Colonic Motility in Profoundly Disabled People: A comparison of massage and laxative therapy in the management of constipation

This pilot study compared abdominal massage with laxative treatment in the management of constipation in 32 profoundly disabled, institutionalised adults. A randomised cross-over design was used. After an initial 16-day baseline measurement phase without any treatment, there followed two seven-week treatment phases separated by a one-week washout period. Each subject received seven weeks of massage and seven weeks on his or her previous laxative regimen. Primary outcome measures were gastro-intestinal and segmental transit times, measured at the end of the baseline phase and of each treatment phase. Secondary measures included stool frequency, size and consistency, the requirement for enemas and an assessment of patient well-being.The median value of total colonic transit time was 183 hours for the baseline phase and 159 hours for all treatment phases. There was no evidence of any statistically significant treatment differences between laxative and massage therapy for right, left or rectosigmoid segments either separately or in total. Analysis of secondary outcome measures also failed to find any treatment preferences.These results reveal the grossly abnormal colonic transit times of the study population at all times. The effects of laxative and massage therapy within this environment were not demonstrably different.     

Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.

Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.     

Multidisciplinary teaching in a formal medical ethics course for clinical students

A successful feature of the 4th-year curriculum in the Medical Faculty of the Queen's University, Belfast has been the development of interdisciplinary teaching in a three-week joint course to which several clinical departments contribute...Co-ordinated teaching of topics of common interest in small groups included, until the academic year 1987/88, a three-hour session on medical ethics. In the spring of 1987 the authors approached the Department of Philosophy at Queen's; subsequently proposals for a formal multidiscipinary course in medical ethics for 4th-year clinical students in the Medical Faculty, for the academic year 1987/88, were approved by the Education Committee of the Medical Faculty.     

Measurement of human and mouse anti-tetanus antibodies and isotype analysis by ELISA

A rapid and sensitive enzyme immunoassay (ELISA) was developed for the quantitation of anti-tetanus antibodies. This technique was used to measure antibody levels in the plasma of immunized donors, in human anti-tetanus IgG preparations and in human and mouse hybridomas producing monoclonal antibodies to tetanus toxoid. The assay was capable of detecting antibody levels as low as 5 X 10(-4) IU/ml. By inclusion of an extra step involving antibodies to mouse Ig isotypes, a sandwich enzyme immunoassay (SEI) was developed which permitted determination of the Ig isotype of mouse anti-tetanus antibodies including tetanus-specific mouse monoclonal antibodies. SEI confirmed Protein A-Sepharose fractionation of mouse ascites fluid containing anti-tetanus antibody. The tetanus toxoid-coated plates have a shelf life of at least 1 year.     

Cryptococcal glucuronoxylomannan inhibits adhesion of neutrophils to stimulated endothelium in vitro by affecting both neutrophils and endothelial cells

Cryptococcal infections are often characterized by a paucity of leukocytes in the infected tissues. Previous research has shown that the capsular polysaccharide glucuronoxylomannan (GXM) inhibits leukocyte migration. In this study we investigated whether the capsular polysaccharide GXM affects the migration of neutrophils (polymorphonuclear leukocytes [PMN]) through the endothelium by interfering with adhesion in a static adhesion model. Pretreatment of PMN with GXM inhibited PMN adhesion to tumor necrosis factor alpha (TNF-alpha)-stimulated endothelium up to 44%. Treatment of TNF-alpha-stimulated endothelium with GXM led to a 27% decrease in PMN adhesion. GXM treatment of both PMN and endothelium did not have an additive inhibitory effect. We demonstrated that GXM-induced L-selectin shedding does not play an important role in the detected inhibition of adhesion. L-selectin was still present on PMN in sufficient amounts after GXM treatment, since it could be further inhibited by blocking antibodies. Furthermore, blocking of GXM-related L-selectin shedding did not abolish the GXM-related inhibition of adhesion. GXM most likely exerts its effect on PMN by interfering with E-selectin-mediated binding. The use of blocking monoclonal antibodies against E-selectin, which was shown to decrease adhesion in the absence of GXM, did not cause additive inhibition of PMN adhesion after GXM pretreatment. The use of blocking antibodies also demonstrated that the inhibiting effect found after GXM treatment of endothelium probably involves interference with both intercellular adhesion molecule-1 and E-selectin binding.     

Detection of antibodies specific to an antigenic cell wall galactomannoprotein for serodiagnosis of Aspergillus fumigatus aspergillosis

Aspergilloma and invasive aspergillosis are important opportunistic infections caused by Aspergillus species, among which Aspergillus fumigatus is the most common species associated with human disease. We developed an enzyme-linked immunosorbent assay (ELISA)-based antibody assay with Afmp1p, a purified recombinant antigenic cell wall galactomannoprotein of A. fumigatus. Evaluation of the test with guinea pig sera against A. fumigatus and other pathogenic fungi indicated that this assay was specific for A. fumigatus. Clinical evaluation revealed that the assay was 100% sensitive for patients with aspergilloma and 33.3% sensitive for patients with invasive aspergillosis. No false-positive results were found for serum samples from 80 healthy blood donors, 6 patients with typhoid fever, 4 patients with melioidosis, 20 patients with penicilliosis marneffei, 5 patients with candidiasis, and 4 patients with cryptococcosis, indicating a high specificity of the test. Thus, this ELISA-based test for the detection of anti-Afmp1p antibody can be of significant value as a diagnostic for aspergillosis.     

A rapid method of genomic array analysis of scaffold/matrix attachment regions (S/MARs) identifies a 2.5-Mb region of enhanced scaffold/matrix attachment at a human neocentromere

Human neocentromeres are fully functional centromeres that arise at previously noncentromeric regions of the genome. We have tested a rapid procedure of genomic array analysis of chromosome scaffold/matrix attachment regions (S/MARs), involving the isolation of S/MAR DNA and hybridization of this DNA to a genomic BAC/PAC array. Using this procedure, we have defined a 2.5-Mb domain of S/MAR-enriched chromatin that fully encompasses a previously mapped centromere protein-A (CENP-A)-associated domain at a human neocentromere. We have independently verified this procedure using a previously established fluorescence in situ hybridization method on salt-treated metaphase chromosomes. In silico sequence analysis of the S/MAR-enriched and surrounding regions has revealed no outstanding sequence-related predisposition. This study defines the S/MAR-enriched domain of a higher eukaryotic centromere and provides a method that has broad application for the mapping of S/MAR attachment sites over large genomic regions or throughout a genome.     

Length polymorphisms in tRNA intergenic spacers detected by using the polymerase chain reaction can distinguish streptococcal strains and species.

Intergenic tRNA spacers from strains of streptococcal groups A, B, and G were amplified by using the polymerase chain reaction (PCR) at low stringency with consensus tRNA gene primers. Cloning and sequencing showed that many of the homologous intergenic spacers differed in length between species. The sequences of the tRNA genes that flank these polymorphic spacers were determined and used to synthesize fully complementary primers. With these primers at high stringency, PCR products which varied in lengths from 53 to 71 bp, depending on the species or strain, were obtained from streptococcal DNAs, even in the presence of a 1,000-fold mass excess of human DNA. PCR products, the lengths of which could also be used for classification, were obtained at high stringency from a few genera closely related to Streptococcus. No products were obtained from genomic DNAs from more distantly related genera. Production of species- or strain-specific tRNA intergenic length polymorphisms with primers that generate characteristic products from a variety of species within the same genus should be applicable to many organisms, including those that would otherwise be difficult to culture or identify.     

A Cross-cultural Investigation of the Factors and Biases Involved in the Allocation of Scarce Medical Resources

In this study Spanish and English lay participants were given minimal demographic information regarding 16 hypothetical patients, and were required to rank them in order of priority for a kidney dialysis machine. The patients differed in terms of their gender, smoking behaviour, political affiliation and place of birth. These factors were combined factorially, so that each of the 16 patients presented a unique combination of attributes. The English sample showed a preference for local, female, non-smoking patients. The results for the Spanish sample were similar with respect to place of birth and gender, but smoking behaviour was not significant. Neither sample demonstrated a preference on the basis of political affiliation. The results suggest that certain demographic factors may bias the decision making of individuals or committees involved in the allocation of scarce medical resources.     

Vitamin A deficiency and the acute phase response among HIV-1-infected and -uninfected women in Kenya

Among HIV-1-infected individuals, vitamin A deficiency has been associated with faster disease progression and greater infectivity in observational studies, but randomized clinical trials have shown no effect of vitamin A supplementation. We conducted a cross-sectional study of 400 HIV-1-infected and 200 HIV-1-uninfected women in Mombasa, Kenya to examine the relations between vitamin A deficiency (serum retinol <30 microg/dL) and HIV-1 status, HIV-1 disease stage, and the acute phase response (serum C-reactive protein >or=10 mg/L and/or alpha1-acid glycoprotein >or=1.2 g/L). Among the HIV-1-infected women, the effect of vitamin A supplementation was examined in a randomized trial. Vitamin A deficiency was independently associated with HIV-1 infection (OR = 2.7, 95% CI: 1.9-4.0) and the acute phase response (OR = 2.8, 95% CI: 1.9-4.1). Among HIV-1-infected women, vitamin A deficiency and the acute phase response were associated with each other and were both independently associated with higher HIV-1 plasma viral load and lower CD4 count. HIV-1-infected women having an acute phase response had no increase in serum vitamin A levels after supplementation. Serum levels increased significantly among women without an acute phase response, although not to normal levels among women who were deficient at baseline. Among HIV-1-infected individuals, it is likely that low serum vitamin A concentrations reflect more active infection and the acute phase response. These results provide possible explanations for the disparity between observational studies and randomized trials of vitamin A for HIV-1 infection.