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David R Thomas

Publications and source records attributed to David R Thomas.

At least 55 records · Page 3Linked to original sources
PubMed2002

SB-656104-A: a novel 5-HT(7) receptor antagonist with improved in vivo properties.

A focused SAR study around the previously reported selective 5-HT(7) receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A.

Animals↗
PubMed2002

Privacy or life: how do women find out about screening mammography services?

AIM: This study investigated how women found out about the Waikato pilot breast cancer screening programme and what influenced them to participate. METHODS: A sample of 1085 women who had undergone screening mammography were sent survey questionnaires in 1999 to investigate how they had found out about the programme and what had influenced them to participate. Data from 599 completed questionnaires were analysed. RESULTS: The most common external sources of information about the availability of screening mammography were: letters of invitation (42%), family doctors (42%), television (32%), and newspapers (27%). The most important external sources of influence for attending screening were: letter of invitation (28%), and knowing someone with breast cancer (27%). CONCLUSIONS: Letters of invitation from the programme provide an important source of influence for attending screening mammography clinics. Up-to-date databases are needed to ensure that women receive information from the screening programme. There was an inconsistency between the government policy to provide a population-based screening programme and the operation of the Privacy Act 1993, which prevents use of other sources of information to update addresses for population groups most likely to benefit from screening. The high gone, no address rate reduced ongoing screening among women who depend on receiving regular recall notices.

Breast Neoplasms↗
PubMed2002

Transurethral prostate resection and bleeding: a randomized, placebo controlled trial of role of finasteride for decreasing operative blood loss.

PURPOSE: Bleeding associated with transurethral prostate resection can often be significant and lead to increased morbidity and occasionally mortality. It has been shown that finasteride decreases bleeding in patients with hematuria of prostatic origin. We hypothesized that bleeding in patients undergoing transurethral prostate resection could be decreased by giving finasteride for 2 weeks before surgery. MATERIALS AND METHODS: A total 70 patients scheduled to undergo elective transurethral prostate resection were randomized to receive 5 mg. finasteride daily or placebo for 2 weeks before surgery. Serum hemoglobin was measured before and after surgery, and the following day. The volume of irrigation fluid used and its hemoglobin concentration as well as resected prostate weight were recorded. RESULTS: Of the 68 patients who underwent transurethral prostate resection 2 were withdrawn before surgery, and so 32 received finasteride and 36 received placebo. There was significantly less mean blood loss in irrigation fluid in the finasteride group than in the control group (43.6 versus 69.3 gm. hemoglobin, p = 0.011). The mean difference was more significant when blood loss per gm. resected prostate was calculated (2.65 versus 4.65 gm. hemoglobin per gm. prostate, p < 0.01). CONCLUSIONS: This study shows that finasteride given for 2 weeks preoperatively decreases bleeding in patients undergoing transurethral prostate resection. Further study is required to determine the optimal timing and dose duration to minimize blood loss and identify how relevant such a decrease in bleeding is in clinical practice.

Aged↗
PubMed2002

Pharmacological profile of SB-357134: a potent, selective, brain penetrant, and orally active 5-HT(6) receptor antagonist.

N-(2,5-Dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134) potently inhibited [125I]SB-258585 and [3H]LSD binding in a HeLa cell line expressing human 5-HT(6) receptors (pK(i)=8.6 and 8.54, respectively). Furthermore, SB-357134 inhibited [125I]SB-258585 binding in human caudate--putamen and in rat and pig striatum membranes (pK(i)=8.82, 8.44, and 8.61, respectively). SB-357134 displayed over 200-fold selectivity for the 5-HT(6) receptor versus 72 other receptors and enzymes. 5-HT-stimulated cyclic AMP (cAMP) accumulation in human 5-HT(6) receptors was competitively antagonised by SB-357134 (pA(2)=7.63). SB-357134 inhibited ex vivo [125I]SB-258585 binding in the rat with an ED(50) of 4.9 +/- 1.3 mg/kg po, 4 h postdose. In the rat maximal electroshock seizure threshold (MEST) test, SB-357134 produced a potent and dose-dependent increase in seizure threshold, with a minimum effective dose of 0.1 mg/kg po. At 10 mg/kg po, maximum activity occurred between 4 and 6 h postdose. Good exposure was observed with SB-357134 at 10 mg/kg po, reaching maximal blood and brain concentrations of 4.3 +/- 0.2 and 1.3 +/- 0.06 microM, respectively, 1 h postdose. In addition, SB-357134 (10 mg/kg po) enhanced memory and learning following chronic administration (twice a day for 7 days) in the rat water maze. Overall, these studies demonstrate that SB-357134 is a potent, selective, brain penetrant, and orally active 5-HT(6) receptor antagonist.

Algorithms↗
PubMed2002

Distinguishing starvation from cachexia.

The poor response to hypercaloric feeding in ill adults may be caused by failure to distinguish cachexia from starvation (Table 1). The chief difference between starvation and cachexia is that refeeding reverses starvation but is less effective for cachexia. The ineffectiveness of refeeding in treating cachexia may explain some of the poor results from direct nutritional interventions in clinical trials. Simple starvation should respond to voluntary or involuntary hypercaloric feedings. The failure to demonstrate a more positive response may be caused by underlying cachexic states.

Aged↗
PubMed2002

Dietary prescription for chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) demonstrate classic signs of undernutrition. A low body mass, weight lose, and decrease in lean body mass have been associated with impaired functional status and poor outcome. The nutritional deficiencies accompanying COPD have been refractory to strategies aimed at increasing calorie intake, indicating that the underlying pathophysiology is not a simple nutritional defect amenable to correction. The association of cytokine-induced inflammatory markers in COPD patients suggests that interventions aimed at controlling cytokine production may be required to reverse the cachexia syndrome and improve functional status.

Aged↗
PubMed2002

Enteral nutrition and enteral tube feeding. Review of the evidence.

Improvements in delivery systems for enteral feeding, in formulas, and in the understanding of complications have made the technology for enteral feeding easy to apply. Adequate nutrients can be delivered, and individual tolerance for feeding is acceptable. The remaining question is when to apply the technology. Formula selection should be as simple as possible. Aspiration and other early complications are a serious risk and are not diminished by route of feeding. Long-term enteral feeding is associated with a high complication rate, with high mortality, and may not be effective.

Aged↗
PubMed2002

Malnutrition in subacute care.

BACKGROUND: Dramatic weight loss and hypoalbuminemia often follow acute hospitalization. OBJECTIVE: The objective was to examine the prevalence of undernutrition in a subacute-care facility. DESIGN: We evaluated 837 patients consecutively admitted over 14 mo to a 100-bed subacute-care center. Nutritional status was assessed by anthropometric measurements, biochemical markers, and a Mini Nutritional Assessment (MNA) score. Primary outcome measures included length of stay and death. Secondary measures included readmission to an acute-care hospital and placement at discharge. RESULTS: The subjects' mean (+/- SD) age was 76 +/- 13 y and 61% were women. Eighteen percent of the subjects had a body mass index (in kg/m(2)) <19. With the use of 35 g/L as a cutoff, 53% of the subjects had hypoalbuminemia. Only 8% of the subjects were classified as being well nourished according to the MNA. Almost one-third (29%) of the subjects were malnourished and almost two-thirds (63%) were at risk of malnutrition. Thus, >91% of subjects admitted to subacute care were either malnourished or at risk of malnutrition. The Geriatric Depression Score was higher in malnourished subjects than in nutritionally at-risk subjects (P = 0.05). Length of stay differed by 11 d between the malnourished group and the nutritionally at-risk group (P = 0.007). In the MNA-assessed group of largely malnourished subjects, 25% of subjects required readmission to an acute-care hospital compared with 11% of the well-nourished group (P = 0.06). Mortality was not found to be related to BMI. CONCLUSION: Malnutrition reaches epidemic proportions in patients admitted to subacute-care facilities. Whether this reflects nutritional neglect in acute-care hospitals or is the result of profound illness is unclear. Nevertheless, strict attention to nutritional status is mandatory in subacute-care settings.

Aged↗
PubMed2002

Therapeutic potential of serotonin antagonists in depressive disorders.

Although the precise neurochemical imbalances in depression are still unknown, a role for the neurotransmitter 5-hydroxytryptamine (serotonin) has been implicated since the identification of the first effective antidepressants, imipramine and iproniazid. This led to the development of the selective serotonin re-uptake inhibitors which are widely used in the treatment of depression and depressive disorders, including generalised anxiety disorder, social phobia, obsessive compulsive disorder etc. Studies involving chronic administration in rats led to the hypothesis that the different classes of antidepressant treatment produce a common neuroadaptive change, namely an enhancement of serotonin neurotransmission, albeit via different pre and postsynaptic mechanisms. From this, it was suggested that serotonin antagonists should induce similar neuroadaptive changes, either directly or through a potentiation of other antidepressant agents. Here, the profiles of novel serotonin antagonists currently in preclinical development are reviewed and their therapeutic potential is assessed.

Animals↗
PubMed2002

Delayed antibiotic prescriptions: what are the experiences and attitudes of physicians and patients?

OBJECTIVE: To explore the experiences and opinions of family physicians and patients regarding the delay of antibiotic prescriptions, to be dispensed if symptoms persist or worsen over time, in treating upper respiratory tract infections. STUDY DESIGN: Qualitative study using semistructured interviews conducted in family practice in Auckland, New Zealand. POPULATION: Thirteen physicians recruited from a study of family physicians' reported antibiotic prescribing and 13 patients recruited from the intervention arm of a randomized controlled trial on delayed antibiotic prescribing. OUTCOMES MEASURED: Patients' and physicians' experiences of delayed antibiotic prescriptions for upper respiratory tract infections. RESULTS: The primary themes identified were value judgments of antibiotics, decreased antibiotic use, patient-centered factors, effects on the physician-patient relationship, patient convenience, adverse effects of delaying prescription, and selectivity for use of antibiotics. Many themes were common to both patients and physicians. Physicians valued empowering patients' decision making about their health care management more highly than did patients. Decreasing antibiotic use was not a key factor for most patients. Both groups acknowledged the value in saving patients time and money. Physicians viewed the strategy as giving patients reassurance and meeting their expectations for antibiotics. Negative implications included perception of physician incompetence and physician loss of management control. Opinions were mixed regarding which patients, under which conditions, were suitable for delayed antibiotic prescriptions. CONCLUSIONS: Although delayed antibiotic prescriptions are effective in decreasing antibiotic use for conditions not clinically warranting antibiotics, neither patients nor physicians universally endorsed this strategy. Research to establish formalized recommendations for patient suitability and instructions for use would be of value.

Adult↗
PubMedDate not supplied

A controlled, randomized, comparative study of a radiant heat bandage on the healing of stage 3-4 pressure ulcers: a pilot study.

OBJECTIVES: Pressure ulcers, like other chronic wounds, fail to proceed through an orderly and timely process to produce anatomical or functional integrity. Treatment of pressure ulcers is directed to improving host factors and providing an optimum wound environment. In addition to providing a moist wound environment, it has been theorized that preventing hypothermia in a wound and maintaining a normothermic state might improve wound healing. DESIGN/SETTING: Forty-one subjects with a stage 3 or stage 4 truncal pressure ulcer >1.0 cm(2) were recruited from outpatient clinics, long-term care nursing homes, and a rehabilitation center. The experimental group was randomized to a radiant-heat dressing device and the control group was randomized to a hydrocolloid dressing, with or without a calcium alginate filler. Subjects were followed until healed or for 12 weeks. RESULTS: Eight subjects (57%) in the experimental group had complete healing of their pressure ulcer compared with 7 subjects (44%) with complete healing in the control group (P = .46). CONCLUSION: Although a 13% difference in healing rate between the two arms of the study was found, this difference was not statistically significant. At almost all points along the healing curve, the proportion not healed was higher in the control arm.

Aged↗
PubMedDate not supplied

Are all pressure ulcers avoidable?

A quality of care debate centers on whether pressure ulcers result from factors largely dependent on caregivers, or whether pressure ulcers result from factors associated with patient morbidity. A reduction in incidence, defined as the development of a new pressure ulcer, is the focus of prevention strategies. Yet epidemiological data demonstrates a stability in the incidence of pressure ulcers despite drastic improvements in understanding of pressure ulcers, increased regulatory oversight, and improvements in technologies available for prevention of pressure ulcers. The explanation for this stable incidence of pressure ulcers includes a failure of known effective preventive treatment to be applied or the failure of prevention strategies to be effective in spite of being applied. No intervention strategy has been reported that consistently and reproducibly reduces the incidence of pressure ulcers to zero. The published data on prevention of pressure ulcers do not support an assumption that all pressure ulcers are preventable. An effective prevention strategy demonstrated to eliminate pressure ulcers across healthcare settings is lacking.

Aged↗
PubMedDate not supplied

Physician misdiagnosis of dehydration in older adults.

INTRODUCTION: Dehydration is a difficult clinical diagnosis in older adults because the physical signs of dehydration are often confusing. The clinical consequences of a diagnosis of dehydration are critical, since dehydration implies increased morbidity and mortality and aggressive rehydration can improve clinical outcome. The diagnosis is a sentinel event for nursing homes, and often is made at transfer to a hospital. OBJECTIVE: To define the accuracy of the clinical diagnosis of dehydration during hospital admission, and to observe persons admitted from long-term care. METHODS: A total of 102 consecutive medical admissions in persons older than 65 years with a diagnostic coding for dehydration either on admission or during the course of hospitalization over a 3-month period at a university teaching hospital were reviewed. The diagnosis of dehydration was considered confirmed if the calculated serum osmolarity was greater than 295 milliosmols (mOsmol). Subjects were considered to have intravascular volume depletion if the ratio of blood urea nitrogen (BUN) to serum creatinine was greater than 20 or the serum sodium was greater than 145 milligrams per deciliter. Subjects were considered to have hypovolemia if the serum osmolarity was greater than 295 and the BUN/creatinine ratio was greater than 20. RESULTS: Among subjects with a clinical diagnosis of dehydration, only 17% had a serum osmolarity >295 mOsm, and only 11% had a serum sodium greater than 145. A BUN/creatinine ratio greater than 20 was present in 68% of the subjects. Clinicians appear to be using the term dehydration synonymously with intravascular volume depletion. Even so, at least a third of the diagnoses of intravascular volume depletion in older adults were incorrect based on laboratory data. CONCLUSION: Physicians who diagnose dehydration during hospital admission may be relying more on physical signs than laboratory data. Little change in laboratory markers for hydration status occurs from the time of diagnosis to hospital discharge, suggesting that the clinical diagnosis does not affect fluid management. The data suggest a need for improvement in the differential diagnosis and management of volume changes in older persons.

Aged↗