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Biomedical subjects

D Dwyer

Publications and source records attributed to D Dwyer.

At least 55 records · Page 3Linked to original sources

Nocturnal patterns of macronutrient intake in freely feeding and food-deprived rats.

Analyses of rats' feeding behavior at the start and the end of the nocturnal cycle have revealed dramatic alterations in macronutrient intake over time. At dark onset, rats displayed a preference for carbohydrate, with the first meal of the night consisting of approximately 60% of this nutrient. This carbohydrate intake was soon followed by a shift toward protein-predominant meals. Superimposed on this pattern of meal-to-meal shifts in nutrient selection appears to be an additional rhythm in which carbohydrate ingestion was favored at dark onset and protein and fat ingestion were favored during the late dark hours. Differential feeding patterns were also apparent following mild food deprivation. A 2-h period of deprivation at dark onset produced a strong compensatory feeding response, particularly of fat and carbohydrate. This pattern was not observed at the end of the dark, when little compensatory feeding was demonstrated. It is suggested that these feeding patterns may be related to the activity of certain hypothalamic neurotransmitters, e.g., norepinephrine and serotonin, known to be important in modulating temporal feeding patterns and nutrient intake.

Animals↗

Esmolol for potentiation of nitroprusside-induced hypotension: impact on the cardiovascular, adrenergic, and renin-angiotensin systems in man.

Esmolol infusion at rates of 200, 300, and 400 micrograms.kg-1.min-1 was used to potentiate hypotension (mean arterial pressure = 60 mm Hg) induced with sodium nitroprusside (SNP) in 10 male patients undergoing radical cancer surgery during nitrous oxide-oxygen and fentanyl anesthesia. Heart rate (HR), blood pressure (radial arterial catheter), and plasma levels of renin activity (PRA), norepinephrine (N), epinephrine (E), and dopamine (D) were measured: 1) while patients were awake; 2) after induction of anesthesia (nitrous oxide, 60% in oxygen, fentanyl = 5 micrograms/kg followed by an infusion at 10 micrograms.kg-1.hr-1); 3) after surgery had begun; 4) after 20 minutes of SNP-induced hypotension; 5) after 20 minutes of esmolol at each of the above infusion rates; and 6) after the completion of surgery. Compared to awake values, SNP-induced hypotension (mean infusion rate = 3.1 micrograms.kg-1.min-1 +/- 0.6 SE) during surgery resulted in significant (P less than 0.05) increases in heart rate, PRA, N, and D. Infusion of esmolol resulted in significant (P less than 0.05) dose-dependent reductions in SNP requirement to maintain MAP = 60 mm Hg. At 200 micrograms.kg-1.min-1, SNP requirement was 2.1 micrograms.kg-1.min-1 +/- 0.4, at 300 micrograms.kg-1.min-1, it was 1.0 micrograms.kg-1.min-1 +/- 0.2, and at 400 micrograms.kg-1.min-1, was 0.5 micrograms.kg-1.min-1 +/- 0.3. Concomitant with the decrease in SNP requirement, there were significant reductions in HR and PRA at all infusion rates of esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

The role of intimal hyperplasia in arterial spasm.

It has been postulated that even moderate spasm in an artery with intimal hyperplasia can produce organ hypoxia because there is an excessive reduction in the diameter of the lumen. To test this hypothesis we created intimal hyperplasia in one femoral artery in five pigs and then induced arterial spasm by administering ergonovine maleate. Arterial spasm did not produce a greater reduction in the luminal diameter of the femoral artery with intimal hyperplasia than it did in the normal femoral artery. Until further evidence appears this hypothesis must be viewed with caution.

Animals↗

Sublingual buprenorphine used postoperatively: clinical observations and preliminary pharmacokinetic analysis.

1 Buprenorphine is a long-acting opiate analgesic. This study was designed to investigate the pharmacokinetics of this drug when given by the sublingual route to ten postoperative patients. Plasma levels of buprenorphine were measured by a specific radioimmunoassay. 2 Plasma levels of the drug following sublingual administration of 0.4 mg showed an apparent delay in absorption and then rose slowly to reach low but significant levels by 3 h. There was considerable variation in the time at which peak levels were achieved. The average systemic availability of the drug by this route was estimated to be 30% by 3 h. 3 Analgesic efficacy and duration of sublingual buprenorphine were assessed using demand analgesia. The analgesia was of about 9 h duration, similar to that achieved by parenteral administration of 0.3 mg of the drug to an equivalent group of patients. The sublingual dose caused a significant fall in the postoperatively elevated group of patients. The sublingual dose caused a significant fall in the postoperatively elevated plasma glucose, and prevented any further rise in plasma cortisol. 4 Reasons for the efficacy of the sublingual route are discussed and it is suggested that this route may be particularly appropriate for highly lipophilic drugs like buprenorphine.

Analgesia↗

Juvenile myasthenia gravis.

We studied 32 children with myasthenia gravis over a period of 12 years. The mean age at onset was 7.7 years. Presentation was ocular in 63% of patients. Another major disease in addition to myasthenia occurred in 44% of patients; a seizure disorder was the most commonly associated disease. Serum IgG antibody to nicotinic acetylcholine receptor was present in 53% of patients and did not correlate with severity of disease or treatment. Medical management was effective in 63%; thymectomy was effective in only 28%. We conclude that myasthenia gravis appears commonly before age 10 and is associated with the risk of some disease other than hyperthyroidism. Serum IgG nicotinic acetylcholine receptor antibody is present less frequently than in normal adults, and vigorous medical management should be attempted before thymectomy.

Adolescent↗

Purification and characterization of nicotinic acetylcholine receptors from muscle.

The nicotinic acetylcholine receptor was purified from normal and denervated rat skeletal muscle. The purification protocol included alpha-cobratoxin biospecific adsorption, ion exchange chromatography, and gel filtration steps. The highest specific activity achieved was 7.5 pmol of 125I-alpha-bungarotoxin binding sites per microgram protein. Sodium dodecyl sulfate gel electrophoresis of purified AChR revealed subunits with molecular weights of 42,000 and 66,000 daltons and a minor component with a molecular weight of 52,000 daltons. Normal muscle AChR is comprised of one toxin binding component. Upon denervation a second component appears, but both components are increased as a consequence of denervation. A dissociation constant of 1.5 x 10(-8)M was determined for d-tubocurarine from receptor from both normal and denervated muscle. A dissociation constant of 1 x 10(-7)M for acetylcholine, perhaps analogous to the high affinity acetylcholine binding observed in electric fish receptor, was determined.

Acetylcholine↗

Patterns of the use of benzodiazepines in Australia.

In six suburban areas of Sydney, chosen to provide a socioeconomic cross-section of the city, complete records of dispensing of benzodiazepine were collected over a four-week period. These drugs constituted 3.7% of all dispensing, female patients outnumbered males by 2.3:1, and 98% of patients were over 20 years of age. The predominance of females, and higher age groups was found in all the areas studied, but no socioeconomic correlation was detected in the use of the drugs. Analysis of national dispensing figures confirmed the higher consumption in higher age groups, and revealed no heterogeneity in per capita prescribing rates amongst the States.

Adolescent↗

A cluster of fulminant myocarditis cases in children, Baltimore, Maryland, 1997.

The true incidence of myocarditis in children is difficult to estimate because many mild cases go undetected. This study describes an unusual cluster of myocarditis cases that occurred in young children living in the greater Baltimore area between May and October 1997. A search of multiple comprehensive databases and interviews with area pediatric cardiologists were conducted to identify unreported cases and determine the background rate of myocarditis in the area. Seven cases of myocarditis were found as well as two with a similar clinical picture and myocardial fibrosis on tissue examination. Six case patients with active myocarditis and one child with fibrosis died. The case children were predominantly black (eight of nine) and male (seven of nine), with no identifiable risk factors. The disease was characterized by a fulminant course with malignant arrhythmias. The greatest number of pediatric myocarditis deaths reported in 1 year prior to 1997 was three. Myocardial tissues were examined using immunohistochemistry, in situ hybridization, and polymerase chain reaction but no etiologic agent was identified. This outbreak is unusual because of both the number of cases and the fulminant course of the disease in this group of children.

Arrhythmias, Cardiac↗

The modulatory effect of anti-idiotypic antibody on hybridoma cells secreting antibody to human myelin basic protein peptide 80-89.

The idiotype (ID) of an antibody is postulated to be involved in immunoregulation by means of the immune network. This hypothesis was examined by studying the effect of a monoclonal antibody (MAb) anti-ID on hybridoma cells secreting an ID-bearing MAb, 845D3, to human myelin basic protein (MBP) peptide 80-89. The monoclonal anti-ID (IgM/kappa), reacted with heavy and light chains of 845D3, an IgG1/kappa MAb, but not with a control MAb of the same isotype specific for an MBP peptide differing by one amino acid residue. Fluorescence-activated cell sorting revealed IgG heavy and kappa light chains on the surface and in the cytoplasm of 90% or more of the 845D3 cells. The anti-ID did not react with the surface of the 845D3-secreting cells, and reacted with the cytoplasm of 14-18% of these cells. In spite of the absence of cell surface ID, the anti-ID significantly decreased antibody production by the ID-secreting cells. There was no effect of the anti-ID on control hybridoma cells secreting MAb to another MBP cells. There was no effect of the anti-ID on control hybridoma cells secreting MAb to another MBP peptide. Anti-ID exerted no cytotoxic effect on ID-bearing hybridoma cells and in fact caused a marginal increase in their proliferation compared to control MAb. These results indicate that an anti-ID may alter the antibody production of ID-secreting cells in a specific manner and without cytotoxicity. This may be one of the means for controlling an immune response against MBP generated by the cells of the immune system or in situ within the nervous system. The cellular mechanism(s) for this effect remains to be defined.

Animals↗