity.
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  • 96
    ISSN: 1573-2584
    Keywords: Bladder injury ; Bowel injury ; Children ; Pelvic trauma ; Renal injury ; Urogenital trauma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We analysed the inter-relationships of the cause and the type of trauma, the presence of pelvic fracture, the associated intraabdominal organ injuries,and the morbidity and mortality rates in 154 patients presenting and being treated for UGT between 1983 and 1997.The cause of injury was blunt in 77% of cases and penetrating in 13%. The most frequently injured organs were kidney followed by urethra and bladder. Bowels, liver and spleen were the most frequently associated injured organs. Moreover, bladder injuries were strongly associated with bowel injuries (p 〈 0.0001). Hemodynamically normal 49 children with minor or major kidney injuries were managed conservatively. Hemodynamically non-stable 11 patients were explored.The majority of urogenital injuries can be managed conservatively evenwhen associated with intraabdominal organ injuries. Solid genitourinary organ injuries may accompany more frequently to intraperitoneal solidorgan injury. Whereas, non-solid genitourinary organ injuries may more frequently associated with injuries of intraperitoneal hollow viscus.
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  • 97
    ISSN: 1573-2649
    Keywords: Asthma ; Children ; Health-related quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study compared the health-related quality of life (HRQL) of 236 children with mild or moderate/severe asthma with that of a large representative sample of children in the general community. The study also examined the relationship between the HRQL of children with asthma and their demographic characteristics, asthma severity and family functioning. Children with asthma had a significantly poorer HRQL than other children in the community. Amongst the children with asthma, parents reported that children living in single-parent families had poorer physical health, mental health and social functioning than children in two-parent families. There was a significant relationship between the mental health of children with asthma and family functioning but no significant relationship between their physical health and family functioning. These findings suggest that the domains comprising the HRQL of children with asthma are related to both disease and non-disease factors. A better understanding of these relationships will facilitate the development of new interventions to help children with asthma.
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  • 98
    ISSN: 1573-2568
    Keywords: apoptosis ; cyclooxygenase-2 ; gastric epithelial cells ; Helicobacter pylori ; prostaglandin E2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Helicobacter pylori induces apoptosis and alters the proliferation of gastric mucosal epithelial cells. Cyclooxygenase-2 (COX-2), the inducible form of prostaglandin (PG) synthesis, is known to cause alteration in epithelial cell growth. The goal of this study was to determine whether COX-2 gene expression by H. pylori infection could influence gastric epithelial cell apoptosis. Expression of COX-2 mRNA and proteins was up-regulated in Hs746T gastric epithelial cell lines infected with H. pylori, when assessed by quantitative RT-PCR and western blot. Inhibition of COX-2 expression using NS-398, a specific COX-2 inhibitor, showed a significant increase of gastric epithelial cell apoptosis and caspase-3 activation in Hs746T cells infected with H. pylori. Moreover, the effect of NS-398 on H. pylori-induced apoptosis was reversed by the addition of PGE2. These results suggest that up-regulated COX-2 expression by H. pylori infection can inhibit apoptosis of gastric epithelial cells.
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  • 99
    ISSN: 1573-2568
    Keywords: chemoprevention ; colorectal cancer ; 5-aminosalicylic acid ; olsalazine ; apoptosis ; bromdeoxyuridine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of 5-aminosalicylic acid and olsalazine to inhibit colonic aberrant crypts and tumors was investigated in 1,2-dimethylhydrazine-treated rats. The effect of these drugs on the rates of tumor apoptosis and proliferation was studied as potential mechanisms for their action. 5-Aminosalicylic acid reduced the number of aberrant crypt foci by over one third, while olsalazine had no effect on this parameter. However, both agents effectively reduced tumor number and load, increased the rate of tumor apoptosis, and reduced the rate of tumor cell proliferation. In conclusion, 5-aminosalicylic acid and olsalazine are both ultimately effective chemopreventive agents in this model; however, only 5-aminosalicylic acid inhibited the formation of aberrant crypt foci. The inhibitory effect of these agents in tumors is related to the inhibition of proliferation and the induction of apoptosis.
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  • 100
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    Child & adolescent social work journal 17 (2000), S. 327-340 
    ISSN: 1573-2797
    Keywords: Death ; Children ; Cope
    Source: Springer Online Journal Archives 1860-2000
    Topics: Sociology
    Notes: Abstract Child welfare workers are in a unique position to help children and youth in out-of-home care who have experienced the death of a significant person. This article discusses the response of children to death from a developmental perspective and offers suggestions on how child welfare workers can use an ecological perspective to help youngsters cope with their grief.
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