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Biomedical subjects

D R Thomas

Publications and source records attributed to D R Thomas.

At least 37 records · Page 2Linked to original sources

Wound management in postacute care.

Decreasing hospital length of stay has dictated that postacute and long-term care facilities bear the brunt of treating acute and chronic wounds. Two types of chronic wounds are discussed: (1) pressure ulcers and (2) diabetic ulcers. The differential diagnosis of these ulcers is imperative because the management of both types of wound differs substantially. Wound therapy includes relieving pain, correcting nutritional deficiencies, maintaining an optimal wound environment, shielding the wound from further damage, removing necrotic debris, promoting granulation tissue formation, protecting against bacterial contamination, choosing an appropriate dressing, and surgical treatment. The application of these principles is discussed, and the differences among wound types are highlighted.

Aged↗

Evidence of persisting serum antibodies to Escherichia coli O157 lipopolysaccharide and Verocytotoxin in members of rural communities in England.

The techniques of enzyme-linked immunosorbent assay (ELISA) and immunoblotting were used to examine a total of 1667 sera, from apparently healthy members of rural communities in England, for antibodies to the lipopolysaccharide (LPS) of Escherichia coli O157 and Verocytotoxins (VT). Twenty-nine sera from 22 individuals were shown to have antibodies specific for E. coli O157 LPS. Some of these lived on livestock farms and had occupational contact with cattle, suggesting that personnel working with farm animals may produce serum antibodies to the O157 LPS antigens. Fifteen people had IgG class antibodies to O157 LPS, suggesting long-term exposure to E. coli O157 and five people had serum antibodies on more than one occasion showing evidence of persistent antibodies to O157 LPS. Thirteen sera from 12 of 22 individuals also contained antibodies to VT1, VT2 or both toxins. Ten sera contained antibodies to VT1 and VT2, three sera contained antibodies to VT2 only.

Adult↗

[(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors.

Binding of the 5-HT(7) receptor antagonist radioligand [(3)H]-SB-269970 to human 5-HT(7(a)) receptors expressed in HEK293 cell membranes (h5-HT(7(a))/293) and to guinea-pig cerebral cortex membranes, was characterized and compared with [(3)H]-5-CT binding. [(3)H]-SB-269970 (1 nM) showed full association with h5-HT(7(a))/293 membranes after 40 min. Specific binding at equilibrium represented >90% of total binding and was fully reversible by methiothepin (10 microM), full dissociation occurring by 100 min. The association (k(+1)) and dissociation (k(-1)) rate constants were 0.05 nM(-1)min(-1) and 0.05 min(-1) respectively, giving a K(D) (k(-1)/k(+1)) of 1.0 nM. [(3)H]-SB-269970 bound saturably and apparently monophasically to both h5-HT(7(a))/293 and guinea-pig cortex membranes, with K(D) values of 1.25+/-0.05 and 1.7+/-0.3 nM respectively. The B(max) for [(3)H]-SB-269970 to both h5-HT(7(a))/293 and guinea-pig cortex membranes (5780+/-380 and 125+/-8.2 fmoles mg protein(-1) respectively) was similar to that for [(3)H]-5-CT (6190+/-940 and 143+/-19 fmoles mg protein(-1) respectively). These data suggest that, in each tissue, both radioligands labelled the same population of receptors, which appear to be present in an agonist high affinity state. The profile of compound inhibition of [(3)H]-SB-269970 binding to h5-HT(7(a))/293 and guineapig cortex membranes correlated well (corr. coeff. 0.98) with those for [(3)H]-5-CT binding and were consistent with the profiles reported previously for the human 5-HT(7(a)) and guinea-pig cortex 5-HT(7) receptors using [(3)H]-5-CT. Hill slopes for inhibition of [(3)H]-SB-269970 and [(3)H]-5-CT binding were close to 1, consistent with binding to a single receptor population in both tissues. [(3)H]-SB-269970 represents the first selective 5-HT(7) antagonist radioligand, which should aid further characterization of 5-HT(7) receptors in recombinant and native tissues and help establish their role in brain function.

Animals↗

Characterization of SB-269970-A, a selective 5-HT(7) receptor antagonist.

The novel 5-HT(7) receptor antagonist, SB-269970-A, potently displaced [(3)H]-5-CT from human 5-HT(7(a)) (pK(i) 8.9+/-0.1) and 5-HT(7) receptors in guinea-pig cortex (pK(i) 8.3+/-0.2). 5-CT stimulated adenylyl cyclase activity in 5-HT(7(a))/HEK293 membranes (pEC(50) 7.5+/-0.1) and SB-269970-A (0.03 - 1 microM) inhibited the 5-CT concentration-response with no significant alteration in the maximal response. The pA(2) (8.5+/-0.2) for SB-269970-A agreed well with the pK(i) determined from [(3)H]-5-CT binding studies. 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes (pEC(50) of 8.4+/-0.2) was inhibited by SB-269970-A (0.3 microM) with a pK(B) (8.3+/-0.1) in good agreement with its antagonist potency at the human cloned 5-HT(7(a)) receptor and its binding affinity at guinea-pig cortical membranes. 5-HT(7) receptor mRNA was highly expressed in human hypothalamus, amygdala, thalamus, hippocampus and testis. SB-269970-A was CNS penetrant (steady-state brain : blood ratio of ca. 0.83 : 1 in rats) but was rapidly cleared from the blood (CLb=ca. 140 ml min(-1) kg(-1)). Following a single dose (3 mg kg(-1)) SB-269970 was detectable in rat brain at 30 (87 nM) and 60 min (58 nM). In guinea-pigs, brain levels averaged 31 and 51 nM respectively at 30 and 60 min after dosing, although the compound was undetectable in one of the three animals tested. 5-CT (0.3 mg kg(-1) i.p.) induced hypothermia in guinea-pigs was blocked by SB-269970-A (ED(50) 2.96 mg kg(-1) i.p.) and the non-selective 5-HT(7) receptor antagonist metergoline (0.3 - 3 mg kg(-1) s.c.), suggesting a role for 5-HT(7) receptor stimulation in 5-CT induced hypothermia in guinea-pigs. SB-269970-A (30 mg kg(-1)) administered at the start of the sleep period, significantly reduced time spent in Paradoxical Sleep (PS) during the first 3 h of EEG recording in conscious rats.

Adenylyl Cyclases↗

Nutritional management in long-term care: development of a clinical guideline. Council for Nutritional Strategies in Long-Term Care.

BACKGROUND: Involuntary weight loss resulting from malnutrition is a major problem among residents in long-term care facilities. Although body weight is easily measured, the evaluation of unintended weight loss in long-term care facilities is difficult. METHODS: The Council for Nutritional Clinical Strategies in Long-Term Care, an expert panel of interdisciplinary thought leaders representing academia and the medical community, derived a structured approach aimed at improving management of malnutrition in long-term care settings, using literature review and consensus development. The Clinical Guide to Prevent and Manage Malnutrition in Long-Term Care is based on a best-evidence approach to the management of nutritional problems in long-term care. RESULTS: The Clinical Guide is divided into two parts, one designed for nursing staff, dietary staff, and dietitians, and a second directed to physicians, pharmacists, and dietitians. CONCLUSIONS: A structured approach to the management of unintended weight loss or malnutrition in long-term care is intended to ensure a comprehensive resident evaluation. While the Clinical Guide is presented in a linear fashion, many of the considerations can be done simultaneously and the order varied dependent on the individual resident's needs. Further research to validate the effectiveness of using the algorithm in long-term care settings will be required.

Humans↗

A simple test of association for contingency tables with multiple column responses.

Loughin and Scherer (1998, Biometrics 54, 630-637) investigated tests of association in two-way tables when one of the categorical variables allows for multiple-category responses from individual respondents. Standard chi-squared tests are invalid in this case, and they developed a bootstrap test procedure that provides good control of test levels under the null hypothesis. This procedure and some others that have been proposed are computationally involved and are based on techniques that are relatively unfamiliar to many practitioners. In this paper, the methods introduced by Rao and Scott (1981, Journal of the American Statistical Association 76, 221-230) for analyzing complex survey data are used to develop a simple test based on a corrected chi-squared statistic.

Agriculture↗

Rotational symmetry of the C ring and a mechanism for the flagellar rotary motor.

FliG, FliM, and FliN, key proteins for torque generation, are located in two rings. The first protein is in the M ring and the last two are in the C ring. The rotational symmetries of the C and M rings have been determined to be about 34 (this paper) and 26 (previous work), respectively. The mechanism proposed here depends on the symmetry mismatch between the rings: the C ring extends 34 levers, of which 26 can bind to the 26 equivalent sites on the M ring. The remaining 8 levers bind to proton-pore complexes (studs) to form 8 torque generators. Movement results from the swapping of stud-bound levers with M ring-bound levers. The model predicts that both the M and C rings rotate in the same direction but at different speeds.

Bacterial Proteins↗

Orf (contagious pustular dermatitis) in farmworkers: prevalence and risk factors in three areas of England.

Orf is a zoonotic skin disease which is commonly self-diagnosed by those who tend sheep and goats. This paper reports the prevalence, incidence and risk factors associated with the infection in a cohort of farmworkers from three areas of England, derived from the results of self-reporting and serology. Twenty-three per cent of those employed or living on a sheep farm reported ever having had orf, and the antibody serological profiles indicated a prevalence of 4 per cent and an annual incidence of 2.8 per cen. The main risk factors associated with the infection were contact with sheep, the size of the sheep flock, and contact with dogs.

Animal Husbandry↗

[Causes of protein-calorie malnutrition].

In developed countries, medical conditions, rather than lack of food, are the main contributors to malnutrition. Undernutrition is especially common in older persons, occurring in 5-12% of community-dwelling older persons, in 30-61% of hospitalized older persons, and in 40-85% of persons in long-term care institutions. The multi-factorial nature of undernutrition in the elderly forces a structured differential diagnostic approach to determine underlying causes. Heightened physician awareness of nutritional problems and prompt risk assessment is imperative to prevent the sequelae of undernutrition. This structured approach to the differential diagnosis is essential to evaluate potentially reversible causes of malnutrition.

Aged↗

Anorexia and aging: pathophysiology.

Aging results in a dysregulation of the ability to regulate food intake. In general, this presents as a decrease in food intake accompanied by early satiation. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the fundus of the stomach resulting in early antral filling. Increased levels and effectiveness of cholecystokinin also play a role in the anorexia of aging. Leptin levels increase with aging in males but not in females. With regard to the central feeding drive, both the opioid and neuropeptide Y effects appear to decline with age. This physiologic anorexia of aging increases the risk for older persons to develop severe anorexia and weight loss when disease occurs.

Aged↗

5-CT stimulation of adenylyl cyclase activity in guinea-pig hippocampus: evidence for involvement of 5-HT7 and 5-HT1A receptors.

1. A number of compounds, including the selective 5-HT7 receptor antagonist SB-258719, were investigated for their effect on [3H]-5-carboxamidotryptamine (5-CT) radioligand binding and 5-CT-stimulated adenylyl cyclase activity in guinea-pig hippocampal membranes, in order to confirm the presence of functionally coupled 5-HT7 receptors in this tissue. 2. The [3H]-5-CT radioligand binding profile was consistent with binding predominantly to 5-HT7 receptors. The affinity of SB-258719 (pKi 7.2+/-0.1) was similar to its reported human 5-HT7 receptor affinity. 3. In the adenylyl cyclase functional assay, 5-CT was a potent and full agonist compared to 5-HT, whereas 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) was a partial agonist (intrinsic activity 0.4+/-0.1). The rank order of potency for agonists (5-CT>5-HT approximately 8-OH-DPAT) was consistent with activation of 5-HT7 receptors. SB-258719 (5 microM) and methiothepin (1 microM) surmountably antagonized the response to 5-CT, consistent with competitive antagonism. The pKB for SB-258719 (7.2+/-0.1) was in good agreement with its reported antagonist potency at the human cloned 5-HT7 receptor. 4. In the functional assay, WAY-100635 (100 nM) and cyanopindolol (1 microM) induced a biphasic 5-CT response curve, consistent with selective antagonism of a component of the response to 5-CT. The estimated pKB values for WAY-100635 and cyanopindolol (9.6 and 8.4 respectively) were in good agreement with their reported 5-HT1A receptor affinities. 5. The data are consistent with the presence of 5-HT7 receptors in guinea-pig hippocampus which are positively coupled to adenylyl cyclase. In addition, 5-HT7 receptor-mediated stimulation of adenylyl cyclase activity in this tissue appears to be augmented by a mechanism involving 5-HT1A receptor activation.

Adenylyl Cyclases↗

Outcomes of 4 methods of debridement using a decision analysis methodology.

OBJECTIVE: To compare the clinical efficacy of 4 debridement alternatives in pressure ulcer management. DESIGN: Nonexperimental design combining computer modeling and a decision analysis methodology. Data input into the model were derived from a literature review of the MEDLINE database for the years 1985 to 1995 (indexing terms: pressure ulcer, decubitus, economics, cost-effectiveness, and outcome) and a Delphi consensus process with an independent panel of 9 specialists in geriatric care. SETTING: Long-term care. PATIENTS: Hypothetical elderly female resident with a new full-thickness pressure ulcer (mild odor, minimal draining, no undermining, intact periulcer skin). INTERVENTIONS: The study patient underwent 1 month of therapy with each of 4 debridement methods: autolysis, wet-to-dry dressings, collagenase (Santyl) or fibrinolysin (Elase). MAIN OUTCOME: Specific clinical outcomes (time to clean wound bed, risk of infection) and relative cost-effectiveness of each debridement method were calculated. RESULTS: The likelihood of achieving a clean wound bed at 2 weeks was 70% for collagenase, 57% for fibrinolysin, 50% for autolysis, and 30% for wet-to-dry dressings. The total cost for 1 month of treatment was $610.96 for collagenase, $920.73 for autolysis, $986.38 for fibrinolysin, and $1,008.72 for wet-to-dry dressings. CONCLUSIONS: The study patient was most likely to have a clean wound bed after 2 and 4 weeks of treatment, less likely to need to switch debridement methods, and of equal or less likelihood of experiencing and infection and subsequent hospitalization when her wound was debrided with collagenase. Treatment with collagenase also resulted in the lowest total cost of treatment. Longer term, prospective studies using actual utilization data are needed to refine these estimates of the clinical and cost-effectiveness of each product.

Aged↗

A comparison of an opaque foam dressing versus a transparent film dressing in the management of skin tears in institutionalized subjects.

Epidemiological studies suggest that at least 1.5 million skin tears occur each year in institutionalized adults. Despite this incidence, very little is known about the management of skin tears in elderly persons. Studies related to wound dressings and healing rates for these skin tears have rarely been reported in the medical literature. A randomized, prospective trial of 37 subjects compared the treatment of skin tears using either an opaque foam dressing or a transparent film dressing. Subjects had either a modified Payne-Martin Category II (25%-75% epidermal loss) or Category III (100% epidermal loss) skin tear. Category I skin tears (linear with no tissue loss) and skin tears greater than 48 hours old were excluded. Mean subject age was 85.1 +/- 9.7 years. Subjects were followed weekly until healed or for up to 21 days. Subjects in the comparison groups did not differ at baseline in age, sex, wound severity score, presence of diabetes, nutrition score, ambulation and mobility score, or mental status score. Complete healing occurred in 94% (16/17) of subjects treated with the foam dressing as opposed to 65% (11/17) of subjects treated with the film dressing (P < 0.05). Complete healing correlated only with dressing type (P < 0.05) and age (P < 0.01). No other factor was associated with the healing outcome. The number of dressing changes was similar in each group, 3.1 +/- 1.2 versus 3.4 +/- 1.1. Based on the results of this study, we conclude that this opaque foam dressing is a superior wound dressing for skin tears.

Activities of Daily Living↗

Influence of long-chain polyunsaturated fatty acids on oxidation of low density lipoprotein.

Enrichment of low density lipoprotein (LDL) with long-chain fatty acids, such as eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3) found in fish oil, is thought to increase its oxidative susceptibility although such an increase has not been clearly demonstrated. The purpose of this study was to determine the composition and fatty acid concentration of LDL obtained from postmenopausal women given a supplement of fish oil and relate these values to its oxidative susceptibility. Fish oil supplementation significantly increased LDL concentration of EPA (P = 0.0001) and DHA (P = 0.0001) and decreased that of linoleic acid P = 0.006). The concentration of free cholesterol, cholesterol ester, phospholipids and protein was unchanged while triglyceride concentration increased 8% (P = 0.02). Cu2+-mediated oxidation resulted in a shorter lag time, slower oxidation rate and similar concentrations of conjugated dienes of EPA/DHA-enriched LDL than EPA/DHA-unenriched LDL. Stepwise multiple regression indicated that the primary predictor of oxidative susceptibility of LDL was linoleic acid, even after enrichment with EPA and DHA. The oxidation rate of EPA/DHA-unenriched LDL correlated with the cholesteryl ester concentration (P = 0.003) while that of EPA/DHA-enriched correlated with the concentration of phospholipids (P = 0.03). These data suggest that EPA/DHA-enriched LDL have decreased oxidative susceptibility and that surface lipids may mediate its rate of oxidation.

Cholesterol↗

Low rates of ehrlichiosis and Lyme borreliosis in English farmworkers.

To determine the occupational significance of tick-borne zoonoses we sought serological evidence of Lyme borreliosis, human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE) in a representative sample of farmworkers. Although around 20% reported ticks on their domestic and companion animals, few (< 2% per year) reported being bitten by ticks. Seroprevalence of Lyme borreliosis (0.2%), HME (0.2%) and HGE (1.5%) was low. Those seropositive for HGE were no more likely to report tick bites nor more likely to report ticks on their animals. This study provides evidence that farmworkers in England are exposed to tick-borne zoonoses but that they are uncommon. Since the severity of these diseases is linked to delays in diagnosis and treatment, clinicians should be aware of these diagnoses in patients from rural communities, with or without a self-reported history of tick bite.

Adult↗