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Biomedical subjects

G D Kirk

Publications and source records attributed to G D Kirk.

12 recordsLinked to original sources
PubMed2005

Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance.

Hepatitis C virus (HCV) is an infectious blood-borne pathogen that usually persists as a chronic infection. However, approximately 15% of the time, patients can clear the virus, indicating that host differences could be critical in determining the course of HCV infection. The inflammatory response is crucial to resolving or failing to resolve an acute HCV infection. Some previous reports have implicated interleukin 10 (IL10) polymorphisms with successful anti-HCV therapy and natural viral clearance. We tested 54 single nucleotide polymorphisms (SNPs) in the IL10 region (+/-300 kb and 24 within the IL10 gene itself), which contains 13 genes including the IL10 immunomodulatory paralogs IL19, IL20, and IL24, for association with HCV clearance vs persistence. SNPs from two haplotype block regions, one at IL10 and the other from IL19/IL20, were associated with HCV clearance in African Americans (91 clearance cases and 183 chronically infected matched controls; P=0.05-0.002) while with expectation-maximization algorithm-reconstructed haplotypes, these associations remained (P=0.05-0.002). However, no significant associations were detected in European Americans (108 clearance and 245 chronic). Our results indicate that variants of the immunomodulatory IL10 and IL19/IL20 genes may be involved in natural clearance of HCV in the African-American population.

Black or African American↗
PubMed2005

Hepatitis B surface antigenaemia and alpha-foetoprotein detection from dried blood spots: applications to field-based studies and to clinical care in hepatitis B virus endemic areas.

In many resource-limited regions with endemic hepatitis B virus (HBV), there is limited infrastructure to collect, process, transport, and store blood samples for identification of persons with chronic HBV infection or with hepatocellular carcinoma (HCC). We describe the application of a simple technique using commercially available kits for detection of HBV surface antigen (HBsAg) and alpha-foetoprotein (AFP) in dried blood spots (DBS) collected on filter paper. Study participants included subjects with and without chronic HBV infection and subjects with HCC or cirrhosis. Three to five blood drops were dried on filter paper. Dried blood (equivalent to 20 muL) was eluted and tested for HBsAg by Determine(TM) HBsAg and for AFP by counter-current immuno-electrophoresis and radio-immunoassay (RIA). The primary analysis focused on comparison of DBS results to serum testing results as the gold standard. The sensitivity of DBS for detecting chronic HBV infection was 96% (98-98) with specificity of 100% (CI 99-100). Sensitivity of DBS in detecting AFP compared with serum RIA was 73% (60-86) with specificity of 90% (81-98). Both HBsAg and AFP recovery were unaffected when DBS were left at room temperature (30-33 degrees C) and under humid conditions for up to 28 days prior to elution. We conclude that DBS can be reliably used as an economical and logical alternative for detection of HBsAg in chronically infected patients and for AFP-based diagnosis of HCC in clinical situations which preclude adequate collection and processing of blood samples. Both research-oriented field studies and routine clinical care may benefit from application of these techniques in resource-limited settings.

Blood Specimen Collection↗
PubMed2000

Environmental and genetic determinants of aflatoxin-albumin adducts in the Gambia.

Aflatoxins together with chronic hepatitis B virus (HBV) infection contribute to the high incidence of hepatocellular carcinoma in developing countries. An understanding of the mechanism of interaction between these factors would provide a strong rationale for developing effective prevention strategies. In this study in The Gambia we examined the effect of environmental (place of residence and timing of sample collection) and host factors (age, sex, HBV status and interindividual variations in carcinogen metabolising enzymes) in determining blood aflatoxin-albumin adduct levels in 357 individuals of whom 181 were chronic HBV carriers. Samples were analysed for aflatoxin-albumin adducts, HBV status and genotypes of glutathione S-transferase (GST) M1, GSTT1, GSTP1 and epoxide hydrolase (EPXH). Urine samples were analysed for 6beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P450 (CYP) 3A4 activity. Adduct levels were significantly higher in subjects resident in rural [geometric mean adduct level 34.9 pg aflatoxin B1-lysine equivalent (28.5-42.8; 95%CI)/mg albumin] than in periurban areas [22.2 pg (14.9-33.4)/mg] and were approximately twice as high in the dry season [mid-February to March; 83.2 pg (53.3-130.8)/mg] than the wet [July to August; 34.9 pg (28.5-42.8)/mg]. In contrast, HBV status, CYP3A4 phenotype, GSTT1, GSTP1 and EPXH genotypes were not associated with aflatoxin-albumin adduct level. However, mean adduct levels were significantly higher in non-HBV infected subjects with GSTM1 null genotype. The main factors which affect aflatoxin-albumin adduct levels in this population are environmental, notably place of residence and timing of sample collection. This study further emphasises the priority to reduce aflatoxin exposure in these communities by primary prevention measures.

Adolescent↗
PubMed2000

Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia.

BACKGROUND: A selective mutation, an arginine-to-serine substitution in codon 249, of the p53 gene has been identified as a "hotspot" mutation in hepatocellular carcinoma (HCC). This mutation occurs in populations that are exposed to aflatoxins and have a high prevalence of hepatitis B virus carriers. We evaluated whether this mutation could be detected in cell-free DNA isolated from the plasma of subjects from The Gambia to detect this mutation that is strongly associated with HCC. METHODS: Fifty-three patients with HCC, 13 patients with cirrhosis, and 53 control subjects were prospectively recruited from The Gambia. Sixty patients, of non-African origin, with various liver pathologies were also selected from France. DNA was extracted and purified from 200-microL aliquots of plasma. The Ser-249 p53 mutation was detected by restriction endonuclease digestion of polymerase chain reaction products from exon 7 and was confirmed by direct sequencing of the amplified DNA. RESULTS: The Ser-249 p53 mutation was detected in plasma DNA from 19 (36%) of the 53 patients with HCC, two (15%) of the 13 patients with cirrhosis, and three (6%) of the 53 control subjects. This mutation was not detected in any plasma DNA from the European patients. The adjusted odds ratio for having the mutation was 16.4 (95% confidence interval = 3.0-90.5) for patients with HCC compared with the control subjects. CONCLUSION: The Ser-249 p53 mutation in plasma DNA is strongly associated with HCC in Gambian patients. This mutation was also detected at a much lower prevalence in plasma DNA from Gambian patients with cirrhosis and in Gambian control subjects, findings that may lead to the earlier detection of HCC. Use of the Ser-249 p53 mutation should facilitate further molecular epidemiologic studies on the development of HCC.

Adult↗
PubMed1999

HPV 16 antibody prevalence in Jamaica and the United States reflects differences in cervical cancer rates.

Human papillomavirus (HPV) is widely accepted as the primary etiologic agent in the development of cervical cancer. DNA of a particular HPV type, HPV 16, is found in about half of tumors tested. Inconsistent with this causal relationship, however, population-based studies of HPV DNA prevalence have often failed to find high rates of anogenital HPV infection in countries with high cervical cancer rates. To examine this issue, we used serology to compare HPV 16 exposure in healthy volunteer blood donors in the United States (n = 278) and similar subjects from a country with 3-fold higher cervical cancer rates, Jamaica (n = 257). Jamaican sexually transmitted disease (STD) patients (n = 831) were also studied to examine in detail the relation of HPV 16 antibodies with sexual history. Serology was conducted using an ELISA employing HPV 16 virus-like particles (VLPs). Age-adjusted seroprevalence rates were greatest among male (29%) and female (42%) STD patients, intermediate in male (19%) and female (24%) Jamaican blood donors and lowest among male (3%) and female (12%) U.S. blood donors. The higher seroprevalence in women was significant, and prevalence tended to increase with age. In multivariate logistic regression, controlling for age and gender, Jamaican blood donors were 4.2-fold (95% CI 2.4-7.2) and STD patients 8.1-fold (95% CI 5.0-13.2) more likely to have HPV 16 VLP antibodies than U.S. blood donors. Among STD patients, HPV 16 antibodies were associated with lifetime number of sex partners and years of sexual activity, as well as other factors. Our data suggest that HPV 16 VLP antibodies are strongly associated with sexual behavior. Moreover, exposure to HPV 16 appears to be much greater in Jamaica than in the United States, consistent with the high rate of cervical cancer in Jamaica.

Adolescent↗
PubMed1999

Jamaica's measles elimination experience.

OBJECTIVES: This article describes the effort to eliminate measles from Jamaica and its impact on measles incidence. METHODS: In addition to routine measles vaccination, the Jamaican Ministry of Health implemented a strategy of a 1-time-only catch-up vaccination campaign, conducted in 1991, and periodic follow-up campaigns, the first of which occurred in 1995. RESULTS: Since 1991, despite careful surveillance, no serologically confirmed indigenous cases of measles have occurred in Jamaica. CONCLUSIONS: Measles virus circulation has been interrupted in Jamaica. The Jamaican experience provides further evidence that global measles eradication is achievable.

Adolescent↗
PubMed1996

Performance-based exposure control limits for pharmaceutical active ingredients.

For many years pharmaceutical companies have established employee exposure limits for the active ingredients used in their products. Historically these limits were derived using traditional risk assessment methods. Because the trend in the pharmaceutical industry is to identify and develop more selective drugs of increasing potency, and because of the difficulty in identifying no-effect levels for certain drugs, a new performance-based approach for setting limits was developed. This method involves assigning materials into one of five hazard categories according to their inherent toxicological and pharmacological properties. The criteria used to assign compounds into performance-based exposure control limit (PB-ECL) categories focus on the degree to which exposure impacts human health. These assignments dictate the level of containment required to assure employee safety that is achieved through the use of engineering controls and safe handling practices. Several matrices were developed to specify general design concepts and controls for unit operations in laboratory and manufacturing operations. Containment options range from conventional handling practices for low potency (PB-ECL Category 1) materials, to technologically advanced systems that result in essentially no open handling for potent or toxic (PB-ECL Category 3) materials, to state-of-the-art facilities employing closed processes and use of robotics for extremely potent (PB-ECL Category 5) materials.

Containment of Biohazards↗
PubMed1990

Evaluation of flu-like symptoms in workers handling xanthan gum powder.

A study was performed to determine the relationship between the handling of xanthan gum powder and reported symptoms. Nose and throat irritation was the most prevalent symptom, and the group with the greatest exposure reported the highest prevalence of nose and throat irritation as well as work-related illness. Employees who reported illness as a result of exposure to materials at work did not show a decrease in pulmonary function over the first day of the workday or workweek. There was no evidence of chronic loss of pulmonary function in employees with either the highest or longest exposure.

Adult↗
PubMed1988

Establishing airborne exposure control limits in the pharmaceutical industry.

In the course of employment, workers in the pharmaceutical industry are exposed to compounds which are designed to produce pharmacological effects. For the most part, exposure occurs in the handling of finely divided solids. Data from laboratory animal studies and clinical trials can be extrapolated to predict possible effects of exposure in the workplace. To that end a procedure for establishing workplace exposure control limits (ECLs) for pharmaceutical products is presented. Workplace exposure limits are given for 32 human health drugs.

Drug Industry↗
PubMed1986

Hazard evaluation of monochloroacetone.

Monochloroacetone was introduced in 1914 as a war gas, and presently it has a number of uses as a chemical intermediate. Apart from its biological properties as a lacrimator and vesicant, it is not a well-studied compound toxicologically. A series of acute toxicity studies were done using different routes of administration. An Ames mutagenicity test also was performed. These data were compared to manufacturing use information and data published in the literature. It is recommended that direct contact with liquid and vapor be prevented through strict engineering controls and that air concentrations be kept below 1 ppm as a ceiling concentration.

Acetone↗
PubMed1980

Correlation of WBGT and botsball sensors.

The standard method for measuring human environmental heat stress is the WBGT. The WBGT apparatus is cumbersome and difficult to relate to standard psychrometric parameters or to other environmental measures such as the Botsball. The work presented in this paper was derived from thermodynamic and heat transfer considerations with corrections applied to be consistent with published experimental results.

Air↗