Chromosomes in colour.
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Chromosomes, Human↗
Biomedical subjects
A Stewart
Publications and source records attributed to A Stewart.
Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam.
BACKGROUND: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone plus lorazepam (M + D + L) over three consecutive courses of cisplatin chemotherapy. PATIENTS AND METHODS: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D + L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M + D + L). RESULTS: On the first course chemotherapy, O + D was significantly superior to the M + D + L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O + D and 20% of M + D + L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly occurring adverse events in the O + D group were constipation (25%) and headache (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group. Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. CONCLUSION: This study show that O + D is significantly more effective and better tolerated than M + D + L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.
Adult↗
Using health status measures with the seriously mentally ill in health services research.
Changes in the delivery of mental health care have prompted interest in using generic health status measures to test the effect of system change on those receiving treatment. Of special concern are those with serious and persistent mental illness who may be neglected when cost containment efforts reduce the availability of treatment services. This population may be affected by these changes, which might go undetected if investigators use scales that measure only pathology and not the full spectrum of well-being. The purpose of this study was to test the feasibility of using self-report health status measures with this population, to describe the psychometric properties of the scales, and to report the health status scores of a random sample of the Medicaid psychiatrically disabled population. We found that the four health status scales had adequate psychometric properties, that score variability was high, the distributions normal, and that patterns of association with more traditional clinical measures were of the expected size and direction. One scale, General Health Perceptions, had reliability and item-to-score correlation below acceptable levels.
Adult↗
Very preterm infants at fourteen years: relationship with neonatal ultrasound brain scans and neurodevelopmental status at one year.
A follow-up study was carried out on a cohort of 1142 very preterm (< 33 weeks) survivors who had ultrasound (US) brain scanning from birth. Follow-up was continued into adolescence, and included magnetic resonance imaging (MRI) of the brain at 14-15 y. Neonatal US findings and neurodevelopmental status at 1 y predicted outcome at 8 and 14 y, including cognitive development, poor interhemispheric interaction and school performance. MR brain imaging indicated that neonatal US accurately identified serious, permanent lesions in the brains of these very preterm infants, although US failed to recognise a large proportion of the abnormalities detected in adolescence by MRI. Atrophy of the corpus callosum was one of the commonest findings on MRI brain scans, supporting the hypothesis that damage to this important commissure may account for the poor school performance reported in very low birthweight infants.
Adolescent↗
Prediction of fractures in perimenopausal women: a comparison of dual energy x ray absorptiometry and broadband ultrasound attenuation.
OBJECTIVE: To consider whether bone mineral density (BMD) measurements can predict traumatic fractures occurring in perimenopausal women. METHODS: One thousand perimenopausal women called up for screening underwent both dual energy x ray absorptiometry (DXA) of the spine and hip, and broadband ultrasound attenuation (BUA) of the heel. Two years later, they were sent a questionnaire to discover those who had since had a fracture, and compare them with those who had not. RESULTS: About 2% of the women had sustained a fracture in the two years since attendance for screening. Fractures in this age group can be predicted weakly, but significantly, by bone mass measurements using DXA and BUA (odds ratios from 1.4 to 2.1). The lumbar spine appeared to be one of the best predictive sites (odds ratio for 1 SD reduction in BMD 2.1 (95% confidence interval 1.2 to 3.8)), but no significant differences were found between the areas under the curve in receiver operator characteristic (ROC) analysis. CONCLUSION: In this preliminary study it appeared that bone mass measurements are predictive of perimenopausal traumatic fractures in addition to postmenopausal fractures related to osteoporosis. DXA of the lumbar spine did not perform significantly better than BUA. The number of fractures occurring was low, however, and further long term follow up is required to confirm the finding.
Absorptiometry, Photon↗
Optimal control of cyclophosphamide-induced emesis.
Cyclophosphamide induces moderate to severe emesis. The severity of emesis is dependent on the dose of cyclophosphamide and on the addition of other cytotoxic drugs. A review of the literature dividing studies according to the dose of cyclophosphamide and the specific cytotoxic combination shows that ondansetron plus dexamethasone provides optimal antiemetic therapy in patients receiving standard or high-dose cyclophosphamide (> or = 450 mg/m2). These studies also show that it is important to give antiemetic therapy to cover the prolonged duration emesis and nausea induced by these regimens, e.g. intravenous CMF/(F)AC/(F)EC. For continuous 'oral' (low-dose) CMF chemotherapy, oral ondansetron or oral metoclopramide plus intravenous (or possibly oral) dexamethasone are effective antiemetic therapies.
Antiemetics↗
Proton magnetic resonance spectroscopy of the brain in normal preterm and term infants, and early changes after perinatal hypoxia-ischemia.
The aims of this study were 1) to define normal perinatal maturational changes in proton metabolite peak-area ratios in two regions of the neonatal brain, the thalamic and occipitoparietal regions, and 2) to investigate abnormalities of these ratios after perinatal hypoxia-ischemia. Fifty-four infants were studied: 35 normal control infants at 31-42 wk of gestational plus postnatal age, and 19 "asphyxiated" infants suspected of cerebral hypoxic-ischemic injury. Proton spectra were collected at 2.4 tesla from (2 cm)3 voxels using the point-resolved spectroscopy technique with a 270-ms echo time. Lactate was detected in all infants studied. In the normal infants, lactate relative to N-acetylaspartate (NAA), choline and creatine was significantly greater in the occipitoparietal region than in the thalamus, and fell with increasing maturity in both regions, whereas NAA/ choline increased. The 19 asphyxiated infants were studied on a total of 34 occasions during the 1st wk of life (median age 1.8 d), at gestational plus postnatal ages of 27-41 wk. Maximum lactate/NAA was above 95% confidence limits for the control data in one or both regions in 11 of the 19 infants. Minimum NAA/choline was below 95% confidence limits in only one asphyxiated infants, who was later found to have congenital hypothyroidism. SD scores for lactate, relative to NAA, choline, and creatine, were higher in both regions in the asphyxiated infants compared with the normal infants, particularly in the thalamus. Early results of 1-y follow-up examinations indicate that raised lactate/NAA carries a poor long-term prognosis.
Asphyxia Neonatorum↗
Wortmannin and its structural analogue demethoxyviridin inhibit stimulated phospholipase A2 activity in Swiss 3T3 cells. Wortmannin is not a specific inhibitor of phosphatidylinositol 3-kinase.
Wortmannin and its structural analogue demethoxyviridin (DMV) have been reported to be specific inhibitors of phosphatidylinositol 3-kinase activity. Here we report that these compounds are not as selective as assumed and demonstrate inhibition of bombesin-stimulated phospholipase A2 activity by both wortmannin and DMV with an IC50 (2 nM) which is slightly more potent than the inhibition of insulin-stimulated phosphatidylinositol 3,4,5-trisphosphate generation in these cells (approximately 10nM). While it has not been possible to fully block in vitro phospholipase A2 activity with wortmannin, inhibition cannot be a consequence of inhibition of PI 3-kinase activity since bombesin fails to generate 3-phosphorylated lipids in the intact cell. Therefore, while wortmannin is indeed a PI 3-kinase inhibitor, it is not as specific as previously reported, and experimental conclusions based solely on its use should be treated with caution.
3T3 Cells↗
Preventable hospitalizations and access to health care.
OBJECTIVE: To examine whether the higher hospital admission rates for chronic medical conditions such as asthma, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and diabetes in low-income communities resulted from community differences in access to care, prevalence of the diseases, propensity to seek care, or physician admitting style. DESIGN: Analysis of California hospital discharge data. We calculated the hospitalization rates for these five chronic conditions for the 250 ZIP code clusters that define urban California. We performed a random-digit telephone survey among adults residing in a random sample of 41 of these urban ZIP code clusters stratified by admission rates and a mailed survey of generalist and emergency physicians who practiced in the same 41 areas. SETTING: Community based. PARTICIPANTS: A total of 6674 English- and Spanish-speaking adults aged 18 through 64 years residing in the 41 areas were asked about their access to care, their chronic medical conditions, and their propensity to seek health care. Physician admitting style was measured with written clinical vignettes among 723 generalist and emergency physicians practicing in the same communities. MAIN OUTCOME MEASURES: We compared respondents' reports of access to medical care in an area with the area's cumulative admission rate for these five chronic conditions. We then tested whether access to medical care remained independently associated with preventable hospitalization rates after controlling for the prevalence of the conditions, health care seeking, and physician practice style. RESULTS: Access to care was inversely associated with the hospitalization rates for the five chronic medical conditions (R2 = 0.50; P < .001). In a multivariate analysis that included a measure of access, the prevalence of conditions, health care seeking, and physician practice style to predict cumulative hospitalization rates for chronic medical conditions, both self-rated access to care (P < .002) and the prevalence of the conditions (P < .03) remained independent predictors. CONCLUSION: Communities where people perceive poor access to medical care have higher rates of hospitalization for chronic diseases. Improving access to care is more likely than changing patients' propensity to seek health care or eliminating variation in physician practice style to reduce hospitalization rates for chronic conditions.
Adult↗
Translation and validation of arthritis outcome measures into Spanish.
OBJECTIVE: To produce Spanish versions of common arthritis outcome measures: the Health Assessment Questionnaire (HAQ) Disability Scale, the Center for Epidemiologic Studies Depression Scale (CES-D), the Medical Outcomes Study (MOS) Pain Severity Scale, the Arthritis Self-Efficacy Scale for Pain and Other Symptoms (with the addition of 2 new items), the Visual Analogue Pain Scale, the MOS Self-Rated Health Item, and a Physical Activities Scale that would be usable by most Hispanics living in the US. We tested these translated measures for reliability and, where appropriate, validity. METHODS: Instruments were translated and back translated by bilingual persons from 5 different countries of origin. Translators met to resolve variations in translation. The instruments were then administered to Hispanic arthritis patients in 6 geographic locations (5 in the United States and 1 in Latin America). All instruments underwent standard psychometric testing. As appropriate, the sample was stratified by level of acculturation, nation of origin, and geographic location. RESULTS: The translated instruments, with slight modification, met acceptable levels of reliability and validity. They are understood and easily usable by diverse Spanish-speaking populations. CONCLUSION: The availability of these translated outcome measures should enable investigators to include monolingual Spanish-speakers into their studies, and should facilitate study of cross-cultural differences with respect to these specific outcomes.
Activities of Daily Living↗
Role of transoesophageal echocardiography in determining the source of peripheral arterial embolism.
Thirty patients with peripheral arterial embolism underwent conventional transthoracic echocardiography. Transoesophageal echocardiography was also performed in ten of the same patients. The detection rate of cardiac abnormalities considered responsible for embolism was five of 20 in patients who received only transthoracic echocardiography and eight of ten in those who underwent transoesophageal echocardiography. One abnormality was detected by transthoracic echocardiography in the ten patients who received both tests, while eight cardiac or aortic abnormalities were discovered by transoesophageal echocardiography (P < 0.05). Transoesophageal echocardiography is significantly better than conventional transthoracic echocardiography at detecting cardiac sources of peripheral arterial embolism.
Adult↗
Childhood cancers and competing causes of death.
From the survey that first identified cancer effects of foetal irradiation and related sources has come support for the following hypotheses: (1) competing causes of death for childhood cancers include abortions (solid tumours) and infections (RES neoplasms); (2) the forms taken by RES neoplasms vary with the nature and intensity of indigenous infections; (3) ideal conditions for developing diffuse RES neoplasms (leukaemia) include the gross immunological incompetence caused by trisomy 21; (4) the unusually localised RES neoplasms found in children who have survived repeated attacks of malaria (Burkitt lymphoma and chloroma) are probably the result of these children having exceptionally high levels of passive as well as active immunity; and (5) when teratogenic effects of in utero mutations include faulty erythropoiesis as well as faulty leucopoiesis, infections are not the only rival causes of death.
Cause of Death↗
Childhood cancer and parental use of alcohol and tobacco.
Reported consumptions of alcohol and tobacco for the parents of 1641 children who died with cancer in England and Wales during the period 1977 to 1981 were compared with similar information for the parents of 1641 control subjects. Consumption of alcohol by fathers was not associated with an increased risk of childhood cancer (relative risk (RR)) = 1.05; 95% confidence interval (CI): 0.86 to 1.28), but for daily consumption of cigarettes was not shown to be associated with an increased risk and consumption of alcohol was associated with a relatively low cancer risk (RR = 0.82; 95% CI: 0.70 to 0.96). Relations between maternal consumption of cigarettes and birth weights suggested that the smoking data were equally reliable for case patients and control subjects.
Alcohol Drinking↗
Carboxylation of osteocalcin in post-menopausal osteoporotic women following vitamin K and D supplementation.
The effect of vitamin supplements on bone metabolism indices in patients with osteoporosis has received scant attention in the literature. Over a 2-week period, vitamin supplements of K and K+D were given to 20 post-menopausal osteoporotic women with previous Colles fractures. Osteoporosis was confirmed by bone mass measurements that demonstrated that broadband ultrasound attenuation (os calcis) was almost as discriminatory as dual energy X-ray absorptiometry (spine and hip) in Colles fracture patients compared with matched controls. Vitamin K corrected the carboxylation defect in osteocalcin and while less marked 4 weeks later, the improvement was still detectable. The result after K+D was similar. The level of carboxylation became the same as in premenopausal women. Total osteocalcin level (bound) osteocalcin. While there was vitamin K correctable undercarboxylation of osteocalcin, simultaneously there was no evidence of undercarboxylation of prothrombin.
Absorptiometry, Photon↗
A New Zealand replication of the IPAM clustering model for low back patients.
OBJECTIVE: This study examined the reliability of the three-cluster model for chronic low back pain patients found using the Integrated Psychosocial Assessment Model (IPAM). A replication study using a sample of patients from a different country was completed. PATIENTS: Seventy patients (average age = 47.05 years, SD = 16.11) with chronic low back pain of noncancer origin participated in the study. Sixty-two of these patients were attending The Auckland New Zealand Regional Pain Service, while a further eight were attending a private practice pain service in Auckland. OUTCOME MEASURES: Subjects were assessed on the IPAM, which measures pain intensity, disability, coping strategies, attitudes towards and beliefs about pain, depression and illness behaviour, the Medical Examination and Diagnostic Information Coding System, and the Multidimensional Pain Inventory. RESULTS: Cluster analyses using the kappa-means algorithm were performed on the IPAM data. The three-cluster solution was preferred according to both the Variance Ratio Criterion and cluster interpretability. Two of the three clusters correlated highly with clusters retrieved in the original study (r = 0.78, r = 0.71), while the third cluster showed partial resemblance (correlation of r = 0.31). Clusters were named "In Control," "Depressed and Disabled," and "High Deniers and Somatizisers." No differences were found on the physical pathology scores between clusters. Decision rules for cluster assignation resulted in 68% of the sample being correctly assigned. CONCLUSIONS: Support for this cluster model from two countries suggests its value in providing a multidimensional picture of patients with chronic low back pain. The possibility of using such cluster groups for determining treatment type is discussed.
Adaptation, Psychological↗
Changes in bone mass and metabolism after surgery for primary hyperparathyroidism.
BACKGROUND AND OBJECTIVE: Bone mass is often reduced in patients with primary hyperparathyroidism (pHPT) and is usually partially reversible after parathyroidectomy. However, site specific and overall skeletal benefits of surgery in mild asymptomatic pHPT remain uncertain. DESIGN: Cross-sectional and longitudinal studies. PATIENTS: Fourteen patients (12 women and 2 men) with pHPT. MEASUREMENTS: Baseline bone mass was assessed at the lumbar spine, left hip and whole body using dual-energy X-ray absorptiometry, and at the left os calcis using broad-band ultrasound attenuation. Changes in bone mass, serum intact PTH and osteocalcin, and urinary pyridinium cross-link excretion were recorded in 10 patients followed for 6 months after surgery. RESULTS: (1) Cross-sectional study: Baseline measurements at the lumbar spine and hip were inversely related to both the serum PTH concentration and the weight of the parathyroid gland removed at surgery. (2) Longitudinal study: Six months after adenectomy, bone mass had increased significantly at the femoral neck, greater trochanter, whole body and os calcis, but not at the lumbar spine or Ward's area. Serum PTH, osteocalcin and pyridinium cross-link excretion all fell significantly after surgery. The percentage increment in whole body bone mineral content at 6 months was proportional to the baseline PTH. CONCLUSION: In primary hyperparathyroidism, preoperative reductions and post-operative gains in bone mass are proportional to the initial serum PTH concentration. Mild primary hyperparathyroidism probably does not cause appreciable bone loss at clinically relevant fracture sites such as the spine and hip, and in such cases the overall skeletal benefits of surgery are likely to be negligible.
Aged↗
Pregnancy ultrasound and childhood cancer: a second report from the Oxford Survey of Childhood Cancers.
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Child↗
Vertebral fractures in men and women: how discriminative are bone mass measurements?
Vertebral fractures are associated with osteoporosis. This study examined men and women with vertebral deformation/fractures, as defined by vertebral morphometry. These were compared with a population derived group measured contemporaneously who were defined as having no vertebral deformation/fracture by the radiographs. All patients underwent a dual energy X-ray absorptiometry (DXA) scan of the spine and hip, and a broadband ultrasound attenuation (BUA) scan of their os calcis. The abilities of these two techniques were compared for their discriminatory powers in this type of fracture. The results showed that DXA hip and spine had a better discriminatory power in the female vertebral group compared with BUA. In males none of the bone measurements could discriminate between the fracture and non-fracture groups.
Absorptiometry, Photon↗