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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 217 records · Page 12Linked to original sources
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↗
PubMed1983

Fenfluramine lowers plasma norepinephrine in overweight subjects.

The effect of fenfluramine on sympathetic nervous system activity was determined in 12 normotensive, obese men. Supine plasma norepinephrine (NE) concentrations decreased (p less than 0.001) from pretherapy levels (298 +/- 39 pg/ml) after one (166 +/- 30 pg/ml) and four weeks (171 +/- 28 pg/ml) of fenfluramine (60 mg daily). Fenfluramine did not alter the sympathetic nervous system responses to orthostasis or exercise. Fenfluramine-induced decreases in heart rate (72 +/- 3 to 67 +/- 4 beats/min, p less than 0.01) and mean arterial blood pressure (90 +/- 2 to 81 +/- 2 mmHg; p less than 0.005) were observed after only one week of therapy despite no significant change in body weight. We conclude that fenfluramine may be a useful agent in the treatment of patients with sympathetic hyperactivity. The effects of fenfluramine on given subsets of patients and control subjects are also defined.

Adult↗
PubMed1982

Irreversible blockade of responses to a partial agonist acting at the histamine H1-receptor.

N,N-Diethyl-2-(1-pyridyl)-ethylamine (E-2-P) has been shown previously to behave as a simple partial agonist at the histamine H1-receptor of guinea-pig ileum. When isolated longitudinal muscle strips from this preparation were tested with E-2-P before and after blockade with 2-haloalkylamines, it was found that these agents produced an irreversible shift to the right in the dose-response curve without significant depression of the maximum response even at very high antagonist concentrations. Under these circumstances the maximum response to the partial agonist may exceed the maximum response to histamine itself since the latter shows a much diminished maximum response at a very high concentrations of antagonist. These findings are not readily explicable in terms the usual "receptor-reserve' model of the histamine receptor system in ileum. A tentative explanation is provided, involving interaction with the antagonist at more than one site.

Animals↗
PubMed1982

Mechanism of acquired right ventricular outflow tract obstruction in patients with ventricular septal defect: an angiocardiographic study.

Right ventricular outflow tract obstruction can complicate the natural history of patients with isolated ventricular septal defect. Although numerous pathologic mechanisms may be responsible for this phenomenon, it is less clear what the frequency is of each of these mechanisms in any cohort of patients studied in a single institution. We identified 20 patients with isolated ventricular septal defect from 1970 to 1981 who acquired a right ventricular outflow tract gradient of 25 mm Hg or more. They ranged in age at the initial catheterization investigation from 4 days to 23 months and at the subsequent study from 13 months to 8 years. Angiographically, 2 mechanisms were implicated in the 20 patients. Hypertrophy of right ventricular anomalous muscle bundles was identified in 19 of the 20 while hypertrophy of a malaligned infundibular septum (that is, classic tetralogy type) was identified in only 1 patient. These data indicate that acquired right ventricular outflow tract obstruction is rarely of the classic tetralogy type.

Aortic Valve↗
PubMed1982

HLA phenotypes in Mexican Americans with tuberculosis.

HLA-A, -B, and -C phenotype distributions in 100 Mexican Americans with active tuberculosis were compared with HLA phenotypes in 50 healthy, tuberculin-skin-test-positive and 50 healthy, tuberculin-skin-test-negative Mexican Americans. Although there existed differences in the phenotype frequencies of 5 antigens (Aw30, Aw33, B7, B15, and B17) among the 3 study groups, these differences were not significant using p values that were corrected for the number of antigens tested. Thus, susceptibility (or resistance) to tuberculosis in Mexican Americans does not appear to be linked to a specific HLA-A, -B, or -C phenotype.

Adult↗
PubMed1982

Quantitative evaluation of cardiac parasympathetic activity in normal and diabetic man.

Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inversely related to the RR variation (r = 0.89, P less than 0.01). Heart rate was increased (P less than 0.0001) and RR variation decreased (P less than 0.05) during beta-adrenergic stimulation with isoproterenol and during parasympathetic blockade with atropine (both P less than 0.0001). Hence, the cardiac effects of beta-adrenergic stimulation may mimic the effects of diminished parasympathetic function. To evaluate parasympathetic control of RR variation, independently of possible effects of increased sympathetic activities, studies were performed during beta-adrenergic blockade with propranolol. RR variation during propranolol was less both in 14 diabetic subjects without clinical symptoms of autonomic neuropathy (P less than 0.005) and in 8 diabetics with clinical symptoms of autonomic neuropathy (P less than 0.001) when compared with 22 age-comparable normal subjects. The measurement of RR variation was very reproducible with a day-to-day coefficient of variation of 9.7 +/- 2.8% (x +/- SEM) in diabetic subjects with stable hyperglycemia. It is concluded that supine RR variation during a deep respiratory rate and during beta-adrenergic blockade is a sensitive, quantitative, and reproducible method to evaluate parasympathetic nervous activity in normal and diabetic subjects. Furthermore, cardiac parasympathetic activity may be diminished in diabetic subjects before clinical symptoms of autonomic neuropathy are evident.

Adult↗
PubMed1980

A scleral buckle pressure gauge for continuous monitoring of intraocular pressure.

An implantable variable resistance pressure gauge has been constructed from a conductive elastomere in the form of a scleral buckle which is suitable for recording intraocular pressure in vivo continuously over an indefinite period of time. The similarity of the pressure transducer to the standard scleral buckles used to reduce retinal detachments suggests that it will be tolerated over a period of years without significant effect on intraocular pressure. The electrical output from these pressure gauges appears to be both well defined and of sufficient magnitude to operate a valve to control intraocular pressure.

Animals↗
PubMed1979

Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary.

Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethmide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients.

Adrenocorticotropic Hormone↗
PubMed1977

The effect of 1alpha-hydroxyvitamin D3 in pre-dialysis renal bone disease.

Assessment of 18 azotaemic patients treated with long-term 1alpha-hydroxyvitamin D3 (1alpha-OHD3) confirms the generally favourable effect of this analogue of 1,25-dihydroxyvitamin D3 in azotaemic osteodystrophy. Growing children with radiological rickets respond very well as do adults showing mild hyperparathyroidism with or without osteomalacia. However, patients with severe 'pure' hyperparathyroidism and features of autonomy do not respond well and in such patients 1alpha-OHD3 alone should be avoided. Phosphate restriction and occasionally a sub-total parathyroidectomy may be indicated in these patients.

Adolescent↗