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Biomedical subjects

S Robinson

Publications and source records attributed to S Robinson.

At least 19 recordsLinked to original sources

Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function has not been evaluated in patients with congestive heart failure. Therefore, the renal effects of indomethacin were examined in patients with chronic heart failure, and the relation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration was assessed. Twenty-five patients with congestive heart failure and an ejection fraction less than 40% were evaluated. At baseline, renal plasma flow and glomerular filtration rate were measured, using disappearance from the serum of intravenously injected 131I-orthodihippurate and urinary accumulation of intravenously injected technetium-99m diethylenetriamine pentaacetic acid, respectively. After 3 days, 75 mg of sustained release indomethacin were administered, and repeat renal function tests were performed. Mean glomerular filtration rate decreased from 40 +/- 21 to 32 +/- 16 ml/min/1.73 m2 (p less than 0.05), and mean renal plasma flow decreased from 242 +/- 122 to 222 +/- 110 ml/min/1.73 m2 (p less than 0.05). There was no correlation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration. It is concluded that 1 dose of an NSAID may cause marked and clinically important alterations in renal function in patients with heart failure. However, the decrease in glomerular filtration rate does not merely reflect a decrease in renal plasma flow, but probably the effects of NSAIDs on the intraglomerular actions of prostaglandins.

Adult

HTLV-I-specific cytotoxic T lymphocytes in the cerebrospinal fluid of patients with HTLV-I-associated neurological disease.

Recently, it has been shown that in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated neurological disease, high levels of HTLV-I-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood. These CTLs predominantly recognized products of the pX region of HTLV-I, had a CD8+ phenotype, and were human leukocyte class I restricted. Moreover, these responses were not detected in asymptomatic, HTLV-I-seropositive individuals. This implied a role for these CTLs in the pathogenesis of the neurological disorder associated with HTLV-I. We have extended these observations by demonstrating HTLV-I-specific CTLs directly from lymphocytes obtained from the cerebrospinal fluid of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Uncultured cerebrospinal fluid lymphocytes were used directly as effectors on a variety of targets expressing HTLV-I. These cells were lysed in a virus-specific and HLA class I-restricted manner. Moreover, the cerebrospinal fluid lymphocytes were sorted into purified CD8+ populations, cloned by limiting dilution, and assayed for CTL activity. An exceedingly high proportion of these resultant lines were shown to be cytolytic and precursor frequency analysis indicated that as many as 1 in 500 cells were HTLV-I-specific CTLs. The majority of these CTL lines recognized HTLV-I gene products encoded within the pX region of HTLV-I. The significance of these HTLV-I-specific CTLs in the central nervous system of patients with HTLV-I-associated neurological disease is discussed with regard to the potential role of CTLs in the pathogenesis of this disease.

Adult

The relation of fetal growth to plasma glucose in young men.

In a study of men aged 59 to 70 years plasma glucose levels 30 min and 2 h after a 75-g glucose load were inversely related to birthweight. To determine whether there are similar relations at a younger age the 30-min plasma glucose levels of 40 men aged 21 years, who were born in one hospital in the United Kingdom, were measured. Lower birthweight was associated with higher 30-min plasma glucose levels. This trend was independent of gestational age, and current body mass, height and social class.

Birth Weight

Determinants of the renal response to ACE inhibition in patients with congestive heart failure.

The objective of the present study was to determine whether pretreatment neurohormonal and renal hemodynamic parameters predict the change in renal function with the administration of quinapril, a new angiotensin-converting enzyme (ACE) inhibitor. Twenty patients with New York Heart Association (NYHA) class III and IV heart failure were evaluated. Following pretreatment determination of renal function and plasma neurohormones, patients were treated daily with 10 mg of quinapril. Measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were repeated after 7 weeks to assess changes in function (delta GFR and delta RPF). Mean GFR increased from 49 +/- 6 to 56 +/- 7 ml/min/1.73 m2 (p = 0.10), but decreased in five patients. Mean RPF increased from 235 +/- 23 to 252 +/- 23 ml/min/1.73 m2 (p = 0.08), but decreased in five patients. There was no relation between delta GFR and baseline determinations of GFR, RPF, plasma renin activity, plasma angiotensin II, or serum Na. Only a high filtration fraction (GFR/RPF) predicted a decreased GFR (r = 0.61, p less than 0.005). In contrast, no baseline renal hemodynamic parameter correlated with delta RPF. We conclude that poor renal function does not increase the risk of renal deterioration with quinapril. However, dependence of renal function upon the renin-angiotensin system may be predicted by a high filtration fraction.

Angiotensin II

Ultrastructural quantification of collagen fibrils in the central region of the articular disc of the temporomandibular joint of the cat and the guinea pig.

This quantitative ultrastructural analysis was made on articular discs from four guinea pigs and four cats. Mean diameters of collagen fibrils were small (approximately 45 nm) and showed unimodal distributions. These features are consistent for connective tissues subjected to compressional forces. The relatively high percentage volume of the extracellular matrix occupied by collagen in the articular disc of the guinea pig (approximately 60 per cent) and the presence of crimping is, however, more typical of a connective tissue subjected to tension. Two differences were discernible between the collagen in the articular discs of the guinea pig and cat. First, the percentage volume occupied by collagen for the guinea pig disc was significantly higher than for the cat. Second, the frequency distribution of collagen fibril diameters for the cat, although unimodal, was skewed. These differences possibly reflect the different types of movement at the temporomandibular joints in the two species.

Actin Cytoskeleton

The psychological, social, and sexual consequences of gestational trophoblastic disease.

Seventy-six women diagnosed with gestational trophoblastic disease (GTD) from 1985 to 1989 completed questionnaires evaluating their status on mood disturbance, marital satisfaction, sexual functioning, psychosocial response to illness, and report of the most stressful event occurring within the past year. Multivariate analyses of variance (MANOVA) were conducted on dependent measures to examine differences between diagnostic groups (partial mole, complete mole, persistent disease), time from diagnosis (less than 1 year, 1-2 years, or 3-5 years from diagnosis), and follow-up status (active disease or remission). MANOVAs revealed no significant differences in the dependent measures based on time from diagnosis, type of medical treatment received, or type of molar disease. The metastatic disease group displayed significantly greater mood disturbance (F(1, 66) = 17.63, P less than 0.0001) and reported suffering clinically significant levels of distress and significantly greater levels of distress in response to the illness (F(33, 39) = 2.32, P less than 0.006). Women with active disease also reported significantly greater levels of distress in response to the illness (F(33, 39) = 2.76, P less than 0.001). Across disease types, GTD patients experience clinically significant levels of anxiety, anger, fatigue, confusion, and sexual problems and are significantly impacted by pregnancy concerns for protracted periods of time.

Adaptation, Psychological

Dissociation of mechanisms of reading in Alzheimer's disease.

The role of spelling-to-sound correspondence rules in oral word reading was investigated by asking patients with Alzheimer's Disease (AD) and normal controls to read aloud pronounceable letter strings that do not happen to be real words. These pseudowords were of two types: those that have orthographically similar "neighbors," and those that have no neighbors. The patients with AD were mildly impaired relative to the normal controls in reading pseudowords with neighbors, but were markedly impaired in reading pseudowords with no neighbors. The results are interpreted as favoring a model of reading in which words and pseudowords are normally read via the same lexical mechanism. An ancillary route involving the conscious application of spelling-to-sound rules is available only to cognitively intact readers.

Aged

Diabetes secondary to genetic disorders.

Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean:fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes.

Diabetes Mellitus

The mechanism of action of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in the control of haematopoietic stem cell proliferation.

The mechanism of action of the haemoregulatory tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP, M(r) = 487 amu), was investigated using an in vitro assay of a murine high proliferative potential colony-forming cell (HPP-CFC) which responds to proliferation regulators of the haematopoietic stem cell population. AcSDKP had no direct inhibitory effect on the number, or the proportion in S phase, of the committed granulocyte-macrophage progenitor (GM-CFC), or cycling HPP-CFC populations. However, AcSDKP blocked the action of a stimulator of haematopoietic stem cell proliferation, preventing the switching of quiescent HPP-CFC into cell cycle. It would appear that AcSDKP exerts its inhibitory haemoregulatory role indirectly, by preventing stimulator action on haematopoietic stem cells.

Amino Acid Sequence

Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance.

OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0-109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92-169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports of hyperinsulinaemia and insulin resistance in polycystic ovary syndrome. Furthermore, polycystic ovary syndrome subjects have a reduced postprandial thermogenesis which is related statistically to the reduced insulin sensitivity. The decreased postprandial thermogenesis may predispose women with polycystic ovary syndrome to weight gain.

Adult

Which hormone tests for the diagnosis of polycystic ovary syndrome?

OBJECTIVE: To assess the frequency of abnormal values for hormone measurements commonly used in the biochemical diagnosis of polycystic ovary syndrome (PCOS). DESIGN: Hormone measurements in 63 unselected women with clinical and ultrasound diagnosis of PCOS attending gynaecological and general endocrine clinics in a District General Hospital were compared with those from a group of 20 normal ovulatory controls in the early follicular phase of their cycles. MEASUREMENTS: Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH ratio, total testosterone, derived free testosterone, sex hormone binding globulin, androstenedione, and dehydroepiandrosterone (DHEA) were measured by radioimmunoassays. LH and FSH measured by two different assays. RESULTS: The mean serum LH and LH/FSH ratio were significantly (P less than 0.01) higher in the women with PCOS compared with the normal group, but these two measurements were in the abnormal range for only 35% and 41-44%, respectively. Absolute gonadotrophin values were significantly different using the two assay methods, which employed the same reference preparation as standard. Mean serum total testosterone concentration was significantly higher in the PCOS group and was the most frequently (70%) abnormal biochemical marker for PCOS. Sex hormone binding globulin (SHBG) did not differ significantly between the two groups but showed a negative correlation with body mass index in women with PCOS. The combination of SHBG and testosterone to derive a free testosterone value did not further aid the biochemical diagnosis of PCOS. Androstenedione was significantly higher in the PCOS group than in the control group, with a frequency of 53%. There was no significant difference in DHEA-S between the two groups. CONCLUSION: When typical ovarian ultrasound appearances plus the clinical features of oligomenorrhea and/or hirsuitism were used to define PCOS total testosterone was the best single hormonal marker of the condition. Testosterone, androstenedione or LH, either alone or in combination, were raised in 86% of women with PCOS and these should be the definitive hormonal tests. Using LH/FSH ratio as a biochemical criterion for diagnosis of PCOS should be abandoned because of its low sensitivity. To be of value the normal range for all hormones should be precisely defined in a group of regularly ovulating women in the early follicular phase of the cycle for the assay used in each laboratory.

Androstenedione

Skin lesion removal: practice by general practitioners in Grampian Region before and after April 1990.

The introduction of new GP contracts in April 1990 incorporated a financial incentive to undertake minor surgical procedures. Previous reports have noted large increases in the number of GP-derived skin specimens after April 1990. Our present study intended to address whether similar changes have occurred in Grampian Region as well as, more specifically, noting whether there have been changes in the quality of practice following the 1st April 1990. A retrospective study of skin biopsies removed by general practitioners in Grampian Region was undertaken. Cases were selected from four periods of six months (1st April to end of September) in 1987, 1988, 1989 and 1990. All skin specimens sent by general practitioners to the Department of Pathology, Aberdeen Royal Infirmary, were included. Following April 1990 there was a two-fold increase in skin specimen numbers--an increase significantly greater than increases observed over previous years (p < 0.01). Of particular note was the contribution made to this increase by Aberdeen City GPs whose contribution rose five-fold (p < 0.0001). Non-benign lesions (ie malignant plus carcinoma-in-situ-) represented 6% of lesions excised. A non-benign clinical diagnosis or an indication of suspicion was written on only one third of request forms for histopathologically diagnosed non-benign lesions. The proportion of histologically incompletely excised lesions rose over the four years (p < 0.01); moreover the increase in total numbers of lesions resulted in a striking increase in the actual numbers of incompletely excised lesions after April 1990.

Biopsy

The Glasgow Coma Scale: a critical look.

Today much of our knowledge about a patient's level of consciousness is given to us by his or her score on the Glasgow Coma Scale (GCS). Since its development at the University of Glasgow in 1974, it has been widely adopted, become an integral component of the hourly "neuro assessment", and is typically incorporated into the graphic assessment portion of the patient's medical record. Once the information has been documented, the pure data itself is lost as the documented form takes on an interpretative meaning or a reality that is different from the clinical state experienced by the patient. The formation of this "new" reality occurs in two separate phases: in the completion of the scale and in its reading. There are various factors or forces that affect the completion and use of the scale. These are important as they are not visible in the scale itself; however, their effects are evident in the coma score obtained. These forces include the design of the GCS and the manner in which the tool is taught and used. The purpose of this paper is to discuss these factors and to delineate how they create a reality that may not accurately depict the patient's level of consciousness.

Glasgow Coma Scale