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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 199 records · Page 11Linked to original sources
PubMed1985

Failure of superoxide dismutase to alter equine arachidonic acid-induced platelet aggregation, in vitro or ex vivo.

Superoxide dismutase (SOD), a free radical scavenger with anti-inflammatory activity, was administered IM to horses. Ex vivo platelet aggregation in response to arachidonic acid was monitored to determine whether exogenous SOD altered equine platelet prostaglandin metabolism. Preparations of platelet-rich plasma obtained before SOD administration were incubated with different concentrations of SOD and were aggregated with arachidonic acid. Superoxide dismutase did not exert a demonstrable effect, either ex vivo or in vitro. Aspirin abolished arachidonic acid-induced platelet aggregation in vitro. This indicates that SOD (in the resting state) does not exert an effect on platelet-derived free radicals that could alter the arachidonic acid pathway of equine platelets, that equine platelets do not release free radicals, or that equine platelets are insensitive to the products formed from free radicals by SOD.

Animals↗
PubMed1985

Congenital heart disease: functional abilities in young adults.

Muscular endurance, motor abilities, childhood activities, school experiences, work plans, and social behaviors of 188 young adults aged 16 to 23 years with congenital heart disease were examined. The subjects had isolated aortic stenosis, pulmonary stenosis, or tetralogy of Fallot. Overall, physical function scores were slightly below average. Childhood activities had been affected in about 30% of the cases, but seriously disrupted in only 17%. School experiences had been positive, and 68% of the students in school planned to continue on to college or university or were already there. Normal social behavior was much more common than antisocial behavior. Subjects had few specific health worries, although many wanted more information about lifestyle implications of their heart disease.

Adolescent↗
PubMed1985

Hemodynamic and plasma catecholamine responses to epinephrine-containing perianal lidocaine anesthesia.

Despite the frequent use of large volumes (30-40 ml) of epinephrine-containing local anesthetic solutions for ano-rectal surgery, little is known about the anesthetic-induced hemodynamic consequences. Therefore, we measured the heart rate, blood pressure, and plasma catecholamine (norepinephrine and epinephrine) responses to the perianal injection of 40 ml of 0.5% lidocaine alone (n = 8) or 0.5% lidocaine with 1:200,000 epinephrine (n = 10) in 18 healthy adults undergoing outpatient ano-rectal surgery. The mean +/- SEM plasma epinephrine concentration increased from a baseline of 42 +/- 7 pg/ml to a peak of 622 +/- 94 pg/ml 4 min after injection of epinephrine-containing anesthetic (P less than 0.001), whereas lidocaine alone increased the mean plasma value from 36 +/- 9 pg/ml (baseline) to only 69 +/- 16 pg/ml (not significantly different) at its peak. Despite the increases in plasma epinephrine levels in the group receiving epinephrine-containing anesthesia, no changes in blood pressure, heart rate, or plasma norepinephrine levels were observed. Given the advantages (including prolongation of the duration of anesthesia) of adding epinephrine to perianal local anesthetics, our data support its safe use in healthy adults.

Adult↗
PubMed1984

A comparison of the artificial pancreas (glucose controlled insulin infusion system) and a manual technique for assessing insulin sensitivity during euglycaemic clamping.

Two main methods are available for assessing insulin sensitivity with the hyperinsulinaemic euglycaemic clamp technique: one employs a glucose-controlled insulin infusion system (the Biostator) with automatic feedback control; the second depends on frequent glucose measurement and the use of an algorithm and a pocket calculator ('manual') to determine the glucose infusion rate. The amount of glucose infused is a measure of insulin sensitivity. The efficiency of the two methods was compared in nine normal subjects (seven lean, two obese). After an overnight fast subjects were infused with insulin at 50 mU X kg-1 X h-1 for 2 h; this rate was doubled during the first 10 min for the manual technique. Blood glucose averaged 4.7 +/- 0.1 and 4.8 +/- 0.1 mmol/l from 0 to 120 min for Biostator and manual techniques and did not deviate significantly from the desired level. Variability of the clamp was also similar over the same period (coefficient of variation 5.1 +/- 0.6% and 6.4 +/- 0.7%, Biostator and manual). Glucose infused to maintain steady state from 60 to 120 min was higher, however, with the manual than the Biostator method (5.7 +/- 0.6 versus 4.4 +/- 0.6 mg X kg-1 X min-1, p less than 0.01) even when the loading dose was omitted, although the two methods correlated closely (p less than 0.05). Glucose infusion rate varied more from minute to minute with the Biostator (coefficient of variation 28.8 +/- 3% versus 12.2 +/- 2.1%). Steady-state serum insulin levels (30-120 min) were the same during both methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Measurement of urinary leukocyte esterase activity: a screening test for urinary tract infections.

We evaluated the efficacy of testing for the presence of esterase (an enzyme released only from leukocytes) in the urine as an indicator of the presence of pyuria. We hypothesized that a "dipstick" test for urinary leukocyte esterase activity would be a rapid and simple screening technique for detecting urinary tract infections (UTI). To test our hypothesis we collected fresh urine specimens from 203 patients (148 outpatients, 55 inpatients) with a suspected UTI. Each specimen was divided into three aliquots; one was used for reagent strip testing (for leukocyte esterase, nitrite, and blood), one for microscopy, and one for culture. Of the 203 specimens, 49 showed significant bacteriuria (greater than or equal to 10(5) organisms/mL). The leukocyte esterase test was 100% sensitive (0% false negatives) with a 76% specificity (24% false positives) in predicting significant bacteriuria. Although a positive nitrite reaction was more specific (99% specificity, 0.6% false positives), it was insensitive (27% sensitivity, 73% false negatives). The high sensitivity of reagent strip leukocyte esterase testing for pyuria makes it a valuable screening test that should lead to the elimination of many needless urine cultures and microscopic examinations.

Adult↗
PubMed1984

Dexamethasone causes less steroid-induced alkalemia than methylprednisolone or hydrocortisone.

Corticosteroid-induced metabolic alkalemia is an important ICU problem because many of these patients may compensate by alveolar hypoventilation. The effects of 3 commonly used steroids on arterial pH, PaCO2, and serum bicarbonate concentrations were studied in 24 healthy male baboons randomly divided into 3 groups. Each group of 8 animals received 7-day dose-equivalent courses of either hydrocortisone (300 mg daily), methylprednisolone (60 mg daily), or dexamethasone (15 mg daily). Treatment with either hydrocortisone or methylprednisolone increased arterial pH (p less than .05) and serum bicarbonate levels (p less than .01) and the animals receiving hydrocortisone showed significant (p less than .05) compensatory alveolar hypoventilation. Dexamethasone therapy did not cause any of these steroid-induced changes.

Acid-Base Imbalance↗
PubMed1984

Right ventricular size and ventricular septal motion after repair of atrial septal defect in children.

An enlarged right ventricle and abnormal ventricular septal motion are characteristic echocardiographic features of atrial septal defect and often persist after the defect has been completely closed, even when the operation clinically is judged to be successful. These features were examined retrospectively 15 to 21 months after operation in a group of children whose atrial septal defect had been closed between January 1976 and July 1979. Despite satisfactory postoperative results in all, about two thirds had an enlarged right ventricular dimension and about the same number had abnormal septal motion when examined echocardiographically an average of 18 months after operation. The best operative strategy seems to be to operate while the right ventricular end-diastolic dimension is still relatively small in echocardiographic terms.

Adolescent↗
PubMed1984

Comparative effects of two cimetidine regimens on 24-hour intragastric acidity in patients with asymptomatic duodenal ulcer.

The effect of 600 mg of cimetidine given twice daily on 24-hour intragastric hydrogen ion (H+) concentration was compared with that of the standard regimen of 300 mg of cimetidine given four times daily in six patients with asymptomatic duodenal ulcer. According to the double-blind, Latin-square, repeated-measures design, all subjects followed each cimetidine regimen and a placebo regimen for one week. Acid secretion studies and determinations of drug and gastrin levels in the blood were carried out on the last day of each treatment week. Although 600 mg of cimetidine BID suppressed H+ after breakfast and during the night, compared with placebo treatment (P less than 0.01), the 300-mg QID regimen suppressed H+ only after breakfast and supper (P less than 0.05). A higher percentage of pH readings greater than or equal to 3.0 were obtained with 600 mg of cimetidine BID than with 300 mg of cimetidine QID during the night (P less than 0.05); compared with percentages when placebo was taken, the percentages of pH readings greater than or equal to 3.0 were greater both overnight and during a 24-hour period only when 600 mg of cimetidine was given BID (P less than 0.01). The observed difference in intragastric H+ suppression after each regimen could not be explained by variations in serum concentrations of cimetidine or serum concentrations of gastrin. Despite similar peaks of serum cimetidine after evening doses of 300 or 600 mg of cimetidine, nocturnal intragastric acidity was lower in subjects given 600 mg BID. Further, H+ levels after lunch were similar in both cimetidine-treated groups, despite markedly higher serum cimetidine concentrations in patients receiving 600 mg BID. Pharmacokinetic studies showed equivalent elimination half-times and 24-hour areas under the curve of serum cimetidine concentration in patients on the two cimetidine regimens. Postprandial integrated gastrin responses were of similar magnitude in patients on either cimetidine regimen. There was no significant difference in mean serum gastrin concentrations during the night in placebo-treated and cimetidine-treated patients. Only a weak correlation was observed between H+ and serum gastrin concentration. Although a fluctuation of the H+:gastrin ratio occurred after each meal in all groups, the ratio was suppressed by both dosages of cimetidine. The findings suggest that a regimen of 600 mg of cimetidine BID is superior to the standard regimen of 300 mg QID in suppressing intragastric acidity in patients with asymptomatic duodenal ulcer.

Adult↗
PubMed1983

Differential changes of autonomic nervous system function with age in man.

To assess the relationship between aging and autonomic nervous system function, cardiovascular and pupillary autonomic nervous system reflexes were measured in subgroups of 103 normal male subjects ranging in age from 19 to 82 years (mean age = 39 years). Both the plasma norepinephrine level, a measure of cardiovascular sympathetic nervous system activity, and the mean arterial blood pressure increased with age (r = 0.68 and 0.67, respectively, both p less than 0.001). In contrast, the plasma epinephrine level, a measure of adrenomedullary sympathetic nervous system activity, was unrelated to age (r = 0.08, p = NS). Respiratory variation of heart rate during beta-adrenergic blockade, an index of cardiac parasympathetic nervous system activity, was reduced in older subjects (r = -0.54, p less than 0.001). Thus, there was evidence of an age-related increase of cardiovascular sympathetic nervous system activity and a reduction of cardiac parasympathetic nervous system activity. These findings are consistent with the hypothesis that there is sympathetic nervous system and parasympathetic nervous system compensation of cardiovascular function in response to an age-related decrease in baroreceptor sensitivity. However, dark-adapted pupil size during parasympathetic nervous system blockade, an index of iris sympathetic nervous system activity, declined with age (r = -0.81, p less than 0.001). The latency time for the pupillary response to a light stimulus, an index of iris parasympathetic nervous system activity, was prolonged in older subjects (r = 0.58, p less than 0.001). Thus, both sympathetic nervous system and parasympathetic nervous system inputs to the iris were diminished in older subjects, findings consistent with the generalized decrease of peripheral somatic nerve function that has been reported with aging in man. It is concluded that autonomic nervous system function also declines with aging, but that other age-related changes such as a decline of baroreceptor sensitivity may lead to compensatory autonomic nervous system response, which could mask underlying functional defects.

Adult↗
PubMed1983

Dopamine blockade inhibits starvation ketosis in man.

The effects of dopamine blockade on the endocrine and metabolic response to starvation have been investigated by administration of metoclopramide, 30 mg daily, or placebo to five normal subjects fasted for sixty hours on two occasions. Blood glucose and alanine concentrations fell with starvation and metoclopramide had no further effect. Concentrations of the other gluconeogenic precursors, lactate and pyruvate, were also unaffected by metoclopramide. The rise in circulating ketone body concentrations with fasting was impaired by metoclopramide, significantly from 44 h onwards (blood total ketone body concentration at 60 h, 3.42 +/- 0.94 mmol/l with placebo; 2.08 +/- 0.67 mmol/l with metoclopramide, P less than 0.05). Blood glycerol and plasma non-esterified fatty acids (NEFA) levels rose with starvation, and metoclopramide had no further effect. Serum insulin concentrations remained low with fasting, while circulating glucagon and growth hormone levels rose. Similar changes were noted with both metoclopramide and placebo. Serum prolactin concentrations during starvation were elevated two to four fold by metoclopramide. The inhibitory effect of dopamine blockade on ketosis thus occurred despite hyperprolactinaemia, and did not result from measurable alterations in insulin, glucagon or growth hormone secretion. The data suggest a stimulatory role for endogenous dopamine on starvation ketonaemia in man.

Acidosis↗
PubMed1983

Longterm pergolide treatment of acromegaly.

The effect of pergolide mesylate, a new potent longacting dopamine agonist, was investigated in eight patients with active acromegaly, none of whom had received pituitary irradiation. Patients were assessed at different dose levels for clinical response and biochemical response by measuring mean fasting growth hormone (GH), mean ambulant GH and glucose-induced GH response. Six patients had definite clinical improvement. No major side effects were noted. All patients showed a statistically significant reduction in GH, although in two reduction was not below 75% of pretreatment levels. On 500 micrograms pergolide daily the overall response for the group of eight patients was a reduction of fasting serum GH, mean ambulant GH and of GH response to glucose to 55% of pretreatment values. When the daily dose was increased to 1000 micrograms there was a further significant reduction in GH in some patients; on this dose the response for the group was a decrease in fasting serum GH and mean ambulant GH to 40% of pretreatment values. In three patients GH concentrations of 5 mU/l or less were achieved. In two patients the daily dose was increased to 1500 micrograms but no extra benefit was obtained. We conclude that pergolide given once daily has a beneficial effect in acromegaly, with significant reduction in serum GH; it promises to be a useful therapeutic agent.

Acromegaly↗
PubMed1983

Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours.

Basal and stimulated secretion of N-terminal pro-opiocortin (Pro-gamma-MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel-chromatographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1-39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.

ACTH Syndrome, Ectopic↗