Turcot syndrome confirmed with molecular analysis

Turcot syndrome is clinically characterized by the occurrence of primary brain tumor and colorectal tumor and has, in previous reports, been shown associated with germline mutations in the genes APC , MLH1 , MHS6 , and PMS2 . To date, only few families have been documented by molecular analysis. We report two new families with Turcot syndrome to illustrate and review its characteristics and facilitate diagnosis. Molecular analysis revealed two germline mutations, one in the MLH1 gene and one in MSH2 . The latter has never been describe in the literature. Personal and familial relevant anamnestic data from patients with glioma might aid in the diagnosis of genetic disorders. The subsequent molecular characterization may contribute to the appropriate care of affected patients and asymptomatic gene carriers.     

Evaluation of a new magnetic resonance imaging method for quantitating adipose tissue areas

We have developed a new magnetic resonance imaging (MRI) protocol to quantitate intraabdominal and subcutaneous fat and have validated it by comparing measurements of fat areas by MRI with those obtained by computed tomography (CT) in 11 asymptomatic volunteers who all had a single CT and MRI image taken at the level of the umbilicus. The new MRI protocol was based on a water-fat separation method by which the slice selection routines excite water and fat protons in different positions along the slice select direction. This method performed more reliably than earlier methods based on phase differences between water and fat signals. Fat areas measured by MRI exceeded those measured by CT by 8-22 percent, and fat areas and ratios obtained by MRI correlated well with CT (r = 0.98 for areas and, for ratios, r = 0.81). The ratio of intraabdominal/subcutaneous fat measured by MRI in seven males was significantly greater than that in four females. We also compared the new method with a previously published inversion recovery (IR) method in seven additional volunteers. Agreement between the two methods was excellent, and the major differences were technical: the IR protocol produced images that may require custom image processing programs when obtained on some scanners. Comparability of the two methods provides further reassurance of the validity of both. MRI presents an attractive opportunity for directly measuring intraabdominal fat in order to correlate this with metabolic parameters and to visualize changes during weight loss.     

Early facial reanimation following radical parotid and temporal bone tumor resections

A retrospective study of 35 patients who underwent early facial reanimation following extirpative parotid and temporal bone surgery requiring facial nerve sacrifice was performed. Regional facial reanimation performed immediately or within several days included 16 patients who underwent temporalis muscle transposition and 27 who underwent gold weight or eyespring lid reanimation with lower lid tightening. Simultaneous nerve grafts or nerve crossover procedures were performed in 22 patients. The authors' favored approaches to facial reanimation are discussed, with an emphasis on the value of early reanimation using properly selected techniques.     

AIDS virus infection and autoimmunity: a perspective of the clinical, immunological, and molecular origins of the autoallergic pathologies associated with HIV disease

The acquired immune deficiency syndrome (AIDS) is a viral-induced disorder of humans that is reaching pandemic proportions. The etiologic agent responsible for AIDS is recognized as a retrovirus termed the human immunodeficiency virus (HIV). This virus is both cytotropic and cytopathic for T lymphocytes in vitro, and patients with AIDS and HIV-related conditions invariably have serious T cell abnormalities, notably a reduced number of the helper/inducer (CD4+) subpopulation. There is now a substantial body of evidence to suggest that the AIDS virus triggers a diverse range of autoimmune phenomena. The purpose of this article is to summarize the clinical and immunopathological manifestations of autoimmunity in HIV infection and to provide a perspective of the possible origins and roles autoimmune reactions play in HIV disease progression.     

The use of monoclonal antibodies against primary myeloid granules in normal and leukemic cells.

Three monoclonal antibodies, K101, D46, and H36/71 (CD15), reactive with membrane components of primary granules of human promyelocytes, were studied to assess their binding to normal and leukemic cells. Using the alkaline phosphatase antialkaline phosphatase technique, these antibodies were applied to sections of normal organs and to peripheral blood and bone marrow films from hematologically normal individuals and patients with hematologic malignancies. In control experiments, antibodies showed reactivity with cytoplasmic constituents of granulocytes from the promyelocytic to the neutrophilic stage. In acute myeloid leukemia, antibody K101 was positive (more than 20% of blasts) in 13 of 21 (62%) cases, while antibody D46 was positive in 11 of 17 (65%) cases. Antibody H36/71 was positive in only 4 of 24 (17%) cases of acute myeloid leukemia. At least one marker was present in 6 of 8 (75%) cases of acute lymphoblastic leukemia with myeloid antigen-positive blasts and was negative in 20 cases of acute lymphoblastic leukemia with myeloid antigen-negative blasts. These results support the view that abnormal granules (with defective expression of the D46, K101, and H36/71 antigens) form in blastic and leukemic cells of patients with acute myeloid leukemia. Data also suggest that membrane components of myeloid granules are made in the cytoplasm of cells from some acute lymphoblastic leukemia patients with myeloid antigen-positive blasts.     

Testing for BRCA1 mutations: a cost-effectiveness analysis

Breast carcinoma is the most common type of cancer affecting women in the Western world. The hereditary forms, which amount from 5 to 10% of all the cases of breast cancer, mainly involve BRCA1 or BRCA2 mutations. Due to the diagnostic strategy used by the patent owner, Direct DNA sequencing (DS) may become the only BRCA1/2 test procedure available, although there exist several alternative strategies. A cost-effectiveness study was carried out using BRCA1 testing as a model. The main techniques available for performing mutation searches were assessed: DS, denaturing high performance liquid chromatography (DHPLC), single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), heteroduplex analysis (HA), fluorescent assisted mismatch analysis (FAMA) and the protein truncation test (PTT). Twenty strategies involving the use of one or more techniques were then devised for performing the complete genetic analysis. DS was adopted as the 'gold standard' for effectiveness. All the strategies except for DS involved a two-step procedure. The first step consisted of pre-screening the 22 coding exons of BRCA1. The second step consisted of performing DS only on the variations detected in the coding sequence. The cost of the strategies tested, including a pre-screening stage, turned out to be 30 to 90% lower than that of DS, whatever annual use was made of the equipment. The most cost-effective strategy, ie, that corresponding to the lowest cost per mutation detected, was found to be a combination between PTT on exon 11 (60% of the coding sequence) and HA on the remaining 21 exons (PTT(11)+ HA(21)). However, since a high false negative rate is associated with this strategy, at least four other strategies are worth mentioning: PTT(11)+ DHPLC(21), DHPLC alone, FAMA(11)+ DHPLC(21) and FAMA alone. Our results on genetic testing for breast cancer show that DS is not the most cost-effective method available. The monopolist approach of the firm which owns the patents on the BRCA1/2 genes, may, therefore limit the use of the most cost-effective strategies.     

Psychoactive drug use among practicing physicians and medical students

We surveyed random samples of 500 practicing physicians and 504 medical students in a New England state during 1984-1985; 70 percent of the physicians and 79 percent of the students responded. Fifty-nine percent of the physicians and 78 percent of the students reported that they had used psychoactive drugs at some time in their lives. In both groups, recreational use most often involved marijuana and cocaine, and self-treatment most often involved tranquilizers and opiates. In the previous year, 25 percent of the physicians had treated themselves with a psychoactive drug, and 10 percent had used one recreationally. Although most of the use was experimental or infrequent, 10 percent of the physicians reported current regular drug use (once a month or more often) and 3 percent had histories of drug dependence. More physicians and medical students had used psychoactive drugs at some time than had comparable samples of pharmacists and pharmacy students. The results suggest a need for renewed professional education about the risks of drug misuse.     

Antigenic and immunologic characterization of an allogeneic colon carcinoma vaccine

In the present prospective, census-based study we have investigated the prevalence of organ-specific and non-organ-specific autoantibodies (AAb) in 152 unselected Cameroonians aged 60 years and older living in the community. AAb were detected in 49% of the participants. Non-organ-specific AAb (47%) predominated over organ-specific AAb (7%). Anti-TPO, anti-Tm, anti-Tg and anti-PC AAb were completely absent. RF was the most frequent AAb, being found in 57 (38%) cases. The prevalences of anti-SMA and RF were significantly higher in women than in men (respectively, P=0.023 and P=0.016). Higher serum concentrations of gammaglobulins were accompanied by a higher prevalence of RF (P < 0.0001) and a lower prevalence of ANA (P=0.036). The overall prevalence of AAb was higher in the filaria-infected (60%) compared to the non-infected (42%) participants (P=0.046). There was no significant influence of the vitamin D status, number of pregnancies, physical activity or medication use on the prevalence of AAb. In this study a heterogeneous pattern for the presence of the various AAb was found. Some AAb, which are commonly encountered in other studies on elderly subjects, were completely absent in this population. This diversified pattern of AAb prevalence therefore argues in favour of exogenous influences in the occurrence of AAb in elderly populations.