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Biomedical subjects

A Ward

Publications and source records attributed to A Ward.

At least 19 recordsLinked to original sources

Arylamine N-acetyltransferase in human red blood cells.

N-Acetyltransferase activities associated with erythrocytes from 20 individuals have been determined with p-aminobenzoic acid as substrate. A three-fold variation in Vmax is found. The N-acetyltransferase genotype of the individuals has been determined and there is no correlation between the extent of acetylation measured in the individuals' erythrocytes and the inheritance of alleles at the polymorphic NAT locus. Folate is confirmed to be an inhibitor of arylamine N-acetyltransferase activity measured in erythrocytes. The content of folate in erythrocytes of individuals also varies. The individual with the maximum folate content has the minimum N-acetyltransferase activity. The monomorphic N-acetyltransferase gene from individuals spanning the range of N-acetyltransferase activity have been amplified, using the polymerase chain reaction. The pattern of restriction enzyme digestion of the monomorphic N-acetyltransferase gene with a series of eight restriction enzymes is the same for individuals spanning the activity range of arylamine N-acetyltransferase in their erythrocytes.

4-Aminobenzoic Acid

Treadmill validation of an over-ground walking test to predict peak oxygen consumption.

The purpose of this study was to determine whether a test developed to predict maximal oxygen consumption (VO2max) during over-ground walking, was similarly valid as a predictor of peak oxygen consumption (VO2) when administered during a 1-mile (1.61 km) treadmill walk. Treadmill walk time, mean heart rate over the last 2 full min of the walk test, age, and body mass were entered into both generalized (GEN Eq.) and gender-specific (GSP Eq.) prediction equations. Overall results indicated a highly significant linear relationship between observed peak VO2 and GEN Eq. predicted values (r = 0.91), a total error (TE) of 5.26 ml.kg-1.min-1 and no significant difference between observed and predicted peak VO2 mean values. The peak VO2 for women (n = 75) was predicted accurately by GSP Eq. (r = 0.85; TE = 4.5 ml.kg-1.min-1), but was slightly overpredicted by GEN Eq. (overall mean difference = 1.4 ml.kg-1.min-1; r = 0.86; TE = 4.56 ml.kg-1.min-1). No significant differences between observed peak VO2 and either GEN Eq. (r = 0.85; TE = 4.3 ml.kg-1.min-1) or GSP Eq. (r = 0.85; TE = 4.8 ml.kg-1.min-1) predicted values were noted for men (n = 48) with peak VO2 values less than or equal to 55 ml.kg-1.min-1. However, both equations significantly underpredicted peak VO2 for the remaining high peak VO2 men (n = 22). In conclusion, the over-ground walking test, when administered on a treadmill, is a valid method of predicting peak VO2 but underpredicts peak VO2 of subjects with observed high peak VO2 values.

Adult

Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.

BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.

Aged

Athletic heart syndrome.

AHS is a benign condition consisting of physiologic adaptations to the increased cardiac work load of exercise. Its primary features are biventricular hypertrophy and bradycardia associated with normal systolic and diastolic function. In addition, the alterations in cardiac structure are related to the type of training with dynamic training causing proportionally greater dilation and static training primarily increased wall thickness. AHS is associated with abnormalities in ECG, radiograph, and echocardiographic findings. It is important to be aware of these changes so that they are not misinterpreted to represent pathologic states. In particular, the distinction between AHS and HCM can be difficult, although certain historic and echocardiographic features can help differentiate the two.

Animals

Estimation of VO2max: a comparative analysis of five exercise tests.

Thirty-eight female subjects (M +/ SD = 33 +/- 3.0 years) had VO2max measured on the cycle ergometer (M +/- SD = 37.3 +/- 6.4 ml.kg-1.min-1) and on the treadmill (M +/- SD = 41.3 +/- 6.6 ml.kg-1.min-1). VO2max was estimated for each subject from heart rate (HR) at submaximal workloads on the cycle ergometer using the Astrand-Rhyming nomogram (A/R) and the extrapolation method (XTP). VO2max was also estimated from three field tests: 1.5-mile run (RUN) (independent variable [IV] = time), mile walk (WALK) (IV = time, age, HR, gender, body weight), and the Queens College Step Test (ST) (IV = HR during 5-20 s recovery). Repeated measure ANOVA revealed significant mean differences between the criterion cycle ergometer VO2max versus A/R and XTP (20 and 12% overestimation). The WALK, RUN, and ST VO2max values were not significantly different from the criterion treadmill VO2max. The correlation between criterion VO2max estimated from the WALK and RUN were r = .73 (SEE = 4.57 ml,kg-1.min-1) and r = .79 (SEE = 4.13 ml.kg-1.min-1), respectively. The ST, A/R, and XTP had higher SEEs (13-13.5% of the mean) and lower r s (r = .55 to r = .66). These results suggest both the WALK and RUN tests are satisfactory predictors of VO2max in 30 to 39-year-old females.

Adult

Development of a single-stage submaximal treadmill walking test.

An equation was developed to estimate maximal oxygen uptake (VO2max, ml.kg-1.min-1) based on a single submaximal stage of a treadmill walking test. Subjects (67 males, 72 females) aged 20-59 yr completed 4-min stages at 0, 5, and 10% grades walking at a constant speed (2.0-4.5 mph) and then performed a VO2max test. Heart rate and respiratory gas exchange variables were measured during the test. Multiple regression analysis (N = 117) to estimate VO2max from the 4-min stage at 5% grade yielded the following model (R2 = 0.86; SEE = 4.85 ml.kg-1.min-1): VO2max = 15.1 + 21.8*SPEED (mph) -0.327*HEART RATE (bpm) -0.263*SPEED*AGE (yr) + 0.00504*HEART RATE*AGE + 5.98*GENDER (0 = Female; 1 = Male). The constant and all coefficients were highly significant (P less than 0.01). To assess the accuracy of the model in a cross-validation group (N = 22), an estimated VO2max value was obtained using the above model. Estimated VO2max then was regressed on observed VO2max yielding the following equation (R2 = 0.92): ESTIMATED VO2max = 0.15 + 1.03*OBSERVED VO2max. The intercept and slope of this equation were not significantly different from 0 and 1, respectively. For 90.9% of the subjects in the cross-validation group, residual scores were within the range of +/- 5 ml.kg-1.min-1. In conclusion, this submaximal walking test based on a single stage of a treadmill protocol provides a valid and time-efficient method for estimating VO2max.

Adult

Attenuation of exercise-induced ST depression during combined isometric and dynamic exercise in coronary artery disease.

ST-segment depression was measured during submaximal dynamic (treadmill) and combined isometric-dynamic (isodynamic) exercise at comparable rate-pressure products in 11 patients (mean age 63 years) with stable coronary artery disease who were participating in an exercise training program. Each patient completed 3 separate trials. Trial 1 (baseline) was a submaximal treadmill exercise test to determine the threshold heart rate-systolic blood pressure (rate-pressure product) for ST-segment depression (greater than or equal to 1.0 mm). During trials 2 and 3, patients performed (in random order) dynamic treadmill exercise and isodynamic exercise (treadmill walking 1.5 to 2.0 mph carrying 15 to 25 kg) until threshold rate-pressure product was achieved. During trial 1, each patient showed significant ST depression (mean 1.7 mm) at target rate-pressure product (mean 18,200). Subsequent dynamic exercise trials 2 and 3 showed similar mean ST depression (1.5 mm) and rate-pressure product (18,000). During isodynamic exercise trials 2 and 3, subjects showed only minimal ST depression (mean 0.4 mm) at a rate-pressure product similar to dynamic exercise (mean 18,590). Heart rates were significantly lower (-10/min) and systolic (+20 mm Hg) and diastolic (+25 mm Hg) pressure was higher during isodynamic exercise (p less than 0.05). The rate-pressure product is not a valid index of ST response during isodynamic exercise in stable exercise-trained cardiac patients. Attenuation of ST depression during isodynamic exercise may be attributed to a combination of increased diastolic perfusion pressure, decreased heart rate and possibly to reductions in venous return and ventricular diastolic wall tension due to increased intrathoracic and abdominal pressure.

Aged

Flurbiprofen in human crevicular fluid analyzed by high-performance liquid chromatography.

The aim of this study was to determine whether the non-steroidal anti-inflammatory drug, flurbiprofen, which has been shown to be an inhibitor of alveolar bone loss in human periodontal disease, is present in human crevicular fluid (CF) following oral dosing. A method is described whereby routine high-performance liquid chromatography is used to detect the drug in only 20 microliters of CF. 5 volunteers abstained from toothbrushing for 21 days to induce experimental gingivitis and increase the resting flow of CF. 100 mg of flurbiprofen was taken by each volunteer on d 21-28. On d 21 and 28, serum and CF samples were taken prior to dosing and afterwards at 1, 2, 4 and 6 hours. On d 21 the mean peak concentration of the drug in serum was about 11 micrograms/ml and was found between 1-2 h after dosing. The respective values for CF (d 21) were 0.32 micrograms/ml and 4 h. On d 28 flurbiprofen was detected in both fluids prior to dosing. The mean peak concentrations after dosing had increased to 13.13 micrograms/ml (serum) and 0.46 micrograms/ml (CF) although the levels of the drug in CF remained relatively constant throughout the observation period on d 28. The results indicate that flurbiprofen may be detected in human CF after oral administration and that the levels are in excess of the plasma level, which in beagles has been shown to inhibit alveolar bone loss in periodontal disease.

Administration, Oral

Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile.

The gonadotrophin releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); gonadorelin] agonist buserelin is a promising new agent in the treatment of a variety of disorders in gynaecology and andrology, paediatrics and oncology. While a single dose of buserelin stimulates the release of pituitary gonadotrophins, multiple doses produce reversible pituitary desensitisation, and this specific blockade of gonadotrophin support to the gonads provides the basis for the drug's efficacy in conditions dependent on sex hormone secretion. Thus, buserelin provides comparable efficacy to orchidectomy or high dose estrogens in the treatment of hormone-sensitive prostate cancer and exhibits a lower incidence of adverse effects. During the early phase of treatment it may be particularly useful in combination with antiandrogens. Buserelin also appears promising in hormone-sensitive premenopausal breast cancer. Extensive studies have proven the value of buserelin in endometriosis, where it produces a transient remission with gradual recurrence of the disease on cessation of treatment. Surgical intervention is necessary in severe disease after buserelin-induced involution of the lesions. In patients with uterine leiomyoma, preliminary data suggest that buserelin may be beneficial in rendering surgery more conservative by reducing fibroid size, although it appears unlikely to preclude surgical intervention. The use of buserelin to induce a state of reversible hypogonadotrophism before administration of exogenous gonadotrophins is a promising strategy in the treatment of infertility associated with polycystic ovary syndrome and other conditions of infertility with underlying ovarian dysfunction; such a strategy also clearly enhances the efficiency of in vitro fertilisation programmes. Initial studies suggest its potential usefulness as a female contraceptive when administered intermittently in conjunction with a progestogen. Buserelin represents a first-line treatment of central precocious puberty. In endometriosis the adverse effect profile of buserelin is generally favourable, with hypoestrogenic effects such as hot flushes and vaginal dryness, and decreased libido, predominating. There is no apparent detrimental effect on lipid metabolism. The potential for adverse hypoestrogenic effects on bone mineral content with long term administration remains to be clarified. Thus, the GnRH agonist buserelin represents an advance in the treatment of a variety of gynaecological and andrological as well as paediatric and oncological conditions, infertility and other sex-hormone dependent conditions, with a low incidence of adverse treatment effects.

Animals

Long-term results of aortoinnominate and aortocarotid polytetrafluoroethylene bypass grafting for atherosclerotic lesions.

Between January 1978 and December 1986, 69 polytetrafluoroethylene bypass grafts on the ascending aorta were placed in 53 patients with atherosclerotic occlusive disease of the innominate and left common carotid arteries. Thirty-six patients had symptoms predominantly of amaurosis fugax, verebrobasilar ischemia, and upper limb ischemia. The remaining 17 patients had no symptoms but had severe hemodynamically significant occlusive disease. All operations were accomplished via median sternotomy. One patient died after surgery (operative mortality rate 1.9%), and one patient had minor postoperative neurologic deficit that partially improved on long-term follow-up. Patency of the reconstruction was routinely assessed by a Doppler device combining (1) a continuous wave Doppler and (2) real-time mechanical sector B-mode imaging with frequencies of 3.5 MHz and 7.5 MHz. There were two early asymptomatic occlusions; one was related to a technical error that was successfully revised and the other to low systemic perfusion. The mean follow-up time was 50.5 months. Two patients were lost to follow-up and a further six patients died, for a cumulative 5-year survival rate of 84.9%. One patient had only partial improvement in symptoms and one patient sustained a late postoperative neurologic deficit after internal carotid occlusion distal to a patent aortocarotid bypass. The remaining patients were free of symptoms. There were no infective complications. All the patients underwent late assessment by Doppler ultrasonography and B-mode scanning. One asymptomatic occlusion was thereby identified to be a result of diminished runoff. The overall secondary patency rate at 5 years was 96.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Morbidity coding in general practice.

If research is to be of any use the phenomena being studied must be clearly defined. Almost 30 years ago the difficulty of classifying primary care problems using the International Classification of Diseases (ICD-8) was demonstrated. This led to the development of the International Classification of Health Problems in Primary Care-2-Defined which is based on ICD-9. Despite the work that has gone into the development of ICHPPC-2-Defined, relatively little work has been undertaken to assess the validity and reliability of its use. This paper describes the results of such a study conducted as a preliminary to the use of ICHPPC-2-Defined in a study of consulting patterns in general practice. The participating general practitioners were trained in the use of ICHPPC-2-Defined and then coded problems which they identified in a set of clinical vignettes. Following the coding exercise, a review session was held in which difficulties and errors in the use of ICHPPC-2-Defined were discussed. Subsequently, the general practitioners were required to code two more sets of vignettes, which included some problems repeated from the preceding sets. Comparisons were then made of changes in the validity and reliability of coding from one round to the next. The results of the study suggest that the reliability and validity of morbidity data collected using ICHPPC-2-Defined can be increased by training sessions for the coders which focus on the main sources of error in the use of ICHPPC-2-Defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Australia

Carboplatin. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of cancer.

Carboplatin is a 'second-generation' platinum compound advocated for use in the treatment of patients with ovarian cancer and it has also shown promise in small cell lung cancer, squamous cell carcinomas of the head and neck, and seminomas. Overall, it would appear to have a similar qualitative spectrum of activity to cisplatin. There have been few comparative trials with carboplatin, either alone or in combination with other chemotherapeutic agents, but the limited data suggest comparable efficacy with cisplatin in ovarian cancer. Importantly, the toxicity profile of carboplatin is markedly different from that of cisplatin, with nephrotoxicity, neurotoxicity and ototoxicity occurring only infrequently with carboplatin. As with cisplatin, nausea and vomiting occur in many patients after carboplatin administration, but symptoms are usually delayed for several hours and are mild to moderate in severity - dose-limiting nausea and vomiting are infrequent with carboplatin. The dose-limiting toxicity of carboplatin is myelosuppression, with severe thrombocytopenia and less often leucopenia, which may be more severe in older patients or in those with renal impairment or those who have had previous chemotherapy. Thus, preliminary data suggest that carboplatin is a therapeutically equivalent alternative to cisplatin, but with a differing toxicity profile that should offer advantages over cisplatin in many patients.

Carboplatin

Arterial complications of the thoracic outlet syndrome: fifty-five operative cases.

Between January 1, 1969, and December 31, 1984, 55 operative procedures were carried out in 47 patients to correct subclavian-axillary artery lesions resulting from compression at the thoracic outlet. The most common causes of compression were a long cervical rib (27) and an anomalous first rib (15). Presenting features included claudication, vasomotor phenomena, digital gangrene, and acute limb-threatening ischemia. A combined supraclavicular and infraclavicular approach was preferred. Decompression was best achieved by excision of the cervical rib and the first rib and division of all soft tissue elements. The most common methods of arterial repair were resection-anastomosis (23) and replacement of vein graft (11). Embolic occlusions were frequently present (35). Axillary emboli were amenable to direct revascularization at the time of subclavian artery repair. If possible, more-distal embolic occlusions were managed without recourse to embolectomy catheter manipulations. The mean follow-up was 5 years 8 months (range 4 months to 16 years). Patients were assessed clinically, and the arterial repair was monitored by Doppler ultrasonography, B-mode scanning, and digital subtraction angiography. Of the 39 patients available for follow-up, 35 had no symptoms and four had residual claudication. There were no amputations. In the remaining cases the subclavian-axillary artery segment showed no hemodynamic or anatomic abnormality.

Adolescent

Walking for health and fitness.

Recent studies have linked regular physical activity with reduced likelihood of developing coronary heart disease. Even low- and moderate-intensity exercise such as walking, when carried out consistently, is associated with important cardiovascular health benefits. Walking has also been shown to reduce anxiety and tension and aid in weight loss. Regular walking may help improve cholesterol profile, help control hypertension, and slow the process of osteoporosis. Recent physiological studies have demonstrated that brisk walking provides strenuous enough exercise for cardiovascular training in most adults. A recently developed submaximal 1-mile walk test provides a simple and accurate means for estimating aerobic capacity and guiding exercise prescription. These new insights and tools will assist the clinician in the prescription of safe and effective walking programs.

Coronary Disease

Detection of specific IgM in varicella and herpes zoster by antibody-capture radioimmunoassay.

A simple and sensitive M antibody-capture radioimmunoassay (MACRIA) is described which utilizes crude commercial VZV antigen and a single monoclonal anti-VZV antibody. This was compared to the immunofluorescence (IF) test for IgM antibody and was used to study IgM responses in sera from 261 patients with varicella and 220 patients with herpes zoster. With MACRIA, IgM antibodies were detected in all patients with varicella. The IgM antibodies appeared shortly after onset of rash, reached peak levels between 1 and 4 weeks after onset and then declined to low or undetectable levels in most, though not all, patients after 3 months. IgM antibodies were also detected in 98.2% of patients with herpes zoster, but the levels of IgM were significantly lower than after varicella and there was wider individual variation both in magnitude and duration of the IgM responses, in some cases only lasting 2-3 weeks. Comparison between MACRIA and IF showed good agreement in the detection of IgM antibodies following varicella. Discordant results were obtained with 13% of sera, of which 81% were taken either early or late after onset of rash and contained very low IgM levels. In contrast, 62 (28%) of the 220 sera from patients with zoster gave discordant results in the two tests, all except five being MACRIA-positive but IF-negative. The largest proportion of discordant results were obtained with sera taken more than 3 months after onset of rash, but 18 (29%) contained high IgM levels and were taken during the period of peak IgM responses. The diagnostic applications of the VZV MACRIA are discussed.

Chickenpox