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D Hopkins

Publications and source records attributed to D Hopkins.

At least 19 recordsLinked to original sources

Relationships between hypothalamic neuropeptide Y and food intake in the lactating rat.

NPYergic neurons in the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nucleus (PVN) are postulated to regulate food intake and energy balance. This projection is overactive in lactation and is thought to drive hyperphagia in this condition. We have explored further the relationship between hypothalamic NPY and food intake in lactation and tested the hypothesis that hypoinsulinemia is the stimulus to NPY neuronal activity. Compared with nonlactating controls (n = 10), freely fed lactating rats (n = 9) showed significantly increased (p < 0.05) NPY levels in the ARC and medial preoptic area (MPO), but there was no significant increase in whole hypothalamic NPY mRNA levels. Lactating rats (n = 8) that were restricted to control rats' food intake for 3 days showed generally higher hypothalamic NPY levels, with significantly higher concentrations than controls (p < 0.05) in the ARC, MPO, PVN, and lateral hypothalamic area (LHA); NPY mRNA levels were also significantly increased (p < 0.05). Across all three experimental groups, there was a significant inverse correlation between plasma insulin concentration and hypothalamic NPY mRNA levels (r = -0.39, p < 0.01). We conclude that the ARC-PVN projection is overactive in lactation and that this is not a consequence of hyperphagia. Hypoinsulinemia may stimulate these neurons, as it is thought to do in other conditions of energy deficit.

Animals

Dissociation of hypothalamic NPY from BAT uncoupling protein mRNA in rats exposed to 24 h thermoneutrality.

Neuropeptide Y (NPY) is increasingly considered to be involved in the central regulation of energy balance. Our previous studies suggest that hypothalamic NPY neurons of the arcuatoparaventricular (ARC-PVN) projection are inhibited in association with the marked increases in brown adipose tissue (BAT) thermogenesis and uncoupling protein (UCP) gene expression in rats exposed to cold. We therefore hypothesized that the NPYergic ARC-PVN system would be activated in a thermoneutral environment, when energy expenditure falls to a minimum, and that this activation could mediate the fall in BAT activity. We measured regional hypothalamic NPY concentrations, hypothalamic NPY receptor binding, and NPY mRNA together with UCP mRNA levels in rats exposed to thermoneutrality (29 degrees C) for 24 h. At thermoneutrality, UCP mRNA levels fell to 42% of those in controls maintained at 22 degrees C, but there were no significant changes in hypothalamic NPY or NPY mRNA levels or in NPY receptor binding. We conclude that the fall in UCP mRNA expression occurring under short-term thermoneutral condition is mediated by neuroendocrine mechanisms other than increased activity of hypothalamic NPY neurons.

Adipose Tissue, Brown

Hydroxyzine premedication--does it provide better anxiolysis than a placebo?

OBJECTIVES: To determine how effective hydroxyzine is compared with a placebo in providing pre-operative anxiolysis in our hospital population, and to assess the anxiolytic effect of our pre-operative visit. DESIGN: Double-blind, randomised, prospective, controlled trial. Anxiety levels assessed with visual analogue scales (VAS), by patient and investigator. Haemodynamic parameters measured: heart rate, blood pressure, respiratory rate. SETTING: Hillbrow Hospital, Johannesburg. PARTICIPANTS: Sixty female patients aged 20-60 years, American Society of Anesthesiologists status I-III, scheduled for elective gynaecological surgery under general anaesthesia. The overall participation rate was 100%. All cases were randomly selected. INTERVENTION: Hydroxyzine (Aterax) 1-2 mg/kg, or a placebo administered orally as anaesthetic premedication. OUTCOME MEASURES: Anxiolytic effect of agents and of pre-operative visit. Time interval between premedication and induction of anaesthesia. Blood pressure, heart rate, respiratory rate, other signs of autonomic hyperactivity (restlessness, tremors, sweating). RESULTS: A statistically significant reduction in anxiety followed the administration of hydroxyzine (P < 0.05) and the placebo (P < 0.03); however, no statistically or clinically significant difference could be demonstrated between the two agents. No significant anxiolysis occurred following the premedication visit. The average premedication-induction interval was 72 minutes. There were no significant differences in haemodynamic parameters between the two groups. CONCLUSIONS: Hydroxyzine, in the dose administered and after an appropriate premedication-induction interval, provided no better anxiolysis than a placebo in the pre-operative period. No significant anxiolytic effect was demonstrated by our routine premedication visit.

Administration, Oral

Neuropeptide Y, the hypothalamus, and diabetes: insights into the central control of metabolism.

Neuropeptide Y (NPY), a major brain neurotransmitter, is expressed in neurons of the hypothalamic arcuate nucleus (ARC) that project mainly to the paraventricular nucleus (PVN), an important site of NPY release. NPY synthesis in the ARC is thought to be regulated by several factors, notably insulin, which may exert an inhibitory action. The effects of NPY injected into the PVN and other sites include hyperphagia, reduced energy expenditure and enhanced weight gain, insulin secretion, and stimulation of corticotropin and corticosterone release. The ARC-PVN projection appears to be overactive in insulin-deficient diabetic rats, and could contribute to the compensatory hyperphagia and reduced energy expenditure, and pituitary dysfunction found in these animals; overactivity of these NPY neurons may be due to reduction of insulin's normal inhibitory effect. The ARC-PVN projection is also stimulated in rat models of obesity +/- non-insulin diabetes, possibly because the hypothalamus is resistant to inhibition by insulin; in these animals, enhanced activity of ARC NPY neurons could cause hyperphagia, reduced energy expenditure, and obesity, and perhaps contribute to hyperinsulinemia and altered pituitary secretion. Overall, these findings suggest that NPY released in the hypothalamuss, especially from the ARC-PVN projection, plays a key role in the hypothalamic regulation of energy balance and metabolism. NPY is also found in the human hypothalamus. Its roles (if any) in human homeostasis and glucoregulation remain enigmatic, but the animal studies have identified it as a potential target for new drugs to treat obesity and perhaps NIDDM.

Animals

The association of an HPV16 oncogene variant with HLA-B7 has implications for vaccine design in cervical cancer.

HLA-restricted cytotoxic T-lymphocyte (CTL) recognition of human papillomavirus (HPV) oncogene products may be important in the control of the HPV infections associated with the development of cervical cancer. We have identified, in HLA-B7 individuals, a consistent variation in the HPV16 E6 oncoprotein sequence, which alters an HLA-B7 peptide binding epitope in a way likely to influence immune recognition by CTLs. These results illustrate a biologically relevant mechanism for escape from immune surveillance of HPV16 in HLA-B7 individuals. Thus, both HLA type and HPV16 strain variation need to be considered in the screening of at-risk individuals and for the rational design of anti-HPV vaccines.

Amino Acid Sequence

Blood use for surgical patients: a study of Scottish hospital transfusion practices.

The use of an effective schedule for ordering blood for transfusion for surgical patients is the accepted standard of practice for hospital blood banks in UK hospitals. The use of maximum surgical blood ordering schedules (MSBOS) was surveyed throughout Scotland in 1992 and 1993. Twenty-seven hospitals participated in the study. Twenty-three (85%) of these 27 operated a schedule. Schedules varied between hospitals both in the way the schedules were implemented and in the amount of blood allocated to operations. The implementation of schedules was compared in three hospitals each for Caesarean section, transurethral resection of the prostate (TURP) and primary hip replacements. Adherence to the schedules averaged 76% (range 10-100%) and varied with operation, tariff, and hospitals. Blood use per operation did not depend on the amount of blood allowed by the schedule. Use of a MSBOS does not appear to influence clinical use of blood for transfusion, indicating that the gains in efficient use of laboratory resources and in safe handling of blood units can be made without compromising patient care.

Blood Banks

A hypermetabolic reaction during anaesthesia and surgery. A case report.

A young man underwent anaesthesia and surgery after multiple fractures. After 2 hours of anaesthesia, the patient developed hypercapnia, acidosis, hyperpyrexia and mild muscle rigidity. He was treated for malignant hyperthermia. Muscle tension studies with caffeine-halothane and muscle histology proved normal. The differential diagnosis of this abnormal metabolic response is briefly discussed.

Adult

A smoking cessation pilot program.

National health-care costs are continuing to climb and employers in Hawaii and across the nation are forced to increase their share of the burden. To limit these costs, worksite health promotion programs are increasing in number and in scope. Smoking control programs in particular now rank as the most prevalent type of worksite program; as the disability, absenteeism, and early death on the part of smokers have been well-documented as contributing to the cost of health care. Our research describes a year-long, pilot smoking-cessation program implemented at Hawaiian Telephone Company. Our program used a combination of behavioral-modification, social support and incentives technique to assist people to stop smoking or to maintain their nonsmoking behavior. The 12 volunteer participants provided a multiethnic, long-term, heavy smoker employee sample. Survey results at 1 year demonstrated that 4 of them quit smoking (quit rate = 50%), 2 reduced their tobacco intake, 2 dropped out of the program and continued to smoke. The 4 who had entered the program for maintenance purposes remained smoke-free. Cost-benefit analysis yielded conservative estimates indicating that the program had paid for itself and saved an additional $350 a year per participant who remained a nonsmoker.

Adult

Extending patient-controlled analgesia to patient-controlled neuroleptanalgesia.

A trial was conducted (among 22 patients) to assess a new use of patient-controlled devices. Using a patient-controlled analgesia (PCA) pump under the anaesthetist's guidance, the patients self-administered a neurolept mixture consisting of droperidol and alfentanil. The patients were then able to undergo minor surgery (dilatation and curettage). The majority remained detached, sedated and pain-free, while able to control the PCA pump during the procedure. Patient-controlled neuroleptanalgesia or PCNA, as we propose to call this technique, appeared practical, effective and safe. The method was generally well accepted and highly rated by the patients.

Adolescent

[Current status of the global campaign to eradicate dracunculiasis (guinea worm disease)].

Dracunculiasis is eradicable because it is easy to diagnose, it is only transmitted by drinking water, there is no animal reservoir, and there are three ways to prevent the infection. Global 2000 is assisting guinea worm eradication Programmes in Pakistan, Ghana and Nigeria. The draft criteria for certification of dracunculiasis elimination and the resolutions adopted during the 3rd African Regional Conference on dracunculiasis were described. The progress of Pakistan's guinea worm eradication Programme, which has nearly achieved its goal and the accomplishments of the eradication Programme in Nigeria, which is thought to have the most case of guinea worm in the world were described. Evidence of socio-economic impact of dracunculiasis, vector control, local treatment and case containment were presented during the question and answer period.

Animals

Surveillance: the foundation for control and elimination of dracunculiasis in Africa.

The International Drinking Water Supply and Sanitation Decade (1981-1990) has stimulated a movement to eradicate human infection with the helminthic parasite Dracunculus medinensis (dracunculiasis), whose victims are disabled for weeks or months during the painful emergence of one or more worms from beneath the skin. Each year, millions of people acquire this infection by drinking unclean water. Among the critical activities that are necessary for the elimination of dracunculiasis, one of the most fundamental is that of epidemiological surveillance. Surveillance activities play a key role in the strategy to target affected villages for improved water supplies and other control activities. Accurate surveillance data also stimulate interest and support for national eradication programmes. Dracunculiasis is a condition with excellent characteristics for reporting through passive surveillance systems. However, active surveillance, as well as other innovative surveillance strategies, should be used to establish baseline information in those villages where cases occur, and later to monitor epidemiologically important indices needed to evaluate the progress of elimination efforts.

Africa

The relation of faculty academic activity to financing sources in a department of medicine.

Academic medical departments confront important changes in funding sources and consequent pressure to change faculty activities. Valid information has often been lacking concerning the existing relations of faculty activity to funding sources. We examined those relations in the Stanford Department of Medicine through a combination of randomized observations of faculty and faculty self-reports over a period of one year. For an average 62-hour workweek, there was approximate consonance between types of activities and sources of salary support. Sensitivity analyses indicated that even sizable errors in self-reports would not have changed the outcomes substantially. Over 60 per cent of the activity involved "joint products," representing two or more categories of activity. There was wide variation in activities and fund sources between divisions. Per full-time faculty equivalent, research generated far more income than the most lucrative specialty practice; thus, at least in this type of department, attempts to compensate for lost research revenue by intensifying clinical practice will probably fail and undermine present research activities. The method of analysis used here may be useful in improving prospective planning by departments and by larger medical-policy bodies, particularly in the public sector.

Academic Medical Centers

Reduction in prostatic concentration of endogenous dihydrotestosterone in rats by hyperprolactinemia.

Persistently high levels of circulating prolactin can be achieved in male rats when pituitaries from female donors are grafted under the renal capsule. Enhanced growth of the lateral prostate can be accomplished by an apparent synergistic effect of excess prolactin with subphysiologic doses of testosterone. To define this effect we measured the endogenous dihydrotestosterone (DHT) concentrations in rat prostate lobes. Twenty Sprague-Dawley male rats (250 g) were castrated and given subcutaneous implants of silastic tubing filled with 1 cm of crystalline testosterone. Ten of these rats simultaneously received two pituitary grafts under the renal capsule. The remaining ten rats received intrarenal skeletal muscle grafts as controls. Four weeks later, the weight (mg +/- SE) of the ventral and dorsal lobes were not significantly different between the two groups, while the lateral lobe was significantly (P less than 0.01) heavier in rats with pituitary grafts (121.4 +/- 7.5) than in controls (81.7 +/- 10.4). Endogenous DHT in the tissue extracts was determined by radioimmunoassay following KMnO4 treatment to eliminate testosterone. The concentration of DHT (ng/g tissue +/- SE) was significantly (P less than 0.01) lower in the lateral prostate of graft-bearing animals (4.40 +/- 0.29) than in the controls (5.98 +/- 0.34). These results indicate that, in the rat, hyperprolactinemia induced by pituitary grafts is associated with a heavier lateral prostate and a lower concentration of endogenous DHT in that tissue. These results also suggest that the action of prolactin in the rat prostate is not mediated through the action of androgen.

Animals