Disseminated cryptococcosis presenting as cellulitis with necrotizing vasculitis.

Patients with disseminated cryptococcosis infrequently present with cutaneous involvement. Skin lesions, when present, are usually multiple and polymorphous in appearance. Cellulitis caused by Cryptococcus neoformans is rare, and necrotizing vasculitis associated with cryptococcal vascular invasion has not to our knowledge been reported. We report here a case of disseminated cryptococcosis in a renal transplant recipient who had cellulitis and necrotizing vasculitis and in whom a diagnostic skin biopsy allowed for early therapy with cure and salvage of the renal allograft.     

Temporal pattern of herpes simplex virus type 1 infection and cell death in the mouse brain stem: influence of guanosine nucleoside analogues

Levels of bystander death occurring in herpes simplex virus type 1 (HSV-1)-infected mouse brain stems were studied, as well as the extent to which bystander death is influenced by guanosine nucleoside analogue treatment. Consecutive sections from brain stems of HSV-1-infected mice were stained alternately for (i) viral infection and (ii) cell death (TUNEL assay). Virus antigen was detectable in brain stems on day 3 of infection, while TUNEL staining was comparatively lower. An increase in the extent of TUNEL staining was observed on day 4 of infection. Despite this increase, however, the ratio of TUNEL-stained to infection marker-stained tissue still indicated that the amount of TUNEL staining remained lower than infection staining at this time point. On days 5 and 6 of infection, TUNEL staining continued to increase and the TUNEL/infection marker ratio switched on day 6 in favour of excess TUNEL staining, which was observed in and around the foci of infection, suggesting bystander death. The excess TUNEL staining on day 6 of infection was further increased on treatment with antivirals. The significance and implications of these results are discussed with respect to the nature and mechanism of action of the TUNEL assay, dynamics of primary HSV-1 infection, immunological influences and potential effects of antiviral treatment. The potential problems of the TUNEL assay are considered in the context of viral infection and the TUNEL assay, in combination with infection marker staining, may potentially provide a model system for quantitative analysis of true bystander death during HSV infection in vivo.     

APOE is a potential modifier gene in an autosomal dominant form of frontotemporal dementia (IBMPFD).

PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be as low as 30% for frontotemporal dementia. Modifier genes could account for decreased frontotemporal dementia penetrance. In this study apolipoprotein-E (APOE) was evaluated for this role in IBMPFD families based on its known modifier effect in Alzheimer's disease. METHODS: From a database of 231 members of 15 families, 174 had APOE genotype available for analysis. Logistic regressions on APOE genotype and frontotemporal dementia were performed, using appropriate covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for membership in pedigrees with at least one APOE 4 genotype. These data suggest a potential link between APOE 4 genotype and the specific form of frontotemporal dementia found in IBMPFD. The molecular basis of this link bears further investigation. We did not observe an association of frontotemporal dementia and H2 MAPT haplotype.     

Neuropathological and clinical correlations in hurler disease

We report studies on two patients (1 and 2) with Hurler disease. They both had all of the non-neurological features of Hurler disease to a similar and extreme degree and similar signs of brain damage on computed tomography. However, intellectual function was unusually well-preserved in patient 1, but seriously and typically impaired in patient 2. The reason for this discrepancy has been investigated by reference to the neuropathological findings, the results of -l-iduronidase assays using different substrates and comparisons to other cases (patients 3 and 4). We suggest that patient 1 is an unusual variant of the disease who may have had a very low residual -l-iduronidase activity in neuronal cells only, and that this could not be demonstrated by either enzyme assays on whole brain using the 4-methylumbelliferyliduronide substrate (Crowet al., 1983) or in studies on fibroblast lysates using a radioactive disaccharide substrate.     

AIDS knowledge and high risk behaviors in the chronic mentally ill

Chronic mentally ill adults are a high risk group for AIDS. In the present study, we used a questionnaire to assess AIDS knowledge, attitudes, and risk behaviors in 54 men and women who were clients at a drop in center for mentally ill adults. Most of the subjects were suffering from schizophrenia and about one-third of them had co-existing drug problems. Results showed widespread misunderstandings about AIDS transmission, high risk groups, and practices. Many of the subjects had been treated for STDs such as syphilis and gonorrhea and were engaging in behaviors that increased their vulnerability to AIDS. These include casual sex, anal sex, sex with an IV drug user, or sex in exchange for money, drugs, or a place to sleep. Subjects expressed a moderately high level of concern about acquiring AIDS/HIV, and 15% of those tested (5/33) said they already had the illness. We observed a significant correlation between misinformation about AIDS and the frequency of high risk behaviors. We also detected ambivalence about using condoms and IV drugs. Although males and females did not differ in AIDS knowledge or risk behaviors, the AIDS knowledge of both groups was significantly lower than a comparison sample of public high school students. Taken together, the results underscore the immediate need for comprehensive AIDS assessment, education, and prevention in this segment of the population.     

Success in Surgical Intervention for Morbid Obesity: Is Weight Loss Enough?

Varieties of gastric surgery have increasingly been used in the management of morbid obesity. Generally, however, research and commentary in this area have related to surgical technique, with weight loss or morbidity being regarded as the most important dependent measures. In the context of the publication of several papers relating to the effects of surgery in the long-term, we believe that it is timely for surgeons to examine their criteria for success. In this paper, we argue that weight loss is inadequate as a primary criterion for success in this context, and that the value of the intervention should be measured against a multidimensional concept of success.