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  • 1
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding ...
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 75 (1997), S. 179-187 
    ISSN: 1432-0584
    Keywords: Key words HIV ; Anemia ; Pathogenesis ; Pathophysiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Anemia occurs frequently among patients seropositive for human immunodeficiency virus (HIV), but its multifactorial origin complicates its differential diagnosis and adequate treatment. In addition, the etiology of anemia in HIV infection often remains unclear. In recent years several attempts have been undertaken to elucidate the mechanisms leading to HIV-associated anemia. Direct infection of erythroid progenitors has been discussed, but could not be proven. Furthermore, soluble factors like HIV proteins and cytokines have been suggested to inhibit growth of hematopietic cells in the bone marrow of HIV-infected patients. However, so far no statements can be made whether these factors are directly involved in myelosuppression or mediate their effect by inhibiting growth-factor synthesis. Opportunistic complications represent the underlying cause for anemia in a large number of HIV-infected patients. Next to this rather obvious reason for anemia, iatrogenic anemia induced by myelosuppressive drugs is also very common. It is of note, however, that modern dosages of 〈600 mg zidovudine (ZDV) daily rarely cause anemia. Instead, other drugs that can induce anemia itself or by enhancing ZDV plasma concentrations must be considered important contributing factors. Deficiency of vitamin B12, folate and iron are frequently reported in HIV patients. However, specific investigations revealed appropriate storage amounts of these micronutrients. Supplementation may be beneficial in some patients, but often fails to reverse anemia in this population. In anemic HIV patients reticulocytopenia is a consistent finding. Additionally, inadequately low endogenous erythropoietin concentrations have been repeatedly reported. Thus, it is speculated that a blunted erythropoietin feedback mechanism contributes substantially to the pathogenesis of anemia in HIV patients.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 69 (1991), S. 325-329 
    ISSN: 1432-1440
    Keywords: Histoplasmosis ; AIDS ; HIV-infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a thirty-year-old patient with AIDS the diagnosis of disseminated histoplasmosis was established via biopsy and culture. The patient had grown up in Argentina, where histoplasmosis is endemic. He had not been in an endemic region during the last two years anteceding the manifestation of systemic histoplasmosis. Accordingly, in patients with a progressive immunodeficiency syndrome, reactivation of a former (possibly inapparent) infection withHistoplasma capsulatum must be considered. Therapy with Amphotericin B lead to a remarkable improvement of clinical, laboratory and sonographic findings. Due to the fact that total eradication ofH. capsulatum from the infected host cannot be achieved with any known drug regimen, a life-long follow-up therapy was begun. The patient showed no signs of relapse after a follow-up of 7 months.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Inzidenz der Übertragung der HIV-Infektion von Männern auf Frauen wurde in einer Population von 198 weiblichen Sexualpartnern von seit 1984 HIV-positiv getesteten Hämophilen untersucht. Die Nachbeobachtungsdauer erstreckte sich über die Jahre 1987–1992. Die Infektion wurde in 20 Fällen (10%) übertragen. Die Analyse von Risikofaktoren für die Übertragung von HIV wurde untersucht durch den Vergleich einer Untergruppe von 57 Hämophilen und seronegativen Partnern mit 8 Überträgern. Die Überträger zeigten zu Beginn als auch am Ende der Beobachtungszeit eine fortgeschrittenere Immundepletion. Darüber hinaus wiesen Überträger am Ende der Studie auch häufiger eine symptomatische Erkrankung auf (75% versus 29% CDC IV; p〈0,01). Darüber hinaus war bei Überträgern 1991/92 häufiger eine positive Viruskultur nachweisbar (71% vs. 42%). Allen Paaren wurde eine regelmäßige Sexualberatung angeboten. Nach 1987 wurden keine neuen Serokonversionen beobachtet. Jedoch wurden zwei Serokonversionen bei Partnerinnen hämophiler HIV-infizierter außerhalb der ursprünglichen Population aufgedeckt. Beide Übertragungen erfolgten in einer Periode schweren klinischen und immunologischen Progresses. Unsere Studie zeigt, daß Sexualpartner von Hämophilen mit fortgeschrittener HIV-Infektion ein höheres Übertragungsrisiko aufweisen. Die Übertragungsfähigkeit von Männern auf Frauen ist auch bei langdauernden Sexualbeziehungen monogamer Paare, die safer sex praktizieren, gering. Das Wissen um das Vorliegen einer HIV-Infektion und Beratung über safer sex scheinen wirksam in der Verhütung von Neuinfektionen.
    Notes: Summary The incidence of male-to-female transmission of HIV infection was studied in a population of 198 sexual partners of hemophiliacs who tested HIV positive since 1984. The follow-up observation period was 1987–1992. Transmission occurred in 20 (10%) cases. The analysis of risk factors for transmission was performed in a subgroup of 57 hemophiliacs with seronegative sexual partners as compared to eight transmitters. Transmitters showed a significantly more advanced immune depletion at enrollment as well as at the end of the observation period. Furthermore, transmitters had a more advanced disease at the end of the study (75% vs. 29% CDC IV; p〈0.01). Also virus cultures were more frequently positive in the transmitters than in the non-transmitters (71% vs. 42%). Regular sexual counseling was offered to all couples. After 1987, no new seroconversions were detected. However, two seroconversions in female partners of hemophiliacs outside the initial study population were observed. Both transmissions occurred during a period of severe clinical and immunological deterioration. This study shows that sexual partners of HIV-infected hemophiliacs with more advanced disease are at higher risk of infection with HIV. The frequency of male-to-female transmission of HIV in long-term monogamous sexual relationships practicing safer sex is low. Overall, disease awareness and counseling for safer sex seem to be effective in reducing transmission rates.
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  • 5
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung DiePneumocystis carinii-Pneumonie (PCP) gehört unverändert zu den potentiell lebensbedrohlichen Komplikationen der HIV-Erkrankung. Trotz wirksamer antimikrobieller Therapie ist sie mit einer Letalität von bis zu 10% verbunden. Die Identifikation von Risikofaktoren für einen tödlichen Ausgang könnte Kriterien für therapeutische Eskalationen begründen und sich in der Ermittlung neuer Pneumocystis-wirksamer Medikamente nützlich erweisen. In einer retrospektiven Studie wurden 58 Erstepisoden einer HIV-assoziierten PCP ohne Prophylaxe analysiert. Im univariaten Ansatz wurden Parameter identifiziert, die signifikant mit einem letalen Ausgang assoziiert waren. Anschließend wurde multivariat mittels der kanonischen Diskriminantenanalyse eine prognostische Regel aufgestellt. Um eine klinisch relevante individuelle Risikoabschätzung zu ermöglichen, wurden Schwellenwerte für eingeschlossene Parameter bestimmt. Univariat waren die mittleren Werte des Hämoglobins, Hämatokrits, Thrombozyten, Albumins, Gesamteiweißes, der γ-Globuline und der AaDO2 signifikant mit dem Ausgang der PCP assoziiert. Keine Unterschiede zwischen Überlebenden und Verstorbenen fanden sich für die mittleren Werte der LDH, der Prozentzahl der Neutrophilen in der BAL und der CD4-Zellzahlen. Die Diskriminantenanalyse ergab die besten Klassifikationsergebnisse bei einer Kombination von Hämoglobin, Albumin und γ-Globulinen (Gesamtrichtigkeit der Klassifikation: 86%). Das Vorliegen von mindestens zwei von drei Werten aus Hämoglobin 〈 10 g/dl, Albumin 〈 3 g/dl und γ-Globulinen 〈 1,2 g/dl war mit einem 14fach erhöhten Risiko eines letalen Ausgangs verbunden. Diese prognostische Regel zeigte eine Sensitivität von 80%, eine Spezifität von 94% und einen negativen Vorhersagewert von 94% bei einer Gesamtrichtigkeit von 91%. Patienten mit einer HIV-assoziierten PCP weisen bei Vorliegen von mindestens zwei der drei prognostisch ungünstigen Werte dieser Regel ein 14faches Risiko eines letalen Ausgangs auf. Diese Regel könnte sich somit als hilfreich erweisen, um Risikopatienten zu identifizieren.
    Notes: Summary Pneumocystis carinii pneumonia (PCP) in HIV-infected patients remains a life-threatening complication in the course of HIV infection. Despite effective treatment, mortality may still be as high as 10%. The identification of risk factors associated with a lethal outcome might be helpful as a guide to therapy for patients at risk and in the evaluation of new drugs with anti-pneumocystic activity. In a retrospective study 58 first episodes of HIV-associated PCP without prophylaxis were analyzed. Variables associatred univariately with higher mortality were identified. A prognostic rule was established in a multivariate approach using canonical discriminant analysis. Cut-off values for parameters included were determined in order to allow a clinically applicable estimate of the individual risk. Variables associated with early mortality were hemoglobin, hematocrit, platelet count, albumin, total protein, γ-globulins, and AaDO2. LDH values, percentage of neutrophils in the BAL, as well as the cellular immunologic state as indicated by CD4-cell count were not significantly associated with the outcome. The discriminant function yielded the best classification results with the inclusion of hemoglobin, albumin, and γ-globulins (overall accuracy 86%). Two or more of the following parameters were associated with a 14-fold increased risk of in-hospital mortality: hemoglobin less than 10 g/dl, albumin less than 3 g/dl, and γ-globulins less than 1.2 g/dl. This prognostic rule was 80% sensitive and 94% specific with a negative predictive value of 94%, yielding an overall accuracy of 91%. Patients with HIV-associated PCP with a positive prognostic rule have a 14-fold increased risk for in-hospital lethal outcome. This discriminant rule may be helpful in identifying patients at risk.
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