A histopathological study of the effects of intravenously administered lambda carrageenan in the mouse, with particular reference to the macrophage system

Intravenously administered lambda-carrageenan rapidly precipitates in the marginal zone of the spleen, the hepatic sinuses and the capillaries of the heart, lung, kidney and adrenal gland. Extensive coagulative necrosis of the liver and myocardium is seen at 24 h. Phagocytosis occurs at 3 days, and is associated with transformation of the lymphocytes of the splenic white pulp. Circulating carrageenan-containing macrophages adhere to vascular endothelium in the lung and at 6 days are situated beneath it. At 30 days carrageenan granulomas have formed in the spleen and liver, probably as a result of macrophage recirculation.     

Serum and tissue autoantibodies to colonic epithelium in ulcerative colitis

Sera and colonic tissue-bound immunoglobulin extracts from patients with ulcerative colitis and disease controls were examined immunohistochemically and by killer cell cytotoxicity assay for the presence of anticolonic epithelial autoantibodies. IgG yields in the tissue extracts from patients with colitis and control subjects were similar, and the extracts were uniformly autoantibody negative. Of 41 sera from patients with inflammatory bowel disease, 'classical' anticolon antibody was present in 41% and was commoner in patients with sclerosing cholangitis. Cytotoxic anticolon antibody was present in 20% overall and was strongly associated with disease activity; it did not correlate with the presence of 'classical' anticolon antibody. The heterogeneous and non-universal antiepithelial autoantibody response and the failure to detect tissue bound autoantibody in vivo argue against the hypothesis that humoral autoimmunity is of major importance in the pathogenesis of ulcerative colitis.     

Use of bi-level biotinylation for concurrent measurement of in vivo recovery and survival in two rabbit platelet populations

BACKGROUND: The objectives of this research were 1) to determine whether two populations of platelets may be labeled with different levels of biotin and followed concurrently in vivo by flow cytometry and 2) to determine whether the level of biotinylation affects the in vivo platelet recovery and survival. STUDY DESIGN AND METHODS: Two platelet aliquots were biotinylated under conditions that resulted in either a lower or a higher number of biotin molecules per platelet. After transfusion, the two populations were distinguished and quantitated by flow cytometry. RESULTS: In five animals, recoveries were 69.8 +/− 27.0 percent for low-biotin platelets and 72.6 +/− 26.7 percent for high-biotin platelets. For each animal, the recoveries agreed closely. Life span, determined by the multiple-hit method, was 2.68 +/− 0.63 days for low-biotin platelets and 2.58 +/− 0.69 days for high-biotin platelets. These values for recovery and life span are consistent with those measured in rabbits by using radioisotope labels. CONCLUSION: Platelet biotinylation offers a nonisotopic method for direct comparison of alternative harvest and storage conditions. It also offers the potential for simultaneous evaluation of the in vivo characteristics of platelets from at least two donors.     

Childhood diabetes: parents' experience of home management and the first year following diagnosis.

AIMS: To explore parents' experience of having a child diagnosed with Type 1 diabetes, managed at home, and their first year following diagnosis. METHODS: A qualitative, longitudinal study based on 40 in-depth interviews with parents of 20 children with newly diagnosed Type 1 diabetes managed at home from diagnosis in South Wales. RESULTS: Many parents were alarmed by the speed of diagnosis following the gradual progress of their child's symptoms. The provision of timely, adequate information was important to all parents. Although five parents had initial concerns about going home, all parents were subsequently pleased their children had not been hospitalized. Home management enabled parents to integrate diabetes management into the family's normal lifestyle from diagnosis. Professional support, particularly accessible telephone advice, was valued by and reassured parents. Parents experienced a loss of spontaneity, a continuing fear of hypoglycaemia and did not want their child to feel different to other children. Acutely aware of the seriousness of diabetes, they did their utmost to achieve optimal glycaemic control but felt that diabetes could not 'dominate' if they were to lead a 'normal' life. CONCLUSIONS: The experience of parents in this study suggests that parents of children with newly diagnosed diabetes are able to cope successfully when given the opportunity to start treatment at home. Therefore, if children with diabetes are clinically well at diagnosis, this study supports home management as a system of care from the parents' point of view. These findings are relevant to clinicians, policy makers and health service managers involved in planning and providing paediatric diabetes care.     

Recent advances in diagnosis of the childhood muscular dystrophies

Abstract: Recent advances in molecular genetics research have revolutionised our understanding of the childhood muscular dystrophies. The first breakthrough came in 1987 with the identification of the gene for dystrophin, the protein that is abnormal in X-linked Duchenne muscular dystrophy. Dystrophin is bound to a complex of proteins in the muscle membrane, and primary abnormalities of these protein have now been identified as the cause of some autosomally inherited forms of muscular dystrophy. A group of transmembrane proteins known as α- (adhalin) β-, γ- and δ-sarcoglycan are deficient in autosomal recessive limb-girdle muscular dystrophy, and the extracellular matrix protein merosin (α2-laminin), is deficient in a subset of patients with congenital muscular dystrophy. Identification of primary deficiencies in these 'dystrophin associated proteins' will result in improved diagnostic accuracy, more accurate genetic counselling and, in some cases, the availability of prenatal diagnosis.     

An investigation into in vitro methods for the detection of chlorhexidine resistance

During an outbreak of catheter-related urinary tract infection, due to Proteus mirabilis, it was suggested that the epidemic strain was resistant to chlorhexidine. In this study, the minimum inhibitory concentrations (MICs) of chlorhexidine to the epidemic Pr. mirabilis and other laboratory isolates were tested in different media. Results were compared with killing times using 1/4 strength Ringers solution, normal human urine and the in vivo killing times in two patients' catheter bags. It was found that the MIC test was unreliable in the assessment of chlorhexidine resistance as it was dependent on the medium used, the inoculum size, and the age of the culture. The test which gave results closest to the in vivo experiments was the killing curve in normal human urine. It is concluded that chlorhexidine resistance is a complex phenomenon which is difficult to evaluate. If in vitro tests are to be used to evaluate the clinical relevance of reduced sensitivity to chlorhexidine, they must mimic the in-use conditions as closely as possible.     

Progressive external ophthalmoplegia. Evidence for a generalised mitochondrial disease with a defect in pyruvate metabolism.

Muscle biopsies from four patients with chronic progressive external ophthalmoplegia and pigmentary retinopathy with symptoms and signs from other organs were studied by means of light and electron microscopy. Examination revealed a marked proliferation of abnormal mitochondria with a degeneration of both muscle and nerve tissue. Blood levels of lactate and pyruvate were measured and abnormal values of these metabolites were found in the three patients with the most pronounced ultrastructural changes. On the basis of these findings it is suggested that there is a biochemical defect in pyruvate-lactate metabolism which could be responsible for the marked proliferation of the abnormal mitochondria.