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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 127 records · Page 7Linked to original sources

Homozygosity at the dopamine DRD3 receptor gene in cocaine dependence.

We examined the hypothesis that the dopamine D3 receptor gene (DRD3) is a susceptibility factor for cocaine dependence. The MscI/BalI polymorphism of the DRD3 gene was examined in 47 Caucasian subjects with cocaine dependence and 305 Caucasian controls. Based on prior studies with a range of psychiatric disorders we hypothesized there would be a decrease in the frequency of the 12 genotype in the patient sample (increased homozygosity). We observed a significant decrease in the frequency of 12 heterozygotes in subjects with cocaine dependence (29.8%) vs controls (46.9%) (P </= 0.028). This percentage was still lower in those who had chronically used cocaine for more than 10 years (25%), or more than 15 years (21.5%). The DRD3 gene accounted for 1.64% of the variance of cocaine dependence. The DRD2 gene had an independent and additive effect on cocaine dependence. These findings support a modest role of the DRD3 gene in susceptibility to cocaine dependence.

Adult↗

The effect of wind speed and direction on the distribution of sewage-associated bacteria.

A study of the relationship between wind and the distribution of sewage-associated bacteria was undertaken at a location where the sewage was discharged into the sea adjacent to the mouth of a river. The numbers of presumptive Escherichia coli were determined in 149 sea-water samples taken from three locations at distances of 1.9, 2.4 and 4.3 km from the outfall. On each sampling occasion, data on the wind speed and direction in the 3 h prior to collection of the samples were also collected. Analysis of these data demonstrated a significant role for wind speed and direction. With respect to wind direction, the numbers of presumptive E. coli present in a sample were significantly higher when the sample site lay downwind of the outfall. Wind speed was shown to have an influence on the numbers of presumptive E. coli only when the sample site was downwind of the outfall. In an analysis of 61 samples, an inverse correlation (r2 = 0.73) between salinity and log presumptive E. coli numbers was demonstrated. These data demonstrate that wind speed and direction at the time of sampling significantly influence the numbers of presumptive E. coli detected in any sea-water sample. It is argued that failure to pay sufficient attention to these parameters in the design of monitoring programmes may result in the generation of data that could provide a seriously distorted picture of the microbiological status of a water body.

Colony Count, Microbial↗

Prophylactic plating of the donor site of osteocutaneous radial forearm flaps.

We carried out a retrospective study of fracture morbidity of radial forearm osteocutaneous donor sites. During a period of three-and-a-half years, 12 patients had had composite flaps taken, and 5 of them had subsequently fractured the radius. We then elected to plate the radius prophylactically and found that over a period of just over two years, none of the 8 patients who had had prophylactic plating at the original harvesting operation had subsequently fractured the radius.

Adult↗

Toxicological evaluations of cyclopiazonic acid and ochratoxin A in broilers.

The individual and combined effects of ochratoxin A (OA) and cyclopiazonic acid (CPA) were evaluated in Petersen x Hubbard broiler chickens from 1 d to 3 wk of age. The experimental design was a 2 x 2 factorial with treatments of 0 and 2.5 mg OA/kg feed and 0 and 34 mg CPA/kg feed. Production performance, serum biochemistry, and gross pathological observations were evaluated. Body weight gain was reduced (P < 0.05) by OA, CPA, and OA-CPA in combination at the end of 3 wk. Ochratoxin A significantly increased the relative weight of the kidney and serum concentrations of uric acid and triglycerides and decreased total protein, albumin, and cholesterol. The toxicity of CPA was expressed primarily through increased relative weights of the proventriculus and increased activity of creatine kinase. Exposure to OA-CPA was characterized by increased relative weights of the liver, kidney, pancreas, and proventriculus; decreased concentrations of serum albumin, total protein, and cholesterol; increased activity of creatine kinase; and increased concentrations of triglycerides and uric acid. Postmortem examination revealed that the chickens fed CPA or OA-CPA had thickened mucosa and dilated proventricular lumen. Data from this study demonstrate that OA, CPA, and the OA-CPA combination can limit broiler performance and adversely affect broiler health. The interaction of the compounds was primarily additive or less than additive in the parameter in which the interaction occurred.

Animal Feed↗

A three-year follow up of tension free vaginal tape for surgical treatment of female stress urinary incontinence.

OBJECTIVE: To study the long term results of tension-free vaginal tape, a new ambulatory surgical procedure for treatment of female stress urinary incontinence. STUDY DESIGN: A prospective open study using a standardised protocol for pre- and post-operative evaluation. PARTICIPANTS: Fifty consecutive women participated in the study. All suffered from genuine stress incontinence. The mean age was 57 years (SD 11), 42 women (84%) were multiparous, 8 (16%) nulliparous. SURGICAL METHOD: Tension-free vaginal tape implies the implantation of a prolene tape around mid-urethra via a minimal vaginal incision. The procedure is carried out under local anaesthesia, allowing the surgeon to check intra-operatively that continence has been obtained. RESULTS: All the women except one could be operated on an ambulatory basis under local anaesthesia. Mean operation time was 29 minutes (range 1647). Ninety percent of the women were able to micturate spontaneously within 24 hours with insignificant residual volumes. In another 10% of the women an in-dwelling catheter had to be used temporarily. There was no need for long term postoperative catheterisation (> 14 days). Post-operative evaluation was carried out after 2 to 6, 12, 24 and 36 months. According to the protocol, 86% of the women were completely cured and another 11% were significantly improved. No signs of deterioration of the results over time were observed. No defect in healing or rejection of the tape occurred. CONCLUSION: We consider the tension-free vaginal tape operation to be a safe and effective surgical procedure for the treatment of female urinary stress incontinence. The technique can be considered as an ambulatory procedure performed under local anaesthesia, allowing the majority of the women to be discharged from the clinic the same day or the day after the procedure.

Adult↗

Second trimester maternal serum beta human chorionic gonadotrophin and pregnancy outcome.

The aim of this prospective, controlled study was to examine the relation between second trimester maternal serum beta human chorionic gonadotrophin (HCG) and birthweight. The study population consisted of 192 women with maternal serum betaHCG > or = 3.5 multiple of the median and a control group with the same number of women with maternal serum betaHCG < or = 2.0 multiple of the median. There was no difference in birthweight and other pregnancy outcomes between the two groups. When used prospectively, elevated betaHCG in the mid-trimester is not a predictor for intrauterine growth restriction or other pregnancy complications.

Biomarkers↗

DiHA Dextran Copolymer, a new biocompatible material for endoscopic treatment of stress incontinent women. Short term results.

BACKGROUND: This study was undertaken to investigate the safety and effect of DiHA, dextranomers in hyaluronan, a new biocompatible material for endoscopic treatment of stress incontinence, and to further develop the injection technique. METHODS: Twenty women aged 38 to 90 years with genuine stress incontinence participated. Seventeen were followed for a minimum of 6 months after treatment and three for a minimum of 3 months. The DiHA implants were administrered by transurethral endoscopically controlled submucosal injections under local anesthesia. Safety was assessed mainly in terms of infection, need for catheterization, residual urine and dysuria. The treatment efficacy was estimated objectively by a short-term pad test with standardized physical exercise and a 48 h pad-test, 7 days, and 1, 3 and 6 months after treatment. The patient's subjective experience of the effect was also studied. RESULTS: The implantation procedure was well accepted by the patients. Four patients required catheterization due to voiding problems during the first 24 postoperative hours. One patient had urinary retention 14 days postoperatively. No UTI or local infection was detected. Some patients had transient urgency. In 17 or 20 patients the treatment resulted in objective cure or improvement. CONCLUSIONS: This substance shows promising qualities for endoscopic treatment of stress incontinence.

Adult↗

A novel approach to monitoring adherence to preventive therapy for tuberculosis in adolescence.

OBJECTIVES: To evaluate the usefulness of a microelectronic tablet-dispenser for monitoring adherence to preventive therapy for tuberculosis infection in adolescents. METHODOLOGY: Twenty-one patients with positive Mantoux tests were treated with isoniazid (INH), dispensed in a microelectronic tablet-dispenser that recorded the date, time and duration that the container was opened. Other measures of adherence included attendance at clinic, patient self-report, tablet count, and measurement of urinary INH metabolites. RESULTS: The mean adherence rates were: 83% using attendance at clinic, 91% using tablet counts, 79% using urine assays, and 66% using the electronic tablet-dispenser. Self-reporting appeared to over-estimate adherence. CONCLUSION: Adherence to 6 months of INH calculated using different measures is higher in this study than in previous reports. Microelectronic tablet-dispensers are an effective method to objectively measure adherence on a daily basis. Other measures are less helpful.

Adolescent↗

Increased leucine turnover and insulin resistance in men with advanced HIV infection.

BACKGROUND: The purpose of this study was to determine if patients with advanced HIV infection exhibit increased rates of leucine turnover and to determine dose effects of insulin on suppression of leucine turnover. We also wished to evaluate hepatic glucose production and re-examine peripheral insulin sensitivity in HIV infected adults. METHODS: Results from 9 males with advanced HIV disease (96-121% ideal body weight, NW-AIDS) and 3 males (80-88% ideal body weight, UW-AIDS) were compared to age and weight matched normal volunteers (NW-C and UW-C). Each subject underwent basal leucine turnover studies followed by insulin dose response studies using a step-up hyperinsulinemic euglycemic clamp (insulin dose: 10, 20 and 120 mU/m2/min) and the stable isotope [1-13C]leucine. Hepatic glucose production was measured using the stable isotope d-6,6(2)H2-glucose. Resting energy expenditure (REE) was measured by indirect calorimetry and a 24-hour food recall was obtained. Viral load, Karnofsky score, and CD4 counts were measured in AIDS subjects. RESULTS: All subjects with AIDS had higher rates of leucine appearance (leucine Ra) than controls. Although both AIDS and Controls demonstrated suppression of leucine Ra with insulin, suppression was less in AIDS subjects. There was a strong relationship between leucine Ra and viral load (r = 0.87, P = 0.02). The AIDS subjects exhibited peripheral insulin resistance when compared to controls. CONCLUSIONS: Our results suggest that patients with HIV have both peripheral insulin resistance and resistance to the anticatabolic effects of insulin.

Adult↗

The influence of acute hypoxia and carotid body denervation on thermoregulation during non-rapid eye movement sleep in the developing lamb.

We investigated the influence of ambient temperature on the thermoregulatory response to hypoxia in developing lambs before (at 4 and 14 days of age) and after (17 and 30 days of age) carotid body denervation (CBD). Lambs were studied during non-rapid eye movement sleep at thermoneutral (23-15 C) and cool (10-5 C) ambient temperatures, during normoxia and acute hypoxia (inspired oxygen content of 13 %). Measurements of oxygen consumption, arterial partial pressures of O2 and CO2, colonic temperature, incidence of shivering and plasma concentrations of thyroid hormones, cortisol, insulin and glucose were made under each condition. Oxygen consumption was higher at cool compared with thermoneutral ambient temperatures and decreased during hypoxia during cooling at all stages. At 4 days of age, only one lamb shivered during cooling in normoxia, but 4 out of 12 lambs shivered during hypoxia and colonic temperature fell, significantly, by 0.2 C. At 14 days, 8 out of 12 lambs shivered during cooling, of which 6 continued to shiver during hypoxia but colonic temperature did not change significantly. Plasma triiodothyronine concentrations increased on cooling at 4 and 14 days, an affect that was inhibited by hypoxia at 4, but not 14 days of age. At 17 days of age, i.e. post-CBD, plasma thyroid hormone concentrations and oxygen consumption were lower during cold exposure compared with intact lambs at 14 days of age. In CBD lambs, imposing further hypoxia resulted in colonic temperature falling 0. 6 C during cooling, with only 2 out of 10 lambs shivering. Plasma glucose and insulin, but not cortisol, concentrations decreased during hypoxia, irrespective of age or CBD. It is concluded that hypoxia has an important influence on metabolism and thermoregulation, which is modulated by age and environmental conditions. Compromised carotid body function, in lambs older than 2 weeks of age, can result in severe hypoxia and thermoregulatory dysfunction even with modest environmental cooling.

Animals↗

A reference terminology for drugs.

GALEN technology for re-usable terminologies using formal classification is being applied to the creation and maintenance of a reference terminology for drugs. GALEN's techniques are being used to address specific deficiencies of existing drug classifications that make it difficult to create and maintain guidelines to support prescribing in the care of patients with chronic diseases. The reference terminology is in two parts; firstly, a re-usable and automatically-classified 'ontology' is built with GALEN technology; this describes generic drugs, their composition in terms of chemicals and chemical classes, their actions, indications and interactions. Secondly, a 'dictionary' of prescribable proprietary products is integrated with this ontology. The result is a drug resource designed to support both the traditional uses of a drug knowledge base (e.g. prescribing and messaging), and the specialized demands of guideline authoring and execution.

Artificial Intelligence↗

A controlled pilot study in the use of telemedicine in the community on the management of heart failure--a report of the first three months.

This is a controlled pilot study of twenty patients to see if heart failure management can be optimised in the community using telemedicine. The study seeks to examine the feasibility, acceptability and reliability of using telemedicine in this context. Heart failure is a common condition. It is an important cause of mortality and morbidity and has large cost implications for the NHS. Most patients are managed in the UK in General Practice based on clinical assessment by the practitioner. Twenty patients with a mean age of 75.1 years and mean New York Heart Association grade of 1.75 were randomised in to two equal groups (telemonitoring and control) and observed for a period of three months. All twenty patients had a Cardiologist assessment and quality of life measurement at the beginning and end of the study. Patients in the telemedicine group had their blood pressure, pulse and weight data collected daily and undertook a weekly video conference with the nurse. Control patients had their blood pressure, weight and pulse measured at six weekly intervals. The study has been extended for a further six months beyond its initial three-month observation period to see if the initial short term benefit in the telemedicine group is maintained.

Community Health Services↗

In vitro metabolism of the HIV-1 protease inhibitor ABT-378: species comparison and metabolite identification.

HIV protease inhibitor ABT-378 (ABT-378) was metabolized very extensively and rapidly by liver microsomes from mouse, rat, dog, monkey, and humans. The rates of NADPH-dependent metabolism of ABT-378 ranged from 2.39 to 9.80 nmol.mg microsomal protein-1.min-1, with monkey liver microsomes exhibiting the highest rates of metabolism. ABT-378 was metabolized to 12 metabolites (M-1 to M-12), which were characterized by mass and NMR spectroscopy. The metabolite profile of ABT-378 in liver microsomes from all five species was similar, except that the mouse liver microsomes did not form M-9, a minor secondary metabolite. The predominant site of metabolism was the cyclic urea moiety of ABT-378. In all five species, the major metabolites were M-1 (4-oxo-ABT-378) and M-3 and M-4 (4-hydroxy-ABT-378). Metabolite M-2 (6-hydroxy-ABT-378) was formed by rodents at a faster rate than by dog, monkey, and human liver microsomes. Metabolites M-5 to M-8 were identified as monohydroxylated derivatives of ABT-378. Metabolites M-9 and M-10 were identified as hydroxylated products of M-1. Metabolites M-11 and M-12 were identified as dihydroxylated derivatives of ABT-378. The metabolite profile in human hepatocytes and liver slices was similar to that of human liver microsomes. The results of the current study indicate that ABT-378 is highly susceptible to oxidative metabolism in vitro, and possibly in vivo, in humans.

Animals↗

Association of HLA profiles with early plasma viral load, CD4+ cell count and rate of progression to AIDS following acute HIV-1 infection. Multicenter AIDS Cohort Study.

BACKGROUND: Host genetic factors, such as HLA alleles, play an important role in mediating the course of HIV-1 disease progression through largely undefined mechanisms. OBJECTIVES: To examine the association of HLA markers with HIV-1 RNA plasma viral load and other factors associated with course of disease progression in HIV-1 infection. DESIGN AND METHODS: A group of 139 HIV-1 seroconverters from the Multicenter AIDS Cohort Study had been typed for a variety of HLA markers. HIV-1 RNA plasma viral load was measured from frozen plasma specimens obtained approximately 9 months following seroconversion. CD4+ cell counts were available from the same study visit. Statistical analysis was performed using survival techniques and linear regression models to quantify the relative associations of an HLA score profile, HIV-1 RNA plasma viral load, CD4+ cell count and age with each other and with rate of progression to AIDS and death. RESULTS: Cox proportional hazards models showed statistically significant differences in time to AIDS by HLA score profile category per unit increase [relative hazard (RH), 0.64; P < 0.0001], HIV-1 RNA plasma viral load per 10-fold increase (RH, 2.04; P = 0.0003), and CD4+ cell count per 100 cell (x 10(6)/l) increase (RH, 0.90; P = 0.02). Multivariate linear regression showed that viral load was 39% lower (P = 0.0001) for each unit increase in HLA score profile and 13% lower (P = 0.002) for each 100 cell (x 10(6)/l) increase in CD4+ cell count. CONCLUSION: The means by which the HLA score profile influences the time to AIDS is probably through immunologic responses that affect the rate of HIV-1 replication, as manifested by the HIV-1 RNA plasma viral load during the first 6-12 months following acute infection.

Acquired Immunodeficiency Syndrome↗

TNF-alpha induction of CD44-mediated leukocyte adhesion by sulfation.

Regulation of cell adhesion is important for immune system function. CD44 is a tightly regulated cell adhesion molecule present on leukocytes and implicated in their attachment to endothelium during an inflammatory immune response. The proinflammatory cytokine tumor necrosis factor-alpha, but not interferon-gamma, was found to convert CD44 from its inactive, nonbinding form to its active form by inducing the sulfation of CD44. This posttranslational modification was required for CD44-mediated binding to the extracellular matrix component hyaluronan and to vascular endothelial cells. Sulfation is thus a potential means of regulating CD44-mediated leukocyte adhesion at inflammatory sites.

Cell Adhesion↗