Biomedical subjects
Publications and source records attributed to M Devlin.
Primary care trusts are similar to US health maintenance organisations in that they act as both commissioners and providers of services. There are already innovative primary care organisations in the NHS and the private sector that can be classed as embryonic PCTs. Experience of these organisations, assessed in relation to HMOs, can inform the development of PCTs.
OBJECTIVE: To quantify the differences in physical disability and handicap experienced by patients with lower extremity sarcoma who required amputation for their primary tumor as compared with those treated by limb-sparing surgery. DESIGN: Matched case-control study. Twelve patients with amputation were matched with 24 patients treated by limb-sparing surgery on the following variables: age, gender, length of follow-up, bone versus soft-tissue tumor, anatomic site, and treatment with adjuvant chemotherapy. PATIENTS: Patients who underwent above-knee amputation (AKA) or below-knee amputation (BKA) for primary soft-tissue or bone sarcoma, who had not developed local or systemic recurrence, and who had been followed up for at least 1 year since surgery. MAIN OUTCOME MEASURES: The Toronto Extremity Salvage Score (TESS), a measure of physical disability; the Shortform-36 (SF-36), a generic health status measure; and the Reintegration to Normal Living (RNL), a measure of handicap. RESULTS: Mean TESS score for the patients with amputations was 74.5 versus 85.1 for the limb-sparing patients. (p = .15). Only the physical function subscale of the SF-36 showed statistically significant differences, with means of 45 and 71.1 for the amputation versus limb-sparing groups, respectively (p = .03). The RNL for the amputation group was 84.4 versus 97 for the limb-sparing group (p = .05). Seven of the 12 patients with amputations experienced ongoing difficulty with the soft tissues overlying their stumps. CONCLUSIONS: There was a trend toward increased disability for those in the amputation group versus those in the limb-sparing group, with the amputation group showing significantly higher levels of handicap. These data suggest that the differences in disability between amputation and limb-sparing patients are smaller than anticipated. The differences may be more notable in measuring handicap.
This paper reports on a research study carried out in an independent hospital in the south east of England. The aim of the study was to assess the basic life support skills of nurses in order to compare the results with those reported for nurses in public hospitals. The findings show that the basic life support skills of the nurses studied are poor but no worse than those of their public sector colleagues.
Lysophosphatidate (LPA; 1-acyl-sn-glycero-3-phosphate) is a novel lipid mediator with diverse biological activity. The intracellular mechanisms that mediate the actions of LPA include activation of phospholipase C and protein kinase C (PKC), increases in intracellular Ca2+, inhibition of adenylyl cyclase, and activation of phospholipase D (PLD). We have shown that thyrotropin (TSH) mediated PLD activation involves both the cyclic adenosine monophosphate (cAMP) and PKC pathways. We determined the effects of LPA (10 or 50 microM; 30 minutes) on TSH- and forskolin-mediated cAMP production in FRTL-5 thyroid cells. Basal cAMP was unaffected by LPA. However, both 10 microM and 50 microM LPA inhibited TSH-mediated cAMP production by 66% and 64%, respectively (p < 0.01, ANOVA). A similar inhibition of forskolin-mediated cAMP production was observed following LPA (p < 0.01, ANOVA). After 30-minutes exposure to 50 microM LPA, TSH-mediated iodide uptake (IU) was unaffected. However, 50 microM LPA enhanced TSH-IU after 24-hour exposure by 23%+/-8% (p < 0.03, ANOVA) and inhibited TSH-IU following 72-hour exposure by 43%+/-10% (p < 0.02, ANOVA). There was no effect of LPA on basal IU. To determine whether PLD activation mediated the effects of LPA, PLD activity was examined in FRTL-5 thyroid cells 30 minutes after LPA exposure. While PLD was increased 3.5-fold compared to control values following 50 microM LPA (p < 0.05, ANOVA), no increase in PLD activation was seen following treatment with 10 microM LPA. Preliminary evidence revealed no effect of a protein kinase C inhibitor on LPA inhibition of cAMP generation. To examine the products of PLD activation, we measured the production of phosphatidate (PA) and diacylglycerol (DAG) in FRTL-5 thyroid cells following treatment with 50 microM LPA or 100 microU/mL TSH. Within 1 minute following LPA, a rapid spike of DAG production was observed (1.5- +/- 0.2-fold above basal, p < 0.05, ANOVA). No similar increases in PA or bisPA were demonstrated. However, TSH caused a steady increase in PA and DAG that reached a maximum after 30 minutes. In summary, the effects of LPA on differentiated thyroid function in FRTL-5 thyroid cells are complex. LPA inhibits TSH- and forskolin-mediated cAMP generation most likely via a direct inhibition of adenylyl cyclase, whereas its effects on TSH-IU involve other mechanisms, possibly including PLD activation.
This article describes and evaluates the Buddy Program, which uses a natural helping network model to enhance the well-being of persons in nursing homes. Thirty-six nondemented patients ("buddies") and 33 persons with dementia completed the 6-month study that involved an educational program for the buddies and regular meetings between buddy-dementia patient pairs. Over the 6 months, compared to a matched control group, the dementia patients showed no advantage on any of the seven outcome measures and actually had significantly more depressive symptoms and greater nursing home dissatisfaction. The nondementia buddies showed no differences from the controls on any of the outcome measures. The results suggest that natural helping network models may not be easily imported into nursing home settings.
PURPOSE: In addition to their bronchodilatory effects, beta(2)-agonists protect against bronchoconstriction, such as that caused by methacholine challenge. However, tachyphylaxis to this beneficial effect develops after chronic use of beta(2)-agonists. We studied whether the frequency or dose of treatment with a long-acting beta(2)-agonist (formoterol) affects the degree of bronchoprotection afforded against methacholine challenge and to compare this with the effects of a short-acting beta(2)-agonist (terbutaline). PATIENTS AND METHODS: In a randomized, parallel group, double-blind study at two centers, patients with stable asthma of mild to moderate severity who were treated with inhaled corticosteroids were treated with formoterol 6 micrograms twice daily, 24 micrograms twice daily, 12 micrograms once daily; terbutaline 500 micrograms four times daily; or placebo. Treatments were given by dry powder inhaler for a period of 2 weeks. Of the 72 patients who were enrolled, 67 completed the study. Methacholine challenge was performed to calculate the provocative dose that caused a 20% fall in forced expiratory volume in 1 second at baseline (unprotected) after an initial 1-week run-in without beta(2)-agonists, 1 hour after the first dose of study treatment, and again 1 hour after 7 and 14 days of study treatment. RESULTS: Each of the four active treatments exhibited significant tachyphylaxis (P < 0.05) to protection against methacholine challenge when comparing first/last dose (as geometric mean protection ratio versus baseline): formoterol 24 micrograms twice daily (9.6-fold/1.6-fold), 12 micrograms once daily (7.1-fold/2.2-fold), 6 micrograms twice daily (6.2-fold/2.3-fold), and terbutaline 500 micrograms four times daily (2.9-fold/2.0-fold). There were no significant differences among treatments after 2 weeks in bronchoprotection against methacholine challenge. For all formoterol regimens, the bronchodilator response 1 hour after inhalation was maintained over the 2-week treatment period. Diurnal control of morning and evening peak flow was significantly better with formoterol 24 micrograms twice daily than with terbutaline. CONCLUSIONS: Tachyphylaxis to bronchoprotection against methacholine challenge develops after 2 weeks of therapy with formoterol, a long-acting beta(2)-agonist, at all three dosage regimens that were tested. In contrast, the bronchodilator effects of formoterol were maintained during the 2 weeks of treatment.
OBJECTIVE: To test the efficacy of clozapine in treatment-resistant manic episodes. CLINICAL PICTURE: Three cases, two with bipolar disorder (manic) and one of schizoaffective disorder (manic), were treated with clozapine. TREATMENT: Clozapine was used after the failure of standard antipsychotics and mood stabilizers. OUTCOME: All three cases were successfully treated. CONCLUSION: A controlled trial of clozapine in treatment-resistant bipolar and schizoaffective manic episodes is indicated.
OBJECTIVE: To determine the value of the Functional Independence Measure (FIM) score as a prognostic indicator for prosthetic use in the lower limb amputee patient. DESIGN: Cohort study of 41 patients with lower limb amputations. SETTING: University hospital rehabilitation unit. MAIN OUTCOME MEASURES: FIM motor subscore and Houghton Scale for prosthetic use. RESULTS: FIM score on admission did not correlate with prosthetic use as measured by the Houghton Scale; however, FIM motor subscore at discharge did. CONCLUSION: The admission FIM score is not useful in predicting successful prosthetic rehabilitation in lower extremity amputee patients. Only the motor subscore at discharge correlates with the use of prosthesis.
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Endothelin stimulates the cells of the zona glomerulosa of the adrenal gland and releases aldosterone. While it is a less potent aldosterone secretagogue than angiotensin II endothelin also potentiates the effects of angiotensin II on aldosterone biosynthesis. Two endothelin receptors have been cloned and are expressed in the adrenal zona glomerulosa. Intravenous infusion of endothelin at a rate of 80 ng/kg/min for 30 min into rats produced increases in blood pressure, adrenal content of aldosterone and stimulated the ouabain-sensitive sodium potassium ATPase in the zona glomerulosa, but not in the zona fasciculata, of the adrenal. The simultaneous infusion of the isopeptide specific endothelin receptor A (ETA) antagonist BQ-123 blocked the pressor effects of endothelin, but did not alter the increase in aldosterone content of the zona glomerulosa or the ouabain-sensitive sodium potassium ATPase activity. Infusion of Sarafotoxin 6b, an ETB agonist, also increased the aldosterone content of the adrenal and stimulated the ouabain-sensitive sodium potassium ATPase in the zona glomerulosa, further indicating that the effect of endothelin is probably mediated by ETB or isopeptide non-specific endothelin receptor. The mechanism by which endothelin stimulates the sodium potassium ATPase is unclear as is the relation between a stimulated sodium potassium ATPase and the potentiation of angiotensin II effect on the adrenal.
Using dual energy x-ray absorptiometry, we studied 16 male patients with unilateral above knee amputations (AKA) with a mean age of 48 years (range, 23 to 66 years) who were full-time prosthetic users for more than 5 years. All prostheses were ischial weight bearing. All 16 subjects were found to have normal bone density in their spines and in the normal femurs when compared to nonamputation controls. However, a significant decrease of mean femoral neck bone density was found on the amputated side (0.68g/cm2, range, 0.52 to 1.01) when compared to the normal side (1.01g/cm2, range, 0.75 to 1.20) (p < .05). The mean bone density percentage difference between the two sides was 28% (range, 4% to 48%). There was a significantly negative correlation between the patient's age at the time of amputation and the severity of osteopenia (-0.73; p < 0.05).
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