Biomedical subjects

G D Gamble

Publications and source records attributed to G D Gamble.

18 recordsLinked to original sources

PubMed1999

Atrial fibrillation: prevalence and management in an acute general medical unit.

BACKGROUND: Atrial fibrillation (AF) is a common comorbid condition in patients admitted to hospital. In managing patients with AF, recent research has highlighted the importance of heart rate control, cardioversion, maintenance of sinus rhythm and anticoagulation for the prevention of thromboembolism. AIM: To determine the prevalence of AF in patients admitted acutely to the general medical service at Auckland Hospital and to assess the adequacy of heart rate control, the number cardioverted and the use of warfarin to prevent thromboembolism. METHODS: Prospective review of all acute admissions to the general medical service over a 12 week period. Information was collected from hospital notes on the patients' present and past medical conditions, admission and discharge cardiac medication and the use of investigations, particularly thyroid function tests and echocardiography. The heart rate on discharge, number cardioverted either during the admission or after discharge and the number given warfarin and aspirin were recorded. RESULTS: One hundred and forty-seven patients (aged 38-96, mean age 76 years and 52% male) were admitted in AF 165 times out of the 1637 admissions over the study period (a prevalence of 10.4%, 95% CI 8.6-11.5%). The main causes of admission were heart failure (23%), pneumonia or sepsis (17%), cerebrovascular accident (CVA) or transient ischaemic attack (TIA) (14%) and ischaemic heart disease (11%). Past medical history included hypertension (46%), ischaemic heart disease (39%), congestive heart failure (58%), valvular heart disease (12%), chronic obstructive airways disease (24%), CVA, TIA or thromboembolic event (24%) and diabetes (17%). Thyroid function tests were performed in 50% of patients and echocardiograms in 38%. Heart rate control at discharge could not be assessed, as this was not recorded prior to any patient's discharge. Seventy-eight per cent of patients were discharged on digoxin but only 29% on drugs that control the heart rate with exercise. Five patients out of 11 considered for cardioversion had a successful cardioversion in hospital and two were later cardioverted as outpatients. Twenty-eight per cent were discharged on warfarin, 33% on aspirin and one patient on both. Fifty-two per cent were considered to have contraindications to warfarin therapy. Prescribing rates for warfarin did not vary according to the patients' clinical risk for thromboembolism. CONCLUSION: AF is a common comorbid condition in the acute general medical ward. Standard investigations were under-utilised. Attention needs to be paid to the recording and control of heart rate at rest and on exercise. Cardioversion is considered infrequently. This patient group had a high risk for thromboembolism and after excluding the large group in whom warfarin was contraindicated, warfarin was still under-utilised.

Adult↗

PubMed1998

Selection bias in clinical research when subjects are excluded because of failure to estimate left ventricular mass by echocardiography.

Quantitative echocardiographic imaging often is used in clinical research, but the method is not successful in all patients. The goals of this study were as follows: (1) to determine the frequency with which left ventricular mass (LVM) could be estimated by echocardiography, (2) to characterize persons in whom LVM could not be estimated from echocardiography, and (3) to determine whether failure to estimate LVM was independently related to any common cardiovascular risk factors, thereby suggesting a potential for selection bias. This research was part of a community-based case-control study of risk factors in hypertension. Five hundred hypertensive subjects and 506 normotensive age- and sex-matched control subjects were studied prospectively. The mean age was 61 years (range: 39 to 76 years), the mean weight was 74 kg (range: 37 to 127 kg), 46% of the subjects were men, and 56% had a history of smoking. Two-dimensionally guided M-mode echocardiography was attempted in all subjects for determination of LVM (Penn convention). LVM was estimated when the endocardial borders could be accurately identified from a true radial cavity diameter. LVM was estimated in 803 subjects (79.8%). Subjects in whom estimates of LVM could not be obtained were older and had the following characteristics: higher systolic blood pressure; larger chest, waist, and abdominal circumferences; higher waist/hip ratio; and larger body mass index (all P <.02). In multivariate analysis the only independent predictors of failure to estimate LVM by echocardiography were advanced age (P =.0001), larger chest size (P =.0001), and history of smoking (P =.004). The inability to estimate LVM in 20% of subjects has important implications to our understanding the strength of association between potential risk factors and LVM, an independent measure of cardiovascular risk. LVM is more likely to be missing in older subjects who have a large chest and a history of smoking. The effects of such a selection bias should be considered in any analysis, and a characterization of the excluded subjects should be developed.

Adult↗

PubMed1996

Left ventricular function in scleroderma.

Scleroderma affects the left heart directly and indirectly via the effects of systemic hypertension. Using transthoracic echocardiography, we evaluated 35 patients with scleroderma and compared them with matched control subjects. Compared with controls, there were no differences between left ventricular dimensions, wall thickness, calculated mass or fractional shortening. However, the left atrium was enlarged (P = 0.006) and the mitral deceleration time was prolonged (P = 0.0005) in patients with scleroderma; suggesting abnormal diastolic function. After adjusting for potential confounders, duration of Raynaud's was found to be an independent predictor of deceleration time (P = 0.04), E/A peak velocity ratio (P = 0.04), A peak velocity (P = 0.004) and A velocity time integral (P = 0.0001), all measures of diastolic function. This group of individuals with scleroderma have evidence of abnormal diastolic function of the left ventricle despite normal left ventricular size and systolic function, and in the absence of hypertrophy. This finding is independent of the use of vasoactive medications and history of systemic hypertension, and thus may be due to primary myocardial involvement by scleroderma. The tendency to abnormal diastolic function of the left ventricle correlated with the duration of Raynaud's phenomenon.

Adolescent↗

PubMed1996

A multi-format interdisciplinary final examination.

Limitations of the traditional final medical examination for the assessment of clinical competence led to such developments as simulated patients and the Objective Structured Clinical Examination (OSCE). An interdisciplinary OSCE incorporating simulated patients and involving nine disciplines was introduced into the final examination in the Auckland School of Medicine to supplement the written papers and the long case. Six-hundred and eight students were assessed over a 6-year period. Each of the three examination modes provided good discriminatory power. Significant correlations were found between the tests, but this does not mean one or more is redundant. Principal component analysis showed that a single significant factor accounted for over half the variance in the final assessment. This factor was equally weighted to the three examinations. A variety of evaluative methods are necessary to assess a student's competence and greater emphasis should be placed on those methods which encourage the learning of clinical skills and concurrently provide an appropriate mechanism for assessing them. The changes introduced have been supported by students and teachers and have fostered the learning of important clinical skills. Efforts to standardize the single long case have not overcome the criticisms surrounding its use, particularly in summative assessment.

Clinical Competence↗

PubMed1995

Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial.

PURPOSE: To determine the long-term effects of calcium supplements or placebo on bone density in healthy women at least 3 years postmenopause. PATIENTS AND METHODS: Eighty-six women from our previously reported 2-year study agreed to continue on their double-blind treatment allocation (1 g elemental calcium or placebo) for a further 2 years, with 78 women (40 on placebo) reaching the 4-year end point. Median (interquartile range) dietary calcium intakes for the whole group were 700 mg (range 540 to 910) per day at baseline, 670 mg (range 480 to 890) per day at 2 years, and 640 mg (range 460 to 880) per day at 4 years. The bone mineral density (BMD) of the total body, lumbar spine, and proximal femur was measured every 6 months by dual-energy, x-ray absorptiometry. RESULTS: There was a sustained reduction in the rate of loss of total body BMD in the calcium group throughout the 4-year study period (P = 0.002), and bone loss was significantly less in the calcium-treated subjects in years 2 through 4 also (difference between groups 0.25% +/- 0.11% per year, P = 0.02). In the lumbar spine, bone loss was reduced in the calcium group in year 1 (P = 0.004), but not subsequently. There was, however, a significant treatment effect at this site over the whole 4-year period (P = 0.03). In the proximal femur, the benefit from calcium treatment also tended to be greater in the first year and was significant over the 4-year study period in the femoral neck (P = 0.03) and the trochanter (P = 0.01). Nine symptomatic fractures occurred in 7 subjects in the placebo group and 2 fractures in 2 subjects receiving calcium (P = 0.037). CONCLUSIONS: Calcium supplementation produces a sustained reduction in the rate of loss of total body BMD in healthy postmenopausal women.

Absorptiometry, Photon↗

PubMed1995

Inter-individual and intra-individual variability of ethanol concentration-time profiles: comparison of ethanol ingestion before or after an evening meal.

1. The magnitude of the variability of ethanol absorption is an important factor for studies that seek to determine the significance of potential interactions between ethanol and drugs. The aim of this study was to determine the extent of inter- and intra-individual variability of ethanol concentration-time profiles in fasted and fed subjects. 2. Twenty-four healthy male subjects were randomized to receive ethanol 0.3 g kg-1 before an evening meal on two study days and ethanol 0.3 g kg-1 after an evening meal on two study days. Plasma ethanol concentrations were measured at intervals from 0-240 min. 3. There were significant differences in the mean area under the ethanol concentration-time curve (AUC), the mean peak ethanol concentration (Cmax), the mean ethanol elimination slope and the time to peak ethanol concentration between the fed and fasted subjects. There were no significant differences between the first and second study days for either fed or fasting subjects for all parameters. 4. There was no statistically significant difference in inter- or intra-subject variance between fed and fasted studies although the coefficients of variation (standard deviation expressed as a percentage of the mean) for the differences between the first and second study day were higher for fed studies. 5. The large inter- and intra-individual variability of alcohol absorption for both fasted and fed subjects must be considered in the design of alcohol-drug interaction studies.

Adult↗

PubMed1994

Determinants of left ventricular hypertrophy and systolic dysfunction in chronic renal failure.

To evaluate determinants of left ventricular hypertrophy (LVH) and left ventricular (LV) systolic dysfunction in chronic renal failure (CRF), M-mode and two-dimensional echocardiography were performed in 38 undialyzed patients with CRF (serum creatinine > or = 3.4 mg/dL), 54 patients receiving continuous ambulatory peritoneal dialysis, 30 patients receiving hemodialysis, and 59 healthy age- and sex-matched volunteers. Left ventricular (LV) wall thickness and LV dimensions were greatest in dialysis patients, intermediate in CRF patients, and least in control subjects. LV mass index calculated from M-mode measurements was 78.7 g/m2 +/- 14.8 g/m2 in controls, 120.5 g/m2 +/- 28.7 g/m2 in CRF patients, and 136 +/- 45.0 g/m2 in dialysis patients (P < 0.0001). LV fractional shortening and LV velocity of circumferential shortening were lower in dialysis patients than in CRF patients and controls (fractional shortening 36.5% +/- 5.6% in controls, 36.2% +/- 7.2% in CRF patients, and 29.8% +/- 8.9% in dialysis patients; P < 0.0001). Echocardiography was normal in only 24 dialysis patients (29%) and 14 CRF patients (37%) (P = NS). Thirty-nine dialysis patients (46%) and 10 CRF patients (26%) had LVH (P = NS). Thirty dialysis patients (36%) and five CRF patients (13%) had LV systolic dysfunction (P < 0.05). LV hypertrophy with LV systolic dysfunction was present in 15 dialysis patients but no CRF patients (P < 0.05). There were no significant differences between hemodialysis patients and continuous ambulatory peritoneal dialysis patients in M-mode echocardiographic measurements or the frequency of LVH and LV systolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Cholesterol-lowering and blood pressure effects of immune milk.

The plasma cholesterol-lowering and blood pressure effects of a skim milk powder (immune milk) produced from dairy cows hyperimmunized with a multivalent bacterial vaccine were assessed in a double-blind crossover study of hypercholesterolemic subjects who consumed daily 90 g immune milk or a normal product. There was a significant reduction in plasma total and LDL cholesterol of 5.2% (95% CI 2.5, 7.9) and 7.4% (95% CI 4.1, 10.7), respectively, with 10 wk of immune milk consumption compared with control, but no change in HDL cholesterol or triglycerides. A significant systolic and diastolic blood pressure-lowering effect (5 and 4 mm Hg, respectively) was also demonstrated. Thus, immune milk may be a useful adjunct in the dietary management of hypercholesterolemia and the mechanisms of its cholesterol-lowering and blood pressure effects warrant further study.

Adult↗

PubMed1994

Uniform experience and assessment during a multisite surgical clerkship.

Major changes in health care delivery and the increased number of clerkship sites used for teaching by many medical schools has resulted in significant implications for medical education. Methods have become necessary to achieve and maintain a comparable clinical experience and a uniform assessment process at each teaching site. Following a review of existing practices, a new core curriculum, a problem-based approach and the Objective Structured Clinical Examination (OSCE) were introduced into this department. Over 1200 students have passed through this revised surgical clerkship over the past 8 years. The introduction of the OSCE has helped to direct student learning, provide an objective assessment to complement the ward grade, and enabled an audit of teaching and learning to be carried out. In one group of 103 students no significant correlation was found between the OSCE and ward grades. Performance at different hospitals was similar and those carrying out their clerkship later in the academic year benefited from their previous other attachments. The OSCE has enabled immediate feedback to be given to learners as well as providing teachers with an opportunity to see for themselves the outcome of their tuition. A clinical performance record card has now been introduced to improve the monitoring of students' clinical experience.

Clinical Clerkship↗

PubMed1994

Determinants of the rate of bone loss in normal postmenopausal women.

Despite a large number of studies assessing relationships between putative risk factors and bone density, it is not known which factors influence the rate of axial bone loss in normal postmenopausal women. We have examined the relationships between the rate of bone loss (delta BMD) and variables related to calcium metabolism, lifestyle, diet (calcium, sodium, caffeine, and protein), body composition, muscle strength, sex hormones, and spinal osteophytosis in 122 normal postmenopausal women participating in a 2-yr prospective randomized placebo-controlled trial of calcium supplementation. Univariate correlation coefficients indicated that delta BMD at most sites was inversely related to baseline BMD and positively related to rate of change in body weight (0.10 < r < 0.36) and fat mass (0.11 < r < 0.42) during the study. Lean mass and its rate of change showed no consistent relationship to delta BMD. There was no correlation between delta BMD and any of the lifestyle, muscle strength, dietary, or hormonal indices or with the severity of spinal osteophytosis. Multiple regression analysis indicated that delta BMD in the total body was directly related to fat mass (P < 0.0001), the rate of change in fat mass (P < 0.0001), the renal tubular reabsorption of calcium (P < 0.01), and calcium treatment (P < 0.01) and inversely to the initial BMD (P < 0.0001; r2 = 0.42; P < 0.0001). Similar effects were seen throughout the skeleton, although the fraction of the variance accounted for was less in the subregions, consistent with the lower precision of measurement of regional bone density. It is concluded that baseline bone density, fat mass, and renal calcium handling are important factors influencing bone loss in normal postmenopausal women.

Body Composition↗

PubMed1994

Continuous therapy with pamidronate, a potent bisphosphonate, in postmenopausal osteoporosis.

There is a need for effective and acceptable therapies for postmenopausal osteoporosis. The bisphosphonates show promise in this role, but the effects of the potent bisphosphonates in established osteoporosis have not yet been reported. We performed a 2-yr, randomized, double blind, placebo-controlled trial of pamidronate (150 mg/day) in 48 postmenopausal osteoporotic women. Bone mineral density of the total body, lumbar spine, and proximal femur was measured every 6 months by dual energy x-ray absorptiometry. Bone mineral density increased progressively in the total body (1.9 +/- 0.7%; P < 0.01), lumbar spine (7.0 +/- 1.0%; P < 0.0001), and femoral trochanter (5.4 +/- 1.3%; P < 0.001) in subjects receiving pamidronate, but did not change significantly in those receiving placebo. There were significant decreases in bone density at both the femoral neck (P < 0.02) and Ward's triangle (P < 0.01) in subjects taking placebo, which did not occur in the pamidronate group. The differences between the treatment groups were significant at all sites (0.0001 < P < 0.05) except Ward's triangle. Vertebral fracture rates were 13/100 patient yr in the pamidronate group and 24/100 patient yr in those receiving placebo (P = 0.07), and there was a nonsignificant trend toward height loss being less in those receiving pamidronate (P = 0.16). It is concluded that pamidronate is an effective therapy in postmenopausal osteoporosis.

Aged↗

PubMed1994

Effect of fosinopril on cardiac and metabolic parameters in patients with NIDDM.

OBJECTIVE: To determine whether the angiotensin-converting enzyme (ACE) inhibitor fosinopril can favorably alter cardiac function in non-insulin-dependent diabetes mellitus NIDDM) patients who have either normal blood pressure (BP) or mild, untreated hypertension. RESEARCH DESIGN AND METHODS: Fifty-five NIDDM subjects with normal BP or mild, untreated hypertension were randomized to treatment with the ACE-inhibitor fosinopril or placebo for 6 months in a randomized, double-blind trial to determine the effect of fosinopril on echocardiographic measurements. RESULTS: Left ventricular mass index (LVMI) fell by 6.5 +/- 4.7% (mean +/- SD) with fosinopril and increased by 8.6 +/- 3.5% during placebo treatment (P < 0.02), and isovolumic relaxation time improved significantly in those with elevated baseline levels (P = 0.02). Systolic BP fell significantly, but this did not correlate with the change in LVMI, suggesting a possible direct action of fosinopril on the heart. CONCLUSIONS: Fosinopril appears to have significant cardiac benefits in patients with NIDDM who have normal or mildly elevated BP. These benefits are achieved without adversely affecting renal status and without impairing metabolic control of diabetes.

Blood Glucose↗

PubMed1993

Effect of calcium supplementation on bone loss in postmenopausal women.

BACKGROUND: The use of calcium supplements slows bone loss in the forearm and has a beneficial effect on the axial bone density of women in late menopause whose calcium intake is less than 400 mg per day. However, the effect of a calcium supplement of 1000 mg per day on the axial bone density of postmenopausal women with higher calcium intakes is not known. METHODS: We studied 122 normal women at least three years after they had reached menopause who had a mean dietary calcium intake of 750 mg per day. The women were randomly assigned to treatment with either calcium (1000 mg per day) or placebo for two years. The bone mineral density of the total body, lumbar spine, and proximal femur was measured every six months by dual-energy x-ray absorptiometry. Serum and urine indexes of calcium metabolism were measured at base line and after 3, 12, and 24 months. RESULTS: The mean (+/- SE) rate of loss of total-body bone mineral density was reduced by 43 percent in the calcium group (-0.0055 +/- 0.0010 g per square centimeter per year) as compared with the placebo group (-0.0097 +/- 0.0010 g per square centimeter per year, P = 0.005). The rate of loss of bone mineral density was reduced by 35 percent in the legs (P = 0.02), and loss was eliminated in the trunk (P = 0.04). Calcium use was of significant benefit in the lumbar spine (P = 0.04), and in Ward's triangle the rate of loss was reduced by 67 percent (P = 0.04). Calcium supplementation had a similar effect whether dietary calcium intake was above or below the mean value for the group. Serum parathyroid hormone concentrations tended to be lower in the calcium group, as were urinary hydroxyproline excretion and serum alkaline phosphatase concentrations. CONCLUSIONS: Calcium supplementation significantly slowed axial and appendicular bone loss in normal post-menopausal women.

Alkaline Phosphatase↗

PubMed1990

Quaternary naloxone blocks morphine analgesia in spinal but not intact rats.

Quaternary derivatives of naloxone and other compounds are assumed not to enter the central nervous system following systemic administration. We report that i.p. naloxone methylbromide (5 mg/kg) completely reversed the antinociceptive effect of systemically administered morphine (6 mg/kg) in acutely spinalised rats, although it had no effect in the same animals prior to the transection. Naloxone hydrochloride was effective both before and after transection. Nuclear resonance spectra confirmed the purity of both compounds. These results suggest that acute spinal transection allows rapid entry of quaternary naloxone into the spinal cord. Quaternary compounds therefore may need to be used with caution in spinalised animals.

Animals↗

PubMed1990

Behavioural modification of bulbospinal serotonergic inhibition and morphine analgesia.

Habituation to the stress of sham nociceptive testing enhances a rat's sensitivity to noxious thermal stimuli and reduces the antinociceptive effect of a subsequent acute dose of morphine. Since serotonin (5-hydroxytryptamine, 5-HT) mediates stress responses, experiments were designed to elucidate the role of 5-HT in these phenomena. Intrathecal methysergide or 5,7-dihydroxytryptamine (5,7-DHT) reduced baseline tail-flick latencies of novice rats to those of habituated animals. Morphine dose-response relationships were fitted to a 4 parameter sigmoidal function. Baseline latencies of novice animals were increased by 5-hydroxytryptophan (5-HTP) and reduced by parachlorophenylalanine (PCPA) in both reflex tests and in the hot-plate test, but latencies of habituated animals were unchanged by either treatment. In both reflex tests, the maximum effect due to morphine was increased by 5-HTP and reduced by PCPA in novice but not in habituated animals. We conclude that the serotonergic component of morphine's bulbospinal action represents the stress of the testing environment rather than an essential part of morphine's action.

5,7-Dihydroxytryptamine↗

PubMed1990

Hypercapnia depresses nociception: endogenous opioids implicated.

Hypoventilation produces hypercapnia which can elevate pain thresholds. Hypercapnia is a potent stressor which releases catecholamines and activates the sympathetic nervous system. Some stressors produce analgesia by releasing endogenous opioids. To determine the roles of endogenous opioids and catecholamines in hypercapnic analgesia, we administered CO2 in the inspired gas mixture to conscious rats. CO2 in the range 5-10% elevated tail flick and leg flexion latencies 2- to 3-fold in both intact and spinalised animals. The effects on reflex latencies but not on paCO2 or pHa were blocked by naloxone (2 mg/kg), and were not present in morphine-tolerant animals. The effects were reduced by dexamethasone but were not changed either by adrenalectomy or by systemic guanethidine, propanolol or phentolamine. Hypercapnia delayed the onset of the late phase of behavioural responses to formalin injected into the plantar surface of the hindpaw. We conclude that moderate hypercapnia powerfully depresses flexor withdrawal responses to noxious stimuli, by a mechanism involving release of endogenous opioids but not systemic catecholamines. This effect may account in part for the elevation in pain threshold during hypoventilation.

Analgesia↗

PubMed1989

Behavioural tolerance to morphine analgesia is supraspinally mediated: a quantitative analysis of dose-response relationships.

Repeated exposure of a rat to a nociceptive testing environment ('habituation') enhances its sensitivity to noxious thermal stimuli20 and reduces the antinociceptive effect of a subsequent acute dose of morphine ('behavioural tolerance'). The present study quantitatively characterises the effects of habituation upon morphine antinociception using hot-plate (50 and 55 degrees C) and reflex withdrawal tests (dipping the tail and hindpaws into water at 49 degrees C). Dose-response relationships were modeled with the empirical function; E = Eo + (EMAX*DN)/(ED50N + DN) where E is the time-integrated response, EMAX is the response attributable to morphine, Eo is the baseline response, D is the dose and N is a steepness parameter. Habituation reduced EMAX in both hot-plate tests and also reduced Eo on the 50 degrees C hot-plate. In both reflex tests, habituation reduced Eo to that of spinal animals and EMAX to a value intermediate between that of intact and spinal animals. Neither the ED50 nor the value of N was altered by habituation. Acute spinal novice and habituated animals had similar dose-response curves and parameters. Sham spinalisation had no significant effect on any of the parameters. It is concluded that habituation to the nociceptive testing environment substantially reduces the bulbospinal contribution to morphine analgesia but has no effect upon the spinal component.

Analgesia↗

PubMed1989

Repeated exposure to sham testing procedures reduces reflex withdrawal and hot-plate latencies: attenuation of tonic descending inhibition?

Five days' repeated exposure of experimentally naive rats to the experimental environment and to sham nociceptive testing procedures ('habituation') reduced the latency for reflex withdrawal of the hindpaw from hot water (49 degrees C) by 43%, to that of spinalised habituated or novice animals. Hot-plate (50 degrees C) paw lick latencies were reduced equally (40%) by habituation or parachlorophenylalanine, and were increased 32% by D,L-5-hydroxytryptophan. Neither drug affected hot-plate latencies of habituated animals. Naloxone had no effect on flexor withdrawal or hot-plate latencies in either novice or habituated animals. These results suggest that habituation substantially attenuates tonic serotonergic inhibition of spinal nociceptive transmission.

Animals↗