Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study.

Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.     

Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV).

OBJECTIVES: To determine the prevalence of antibodies to hepatitis C virus (HCV) in female sexual partners of multitransfused men with hemophilia and to compare the frequency of transmission of HCV and human immunodeficiency virus (HIV). STUDY DESIGN: Cross-sectional measurement of HCV and HIV antibodies. SETTING: Ten hemophilia treatment centers. PATIENTS: A total of 234 female sexual partners of 231 multitransfused men with hemophilia. MEASUREMENTS AND MAIN RESULTS: The prevalence of antibodies to HCV (anti-HCV) among female sexual partners of HCV-positive men was 5 of 194 (2.6%). Anti-HIV prevalence among female sexual partners of HIV-positive men was 25 of 196 (12.8%). Five (3%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HCV compared with none of the 30 female sexual partners of HIV-negative/HCV-positive men. Twenty-one (13%) of the 164 female sexual partners of HIV-positive/HCV-positive men were infected with HIV compared with 4 (13%) of 32 female sexual partners of HIV-positive/HCV-indeterminate men. The co-infected men were five times more likely to transmit both viruses than would be expected by chance (P = 0.01). When a single virus was transmitted to a female sexual partner, it was more often HIV than HCV (18 of 164 compared with 2 of 164, P = 0.001; odds ratio, 8.5; 95% Cl, 2.2 to 33.1). CONCLUSIONS: The higher prevalence of HCV in female sexual partners of men with hemophilia than in blood donor and other low-risk groups suggests that there is a low level of sexual transmission. Male to female sexual transmission of HCV is less efficient than that of HIV. The frequency of HCV transmission to sexual partners is five times higher when HIV is also transmitted, suggesting that HIV may be a cofactor for the sexual transmission of HCV.     

Response to androgen therapy in patients with dyskeratosis congenita

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and telomere biology disorder characterized by dysplastic nails, reticular skin pigmentation and oral leucoplakia. Androgens are a standard therapeutic option for bone marrow failure in those patients with DC who are unable to undergo haematopoietic stem cell transplantation, but there are no systematic data on its use in those patients. We evaluated haematological response and side effects of androgen therapy in 16 patients with DC in our observational cohort study. Untreated DC patients served as controls. Seventy percent of treated DC patients had a haematological response with red blood cell and/or platelet transfusion independence. The expected age‐related decline in telomere length was noted in androgen‐treated patients. All treated DC patients had at least one significant lipid abnormality. Additional treatment‐related findings included a significant decrease in thyroid binding globulin, accelerated growth in pre‐pubertal children and splenic peliosis in two patients. Liver enzymes were elevated in both androgen‐treated and untreated patients, suggesting underlying liver involvement in DC. This study suggests that androgen therapy can be effectively used to treat bone marrow failure in DC, but that side effects need to be closely monitored.     

Sources of Uncertainty and Their Association with Medical Decision Making: Exploring Mechanisms in Fanconi Anemia

Background

Effects of different sources of medical uncertainty on people’s health-related cognitions, emotions, and decision making have yet to be systematically examined.

Purpose

The aim of this study is to examine how uncertainties arising from different sources are associated with decision making regarding stem cell transplantation in Fanconi anemia, a rare, inherited bone marrow failure syndrome that typically presents during childhood.

Methods

Data were collected through a cross-sectional survey of 178 parents of 126 Fanconi anemia patients.

Results

Two distinct sources of uncertainty were associated with decision outcomes: probability was associated with a lower likelihood of choosing stem cell transplantation, and ambiguity due to conflicting expert opinions was associated with greater decision-making difficulty. Concern about transplantation may mediate these associations.

Conclusions

Different sources of uncertainty have different effects on Fanconi anemia treatment decisions, which may be mediated by parents’ emotional reactions. Further research is needed to elucidate these effects and help Fanconi anemia families cope with uncertainty.     

Clinical and molecular features associated with biallelic mutations in FANCD1/BRCA2

Patients with biallelic mutations in BRCA2 are in Fanconi anaemia group D1. We analysed the severity of the mutations in 27 cases, classified according to their association with breast cancer in heterozygotes, and their predicted functional effect. Twenty mutations were frameshifts or truncations, three involved splice sites, five were missense variants of unknown severity and two were benign polymorphisms. Five patients had VACTERL-H association. Leukaemia was reported in 13 patients, and solid tumours in 15; 6 patients had two or more malignancies. The cumulative probability of any malignancy was 97% by age 5.2 years. IVS7+1G-->A and IVS7+2T-->G were associated with AML, and 886delGT and 6174delT with brain tumours. However, patients with other alleles remained at very high risk of these events. Missense mutations formed a distinct cluster in a highly conserved region of the BRCA2 protein. The small group of patients with biallelic mutations in BRCA2 is distinctive in the severity of the phenotype, and early onset and high rates of leukaemia and specific solid tumours, and may comprise an extreme variant of Fanconi anaemia. Several of the alleles were not associated with cancer in presumed carriers, and thus counselling presents more uncertainties than usual.     

Retroperitoneal varices simulating masses

Retroperitoneal varices in portal hypertension may simulate the appearance of neoplastic masses or adenopathy. Contrast-enhanced CT scans clarify the diagnosis of large vascular channels. Three patients with large retroperitoneal varices demonstrated on CT had confirmation by angiography.