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Biomedical subjects

D R Thomas

Publications and source records attributed to D R Thomas.

At least 55 records · Page 3Linked to original sources

Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719.

1. The functional profile of the long form of the human cloned 5-HT7 receptor (designated h5-HT7(a)) was investigated using a number of 5-HT receptor agonists and antagonists and compared with its binding profile. Receptor function was measured using adenylyl cyclase activity in washed membranes from HEK293 cells stably expressing the recombinant h5-HT7(a) receptor. 2. The receptor binding profile, determined by competition with [3H]-5-CT, was consistent with that previously reported for the h5-HT7(a) receptor. The selective 5-HT7 receptor antagonist SB-258719 ((R)-3,N-Dimethyl-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]ben zene sulfonamide) displayed high affinity (pKi 7.5) for the receptor. 3. In the adenylyl cyclase functional assay, 5-CT and 8-OH-DPAT were both full agonists compared to 5-HT and the rank order of potency for agonists (5-CT > 5-HT > 8-OH-DPAT) was the same in functional and binding studies. 4. Risperidone, methiothepin, mesulergine, clozapine, olanzapine, ketanserin and SB-258719 antagonised surmountably 5-CT-stimulated adenylyl cyclase activity. Schild analysis of the antagonism by SB-258719 gave a pA2 of 7.2+/-0.2 and slope not significantly different from 1, consistent with competitive antagonism. 5. The same antagonists also inhibited basal adenylyl cyclase activity with a rank order of potency in agreement with those for antagonist potency and binding affinity. Both SB-258719 and mesulergine displayed apparent partial inverse agonist profiles compared to the other antagonists tested. These inhibitory effects of antagonists appear to be 5-HT7 receptor-mediated and to reflect inverse agonism. 6. It is concluded that in this expression system, the h5-HT7(a) receptor shows the expected binding and functional profile and displays constitutive activity, revealing inverse agonist activity for a range of antagonists.

Adenylyl Cyclases↗

A retrospective cohort study of risk factors for missing preschool booster immunisation.

AIM: To identify factors associated with non-uptake of preschool booster immunisation. DESIGN: Data from the computerised child health system was used to study all children born in 1990 and living in South Glamorgan, Wales, on their 5th birthday. Factors associated with preschool booster uptake were investigated using multiple logistic regression. RESULTS: Preschool booster coverage in the study cohort was 91.4%. After adjustment for other variables, uptake was associated most strongly with completed primary immunisation for diphtheria, tetanus, and polio vaccine or first dose measles, mumps, and rubella vaccine. Identifying children who miss either of these predicts 52.4% of those who miss the preschool booster. CONCLUSION: Effective targeting of children who have missed previous immunisations could improve preschool booster uptake and ensure maximum uptake of at least one dose of measles, mumps, and rubella vaccine. Achieving optimum measles vaccine coverage is vital to achieve the goal of measles elimination.

Child, Preschool↗

An audit of prostate-specific antigen and clinical symptoms in general practice.

The objective was to devise local guidelines for the referral of patients with suspected prostatic carcinoma following evaluation by a retrospective audit of the value of the prostate-specific antigen concentration, together with age, urological symptoms, and digital rectal examination in the diagnosis of carcinoma of the prostate. Relevant details were collected from the notes of 582 patients from general practice and hospital. The significant diagnostic factors were ascertained by stepwise logistic regression. Prostate-specific antigen concentration, digital rectal examination and significant terminal dribbling were the most powerful factors in the diagnosis of carcinoma of the prostate. When prostate-specific antigen concentration was considered in isolation, a value of 6.5 ng/ml appeared appropriate for referral. Age was not significant, perhaps due to the narrow patient age range. The significant diagnostic factors were built into an algorithm calculating the probability of carcinoma of the prostate. This algorithm, together with prostate-specific antigen concentration results and digital rectal examination findings, forms the basis of the referral guidelines and a subsequent prospective study.

Adult↗

Home-based primary care in the VA setting, with a focus on Birmingham, Alabama.

The Veterans Administration Hospital-Based Home Care Program provides comprehensive primary care to homebound veterans. Unlike Medicare-funded home care, it is not oriented to episodic provision of skilled nursing care, but rather to long-term primary care in the home. The interdisciplinary composition of HBPC teams allows for innovative approaches to care and coordinated implementation of treatment plans. Outcomes assessment of care provided through HBPC has been positive, suggesting an overall improvement in function and decrease in health care costs among those using the HBPC Program. The HBPC Program offers a tested model of primary home care within a "managed care" model. Its positive features should be considered by those initiating managed primary home care within the private sector.

Aged↗

Acemannan hydrogel dressing versus saline dressing for pressure ulcers. A randomized, controlled trial.

Aloe vera has been used for centuries as a topical treatment for various conditions and as a cathartic. An amorphous hydrogel dressing derived from the aloe plant (Carrasyn Gel Wound Dressing, Carrington Laboratories, Inc., Irving, TX) is approved by the Food and Drug Administration for the management of Stages I through IV pressure ulcers. To evaluate effectiveness of this treatment, 30 patients were randomized to receive either daily topical application of the hydrogel study dressing (acemannan hydrogel wound dressing) or a moist saline gauze dressing. Complete healing of the study ulcer occurred in 19 of 30 subjects (63%) during the 10-week observation period. No difference was observed in complete healing between the experimental and the control groups (odds ratio 0.93, 95% CI 0.16, 5.2). This study indicates that the acemannan hydrogel dressing is as effective as, but is not superior to, a moist saline gauze wound dressing for the management of pressure ulcers.

Adjuvants, Immunologic↗

Uptake of measles containing vaccines in the measles, mumps, and rubella second dose catch-up programme in Wales.

A two dose schedule for measles, mumps, and rubella (MMR) vaccination was introduced in England and Wales on 1 October 1996 in order to prevent the accumulation of susceptible individuals and thus prevent future epidemics. A routine second dose of MMR vaccine is now offered with the diphtheria, tetanus and polio (DTPol) preschool booster. In addition a second dose of MMR is being offered to all children born since 1 January 1990 without documented histories of two doses of measles containing vaccine in a catch up programme due to end in March 1998. Progress in the catch up programme in Wales was assessed by examining uptake of all possible combinations of measles containing vaccines in four birth cohorts by 1 May 1997. Of 126,550 children born between January 1990 and March 1993 (aged 4 years, 1 month to 7 years, 3 months) and living in Wales on 1 May 1997, 63,855 (50.5%) had received two doses of measles containing vaccine and 120,668 (95.4%) had received at least one dose, but 5882 children (4.6%) had no record of having received any measles containing vaccine. Uptake of the preschool DTPol booster in the same cohort was 87.2%. Uptake of two measles containing vaccines varied between health authority (range: 35.4-58.3%) and between birth cohorts (range: 40.0-81.8%). Few (18.4%) previously unimmunised children had attended for the MMR catch-up dose. Successful elimination of measles may depend on targeting this group in order to improve coverage. Although this analysis was carried out during the catch-up programme, these data suggest that the programme may not reach the children who most need to be immunised.

Child↗

Surveillance of influenza in Wales: interpreting sentinel general practice rates using contemporaneous laboratory data. Opportunities and limitations.

OBJECTIVES: To evaluate the opportunities and limitations of using laboratory data to enhance sentinel general practice surveillance of influenza. DESIGN: Descriptive study of active sentinel surveillance of clinically diagnosed influenza in general practice and passive total population surveillance of laboratory reports of influenza A, influenza B, Mycoplasma pneumoniae, and respiratory syncitial virus infections. SETTING: Wales. SUBJECTS: Total sentinel practices population (currently 228,130); population of Wales (2,913,000, 1994 mid-year estimate). MAIN OUTCOME MEASURES: Simplicity, flexibility, acceptability, sensitivity, predictive value positive, representativeness, and timeliness of a surveillance system. Rate of influenza and other respiratory infections. RESULTS: Sentinel general practice surveillance of influenza in Wales is simple, flexible, acceptable, timely, representative, and relatively sensitive. Current laboratory surveillance is complex and less timely than sentinel practice surveillance but is complete and has a relatively high positive predictive value. For the period January 1993 to September 1996, peaks in rates of influenza reported by sentinel practices during winters 1993/94 and 1995/96 were temporally associated with increased rates of laboratory confirmed influenza A and respiratory syncitial virus, whereas the peak in 1994/95 was associated with increased rates of laboratory confirmed influenza B, M pneumoniae, and respiratory syncitial virus. CONCLUSIONS: Timely laboratory data can add value to influenza data already obtained from sentinel general practice surveillance. However continuous audit is essential to resolve the possible limitations of either surveillance system.

Evaluation Studies as Topic↗

The role of nutrition in prevention and healing of pressure ulcers.

Among the many risk factors for pressure ulcers, malnutrition is potentially reversible. This article examines the relationship of malnutrition to the prevention and healing of pressure ulcers. Evidence for nutrition in preventing and healing pressure ulcers is presented. Specific nutrients, including some amino acids, vitamins, and minerals, have been evaluated for their effects on wound healing.

Humans↗

Pressure ulcers. Local wound care.

Local care of pressure ulcers includes wound cleansing, débridement, and dressings. Wound cleansing should remove loose debris and exudate but should not damage viable tissue. Saline irrigation is the standard. Débridement is often necessary for Stage III and IV pressure ulcers and can be performed autolytically, mechanically, enzymatically, or sharply. Prompt débridement is essential for infected wounds. Dressings should keep the wound bed continuously moist, should not be toxic to granulation tissue, and should keep the surrounding intact skin dry. Randomized, controlled clinical trials are necessary to define optimal local wound care further.

Anti-Infective Agents, Local↗

Existing tools: are they meeting the challenges of pressure ulcer healing?

The measure of a chronic wound's progress (or lack of progress) toward healing is difficult. An instrument designed to measure healing in pressure ulcers must conform to two statistical concepts: validity and reliability. Existing tools are examined, based on this conceptual statistical framework. A model for the perfect wound healing instrument can be described.

Chronic Disease↗

Using principal component analysis to describe wound status.

Principal component (PC) analysis was used to assess the status of pressure ulcers over time in 37 subjects. Content validity was established by literature review and expert opinion. The primary variables in the wound healing model are ulcer surface area, exudate amount, and surface appearance. A linear function based on PC analysis of these values was established at each time point with an appropriate weighting of 2:3:3. This function explained 55% to 65% of the variation in the data. Other variables were considered in the model as well. However, because of the correlation of these variables with the original three, the modeling was not improved. A decreasing function from week 0 to week 8 established a good linear fit to the data and reasonable discrimination between time points, given the limitations of the sample size. There is good discrimination among the time points, at least for the earlier times compared with the later times. The procedure, although promising, requires validation with a larger data set.

Discriminant Analysis↗

Pressure ulcer scale for healing: derivation and validation of the PUSH tool. The PUSH Task Force.

Measuring progress toward healing is fundamental to the management of pressure ulcers. A method to assess progress of an individual ulcer over time is lacking. Given the limitations of currently available instruments and the need for a precise and practical method of monitoring healing in clinical practice, the National Pressure Ulcer Advisory Panel initiated the development of a new tool for measuring pressure ulcer healing. The key elements in developing an instrument include simplicity of use in clinical settings, validity for measuring whether ulcers are improving or worsening, and sensitivity to changes in the ulcer between observations. A new tool incorporating surface area, exudate amount, and surface appearance is proposed. Content validity, correlation validity, prospective validity, and sensitivity to change can be met by the proposed Pressure Ulcer Scale for Healing instrument.

Humans↗

m-Chlorophenylpiperazine (mCPP) is an antagonist at the cloned human 5-HT2B receptor.

The behavioural effects of m-chlorophenylpiperazine (mCPP) in rats and its clinical effects in man are thought to be related to its action at 5-HT2B/2C receptors. However, although mCPP is a partial agonist at these subtypes in rat, its efficacy at human 5-HT2B/2C receptors is unknown. We therefore investigated the activity of mCPP at cloned human 5-HT2B and 5-HT2C receptors. mCPP was a partial agonist at the human 5-HT2C receptor but antagonized the human 5-HT2B receptor. Therefore, while supporting the proposal that at least some of the clinical effects of mCPP are likely to be mediated via stimulation of the 5-HT2C receptor, this study also suggests that any 5-HT2B receptor-mediated effects are more likely to result from receptor blockade than from receptor activation.

Animals↗

Functional effects of the bacterial insecticide Bacillus thuringiensis var. kurstaki on aquatic microbial communities.

Epilithic microbial communities were colonized on leaf disks and exposed to commercial preparations of Bacillus thuringiensis var. kurstaki (Btk) in aquatic microcosms. Responses in terms of microbial respiration, bacterial cell density, protozoan density, and microbial decomposition activity were measured. Test concentrations for treatments with Dipel 64AF and Dipel 8AF in microcosms were the expected environmental concentration (EEC) of 20 IU/ml, 100x the EEC, and 1000x the EEC. Bacterial cell density in the biofilm of leaf disks was significantly increased at concentrations as low as the EEC. There were no concomitant alterations in protozoan density. Microbial respiration was significantly increased, and decomposition activity was significantly decreased, but only at the artificially high concentration of 1000x the EEC. This effect was attributed to the spore-crystal component rather than formulation ingredients. Microbial decomposition of leaf material was also determined in outdoor stream channels treated at concentrations ranging from the EEC to 100x the EEC. Although there tended to be reduced decomposition activity in treated channels, there were no significant differences in mass loss of leaf material between treated and control channels. Various regression, classification, and ordination procedures were applied to the experimental data, and none indicated significant treatment effects. These results from laboratory and controlled field experiments indicate that contamination of watercourses with Btk is unlikely to result in significant adverse effects on microbial community function in terms of detrital decomposition.

Agammaglobulinaemia Tyrosine Kinase↗

Hospital-acquired pressure ulcers and risk of death.

OBJECTIVE: To evaluate the impact of in-hospital pressure ulcer development on mortality among older, high-risk, hospitalized patients up to 1 year post-hospital discharge, after adjusting for baseline patient characteristics, disease severity, hospital complications, and discharge activity level. DESIGN: A prospective, inception, cohort study. SETTING: An urban, tertiary, acute care, university teaching hospital. PATIENTS: A total of 286 patients aged 55 or older, expected to be confined to bed or chair for at least 5 days, who were admitted to the hospital without a Stage 2 or greater pressure ulcer. MEASUREMENTS: The primary outcome measurement was time to death from admission to 1-year post-hospital discharge. Baseline information included demographic, medical, functional, and nutritional variables known to be associated with increased mortality. Measures of global disease severity and co-morbidity included the admitting physician's estimate of illness severity and life expectancy, the acute physiology score of APACHE II, the Co-morbidity Damage Index, and the Medicus Nursing Classification Score. Baseline infections, incident infections, and noninfectious hospital complications were determined. Functional activity level was determined at hospital discharge. Post-discharge vital status was determined by telephone interviews at 3,6,9, and 12 months after discharge and confirmed by death certificate review. MAIN RESULTS: Development of an in-hospital pressure ulcer was associated with greater risk of death at 1 year (59.5% vs 38.2%, P = .02). However, pressure ulcer development did not remain independently associated with decreased survival after adjusting for other predictors of mortality. Predictors of mortality at hospital admission by multivariate Cox regression analysis included weight loss in the 6 months before admission (RR 2.4, CI 1.6, 3.6), physician estimate of life expectancy (RR 2.1, CI 1.7, 2.6), and the Co-morbidity Damage Index (RR 1.1, CI 1.0, 1.2). Multivariate predictors of 1-year mortality at discharge included physician estimate of life expectancy (RR 2.2, CI 1.8,2.6), weight loss in the 6 months before admission (RR 2.2, CI 1.5,3.2), remaining confined to bed or chair (RR 1.9, CI 1.2,3.1), and the total number of hospital complications (RR 1.3, CI 1.2,1.5). CONCLUSIONS: Pressure ulcers that develop during acute hospitalization are not associated with reduced 1-year survival among high risk older persons after adjusting for nutritional and functional status, global measures of disease severity and co-morbidity, and noninfectious hospital complications.

APACHE↗

Nutritional factors affecting wound healing.

The consistent relationship between poor nutritional status and risk of complications forms the cornerstone of nutritional support. Yet there is controversy about the ability of nutritional support to reduce complications or improve wound healing. This controversy stems from a number of issues. Diagnosing poor nutrition is not always easy and straight forward. There is sometimes a question whether a patient is malnourished or simply in overall poor health. Studies examining the relationship between nutrition and patient outcome are typically based on animal rather than human models. Even in clinical settings, aspects of care such as enteral or parenteral nutrient delivery may decrease the benefit of nutritional support, making outcomes even harder to measure. The effect of specific nutrients have been examined, such as protein, amino acids, vitamins C and A, and zinc. However, there are still questions regarding how much individual supplementation of a nutrient will positively affect overall outcomes. Although the relationship between specific nutrients and wound healing is not clearly defined by current studies, each patient should be provided with a complete, balanced therapeutic diet. There is at least suggestive evidence that improvement in nutritional status can improve outcomes of wound healing.

Animals↗

Preoperative assessment of older adults.

Caring for older patients who need surgery presents challenging medical situations. The clinical paradigm involves identifying coexisting disease, defining the urgency of the intervention, and predicting postoperative complications based on the type of surgery planned. The prime function of the medical consultant is searching for correctable medical conditions. The consultant must carefully identify coexisting and comorbid conditions. Emergency surgery should be avoided, if possible, by elective planning. The risk of surgery varies with the procedure. Non-body cavity surgery, with the exception of hip fracture repair, is usually tolerated well. Age is a risk factor for surgery, but coexisting disease is more important than age alone. The net effect of improvements in surgical outcome advances the age at which surgical risk becomes prohibitive.

Age Factors↗