Biomedical subjects
Publications and source records attributed to P Sharp.
Rhabdomyolysis is a rare but potentially fatal complication of hyperosmolar states. We report a case of severe hyperosmolar non-ketotic diabetic coma causing rhabdomyolysis in a young man. Despite very high levels of creatine kinase there was no detectable myoglobinuria. Creatine kinase estimation should be a standard investigation in all patients presenting with a hyperosmolar state.
Forty-one adults with established hypopituitarism and deficiency of growth hormone (GHD) were compared to an age and sex-matched group with another chronic metabolic disorder (diabetes mellitus) using standardized psychiatric rating and diagnostic measures. Nineteen (46%) of the GHD group were identified as definite psychiatric cases compared with 10 (24%) of the diabetics (odds ratio 1:9:1). The most frequent DSM III-R axis I psychiatric diagnoses were major depression (32% GHD patients and 10% of diabetic patients) and dysthymia. The risk of being a psychiatric case showed an association with duration of illness in the diabetic group, but not in the GHD group. Biochemical indices were not related to the risk of being a case in either group. Hypopituitarism is associated with a higher prevalence of psychiatric disturbance than can be attributed solely to the presence of a chronic disorder.
In the present study the effects of replacement with biosynthetic human growth hormone (GH) in a large group of hypopituitary adults on cardiac structure and function were investigated. Thirty-six GH-deficient, hypopituitary patients (17 males and 19 females; aged 19-67 years) on conventional replacement therapy without GH were studied. Twenty-nine of the patients had acquired hypopituitarism in adult life, mainly due to pituitary tumours. The design of the study was a prospective, randomized, double-blind placebo-controlled trial for 6 months. Growth hormone (17 patients) was given in a daily dose of 0.02-0.05 IU/kg body wt sc (or a placebo, 19 patients) according to the patients' tolerance. Other pituitary replacement treatment was unchanged. Resting and exercise electrocardiography using the Bruce protocol, two-dimensional echocardiography, Doppler ultrasound scanning and serum insulin-like growth factor I (IGF-I) were assessed at 0 and 6 months. Resting blood pressure was measured at 0, 1, 3 and 6 months. Serum IGF-I increased significantly on GH treatment (mean +/- SD) GH: 293 +/- 197 vs placebo: 82 +/- 40 micrograms/l; p < 0.0001 at 6 months). Exercise time increased significantly on GH but not on placebo (GH: 8.45 +/- 3.16 to 9.38 +/- 2.42 min.sec, p < 0.01; placebo 9.08 +/- 4.35 to 9.50 +/- 4.14 min.sec, NS), although the change was not significantly different between the two. There was no change in the heart rate or the blood pressure either at rest or at the peak of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Human skin fibroblasts in culture can oxidize beta-methyl fatty acids, such as phytanic acid and 3-methylhexadecanoic acid, to CO2 and water-soluble products. The latter are released largely into the culture medium. The major water-soluble product formed from [1-14C]phytanic and [1-14C]3-methylhexadecanoic acids is [14C]formic acid. As phytanic acid and 3-methylhexadecanoic acids contain beta-methyl groups and theoretically cannot be degraded by beta-oxidation, we postulate that formic acid is formed from fatty acids by alpha-oxidation. The marked reduction in formic acid production from beta-methyl fatty acids in peroxisome-deficient skin fibroblasts suggests that peroxisomes are involved in the generation of C1 units.
Retinal exudates are a common manifestation of vascular damage in a variety of retinal diseases. We have used computerized image analysis to detect and measure the area of exudates from digitized colour fundus slides of patients with diabetic retinopathy and have assessed the repeatability, reproducibility, and accuracy of the technique. The analysis was entirely independent of the operator apart from choice of the region to be analysed. The coefficient of variation for repeatability was between 3% for large areas of exudate and 17% for small areas of exudate. The reproducibility was also within this range. Sensitivity was between 61 and 100% (mean 87%). False-positives were observed in 5 of 30 regions analysed, and these could have been eliminated by using more stringent criteria for selection of images for analysis. Time taken for the analysis was approximately 3 min.
Retrospective analysis suggests that there is increased mortality from vascular disease in hypopituitary adults, but vascular status before death is unknown. High resolution B-mode ultrasonic imaging of both carotid and femoral arteries was therefore done in 34 adult hypopituitary patients on routine replacement therapy and was compared with that in 39 matched controls. Changes were related to risk factors for vascular disease. Carotid intima-media thickness was greater in patients than in controls (mean [SD] 0.74 [0.16] vs 0.65 [0.13] mm, p < 0.02). This difference was seen in middle-aged and elderly patients. More patients than controls had one or more atheromatous plaques (65% vs 41%, p < 0.05). The percentage of individual arteries with a plaque was also higher in patients (32% vs 18%, p < 0.005). In multiple regression analysis, patients' age was the dominant factor determining carotid intima-media thickness. Symptom-free adults with hypopituitarism show an increased prevalence of atherosclerosis.
Fatty acids with from 24 to 28 carbon atoms (very long-chain fatty acids, VLCFA) are present in small amounts in all mammalian tissues. Even longer chain fatty acids with from 30 to 38 carbon atoms (ultra-long-chain fatty acids, ULCFA) are found in certain specialized tissues including retina, brain, and spermatozoa. In patients with inherited defects in peroxisomal structure and/or function, there is an accumulation of VLCFA in most tissues, while VLCFA and ULCFA levels are increased in brain. The most pronounced changes occur in those patients who have defects in peroxisomal assembly (Zellweger syndrome, infantile Refsum's disease, and neonatal adrenoleukodystrophy). In the brain of these individuals, ULCFA are distributed largely in molecular species of phosphatidylcholine with penta-, hexa-, and heptaenoic acids. In contrast, patients with X-linked adrenoleukodystrophy have increased levels of phosphatidylcholine with monoenoic rather than polyenoic ULCFA. A defect in a peroxisomal VLCFA CoA synthetase or ligase has been reported for these patients, but assembly of their peroxisomes is apparently normal. We speculate that ULCFA are normal products of carbon chain elongation. We have confirmed this by demonstrating the elongation of [1-14C]hexacosatetraenoic acid (26:4n-6) by rat brain in vivo to a series of longer chain tetraenoic acids with carbon chain lengths up to 34. Elongation to ULCFA can occur as well in non-neural tissues as shown by detection of labeled saturated and monoenoic fatty acids with up to 32 carbon atoms after incubation of normal and Zellweger syndrome fibroblasts with [2-14C] acetate. Increased labeling of VLCFA and ULCFA is observed in cells from patients with peroxisomal disorders. Our data suggest that ULCFA with up to at least 32 carbon atoms are formed normally, as a part of the elongation process in most mammalian tissues, and that control of carbon chain elongation is a major function of peroxisomes. Impairment of this function as occurs in peroxisomal disease results in the accumulation of VLCFA and ULCFA. The relative enrichment in normal tissues of ULCFA such as 32:6n-3 in ram and bull spermatozoa and 36:4n-6 in human and rat brain suggests a probable physiological role for this class of fatty acids in these tissues.
A little more than half a century has passed since the death of Julius Wagner von Jauregg, a significant figure in the history of modern psychiatry. We believe that after this passage of time the life and work of Wagner von Jauregg deserve reappraisal.
The adherence of viable and heat-treated Mycoplasma bovis to bovine peripheral blood neutrophils was studied by specific immunofluorescence staining and flow cytometry. Viable and heat-treated M. bovis cells, adhered to bovine neutrophils in dose-dependent fashion within a 30 min incubation. Fluorescence quenching using crystal violet indicated that unopsonized M. bovis cells remained on the surface of bovine neutrophils without experiencing significant ingestion. The effect of M. bovis adherence on neutrophil microbicidal function was examined by measuring luminol enhanced chemiluminescence (CL). Adherent M. bovis cells did not elicit a bovine neutrophil CL response over a 75 min incubation period. M. bovis inhibited the capacity of bovine neutrophils to mount a CL response. Inhibition occurred whether viable or heat-treated M. bovis cells were used and it occurred when neutrophils were stimulated with opsonized zymosan (OZ) or phorbol myristate acetate (PMA). Inhibition of the PMA stimulated neutrophil CL response required cytadherence by M. bovis cells. These findings suggest that activation of the bovine neutrophil respiratory burst was inhibited at or distal in the pathway to the activation of protein kinase C (PKC), the site of PMA stimulation, and that it was mediated by a direct interaction between the adhering M. bovis cells and the bovine neutrophil membrane.
The Forsyth County Cervical Cancer Prevention Project (FCP) is a community-based health education project funded by the National Cancer Institute. The target population includes around 25 000 black women age 18 and older who reside in Forsyth County, North Carolina. The overall goal of the program is to prevent mortality from cervical cancer by promoting Pap smears and return for follow-up care when needed. Based on the principles of social marketing, a plan to reach the target population with mass media educational messages through electronic and print channels was developed. Guided by marketing objectives, the target population was divided into relatively discrete segments. The segments included church attenders, patients in waiting rooms of public and selected health providers, female students at local colleges, shoppers, viewers of radio and television, newspaper readers, and business owners and managers. Introduction of the program was based on strategies developed for reaching the target population in each segment with television, radio and print mass media messages. Qualitative assessment of the mass media developed by the program indicated that all forms of communication helped to increase awareness of the program.
OBJECTIVES: To investigate whether growth hormone (GH) absorption is site dependent. DESIGN AND MEASUREMENTS: Human growth hormone (hGH, Norditropin) 4 IU, was injected subcutaneously on two separate occasions: into the thigh on one occasion and into the abdomen on a second occasion. Blood was sampled for GH, insulin, glucose, non-esterified fatty acids and glycerol at baseline and hourly for 12 hours. Serum insulin-like growth factor I was measured at baseline, and after 12 and 24 hours. SUBJECTS: Eleven healthy young adults (8 M, 3 F). RESULTS: Following the injection serum GH had risen by 1 hour and peaked by 3-6 hours. The peak GH and growth hormone area under the curve were significantly higher after injection in the abdomen compared with the thigh (GH peak (mean +/- SEM) 103 +/- 20 vs 41 +/- 8 mU/l, P = 0.002 and GH area 528 +/- 86 vs 239 +/- 34 mU/l h, P = 0.003 respectively). Serum insulin-like growth factor I at 12 and at 24 hours showed a significant rise from the baseline level, but no significant difference was observed between the two injection sites. No significant difference in plasma insulin, glucose, non-esterified fatty acids or glycerol was observed between the two methods of injection. CONCLUSION: Subcutaneously injected GH is better absorbed from the abdominal site than from the thigh.
1-O-Alkyl and 1-O-alk-1-enyl (plasmalogens) glyceryl ether lipid levels were measured in post-mortem brain and/or liver biopsies from 7 patients with ultrastructural and biochemical evidence of a defect in peroxisomal biogenesis and/or enzymological evidence of a disturbance in ether lipid synthesis. Near normal levels of both species of glyceryl ether lipids were found in neonatal adrenoleukodystrophy and infantile Refsum's disease but marked deficiencies were found in Zellweger's syndrome and rhizomelic chondrodysplasia punctata, the latter manifesting the most profound reduction in ether lipid levels. These observations suggest that little ether lipid biosynthesis occurs in vivo in rhizomelic chondrodysplasia punctata or Zellweger's syndrome. However, in some phenotypes with apparently gross reductions in peroxisomal numbers, e.g. neonatal adrenoleukodystrophy and infantile Refsom's disease, there is significant ether lipid synthesis in liver and brain.
Molecular species of phosphatidylcholine containing unsaturated (i.e., monoenoic and polyenoic) 32- to 40-carbon (very long chain) fatty acids (VLCFA-PC) are present in normal human brain, the fatty acid composition changing significantly with development. There is a marked increase in the concentration and a change in the polyenoic VLCFA composition of these molecular species in brains of patients with inherited defects in peroxisomal biogenesis [Zellweger's syndrome, neonatal adrenoleukodystrophy (ALD), and infantile Refsum's disease]. In contrast, there is a marked increase in monoenoic VLCFA-PC in X-linked ALD whereas molecular species containing polyenoic VLCFA are minor components.
Our studies show that obese women with polycystic ovary syndrome are more likely to have hirsutism and menstrual disturbances than are lean women with PCOS. The most obvious biochemical differences between obese and lean women with PCOS is that SHBG concentrations are much lower in women with obesity. The SHBG levels are inversely related to insulin, and insulin has been shown to have a direct inhibitory action on SHBG secretion. Other factors, however, may contribute to the mechanism of the increased prevalence of hirsutism and anovulation in obese women with PCOS, such as a direct effect of insulin or increased activity of 5 alpha-reductase in peripheral tissues. Finally we have been able to show that weight reduction of more than 5% is associated with an improved biochemical profile and, importantly, with restoration of fertility.
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Focus groups were used in the development of community-based public health education designed to reduce mortality from cervical cancer among black women in Forsyth County, North Carolina. The educational goals of this National Cancer Institute (NCI) funded project were to increase the proportion of black women, age 18 and older, who obtain Pap smears on a regular basis and return for followup care when necessary. A series of four focus groups were conducted to help develop the conceptual basis for designing educational messages and materials. The groups were led by a black, female professional focus group moderator, and explored a variety of health-related topics ranging from general, ordinary concerns of daily living to knowledge and attitudes about cancer screening. The group discussions suggested that health is regarded as very important to the target population, particularly when related to family functioning. Regarding the Pap smear, most women knew about the test, but had little awareness of its role in the early detection of cervical cancer. Fear and fatalism were clearly the dominant, top-of-mind reactions to cancer, and there was little differentiation among sites or types of cancer. Despite the overall pessimism, the groups agreed that early diagnosis and treatment provide the best hope for good outcomes with cancer.
The effect of viable Mycoplasma bovis on the in vitro bovine peripheral blood lymphocyte response to phytohemagglutinin (PHA) was studied. Results showed that M. bovis did not act as a mitogen for bovine lymphocytes. Viable M. bovis produced a dose and time dependent suppression of the PHA stimulated lymphocyte response. Suppression was not a result of differences in the viability of infected or control lymphocyte cultures. The suppressive effect of M. bovis was found to be independent of the concentration of PHA used in the test and the lymphocyte response could not be restored by supplementation of the culture medium with arginine. Delay for 48 h after PHA stimulation before adding M. bovis to the lymphocyte cultures diminished, but did not prevent, the suppression of the lymphocyte response. These results show that suppression of the lymphocyte response does not require the presence of M. bovis during the period of PHA stimulation, and that M. bovis was capable of interrupting [3H]-thymidine incorporation in lymphocytes which were actively synthesizing DNA.
The results of a program of low birthweight prevention in 17 rural (20,727 births) and three urban counties (15,561 births) for calendar years 1985 and 1986 are described. Records for women in the program were matched with birth certificate data by computer. Rural and urban women in and out of the program were compared by race on the following risk factors: age less than 18 years, unmarried, education less than 12 years, Medicaid recipient, not WIC recipient, inadequate prenatal care, and previous fetal or live born death. Adjusting for these risk factors, logistic regression was used to estimate program effects on low birthweight (LBW), very low birthweight (VLBW), and preterm low birthweight (PLBW) among rural women. There was a statistically significant difference (p less than or equal to 0.01) favoring women in the program for very low birthweight and preterm low birthweight in white women, and low birthweight and preterm low birthweight in nonwhite women. The differences in rural areas exceed those in urban areas for all but one mean, very low birthweight births among white women.