Biomedical subjects

H Henderson

Publications and source records attributed to H Henderson.

At least 19 recordsLinked to original sources

PubMed2005

Enzyme-linked immunospot assay responses to early secretory antigenic target 6, culture filtrate protein 10, and purified protein derivative among children with tuberculosis: implications for diagnosis and monitoring of therapy.

BACKGROUND: The ability to detect tuberculosis-specific lymphocytes by enzyme-linked immunospot (ELISPOT) assay may have important implications for the diagnosis and monitoring of tuberculosis in children, for which routine methods lack sensitivity. We conducted a study to determine the presence and time course of ELISPOT responses in children with tuberculosis. METHODS: Blood samples were obtained from children with a clinical diagnosis of tuberculosis, and interferon-gamma ELISPOT assays were performed using purified protein derivative (PPD), early secretory antigenic target 6 (ESAT-6), and culture filtrate protein 10 (CFP10) as stimulants. A subset of children were retested after 1, 3, and 6 months of therapy. RESULTS: Detectable responses to ESAT-6 or CFP10 were found in 49 of 70 children with clinical tuberculosis but were more frequently found in those with culture-proven disease (P = .05). The number of subjects with responses to PPD increased after 1 month of therapy (P = .0004) and decreased at 3 and 6 months. CONCLUSION: Tuberculosis-specific ELISPOT testing is a promising tool that should be evaluated as a potential diagnostic test for childhood tuberculosis. We caution against the use of an early decrease in response as a marker of successful antituberculous chemotherapy.

Antigens, Bacterial↗

PubMed2001

Cryptococcosis in human immunodeficiency virus-negative patients in the era of effective azole therapy.

We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age > or =60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.

Adolescent↗

PubMed2001

Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.

We conducted a multicenter case-control study to identify risk factors for histoplasmosis among persons with acquired immunodeficiency syndrome (AIDS) and to evaluate predictors of a poor outcome (defined as death or admission to the intensive care unit). Patients with histoplasmosis were each matched by age, sex, and CD4 lymphocyte count to 3 controls. From 1996 through 1999, 92 case patients and 252 controls were enrolled. Of the case patients, 81 (89%) were men, 50 (55%) were black, 78 (85%) had a CD4 lymphocyte count of <100 cells/microL, 80 (87%) were hospitalized, and 11 (12%) died. Multivariable analysis found that receipt of antiretroviral therapy and of triazole drugs were independently associated with a decreased risk of histoplasmosis. Chronic medical conditions and a history of infections with herpes simplex virus were associated with poor outcome. Triazoles should be considered for chemoprophylaxis for persons with AIDS, especially those who take part in high-risk activities that involve frequent exposure to soil, who have CD4 lymphocyte counts of <100 cells/microL, and who live in areas where histoplasmosis is endemic.

AIDS-Related Opportunistic Infections↗

PubMed2000

Healthcare provider characteristics and perceived confidence from HIV/AIDS education.

This study reports findings from six training projects designed to keep health providers up-to-date on emerging developments and approaches in HIV/AIDS care. Participants were 3,779 individuals who described themselves, their professional background, and their specific experience in the HIV/AIDS field. These characteristics were compared with their self-reported confidence in managing clients, counseling clients, providing services, and the training topics. A repeated-measures design examining level and change of confidence showed little support for links between provider characteristics and confidence due to HIV/AIDS training experience. Thus, knowing a provider's background does not necessarily provide diagnostic information about who might most benefit in improved confidence from HIV/AIDS educational training. These results suggest that HIV/AIDS training programs may be targeted broadly-to a wide range of healthcare providers of diverse backgrounds-with little or no impact on overall levels and changes in provider confidence.

Attitude of Health Personnel↗

PubMed2000

Trainee characteristics and perceptions of HIV/AIDS training quality.

HIV/AIDS education and training have played a vital role in keeping health providers up to date on emerging developments and approaches. This study reports findings from seven HIV/AIDS education and training projects. Participants in more than 600 training sessions described themselves, their professional background, and their general reasons for taking the training. Immediately following the training, they also rated the quality of their educational experience along several dimensions. Trainee characteristics were related to assessments of training quality, using a regression decision-tree analytic approach. Although effect sizes were generally small, quality ratings of the HIV/AIDS training experiences were associated with certain projects, basic trainee demographic characteristics, professional background, and experience in the HIV field. Greater understanding about participant characteristics can provide clues about how these training experiences are perceived and processed and may inform decision making about instructional HIV/AIDS curricula.

Adult↗

PubMed2000

Effects of HIV/AIDS education and training on patient care and provider practices: a cross-cutting evaluation.

Initial and continuing training in HIV/AIDS service provision is a critical way to enable the nation's health providers to use state-of-the-art developments and perspectives. Typically, the efficacy of HIV/AIDS training programs is evaluated using assessments administered to trainees immediately following the training. This study reports cross-cutting findings from telephone interviews conducted with 218 trainees an average of 8 months after training. Long-term training effects are examined in three domains: (a) general perspectives on HIV/AIDS; (b) health care provider service provision; and (c) changes in procedures and operations at the health care system level. The findings show the different ways that the training experience had long-term positive and observable effects in these three domains. In some cases, background characteristics and job positions predicted the specific type of reported training effects. The pattern of results suggests ways in which training methods can be targeted to specific audiences.

Acquired Immunodeficiency Syndrome↗

PubMed2000

Do characteristics of HIV/AIDS education and training affect perceived training quality? Lessons from the evaluation of seven projects.

Initial and continuing HIV/AIDS education and training has been a critical way to bring the nation's health providers up to date on emerging developments and approaches. This study reports cross-cutting findings from seven HIV/AIDS education and training projects. Trainers described over 600 training sessions from these projects in terms of their structural characteristics and design elements, while trainees described these sessions on several dimensions related to training quality. Training characteristics were compared to trainee assessments of training quality. Using a decision-tree analytic approach for major training attributes, considerable support emerged for links between training characteristics and perceived quality of the HIV/AIDS training experience. More favorable quality ratings were associated with certain projects, the training setting, the types of trainees served by the training, the intended training impact, discussion of special populations, and training methods involving interactive learning. With increased knowledge regarding how these educational experiences relate to the ways they are perceived and processed, more targeted approaches to training design on HIV/AIDS can be developed.

Adult↗

PubMed1999

A comparison of 1% ropivacaine with a mixture of 0.75% bupivacaine and 2% lignocaine for peribulbar anaesthesia.

In a single centre, randomised, double-blind study, 54 patients underwent intraocular surgery under peribulbar anaesthesia with either ropivacaine 1% or a mixture of bupivacaine 0.75% and lignocaine 2%, both with hyaluronidase 7.5 iu.ml-1. There were no significant differences in volume of anaesthetic required, time to onset of block, peri-operative pain scores or frequency of adverse events between the ropivacaine group and the lignocaine and bupivacaine group.

Aged↗

PubMed1999

Effects of the height of the internal features of faces on adults' aesthetic ratings and 5-month-olds' looking times.

We examined the influence of the height of the internal features of faces on adults' ratings of attractiveness and on 5-month-olds' looking times. Subjects viewed drawings or coloured photographs of faces presented in pairs that were identical except that the internal features were at a low height, with a large forehead and small chin; at a high height, with a small forehead and large chin; or at a medium height. Adults rated faces with their features at the medium and low heights as more attractive than faces with their features at the high height, and, at least for drawings, rated faces with medium features as more attractive than faces with low features. Babies looked equally long at faces with their features at various heights except for looking slightly longer at faces with high rather than low features. The results suggest that the influence of feature height on reactions to faces is different for adults and 5-month-olds, and hence that it may be shaped by cultural learning and/or experience with faces sometime after early infancy.

Adolescent↗

PubMed1999

Systems change resulting from HIV/AIDS education and training. A cross-cutting evaluation of nine innovative projects.

An evaluation of nine diverse HIV/AIDS training programs assessed the degree to which the programs produced changes in the ways that health care systems deliver HIV/AIDS care. Participants were interviewed an average of 8 months following completion of training and asked for specific examples of a resulting change in their health care system. More than half of the trainees gave at least one example of a systems change. The examples included the way patient referrals are made, the manner in which agency collaborations are organized, and the way care is delivered.

Adolescent↗

PubMed1998

A novel Glu421Lys substitution in the lipoprotein lipase gene in pregnancy-induced hypertriglyceridemic pancreatitis.

Severe hypertriglyceridemia is an uncommon pathological finding in pregnant women if there is no prior history of hyperlipidemia. A partial reduction in lipoprotein lipase (LPL) activity due to a mutation in the LPL gene, is often an associating factor. Here we report a novel LPL gene mutation (Glu421Lys), in a previously healthy primigravid woman who died from hypertriglyceridemia-induced pancreatitis during the last trimester of pregnancy. The patient was heterozygous for this mutation which a charge inversion in the C-terminal domain of LPL resulting in a moderate reduction in catalytic activity, both in vivo and in vitro. These data support the role of partial LPL deficiency in the pathogenesis of severe gestational hypertriglyceridemia.

Adult↗

PubMed1998

Extracorporeal membrane oxygenation in the treatment of inhalation injuries.

Smoke inhalation is a leading cause of death in burns patients. Conventional ventilation cannot always maintain adequate tissue oxygenation. Extracorporeal membrane oxygenation (ECMO) has rarely been used in the treatment of smoke inhalation injuries. ECMO is a proven therapy in severe neonatal respiratory failure and has also been used to good effect in the treatment of children and adults. We report the cases of two children who developed severe respiratory failure refractory to maximal ventilation, one case followed smoke inhalation alone, the other followed smoke inhalation and burns. Pre-ECMO PaO2/FIO2 ratios were 6.5 and 8 kPa, respectively. The patients were treated with veno venous ECMO for 72 and 144 h, respectively. The use of ECMO for respiratory failure due to smoke inhalation and thermal injury is discussed.

Accidents, Home↗

PubMed1998

The Asn9 variant of lipoprotein lipase is associated with the -93G promoter mutation and an increased risk of coronary artery disease. The Regress Study Group.

Two mutations in the lipoprotein lipase (LPL) gene, a T to G transition at position -93 of the proximal promoter region and an Asp9Asn substitution in exon 2, were examined in 762 Dutch males with angiographically-diagnosed coronary artery disease (CAD) and 296 healthy normolipidemic Dutch males. The two mutations exhibited strong linkage disequilibrium (D' = 0.975). A significantly higher proportion of cases (4.86%) than controls (1.37%) carried the -93G/Asn9 allele (p = 0.008). In the combined sample of cases and controls, adjusted mean plasma total cholesterol (TC) levels were significantly higher in -93G/Asn9 carriers (6.20+/-0.13 mmol/l) than in non-carriers (5.93+/-0.03 mmol/l; p = 0.048), while mean high-density lipoprotein cholesterol (HDL-C) levels were lower in carriers (0.88+/-0.03 mmol/l) than in non-carriers (0.98+/-0.01 mmol/l; p = 0.002). There was a trend towards higher triglyceride (TG) levels in carriers (1.96+/-0.14 mmol/l) compared with non-carriers (1.73+/-0.03 mmol/l) (p = 0.08). Additionally, carrier frequencies in tertiles of TC, HDL-C, TG, and LPL activity, suggested an association of the -93G/Asn9 variant with higher TC and TG levels, and with lower HDL-C and LPL activity levels. Logistic regression revealed a significant odds ratio (OR) for the combined -93G/Asn9 genotype in CAD cases relative to controls (OR: 5.36; 95% CI: 1.57-18.24), with age, body mass index (BMI), smoking, and plasma total- and HDL-cholesterol levels included in the model. In conclusion, we show that the LPL Asp9Asn mutation is in non-random association with a T G substitution at position -93 of the proximal promoter region and that the combined -93G/Asn9 genotype predisposes to decreased HDL-C levels and an increased risk of CAD.

Asparagine↗

PubMed1997

Ethnic variation and in vivo effects of the -93t-->g promoter variant in the lipoprotein lipase gene.

Recently, a (t-->g) transition at nucleotide -93 in the lipoprotein lipase (LPL) gene promoter has been observed in Caucasians. Here, we have compared the frequency of the -93g carriers in three distinct populations (Caucasians, South African Blacks, and Chinese). The carrier frequency in the Caucasian population was 1.7% (4/232), which was in contrast to the South African Black population, which had a frequency for this allele of 76.4% (123/161) of the individuals tested. This transition was not observed in the Chinese population under study. Near complete linkage disequilibrium between the -93g and the previously described D9N mutation was observed in the Caucasian population but not in South African Blacks. To further assess the ancestral origins of these DNA changes, DNA haplotyping using a CA repeat 5' to these substitutions was performed. The -93t allele was associated with only a few specific dinucleotide repeat sizes. In contrast, the -93g allele occurred on chromosomes with many different repeat lengths. The broad distribution of repeats on -93g carrying chromosomes, their high frequency in the South African Black population, and the conservation of the -93g allele among different species may suggest that the -93g allele is the ancestral allele on which a transition to t and the D9N mutations arose. The very high frequency of the -93g allele distinct from the N9 allele in a cohort of Black South Africans allowed us to specifically assess the phenotypic effects of the -93g allele on lipids. Individuals homozygous for the g allele at -93 showed mildly decreased triglycerides compared with individuals homozygous for the t allele (1.14 +/- 0.66 mmol/L versus 0.82 +/- 0.3; P = .04). Thus, the -93g allele in this cohort is associated with low plasma triglyceride levels.

Adult↗

PubMed1996

Common sequence variants of lipoprotein lipase: standardized studies of in vitro expression and catalytic function.

We have assessed the functional activity of three common sequence variants of human lipoprotein lipase (LPL). Two of these, Asn291Ser and Asp9Asn arise from missense mutations while the third, Ser447Ter, derives from a nonsense mutation, truncating LPL by two residues. As previous in vitro studies have produced conflicting results, we have re-analyzed the catalytic function of these variants using the COS cell transfection system, under optimized and standardized experimental protocols. We found the Asn291Ser variant to manifest with a decrease in catalytic activity (57% of normal) due to a reduction in secretion and stability of the active homodimeric form. The Asp9Asn variant also showed a significant decrease in catalytic activity (85% of normal), but this was found to be due to a decreased rate of secretion only, as the homodimeric form was stable. The findings for these mutants contrasted with those of the Ser447Ter truncation variant which proved to be catalytically normal; this variant also manifested normal homodimer stability. The truncated variant did however, present with a higher total secreted mass level (131%) than control LPL. This was most likely due to enhanced secretion of the monomeric form. None of these mutations exhibited defects in binding affinity to cell surface proteoglycans. Each of these variants deviated significantly from normal as regards to their secreted activity or mass levels in the COS cell transfection system.

Catalysis↗

PubMed1996

HIV-1 disease association with HLA-DQ antigens in African Americans and Caucasians.

Previously, we have shown that CD4 levels in African Americans infected with human immunodeficiency virus-1 (HIV-1) were lower than those in Caucasians. To determine whether or not HLA type is associated with susceptibility to HIV-1 infection, we demonstrated serologically that HLA-DQ6(1) and HLA-DQ7(3) were associated with HIV-1 infection in both African Americans and Caucasians. The present investigation was designed to demonstrate whether or not HLA-DQB1 alleles were associated with HIV-1 infection or protection from infection within these two ethnic groups. Oligonucleotide typing was employed and results were analyzed by chi 2 with Fisher's exact test to compare HLA-DQ marker frequencies in the regional control population (98 African Americans, 143 Caucasians) to the disease population (n = 52; 30 African Americans and 22 Caucasians). We found a statistically significant increased risk of HIV infection associated with HLA-DQB1*0605 in African Americans, and with HLA-DQB1*0602 in Caucasians. By contrast, HLA-DQB1*0603 was associated with protection in Caucasians.

Adolescent↗

PubMed1995

Progression of HIV infection is associated with HLA-DQ antigens in Caucasians and African Americans.

In our previous work with human leukocyte antigen (HLA) association in human immunodeficiency virus (HIV) infection, African Americans (Afr Ams) and Caucasians (Caucs) exhibited HLA markers that were associated with protection or disease. The present study was designed to establish if HLAs were associated with the severity of HIV infection and progression to AIDS in Afr Am and Cauc adults. The frequency of serologically determined antigens (Ags) in the regional control population was compared to the HIV-infected population and the HIV-infected slow progressors were compared to rapid progressors by race. chi 2 analysis with Bonferroni adjustment, Kaplan-Meier survival analysis, linear logistic regression, Cox model of proportional hazards and standardized deltas were applied as applicable. Immune parameters were monitored over a mean follow-up period of 23 +/- 2 months for Afr Ams (n = 35) and 25 +/- 5 months for Caucs (n = 24). A better prognosis in the HIV+Afr Am group was associated with HLA-DQ1 with a risk ratio of 0.295. In the HIV+Cauc group, a preferable prognosis was associated with HLA-DQ3 with a risk ratio of 0.11, and a poor prognosis was associated with HLA-DQ2 with a risk ratio of 7. Afr Am haplotypes that appeared to have the greatest association with rapid progression of HIV infection were A69(28)-B40 and related haplotypes as well as B12-DR14(6). Cauc haplotypes with the strongest association with rapid and slow progression of HIV infection were A28-B17-DR9 and A30(19)-B67, respectively. The DR Ags of at least one haplotype that led to rapid progression in both races were associated with DQ9(3). An 'immune response' gene (DQ region) may control the progression of HIV infection in adults. The rapidly progressive DQ-associated peptide might block the progression of HIV if given as a novel vaccine.

Adolescent↗

PubMed1994

Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase.

Lipoprotein lipase (LPL) is a key enzyme required for the hydrolysis of triglyceride-rich particles. To assess the effects of increased plasma LPL on lipoprotein levels, transgenic mice expressing human LPL (hLPL) were produced. Abundant hLPL transcripts were detected in RNA from different tissues of transgenic mice which resulted in an increase in post-heparin plasma LPL activity of approximately 154%. On rodent chow (p = 0.01) and after a 16-h fast (p = 0.001), plasma triglycerides in transgenic mice were decreased by approximately 50% as compared to littermate controls. Gel filtration chromatography showed a 2-3-fold decrease in very low density lipoprotein triglycerides and cholesterol enrichment of low density lipoprotein. Transgenic mice maintained on a high carbohydrate diet exhibited a 78% (p = 0.03) lowering of low density lipoprotein and very low density lipoprotein cholesterol levels, in addition to a 68% (p = 0.01) lowering of total to high density lipoprotein cholesterol (TC/HDL-C) ratios compared to controls. The distribution of apoA-I and A-II were similar in the transgenics and their non-transgenic littermates, while the apoE distribution was mildly altered in the plasma from the transgenic mice. These data demonstrate that moderate increases in total LPL activity are associated with significant changes in lipoprotein levels and altered composition of lipoprotein particles.

Animals↗