What went wrong: why programs failed.
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Black or African American↗
Biomedical subjects
C Sims
Publications and source records attributed to C Sims.
Angiotensin II-induced changes in guanine nucleotide binding and regulatory proteins.
Systemic infusion of angiotensin II, a potent agonist, using doses that are initially subpressor, eventually produces sustained blood pressure elevation and reductions in glomerular capillary ultrafiltration coefficient characterized by enhanced signal transduction to angiotensin II and other agonists. In this setting, there is a significant increased affinity of angiotensin II binding to smooth muscle and glomerular mesangial receptors and enhanced sensitivity and magnitude of angiotensin II-induced decrements in cyclic AMP. Since G proteins are important modulators of binding and signal transduction, the present studies were designed to test the hypothesis that differences in the relative amounts of G proteins may be present and have accounted for differences observed. G proteins were identified and quantitated by isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis, radiolabeling in the presence of activated toxins with [gamma-32P]NAD+, immunoprecipitation, and immunoblotting. A 168% and 465% increase in pertussis toxin-catalyzed ADP ribosylation of alpha 40-41 was found in angiotensin II-treated groups over control groups for glomerular and mesenteric membranes, respectively. Immunoblotting revealed a 250% and 35% increase in the levels of the Gi isoforms alpha i-2 and alpha i-3, respectively, and a decrease of 53% in alpha i-1 from the angiotensin II-treated group. No differences were observed in cholera toxin labeling or immunoblotting of Gs. These results demonstrate multiple mechanisms whereby angiotensin-induced signal transduction can be modulated involving both the receptors and G proteins. These observed differences in G proteins in systemic and renal vasculature accompanying angiotensin II infusion suggest the possibility of a regulatory role in the pathophysiology of angiotensin II-induced hypertension and renal disease.
Adenosine Diphosphate Ribose↗
Magnetic resonance imaging of the head and spine: effective for the clinician or the patient?
OBJECTIVES: To test how the results of magnetic resonance imaging influence clinicians' diagnoses and management plans for patients with cranial and spinal problems and to assess changes in the quality of life of these patients. DESIGN: Survey of patients undergoing cranial and spinal magnetic resonance imaging with questionnaires about diagnoses and intended management plans before and after imaging and quality of life questionnaires at the time of imaging and again four months later. SETTING: Regional magnetic resonance imaging and spectroscopy unit. SUBJECTS: 100 consecutive patients referred for cranial imaging in early 1989; 100 similar patients referred for spinal imaging. MAIN OUTCOME MEASURES: Changes in clinicians' leading diagnoses after magnetic resonance imaging and their confidence in these diagnoses; changes in intended management plans; assessment of the contribution to the future management of the patient; changes in patients' quality of life. RESULTS: Magnetic resonance imaging altered the clinicians' leading diagnoses in 35 of 169 (21%) cases. The clinicians became more confident about their leading diagnoses in 90 of 167 (54%). There was a change in management plan in 113 of 182 (62%). The clinicians considered that magnetic resonance imaging made an important contribution to management in 119 of 162 (73%) patients. Overall, the patients' quality of life was unchanged at the four month assessment. CONCLUSIONS: Magnetic resonance imaging of patients with cranial and spinal problems influences clinicians' diagnoses and management plans, but the quality of life of these patients remains unchanged.
Adolescent↗
Magnetic resonance imaging: when is one sequence sufficient?
We have studied 100 patients undergoing magnetic resonance imaging (MRI) in eight well-defined clinical problems. The relative values of the clinical details and the initial imaging sequence in reaching the final MR diagnoses were assessed. For each patient, two radiologists independently predicted the likely radiological findings from the clinical details. They then assessed the radiological appearances shown by the initial imaging sequence (which was chosen according to the clinical problem). Lastly, they made a final interpretation using all the available information. Prediction of likely radiological abnormalities from the clinical details proved unreliable. However, the radiological assessment of the initial imaging sequence was reliable for clinical problems related to the pituitary fossa, posterior fossa, internal auditory meatus and for suspected multiple sclerosis. In these patient groups additional sequences might be reserved for those with equivocal findings. Conversely, assessment of the initial imaging sequence proved unreliable compared with the full radiological assessment for clinical problems in the lumbar spine, the axilla and the knee. This study has led us to reduce the number of sequences performed for some clinical problems, with a commensurate increase in the throughput of patients.
Clinical Competence↗
Thickly and thinly applied lignocaine-prilocaine cream prior to venepuncture in children.
EMLA cream (Astra Pharmaceuticals) which contains lignocaine and prilocaine, is widely used in a thick layer to reduce the pain associated with venepuncture. Application of smaller amounts of cream lowers cost and may reduce side-effects. The efficacy of a thick layer (using 2.0 ml) and a thin layer (using 0.5 ml) of lignocaine-prilocaine cream prior to venepuncture was compared in a randomised study of one hundred children. Pain with venepuncture was assessed using a behavioural rating scale as none, slight, moderate or severe. Children in the thin layer study group experienced slight pain more often than children in the thick layer study group (P less than 0.01). No child in either group experienced moderate or severe pain. It is concluded that a thin layer of lignocaine-prilocaine cream is not as effective as a thick layer in producing the pain-free venepuncture which is desirable in children.
Administration, Cutaneous↗
Measurement of regional left ventricular function using labelled magnetic resonance imaging.
A technique for assessing regional left ventricular function using magnetic resonance imaging is described. Spatial modulation of magnetization (SPAMM) is effected immediately before images are obtained at various intervals during the cardiac cycle using a modified field echo even rephasing technique (FEER). By performing such modulation in two planes, a grid pattern of labelling can be produced across the image. On the resulting labelled short axis images of the left ventricle, the systolic increase in thickness (thickening) and decrease in length (shortening) of different regions of myocardium can then be measured. The findings in five normal volunteers are presented. Radial shortening was twice as great in the endocardium (mean 20.4%, standard deviation (SD) 5.7) than in the epicardium (mean 10.2%, SD 5.5) and appears to offer more promise as a marker of regional function than simple thickening (mean 9.8%, SD 13.6).
Adult↗
Axillary fibrosis or recurrent tumour. An MRI study in breast cancer.
Magnetic resonance imaging was performed in 35 patients with breast carcinoma in an attempt to elucidate the cause for arm oedema or neurological symptoms. In each patient the clinician was asked to predict at the outset whether tumour recurrence or radiation fibrosis was more likely on clinical grounds. MRI demonstrated features compatible with fibrosis in 21 and tumour recurrence in 10; the MRI findings were equivocal in four patients. The range of these appearances is described and demonstrated. The MRI findings were at gross variance with the clinical opinion in 10 patients, upgrading eight patients to tumour recurrence and downgrading two to radiation fibrosis. Although histological confirmation is only available in three patients, corroborative evidence (that is repeat MRI, clinical follow up) is presented which suggests that the MRI interpretation was correct in the remaining patients. MRI can provide a working diagnosis in these patients; this allows a more rational approach to treatment than a diagnosis based on clinical examination alone.
Adult↗
Proximal tubular epithelial cells possess a novel 42-kilodalton guanine nucleotide-binding regulatory protein.
The proximal tubule of the kidney represents an important location where adenylate cyclase regulates salt and water transport; yet a detailed characterization of the distribution and classification of guanine nucleotide-binding protein (G protein) and adenylate cyclase is lacking. We used purified brush border (20-fold) and basolateral membranes (14-fold) to characterize parathyroid hormone- and G protein-regulated adenylate cyclase and G-protein distribution. Adenylate cyclase was predominantly localized to basolateral membranes, while the 46-kDa alpha subunit of the stimulatory G protein (Gs) was 2-fold higher in brush border membranes than in basolateral membranes. The alpha subunit of the inhibitory G protein (Gi; 41 kDa) was equally distributed on immunoblotting but was 2-fold higher in brush border membranes than in basolateral membranes on radiolabeling with pertussis toxin. A 42-kDa cholera toxin substrate that cross-reacted with antisera to the common alpha subunit of G proteins and to Gs on immunoblotting and that was not immunoprecipitated with two Gi antisera was the most abundant alpha subunit and comprised approximately 1% of the total membrane proteins. These observations suggest that G proteins are important regulators of proximal tubular transport independent of adenylate cyclase.
Adenosine Diphosphate Ribose↗
Magnetic resonance imaging of the brain and brain-stem in elderly patients with dizziness.
Twenty elderly patients (mean age 82 years) with dizziness were examined by magnetic resonance imaging (MRI). The findings have been compared with those from nine healthy subjects of similar age who acted as a control group. The technique proved acceptable to all these patients, and in the majority (65%) the overall radiographic quality of the resulting images was adequate, good or excellent. Nineteen of the 20 patients showed evidence of abnormal high signal intensity within white matter, often close to the frontal horns but also more widely scattered within the cerebral hemispheres; similar lesions were seen in the brain-stem in eight of the patients. However these white matter changes were equally prevalent in the control group. No cause for dizziness has been shown by MRI.
Aged↗
Fatal air embolism following anesthesia for insertion of a peritoneovenous shunt.
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Anesthesia, General↗
Subarachnoid haemorrhage of unknown cause: a long term follow-up.
Three hundred and sixteen patients who suffered a subarachnoid haemorrhage of unknown cause were followed up by questionnaire after 2 to 23 years, the average interval being 10 years. Two hundred and fifty one (79.5%) are known to be alive, 49 (15.5%) had died, and 16 (5%) patients were untraceable. The cumulative survival for the whole group after 22 years was 69%, the expected survival being 89%. The certified cause of death of 30 patients was from diseases of the circulatory system, mainly myocardial infarction and cerebrovascular disease, the expected number being 21.8. The results of this survey show a reduced life expectancy for both males and females and suggest that a more guarded view should be taken than is presently the case about the long term prognosis of these patients.
Adult↗
Treatment of tumours of the parotid gland and middle ear using obliquely reconstructed computed tomographic images.
Conventional planning of radiotherapy of tumours of the parotid, middle ear and other tumours in the head and neck often requires the treatment plane to be non-transverse. This produces major problems in delineating the tumour as well as verifying that vital structures such as the spinal cord are not included in the target volume. The use of computed tomography (CT) generally overcomes some of these problems and we have developed an algorithm to reconstruct transverse CT images into the appropriate oblique plane. Software has been written on the Picker Independent Treatment Planning System (ITPS) to allow planning on central axis and off-axis oblique planes. In addition we have used a beam's eye view facility to aid in the verification process.
Ear Neoplasms↗
Kinking of the Mera-F-Circuit.
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Anesthesia, Inhalation↗
A radiation safety survey on a Clinac-20 linear accelerator.
The radiation protection problems associated with a 20 MV linear accelerator are discussed, in particular those due to the considerable neutron production accompanying the 18 MV photon beam. These include the potential neutron dose to the patient, the special shielding requirements and the neutron activation of the accelerator and its surroundings. The results of the structural protection survey are described. In particular, the methods recommended by the NCRP for predicting the neutron dose equivalent at the end of a maze are shown to be reliable. Dose rates due to activation of the treatment room and various parts of the accelerator were measured, and potential doses to staff were assessed. Neutron dose equivalents were measured in the specified two metre diameter patient plane using the standard NRPB neutron badges and also with the recently developed CR-39 dosimeters. The latter appear to give sensible results.
Equipment Design↗
Spiritual care as a part of holistic nursing.
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Holistic Health↗
The effect of exercise training on insulin resistance in sedentary year old rats.
The purpose of this study was to determine if exercise training of 12-month-old Sprague-Dawley rats could reverse the resistance to insulin-induced glucose uptake that has been shown to occur in these animals. Twelve-month-old rats were trained to run 1 1/2 miles/day in motorized exercise wheel cages, and the ability of insulin to stimulate glucose uptake in these rats was compared with values observed in two groups of similar aged sedentary rats--one fed rat chow ad libitum and the other a calorie-restricted diet for 4 months. Body weight increased and insulin-stimulated glucose uptake decreased as rats fed chow ad libitum grew from 12 to 16 months of age. In contrast, 4 months of either exercise training or calorie restriction prevented weight gain and loss of insulin-stimulated glucose uptake. Thus, the intensity of exercise training attained in this study did not result in an improvement in insulin action in older rats above and beyond that related to the reduction in rate of body weight gain.
Aging↗
Effects of dimethyl sulfoxide on humoral immune responses to acetylcholine receptors in the rat.
The effects of dimethyl sulfoxide (DMSO) on the humoral immune responses to acetylcholine receptors (AChR) were studied in rats with experimental autoimmune myasthenia gravis. DMSO was administered during primary, ongoing, and secondary phases of the immune response to AChR. Anti-AChR antibody titers were measured to determine the effect of the treatment. DMSO had pronounced effects on the humoral immune response, which differed depending on the stage of the response and the strength of antigenic stimulation. When given during an ongoing immune response, DMSO suppressed anti-AChR antibody levels by an average of 53-76%. This effect was similar whether DMSO was given by oral, rectal, or intraperitoneal routes. DMSO treatment also suppressed the anti-AChR antibody response to a weak primary antigenic stimulus to a similar extent. In contrast, when administered during a secondary or a strong primary immunization, DMSO enhanced the anti-AChR antibody response 1.7- to 2.8-fold. These results show that DMSO may either enhance or suppress humoral immune responses. Further studies will be required to analyze the cellular mechanisms underlying the actions of DMSO.
Animals↗