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Biomedical subjects

M R Nelson

Publications and source records attributed to M R Nelson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Energy balance in asymptomatic HIV infection.

OBJECTIVES: Body weight is regulated by the balance between energy intake and energy expenditure, but the influence of HIV infection on energy balance has not been fully examined. The main objectives of this study were (1) to assess the effect of HIV on energy balance, (2) to examine the relationship of parameters of immunodeficiency to energy balance, and (3) to examine the interrelationship of different components of energy balance in asymptomatic HIV-seropositive men. DESIGN: A cross-sectional study of nutrition and metabolism in asymptomatic HIV-seropositive men METHODS: Components of energy balance were examined in 104 asymptomatic HIV-seropositive men (CD4 count 4-482 x 10(6)/l) and 57 age-matched HIV-seronegative male controls. Energy and protein intake were measured using 5-day diaries, and small bowel absorption and permeability was assessed using four sugar probes. Resting energy expenditure was calculated from indirect calorimetry and nitrogen loss estimated from 24 h urine collection. Four methods were used to assess the effect of HIV infection on body composition (anthropometry, dual energy X-ray absorptiometry, bioelectrical impedance and 24 h urine creatinine). RESULTS: Resting energy expenditure per kilogram of fat-free mass was raised (P < 0.0001), fat mass was decreased (P = 0.001), fat-free mass was increased (P = 0.05), energy intake was higher (P = 0.05), absorption of L-rhamnose (P = 0.01) and 3-O-methyl-D-glucose was decreased (P = 0.003), and small bowel permeability was increased (P < 0.0001) in HIV-seropositive men compared with HIV-seronegative controls. HIV-seropositive subjects with a CD4 count less than 100 x 10(6)/l had decreased absorption of L-rhamnose (P < 0.05), D-xylose (P < 0.05) and 3-O-methyl-D glucose (P < 0.05) compared with HIV-seropositive subjects at higher CD4 counts, and had a similar resting energy expenditure to HIV-seronegative controls. Protein intake, carbohydrate, fat and protein oxidation. 24 h nitrogen excretion and appendicular muscle mass were similar in HIV-seropositive men and controls. CONCLUSION: HIV infection exerts a direct effect on parameters of energy balance that varies with the severity of immunosuppression.

Adult↗
PubMed1996

Faecal tumour necrosis factor-alpha in individuals with HIV-related diarrhoea.

OBJECTIVE: HIV-related gastrointestinal infection is associated with diarrhoea, weight loss, mucosal inflammation and increased intestinal permeability. As tumour necrosis factor (TNF)-alpha may mediate these features this cytokine was measured in the faeces of HIV-seropositive individuals with diarrhoea to assess its role in the pathogenesis of HIV-related gastrointestinal disease and the association with specific intestinal pathogens. DESIGN: Prospective study. METHODS: Two hundred and four HIV-seropositive individuals provided stool samples that were analysed for faecal TNF-alpha (FTNF-alpha) using a standard sandwich enzyme-linked immunosorbent assay. RESULTS: Stool from patients with bacterial, cytomegalovirus (CMV) and microsporidial diarrhoea had significantly elevated FTNF-alpha compared with those who had pathogen-negative diarrhoea (P < 0.05). FTNF-alpha was not raised in cryptosporidiosis, pathogen-negative or solid stool. In subjects with diarrhoea of more than 2 weeks duration and three stool samples negative for enteric pathogens, FTNF-alpha greater than 15 U/ml has a sensitivity of 88% and a specificity of 66% for the diagnosis of diarrhoea-related CMV enteritis. CONCLUSION: TNF-alpha production may have a role in the pathogenesis of bacterial, microsporidial and CMV-related diarrhoea in HIV-seropositive individuals. Thus, anti-TNF-alpha agents may have a therapeutic role in the management of these conditions. FTNF-alpha greater than 15 U/ml in apparently pathogen-negative diarrhoea may suggest endoscopic gastrointestinal biopsy to diagnose CMV enteritis.

AIDS-Related Opportunistic Infections↗
PubMed1996

An efficient method for isolating putative promoters and 5'-transcribed sequences from large genomic clones.

Efficient strategies to isolate promoters and flanking exons from large genomic clones would facilitate the assembly of transcription units, complement existing techniques to isolate expressed sequences, and provide 5' regulatory elements. We have developed a rapid and simple method to isolate promoters from large mammalian genomic DNA clones by exploiting the abundance of binding sites for the ubiquitous transcription factor Sp1 in gene promoters. Using this method, putative promoter sequences with Sp1-binding sites are enriched approximately 100-fold from fragmented P1 clone DNA. Based on the abundance of Sp1-binding motifs in promoters, we predict that a significant subset of vertebrate promoters could be isolated by this method.

Base Sequence↗
PubMed1996

Mycobacterium kansasii: its presentation, treatment and outcome in HIV infected patients.

AIM: To report the clinical significance and treatment of Mycobacterium kansasii infection in the context of HIV disease. DESIGN/METHODS: Retrospective case review of all isolates of M kansasii until June 1994. RESULTS: Ten cases of M kansasii were isolated. All but one patient with this infection had clinical symptoms compatible with generalised infection. The majority had chest infections with the organism isolated on induced sputum but not routine sputum. All isolates were sensitive to ethambutol and nine of 10 to rifampicin. All isolates were resistant to isoniazid and pyrazinamide. CONCLUSION: M kansasii is a pathogen in HIV infected patients and should be treated when isolated. Treatment should be with rifampicin and ethambutol but not isoniazid, as has been recommended previously.

AIDS-Related Opportunistic Infections↗
PubMed1996

Pneumothorax in AIDS: case reviews and proposed clinical management.

BACKGROUND: Pneumothorax is a not uncommon complication of advanced HIV infection, and may prove difficult to manage in view of its recalcitrant and recurrent nature. In this group where immunosuppression and reduced life expectancy are a feature, standard protocols are often abandoned in favour of a more conservative approach. This is often unsuccessful. METHODS: Patients attending the Department of Genitourinary Medicine, Chelsea and Westminster Hospital who sustained pneumothorax between 1988 and 1992 were identified retrospectively and their notes reviewed. RESULTS: Fifteen patients were identified of whom three had post-procedural pneumothoraces. In the remaining 12 patients, 10 had previously had Pneumocystic carinii pneumonia (PCP), whilst all 12 had some evidence to suggest current PCP (seven proven, five presumptive). In those six patients with a single, unilateral pneumothorax, four were managed successfully with intercostal drainage alone (one patient died early, one required pleurectomy). In those with recurrent pneumothoraces or pneumothoraces that did not respond to prolonged intercostal drainage, failure of medical treatment was judged to have occurred and surgery was performed. Overall, conservative management failed in 7/11 patients. Conversely surgery resulted in resolution in 7/7 with recurrence seen in one individual. Median survival was similar in the two groups. CONCLUSIONS: Pneumothorax in patients with AIDS is associated with a high rate of intercurrent PCP; a low threshold for treating this infection presumptively is indicated. Intercostal drainage was successful in patients with a single, unilateral pneumothorax. However, in patients with recurrent or bilateral pneumothorax extended periods on intercostal drainage were uniformly unsuccessful. Early surgical referral should be considered in this group.

AIDS-Related Opportunistic Infections↗
PubMed1996

Mainstream legitimization of homosexual men through Valentine's Day gift-giving and consumption rituals.

Recently, the gay community has received increased attention from marketers through specially-made television commercials, direct mail pieces, and other media messages. However, little research in consumer behavior has examined the potential attitudinal and behavioral differences and similarities between heterosexuals and homosexuals. Specifically, this paper provides an exploratory look at the meaning and practices surrounding the consumer ritual of Valentine's Day from the perspective of homosexual men. Using depth interviews within an interpretative framework, our research suggests similarities exist for the celebration of Valentine's Day between homosexual and heterosexual singles, while differences may exist for the functions of Valentine's Day gift-giving between these groups. Some homosexual couples feel they cannot "legitimately participate" in the dominant rituals associated with the holiday due to oppression by a "heterosexual society". Marketing implications are discussed.

Adult↗
PubMed1995

Combinatorial mutagenesis of the four domains of annexin IV: effects on chromaffin granule binding and aggregating activities.

This study addresses the roles of individual annexin IV domains in calcium-dependent membrane binding and aggregation through an analysis of the activities of mutant annexin IV proteins in which critical residues in one or more domains have been altered. The consensus sequence for high-affinity Ca(2+)-binding pockets obtained from the annexin V crystal structure is GXGT-38 residues-D/E [Huber, R., et al. (1992) J. Mol. Biol. 223, 683-704]. Site-directed mutagenesis was used to change the conserved acidic residues (D/E) in these sequences to alanine residues in each of the four domains of bovine annexin IV, singly or in combinations. Fourteen mutants with one, two, three, or four mutated domains were constructed and expressed in Escherichia coli. Purified recombinant product was evaluated for Ca(2+)-dependent binding to and aggregation of bovine chromaffin granules. Increases in the number of mutated domains resulted in increased Ca2+ requirements for both granule binding and aggregation. Further analysis revealed that mutations in individual domains had preferential effects on the binding or aggregating activities of the protein. For example, mutation of the first or fourth domains had a greater effect on membrane binding than aggregation, while conversely, mutation of the second domain had a more dramatic effect on membrane aggregation. Mutation of the third domain was largely silent in these assays. An additional mutation was made in the fourth domain to substitute a serine for a highly conserved arginine residue (Arg274) present at the C-terminus of the fourth endonexin fold. This mutation increased the calcium requirement for membrane binding 2-fold and for membrane aggregation 3-fold. This mutant protein was found to be an effective inhibitor of membrane aggregation by native annexin IV at intermediate levels of calcium.

Amino Acid Sequence↗
PubMed1995

Comparison of the expression of native and mutant bovine annexin IV in Escherichia coli using four different expression systems.

Bovine annexin IV, a Ca(2+)-dependent, membrane-binding protein, was expressed in E. coli using four different prokaryotic expression vector systems. An annexin IV cDNA was mutated in the 5' noncoding region to introduce an NcoI restriction site at the translation initiation site. The coding sequence was then excised and ligated into the expression vectors: pKK233-2 (which uses a hybrid trc promoter), pFOG405 (which uses the alkaline phosphatase promoter and generates a fusion protein with the alkaline phosphatase signal sequence that targets the protein for secretion), pOTSNco12 (which provides temperature-sensitive expression from the lambda phage promoter), and pET11d (which uses the T7lac promoter and a protease-deficient host). Expression of wild type and mutant annexin IV in the various systems was compared. Differences in level of expression, formation of inclusion bodies, and yield of purified protein were observed. The pET11d system was found to be the most effective expression system for annexin IV and various annexin IV mutant constructs, providing the highest yield of functional protein from the soluble fraction of cell lysates. Bovine chromaffin granule binding and aggregating activities of recombinant annexin IV were found to be virtually indistinguishable from those of bovine annexin IV isolated from liver tissue. Truncation constructs containing one, two, or three of the four conserved 70-amino-acid domains of native annexin IV were successfully created and expressed in E. coli, but the recombinant proteins were generally insoluble. pET11d annexin constructs containing point mutations in residues involved in binding calcium produced soluble protein at levels comparable to those of constructs expressing wild type protein.

Alkaline Phosphatase↗
PubMed1994

The role of azoles in the treatment and prophylaxis of cryptococcal disease in HIV infection.

OBJECTIVE: To assess the role of azole therapy in the treatment and prophylaxis of cryptococcosis in HIV-seropositive individuals. STUDY DESIGN: Retrospective case review. SETTING: A dedicated HIV unit in London, UK. PATIENTS: Fifty individuals with a positive cryptococcal antigen or culture from any site between 1 January 1985 and 31 December 1992. RESULTS: Thirty-eight patients initially presented with meningitis and 12 with alternative disease, five of whom subsequently developed meningeal disease. The 12 patients who presented without meningitis received chronic suppressive therapy after the diagnosis of cryptococcal disease. Two patients receiving itraconazole developed meningitis as did three out of four treated with 200 mg fluconazole daily, but none of the six receiving 400 mg fluconazole daily. Treatment of cryptococcal meningitis was successful in 17 of the 19 patients given fluconazole but only three of the six receiving itraconazole. Following successful treatment of meningitis five out of seven patients given itraconazole and five out of seven given 200 mg fluconazole daily relapsed compared with three out of 25 receiving 400 mg fluconazole daily. CONCLUSION: Fluconazole is an effective treatment for cryptococcal meningitis. For prophylaxis following meningitis, a dose of 400 mg fluconazole is the preferred treatment; lower doses are associated with a higher relapse rate.

AIDS-Related Opportunistic Infections↗
PubMed1993

Birth-weight-specific infant mortality risks and leading causes of death. Illinois, 1980-1989.

OBJECTIVE: To describe birth-weight-specific differences in mortality risks between white and black Illinois infants by age at death and leading cause of death. DESIGN: Population-based birth cohort study. SETTING: State of Illinois. PATIENTS: All Illinois infants who were born from 1980 through 1989 and reported to the Illinois Department of Public Health. The death certificates of these infants were matched to corresponding birth certificates using a computerized linkage algorithm. INTERVENTIONS: None. RESULTS: The high black infant mortality rate is attributable to higher mortality risks in the neonatal period for black, normal birth-weight infants and in the postneonatal period for all black infants, regardless of birth weight. CONCLUSION: Efforts to narrow the black-white gap in infant mortality and to reduce black mortality should not be limited to reduction of low birth weight and premature birth in black infants but should also include efforts to reduce risk factors associated with mortality among normal birthweight black infants.

Birth Weight↗
PubMed1993

Use of didanosine in zidovudine-intolerant patients infected with human immunodeficiency virus.

One hundred fifty-one patients who were positive for antibody to human immunodeficiency virus (HIV) and intolerant of zidovudine received oral didanosine at a dose adjusted by weight to a maximum of 12.5 mg/(kg.d). After 1 year of follow-up, 49 patients were still receiving didanosine; 19 had died during therapy and 23 thereafter. Therapy had been discontinued in 10 cases because of continued deterioration in health and in the remainder because of adverse reactions. Only 11 of 38 patients with positive results in an ELISA for p24 antigen before therapy had a significant reduction in titer. CD4 lymphocyte subset counts were more likely to rise for patients who had only constitutional disease due to HIV than for those with AIDS. Eleven percent of treated patients gained > 2.5 kg. Diarrhea was the commonest side effect, occurring in 60% of cases. Pancreatitis developed in six cases (with two deaths) and asymptomatic hyperamylasemia in 13. Seven patients developed glucose tolerance in the diabetic range. Peripheral neuropathy was documented in 12 instances but was reversible on cessation of therapy in six.

CD4-Positive T-Lymphocytes↗