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Biomedical subjects

A D Grant

Publications and source records attributed to A D Grant.

At least 19 recordsLinked to original sources
PubMed2003

Attitudes to HIV voluntary counselling and testing among mineworkers in South Africa: will availability of antiretroviral therapy encourage testing?

We conducted a study to identify attitudes that influence uptake of HIV voluntary counselling and testing (VCT) amongst gold mine workers in South Africa; 105 healthy men were interviewed. The level of basic knowledge of HIV was high, but reported awareness of the extent of HIV infection in the workforce and perceived personal risk of HIV infection was low. Health issues were considered the most important indication for HIV testing and one-third had been tested. Fear of testing positive for HIV and the potential consequences, particularly stigmatization, disease and death, were the major identified barriers to VCT. Half of the participants felt workplace education programmes needed to be improved to promote VCT access. Twenty-six per cent became more favourably inclined towards HIV testing in response to information on improvements that have been made to the confidentiality and convenience of the company's VCT service. Only 14% then indicated that they would be more likely to access VCT if antiretroviral therapy became available. A vigorous community education programme is essential if the introduction of ART is to be effective in promoting uptake of VCT.

Adult↗
PubMed2003

Lactic acidosis in HIV infected patients: a systematic review of published cases.

OBJECTIVE: To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication. METHODS: Systematic review of cases reported in the medical literature. RESULTS: 217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16-69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men. CONCLUSIONS: NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA.

Acidosis, Lactic↗
PubMed2002

Use of UNAIDS tools to evaluate HIV voluntary counselling and testing services for mineworkers in South Africa.

HIV voluntary counselling and testing (VCT) is now an integral part of many HIV care and control programmes. However, very little work has been done to assess the quality of VCT services. An evaluation of VCT services for mineworkers in Welkom, South Africa was conducted to assess client and counsellor satisfaction, the quality of the services and to identify barriers to uptake of VCT. A cross-sectional survey was carried out using tools developed by UNAIDS, consisting of semi-structured interviews and observation of counselling sessions. Twenty-two nurse counsellors and six community volunteers were interviewed. Twenty-four counselling sessions were observed and 24 client exit interviews were conducted. Although nine of the 22 nurse counsellors had only in-service rather than formal training for HIV counselling whereas all community volunteers had been formally trained, nurse counsellors demonstrated better interpersonal skills than did community volunteers. Both clients and counsellors identified fear of a positive result as a major barrier to HIV testing. Clients also raised concerns about confidentiality. UNAIDS evaluation tools were a feasible and an acceptable method of assessing VCT in this operational setting. The study identified areas where training needs to be strengthened and suggested ways of improving the services, and changes to the service have now been implemented in line with these recommendations.

Counseling↗
PubMed2002

Use of spoligotyping for accurate classification of recurrent tuberculosis.

The spoligotyping method has become an important tool for the tracking of Mycobacterium tuberculosis strains in different epidemiological settings. In this study, we demonstrate the ability of the spoligotyping technique to accurately determine the pathogenetic mechanism of recurrent disease. This methodology has advantages over conventional restriction fragment length polymorphism methods which may be useful in large-scale intervention studies.

Diagnostic Techniques and Procedures↗
PubMed2001

Lack of a significant effect of deletion of the tachykinin neurokinin-1 receptor on wound healing in mouse skin.

The tachykinin neurokinin-1 (NK(1)) receptor mediates the vasoactive effects of substance P and related members of the tachykinin family. Substance P acts via the NK(1) receptor to mediate increased microvascular permeability leading to oedema formation as confirmed in NK(1) receptor knockout mice. In addition there is evidence that neuropeptides such as substance P can have a modulatory effect on the wound-healing process. In this study male and female wild-type and NK(1) knockout mice were investigated for their comparative ability to induce acute oedema formation in response to topical application of capsaicin, as measured by the extravasation of intravenous radiolabelled-albumin, and wound healing in response to a cut, as measured by area of wound over the following days. Significant (P<0.001) oedema, approximately three-fold over basal, was induced by capsaicin in both male and female wild-type mice, an indicator of a similar responsiveness irrespective of sex. However, as expected, the oedema was not observed in the knockout mice. Wounding was achieved through a 1-cm full-thickness cut into the interscapular area of dorsal skin. Wound healing was then followed in two different protocols. The wound was left to heal naturally over 14 days in the first protocol and no significant changes in healing were observed in wild-type compared to knockout. In the second protocol, the skin was sutured open for the first 48 h, to prevent the elasticity of the skin from initiating a natural healing process through flap formation. This caused a significant increase in the area of the wound. Despite this, wounds in both wild-type and knockout mice healed in an identical manner that was complete after 17 days. In conclusion, it is shown that deletion of a functional NK(1) receptor has little effect on wound healing in response to a simple cut in mouse skin.

Animals↗
PubMed2001

Genomic dissection reveals locus response to stress for mammalian acetylcholinesterase.

The mammalian acetylcholinesterase (ACHE) locus was investigated using computational predictive methods and experiments of reverse transcription polymerase chain reaction (RT-PCR). Computational analysis identified two genes downstream to ACHE, an inversely oriented arsenite resistance gene homologue (ARS), and a novel previously unidentified gene (PIX), co-oriented with ACHE. Experimental evidence shows coregulation of murine ACHE and ARS following confined swim, indicating coordinated locus response to stress, that is possibly mediated by altered cholinergic neurotransmission.

Acetylcholine↗
PubMed2001

Preventing opportunistic infections among human immunodeficiency virus-infected adults in African countries.

The burden of human immunodeficiency virus (HIV)-related disease in sub-Saharan Africa continues to increase; providing adequate care for the huge number of people affected is a daunting task, especially given the limited resources available. Recent studies have shown that low-cost regimens can prevent some of the most important causes of HIV-related disease in African countries. Isoniazid preventive therapy can reduce the incidence of tuberculosis; priorities are to seek opportunities for implementation, to assess effectiveness under operational conditions, and to monitor its effect on resistance patterns. Cotrimoxazole was shown to be highly effective in reducing morbidity and mortality among individuals with symptomatic HIV disease in Côte d'Ivoire, and should be implemented where it is likely to be of benefit. Pneumococcal polysaccharide vaccine was disappointingly ineffective among HIV-infected Ugandan adults, but newer conjugate vaccines are becoming available that should be investigated. The benefit of these preventive regimens to the individual may be modest when compared with the effect of antiretroviral therapy. However, simple preventive therapies could reach a much wider population than is immediately feasible for expensive and complex antiretroviral regimens, and thus have the potential for substantial benefit at the population level. The availability of effective and affordable regimens to prevent HIV-related disease may also encourage people to seek HIV testing, combat denial, and help overcome the sense of powerlessness in countries where the HIV epidemic has hit hardest.

AIDS-Related Opportunistic Infections↗
PubMed2000

What a test for recent infection might reveal about HIV incidence in England and Wales.

BACKGROUND: A laboratory method has been developed that detects recent HIV infection and allows incidence to be estimated by testing single stored antibody-positive specimens. A theoretical exploration of the method's surveillance utility was carried out. METHODS: Using various data sources, HIV incidence rates were postulated. The confidence intervals (CI) for these postulated incidences were calculated using the expected number of recent infections for each postulated incidence, the actual number tested for HIV, and the known number of HIV-1 positives. A test for trend was used to determine when an important change in incidence could be recognized. RESULTS: If the incidence was 5% per annum (p.a.) in homosexual/bisexual men attending sexually transmitted diseases (STD) clinics in London, 64 recent infections would be expected in the 392 HIV-seropositive specimens and, if observed, would result in a 95% CI of 3.1-7.9% p.a. for the incidence rate. An incidence of 1% p.a. in pregnant women would be most unlikely as this would require detection of 193 recent infections, 26 more than the total 167 HIV-seropositive specimens found in 1997. In African women attending STD clinics in London, 30% of prevalent infections would be classified as recent if the incidence was 5% p.a. Further, if the incidence in homosexual/bisexual men were to fall by 50% over 3 years, a decrease of this magnitude would be recognized as significant within 2 years. CONCLUSIONS: The detuned assay will increase the information from HIV serosurveys even where prevalence and incidence are relatively low. Existing surveillance systems should be redesigned to take full advantage of the method.

Confidentiality↗
PubMed2000

A transcription-activating polymorphism in the ACHE promoter associated with acute sensitivity to anti-acetylcholinesterases.

Hypersensitivity to acetylcholinesterase inhibitors (anti-AChEs) causes severe nervous system symptoms under low dose exposure. In search of direct genetic origin(s) for this sensitivity, we studied six regions in the extended 22 kb promoter of the ACHE gene in individuals who presented adverse responses to anti-AChEs and in randomly chosen controls. Two contiguous mutations, a T-->A substitution, disrupting a putative glucocorticoid response element, and a 4-bp deletion, abolishing one of two adjacent HNF3 binding sites, were identified 17 kb upstream of the transcription start site. Allele frequencies for these mutations were 0.006 and 0.012, respectively, in 333 individuals of various ethnic origins, with a strong linkage between the deletion and the biochemically neutral H322N mutation in the coding region of ACHE. Heterozygous carriers of the deletion included a proband who presented with acute hypersensitivity to the anti-AChE pyridostigmine and another with unexplained excessive vomiting during a fourth pregnancy following three spontaneous abortions. Electromobility shift assays, transfection studies and measurements of AChE levels in immortalized lymphocytes as well as in peripheral blood from both carriers and non-carriers, revealed functional relevance for this mutation both in vitro and in vivo and showed it to increase AChE expression, probably by alleviating competition between the two hepatocyte nuclear factor 3 binding sites. Moreover, AChE-overexpressing transgenic mice, unlike normal FVB/N mice, displayed anti-AChE hypersensitivity and failed to transcriptionally induce AChE production following exposure to anti-AChEs. Our findings point to promoter polymorphism(s) in the ACHE gene as the dominant susceptibility factor(s) for adverse responses to exposure or to treatment with anti-AChEs.

Acetylcholinesterase↗
PubMed2000

Congenital pseudoarthrosis of the tibia.

Congenital pseudoarthrosis of the tibia remains one of the most difficult conditions to treat in orthopedic surgery. Seven cases were treated in our hospital by different methods. Three out of seven patients were healed, two of these refractured. At follow-up, the success rate was 14% (one out of seven cases). It is our recommendation that early primary amputation with an appropriate prosthesis should be considered, and that the final evaluation should not be based on obtaining bone union, but on the level of function of the lower extremity.

Adolescent↗
PubMed1999

Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.

BACKGROUND: There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS: Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS: Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION: In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

AIDS-Related Opportunistic Infections↗
PubMed1998

Crutch handle design: effect on palmar loads during ambulation.

OBJECTIVE: To compare loads, load distributions, pressures, and areas of weight-bearing on the palm for forearm crutches with cylindrical and wide handles during ambulation to determine if one handle type produced greater loads on the carpal tunnel region. DESIGN: Single-group repeated measures of normal adults; descriptive study of patients who were long-term crutch users. Data were collected from six palmar regions using an F-Scan system. SETTING: Center for neuromuscular disorders in a hospital. PARTICIPANTS: Thirty normal volunteers and 6 patients. MAIN OUTCOME MEASURE: Differences in loads for the palmar regions between the two handles, particularly the carpal tunnel region. RESULTS: For the normal adults, significantly greater loads were found in two distal regions for the cylindrical handle and in one proximal region for the wide handle. Distribution of weight-bearing loads showed a similar pattern for both handles with the palm's proximal and distal radial sides having the greatest loads and the carpal tunnel region having the third highest load. The area of weight-bearing was significantly greater for the wide handle than for the cylindrical. CONCLUSIONS: Cylindrical and wide crutch handles have similar load distributions, making it impossible to recommend one type over the other to reduce the occurrence of carpal tunnel syndrome. The wide handle distributes the loads over a greater surface area, producing less focal pressure.

Adult↗
PubMed1998

The growing challenge of HIV/AIDS in developing countries.

The burden of HIV infection and disease continues to increase in many developing countries. An emerging theme is of an HIV pandemic composed of mini-epidemics, each with its own characteristics in terms of the trends in HIV prevalence, those affected, and the HIV-related opportunistic diseases observed. A number of explanations for the observed differences in the spread of HIV infection have been proposed but since the factors concerned, such as sexual behaviour and the prevalence of other sexually transmitted diseases, are closely interrelated, it is difficult to tease out which are the most important. Among HIV-related opportunistic diseases, tuberculosis stands out as the most important cause of morbidity and mortality in most developing countries, but the relative prevalence of other diseases shows considerable regional variation. Thus, there is a need for local approaches to the global problem of managing HIV disease. The most pressing public health challenges are to use existing knowledge of strategies to reduce HIV transmission, and to apply them in ways appropriate to the local situation, and to develop, evaluate and implement interventions to prolong healthy life in those already infected.

AIDS-Related Opportunistic Infections↗
PubMed1998

Spectrum of disease among HIV-infected adults hospitalised in a respiratory medicine unit in Abidjan, Côte d'Ivoire.

SETTING: Respiratory medicine wards of the University Teaching Hospital, Abidjan, Côte d'Ivoire. OBJECTIVES: To describe the spectrum of opportunistic infection among human immunodeficiency virus (HIV) infected adults hospitalised in the respiratory medicine unit in Abidjan, and the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. RESULTS: Overall, 75% of patients were HIV-positive: among these patients, the most frequent diagnosis was tuberculosis, in 61%, followed by bacterial pneumonia (15%), Gram-negative septicaemia (particularly non-typhoid Salmonella) (9%) and empyema (5%). Atypical pneumonias appeared to be rare. Most HIV-positive patients had CD4 counts indicative of advanced immunosuppression: 36% had CD4 counts below 100 x 10(6)/l, 19% between 100 and 199 x 10(6)/l, 29% between 200 and 499 x 10(6)/l, and 16% above 500 x 10(6)/l. Overall in-hospital mortality was 27% for HIV-positive patients and 22% for HIV-negative patients (P = 0.5). In a multivariate analysis, the strongest independent risk factors for death were cachexia (odds ratio [OR] 7.4, 95% confidence interval [CI] 2.1-26.3), male sex (OR 4.5, 95% CI 1.2-17.4) and age over 40 (OR 4.1, 95% CI 1.0-17.2). CONCLUSIONS: Tuberculosis and bacterial infections are the major causes of respiratory morbidity in immunosuppressed HIV-infected adults in this population. Efforts to improve the management of HIV-related disease need to focus on prevention and treatment of these infections.

AIDS-Related Opportunistic Infections↗