Anin vitro electrophysiological study of the colon from patients with idiopathic chronic constipation

Preparations of the circular muscle layer from the sigmoid colon resected from patients with idiopathic chronic constipation were compared, at an electrophysiological level using the sucrose-gap technique, with preparations of the same region of the intestine resected from patients with rectal carcinoma. Non-adrenergic, non-cholinergic inhibitory neuromuscular transmission, represented by inhibitory junction potentials, was present in preparations from both groups. However, the inhibitory response in preparations from constipated patients had a slower or longer time-course than in those from cancer patients. Also, rebound activity following inhibitory transmission was observed in 34% of preparations from constipated patients but was observed in 67% of preparations from cancer patients. Preparations from both groups displayed the same patterns of spontaneous activity and the same proportion of each group was quiescent. The threshold for generation of action potentials and the passive resistance of the smooth muscle membrane were the same in both groups. However, quiescent preparations from constipated patients were less likely to discharge trains of action potentials when the smooth muscle membrane was depolarized than were preparations from cancer patients. These changes in transmission processes and excitability in tissue from constipated patients are discussed in relation to altered states of colonic motility found in people with idiopathic chronic constipation.     

Genetic services for men: the preferences of men with a family history of prostate cancer.

PURPOSE: Men have a lower uptake of genetic services than women; however, the specific needs and preferences of men at risk of genetic conditions other than hereditary breast ovarian cancer are not known. We ascertain the information preferences of men with a family history of prostate cancer. METHODS: Unaffected men and their partners were administered a written questionnaire. RESULTS: Responses were received from 280 men (response rate: 59.2%) and 174 partners (response rate: 74%). Most men (59.6%) reported having insufficient information about their risk and wanted further information about personal risk (93.2%) and risk management (93.6%). Strikingly, 56.3% preferred to receive information related only to positive outcomes. Urologists were the preferred source of information, but there was considerable interest in a multidisciplinary service approach significantly associated with the number of affected relatives (odds ratio = 1.94, P < .002). Partners' level of concern was not associated with interest in multidisciplinary services, satisfaction with information, or support received. CONCLUSIONS: Delivering services to men at risk will require a multifaceted approach by primary care providers and specialists. Challenges include meeting men's expectations in the face of uncertain medical knowledge, engaging those at high risk in multidisciplinary services, and delivering tailored information to those at lower risk.     

Brain dysfunction in social drinkers

Thirty-four social drinkers who had referred themselves to the Regional Brain Damage Unit for assessment of the effects of drinking alcohol were compared with 42 volunteer control subjects of equivalent age but with low alcohol intake, using two 'learning' tests — the Rey Auditory Verbal Learning Test (RAVLT) and the Austin Button Maze. The Maze Test gave no evidence of disorder, but the two groups were significantly different on the RAVLT. No abnormalities in standard cognitive tests were apparent. These results suggest that a deficit in learning ability may be an early feature of the brain dysfunction associated with excessive alcohol consumption.     

Acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system.

BACKGROUND: A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. METHODS: Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for alphavbeta3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). RESULTS: Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of alphavbeta3 (1.9-fold, p < 0.001), tissue factor (1.8-fold, p < 0.001), and EMMPRIN (1.5-fold, p < 0.001). All patients in the AVR group received plasmapheresis; 11 of 14 patients had evidence of ischemic necrosis on biopsy specimens, and 3 of 14 patients experienced hemodynamic compromise and graft dysfunction and died within 3 weeks of transplant. Another patient died at 10 months after transplant. CONCLUSIONS: Acute vascular rejection is associated with up-regulation of alphavbeta3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.     

A phase I study of a new 5HT3-receptor antagonist,BRL43694A,an agent for the prevention of chemotherapy-induced nausea and vomiting

Summary In a phase I study of BRL43694A, a 5HT₃-receptor antagonist, a single dose of 40 g/kg was given to 24 patients. All patients received cytostatic treatment expected to cause nausea and vomiting. During the first 24 h, 12 patients were completely protected from nausea and vomiting, 4 experienced nausea and 8 had moderate vomiting; mild headache occurred in 10 patients. No cardiovascular (including ECG) changes took place. Apart from headache, no neurological side effects occurred.Supported by a grant from the National Cancer Association of South Africa     

Associations between MHC class I and susceptibility to HIV-2 disease progression

OBJECTIVES: Human immunodeficiency virus type 2 (HIV-2) progression to disease is significantly slower than that of human immunodeficiency virus type 1 (HIV-1). Genetic determinants for susceptibility to disease progression were hypothesized to play a more significant role in this infection compared with HIV-1. We sought to identify common human lymphocyte antigen (HLA) alleles in the Senegalese population and to compare HLA profiles between HIV-2-infected individuals with low and high risk for disease progression. STUDY DESIGN/METHODS: We conducted a case-control study investigating possible associations between MHC class I genes and the risk of disease progression in HIV-2-infected individuals. The MHC class I genotype was molecularly defined using polymerase chain reaction with sequence specific primers (PCR-SSP) in 62 female sex workers from the Dakar, Senegal cohort. Lack of antibodies to the HIV-2 antigen p26 has been previously shown to predict disease progression and was used in this study as a surrogate marker. Twenty-one cases were identified lacking antibodies to p26, therefore at a higher risk of disease progression, and were compared with 41 p26 antibody-positive, randomly selected controls. RESULTS: Statistical analysis showed that HLA B35 was significantly associated with lack of p26 antibodies, and higher risk of disease progression ( < 0.05). The same association was found for the self-defined class I haplotypes B35-Cw4 and A23-Cw 7 ( < 0.05). The HLA B 53 allele was associated with slower disease progression; however, this association was not statistically significant. We observed a trend whereby heterozygotes were at lower risk for HIV-2 disease progression, as previously reported in HIV-1 disease. CONCLUSIONS: In this West African population, a distinct profile of HLA class I alleles was observed, and many of these appear to influence disease progression in HIV-2 infection.     

Natural killer cells and reproductive failure--theory, practice and prejudice

The relationship between peripheral blood natural killer (NK) cells and reproductive failure is one of the most controversial areas in reproductive medicine. Amidst much publicity, peripheral blood NK cell testing is being promoted as a useful diagnostic test to guide the initiation of a variety of immunosuppressive therapies amongst patients with either recurrent miscarriage or infertility. We contend (i) that at present there is no scientific basis for the introduction of NK cell testing into routine clinical practice, and (ii) that the use of immunosuppressant agents based on the results of such testing may potentially be harmful.     

Patterns of upper gastrointestinal diseases based on endoscopy in the period 1998-2001

Upper gastrointestinal complaints are common in Kenya. Though these have remained unchanged over the last 20 years, the pattern of upper gastrointestinal disease on endoscopic examination seems to be changing. There appears to be progressive increase in oesophagitis and cancer of the stomach. Peptic ulcer disease has remained stable while Cancer of the oesophagus is still common. The paper intends to report on endoscopic findings at the Centre for Clinical Research, Kenya Medical Research Institute (KEMRI) over the period October 1998 and May 2001. The sources of information are records made at the time of endoscopy and histology reports on biopsies taken. Seven hundred and sixty eight patients were endoscoped. The male to female ratio was 1.7:1 with mean age +/-SD of 40.8 +/-20.1 years and age range was 3 to 96 years. Majority of the patients had abnormal findings with gastritis being the most common ( 25.8%). It is concluded that gastritis is an important cause of morbidity in Kenya. Oesophagitis, mainly due to gastroesophageal reflux disease, seems to be on the increase. Gastric cancer is not as rare as previously thought and peptic ulcer disease is still common.