Does smoking protect from Alzheimer's disease? Alzheimer-type changes in 301 unselected brains from patients with known smoking history

The objective of this report is to investigate whether smoking exerts any influence on the number of senile plaques and Alzheimer neurofibrillary tangles. A retrospective study was based on unselected consecutive autopsy findings on the brains of 301 patients aged 65 years or older examined at the Institute of Pathology, Basel. Brains were investigated according to a fixed protocol. Histological examination was performed on 15 paraffin-embedded tissue blocks per brain using staining with silver impregnation specific for Alzheimer neurofibrillary tangles and for senile plaques, and Alzheimer-type changes were quantified. Retrospective assessment of smoking history was also based on a fixed protocol. Statistical analysis of the relationship between the smoking habits and the amount of Alzheimer-type changes was performed and included analysis of 72 age- and sex-matched smoker-nonsmoker pairs from within the total of 301 cases to compensate for variations in these changes due to age/sex alone. The influence of smoking on the total of 301 cases cannot be proven statistically. But a protective action against senile plaque formation could be demonstrated in 28 age matched pairs of smoking-nonsmoking women. Furthermore a positive correlation between the amount of smoking and the neurofibrillary changes as expressed in Braak stages in smokers of both sexes was present. Thus, there seems to be an influence of nicotine on the structural alterations of Alzheimer's disease which can exert itself in opposite directions.     

Hepatitis G virus infection in hemodialysis patients and the effects of interferon treatment

OBJECTIVE: To characterize the nature of hepatitis G virus (HGV) infections in hemodialysis patients and to determine the responsiveness of HGV to antiviral therapy in these patients. METHODS: HGV, a recently identified flavivirus, is associated with non-A-E viral hepatitis infections. We studied HGV infections in hepatitis C virus (HCV)-infected hemodialysis patients over a 1-yr period, using two independent PCR assays and nucleic acid sequencing. Thirty-four of 63 study patients were treated with interferon. RESULTS: We observed a 27% prevalence (17/63 patients) and a 4% annual incidence of HGV infections in the study population. HGV was not detected in any of the 10 HGV-infected patients immediately after interferon therapy. Although seven of these 10 patients developed HGV relapses, three had long-term responses. The interferon responsiveness of HGV and HCV appeared to be unrelated. In contrast, all seven untreated HGV-infected patients remained viremic. Sequence analyses of the different HGV isolates revealed only very limited genetic variability in the polymerase chain reaction-amplified regions of HGV during 1 yr of observation. CONCLUSIONS: Our data suggest that HCV-infected hemodialysis patients are at substantial risk of acquiring HGV infection and that HGV infections are prevalent in this population. In addition, HGV infections become chronic but are responsive to interferon treatment.     

Metallothionein and Fas (CD95) are expressed in squamous cell carcinoma of the tongue

Metallothionein (MT) is a chelator present in myoepithelial cells, whilst the Fas-receptor (APO-1, CD95) has been described primarily in human T Jurkat cells. 20 cases of carcinoma of the tongue were investigated immunocytochemically with regard to MT, Fas and Bcl-2. In normal oral squamous epithelium, MT is located in the basal/parabasal dividing cells only. In well-differentiated nests of carcinomas, MT is observed almost entirely in peripherally located cells. In situ end-labelling indicates apoptosis in the centre of these nests, but not in the peripheral areas. Less-differentiated areas show more general MT-positivity, but little apoptosis. All 24 tumours are Fas-positive, but normal epithelia are mainly negative (P < 0.0001). Bcl-2 protein was sparse in the tumours compared with MT and Fas (P < 0.0001). We thus suggest that MT, possibly due to its chelating properties, may contribute to delaying cells entering apoptosis, both in normal epithelium near the base and in less-differentiated regions of carcinoma. Moreover, Fas may be present in cells of human malignancies, as well as those of established malignant cell lines.     

Targeting acetylcholinesterase molecules to the neuromuscular synapse

The functional integrity of the neuromuscular synapse requires that sufficient numbers of acetylcholinesterase (AChE) molecules be localized on the specialized extracellular matrix between the nerve terminal and the post-synaptic membrane. Multiple interrelated levels of regulation are necessary to accomplish this complex task including the spatial and temporal restriction of AChE mRNA expression within the muscle fiber, local translation and assembly of AChE polypeptides, and focused accumulation of AChE molecules on the extracellular matrix. This is accomplished in part through the organization of other extracellular matrix molecules into a complex which further associates with acetylcholine receptors and their accompanying molecules. Finally, the mature neuromuscular junction contains molecules which can act as receptors for the attachment of AChE which in turn may allow for the turnover of this enzyme at the synapse. This brief review will focus mainly on contributions from our laboratory towards understanding the mechanisms involved in organizing AChE molecules at the neuromuscular synapse.     

Angiotensin II mediates systemic rebound hypertension after cessation of prostacyclin infusion in sheep

Prostacyclin (or epoprostenol), an arachidonic acid metabolite, is an effective treatment for patients with primary pulmonary hypertension. Interruption of chronic prostacyclin infusion can result in recurrent symptoms of dyspnea and fatigue. The etiology of this phenomenon is unknown. We hypothesized that sympathoadrenal activation could lead to increased vascular tone after abrupt termination of the infusion. To evaluate this effect, we monitored six chronically instrumented, awake sheep during and after infusion of prostacyclin. Prostacyclin decreased mean arterial pressure (MAP) by 14% and increased cardiac output by 33%. After the infusion ceased, MAP rebounded 23% above baseline, and cardiac output decreased by 28% from peak values within 10 min. We were unable to demonstrate an increase in norepinephrine levels after cessation of prostacyclin, nor did alpha-adrenergic blockade affect postinfusion hemodynamics. However, plasma renin activity increased >10-fold at peak infusion and remained elevated for up to 2 h after discontinuation of prostacyclin. Coinfusion of the angiotensin II-receptor antagonist L-158,809 resulted in complete abrogation of the postcessation rise in MAP. We conclude that renin-angiotensin system activation is primarily responsible for systemic hypertension occurring after abrupt cessation of prostacyclin infusion in sheep and that angiotensin II receptor blockade prevents this response. Our data do not support a role for sympathetic nervous system activation in the systemic pressor response after prostacyclin infusion.     

Enterocutaneous fistulas: an unusual solution

Enterocutaneous fistulas are not a minor problem in gastrointestinal tract surgery. Significant reduction of mortality and morbidity has been attained but they still remain high. The authors report three clinical cases in which they sealed and treated enterocutaneous, chronic, iatrogenic fistulas by injecting biological glue (N-Butil 2-Cyanoacrylate-Histoacryl) into the internal opening and fistulous tract. We believe that the technic we propose here, in the proper setting, may be an important contribution to the management of iatrogenic (postoperative) enterocutaneous fistulas.     

Coincident DiGeorge anomaly and renal agenesis and its relation to maternal diabetes

We describe 2 cases of DiGeorge anomaly with bilateral renal agenesis-one, who also had hemivertebrae, in an infant of an insulin-dependent diabetic mother (IDDM). In a review we identified 2 other instances of this combination, both in IDDMs. The currently accepted notion that DiGeorge anomaly and renal agenesis are developmental field defects, coupled with their coincidence in IDDM, suggests that this combination is an association.