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Biomedical subjects

D Rabin

Publications and source records attributed to D Rabin.

At least 73 records · Page 4Linked to original sources
PubMed1981

Papilledema in two patients with acromegaly and intrasellar pituitary tumors.

Two patients had bilateral papilledema complicating acromegaly. Both patients had enlarged blind spots, but otherwise visual fields were normal. Suprasellar extension of the pituitary tumors was diligently sought with the use of visual field examination, pneumoencephalography, internal carotid arteriography, and computed axial tomography, and tumor extension did not exist. Transphenoidal and transethmoidal routes were used to perform partial hypophysectomies in these patients. The procedure was completely successful in one patient and partially successful in the other patient. After hypophysectomy, papilledema resolved in both patients. This beneficial effect may be the result of anatomical changes, the reduction in growth hormone levels, or both. These observations suggest that the acromegaly may be different from papilledema that occurs secondary to suprasellar expansion of pituitary tumors.

Acromegaly↗
PubMed1980

Metabolic effects and pharmacokinetics of intravenously administered dichloroacetate in humans.

Dichloroacetate decreases plasma glucose, lactate, and alanine concentrations in normal and diabetic subjects, and lowers lactate concentrations and increases survival in animals with experimentally induced lactic acidosis. The relationship between these effects and plasma dichloroacetate concentrations have not been previously studied in man. Dichloroacetate (1-50 mg/kg) was infused over 30 min to 16 healthy subjects and plasma drug concentrations were followed by gas chromatography over the next 8 h. Peak plasma concentrations were linearly related to the dose (r = 0.98, p < 0.001) up to 30 mg/kg, above which 4 of 7 subjects had disproportionately high plasma drug concentrations. Nonlinear disposition was also indicated by the convex decreasing plasma elimination curves; levels declining less rapidly initially than later. At plasma concentrations below 10 micrograms/ml, elimination was monoexponential with a half-life of 32 +/- 11 min (mean +/- SD). Plasma drug clearance also decreased with doses greater than 20 mg/kg. Within 2 h of administration of the maximally effective dichloroacetate dose of 35 mg/kg, plasma lactate concentrations fell 75% below baseline and alanine fell 50% below baseline, while blood glucose was unaffected.

Acetates↗
PubMed1980

Molecular weight forms of immunoreactive calcitonin in a patient with medullary carcinoma of the thyroid: dynamic studies with calcium, pentagastrin and somatostatin.

We have examined the characteristics of circulating immunoreactive human calcitonin (IR-hCT) by studying its different molecular weight (MW) forms under various secretory conditions in a patient with medullary carcinoma of the thyroid. Plasma IR-hCT (318 mg/l basal) increased 9 and 12 times, respectively, after calcium (0 . 3 mg/kg/min over 10 min i.v.) and pentagastrin (3 . 2 microgram i.v.) administration. Somatostatin infusion (500 microgram/h) caused a 41% decrease in plasma IR-hCT and markedly diminished the responses to both pentagastrin and calcium. Sephadex G50 chromatography separated different IR-hCT forms: hCT itself predominated after stimulation with either calcium or pentagastrin (52% and 62%, respectively), while it was reduced in the basal state (33%) and following somatostatin (11%); reciprocal changes were observed for the higher MW forms. Under denaturing conditions, with or without reducing agent, total plasma IR-hCT was resolved into one major peak co-eluting with 125I-hCT. Thus, the hCT monomer appears to be the major secretory product of the medullary carcinoma of the thyroid studied here. The predominance of higher MW forms in the basal state reflects their slower plasma disappearance rate. These high MW forms are mainly the result of aggregation or non-covalent protein binding of the hCT monomer.

Adult↗
PubMed1980

Genetic and endocrine findings in a 48,XXYY male.

Characteristics of a 16-yr-old male with a 48,XXYY karyotype are presented; this chromosome constitution was demonstrated consistently in four tissue studied. Basal gonadotropins were elevated, and serum testosterone varied between 3.2-4.0 ng/ml. A pronounced rise was observed in LH after LRH administration with a lesser rise of FSH. The testis displayed hyperplasia of the interstitial cells, tubular atrophy, absent spermatogenesis with preservation of some Sertoli cells, and peritubular fibrosis. The phenotypic, behavioral, endocrine and pathological features of this patient are compared with those found in males with the 47,XXY and 47,XYY syndromes. The 48,XXYY phenotype may result from compounding effects of the additional X and Y chromosomes.

Adolescent↗
PubMed1980

Pituitary and gonadal desensitization after continuous luteinizing hormone-releasing hormone infusion in normal females.

Three normal females were studied during the early follicular phase of the menstrual cycle employing a continuous infusion of LHRH (1.4 micrograms/min) for 72 h. Blood samples were taken every 4 h. LH concentrations climbed from 9.3 mIU/ml basally to peak values of 120 mIU/ml at 12 h, then fell to a plateau between 23-31 mIU/ml from 36-72 h. FSH levels rose from 5.4 to 36 mIU/ml at 4 h of infusion and then returned to baseline. 17 beta-Estradiol increased from 48 to 184 pg/ml at 32 h, but subsequently fell toward basal concentrations. 17-Hydroxyprogesterone increased from 0.5 to 1.23 ng/ml at 12 h and remained elevated for the remainder of the infusion period. Serum progesterone levels remained constant. Three females with premature ovarian failure were studied, and the pattern of gonadotropin release was similar to that of normal subjects. Studies demonstrate that continuous LHRH infusion in normal females causes pituitary and gonadal desensitization. The desensitization of the pituitary is independent of gonadal activity.

Adult↗
PubMed1980

Gonadal dysfunction in adult men with congenital adrenal hyperplasia.

Two adult males are described with congenital adrenal hyperplasia (21-hydroxylase deficiency). Patient 1 was receiving therapy with cortisone acetate and presented with clinical features of glucocorticoid excess and uncontrolled adrenal androgen activity. It was established that the short-acting steroid which the patient was receiving was cleared so rapidly that endogenous ACTH secretion was not inhibited. Patient 2 presented with enlarged and painful testes in association with poor compliance with corticosteroid therapy. The histologic picture of the testis was compatible with 'Leydig cell hyperplasia'. However, successful response to dexamethasone therapy suggests that the testes harboured an adrenal rest. These observations highlight the need for careful follow-up and treatment of adult male patients with congenital adrenal hyperplasia.

Adrenal Hyperplasia, Congenital↗
PubMed1980

Dichloroacetate--its in vivo effects on carbohydrate metabolism in the conscious dog.

The effects of sodium dichloroacetate (DCA) on carbohydrate metabolism in conscious, 48-h-fasted dogs were examined using the hepatic A-V difference technique and a double isotope infusion technique (3H-glucose to measure glucose production and 14C-alanine to assess gluconeogenesis). DCA infusion (0.4 mg/kg-min) resulted in an 82 +/- 1% fall in the arterial plasma alanine level and a 53 +/- 8% fall in the arterial whole blood lactate level. Hepatic uptake of alanine and lactate fell 67 +/- 5% and 59 +/- 15%, respectively, although the fractional extraction of these intermediates was not altered. DCA decreased the conversion of circulating alanine and lactate to glucose but by only 41 +/- 7%, suggesting that a slight increase in the efficiency of the intrahepatic gluconeogenic process took place. This may be explained by the decrease in the plasma insulin level (39 +/- 9%) that occurred in the presence of an unchanged plasma glucagon concentration. Despite the substantial fall in the levels of gluconeogenic precursors in blood and the considerable decrease in their rate of conversion to glucose, the overall rates of glucose production and the blood glucose concentration were not altered by DCA. These data indicate that the alanine and lactate supplied by the periphery after a 48 h fast in the dog are not essential for the acute maintenance of glucose production or euglycemia. They suggest, further, that a compensatory increase in glucose production can occur by drawing on an alternate intrahepatic carbon source, the nature of which and signal for which remain unclear.

Acetates↗
PubMed1979

Analysis of RNA secondary structure by photochemical reversal of psoralen crosslinks.

Aminomethyltrioxsalen (AMT), a psoralen, is known to cause interstrand crosslinks in double stranded nucleic acids. We have demonstrated the photochemical reversal of this reaction, and have used this result to develop a method for identification of specific sequences which are adjacent because of RNA secondary structure formation. E. coli 5S rRNA is used as a model system. We isolated and characterized a product that is derived from the stem region of 5S RNA.

Base Composition↗
PubMed1979

Seventy-two hour infusions of LHRH in normal men: gonadotropin and testicular steroid responses.

Four normal male subjects received LHRH by continuous infusion for 72 hrs at 1.4 microgram/min. Mean basal LH was 7.7 +/- 1.0 mIU/ml, increased to a maximum of 120 +/- 22.7 mIU/ml, and then declined to levels between 28--34 mIU/ml for the last 30 hrs of infusion; FSH rose from 3.7 to 11.4 mIU/ml (p less than 0.05) at 16 hrs and then returned to baseline. Testosterone levels rose by 50% at 12 hrs, and remained elevated throughout with maximum values between 6.6 and 12 ng/ml. Estradiol-17beta levels were 26.2 +/- 4.7 pg/ml basally, rose to 104 +/- 8 pg/ml and while levels declined therafter, they were significantly above baseline throughout the 72 hrs. Plasma androstenedione and dehydroepiandrosterone levels also showed significant increases. By contrast, transient elevations in pregnenolone and 17-hydroxypregnenolone levels probably corresponded to the nomral morning rise in plasma levels of these steroids; 17-hydroxyprogesterone rose from 1.3 +/- 0.15 to 3.9 +/- 0.26 ng/ml at 12 hrs and remained elevated through the infusion. An increase in 17-hydroxyprogesterone:testosterone ratio was observed in all subjects. Thus, chronic LHRH infusion effected a persistent increase in endogenous LH with, in turn, prolonged stimulation of gonadal steroid secretion.

17-alpha-Hydroxypregnenolone↗
PubMed1979

Lack of a role for glucagon in the disposal of an oral glucose load in normal man.

The present study was undertaken to determine the role of glucagon in determining the disposition of an oral glucose load in normal man. To accomplish this, the plasma glucose response to an oral glucose load was determined in four normal men who were studied on two occasions. During one study, glucagon (3 ng/kg.min) was administered to prevent the fall in plasma glucagon noted after oral glucose ingestion. Despite elevation of plasma glucagon levels to 350 pg/ml in this protocol, the plasma insulin and glucose levels achieved were virtually identical to those obtained after oral glucose alone. These results indicate that neither physiological elevations of plasma glucagon nor the suppression of plasma glucagon seen during oral glucose administration alter glucose tolerance in normal man. Thus, in a normal man capable of secreting appropriate amounts of insulin in response to the ingestion of glucose, glucagon plays no appreciable role in the disposition of this glucose load.

Adult↗
PubMed1979

Gigantism associated with a pituitary tumour secreting growth hormone and prolactin and cured by transsphenoidal hypophysectomy.

An 18-year old male is reported who presented with a history of a growtn spurt over the year preceding his admission. His height was above the 97th percentile, and he had incompletely developed secondary sexual characters. Pituitary evaluation demonstrated a moderately elevated level of growth hormone (hGH) not suppressible by a glucose load and not stimulable by TRH or by L-DOPA. Serum prolactin (PRL) concentration was also increased while gonadotrophin, thyroid and adrenal function were all subnormal. There was clear radiological evidence of a large pituitary tumour with suprasellar extension and transsphenoidal total hypophysectomy was performed. A mixed chromophobe and acidophilic adenoma was found and both growth hormone and prolactin were demonstrable in different cells of the tumour by the immunoperoxidase technique. Post-operatively the patient has hypopituitarism and levels of growth hormone and prolactin have remained low or undetectable after 6 months. Thus early diagnosis and surgical treatment of gigantism of this mixed hGH-PRL secreting pituitary tumour was associated with a cure, which contrasts with the unfavourable outcome of many of the patients previously reported.

Adenoma, Acidophil↗
PubMed1979

Testicular activity in Cushing's disease.

Plasma testosterone levels were suppressed in 6 of 8 mature male patients with Cushing's disease, all of whom complained of loss of libido and decreased sexual potency. Gonadotrophin levels, both under basal conditions and in response to LH-RH, were generally normal. The testicular response to stimulation with hCG was brisk in the 2 patients examined. Oestradiol levels were slightly elevated in 2 patients and prolactin levels were normal in all patients. Thus, male patients with Cushing's disease demonstrated normal gonadotrophin levels in the presence of suppressed testosterone, or, viewed from a slightly different prospect, low testosterone levels despite normal gonadotrophins. Neither oestradiol nor prolactin excess appeared to account for the observations. Possible explanations for these findings include (a) a combination of impaired hypothalamic and testicular function, and (b) a resetting downwards of the level of testosterone that is seen as appropriate by the disordered bypothalamic-pituitary unit. Following correction of cortisol excess in Cushing's disease, testosterone levels rose into the normal range.

17-Hydroxycorticosteroids↗
PubMed1979

Splanchnic metabolism of alanine in intact man. Effects of somatostatin and somatostatin plus insulin.

We examined splanchnic metabolism of alanine in 15 normal males under three sets of conditions: infusion of saline (control studies); infusion of somatostatin (SRIF) (bihormonal deficiency of insulin and glucagon); and infusion of somatostatin plus insulin (selective glucagon deficiency). Net splanchnic alanine uptake (NSAU) remained stable over 2 h during infusion of saline. Infusion of SRIF was associated with a fall in estimated hepatic plasma flow (EHPF) whether or not insulin was infused concomitantly. With SRIF only, arterio-hepatic venous alanine differences increased such that NSAU remained stable over 2 h, despite the fall in EHPF. In contrast, with selective glucagon deficiency, NSAU fell significantly after 2 h, an effect consequent on a fall in EHPF and a delayed fall in arterio-hepatic venous (A-HV) alanine differences. Our studies are compatible with a role for basal glucagon in maintenance of splanchnic extraction of alanine in normal man. However, the SRIF-initiated fall in EHPF may exert an influence on A-HV alanine differences independent of changes in pancreatic hormone secretion.

Adult↗
PubMed1975

The syndromes of isolated gonadotropin deficiency.

Six theoretically possible syndromes of IGD are shown in Table 1. 1) IBGD is well-substantiated both in males and in females, and appears to be either of pituitary or more frequently of nonpituitary origin. 2) An example of isolated FSH deficiency has been described. The defect appears to reside at the pituitary level and may be localized to the FSH beta subunit. Recently a male patient has been studied with isolated FSH deficiency and a concordant testicular picture viz germinal cell aplasia. However, the syndrome is complicated by an associated chromosomal abnormality (XO/XXY/XY) whose significance is unclear. 3) Several examples of isolated hLH deficiency have been described. Several questions remain about the exact nature of the defect in some of the published reports of this syndrome.

Amenorrhea↗