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Biomedical subjects

P Sharp

Publications and source records attributed to P Sharp.

At least 37 records · Page 2Linked to original sources

The occurrence of mycoplasmas in selected wild North American waterfowl.

We determined the prevalence of mycoplasma infection in breeding mallard (Anas platyrhynchos) and canvasback (Aythya valisineria) hens and their broods from the central United States (1988 to 1990); and wintering American black duck (Anas rubripes) and mallard hens from the eastern United States (1990 to 1993). Mycoplasmas were isolated by culturing tracheal swabs from 656 live birds and tissue samples from 112 dead waterfowl. Nine (18%) of 51 mycoplasma isolates were identified as Mycoplasma anatis; M. anatis was recovered from four mallards, a black duck, and a gadwall (Anas strepera) duckling. Nineteen (37%) of 51 mycoplasma isolates were identified as Mycoplasma cloacale; these isolates were obtained from mallard, canvasback, and black duck adults, and from a mallard duckling. Additional unspeciated mycoplasmas were isolated from mallards, black ducks, and one canvasback.

Animals

Development of a cervical cancer education program for native American women in North Carolina.

The North Carolina Native American Cervical Cancer Prevention Project is a five-year, NCI-funded public health education program. The project was developed to address the problem of excess mortality from cervical cancer among Native American women by increasing screening and follow-up of abnormal cervical smears. This paper describes the process of developing and implementing the intervention, an individualized health education program. Development of the intervention was guided by the health belief model, social learning theory, self efficacy theory, and PRECEDE, a planning model. Community analysis revealed that the target populations had limited awareness of cervical cancer as a specific type of cancer, and had an experientially-based pessimistic outlook regarding survival with cancer. Steps in developing the cervical-cancer prevention program included 1) development of objectives, 2) selection of strategies and development of cervical cancer education materials, 3) pretesting and revision, and 4) implementation, monitoring, and further revision. Native American lay health educators were recruited and trained to deliver the program. The experience of developing and implementing the individualized health education program suggests that the design of health education programs for Native Americans should begin with examination of basic assumptions regarding the nature of health and illness in the target population. The unique cultures and the diversity of Native American populations are critical factors in the development of health education programs for them.

Adolescent

Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil.

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.

Adolescent

Pitfalls in the prenatal diagnosis of peroxisomal beta-oxidation defects by chorionic villus sampling.

Variability in the level of expression of very long chain fatty acids (VLCFAs) is documented in cultured chorionic villus (CV) cells derived from two fetuses, one at risk for an unusual peroxisomal fatty acid beta-oxidation defect, and the other at risk for the X-linked form of adrenoleucodystrophy (ALD). Cells from early subcultures of chorionic cells from both cases gave normal values for VLCFA ratios. The results for the fetus at risk for the beta-oxidation defect were interpreted to indicate that the fetus was not affected; however, at birth, the infant was clinically and biochemically affected. In the case of the fetus at risk for X-linked ALD, although VLCFAs were normal in subculture 1, the levels of these fatty acids increased dramatically in subculture 3, suggesting an abnormal fetus. Termination of the pregnancy and subsequent biochemical and morphological follow-up confirmed that the fetus was indeed affected by ALD.

Adrenal Cortex

The effect of growth hormone replacement therapy in hypopituitary adults on calcium and bone metabolism.

OBJECTIVE: The importance of growth hormone (GH) for normal skeletal growth in childhood and adolescence is well established but much less is known about its action on the adult skeleton. We therefore wished to investigate the effects of replacement treatment with biosynthetic human GH in hypopituitary adults on aspects of calcium homeostasis, bone metabolism and bone mineral mass. PATIENTS: Forty hypopituitary adults (21 females and 19 males; aged 19-67 years). DESIGN: A prospective randomized double-blind placebo-controlled trial lasting for 6 months. PROTOCOL: Following baseline assessments, GH was given in a daily dose of 0.02-0.05 IU/kg body weight subcutaneously (or a placebo (P)) at bedtime. Patients were reviewed at 1, 3 and 6 months. MEASUREMENTS: Plasma calcium, phosphate and total plasma alkaline phosphatase were measured at 0, 1, 3 and 6 months. Serum insulin like growth factor I (IGF-I), osteocalcin, procollagen 1 carboxyterminal peptide (P1CP) and intact parathyroid hormone (PTH) level, 24-hour urinary calcium and creatinine excretion were all measured at 0 and 6 months. Bone mineral density of total body and lumbar spine was also measured by dual energy X-ray absorptiometry at 0 and 6 months in 12 patients on GH and 14 on placebo. RESULTS: Thirty-eight patients completed the study (18 on GH, 20 on placebo). Serum IGF-I increased significantly on GH treatment (mean +/- SD) (GH: 276 +/- 197 vs P: 88 +/- 50 micrograms/l, P < 0.0001 at 6 months). Plasma calcium increased slightly but significantly in the GH-treated group (2.23 +/- 0.11-2.29 +/- 0.11 mmol/l, P < 0.05). At the end of the study, plasma calcium was however similar on GH and placebo (GH, 2.29 +/- 0.11; P, 2.26 +/- 0.09 mmol/l). Plasma phosphate increased on GH (GH: 1.02 +/- 0.23-1.32 +/- 0.19; P: 0.99 +/- 0.16-0.96 +/- 0.12 mmol/l over the 6 months of treatment, P < 0.001). There was no significant change in the urinary calcium excretion on GH therapy. Plasma total alkaline phosphatase, osteocalcin and P1CP were significantly higher on GH than P at 6 months (alkaline phosphatase: GH: 104 +/- 32 vs P: 69 +/- 32 U/l, P < 0.01, osteocalcin: GH: 17.2 +/- 8.0 vs P: 5.3 +/- 3.2 micrograms/l, P < 0.001 and P1CP: GH: 207 +/- 152 vs P: 93 +/- 31 micrograms/l, P < 0.01). There was no difference in the intact parathyroid hormone level (GH: 31 +/- 14 vs P: 31 +/- 15 ng/l, NS). No significant change was observed in bone mass after 6 months of GH treatment, either in total body bone mineral content or in the lumbar spine. CONCLUSION: In this large study, GH replacement in hypopituitary adults for 6 months increased bone turnover but did not affect bone mineral content. Longer-term studies are required to assess further any effect on bone mass.

Adult

Hyperosmolar non-ketotic diabetic coma and rhabdomyolysis.

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.

Adult

Psychiatric morbidity in adults with hypopituitarism.

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.

Adult

Cardiovascular effects of growth hormone replacement therapy in hypopituitary adults.

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)

Adult

Formic acid is a product of the alpha-oxidation of fatty acids by human skin fibroblasts: deficiency of formic acid production in peroxisome-deficient fibroblasts.

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.

Cells, Cultured

Automated detection and quantification of retinal exudates.

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.

Diabetic Retinopathy

Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults.

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.

Adult

Very long-chain fatty acids in peroxisomal disease.

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.

Adolescent

Julius Wagner von Jauregg: a reappraisal.

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.

Australia

Adherence to bovine neutrophils and suppression of neutrophil chemiluminescence by Mycoplasma bovis.

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.

Animals

Implementation of mass media community health education: the Forsyth County Cervical Cancer Prevention Project.

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.

Adolescent

The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh.

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.

Abdomen

Glyceryl ethers in peroxisomal disease.

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.

Adrenoleukodystrophy

Molecular species of phosphatidylcholine containing very long chain fatty acids in human brain: enrichment in X-linked adrenoleukodystrophy brain and diseases of peroxisome biogenesis 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.

Adolescent