Bibliothek

Notizen: The process by which wounds reepithelialize remains controversial. Two models have been proposed to describe reepithelialization: the “sliding” model and the “rolling” model. In the “sliding” model, basal keratinocytes are the principal cells responsible for migration and wound closure. In this model, basal and suprabasal keratinocytes remain strongly attached to leading edge basal keratinocytes and are then passively dragged along as a sheet. The “rolling” model postulates that basal keratinocytes remain strongly attached to the basement membrane zone while suprabasal keratinocytes at the wound margin are activated to roll into the wound site. The purpose of this study was to determine which populations of keratinocytes are actively involved in reepithelialization. We evaluated expression of keratins K14, K15, K10, K2e, and K16 as well as the proliferation marker Ki67 in the migrating tongue of normal human incisional 1-hour to 28-day wounds and normal human 3 mm diameter excisional 1- to 7-day wounds. Our results show dramatic changes in phenotype and protein expression of keratins K10, K2e, K14, K15, and K16 in suprabasal keratinocytes in response to injury. We conclude that this large population of suprabasal keratinocytes actively participates in wound closure.

Notizen: Background: A nonexcitatory, nonpropagating atrial extrastimulus delivered in the refractory period of the preceding cycle can prolong the atrial effective refractory period (AERP) and prevent the induction of atrial fibrillation by another AE introduced in the vulnerable period. Whether the effect of this nonexcitatory stimulation (NE) is confined only to its application site is unknown. Methods and Results: Sixteen consecutive patients were recruited into the study and 2 patients were excluded because of development of more sustained atrial fibrillation. NE was commenced by introduction of a 2.0 msec, 20-mA impulse at 50 msec after the preceding captured pacing impulse. AERP of right atrial septum, a distant site to NE application, was determined at baseline and after 5 minutes of steady pacing at six different protocols: protocol 1, 2, and 3 were conventional pacing at high right atrium, distal coronary sinus, and biatrial sites, respectively, and protocol 4, 5, and 6 were conventional pacing together with NE applied to the same sites as protocol 1, 2, and 3. Biatrial NE (protocol 6 with median AERP = 212.5 msec) significantly prolonged AERP compared with baseline (median AERP = 202.5 msec and P 〈 0.05), conventional pacing (protocol 1, 2, and 3 with median AERP = 205.0 msec, 205.0 msec, and 205.0 msec, respectively, and all P 〈 0.05), and single-site NE (protocol 4 and 5 with median AERP = 207.5 msec and 207.5 msec, respectively, and both P 〈 0.05). Conclusion: Biatrial NE resulted in AERP prolongation even at sites distant to NE application. The study result suggests that by adding NE to multi-sites pacing for atrial fibrillation prevention may have additional benefit.

Notizen: Background: A diagnostic ECG sign of a ventricular aneurysm (VA) consequent to a myocardial infarction (MI) in the presence of complete left bundle branch block was recently described, and consists of the presence of ST-segment elevation (+ST), instead of the expected ST-segment depression (−ST), in leads V4–6. Generally, complete right bundle branch block (RBBB) is associated with −ST in ECG leads V1–3. We hypothesized that stable +ST, instead of the expected −ST in leads V1–3 in patients with RBBB could be also diagnostic of a VA and other severe segmental left ventricular dysfunction (VA/SSD). Thus, this study was performed to explore the feasibility of using the ECG to diagnose a VA/SSD in the presence of RBBB, and to evaluate the determinants of such diagnosis. Methods: The frequency of +ST ≥1 mm in leads V1–3 was assessed in patients with RBBB, prior MI, and a VA/SSD diagnosed by echocardiography and/or contrast left cine-ventriculography. The ECG correlates for a positive or negative diagnosis of a VA/SSD were explored. Results: Out of 4197 files of our cohort of the Cardiology Clinic, RBBB was detected in 175 patients. Of these, 28 had an old MI, and had a VA/SSD diagnosed by ≥1 of noninvasive and/or invasive non-ECG tests. Twenty-one of these 28 patients had stable +ST in ≥1 of leads V1–3 (Group 1), and 7 did not (Group 2). Thus, the sensitivity of this ECG criterion for the diagnosis of VA/SSD was 75%, and the specificity was 100% in this highly selective group. VA/SSD in the septal and anterior myocardial regions was more frequent in the patients of Group 1, than in the patients of Group 2 (P = 0.03 and 0.02, correspondingly). The number of myocardial territories involved with the VA/SSD, or the ejection fraction were not different in the two groups (P = 0.65 and 0.55, correspondingly). Conclusion: VA/SSD can be diagnosed in the presence of RBBB by the concordant to the QRS repolarization changes (+ST) in leads V1–3. Positivity of this ECG marker for VA/SSD correlates with involvement of the septal or anterior myocardial regions, and represents mechanistically a superimposition of primary repolarization alterations, overcoming the secondary such changes.

Notizen: Background: Increase in the amplitude of electrocardiogram (ECG) QRS complexes has been observed in patients treated for heart failure (HF), but the underlying mechanism has not been delineated. Also, correlation of augmentation of the QRS potentials with loss of weight has been noted in patients recovering from anasarca of varying etiology, or after hemodialysis. We assessed the effect of diuresis-based fluid loss in patients treated for HF on the amplitude of ECG QRS complexes. Methods: This is a cohort study based on ECG and other data from a previously published investigation of patients with HF conducted at a university affiliated hospital, which used new measurements and analysis, performed by a totally blinded investigator based at another institution. Twenty-one patients (10 men) aged 70.5 ± 12.7 years, 13 with ischemic, and 8 with nonischemic cardiomyopathy, were admitted to the hospital for management of exacerbated HF and were observed for 48 hours. The patients received diuresis, and had routine laboratory testing, documentation of the net fluid lost, and recording of ECGs prior to the initiation of therapy and at 24 and 48 hours. Percent change (%Δ) over the course of observation in the sums of the amplitude of QRS complexes from 12 leads (ΣQRS12), 6-limb leads (ΣQRS6), and leads 1 + 2 (ΣQRS2) in mm of standard ECGs were correlated with net fluid loss corrected for admission weight in mL/kg. Results: Fluid loss amounted to 3204.9 ± 1399.5 mL in the course of 40 ± 23 hours of diuresis. ΣQRS12 was 160.9 ± 42.3 mm before and 170.0 ± 50.7 mm after diuresis (P = 0. 024). Percent change in ΣQRS12, ΣQRS6, and ΣQRS2 correlated well with the net fluid loss (r =−0.70, −0.82, −0.61, and P = 0.002, 0.0005, 0.001) correspondingly. Conclusion: Changes in sums of the amplitude of QRS complexes of the standard ECG correlates well with net fluid loss in response to short-term diuresis in patients with HF. Change in the ΣQRS12, ΣQRS6, and ΣQRS2 from ECGs before and after diuresis can be used as an easily obtainable and universally available bedside index of the net fluid loss experienced by bedridden patients with HF undergoing therapy.

Notizen: Increases in the P-wave duration (P-du) and P-wave dispersion (P-d) following hemodialysis (HD) are attributed to changes in the electrolytic milieu with HD, or are considered to be due to an unknown mechanism. Such changes are thought to be proarrhythmic, and thus have potential clinical implications. Increase in the amplitude of QRS complexes following HD has been amply documented in the literature. Also, recent work linking attenuation/augmentation of amplitude of QRS and P-wave complexes in patients with increase/subsequent decrease weights due to anasarca peripheral edema/and its alleviation, or before/after hemodialysis (HD) suggests that the increase in the P-du and P-d after HD may be totally (or partially) mediated by the alleviation of the fluid overload by the procedure. This is supported by the decrease/increase in the QRS duration noted with anasarca/and its alleviation. To further clarify this issue, and prove or refute the above hypothesis, it is recommended that correlations of changes in the P-du and P-d with the loss of weight or net fluid dialyzed are carried out, in addition to the traditional considerations of electrolytic alterations after HD.

Notizen: Introduction: Cardiac resynchronization therapy (CRT) is now an established nonpharmacologic therapy for advanced heart failure with electromechanical delay. Despite compelling evidence of the benefits of CRT, one troubling issue is the lack of a favorable response in about one-third of patients. Methods and Results: Currently, there is no unifying definition of responders, and published data were based on acute hemodynamic changes, chronic left ventricular reverse remodeling, as well as the intermediate or long-term clinical response. The lack of improvement with CRT can be due to many factors including the placement of the left ventricular pacing lead in an inappropriate location, the absence of electrical conduction delay or mechanical dyssynchrony despite wide QRS complexes, and possibly failure to optimize the CRT settings after device implantation. In acute hemodynamic studies, placing the left ventricular leads at the free wall region has been suggested to generate the best pulse pressure and positive dp/dt. The degree of mechanical dyssynchrony has recently been assessed noninvasively in CRT patients by echocardiography and in particular by tissue Doppler imaging. These studies suggested that responders of left ventricular reverse remodeling or systolic function had more severe systolic dyssynchrony. However, further studies are needed to examine the clinical utility of these parameters when applied to the standardized anatomic or functional endpoints. Optimization of atrioventricular and interventricular pacing intervals may also reduce the number of nonresponders, though newer methods, especially interventricular pacing intervals, are still under clinical investigation. Conclusion: With the adjunctive use of imaging technology, physicians are able to characterize the response to CRT objectively, and cardiac imaging is an important clinical tool for determining more precisely the presence and degree of mechanical dyssynchrony.

Notizen: In vitro assays have demonstrated that peptides derived from the recently–identified proSAAS precursor inhibit prohormone convertase 1 (PC1) suggesting that this novel peptide may function as an endogenous inhibitor of PC1. To further understand the role of proSAAS in vivo, we have investigated the expression of proSAAS mRNA and processing of proSAAS during pre- and early postnatal rodent development. In situ hybridization showed that, by embryonic day 12.5 (e12.5) in the rat, proSAAS mRNA was present in essentially all differentiating neurons in the mantle layer of the myelencephalon, metencephalon, diencephalon, spinal cord and several sympathetic ganglia. During later stages of prenatal development, widespread proSAAS expression continues in post-mitotic neurons of both the CNS and PNS and begins in endocrine cells of the anterior and intermediate pituitary. Although proSAAS expression overlaps with PC1 in several regions, its overall expression pattern is significantly more extensive, suggesting that proSAAS may be multifunctional during development. Processed forms of proSAAS are present by at least mid-gestation with marked accumulation of two C-terminal forms, comprising the PC1 inhibitory fragment of proSAAS.

Notizen: Background:  Children with Kawasaki's syndrome (KS), also known as Kawasaki's disease or ‘mucocutaneous lymph node syndrome’, have approximately 20–25% incidence of developing coronary artery aneurysms (CAA), stenosis or obliteration if not appropriately diagnosed and treated. In addition some children have myocarditis, pericardial effusions and/or cardiac arrhythmias during the acute phase of KS. Even with current treatment protocols, 2–4% will still be at risk of coronary artery pathology and the long-term implications regarding future coronary artery disease are unknown. Many of these children present for surgical or diagnostic procedures requiring general anesthesia or deep sedation. Only sporadic case reports have been published on the anesthetic experiences of such patients.Methods:  With Institutional Review approval, we reviewed the medical records of all children with discharge diagnosis of KS from 1985 to 2000 for those receiving general anesthesia or deep sedation. Data abstracted from the medical records included information on any surgical procedures performed any time after onset of KS symptoms, type of anesthetic, perioperative monitoring and presence or absence of operative or perioperative complications.Results:  A total of 178 children with KS were identified of whom 47 (26.4%) received either general anesthesia (34) or deep sedation (13). There were no deaths; one child developed congestive heart failure in the immediate postoperative period associated with KS myocarditis. Five (15%) of those having general anesthesia initially were either not diagnosed as having KS or had no preoperative cardiac evaluations. None of the children having general anesthesia had ST segment analysis, invasive monitoring or troponin measurements perioperatively.Conclusions:  The high incidence of serious myocardial complications attributable to KS reported in the pediatric literature is rarely noted in the anesthesia literature. We feel there is a potential for more serious perioperative complications among KS children, although we can only speculate why complications are not more frequently encountered. Anesthetists involved in pediatric services are encouraged to consider KS in their diagnosis of children presenting with febrile illnesses with rashes and to consider the possibility of KS myocardial compromise if they encounter unexpected deterioration perioperatively. Preoperative ultrasound examination and perioperative monitoring (e.g. ST segment analysis and troponin measurements) for myocardial compromise are encouraged if KS is suspected.

Notizen: Abstract:  Background: Despite extensive literature on the topic, it is uncertain if grand (para ≥ 5) and great grand (para ≥ 10) multiparity are associated with adverse birth outcomes. We critically evaluate the evidence for and against the existence of adverse maternal and/or fetal outcomes in high parity women. Methods: An electronic search of MEDLINE and other bibliographic databases (Current Contents, EMBASE, and CAB) was conducted, and all relevant articles in English language were retrieved. Results: Findings on the association between high parity and maternal-fetal birth outcomes are not consistent. Although the older literature tends to suggest that multiparity is a risk factor for negative birth outcomes, more recent reports are not supportive. Comparison across studies was further complicated by confounding factors like maternal age, socioeconomic status, and levels of prenatal care, as well as by variations in study designs and in the definition of parity itself. Furthermore, most studies that examined women of extreme parity (para ≥ 10) were handicapped by inadequate power. Conclusions: After accounting for quality, culture, and degrees of associations, the preponderance of evidence seems to point to possible existence of heightened risk for certain medical complications and placental pathologies among women of extreme parity. The literature also provides reasonable evidence for a higher-than-expected likelihood for occurrence of fetal macrosomia with advanced parity.

Notizen: Autonomous agents that learn about their environment can be divided into two broad classes. One class of existing learners, reinforcement learners, typically employ weak learning methods to directly modify an agent's execution knowledge. These systems are robust in dynamic and complex environments but generally do not support planning or the pursuit of multiple goals. In contrast, symbolic theory revision systems learn declarative planning knowledge that allows them to pursue multiple goals in large state spaces, but these approaches are generally only applicable to fully sensed, deterministic environments with no exogenous events. This research investigates the hypothesis that by limiting an agent to procedural access to symbolic planning knowledge, the agent can combine the powerful, knowledge-intensive learning performance of the theory revision systems with the robust performance in complex environments of the reinforcement learners. The system, IMPROV, uses an expressive knowledge representation so that it can learn complex actions that produce conditional or sequential effects over time. By developing learning methods that only require limited procedural access to the agent's knowledge, IMPROV's learning remains tractable as the agent's knowledge is scaled to large problems. IMPROV learns to correct operator precondition and effect knowledge in complex environments that include such properties as noise, multiple agents and time-critical tasks, and demonstrates a general learning method that can be easily strengthened through the addition of many different kinds of knowledge.