Drugs, sex, money and power: An HPV vaccine case study

In this paper we compare the experiences of seven industrialized countries in considering approval and introduction of the world's first cervical cancer-preventing vaccine. Based on case studies, articles from public agencies, professional journals and newspapers we analyse the public debate about the vaccine, examine positions of stakeholder groups and their influence on the course and outcome of this policy process. The analysis shows that the countries considered here approved the vaccine and established related immunization programs exceptionally quickly even though there still exist many uncertainties as to the vaccine's long-term effectiveness, cost-effectiveness and safety. Some countries even bypassed established decision-making processes. The voice of special interest groups has been prominent in all countries, drawing on societal values and fears of the public. Even though positions differed among countries, all seven decided to publicly fund the vaccine, illustrating a widespread convergence of interests. It is important that decision-makers adhere to transparent and robust guidelines in making funding decisions in the future to avoid capture by vested interests and potentially negative effects on access and equity.     

Translation molekularer Zusammenhänge in die klinische Anwendung

For patients with metastatic renal cell cancer (RCC), therapeutic options after cytokine failure are rather limited. There is a considerable need to identify new substances for systemic therapy. Due to upregulation after the loss of a functional von Hippel Lindau gene product, the vascular endothelial growth factor (VEGF) pathway is a promising target for a molecular based therapy. Over the last few years, therapeutic agents have been developed which inhibit this pathway at various levels. Here, we provide an overview of the molecular background and currently used drugs which have entered clinical trials in the setting of metastatic RCC disease. Until now, the results from early clinical trials are very promising, however, the best schedule, dosage, potential combination regimens, as well as long time efficacy, are still to be determined.     

The effects of carbidopa on uptake of 6-18F-Fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma.

6-(18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET is a useful tool for the detection of certain neuroendocrine tumors, especially with the preadministration of carbidopa, an inhibitor of DOPA decarboxylase. Whether carbidopa also improves (18)F-DOPA PET of adrenal pheochromocytomas and extraadrenal paragangliomas is unknown. The aim of this study was to investigate the sensitivity of (18)F-DOPA PET in the detection of paraganglioma and its metastatic lesions and to evaluate whether tracer uptake by the tumors is enhanced by carbidopa. METHODS: Two patients with nonmetastatic adrenal pheochromocytoma, and 9 patients with extraadrenal abdominal paraganglioma (1 nonmetastatic, 8 metastatic), underwent whole-body CT, MRI, baseline (18)F-DOPA PET, and (18)F-DOPA PET with oral preadministration of 200 mg of carbidopa. The dynamics of tracer uptake by these lesions and the physiologic distribution of (18)F-DOPA in normal tissues were recorded. RESULTS: Seventy-eight lesions were detected by CT or MRI, 54 by baseline (18)F-DOPA PET (P = 0.0022 vs. CT/MRI), and 57 by (18)F-DOPA PET plus carbidopa (P = 0.0075 vs. CT/MRI, not statistically significant vs. baseline). In reference to findings on CT and MRI, the sensitivities of baseline (18)F-DOPA PET were 47.4% for lesions and 55.6% for positive body regions, versus 50.0% (lesions) and 66.7% (regions) for (18)F-DOPA PET plus carbidopa (neither is statistically significant vs. baseline). Compared with baseline, carbidopa detected additional lesions in 3 (27%) of 11 patients. Carbidopa increased the mean (+/-SD) peak standardized uptake value in index tumor lesions from 6.4 +/- 3.9 to 9.1 +/- 5.6 (P = 0.037). Pancreatic physiologic (18)F-DOPA uptake, which may mask adrenal pheochromocytoma, is blocked by carbidopa. CONCLUSION: Carbidopa enhances the sensitivity of (18)F-DOPA PET for adrenal pheochromocytomas and extraadrenal abdominal paragangliomas by increasing the tumor-to-background ratio of tracer uptake. The sensitivity of (18)F-DOPA PET for metastases of paraganglioma appears to be limited.     

In-hospital maternal mortality risk by cesarean and vaginal deliveries in two less developed countries--a descriptive study

Cesarean deliveries are increasing in both developed countries and less developed countries (LDCs). Recent studies in the U.S. have revealed a significantly higher mortality risk for women who delivered abdominally than for those who delivered vaginally, even when the effect of the conditions which necessitated cesarean delivery was taken into account. We chose for study from an international maternity monitoring network, five centers from two LDCs that reported an in-hospital maternal mortality rate (MMR) of around 10 per 1000 parturient women. The pooled data revealed an MMR of 5.1 per 1000 women with vaginal deliveries. For women with cesarean delivery, the total MMR was 36.2 and the MMR attributable to cesarean section was estimated to be 12.8; both rates were per 1000 procedures. The leading cause of death was eclampsia for the vaginal deliveries and sepsis for the cesarean deliveries. The risk of maternal mortality inherent with the cesarean section procedure per se (not counting the risk associated with the labor and delivery complications that necessitated cesarean section) as well as the practical avoidability of maternal deaths for either mode of delivery in these LDC hospitals are discussed.     

Die Gewichtsregulation im Rahmen der Anorexia nervosa unter besonderer Berücksichtigung der Leptinsekretion

Untergewicht ist ein Leitsymptom der Anorexia nervosa. In dieser übersicht fassen wir neuere Untersuchungen zur Gewichtsregulation im Rahmen dieser E?st?rung zusammen. Klinisch relevant ist die Beobachtung, da? ein Body Mass Index von unter 13 kg/m2 zum Zeitpunkt der Aufnahme in eine station?re Behandlung mit einer erh?hten Mortalit?t und dem langfristigen Fortbestehen von Untergewicht assoziiert ist. Eine erniedrigte Leptinsekretion, die als Folge der Gewichtsabnahme entsteht, ist mutma?lich für das Auftreten der ebenfalls charakteristischen Amenorrh? von zentraler Bedeutung. Wir diskutieren Befunde, die auf das geh?ufte Vorkommen von Untergewicht auch bei anderen psychiatrischen St?rungen im Jugendalter hinweisen vor dem Hintergrund der Konstitutionslehre von Kretschmer.     

Planning for children whose parents are dying of HIV/AIDS. American Academy of Pediatrics. Committee on Pediatric AIDS, 1998-1999

Although the character of acquired immunodeficiency syndrome is changing into a chronic illness, it is estimated that by the end of this century, 80 000 children and adolescents in the United States will be orphaned by parental death caused by human immunodeficiency virus infection. Plans for these children need to be made to ensure not only a stable, consistent environment that provides love and nurturing, but also the medical and social interventions necessary to cope with the tragic loss. Pediatricians should become aware of local laws and community resources and initiate discussion early in the course of parental illness to facilitate planning for the future care and custody of the children. States need to adopt laws and regulations that provide flexible approaches to guardianship and placement of children orphaned by acquired immunodeficiency syndrome.     

Metabolic,Enzymatic and Endocrine Status in High‐Yielding Dairy Cows – Part 2

Pairs of 29 high‐yielding (HC) dairy cows (≥45 kg/day reached at least once during lactation) and 29 corresponding control (CC) cows (with milk yields representing the average yield of the herds) were studied in 29 Swiss farms from March 1995 to September 1996. The hypothesis tested was that there are differences in metabolic, enzymatic and endocrine status between HC and CC cows. Cows were studied 2 weeks before and at 5, 9, 13, 17 and 40 weeks post‐partum. Concentrations of metabolites, minerals and hormones and enzyme activities were in the normal range in both HC and CC cows. Changes in metabolic and endocrine traits in early lactation expressed insufficient energy intake, but were similar in both HC and CC cows. Homeorhetic and homeostatic control of metabolism in HC cows was thus adequate to adjust to and allow high milk yields. Under adequate husbandry, management and feeding conditions, metabolic disease problems in HC cows [10 500 kg energy‐corrected milk (ECM)/lactation, peak yields of ≥45 kg ECM/day] can be avoided.     

Blockade of clearance of immune complexes by an anti-F(cγ) receptor monoclonal antibody

Clearance of immune complexes by the mononuclear phagocyte system is important for maintaining normal host defenses against bacterial and viral assault (1), but also contributes to the pathogenesis of a variety of immune- mediated diseases . For example, removal from the circulation of IgG-coated erythrocytes and platelets by the MPS is the sine qua non of immune-mediated cytopenias (2, 3). On the other hand, abnormally decreased removal by the MPS of smaller, soluble immune complexes may play a role in the pathogenesis of immune complex-mediated tissue damage found in such autoimmune diseases as SLE (4). Although the physicochemical nature and the size of immune complexes can influence rates of clearance and sites of deposition (reviewed in 5), interactions between immune complexes and the MPS in vivo are poorly understood. The inability to directly measure binding or internalization of immune complexes by cells in the liver and spleen has made the analysis of the molecular basis of immune complex clearance very difficult . Receptors for the Fc portion of IgG (FcγR) and for complement (CR) undoubtedly play a role in the removal of immune complexes, but the relative importance of these receptors is not known.     

Familial deficiency of two subunits of the first component of complement. c1r and c1s associated with a lupus erythematosus-like disease

Complete absence of C1r and almost complete absence of C1s were found in 4 of 8 living siblings. Two of the 4 suffer from a syndrome that combines discoid lupus erythematosus and nondeforming rheumatoid-like arthritis; one of the siblings has mild nephritis. The other 2 C1 deficient family members are clinically well. Evidence from this and other families suggests that deficiency of C1 components or C4 is associated with higher risk of developing a lupus-like disease than is deficiency of C2.