Characterization of apoptosis in intestinal ischaemia-reperfusion injury — a light and electron microscopic study.

Intestinal ischaemia-reperfusion (IR) injury has largely been attributed to cellular necrosis. Apoptosis, a distinct form of cell death has been observed following IR to the brain, heart, adrenals and the kidneys. In order to characterize the role of apoptosis in intestinal IR, small bowel grafts were stored in saline ( n  = 6) or modified University of Wisconsin solution ( n  = 6) at 4 °C for 12 h and reperfused for 6 h in syngeneic rats. Samples of normal, stored and reperfused intestines at 1, 3 and 6 h were analysed by light and electron microscopy. Following reperfusion, there was crypt and villous epithelial apoptosis, loss of crypt and villous structures, and an increase in mucosal inflammatory cell infiltration. Ongoing apoptosis was maximum at 1 h, its degree decreasing with increasing reperfusion intervals. Large numbers of apoptotic bodies dominated the picture from 3 h of reperfusion. This study has demonstrated the induction of apoptosis by intestinal IR injury, which begins within an hour of reperfusion and is probably responsible for the observed crypt and villous loss. This has potential therapeutic implications as, opposed to necrosis, apoptosis is an active process with genetic regulators and biochemical effectors, which can be specifically targeted to prevent or alleviate IR injury.     

Binding of cardiolipin to polystyrene beads: evidence for a lamellar phase orientation

Summary. The association of cardiolipin with polystyrene beads was studied using ³¹P-NMR and electron microscopy. In the presence and absence of fetal calf serum, cardiolipin appeared to bind to the polystyrene beads in lamellar phase as assessed by ³¹P-NMR imaging. Electron microscopic analysis revealed an even coating of phospholipid about the beads with extensive micelle binding. Cardiolipin-coated beads challenged with ACA-positive sera followed by immunogold indicated antibody bound to micelles associated with the bead. Studies conducted with ACA IgG purified from patient sera indicated that some ACA bound to CL beads in the absence of a source of ACA cofactor (i.e. gelatin-blocked beads), some ACA required β₂-GPI for binding (i.e. no binding in the presence of β₂-GPI-depleted plasma), whereas other ACA which showed negliglible binding with gelatin-blocked beads, showed enhanced binding in the presence of /?₂-GPI-depleted plasma. The data indicate that: (1) cardiolipin binds to polystyrene beads in lamellar phase, (2) ACA bind to phospholipid micelles bound directly to the polystyrene beads, and (3) ACA differ between individuals displaying varying phospholipid and phospholipid/cofactor substrate specificities.     

Coronary Reperfusion Following Experimental Myocardial Infarction

Numerous studies have shown that early coronary reperfusion is feasible in the setting of evolving acute myocardial infarction in man. While early reperfusion reduces myocardial infarct size, there are potentially deleterious consequences of reperfusion. The concept of "reperfusion injury", oxygen-free radical damage, no reflow phenomenon, and stunned myocardium are discussed.     

The Nominal Group Technique: A Research Tool for General Practice?

Qualitative methods are increasingly recognized as valuable,yet practitioners face difficult decisions in their choice ofmethod and the process of analysis. The nominal group techniquecombines quantitative and qualitative data collection in a groupsetting, and avoids problems of group dynamics associated withother group methods such as brainstorming, Delphi and focusgroups. Idea generation and problem solving are combined ina structured group process, which encourages and enhances theparticipation of group members. The stages involved in conductinga nominal group are described, and practical problems of itsuse in a health care setting are discussed with reference toa study of the priorities of care of diabetic patients, carersand health professionals. Some potential applications of thetechnique in audit and exploratory research are also outlined.     

Prevalence of markers for hepatitis B virus and HIV-1 among drug injectors in London: injecting careers, positivity and risk behaviour

Concerns about the risks of HIV infection among drug injectors have eclipsed concerns about the prevalence and transmission of hepatitis, and in particular hepatitis B virus infection. Findings are reported from surveys undertaken with two separate community-recruited samples of drug injectors in London collected in 1992 (n = 505) and in 1993 (n = 507). Anonymized confirmed testing of saliva snows 51.5% of drug injectors in 1992 and 47.9% in 1993 to be antibody positive to the core antigen of hepatitis B virus (anti-HBc). Approximately half of the drug injectors confirmed as anti-HBc positive were unaware that they had been infected with hepatitis, Anti-HIV-1 prevalence was considerably lower at 7.0% in 1992 and 6.9% in 1993. Multivariate analyses showed anti-HBc positivity to be most likely among older injectors with longer injecting careers who had a history of having shared used needles and syringes. HIV-1 positivity was also associated with a history of having shared injecting equipment as well as with recent sharing (i.e. in the last 6 months). Unlike anti-HBc positivity, there were no associations between HIV-1 positivity and age or length of injecting career. Younger injectors with shorter injecting careers were more likely to report recent sharing of used injecting equipment than older injectors with longer injecting careers. We note the potential for continued transmission of HBV and HIV-1, particularly among younger injectors. We recommend an integrated strategy to maximize the health of drug injectors, of which HIV and HBV prevention is a part. There is a need to widen the availability of HBV vaccinations for HBV negative drug injectors and their sexual partners and for clear guidelines to drug injectors about the relative efficacy of bleach to disinfect injecting equipment of HBV and HIV.     

Ki-ras MUTATIONS IN ADENOMAS: A CHARACTERISTIC OF CANCER-BEARING COLORECTAL MUCOSA

Activating mutations in the Ki- ras 2 oncogene are frequently observed in sporadic colorectal adenomas and their incidence is reported to rise in large and tubulovillous adenomas to values close to those in carcinomas. This study shows that this property is a feature of adenomas growing in large bowel that has already demonstrated its propensity to engender malignant tumours: i.e., bowel in which there is a synchronous carcinoma. Adenomas from cancer-free bowel do not share this high incidence of Ki- ras mutations. This difference in mutation incidence between adenomas from cancer-free and cancer-bearing patients does not appear to derive from sampling bias relative to adenoma size, site, or patient age, nor is it found in another gene (APC) known to be of importance in adenoma formation. Large, dysplastic adenomas from cancer-bearing bowel, however, are particularly liable to carry Ki- ras mutations when they arise in patients over 70 years old. The observations suggest that the role of Ki- ras mutations may be more subtle than merely enhancing adenoma growth. Adenoma cells of cancer-prone individuals may suffer more mutational events than those in persons selected as cancer-free.