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Biomedical subjects

M Prince

Publications and source records attributed to M Prince.

At least 37 records · Page 2Linked to original sources

Screening women for high risk of postnatal depression.

A ten-item screening questionnaire was constructed from previous reports on risk factors for postnatal depression, and its ability to predict antenatally the development of postnatal depression was tested. Women attending an antenatal clinic at 36 wk gestation completed the questionnaire and, at 8 wk postpartum, were assessed for the presence of depression using the Edinburgh Postnatal Depression Scale (EPDS). Although antenatal questionnaire scores correlated significantly with postnatal EPDS scores, this was largely because the questionnaire was able to identify correctly those who would not become depressed. Neither the questionnaire as a whole, nor groups of items, was able to discriminate well between women who later did or did not become depressed. However, women who reported previous or current treatment for depression were at a threefold greater risk of becoming or remaining depressed postnatally. Possible reasons for the negative results are discussed, including the heterogeneity of depression occurring in the postnatal period.

Adult

Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus.

Vitamin D has been shown to increase insulin release from pancreatic islet cells in vitro, and to improve insulin secretion in vitamin D-deficient animals. Few attempts have been made to evaluate this issue directly in humans. We studied 35 otherwise healthy diabetic subjects in the early spring at the seasonal nadir of 25-hydroxyvitamin D [25(OH)D] concentrations (mean 35 +/- 7 nmol/L). Fasting glucose, insulin, C-peptide, and glucagon concentrations, and their responses to Sustacal stimulation were not related to indexes of mineral metabolism. In 20 subjects, a double-blinded, placebo-controlled, crossover trials of 1,25-dihydroxyvitamin D[1,25](OH)2D] treatment (1 micrograms/d for 4 d) had no effect on fasting or stimulated glucose, insulin, C-peptide, or glucagon concentrations. However, insulin and C-peptide responses to Sustacal after 1,25(OH)2D treatment were related to duration of diabetes (r2 = 0.28, P = 0.052 and r2 = 0.25, P = 0.002, respectively) in that short duration correlated with improvement after 1,25(OH)2D treatment. Hence, vitamin D nutrition, or 1,25(OH)2D therapy, had no major effect on glucose homeostasis in non-insulin-dependent diabetes mellitus.

Adult

Risk factors for Alzheimer's disease and dementia: a case-control study based on the MRC elderly hypertension trial.

We surveyed 1,545 subjects--recruited into the UK Medical Research Council elderly hypertension treatment trial between 1982 and 1987--to detect incident cases of dementia, identifying 50 cases of dementia, including 31 cases of probable or possible Alzheimer's disease (AD). These we compared with 223 unimpaired, unmatched controls from the same population for exposure to familial, cardiovascular, educational, and geographic risk factors for dementia. Our study confirms the association of family history of dementia with dementia (odds ratio [OR] = 4.36) and AD (OR = 4.69), and of advanced age with dementia (OR = 2.81). Rural residence exerted a protective effect for dementia (OR = 0.21) and AD (OR = 0.28). We report near-significant associations between AD and dementia and several cardiovascular risk factors (ECG ischemia, systolic hypertension, and smoking) among subjects lacking a family history of dementia. We postulate the existence of a nonfamilial form of dementia transcending traditional categories of multi-infarct dementia and AD, more common among urban residents, and mediated through vascular pathology. Risk factors reported elsewhere but not confirmed in this study were advanced maternal age and winter season of birth.

Aged

Time of flight renal MR angiography: utility in patients with renal insufficiency.

We studied the renal arteries prospectively in 16 patients with renal insufficiency using a combination of two-dimensional and three-dimensional time of flight magnetic resonance angiography (MRA). Results were compared with conventional angiography. All renal arteries were identified by MRA. Accuracy for classifying renal arteries into patent, moderately (30-70%) stenotic, severely (> 70%) stenotic, or occluded was 91%. With regard to the presence or absence of severe occlusive disease (> 70% stenosis or occlusion) the sensitivity was 100%, with a specificity of 93%.

Aged

A study of 'inappropriate' attendances to a paediatric Accident and Emergency Department.

'Inappropriate' attendance to Accident and Emergency Departments (AEDs) has been shown in many studies to be a sizeable problem. However, only one previous study has investigated inappropriate attendance to these departments amongst children. In this paper we report an investigation of 'inappropriate' usage of a children's AED in Nottingham. Information was collected relating to a representative sample of children who attended this department during September and October 1989 by interviewing the adults accompanying them to the AED and by examining the children's AED medical records. Using defined criteria, the doctors treating each child within the AED assessed whether their attendance was 'appropriate' to the department. Nearly a third (30.1 per cent) of the patients studied were subsequently considered to be inappropriate attenders to this department. This proportion was highest amongst younger children, those from families of lower social class and those living closest to the hospital. 'Inappropriate' attendance was not found to relate to the availability of general practitioners. The reasons stated for choosing to attend the AED suggested that these attendances resulted from perceptions of the adult(s) accompanying the children to the department. In view of this finding, action is required to correct these perceptions, although it is recognized that this may be difficult to achieve.

Adolescent

Transfusion associated graft-versus-host disease after cardiac surgery: response to antithymocyte-globulin and corticosteroid therapy.

A 63-year-old patient developed graft-versus-host disease (GVHD) after the transfusion of stored, random donor red cell concentrates with coronary artery surgery. The disease was characterised by skin rash, fever, diarrhoea, hepatic dysfunction, pancytopenia and the acquisition of cells bearing human leukocyte antigens of a blood donor. Clinical and histologic improvements were noted with antithymocyte-globulin and corticosteroid therapy, as seen in some patients with acute GVHD following allogeneic bone marrow transplantation, but the pancytopenia failed to resolve prior to a fatal cerebral haemorrhage. Early aggressive immunosuppressive therapy may be beneficial for transfusion-associated GVHD but strategies for its prevention by limitation of the use of homologous blood need to be addressed.

Antilymphocyte Serum

Blood contamination during venepuncture and laboratory manipulations of specimen tubes.

The contamination of the working environment was assessed using a forensic screening test for blood during venepuncture, transport and laboratory manipulation of specimen tubes. Different methods of collecting blood and different commercially available specimen tubes were also assessed using an in vitro system. Blood collected by needle and syringe caused more environmental contamination than did an evacuated container system. Of the commercially available specimen tubes, those with screw tops produced least environmental contamination.

Blood

Insulin resistance in non-insulin dependent (type II) and insulin dependent (type I) diabetes mellitus.

Insulin resistance is a characteristic feature of non-insulin dependent diabetes mellitus (NIDDM) due to target tissue defects in insulin action. Abnormalities of cellular insulin action can be divided into receptor and post-receptor defects. Patients with impaired glucose tolerance are insulin resistant due to decreased insulin receptors resulting in decreased insulin sensitivity and rightward shifted in vivo dose response curves. Patients with NIDDM are insulin resistant due to a combination of receptor and post-receptor defects. The greater the severity of the diabetes (greater fasting hyperglycemia) the greater the post-receptor defect, and in those patients with more significant fasting hyperglycemia the post-receptor defect is the predominant abnormality leading to the insulin resistant state. At least one of the abnormalities underlying this post-receptor defect involves a decrease in glucose transport system activity in freshly isolated adipocytes. This defect in glucose transport, is not expressed in cultured fibro-blasts, indicating that the abnormality in glucose disposal seen in vivo and in glucose transport seen in freshly isolated cells is an acquired phenomenon. Consistent with this, the post-receptor defect is partially reversible by insulin therapy, which leads to a 50-70% reversal of the reduced rates of in vivo glucose disposal and in vitro glucose transport. Insulin resistance also exists in poorly controlled IDDM patients, due to a postreceptor defect in insulin action. This insulin resistance is not present in well controlled IDDM patients, and is completely reversible when poorly controlled patients are treated with intensive insulin therapy. Insulin is produced in the pancreatic beta cell as the primary biosynthetic product preproinsulin. This peptide is rapidly converted to proinsulin (MW approximately 9000). Proinsulin is converted to insulin (MW approximately 6000) plus C-peptide in the secretory granule with a small amount (approximately 5 percent) of the proinsulin remaining unconverted. After a brief time in the peripheral circulation (half-life six to 10 minutes), insulin interacts with target tissues to exert its biologic effects. One of insulin's major biologic effects is the promotion of overall glucose metabolism, and abnormalities of this aspect of insulin action can lead to a number of important clinical and pathophysiologic states including Type II diabetes, also known as non-insulin-dependent diabetes mellitus (NIDDM). Since insulin travels from the beta cell through the circulation to the target tissues, abnormalities at any of these loci can influence the ultimate action of the hormone. These abnormalities, all

Diabetes Mellitus

Detection of gastrointestinal bleeding by radionuclide scintigraphy.

Scanning with Technetium 99m labeled autologous red blood cells was performed in 59 patients with clinical suspicion of acute and/or intermittent, chronic gastrointestinal bleeding. In 36 patients (61%), a definite site of bleeding could be demonstrated. A strong correlation with other modalities such as upper and lower gastrointestinal endoscopy, contrast angiography, and surgical exploration was found. Overall sensitivity of the procedure was 91%; specificity 100% and accuracy 93.3%. It is suggested that radionuclide scintigraphy provides a completely noninvasive, simple, and sensitive procedure which may be routinely used for the detection and localization of gastrointestinal bleeding.

Adult

Phosphate depletion therapy in two ectopic calcification syndromes.

Ectopic calcification may be a complication of a wide variety of pathologic conditions. Subcutaneous calcification frequently results in restriction of motion at joints in addition to cosmetic deformity. Parenchymal tissue calcification may result in decreased organ function. Dietary phosphate restriction and total body phosphate depletion with aluminum containing antacids were used in an attempt to decrease the deposition of subcutaneous calcium phosphate which occurs with two separate syndromes. Two subjects with hyperphosphatemic tumoral calcinosis were studied by metabolic balance, by long-term clinical evaluation, and routine laboratory and radiographic techniques before and after 1 year of phosphate depletion. One patient with a newly described syndrome--normocalcemic, hypercalciuric, subcutaneous calcification--was similarly studied. The etiology of this disorder is unknown. No consistent clinically significant evidence of regression of the lesions was noted in either syndrome, although one patient with tumoral calcinosis did demonstrate some regression of his lesions. It is not clear if this response failure was due to the intrinsic nature of the diseases or to failure of patient compliance secondary to a relatively unpalatable diet.

Adolescent

Comparative in vitro evaluation of the nitinol inferior vena cava filter.

An inferior vena cava filter made from nitinol, a thermal shape memory alloy, was evaluated. A series of in vitro experiments was designed to assess its shape recovery, orientation, and positioning after delivery and its embolus-capturing efficiency. For comparison, the Mobin-Uddin and Kimray-Greenfield filters were also tested. The results indicate that the nitinol filter is easily and accurately delivered and is superior to the other filters in its ability to capture emboli. In addition, it showed no tendency to migrate or to elevate the upstream hydrostatic pressures significantly.

Alloys

Insulin binding, internalization, and receptor regulation in cultured human fibroblasts.

Insulin binding to receptors was studied using monolayers of cultured normal human fibroblasts. Binding was rapid and inversely related to the incubation temperature; prolonged periods of steady-state binding were achieved at all temperatures studied and the amount of degradation of extracellular insulin was minimal. Competition curves demonstrated half-maximal inhibition of 125I-insulin binding at an unlabeled insulin concentration of 125I-insulin binding at an unlabeled insulin concentration of 7 ng/ml. Scatchard plots of the binding data were curvilinear and revealed that fibroblasts contained about 7,000 receptor sites per cell. Bound 125I-insulin dissociated from fibroblasts with a t 1/2 of 10 min at 30 degrees C and 35 min at 16 degrees C. After 60 min dissociation at 30 degrees C, 45% of the dissociated radioactivity consisted of 125I-insulin degradation products, whereas only 8% of the dissociated material was in the form of degraded products after 60 min of dissociation at 16 degrees C. This indicates that fibroblasts possess a temperature-sensitive receptor-mediated process for insulin degradation. Preincubation of the monolayers with insulin led to a hormone-induced loss of insulin receptors. Thus, incubating cells with 25 ng/ml insulin for 6 h at 37 degrees C caused a 50% reduction in subsequently measured 125I-insulin binding. This hormone-induced receptor loss was sensitive to physiologic insulin levels, with approximately 5 ng/ml causing a half-maximal receptor loss. When monolayers were treated with the lysosomotropic agent chloroquine and subsequently incubated with 5 X 10(-11) M 125I-insulin, a 130% increase in cell-associated radioactivity was observed after 120 min at 30 degrees C. In summary, 1) cultured normal human fibroblasts possess insulin receptors that exhibit kinetic properties and specificity identical to that of other insulin target cells; 2) incubation of fibroblasts with physiologic concentrations of insulin causes a marked loss of cell-surface insulin receptors; and 3) receptor-bound 125I-insulin is internalized through an energy-dependent endocytotic pathway and subsequently degraded by a chloroquine-sensitive reaction.

Cells, Cultured

Regulation of insulin receptors: evidence for involvement of an endocytotic internalization pathway.

Cultured human fibroblasts degrade insulin by a receptor-mediated process. When intracellular hormone degradation is inhibited by chloroquine, 125I-labeled insulin internalizes and accumulates intracellularly. In contrast, cultured IM-9 lymphocytes do not degrade receptor-bound insulin or accumulate 125I-labeled insulin in the presence of chloroquine. Insulin-induced receptor loss occurs in both cell types, and chloroquine inhibits this process in fibroblasts but not in IM-9 lymphocytes. Transglutaminase is a membrane-associated enzyme thought to mediate the process of ligand-induced receptor aggregation and internalization; levels of this enzyme were high in fibroblasts but barely detectable in IM-9 lymphocytes. Furthermore, dansylcadaverine--a potent inhibitor of transglutaminase--blocked insulin-induced receptor loss in fibroblasts but was without effect in IM-9 lymphocytes. These results support the concept that insulin receptor regulation is mediated via an endocytotic internalization pathway in human fibroblasts and that the mechanisms of this process differ among cell types.

Cadaverine