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Biomedical subjects

D Hopkins

Publications and source records attributed to D Hopkins.

At least 19 recordsLinked to original sources
PubMed1998

Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery.

PURPOSE: To compare subcutaneous PCA tramadol with subcutaneous PCA morphine for postoperative pain relief after major orthopaedic surgery and for the incidence of side-effects. METHODS: In a double-blind randomised controlled study 40 patients (20 in each group) self-administered either tramadol or morphine for 72 hr after surgery via s.c. PCA. The following variables were recorded at various time intervals: (i) pain score by means of a visual analogue scale, (ii) drug consumption and total PCA demands, (iii) vital signs (blood pressure and heart rate), (iv) oxygen saturation and respiratory rate, and (v) side-effects (sedation, nausea/vomiting, pruritus, urinary retention and constipation). RESULTS: Both drugs provided effective analgesia. The mean consumption in the first 24 hr was 792 +/- 90 mg tramadol and 42 +/- 4 mg morphine. Thereafter, consumption of both drugs declined markedly. Moderate haemodynamic changes were observed in both the tramadol and morphine groups (with a maximum 20% decrease in mean blood pressure and a maximum 17% increase in heart rate) during the 72 hr period. Both tramadol and morphine were associated with a clinically and statistically significant (P < 0.001) decrease in oxygen saturation, but without changes in respiratory rates. Desaturation was less marked with tramadol. Tramadol appeared to cause more nausea and vomiting than morphine. Sedation was mild and only seen during the first few hours after surgery in both groups. CONCLUSION: Tramadol is an effective analgesic agent for the relief of acute postoperative pain when administered by PCA via the subcutaneous route. Under these conditions tramadol behaves much like morphine with a similar side-effect profile.

Adult↗
PubMed1998

Direct stimulation of BAT thermogenesis does not affect hypothalamic neuropeptide Y.

Acute cold exposure which significantly stimulated thermogenesis in brown adipose tissue (BAT), also increased neuropeptide Y (NPY) levels in its hypothalamic sites of release without affecting NPY synthesis, suggesting that NPY release is acutely inhibited. To clarify whether these changes in NPY are the cause or consequence of BAT activation, we studied whether hypothalamic NPY and NPY mRNA levels in rats were affected by acute intraperitoneal injection of the beta 3-adrenoceptor agonist BRL 35135 (500 micrograms/kg), which directly activates BAT thermogenesis. BRL 35135 treatment doubled BAT uncoupling protein mRNA levels (p < 0.05), and increased core temperature by 0.4 degree C (p < 0.05), but neither hypothalamic regional NPY levels nor hypothalamic NPY mRNA levels were affected by BRL 35135. This suggests that the NPY changes induced by cold exposure are not the result of BAT activation, and is consistent with the hypothesis that decreased NPY release during cold exposure might disinhibit the sympathetic innervation that drives BAT thermogenesis.

Adipose Tissue, Brown↗
PubMed1998

The action profile of lispro is not blunted by mixing in the syringe with NPH insulin.

OBJECTIVE: To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile. RESEARCH DESIGN AND METHODS: A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separate occasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures. RESULTS: Peak plasma insulin levels (2.6 +/- 0.8 vs. 2.2 +/- 0.6 vs. 1.9 +/- 0.6 ng/ml, P = 0.075), total glucose infused (121.5 +/- 32.8 vs. 135.0 +/- 49.0 vs. 117.3 +/- 39.9 mg.kg-1.min-1, P = 0.53), and maximum glucose infusion rate (GIRmax) (8.3 +/- 0.9 vs. 8.0 +/- 1.7 vs. 7.1 +/- 2.4 mg.kg-1.min-1, P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly shorter than in treatment group C (0.9 +/- 0.3 and 1.2 +/- 0.2 vs. 2.0 +/- 0.4 h, respectively, P = 0.042). The times until GIRmax were also not different (113.9 +/- 41 and 122.0 +/- 45 vs. 209.0 +/- 51.3 min, respectively, P = 0.002). The glucose infusion rate (GIR) then fell to 50% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 +/- 40.5 vs. 292.4 +/- 133.3 vs. 399.5 +/- 78.3, respectively, P = 0.005). CONCLUSIONS: The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine types of insulin before injection to achieve optimal diabetes control.

Adult↗
PubMed1998

Effects of glycemic control on protective responses against hypoglycemia in type 2 diabetes.

OBJECTIVE: To determine the effects of glycemic control on the counterregulatory responses to hypoglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: Seven poorly controlled type 2 diabetes patients (mean HbA1c, 11.3 +/- 1.1%) were studied by stepped hyperinsulinemic hypoglycemic clamp (nadir, 2.4 mmol/l) before and after improving glycemic control with insulin treatment. Counterregulatory hormones, symptoms, and four-choice reaction time were measured at each glucose plateau. RESULTS: In patients with poorly controlled type 2 diabetes, counterregulatory hormone responses began at higher plasma glucose levels than did those in healthy subjects (epinephrine, 4.4 +/- 0.2 vs. 3.7 +/- 0.2 mmol/l, P = 0.011). After significant improvement in glycemic control (mean HbA1c, 8.1 +/- 0.9%, P < 0.001) was achieved without severe hypoglycemia, hormonal responses started at much lower plasma glucose levels (e.g., epinephrine, 3.5 +/- 0.3 mmol/l, P = 0.005) and were significantly reduced in magnitude (e.g., area under epinephrine response curve, 306 +/- 93 vs. 690 +/- 107 nmol.min-1.l-1, P = 0.012). This was accompanied by a change in the plasma glucose threshold at which hypoglycemic symptoms first developed from 3.6 +/- 0.2 to 3.0 +/- 0.2 mmol/l (P = 0.019). In contrast, the plasma glucose threshold at which four-choice reaction time deteriorated did not change significantly (3.1 +/- 0.1 vs. 2.9 +/- 0.1 mmol/l, P = 0.125). CONCLUSIONS: Counterregulatory responses begin at normoglycemia in poorly controlled type 2 diabetes. Improving glycemic control with insulin therapy normalizes hormonal responses but lowers the plasma glucose levels at which hypoglycemic symptoms develop to levels associated with impairment of four-choice reaction time, a marker of cognitive function. This process potentially increases the risk of severe hypoglycemia, but to a lesser extent than occurs in type 1 disease.

Blood Glucose↗
PubMed1998

Effects of feeding a liquid diet for one year to New Zealand White rabbits.

We compared the long-term effects of a newly designed liquid diet with a commercially available dry diet in New Zealand White rabbits. Body weight gain, feed consumption, and plasma lipid concentrations were measured periodically throughout the 1-year study. In addition, specific hepatic enzyme activities in serum were quantified to examine the effects of liquid diet on the liver over the 1-year feeding trial. At 52 weeks, body weight gains between the liquid- and dry-fed groups were similar. Regardless of sex, plasma phospholipid concentrations were higher in the control group than in the liquid-fed group. Plasma triglyceride concentrations were increased in liquid-fed female rabbits, compared with either male group or control-fed females. A somewhat similar effect was observed in plasma cholesterol concentration, which was higher in female rabbits regardless of diet type. After the 52-week trial, the rabbits had no clinical biochemical signs of liver damage. Results of this study indicate that a liquid diet can be fed to New Zealand White rabbits for a long period, and may provide an alternative route (food source) for future pathophysiologic studies.

Animals↗
PubMed1998

Fixed polarizer ellipsometry for simple and sensitive detection of thin films generated by specific molecular interactions: applications in immunoassays and DNA sequence detection.

Biological thin films may form on a surface by specific molecular interactions. The fixed polarizer ellipsometer (FPE) is a sensitive instrument that detects biological thin films either qualitatively or quantitatively. The design is simple and inexpensive. The assays are formatted on an optical surface, and the FPE detection is based on the phase shift of linearly polarized light after reflection through a thin film. We have constructed mathematical models of the FPE response to reflection through single-layer and two-layer films that agree closely with experimental data. Several biological assays have been measured with the FPE to demonstrate the application of this technology to clinical targets, including ultrasensitive immunoassays for hepatitis B surface antigen (0.1 ng/mL) and alpha-fetoprotein (0.01 ng/ mL) and DNA hybridization (0.5 fmol/microL target probe). A clinical study for detection of group A streptococcus from patient throat swabs demonstrated the qualitative application of the FPE to infectious disease targets. The flexibility and sensitivity of the FPE makes this technology suitable for numerous target analytes and applications.

Antigens, Bacterial↗
PubMed1997

Increased feeding in fatty Zucker rats by the thiazolidinedione BRL 49653 (rosiglitazone) and the possible involvement of leptin and hypothalamic neuropeptide Y.

1. The thiazolidinedione BRL 49653 (rosiglitazone) induces hyperphagia and weight gain in obese, insulin-resistant fatty Zucker rats but not in lean insulin-sensitive rats. We investigated whether these responses might involve neuropeptide Y (NPY), leptin and insulin. 2. BRL 49653 (1 mg kg(-1) day(-1), orally) was given for 7 or 20 days to fatty and lean Zucker and Wistar rats. 3. In lean rats of either strain, BRL 49653 had no effect on food intake, body weight, plasma insulin and corticosterone, NPY or NPY mRNA levels. 4. Fatty rats given BRL 49653 showed a 30% increase in food intake and accelerated body weight gain (both P<0.01) after 7 and 20 days, but without significant changes in regional hypothalamic NPY or NPY mRNA levels. 5. Plasma leptin levels were twice as high in untreated fatty Zucker rats as in lean rats (P<0.01), but were unaffected by BRL 49653 given for 20 days. However, BRL 49653 reduced insulin levels by 42% and increased corticosterone levels by 124% in fatty rats (both P<0.01). 6. Hyperphagia induced in fatty Zucker rats by BRL 49653 does not appear to be mediated by either a fall in circulating leptin levels or increased activity of hypothalamic NPYergic neurones. The fall in plasma insulin and/or rise in corticosterone levels during BRL 49653 treatment may be involved, consistent with the postulated role of these hormones in the control of food intake.

Animals↗
PubMed1997

Alcohol increases plasma levels of cholesterol diet-induced atherogenic lipoproteins and aortic atherosclerosis in rabbits.

The purpose of the present study was to reexamine the relationship between alcohol and atherosclerosis. Two experiments were performed: The first contained three groups of New Zealand White (NZW) female rabbits. The control group was fed a cholesterol-containing liquid diet and the other two groups were fed the same diet with either 20% or 30% of the calories supplied by alcohol. The second experiment had two treatments: one control group and another group fed a 10% alcohol diet. In experiment 1, alcohol at the 20% and 30% levels increased VLDL and LDL but not HDL compared with levels in control rabbits. Hepatic mRNA levels of apolipoprotein (apo) A-I, apoB, and 7 alpha-hydroxylase were not affected by alcohol. However, the LDL-receptor mRNA was decreased to half of control values by either 20% or 30% alcohol. Lesion areas and aortic cholesterols were significantly increased in the 20% and 30% alcohol-treated groups. Also, significant correlations were found between plasma cholesterol levels and total lesion area or lesion cholesterol contents. In experiment 2, the 10% alcohol-treated rabbits showed no differences in circulating lipoproteins, LDL-receptor mRNA, or lesion formation above that observed in controls. These experiments suggest that alcohol substituted at 20% or 30% of the dietary calories induces hypercholesterolemia and more aortic atherosclerotic lesions. The alcohol-induced accumulation of VLDL and LDL was accompanied by low hepatic LDL-receptor mRNA levels, suggesting that alcohol may affect LDL-receptor expression and rates of lipoprotein clearance, but more experiments are needed to evaluate this possibility.

Animals↗
PubMed1996

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↗
PubMed1996

Intraoperative bleeding: a mathematical model for minimizing hemoglobin loss.

BACKGROUND: The rationale for intraoperative blood transfusion is often based on incorrect concepts and criteria. STUDY DESIGN AND METHODS: A mathematical model based on physiologic measures and describing the usual pattern of surgical blood loss is presented, and a theoretical means of minimizing intraoperative hemoglobin loss with hypervolemic hemodilution is proposed. RESULTS: Intraoperative hemoglobin loss is often overestimated especially in connection with high-volume blood loss. The model of intraoperative hypervolemic hemodilution shows significant improvement in hemoglobin concentration in the immediate postoperative period, compared with normovolemic conditions. The difference is most marked at a high volume of blood loss and a high degree of maintained hypervolemia. CONCLUSION: The practice of intraoperative blood transfusion according to volume of blood lost is to be discouraged, and regular monitoring of the hematocrit is necessary to avoid unnecessary transfusion. The theoretical advantages of hypervolemic hemodilution warrant further testing of the model in a clinical setting.

Blood Loss, Surgical↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1993

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↗
PubMed1993

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↗