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Biomedical subjects

J M Kaufman

Publications and source records attributed to J M Kaufman.

At least 109 records · Page 6Linked to original sources
PubMed1990

Neuroendocrine regulation of pulsatile luteinizing hormone secretion in elderly men.

Leydig cell function is driven by LH, secreted in a pulsatile manner by the anterior pituitary in response to episodic discharge of hypothalamic LHRH into the pituitary portal circulation, under control of a yet to be defined neural mechanism, the "hypothalamic LHRH pulse generator". The normal aging process in elderly men is accompanied by a decline in Leydig cell function. Whereas primary testicular factors undoubtedly play an important role in the decrease of circulating (free) testosterone levels with age, recent studies demonstrated that aging also affects the central compartment of the neuroendocrine cascade. Hypothalamic alterations comprise changes in the regulation of the frequency of the LHRH pulse generator with an inappropriately low frequency relative to the prevailing androgen impregnation and opioid tone, and with an increased sensitivity to retardation of the LHRH pulse generator by androgens. As observed by some authors in basal conditions and by others after endocrine manipulations. LH pulse amplitude seems also to be reduced in elderly men as compared to young subjects. This is most probably the consequence of a reduction in the amount of LHRH released by the hypothalamus. Indeed, challenge of the gonadotropes with low, close to physiological doses of LHRH in young and elderly men reveals no alterations in pituitary responsiveness when looking at either the response for immunoreactive LH or bioactive LH. Deconvolution analysis on data obtained after low-dose LHRH suggests a markedly prolonged plasma half-life of LH in elderly men, a finding which may explain the paradoxical increase of mean LH levels in face of the reduced or unchanged frequency and amplitude of LH pulses.

Aging↗
PubMed1990

Reduced forearm bone mineral content and biochemical evidence of increased bone turnover in women with euthyroid goitre treated with thyroid hormone.

We used single-photon absorptiometry to assess forearm bone mineral content (BMC/BW) (arbitrary units normalized for bone width) at a proximal site (PBMC/BW) and at a more distal site (DBMC/BW) in 60 women treated with 25-50 micrograms T3 or 50-100 micrograms T4 for euthyroid goitre, in 13 untreated goitre patients, and in 2 controls matched for age and menopausal state for each goitre patient. BMC/BW was not significantly different between untreated goitre patients and controls. In 36 premenopausal patients, treated for 5.8 +/- 5.4 years (mean +/- SD) a slight decrease in PBMC/BW of about 5% compared to controls to controls was observed (PBMC/BW 1.42 +/- 0.19 vs 1.49 +/- 0.13, P less than 0.05). In 24 postmenopausal patients, treated for 10.0 +/- 5.8 year, a 20% deficit in BMC/BW compared to controls was found (DBMC/BW 0.80 +/- 0.18 vs 1.06 +/- 0.20, P less than 0.001 and PBMC/BW 1.14 +/- 0.20 vs 1.42 +/- 0.19, P less than 0.001). Biochemical indices of bone metabolism in 43 pre and post-menopausal patients and 43 controls showed in the patients a higher serum alkaline phosphatase activity (AP) (P less than 0.01 and P less than 0.05 and serum osteocalcin (NS and P less than 0.05). AP was negatively correlated with TSH levels and, in postmenopausal patients, with DBMC/BW and PBMC/BW. Our results suggest that treatment of euthyroid women with moderate doses of thyroid hormone increases bone turnover with clear adverse effects on bone mineral status in postmenopausal patients.

Adult↗
PubMed1989

Persistence of increased bone resorption and possible role of dehydroepiandrosterone as a bone metabolism determinant in osteoporotic women in late post-menopause.

Specific data on bone metabolism in the late post-menopause are relatively scarce. This study presents data on the biochemical, hormonal and bone mineral status of a selected group of 22 osteoporotic women with at least 1 vertebral fracture who had been post-menopausal for a minimum of 5 yr. Bone resorption parameters were elevated in over two-thirds of these patients. The serum levels of dehydroepiandrosterone and its sulphate were negatively correlated with age and years since menopause but positively correlated with bone mineral content, bone turnover parameters (urinary calcium/creatinine, osteocalcin), 1,25-dihydroxy-vitamin D levels and the 1,25-dihydroxy-vitamin D/25-hydroxy-vitamin D ratio. These findings indicate that careful evaluation of the bone turnover rate in the late post-menopause can still have an important bearing on therapeutic decisions. They also support the theory that adrenal androgens play a role in bone mineral metabolism in the late post-menopause.

Age Factors↗
PubMed1989

Lack of effect of the alpha-adrenergic agonist clonidine on pulsatile luteinizing hormone secretion in a double blind study in men.

This study was designed to evaluate the effects of alpha-adrenergic stimulation on the hypothalamic LHRH pulse generator in men. In 10 normal men, venous blood was sampled on 2 occasions at 10-min intervals for 8 h, beginning 30 min after oral administration of either placebo or 0.3 mg clonidine according to a randomized double blind protocol. Compared to placebo, clonidine induced a marked release of GH (P less than 0.0001 for response areas under the curve after placebo and clonidine), a fall in systolic and diastolic blood pressure and in heart rate (P less than 0.002 for areas under the curve after placebo and clonidine), and feelings of sedation and dry mouth (P less than 0.002 and P less than 0.05 for areas under the cumulative scores for changes in alertness and salivation, respectively). There was no difference between the results obtained after placebo and clonidine for the mean number of LH pulses [3.3 +/- 0.4 (+/- SE) and 3.3 +/- 0.3 pulses/8 h], for the mean amplitude of all LH pulses (3.8 +/- 0.4 and 4.1 +/- 0.5 IU/L), or for the areas under the LH concentration-time curve (2741 +/- 251 and 2728 +/- 215 IU/L.min). The lack of effect of clonidine on LH secretion at a dose that effectively induced GH secretion and other centrally mediated effects indicates that the actions of testosterone and opiates to decelerate the frequency of the LHRH pulse generator in men are not mediated by diminished alpha-adrenergic stimulation. From these results, taken together with previous data, we conclude that alpha-adrenergic systems do not play a major role in the regulation of episodic LH release in men.

Adult↗
PubMed1989

Influence of antiopioids on luteinizing hormone pulsatility in aging men.

To investigate whether changes in opioid tone play a role in the age-associated changes in LH release in men, the influence of an antiopioid, naltrexone, on plasma LH levels and LH pulses was studied in a group of young and elderly normal men. The young and elderly men had similar basal LH pulse frequencies, but the frequency of high amplitude (greater than 2 IU/L) LH pulses, mean LH pulse amplitude, maximal LH pulse amplitude and pulse area, were lower in the elderly men. Naltrexone administration (40 mg at 0630 and 2200 h the day before blood sampling and at 0630 h, 30 min before starting frequent blood sampling at 10-min intervals for 12 h) to young men (n = 8) induced a significant increase in individual mean baseline plasma LH levels, LH pulse frequency, and the sum of LH pulse amplitudes. In elderly men (n = 11) only a borderline significant increase in baseline plasma LH levels occurred, and neither LH pulse frequency nor the sum of the amplitudes of LH pulses increased. We suggest that in elderly men either opioid tone or the response of the gonadotrophs to endogenous LHRH is decreased.

Adult↗
PubMed1988

Testicular toxicity induced by single dosing of di- and mono-(2-ethylhexyl) phthalate in the rat.

The testicular toxicity of di-(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, and of its major metabolite, mono-(2-ethylhexyl) phthalate (MEHP), was assessed after a single dose in rats. Treatment with a single dose of 2.8 g/kg DEHP or 0.8 g/kg MEHP was sufficient to induce testicular atrophy as observed 7 days after dosing. Such a treatment had no effect on plasma FSH levels, and had varying effects on testicular zinc concentrations. After a single dose of 0.8 g/kg MEHP the testicular toxicity was age-dependent, in that only prepubertal rats were susceptible.

Animals↗
PubMed1988

Study with positron emission tomography of the osmotic opening of the dog blood-brain barrier for quinidine and morphine.

A canine model was used to evaluate the possibilities offered by positron emission tomography (PET) for the study of drug distribution in the brain during altered states of the blood-brain barrier (BBB). PET was used to monitor the changes in the distribution of [11C]quinidine and [11C]morphine resulting from BBB-disruption by intracarotid infusion of a hyperosmolar mannitol solution. Injection of Evans blue dye allowing post-mortem evaluation of the degree of BBB-opening was used as a reference method. Brain radioactivity concentrations observed after i.v. injection of either [11C] quinidine or [11C]morphine were markedly increased by intracarotid mannitol infusion, whereas they were not affected by saline infusion. For both drugs a close correlation was found between the radioactivity concentrations and the degree of Evans blue staining within the brain hemispheres and within smaller regions of interest corresponding to quadrants of a hemisphere. This parallelism between the findings for radioactivity concentrations and Evans blue staining suggests that PET allows the detection of in-vivo changes in brain distribution of drugs resulting from alterations of the BBB permeability.

Animals↗
PubMed1987

Unexpected responses of the hypothalamic gonadotropin-releasing hormone "pulse generator" to physiological estradiol inputs in the absence of the ovary.

In the rhesus monkey (Macaca mulatta), the frequency of pulsatile gonadotropic hormone release is relatively constant in the face of widely varying levels of estradiol (E2) in the peripheral circulation--e.g., in the course of the follicular phase of the menstrual cycle and after ovariectomy. This suggests that modulation of the hypothalamic gonadotropin-releasing hormone (GnRH) "pulse generator" by this steroid is not of major physiological importance. Herein is described the unexpected inhibition or total blockade of the electrical activity of this pulse generator in ovariectomized monkeys by physiological levels of exogenous E2. This inhibition began 2-4.5 hr after the initiation of E2 infusion and was noted 1 to 3 weeks after subcutaneous implantation of E2-containing capsules. Pulse generator activity was also arrested during the initiation and subsequent development of estrogen-induced surges of luteinizing hormone. We propose that this inhibition of hypothalamic GnRH pulse generator activity by E2 in ovariectomized monkeys reflects the absence of an ovarian factor that normally protects this neuronal system from the inhibitory action of estrogen during the menstrual cycle.

Action Potentials↗
PubMed1987

Influence of age on pulsatile luteinizing hormone release and responsiveness of the gonadotrophs to sex hormone feedback in men.

The influence of aging on serum LH and testosterone (T) pulse frequency and gonadotroph sensitivity to androgen and estrogen feedback was studied in young (less than 55 yr old) and elderly (greater than 65 yr) Trappist monks. LH pulse frequency (sampling interval, 20 min) was significantly lower [0.25 +/- 0.03 (+/- SEM) vs. 0.38 +/- 0.02 pulses/h; P less than 0.01] in elderly (n = 21) than in young monks (n = 27); the pulse amplitudes were similar. Similarly, T pulse frequency was lower in the elderly than in the young monks (0.13 +/- 0.04 vs. 0.23 +/- 0.02 pulses/h; P less than 0.01). In elderly men, the hypothalamo-pituitary complex was more sensitive to 5 alpha-androstan-17 beta-ol-3-one feedback, as determined by the decrease in serum LH and T levels. Moreover, during 5 alpha-androstan-17 beta-ol-3-one (125 mg/day, percutaneously, for 10 days) administration, the LH response to LHRH (100 micrograms, iv) was significantly higher in the elderly men compared to the pretreatment response. During estradiol (1.5 mg/day, percutaneously for 10 days) administration, the LH response to LHRH was decreased in the elderly men, but unchanged in the young men, suggesting greater responsiveness to estradiol in the elderly men. We conclude that in aged men, decreased testicular androgen secretion is not exclusively the consequence of a primary testicular alteration, but that important changes occur in hypothalamo-pituitary function, specifically decreased LH pulse frequency and increased LH responsiveness to sex hormone feedback.

Adult↗
PubMed1986

On the short-loop feedback regulation of the hypothalamic luteinizing hormone releasing hormone 'pulse generator' in the rhesus monkey.

The characteristic electrophysiological manifestations of LHRH 'pulse generator' activity were unaffected by prolonged elevations in plasma LH concentrations achieved by the administration of a long-acting LHRH agonist. These findings do not lend support to the existence of a 'short-loop feedback' inhibition of LHRH 'pulse generator' activity by LH.

Animals↗
PubMed1986

The effect of morphine on the electrophysiological activity of the hypothalamic luteinizing hormone-releasing hormone pulse generator in the rhesus monkey.

In ovariectomized rhesus monkeys, the electrophysiological manifestation of luteinizing hormone-releasing hormone (LHRH) pulse generator activity was arrested by morphine and reinitiated by naloxone. These responses were noted within 1 and 2 min, respectively, after the intravenous injection of the drugs. Naloxone given alone had no effect. These results support the view that opioids modulate pulsatile gonadotropin release by an action on the hypothalamic LHRH pulse generator.

Animals↗
PubMed1985

Electrophysiological manifestation of luteinizing hormone-releasing hormone pulse generator activity in the rhesus monkey: influence of alpha-adrenergic and dopaminergic blocking agents.

Characteristic increases in neuronal electrical activity associated with the initiation of each LH pulse were recorded from ovariectomized rhesus monkeys bearing multiple chronic electrodes in the medial basal hypothalamus. These electrophysiological manifestations of hypothalamic LHRH pulse generator activity were inhibited by the alpha-adrenergic blocker phentolamine or the alpha 1-adrenoceptor blockers phenoxybenzamine and prazosin. At the dosages used, the effects of single injections of these drugs ranged from a reduction in the frequency of LHRH pulse generator activity to its complete arrest. This was faithfully reflected in the pattern of pulsatile LH discharges. The dopaminergic blocking agent metaclopramide similarly reduced the frequency of the pulse generator or arrested its activity altogether. The alpha 2-adrenoceptor blocker yohimbine had no demonstrable effect on hypothalamic electrical activity at the doses studied. These findings support the view of a central action of alpha 1-adrenergic and dopaminergic blockade on LHRH pulse generator activity and the concept that central adrenergic and dopaminergic inputs can modulate the frequency of the LHRH pulse generator.

Adrenergic alpha-Antagonists↗
PubMed1984

Inhibition of adenylate cyclase activity of human thyroid membranes by gangliosides.

Gangliosides inhibit basal, thyrotropin-induced and fluoride-induced adenylate cyclase activity of human thyroid membranes in physiological conditions. In contrast neutral glycolipids, phospholipids and neuraminic acid containing oligosaccharides show no effect. The efficacy of inhibition is more dependent upon the position of the sialic acid residues than upon their absolute number. In general gangliosides with disialyl groups are more inhibitory than those with single sialyl moieties. The inhibitory effects of the individual gangliosides on the two modes of stimulation are parallel. This parallelism suggests that the inhibitory effect is located at the postreceptor level and that the gangliosides interact directly with the adenylate cyclase system. A possible role of thyroid membrane gangliosides as suppressive cofactors of adenylate cyclase is discussed in relation to recent findings of stimulating anti-ganglioside antibodies in Graves' disease.

Adenylyl Cyclase Inhibitors↗
PubMed1984

Torsion of the spermatic cord in the postnatal period.

Neonatal testicular torsion is usually extravaginal and occurs either in utero or in the first day of life before the testicular tunics are firmly attached to the scrotum. An unusual case is presented of testicular torsion in a 5-week-old male newborn whose delivery was approximately 4 weeks premature.

Humans↗
PubMed1984

Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey.

Characteristic increases in neuronal activity coincident with the pulsatile release of luteinizing hormone from the pituitary gland have been recorded from electrodes chronically implanted in the medial basal hypothalamus of the rhesus monkey. This electrophysiologic manifestation of the hypothalamic 'pulse generator' which governs the secretion of hypothalamic luteinizing hormone releasing hormone provides, for the first time, direct access to the central component of the neuroendocrine control system which regulates reproductive processes in this higher primate.

Anesthesia↗
PubMed1983

Neonatal bladder injury occurring after umbilical artery catheterization by cutdown.

Umbilical artery catheterization is a widely used technique for monitoring sick neonates. When it is performed by cutdown, the proximity of peritoneum, urachus, and bladder makes these structures vulnerable to injury. Three neonates experienced bladder perforation that resulted from umbilical artery catheterization by cutdown. The diagnosis was aided by measuring electrolyte levels in the umbilical fluid and was confirmed by cystography. Conservative treatment was successful in one neonate, but two required operative repair of the bladder laceration.

Catheterization↗
PubMed1983

Immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) in human cord blood: high circulating serum levels but possible non-identity with hypothalamic TRH.

Levels of immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) were measured in paired maternal and umbilical cord serum samples (n = 45) and in serum of non-pregnant women (n = 63), using a sensitive and specific radioimmunoassay. In all pairs IR-TRH LM in venous cord serum (mean 91.3 pg/ml, range 20-270) was markedly elevated as compared to maternal serum (mean 13.5 pg/ml, range 0-37, P less than 0.001, the maternal levels being similar to those in non-pregnant women (mean 12.0 pg/ml, range 0-39, P greater than 0.1). In 23 cases IR-TRH LM was also measured in arterial cord serum: arterial and venous cord levels were highly significantly correlated (r = 0.904) with higher arterial levels in 22 out of 23 cases (mean 117.8 pg/ml, range 32-280 and 90.6 pg/ml, range 20-270, P less than 0.001), suggesting that cord IR-TRH LM is not of placental origin. There was no correlation between individual levels of IR-TRH LM and either TSH, T4, T3 or FT4 levels in either maternal or cord serum. Agar gel electrophoresis and equilibrium dialysis of adult and cord serum pre-incubated with [125I]TRH or [3H]TRH revealed no protein binding. Cord IR-TRH LM was immunologically, as well as in paper electrophoresis and in gelfiltration, indistinguishable from synthetic and hypothalamic TRH. In vitro degradation of synthetic TRH was much slower in cord serum as compared to maternal and control serum (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗