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Biomedical subjects

B Harris

Publications and source records attributed to B Harris.

At least 91 records · Page 5Linked to original sources

Cardiff puerperal mood and hormone study. 1. Saliva steroid hormone profiles in late pregnancy and the puerperium: endocrine factors and parturition.

Participants were 120 primiparous women who had vaginal delivery of a non-handicapped child. Saliva was collected twice daily through parturition to day 35 post-partum. In the prepartum, a highly significant circadian rhythm was seen in cortisol, with a lower-amplitude rhythm in progesterone (AM/PM = 1.12). Evening samples showed a rise in cortisol, with a highly significant rise on day -1. The rise was small. The fall in progesterone in the 3 days before parturition was also small (approximately 6%). Neither change provides an obvious trigger for parturition.

Adolescent↗

Load concentrations around crystal aggregates in articular cartilage under short-term loading.

The deposition of crystals in joints is a feature of a number of joint diseases. Crystals are frequently observed on the surface of articular cartilage and in the mid-zone. The purpose of this investigation was to model the stress concentrations in the mid-zone of the cartilage layer arising from the presence of large crystal aggregates. Scanning electron microscopy was used to determine the geometry and distribution of crystal aggregates within the cartilage layer. Finite element and photoelastic approaches were then used to predict the stress distribution around spherical aggregates 50 and 100 microns in diameter. The implication of the results is that very densely packed and tightly bound spherical aggregates will themselves carry a certain amount of load. However, less tightly packed aggregates, perhaps interspersed with fibrous tissue, are potentially much more damaging.

Cartilage, Articular↗

Wear of articular cartilage: the effect of crystals.

An investigation of the effect of crystals in a lubricant on the wear of articular cartilage in vitro was carried out in order to examine the hypothesis that crystals present in synovial fluid could cause abrasive damage of the articular surface. Plugs of cartilage were worn against a stainless steel counterface in a pin-on-disc wear rig. The concentration of cartilage debris present in the lubricant was assessed by measuring the bound sulphate originating from the glycosaminoglycans by ion chromatography. Results indicated that the presence of crystals in the lubricant significantly increased the concentration of wear debris and that the crystal size and morphology influenced the type of damage sustained by the cartilage. Other experimental evidence suggested that cartilage scratched in vivo was no more susceptible to further in vitro damage in this experimental model than normal cartilage. These results implied that crystals present in the synovial fluid of arthritic joints have the potential to cause excessive wear of the articular surface, but that if such crystals are removed the scratched cartilage may not be susceptible to any further damage by abrasive wear.

Animals↗

Health services in the New England region and their relevance to Aboriginal people.

Public hospitals provide the vast majority of available health services in rural areas of Australia. These services reflect their clinical European origins in terms of organisation and delivery. This is one reason why they remain largely foreign and irrelevant to Aboriginal people, who are reluctant users of the services and facilities available. In this article we examine what is being done in the New England region of New South Wales to improve the relevance of existing health services for Aboriginal people; this is an important first step in improving the third world health status which they presently endure.

Attitude↗

Demographic characteristics of retroviral infections (HIV-1, HIV-2, and HTLV-I) among female professional sex workers in Lagos, Nigeria.

In 1990/1991, 885 prostitutes residing in 11 of the 12 Local Government Areas (LGAs) of Lagos State, Nigeria, participated in a cross-sectional study to determine current seroprevalence of antibodies to human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), and human T-cell lymphotropic virus type I (HTLV-I). The overall prevalence of HIV-1 was 12.3%, of HIV-2, 2.1%, and of HTLV-I, 2.8%. HIV-1 seropositivity did not vary significantly by age, socioeconomic class, or nationality, but HIV-1 seroprevalence was significantly elevated for prostitutes resident in the Port area of Lagos which serves as a crossroads for international and national commerce (OR = 2.3; 95% CI = 1.1, 4.6). HIV-2 infection was significantly associated with low socioeconomic class (OR = 3.7; 95% CI = 1.2, 10.8) and non-Nigerian nationality (OR = 6.7; 95% CI = 2.5, 18.4). Prevalence of HTLV-I infection increased significantly with age (OR = 2.3; 95% CI = 1.0, 5.3). The high seroprevalence of HIV-1 in this survey, compared with previous surveys reported in the last several years and the correlation between high prevalence and areas of international commerce suggest that HIV-1 is spreading in this area of Nigeria. Intensified prevention campaigns are needed to address this possible emerging epidemic.

Adolescent↗

Neurochemical actions of inhalational anesthetics at the GABAA receptor complex.

Pharmacologically relevant concentrations of inhalational anesthetics such as halothane, enflurane and isoflurane enhance [3H]flunitrazepam (FLU) binding to benzodiazepine receptors prepared from well-washed membranes of murine cerebral cortex and cerebellum. These effects were concentration dependent and markedly enhanced by addition of chloride to the incubation medium. Using halothane as a prototype inhalational agent, it was observed that like barbiturates, increases in [3H]FLU binding were effected through an increase apparent in the apparent affinity of this radioligand with no accompanying change in the maximum number of binding sites. Although previous reports have demonstrated barbiturates augment gamma-aminobutyric acid-enhanced [3H]benzodiazepine binding, halothane exerts an additive effect in the nominal absence of chloride. Isoflurane produces a significant reduction in the EC50 of pentobarbital-augmented [3H]FLU binding. Halothane modestly reduced the binding of a benzodiazepine receptor inverse agonist, [3H]Ro 15-4513. Significant differences were also observed in the potencies and efficacies of both isoflurane and enflurane to enhance [3H]FLU binding to benzodiazepine receptors in cerebellar and cortical membranes. These findings provide a possible molecular basis for the clinical observation that benzodiazepines and barbiturates augment the anesthetic properties of inhalational agents. Moreover, the regional differences in anesthetic potency and efficacy reported here suggest a differential interaction of these inhalational agents among gamma-aminobutyric acidA receptor isoforms.

Administration, Inhalation↗

Association between postpartum thyroid dysfunction and thyroid antibodies and depression.

OBJECTIVE: To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery. DESIGN: Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum. SETTING: Outpatient department of district hospital. PATIENTS: 145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989. MAIN OUTCOME MEASURES: Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale. RESULTS: Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003). CONCLUSION: Depressive symptoms are associated with positive thyroid antibody status in the postpartum period.

Autoantibodies↗

Isoflurane anesthesia is stereoselective.

The anesthetic effects of the (+) and (-) isomers of isoflurane were determined in mice. Like the clinically important racemate, both isomers produced dose-dependent increases in anesthetic sleep time. A statistically significant (P less than 0.005, ANOVA) difference in the potencies of these isomers ((+) greater than (-)) was observed. To our knowledge, this is the first demonstration of a stereospecific action of a volatile anesthetic in vivo.

Analysis of Variance↗

Inhibition of DNA primase and polymerase alpha by arabinofuranosylnucleoside triphosphates and related compounds.

Inhibition of DNA primase and polymerase alpha from calf thymus was examined. DNA primase requires a 3'-hydroxyl on the incoming NTP in order to polymerize it, while the 2'-hydroxyl is advantageous, but not essential. Amazingly, primase prefers to polymerize araATP rather than ATP by 4-fold (kcat/KM). However, after incorporation of an araNMP into the growing primer, further synthesis is abolished. The 2'- and 3'-hydroxyls of the incoming nucleotide appear relatively unimportant for nucleotide binding to primase. Polymerization of nucleoside triphosphates by DNA polymerase alpha onto a DNA primer was similarly analyzed. Removing the 3'-hydroxyl of the incoming triphosphate decreases the polymerization rate greater than 1000-fold (kcat/KM), while a 2'-hydroxyl in the ribo configuration abolishes polymerization. If the 2'-hydroxyl is in the ara configuration, there is almost no effect on polymerization. An araCMP or ddCMP at the 3'-terminus of a DNA primer slightly decreased DNA binding as well as binding of the next correct 2'-dNTP. Changing the primer from DNA to RNA dramatically and unpredictably altered the interactions of pol alpha with araNTPs and ddNTPs. Compared to the identical DNA primer, pol alpha discriminated 4-fold better against araCTP polymerization when the primer was RNA, but 85-fold worse against ddCTP polymerization. Additionally, pol alpha elongated RNA primers containing 3'-terminal araNMPs more efficiently than the identical DNA substrate.

Animals↗

Demonstration by S-100 protein staining of increased numbers of nerves in the papillary dermis of patients with prurigo nodularis.

BACKGROUND: We hypothesized that hyperplasia of papillary dermal nerves was a constant feature of prurigo nodularis. OBJECTIVE: We tested this hypothesis by examining sections from 25 cases of prurigo nodularis, 25 cases of skin lesions characterized by epidermal hyperplasia without clinical pruritus, and 22 cases of clinically pruritic dermatoses with variable degrees of epidermal response for the presence of papillary dermal nerves. METHODS: We used a standard immunohistochemical assay with an antibody to S-100 protein as a means of identification of nerves. RESULTS: In 24 of 25 cases of prurigo nodularis, papillary dermal nerves were identified by immunostaining. Cutaneous nerves were present in 1 of 22 cases of epidermal hyperplasia with pruritus and were absent in the papillary dermis in nonpruritic cases. CONCLUSION: We conclude that hypertrophy of cutaneous papillary dermal nerves is a relatively constant feature of prurigo nodularis. The presence of papillary dermal nerves suggests a neurocutaneous component in the pathogenesis of prurigo nodularis.

Humans↗

Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers.

A great deal of interest has been focused recently on the potential use of synthetic polypeptide growth factors to stimulate healing of chronic wounds. In this pilot double-blind randomized study conducted at a single center, we used human recombinant epidermal growth factor (h-EGF) to treat 44 patients with venous ulceration of the lower extremities. An aqueous solution (10 micrograms/mL) of h-EGF was applied topically to the ulcers twice a day until healing occurred or for a maximum of 10 weeks. Patients were evaluated weekly for measurements of ulcer size and for the formation of granulation tissue suitable for grafting. Nine patients were excluded from efficacy evaluation because of protocol violations. Therefore, 35 patients (17 h-EGF, 18 placebo) were evaluable for efficacy, and 44 patients (22 h-EGF, 22 placebo) were available for safety. The median baseline ulcer size for all patients was 18.5 cm2, and was not significantly different between h-EGF and placebo group (12.9 cm2 versus 19.2 cm2, respectively, P = .27). By study end, six (35%) of h-EGF treated patients and two (11%) in the placebo group had healed completely (P = .10). Another 6 patients (2 of 17 h-EGF, 4 of 18 placebo; P = .50) developed healthy granulation tissue that was suitable for grafting. The median ulcer size reduction was 7% for h-EGF versus 3% for placebo per week (P = .29), and 73% versus 33% at study end (P = .32). No untoward side effects were related to the application of h-EGF. We conclude that topical application of h-EGF, in the dose and manner used in this study, was safe but failed to significantly enhance re-epithelialization of venous ulcers. However, a greater reduction in ulcer size and a larger number of healed ulcers with the use of h-EGF are encouraging results.

Administration, Topical↗

The effects of occlusive dressings on the recruitment of mononuclear cells by endothelial binding into acute wounds.

Mononuclear cell infiltration is a characteristic feature of wounds and may play an important role in the healing process. We have previously shown that the recruitment of peripheral blood mononuclear cells into wounded skin is an active, dynamic, and regulated process mediated at least in part by specific interactions between mononuclear leukocytes and specialized dermal microvascular endothelial cells in the wounded skin. The purpose of this study was to investigate the capacity of dermal microvascular endothelial cells in wounds exposed to air or covered with occlusive dressings to promote the adhesion of monocytes and lymphocytes. The results showed that dermal microvascular endothelial cells in both air-exposed and occluded wounds were capable of supporting peripheral blood mononuclear cell and monocyte adherence. However, in comparison with air exposed wounds, the level of peripheral blood mononuclear cell binding was significantly higher in occluded biopsies obtained at 0 to 9, 12, 15, and 21 days after wounding. In addition, monocyte and peripheral blood mononuclear cells binding to occluded wounds peaked earlier than peripheral blood mononuclear cell binding to air exposed wounds. These studies provide evidence that differences in the kinetics and magnitude of mononuclear cell adherence may account at least in part for the beneficial effects of occlusive dressing on wound healing.

Animals↗

Salivary testosterone levels and major depressive illness in men.

Studies of testosterone levels in patients with major depressive illness have produced varying results, plasma levels usually being reported. Saliva levels reflect 'free' plasma testosterone, and a pilot study of 11 men with major depression with melancholia, who underwent a standard dexamethasone suppression test, is described. There were no significant differences in testosterone levels compared with an age-matched control group. In the patient group, pre-dexamethasone levels correlated significantly and negatively with depression ratings on the 21-item Hamilton and the Montgomery and Asberg depression scales, and also with state anxiety measured on the Spielberger scale.

Adult↗

Differences in basal and poststimulation glucose homeostasis in nondiabetic first degree relatives of black and white patients with type 2 diabetes mellitus.

Black Americans (blacks) have a higher prevalence and earlier onset of type 2 diabetes than white Americans (whites). To examine metabolic differences in both races, we measured the basal glucose turnover rates (D-]3-3H]glucose technique) and plasma glucose, insulin, and C-peptide levels before and after an oral glucose load in 24 glucose-tolerant black and 14 white female relatives of patients with type 2 diabetes. Eight black and 8 white female subjects with no family history of diabetes served as controls. Mean fasting and postglucose plasma glucose levels were not significantly different between the black and white relatives and the control subgroups. Mean fasting plasma insulin and C-peptide levels were slightly greater but not significantly different between the relatives. After oral glucose ingestion, mean incremental integrated plasma insulin areas were significantly (P less than 0.02) greater in the black than the white relatives (70 +/- 14 vs. 29 +/- 6 nM.min). In addition, incremental integrated C-peptide areas were greater in the black than the white relatives (303 +/- 55 vs. 115 +/- 33; P less than 0.005). Similarly, we found significantly greater integrated incremental insulin (61 +/- 11 vs. 22 +/- 3 nM.min; P less than 0.02) and C-peptide (248 +/- 58 vs. 47 +/- 16; P less than 0.005) areas in the black than the white controls, respectively. The estimated basal and postglucose hepatic insulin extraction values, expressed as molar ratios of C-peptide and insulin, were not significantly different between the relatives. While basal hepatic insulin extraction was significantly (P less than 0.05) lower in the black controls, the postprandial insulin clearance was not different between the black and white controls. Mean basal hepatic glucose production was greater (P less than 0.02) in the black than the white relatives (2.49 +/- 0.13 vs. 2.02 +/- 0.12 mg/kg.min). Similarly, the black controls had greater hepatic glucose production than the white controls (2.36 +/- 0.15 vs. 1.81 +/- 0.08 mg/kg.min; P less than 0.001). We conclude that basal and poststimulation glucose homeostatic regulation appear to be different in black and white females, regardless of family history of type 2 diabetes.

Adult↗

Effects of concentration of dietary phosphorus on amount and route of excretion.

Objectives were to determine the effect of dietary concentration of P in DM on routes of excretion of P and to evaluate direct and indirect measures of calculating DM digestibility and P excretion. Twelve lactating Holstein cows were fed 20 kg of DM containing .41% P daily for 4 wk and then were assigned randomly to one of three diets: low (.30%), medium (.41%), or high (.56%) in P for 9 wk. Total collections of excreta (feces and urine) and milk were made during wk 4, 7, 10, and 13. At wk 4, cows excreted 88.2% of P consumed daily: 68.6% of excreted P in feces, 1.0% in urine, and 30.3% secreted in milk. Cows assigned to the low P diet decreased intake by 26.8% and excretion of P in feces by 22.7% in wk 13 compared with wk 4, whereas cows fed the high P diet increased intake by 36.5% and excretion of P in feces by 48.6%. Digestibility of DM was 62.6% when calculated from total collection of feces but only 55.7 or 56.5% when estimated indirectly using Cr or acid detergent lignin as indigestible markers. Apparent excretion of P was less than that estimated using either of the marker techniques (49.7 vs. 59.1 and 58.1 +/- .7 g/d of P) because digestibility of DM was underestimated. A prediction equation was developed for P excretion based on P intake and milk production.

Animals↗