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Biomedical subjects

R Taylor

Publications and source records attributed to R Taylor.

At least 271 records · Page 15Linked to original sources

Keeping an eye on Crohn's disease: orbital myositis as the presenting symptom.

Episodic periorbital swelling due to presumed orbital inflammation and myositis caused intermittent apparent proptosis and was the presenting symptom of ileocecal Crohn's disease (CD) in a teenage female with a family history of autoimmune disorders and CD. Orbital myositis, a very rare extraintestinal manifestation of inflammatory bowel disease (IBD), likely represents a process of impaired immunoregulation related to the underlying intestinal inflammation. This rare manifestation of IBD simulates the more commonly encountered thyroid orbitopathy (ophthalmopathy), but IBD should be considered if all thyroid tests are negative. It is important to recognize that orbital myositis may be an extraintestinal manifestation of Crohn's disease so that the diagnosis can be made and appropriate therapy commenced.

Autoimmune Diseases↗

Acidosis and coma after hemodialysis.

Ethylene glycol poisoning is a rare yet potentially fatal illness seen most commonly in association with ingestion by alcoholics or in suicide attempts. It is characterized by an elevated anion gap metabolic acidosis, osmolal gap, calcium oxalate crystals in the urine, and a well-defined clinical picture. Prompt treatment is crucial because effective intervention can prevent the neurologic, cardiac, pulmonary, and renal sequelae associated with ethylene glycol poisoning. Hemodialysis offers rapid clearance of ethylene glycol and its toxic metabolites. In this article, the case of a hemodialysis patient who suffered contamination of the dialysate solution with ethylene glycol, leading to altered mental status, coma, and severe anion gap metabolic acidosis, is reported. Despite prolonged dialysis and correction of the acidosis, the patient remained comatose and subsequently died.

Acidosis↗

Characterising non-covalent interactions with the Cambridge Structural Database.

This review describes how the CSD can be used to study non-covalent interactions. Several different types of information may be obtained. First, the relative frequencies of various interactions can be studied; for example, we have shown that the terminal oxygen atoms of phosphate groups accept hydrogen bonds far more often than the linkage oxygens. Secondly, information can be obtained about the geometries of nonbonded contacts; for example, hydrogen bonds to P-O groups rarely form along the extension of the P-O bond, whereas short contacts between oxygen and carbon-bound iodine show a strong preference for linear C-I ... O angles. Thirdly, the CSD can be searched for novel interactions which may be exploited in inhibitor design; for example, the I ... O contacts just mentioned, and N-H ... pi hydrogen bonds. Finally, the CSD can suggest synthetic targets for medicinal chemistry; for example, molecules containing delocalised electron deficient groups such as trimethylammonium, pyridinium, thaizolium and dinitrophenyl have a good chance of binding to an active-site tryptophan. Although the CSD contains small-molecule crystal structures, not protein-ligand complexes, there is considerable evidence that the contacts seen in the two types of structures are similar. We have illustrated this a number of times in the present review and additional evidence has been given previously by Klebe. The major advantages of the CSD are its size, diversity and experimental accuracy. For these reasons, it is a useful tool for modellers engaged in rational inhibitor design.

Crystallography, X-Ray↗

Stereotactic biopsy of nonpolar tumors in the dominant hemisphere: a prospective study of effects on language functions.

A prospective study of patients undergoing computerized tomography (CT)-guided stereotactic biopsy of nonpolar tumors in the dominant hemisphere was undertaken to determine if stereotactic biopsy caused a deterioration of language functions. Language was assessed using the Western Aphasia Battery (WAB) and the Boston Naming Test (BNT) before and after a biopsy sample was obtained. Of 16 patients studied, five (31%) were dysphasic preoperatively. After the biopsy the Aphasia Quotient (AQ), derived from the WAB, had significantly deteriorated in four (80%) of these patients, whereas in the fifth it remained relatively unchanged. One of these patients with an extensive infiltrating hemispheric oligoastrocytoma subsequently recovered normal language function after radiotherapy. In 10 of the 11 patients who had normal language function preoperatively there were no deleterious changes after biopsy in either the WAB subtest or BNT scores. In the other patient whose WAB score was normal preoperatively, there was a significant deterioration in postoperative AQ. This patient, who declined steroid therapy before and after biopsy, had a glioblastoma multiforme in Wernicke's area. A postoperative CT scan revealed no changes from what was shown on preoperative scan. This clinical study shows that CT-guided stereotactic biopsy of nonpolar tumors in the dominant hemisphere using the Brown-Roberts-Wells system and the Sedan-Nashold biopsy cannula carries a 9% risk (95% confidence intervals 0-26%) of impairing language functions if the patient is not dysphasic preoperatively. If the patient is dysphasic preoperatively, there is a very high risk of aggravating the dysphasia with stereotactic biopsy.

Adult↗

The discipline and literature of general practice.

In response to a review recently carried out by the Royal College of General Practitioners, the British Journal of General Practice is soon to be issued in a new and expanded format. While continuing to develop its primary role as a leading scientific journal of record, the journal will accommodate a monthly selection of integrated news, information and features. The editorial board welcomes the opportunities provided by these changes, but wishes to emphasize the continuing importance of general practice as a scientific discipline in its own right and to reaffirm its commitment to the publication of high-quality, peer-reviewed original research papers. It is hoped that the newlook journal will have a wide appeal. But, as the first-and still the foremost-journal of general practice in the world, it will continue to be a journal of record serving both its authors and the academic community worldwide.

Family Practice↗

Sweat analysis following pressure ischaemia in a group of debilitated subjects.

This article examines the application of a simple technique for the collection of sweat to the investigation of tissue metabolites in 11 debilitated subjects attending a rehabilitation unit. It is applicable to subjects with a range of clinical conditions. Sweat was collected at the sacrum with the subjects either seated in a wheelchair or lying in bed, which was representative of their usual daily routine. The tissues could be loaded during sweat collection by sacral support in either of these positions. Collections were made for about 10 hours and interface pressures were recorded on at least two occasions. After the prescribed period, the sweat pads were removed and a quantitative analysis of a range of metabolites was performed. Metabolite concentrations may reflect local tissue viability and responses to loading. In unloaded tissues the metabolite concentrations were similar to those observed in nondisabled subjects in an earlier study. During prolonged loading at relatively low levels of pressure, there was elevation in the levels of some metabolites; for example 39 and 28% increases for lactate and urea respectively. Successive measurements on an individual over a period of months showed variations, which were small compared to those observed in either groups of nondisabled or debilitated subjects. These observations suggest that the technique may be best applied in clinical practice to monitor sequential changes in individual subjects.

Adult↗

The utility of the Right Hemisphere Language Battery in patients with brain tumours.

The Right Hemisphere Language Battery (RHLB) (Bryan, 1989) was devised to assess the presence of language disorders in patients with damage to the right cerebral hemisphere and to permit an evaluation of the efficacy of therapeutic techniques. To evaluate the utility and sensitivity of the RHLB in patients with solitary right hemispheric brain tumours 20 patients were assessed before and after neurosurgery. Twenty control subjects with no signs or symptoms of brain disease who were undergoing lumbar spinal surgery were also assessed. On six of the seven RHLB subtests there was no significant difference between the scores obtained preoperatively by patients with right hemispheric brain tumours and the control subjects. There was also no significant change in the scores of the patients with tumours before and after resection of the lesion. The RHLB is therefore not recommended for either evaluating communication deficits or for measuring the efficacy of therapeutic techniques in patients with right hemisphere brain tumours. This study does, however, show that there are statistically significant differences between the control and brain tumour groups on the discourse analysis subtest preoperatively. The implications of the study are discussed together with possible reasons for the findings.

Adult↗

In vitro effect of adenosine agonist GR79236 on the insulin sensitivity of glucose utilisation in rat soleus and human rectus abdominus muscle.

The dose-response effects of a new adenosine agonist, GR79236, were examined in isolated rat soleus muscle strips and human rectus abdominus muscle strips. Effects on the insulin sensitivity of carbohydrate metabolism were examined, in particular upon insulin stimulated glycogen synthesis and glycolytic flux. In the presence of adenosine deaminase (ADA), GR79236 increased insulin sensitivity of pyruvate release from rat soleus muscle strips by 24% from 82.5 +/- 10.0 to 102.5 +/- 10.0 (P < 0.01), by 27% to 105.0 +/- 12.5 (P < 0.01) and by 24% to 102.5 +/- 10.0 (P < 0.01) nmol/25 mg per h at 0.1 and 10 microM GR79236, respectively. Rates of lactate release followed a similar but non-significant trend. Addition of GR79236 in the presence of ADA had no effect on rates of glycogen synthesis. Insulin stimulated rates of pyruvate or lactate release or of glycogen synthesis were unaffected by the addition of adenosine deaminase or GR79236 in human rectus abdominus muscle strips. Adenosine agonists may act indirectly to modulate insulin sensitivity of carbohydrate metabolism.

Adenosine↗

Clonal evolution of lung tumors.

Lung tumors, particularly squamous cell carcinomas, are believed to develop through a series of morphological abnormalities, driven by underlying somatic genetic changes. One way of studying this process is to analyze candidate somatic genetic changes in samples of squamous metaplasia and bronchial dysplasia of varying degrees of severity as well as tumor from the same patient. This assumes a clonal relationship between these lesions. In this article, we provide evidence that adjacent, physically distinct bronchial abnormalities are clonally related. This has been achieved using a plaque assay technique to detect the same p53 mutation, present throughout a tumor specimen, in a small proportion of cells in an adjacent squamous metaplasia. In addition, we have obtained two dysplasia samples from a tumor-free patient over a 9-month interval. The earlier sample had one p53 mutation, whereas the later sample has to p53 mutations on different alleles. Thus, the pattern of clonal evolution detected in the parallel samples mimics the pattern seen in longitudinal samples and supports the analysis of synchronously collected samples for the study of tumor progression.

Base Sequence↗

Direct assessment of liver glycogen storage by 13C nuclear magnetic resonance spectroscopy and regulation of glucose homeostasis after a mixed meal in normal subjects.

Despite extensive recent studies, understanding of the normal postprandial processes underlying immediate storage of substrate and maintenance of glucose homeostasis in humans after a mixed meal has been incomplete. The present study applied 13C nuclear magnetic resonance spectroscopy to measure sequential changes in hepatic glycogen concentration, a novel tracer approach to measure postprandial suppression of hepatic glucose output, and acetaminophen to trace the pathways of hepatic glycogen synthesis to elucidate the homeostatic adaptation to the fed state in healthy human subjects. After the liquid mixed meal, liver glycogen concentration rose from 207 +/- 22 to 316 +/- 19 mmol/liter at an average rate of 0.34 mmol/liter per min and peaked at 318 +/- 31 min, falling rapidly thereafter (0.26 mmol/liter per min). The mean increment at peak represented net glycogen synthesis of 28.3 +/- 3.7 g (approximately 19% of meal carbohydrate content). The contribution of the direct pathway to overall glycogen synthesis was 46 +/- 5 and 68 +/- 8% between 2 and 4 and 4 and 6 h, respectively. Hepatic glucose output was completely suppressed within 30 min of the meal. It increased steadily from 60 to 255 min from 0.31 +/- 32 to 0.49 +/- 18 mg/kg per min then rapidly returned towards basal levels (1.90 +/- 0.04 mg/kg per min). This pattern of change mirrored precisely the plasma glucagon/insulin ratio. These data provide for the first time a comprehensive picture of normal carbohydrate metabolism in humans after ingestion of a mixed meal.

Adult↗

Fetal growth and insulin resistance in adult life: relationship between glycogen synthase activity in adult skeletal muscle and birthweight.

Growth retardation during fetal life is associated with insulin insensitivity and an increased prevalence of impaired glucose tolerance in adult life. Because insulin-mediated stimulation of glycogen synthase may be an important rate-limiting step for insulin action at the cellular level, we have sought to determine whether impaired activation of muscle glycogen synthase is linked with early growth retardation. Postprandial glycogen synthase activity was therefore measured in muscle biopsies from a group of 27 women with normal glucose tolerance aged around 50 who were born in Preston, Lancashire, whose birthweight and body size at birth were recorded. Glycogen synthase activity measured at 0.1 mmol 1(-1) glucose-6-phosphate correlated with insulin sensitivity as measured by a short insulin tolerance test (r = 0.42, p < 0.05) and the waist to hip ratio (r = -0.48, p < 0.01), but not body mass index, body fat percentage or age. Within the group of women with normal glucose tolerance there was no relationship between intra-uterine growth as evidenced by birthweight or body size at birth and the response to insulin of skeletal muscle glycogen synthase in adult life. Thus we found no evidence for a direct link between fetal growth and insulin sensitivity in this pathway.

Biopsy↗

Practical community screening for diabetic retinopathy using the mobile retinal camera: report of a 12 centre study. British Diabetic Association Mobile Retinal Screening Group.

OBJECTIVE: To document the performance of 12 diabetes eye screening units in different health districts which were financed by a single charitable donation. DESIGN: Each location was equipped with a retinal camera and screening vehicle, and the lead clinician developed the screening service configuration to suit local conditions. SETTINGS: Districts were chosen on the basis of interest in developing effective diabetes eye screening services. Characteristics of districts varied from largely rural to exclusively urban. SUBJECTS: People with diabetes who attended either general practice or hospital diabetes services were screened. MAIN OUTCOME MEASURES: Referral for ophthalmological opinion and use of laser therapy for new vessel formation or exudative maculopathy. RESULTS: A total of 64,905 screening episodes were recorded. Full data were available on 42,803 episodes which led to 2400 referrals (5.6%) and 516 of which resulted in laser therapy (1.2% of those screened or 21.5% of those referred). Where sequential data were available a year by year fall in sight threatening retinopathy incidence was demonstrated as the screening programmes detected incipient problems in the initial cycles of screening. The average cost of screening was Pounds13.11 per patient and the average cost of identifying a person requiring laser therapy was Pounds1110. Financial responsibility for running the service has been taken on by 10 of the 12 health districts. CONCLUSIONS: Diabetes eye screening using a mobile retinal camera is effective, efficient and robust. It is important that the service specification is designed to suit the geography and existing diabetes services in each district.

Costs and Cost Analysis↗

Comparison of conformer distributions in the crystalline state with conformational energies calculated by ab initio techniques.

The conformational preferences of 12 molecular substructures in the crystalline state have been determined and compared with those predicted for relevant model compounds by ab initio molecular orbital calculations. Least-squares regression shows that there is a statistically significant correlation between the crystal-structure conformer distributions and the calculated potential-energy differences, even though the calculations relate to a gas-phase environment. Torsion angles associated with high strain energy (> 1 kcal mol-1) appear to be very unusual in crystal structures and, in general, high-energy conformers are underrepresented in crystal structures compared with a gas-phase, room-temperature Boltzmann distribution. It is concluded that crystal packing effects rarely have a strong systematic effect on molecular conformations. Therefore, the conformational distribution of a molecular substructure in a series of related crystal structures is likely to be a good guide to the corresponding gas-phase potential energy surface.

Benzene Derivatives↗

Catastrophic circulatory collapse following re-expansion pulmonary oedema.

Re-expansion pulmonary oedema is a recognised but rare complication following the rapid drainage of a large pleural effusion or pneumothorax [1,2], usually occurring on the side of re-inflation. The pathogenesis of the pulmonary oedema is poorly understood but is thought to be due to micro-vascular shearing resulting in neutrophil activation and adhesion to the vascular endothelium resulting in increased micro-vascular permeability [3-7]. Few reports appear in the literature of invasive haemodynamic monitoring following this catastrophe. We describe a patient who sustained fatal pulmonary oedema arising in the contralateral lung, with pulmonary flow catheter data documenting the initial circulatory collapse following the aspiration of a massive pulmonary effusion.

Adult↗