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Biomedical subjects

J N Carter

Publications and source records attributed to J N Carter.

At least 19 recordsLinked to original sources

Noninvasive laser-based blood pressure measurement in rabbits.

To obtain serial blood pressure measurements without trauma in rabbits, we developed a laser-based method which permits noninvasive determination of systolic and diastolic arterial blood pressure. The ease and accuracy of this method were evaluated over a range of blood pressures in five New Zealand White rabbits. Laser-based pressures from the central ear artery were compared with cannula-based pressures from the contralateral central ear artery. Pressures were measured before and during infusions of saline (control), nitroprusside, or epinephrine, and following induction of anesthesia. Noninvasive measurements correlated highly with direct measurements (systole: r = 0.89; diastole: r = 0.93). The difference between the non-invasive and direct pressure measurements during saline, nitroprusside, and epinephrine infusions, and following anesthesia, respectively, were (mean +/- SD, systole/diastole): 4.2 +/- 2.4 (P = NS)/9.3 +/- 1.4 (P less than .001), 4.1 +/- 1.6 (P less than .02)/3.2 +/- 1.1 (P less than .01), 0.6 +/- 2.4 (P = NS)/-3.0 +/- 2.7 (P = NS), and -5.1 +/- 2.9 (P = NS)/0.3 +/- 1.3 (P = NS). The noninvasive method did not result in observable agitation of the animals. To optimize results, visual inspection was required to assure that the instrument's diaphragm was not deformed or dried from previous use, and that the diaphragm was placed over the center of the arterial lumen. It was also necessary to dim room lights and to direct heating lights away from the ears to avoid degrading light signal quality. These results, albeit involving a small number of animals, indicate the potential utility of this method in the study of chronic pathophysiological processes requiring long-term repeated determination of systolic and diastolic blood pressure.

Animals

Left ventricular diastolic and systolic performance during chronic experimental aortic regurgitation.

To study the time course of left ventricular structural and functional responses to chronic aortic regurgitation, aortic regurgitation was surgically induced in rabbits, and Doppler echocardiography was performed preoperatively and serially postoperatively for up to 2.5 yr. Twenty-five New Zealand White rabbits underwent surgical induction of aortic regurgitation and 13 control animals underwent sham operation. Left ventricular endocardial and epicardial surfaces were digitized from M-mode echocardiograms to measure the rates of change of cavity dimensions and wall thicknesses during diastolic relaxation and systolic contraction. Aortic regurgitant animals developed left ventricular dilatation and eccentric hypertrophy that remained relatively stable throughout the follow-up period. Compared with baseline values, left ventricular mass increased 120% and left ventricular internal dimension at end diastole increased 40%, whereas posterior wall thickness at end diastole and fractional shortening remained relatively stable. Left ventricular diastolic performance was enhanced at 6 mo after operation, a finding associated with increased volume load and heart rate following induction of aortic regurgitation. Diastolic performance was then reduced at 12 mo after operation and demonstrated no further decline throughout the remainder of the follow-up period. In contrast, left ventricular systolic performance was not altered following operation and remained preserved until the final assessment at up to 2.5 yr. Thus alterations in diastolic performance occurred without impairment of systolic performance during long-term follow-up of chronic experimental aortic regurgitation.

Animals

Graves' ophthalmopathy--a clinical review.

Graves' ophthalmopathy occurs in 2% to 7% of patients with Graves' disease with the major manifestations being proptosis, ophthalmoplegia, optic neuropathy and/or eyelid retraction. Although autoimmune in nature, the precise pathophysiology is unknown. The course of the ophthalmopathy is not influenced by the mode of treatment of the hyperthyroidism. In addition to restoration of the euthyroid state, the aims of treatment include relief of eye pain, correction of extraocular muscle dysfunction, protection of visual acuity and improvement of appearance. Specific therapy depends on the severity of the ophthalmopathy and varies from lubricating eye drops in mild disease to high-dose steroids and radiotherapy or decompressive surgery in severe cases.

Eye Diseases

Effects of combined insulin-sulfonylurea therapy in type II patients.

We conducted a double-blind crossover study to determine which patient characteristics best predict a beneficial response to combined insulin-glyburide therapy. Glyburide (15 mg/day) or placebo was added to the treatment regimen of 31 insulin-treated type II (non-insulin-dependent) diabetic subjects. During glyburide therapy, there was a significant improvement in glycemic control with a reduction in glycosylated hemoglobin from 9.9 +/- 1.3 to 9.1 +/- 1.3% (P less than .001). Patients who responded had higher fasting C-peptide levels (P less than .001) and shorter durations of insulin therapy (P less than .01) than those who did not respond. Glyburide withdrawal was associated with a greater than expected deterioration in glycemic control. Patients on insulin therapy for greater than 8 yr are unlikely to benefit significantly from the addition of glyburide to their treatment regimen.

Aged

Candidiasis-endocrinopathy syndrome with progressive myopathy.

A women suffering from the candidiasis-endocrinopathy syndrome, developed severe myopathy in her fourth decade and died from it at the age of 37 years. Associated conditions were hypoparathyroidism, vitiligo, chronic mucocutaneous candidiasis, short stature, intellectual disability, ovarian failure and alopecia totalis. Muscle biopsy findings were non-specific with focal atrophy of type 2 fibres. Serum immunoglobulin levels were normal. The only demonstrable abnormalities of her immune system were impaired T-cell function and antibody production by B-cells (detectable to smooth muscle, mitochondria and gastric parietal cells). The T-cell abnormality may have been part of a more generalized cell defect, resulting from an unidentified genetic abnormality, whilst the circulating antibodies could have been a response to tissue damage. There was no convincing evidence of primary autoimmune damage.

Adult

Hypertrophic and functional response to experimental chronic aortic regurgitation.

Aortic regurgitation was induced by retrograde perforation of an aortic valve cusp under hemodynamic guidance in 12 New Zealand White rabbits. Regurgitant fraction was documented by electromagnetic flow probe and six sham-operated animals served as controls. Two-dimensional, M-mode and Doppler echocardiography was performed pre-operatively and serially post-operatively for 3 to 6 months. Animals with aortic regurgitation developed progressive left ventricular dilatation and eccentric hypertrophy. Left ventricular internal dimension at end-diastole and left ventricular mass were increased from baseline values by 41 and 94% (P less than 0.001), respectively; fractional shortening was stable while end-systolic stress increased 50% (P less than 0.01. Thus, acutely induced aortic regurgitation in rabbits results in a chronic model which may be appropriate for stimulation of the hypertrophic response to aortic regurgitation in humans.

Animals

Reduced adrenal androgens in patients with myotonic dystrophy.

Endocrine disturbances associated with myotonic dystrophy (MD) include testicular atrophy, hyperinsulinemic glucose intolerance, thyroid abnormalities, and low or low normal urinary 17-ketosteroid (17-KS) excretion. Since the major circulating precursors of urinary 17-KS are dehydroepiandrosterone sulfate (DHAS) and dehydroepiandrosterone (DHA), a decrease in adrenal androgen production has been suggested. This possibility was studied in 19 MD patients and 19 age- and sex-matched normal subjects. Each patient had a 24-h urine collection for 17-KS and cortisol determinations, a 4-h iv infusion of 25 micrograms tetracosactrin with serial measurements of serum DHAS, DHA, and cortisol, and an insulin-induced hypoglycemia test. Sixteen patients had 0800 and 2400 h serum collections for cortisol estimations. Serum DHAS [1.0 +/- 0.5 (+/- SD) vs. 3.9 +/- 1.9 mumol/liter; P less than 0.0005] and DHA (5.9 +/- 2.7 vs. 11.0 +/- 7.1 nmol/liter; P less than 0.005) levels were significantly lower in MD patients than in normal subjects; cortisol levels were higher (540 +/- 222 vs. 394 +/- 128 nmol/liter; P less than 0.01), almost certainly a reflection of stress. A normal diurnal cortisol rhythm was found in all 16 subjects. Cortisol responses to insulin-induced hypoglycemia were normal, increasing from 345 +/- 243 nmol/liter to a maximum of 831 +/- 282 nmol/liter. Urinary 17-KS excretion was low or low normal, while urinary cortisol levels were normal in 18 and mildly elevated in 1 patient. There was a significant correlation between 17-KS and DHAS levels (r = 0.46; P less than 0.05). DHAS, DHA, and cortisol responses to tetracosactrin infusion were similar in patients and normal subjects. It is concluded that 1) in MD patients, serum DHAS and DHA concentrations are significantly lower than those in normal subjects, explaining the frequent reports of low or low normal 17-KS excretion; 2) the reduced DHAS and DHA concentrations are most likely due to decreased production rather than increased clearance; and 3) glucocorticoid production is normal.

Adolescent

The relationship of adrenal androgens to the secretory patterns for cortisol, prolactin, and growth hormone during early puberty.

Serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHA-sulfate), cortisol, prolactin, and growth hormone were measured at half-hour intervals for 24 hr in five healthy children aged 8--13 yr. Their adolescent development was assessed by clinical staging, plus determinations of serum FSH, LH, testosterone and estradiol during both wakefulness and sleep. Correlative analysis indicates that there was synchronous secretion of DHA and cortisol, implying regulation of both by ACTH. With advancing age and sexual maturation, there was a progressive rise in mean serum DHA and DHA-sulfate levels, but no similar change in serum cortisol concentrations. There was evidence for enhanced secretion of both growth hormone and prolactin during sleep in all subjects (including one who was hyperprolactinemic), but there was no obvious relationship between levels of these pituitary hormones and the early pubertal rise in adrenal androgens.

Adolescent

Prolactin-secreting tumors and hypogonadism in 22 men.

We studied 22 men with prolactin-secreting pituitary tumors and hypogonadism. Twenty complained of impotence, nine had visual impairment, and three experienced galactorrhea. None of the 17 patients undergoing operation or radiotherapy, or both, were subsequently normoprolactinemic. In all 13 patients treated with bromocryptine major clinical improvement was associated with a decrease in serum prolactin levels and in nine with an increase in serum testosterone. Two patients receiving testosterone replacement therapy showed improved potency only after bromocryptine was administered. The results indicate that hyperprolactinemia frequently induces hypogonadism in men, that bromocryptine ameliorates symptoms of disease previously unchanged by operation or radiotherapy, and that the impotence observed may not be solely the result of hypogonadism.

Adenoma, Acidophil

Nursing-mediated prolactin and luteinizing hormone secretion during puerperal lactation.

Alterations in plasma prolactin (PRL) concentrations in response to nursing in puerperally lactating women are often significant beyond the 90th postpartum day, yet the increment appears unrelated to the frequency or duration of the nursing stimulus. Tonic gonadotropin secretion is low, assuming a more episodic secretory pattern either when the frequency of breast-feeding is reduced or when weaning takes place. Significant increments in peripheral concentrations of luteinizing hormone can be seen in response to weaning coincident with a fall in peripheral plasma PRL concentration. At the same time, peripheral estrogen concentrations increase, suggesting that a specific set point for ovarian responsiveness to gonadotropins exists. Whether this set point is related solely to the peripheral concentration of gonadotropins or whether it is also related to the peripheral PRL concentration is not known at this time.

Female

Hormonal changes in girls with precocious adrenarche: a possible role for estradiol or prolactin.

Serum concentrations of dehydroepiandrosterone, DHA sulfate, estradiol, and prolactin in 20 girls with precocious adrenarche were compared with those of healthy girls of varying age and degrees of breast and sex hair development. Production of adrenal androgens, as reflected by serum DHA and DHA-sulfate concentrations, was significantly increased in PA above that in age-matched control subjects. Surprisingly, in spite of their lack of breast growth, the patients with PA also had serum estradiol levels that were higher than in the prepubertal girls and similar to those found in girls with both breast and pubic hair development. Serum prolactin concentrations in the patients with PA were not increased over those of the age-matched (less than 8 years) prepubertal girls. In the older prepubertal ( greater than 8 years) and early pubertal girls serum prolactin levels were lower. The finding of increased estradiol levels suggests that precocious adrenarche is not a distinct endocrine entity, but merely represents a variant of early adolescence in which estrogen secretion is sufficient to influence adrenal 3beta-hydroxysteroid dehydrogenase activity with a resultant rise in DHA production, but not sufficient to produce clinically apparent breast changes. The data do not support a similar role for prolactin.

Adrenal Cortex

Effects of triiodothyronine administration in patients with chronic renal failure.

Clinically euthyroid patients with severe, chronic, non-thyroidal illnesses usually have decreased serum total and absolute free T3 concentrations. Since T3 is the metabolically more active of the two thyroid hormones, it has been suggested that these patients may be hypothyroid and thus may benefit from T3 therapy. To test this hypothesis, five patients with chronic renal failure requiring maintenance haemodialysis were treated with 5 microgram T3 eight hourly, increasing at three weekly intervals to 10 microgram eight hourly, 20 microgram eight hourly and finally 30 microgram eight hourly. The mean +/- SD serum T3 level did not change over the 12 week period (1.42 +/- 0.17 vs. 1.41 +/- 0.26 nmoll-1 whilst the mean serum T4 and TSH levels fell from 87.0 +/- 15.2 to 47.5 +/- 18.8 nmoll-1 and 1.9 +/- 0.9 to 1.3 +/- 1.6 mUl-1 respectively. Only the change in T4 levels was significant (P less than 0.005). A significant decrease in mean serum T4 levels was apparent even after the treatment period with 5 microgram T3 eight hourly (87.0 +/- 15.2 vs. 51.2 +/- 15.7; P less than 0.005). The mean fasting serum triglyceride level fell from 1.16 +/- 0.74 to 0.94 +/- 0.74 mmoll-1 (P less than 0.05) and the mean fasting serum cholesterol level fell from 6.06 +/- 1.13 to 4.69 +/- 1.10 mmoll-1 (P less than 0.05). There were no subjective improvements in any of the patients. From the marked changes in serum T4 levels during the administration of T3, it is concluded that, prior to treatment, the patients were biochemically euthyroid and not hypothyroid and thus did not require T3 therapy.

Adult

Adrenocortical function in hyperprolactinemic women.

To study the effects of prolactin (PRL) on adrenocortical function in humans, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta) and testosterone (T) were measured in serum obtained from 35 hyperprolactinemic women with galactorrhea and amenorrhea before and after treatment with bromocriptine-induced fall in mean PRL levels from 82 +/- 8 (SE) to 14 +/- 2 ng/ml (n = 39, P less than 0.0005), DHAS fell from 322 +/- 21 to 237 +/- 21 microgram/dl (n = 39); P less than 0.0005), DHA fell from 492 +/- 47 to 378 +/- 30 ng/dl (n = 39; P less than 0.01) while T (n = 16) and delta (n = 13) levels were unchanges (44 +/- 4 vs. 49 +/- 4 ng/dl and 280 +/- 55 vs. 236 +/- 40 ng/dl, respectively). In addition, 4 women were infused iv with 25 microgram synthetic ACTH over 4 h and serial blood samples drawn while hyperprolactinemic, and again 2-4 months later following normalization of PRL levels by bromocriptine. Although pre-infusion levels of DHAS were lower when PRL levels were normalized, no significant differences in responses of circulating DHAS, DHA, T, cortisol and 17-hydroxyprogesterone concentrations were detected between the two infusions. Since DHAS is virtually an exclusive product of the adrenal cortex, and since high PRL levels appear to inhibit ovarian steroid production, the findings suggest that hyperprolactinemia selectively stimulates adrenocortical androgen production.

Adrenal Cortex Hormones