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Biomedical subjects

A Grossman

Publications and source records attributed to A Grossman.

At least 181 records · Page 10Linked to original sources
PubMed1988

The cortisol response to corticotrophin-releasing factor is blunted in obesity.

Abnormalities of the adrenal cortex may be associated with extreme obesity but there is little information about hypothalamic-pituitary function. We have investigated this by measuring plasma ACTH and cortisol responses to ovine corticotrophin releasing factor (CRF-41), 0.5 microgram/kg/body weight, in 10 obese women and seven age-matched normal weight women. The cortisol response to insulin-induced hypoglycaemia and intravenous synacthen (2.5 ng/kg/body weight) were also measured on different occasions in some of the subjects. The peak ACTH response to CRF was less in the obese but this was not significant (obese ACTH +/- SEM, 31 +/- 4 ng/l, controls 39 +/- 4 ng/l) whereas the peak cortisol was significantly reduced in the obese (obese cortisol, 456 +/- 21 nmol/l, controls 638 +/- 50 nmol/l). Doubling the dose of CRF did not significantly alter either ACTH or cortisol responses in six of the obese patients. The peak cortisol response to symptomatic hypoglycaemia and following i.v. low dose synacthen stimulation was similar in the obese and normal weight women. We conclude that obese women have a normal cortisol response to hypothalamic-pituitary stimulation by hypoglycaemia and direct adrenal stimulation by synacthen but an impaired adrenal response to pituitary stimulation with CRF. Although the explanation for these findings is uncertain, our study underlines the importance of considering an individual's body weight when assessing the cortisol response to CRF stimulation.

Adrenocorticotropic Hormone↗
PubMed1988

A bromocriptine-responsive corticotroph adenoma secreting alpha-MSH in a patient with Cushing's disease.

Clinical and in-vitro investigations have been performed on a corticotroph adenoma removed from a patient suffering from Cushing's disease. Prior to surgery, the patient's Cushing's disease had been successfully controlled, clinically and biochemically, by long term administration of bromocriptine. After selective adenomectomy, tumour tissue was investigated by a perfused isolated cell column technique. It was shown that the tumour cells secreted immunoreactive- (IR)- ACTH and IR-alpha-MSH and that the release of both peptides was promptly suppressed by dopamine. Chromatographic analysis of the secreted IR-alpha-MSH revealed a high proportion of acetylated alpha-MSH; smaller amounts of desacetyl alpha-MSH and diacetyl alpha-MSH were present. The relevance of these findings to the proposal that certain corticotroph adenomas are derived from the intermediate lobe of the pituitary is discussed. It is concluded that there is little direct evidence for involvement of the residual zona intermedia of the adult human pituitary in the development of Cushing's disease.

Adenoma, Chromophobe↗
PubMed1988

Acetylcholine and norepinephrine stimulate the release of corticotropin-releasing factor-41 from the rat hypothalamus in vitro.

The effects of the two putative neurotransmitters acetylcholine and norepinephrine on immunoreactive CRF-41 release from incubated rat hypothalami were studied. Acetylcholine at concentrations of 10(-11) to 10(-7) M stimulated CRF-41 release. This effect was blocked in a dose-dependent manner by the muscarinic antagonist atropine (10(-9) to (-7) M). The nicotinic antagonist hexamethonium was ineffective at a dose of 10(-7) M, but produced slight inhibition of this response at 10(-5) M. Norepinephrine at concentrations of 10(-10) to 10(-6) M also produced a dose-dependent stimulation of CRF-41 release. The beta-adrenoceptor antagonists propranolol (10(-5) M) and timolol (10(-6) M) blocked norepinephrine-induced CRF-41 release. The alpha 1-adrenoceptor antagonists thymoxamine (10(-5) M), prazosin (10(-5) M), and corynanthine (10(-4) M), and the alpha 2-antagonist idazoxan (10(-5) M), were ineffective. Potassium depolarization (56 mM) caused stimulation of CRF-41 release which was dependent on the presence of calcium in the incubation medium. Authenticity of immunoreactive CRF-41 released was demonstrated by chromatographic criteria using gel filtration and reversed phase HPLC. These results provide evidence for a stimulatory role of acetylcholine and norepinephrine on CRF-41 release, and consequently on hypothalamo-pituitary-adrenal axis in the rat, through actions at a hypothalamic level. The stimulatory effect of acetylcholine is mediated principally through muscarinic receptors and that of norepinephrine through beta-adrenoceptors.

Acetylcholine↗
PubMed1988

Opioid peptides do not modulate atrial natriuretic peptide or aldosterone release under basal conditions in man.

The effect of two analogues of [Met]-enkephalin, [D-Ala2,N-Phe4,Met(0)-ol5]-enkephalin and its guanyl derivative, on plasma concentrations of atrial natriuretic peptide (ANP) and serum aldosterone in six normal subjects was investigated. All subjects were given a 1 litre water load to inhibit vasopressin release. Both analogues, when injected i.v. at a dose of 100 micrograms, stimulated release of prolactin and GH and inhibited serum cortisol; there was no significant change in blood pressure, pulse rate or urine output. Neither plasma concentrations of ANP nor serum aldosterone levels changed significantly after injection of either analogue at a low or high dose. Naloxone, given i.v. as an 8 mg bolus, also failed to alter concentrations of either ANP or aldosterone, while it significantly stimulated the release of serum LH and cortisol. It was concluded that under basal conditions opiate receptors are unable to modulate plasma ANP or serum aldosterone concentrations.

Adult↗
PubMed1988

A rare restriction enzyme site polymorphism in the breakpoint cluster region (bcr) of chromosome 22.

Detection of rearrangement of the breakpoint cluster region (bcr) of chromosome 22 by Southern blot analysis can be used for the routine diagnosis of CML. Restriction fragment length polymorphisms (RFLPs) in the bcr can potentially be confused with translocation since both alter the size of DNA fragments obtained. By digesting DNA with the restriction enzyme BamHl and analyzing with probes commonly used for identifying rearrangement of the bcr, we have observed a RFLP within the bcr. For one CML patient studied in detail, the presence of the polymorphism was confirmed by comparing the results of analyses of granulocytes and a T cell-enriched population. The same polymorphism was detected in three additional CML patients and a patient with thrombocytosis. For the diagnosis of CML, verification of rearrangement with multiple probes and/or restriction enzyme combinations is necessary to rule out false positives, as well as to reduce the chance of false negatives due to co-migration of DNA fragments.

Adult↗
PubMed1987

The relative value of fecal occult blood tests and flexible sigmoidoscopy in screening for large bowel neoplasia.

The secondary prevention of colorectal cancer is based on the early detection of noninvasive cancer and removal of adenomatous polyps. The two commonly used screening tests are flexible sigmoidoscopy and guaiac fecal occult blood testing. Both were performed simultaneously and independently on 1176 asymptomatic volunteers followed by colonoscopic examination if either occult blood or a neoplasm was detected. Neoplasia (adenomatous polyps or cancer) were found in 48 screenees. Only ten had positive stool occult blood while 45 were detected by sigmoidoscopy. Analysis of sensitivity for neoplasia was 93.8% for sigmoidoscopy but only 20.8% for the occult blood tests, while the positive predictive values for neoplasia were 100% and 23.8% respectively. The fecal occult blood test detected only 18% of screenees with adenomas and 60% with invasive cancer. Flexible sigmoidoscopy detected 95% and 80% respectively. Analysis (kappa statistic) demonstrated little agreement between the two tests (P greater than 0.05), indicating that they are diagnosing different neoplasia. Evaluation of expected gain in diagnosing neoplasia, by combining both tests, gave 18% for the fecal blood test and 94% for the endoscopic test. These results confirm the complementary value of performing both tests, but especially the high sensitivity and predictive value positive of flexible sigmoidoscopy for adenomas, including those with severe dysplasia, and the converse for the fecal occult blood test. This latter test must be recommended and used within a screening program with caution and full understanding of its limitations.

Adult↗
PubMed1987

Treatment of growth-hormone deficiency with growth-hormone-releasing hormone.

18 prepubertal growth-hormone (GH)-deficient children were treated with twice-daily subcutaneous injections of a growth-hormone-releasing hormone analogue, GHRH (1-29) NH2. In 12 of the children the height velocity rose on GHRH treatment, and 8 were judged to have shown a worthwhile response to therapy in that their height velocities during the first 6 months of treatment increased by greater than 2 cm/yr (range 2.7-11.2 cm/yr). These 8 children have now been treated for 6 to 18 months and their increase in height velocity has been maintained. In the 14 patients who had previously received human GH (hGH) height velocity on hGH correlated with that on GHRH. 4 of these patients showed growth deceleration with GHRH, for unknown reasons. A pretreatment peak serum GH response of above 30 mU/l during an intravenous GHRH test was predictive of a good growth response to GHRH but a lower peak did not preclude a growth response. There was no consistent evidence of a priming or desensitisation effect of therapy on the GH responses to GHRH. Although anti-GHRH antibodies developed in 14 patients, these did not seem to have adverse effects on either growth or the GH responses to GHRH. GHRH (1-29) NH2 therapy is an alternative to conventional hGH in the treatment of some GH-deficient children. Ideal dose regimens need to be established.

Adolescent↗
PubMed1987

Lack of pancreatic [3H]estradiol-binding activity in cystic fibrosis.

A major characteristic of cystic fibrosis (CF) is the progressive degeneration of acinar cells in the pancreas. It is now well established that the normal pancreas contains an abundant amount of an [3H]estradiol-binding protein. Although the physiological function of this protein is unknown, available evidence suggests that it modulates resting secretion from acinar cells. Analysis of pancreatic autopsy samples from 13 patients who had CF demonstrated a high degree of correlation between loss of acinar cells and loss of [3H]estradiol-binding activity. Autopsy samples taken from individuals unaffected by CF contained large amounts of the [3H]estradiol-binding protein that were significantly correlated with the tissue content of amylase. This biological model demonstrates that the [3H]estradiol-binding protein in pancreas is localized primarily within acinar cells. Based on the presumed regulatory role this protein has on pancreatic secretion, an hypothesis is offered to account for acinar cell degeneration in individuals suffering from cystic fibrosis.

Adolescent↗
PubMed1987

Naloxone has no effect on hormonal responses to ECT in man.

Although there is clear evidence in other species that electroconvulsive therapy (ECT) is associated with changes in endogenous opioid activity, there are few data available for such a role in man. Since ECT leads to changes in certain hormones in man, particularly serum prolactin, it was postulated that such changes may represent an increase in endogenous opioids. Six unmedicated patients with major depressive illness were therefore administered either 4 mg i.v. of the opiate antagonist naloxone or a saline control infusion, just before successive treatments with ECT, in a double-blind, randomized crossover design. Blood was sampled at intervals for serum prolactin, growth hormone (GH), and cortisol. ECT led to a clear rise in serum prolactin, with no significant change seen in either serum GH or serum cortisol during the 20-min sampling interval. Naloxone had no significant effect on any of these changes. It is concluded that the rise in serum prolactin in response to ECT is not mediated by changes in endogenous opioid peptide activity.

Adult↗
PubMed1987

Frequent alterations of specific reiterated DNA sequence abundances in human cancer.

An in-gel renaturation method allows the visualization, quantitation, and initial characterization of reiterated DNA restriction fragments (RRFs) without prior possession of their probes. Using this method we analyzed EcoRI restricted DNAs from ten human tumors, paired normal tissues from these patients, ten unpaired tumors, and 26 noncancer patients. Frequent qualitative and quantitative differences in the relative radioactive intensities of all or specific RRFs in the DNA from different individuals have been observed. However, we also report frequent two- to ten-fold alterations in the relative radioactive intensities of several specific RRFs in tumor-control analyses of DNA from the same individual. A 0.65-kb alphoid-like DNA RRF was decreased in six tumors and increased in none. Moreover, a new 1.55-kb RRF was observed in two colon cancer DNAs. Several new RRFs, suggestive of gene amplification, were detected in a neuroblastoma, two of which were also seen in a glioma. These data support frequent qualitative and quantitative alterations of specific reiterated DNA sequences in human cancer when compared with paired controls. This approach will allow the future characterization of specific DNA sequences whose patterns of altered reiteration suggest a role in the emergence of specific malignancies.

DNA, Neoplasm↗
PubMed1987

The effect of enkephalin analogue on pituitary hormone release in human obesity.

To elucidate further the role of opioid systems in the neuroendocrine alterations associated with obesity, we investigated the effect of the synthetic enkephalin analogue DAMME in 11 obese subjects and 10 lean controls. Prolactin responses to DAMME were similar in lean and obese, even in those obese subjects who had absent prolactin responses to insulin-induced hypoglycaemia. The obese showed impaired growth hormone release after both DAMME and insulin-induced hypoglycaemia compared to the lean subjects. The discordance of prolactin responses to DAMME and insulin-induced hypoglycaemia in the obese suggests that altered opioid systems are unlikely to account for the hypothalamic dysfunction present in obesity.

Adult↗
PubMed1987

A comparative study of metronidazole and sulfasalazine in active, not severe, ulcerative colitis. An Israeli multicenter trial.

Since metronidazole (M) was found to be effective in Crohn's disease, we evaluated its efficacy in the treatment of active ulcerative colitis (UC). Forty-six outpatients with acute, nonsevere UC were studied. Forty-two concluded the trial. Twenty-three received M 1.35 g/day and 19 received sulfasalazine (S) 4.5 g/day for 28 days in a randomized double-blind study. Six of 23 receiving M improved (26%) as against 13 of 19 patients receiving S (68%) (p less than 0.01). No significant side effects were noted. We conclude that M is ineffective in the therapy of an acute attack of UC.

Acute Disease↗
PubMed1987

Thymoxamine: lack of antihistaminic effects in clinical doses in man.

The purpose of this study was to investigate whether the alpha 1-adrenoceptor antagonist thymoxamine possesses antihistaminic activity in clinical doses in man, as has been reported on the guinea pig ileum in vitro. Five normal subjects were given on three separate occasions intravenous infusions of thymoxamine (0.15 mg kg-1 loading dose followed by 0.15 mg kg-1 h-1), chlorpheniramine (1.5 mg loading dose followed by 1.5 mg h-1) and normal saline (placebo). Intravenous bolus doses of histamine (1 and 2 micrograms kg-1) were given after pretreatment with propranolol 10 mg to block the beta-adrenoceptor agonist effects of the catecholamines released by the histamine injections. Histamine caused a dose-dependent reduction of FEV1 and FVC that was antagonised by chlorpheniramine but not by thymoxamine, suggesting that thymoxamine has no antihistaminic activity in the doses used in man. Thymoxamine caused a small enhancement of the bronchoconstrictor effect of the lower dose of histamine. The relatively selective action of thymoxamine makes it a suitable agent for the investigation of alpha 1-adrenoceptors.

Chlorpheniramine↗
PubMed1987

Stilboestrol pretreatment of children with short stature does not affect the growth hormone response to growth hormone-releasing hormone.

Oestrogens are known to enhance both basal and stimulated GH secretion. To examine whether this effect is mediated through the hypothalamus or the pituitary we performed insulin tolerance and GH-releasing hormone (GHRH) tests with and without oestrogen priming in a group of 14 short children. Pretreatment with stilboestrol increased basal levels of GH and both peak and incremental levels during insulin hypoglycaemia. In contrast, there was no effect of stilboestrol priming on the GH response to either an i.v. bolus of 100 micrograms or 0.1 microgram/kg (range 2-6 microgram) of GHRH. The children had significantly higher GH responses to an unprimed GHRH than unprimed insulin tolerance test. We conclude stilboestrol priming acts through the hypothalamus presumably by increasing endogenous GHRH release, and that short children with a subnormal GH response to insulin hypoglycaemia show a greater response to GHRH; this suggests the presence of a hypothalamic cause for their decreased GH secretion.

Body Height↗
PubMed1987

GH feedback occurs through modulation of hypothalamic somatostatin under cholinergic control: studies with pyridostigmine and GHRH.

We have studied the effect of increased cholinergic tone on the GH response to growth hormone-releasing hormone (GHRH) and on GH feedback, using pyridostigmine, an acetylcholinesterase inhibitor. In six healthy male adult volunteers 120 mg oral pyridostigmine increased basal GH secretion compared to placebo and augmented the GH response to 100 micrograms i.v. GHRH (1-29) NH2; the effect was more than the additive effect of pyridostigmine and GHRH when each was given alone. Pretreatment with 2 IU methionyl-hGH given i.v. abolished the serum GH response to GHRH given 3 h later, demonstrating a negative feedback loop of GH on the response to GHRH; this inhibited response to GHRH was restored in subjects given pyridostigmine as well as methionyl-hGH. The data demonstrate that enhanced cholinergic tone releases GH, augments the serum GH response to GHRH and unblocks the negative feedback effect of methionyl-hGH pretreatment on the GH response to GHRH. These results suggest that GH negative feedback effects on its own secretion occur predominantly through increased hypothalamic somatostatin secretion; this somatostatin secretion is under inhibitory cholinergic control.

Adult↗