PubMed HealthSearch

Biomedical subjects

N H Ertel

Publications and source records attributed to N H Ertel.

At least 19 recordsLinked to original sources

Decreased 3 alpha-androstanediol glucuronide levels in plasma and random urines in male pseudohermaphroditism caused by 5 alpha-reductase deficiency.

Concentrations of 3 alpha-diol glucuronide (3 alpha-diol G) in plasma and/or random urine samples were determined in seven subjects with familial male pseudohermaphroditism (FMP) due to 5 alpha-reductase deficiency (5 alpha-RD). All subjects were natives of an isolated Turkish village with a high incidence of consanguineous marriage. A specific and sensitive antibody to 3 alpha-diol was used for radioimmunoassay of 3 alpha-diol G after hydrolysis and chromatographic purification. The mean plasma 3 alpha-diol G in three subjects (31 ng/dL) was much lower than the normal male concentration (516 +/- 50) (+/- SE) and was even lower than normal female values (119 +/- 10.9 ng/dL). In five subjects, mean urinary 3 alpha-diol G in random urine samples was 7.6 (range 2.1 to 12.7) ng/mg creatinine. This was considerably decreased compared with the mean adult male concentration of 65.4 +/- 9.4 and even lower than normal age-matched nonhirsute female values (19.6 +/- 2.1 ng/mg Cr). To validate the use of 3 alpha-diol G/creatinine ratios in random urine samples, correlations of three consecutive eight-hour samples with 24-hour values were determined in 8 male and 3 female age-matched controls. There was an excellent correlation (r = .95) and the linear regression line (y = 0.51x + 2.58) indicates that the 24-hour excretion of 3 alpha-diol G in microgram/24 h is approximately twice the random urinary concentration in ng/mg Cr.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Insulin and C-peptide in ascitic fluid and plasma and their relative responses to glucagon in patients with cirrhosis.

Insulin (IRI) and C-peptide dynamics were studied after iv glucagon in 5 nondiabetic patients with ascites due to cirrhosis of the liver. Plasma and ascitic fluid samples for glucose, IRI and C-peptide determinations were obtained before and 6, 10, 15, 20 and 30 min after glucagon injection. Ascitic fluid volumes, estimated by dilution of ip injected PAH, were 6.2 to 20.5 L. The mean fasting plasma glucose [88 +/- 6.7 mg/dl (SE)] and C-peptide (1.40 +/- 0.42 ng/ml) levels were normal; mean plasma insulin was increased (17.4 +/- 3.0 microU/ml). After glucagon injection, there was a subnormal rise in plasma glucose (PG) compared to 5 mild diabetic patients without liver disease (8.4 +/- 3.5 vs 76 +/- 7.4 mg/dl). The plasma C-peptide rise was less than that of plasma IRI (54% vs 192%). The mean basal ascitic fluid concentration of glucose was 86 +/- 9.4 mg/dl, IRI 13.2 +/- 2.9 microU/ml and C-peptide 3.09 +/- 0.49 ng/ml. Total calculated basal ascitic fluid contents of glucose was 5.2-23.3 g, IRI 47, 120-290,000 microU and C-peptide 15,750-66,420 ng. These were 3-10 times the quantity of these substances circulating in the plasma volume. After glucagon injection, there was no significant increase in ascitic fluid glucose or IRI, but there was a 43% increase in C-peptide concentration at 10 min. In ascitic fluid, the molar concentration of IRI was lower and C-peptide higher than plasma, resulting in a C-peptide: IRI molar ratio of 11.31, markedly higher than the published normal plasma ratio of 4.63.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Medical adrenalectomy for advanced prostatic cancer: clinical and hormonal effects.

We examined the effect of medical adrenalectomy on the clinical and hormonal responses in 50 men with disseminated prostatic carcinoma. Patients refractory to initial hormonal therapy were treated with aminoglutethimide and hydrocortisone (AG-HC) and evaluated by the criteria of the National Prostatic Cancer Project. Eight patients showed a partial response (PR), and 17 remained stable while receiving these medications. Survival times for these two groups averaged 87.8 and 38 weeks, respectively. In contrast, 17 men were unresponsive to this therapy, exhibiting progressive disease with a mean survival time of 18 weeks. Eight patients could not tolerate the drug regimen or were lost to follow-up. Serum and urinary hormone profiles determined serially during AG-HC therapy revealed that all measured serum androgens and estrogens were significantly lowered by AG-HC treatment; however, specific hormones, including free testosterone, dihydrotestosterone, estrone, and estradiol were suppressed to a greater degree in responders (R) as compared with nonresponders (NR). Urinary excretion of 17-ketosteroids did not change during AG-HC therapy, but specific androgen metabolites, including testosterone glucuronide and androstanediol glucuronide, were suppressed by 50% during AG-HC therapy. We showed modest clinical benefit of AG-HC therapy in advanced prostatic cancer. That greater hormonal suppression was associated with greater responsiveness to this therapy raises the hope that further manipulations directed against suppression of extratesticular androgens may be a useful approach as second-line treatment of advanced prostatic cancer.

Aged

An eight-year experience with a very-low-calorie formula diet for control of major obesity.

We have utilized a very-low-calorie formula diet (VLCD) along with multidisciplinary group counselling in an attempt to achieve and maintain major weight loss in 4026 morbidity obese patients. Using a 420-cal protein supplement (Optifast), men lost weight, at an average of 4.6 +/- 0.9 lb/week and women, 3.1 +/- 1.1 lb/week. Men remained on the VLCD an average of 13.2 weeks, resulting in a mean weight loss of 66.0 +/- 8.1 lb; women remained on the fast an average of 14.1 weeks, with an average loss of 47.3 +/- 4.2 lb. Outcome analysis revealed that 25 percent of patients were unable to adapt to this approach, dropping out within the first 3 weeks. Of the patients remaining in the program, 68 percent lost considerable weight, but did not reach their goal; of this group, recidivism was extremely high, with only 5-10 percent maintaining weight loss after 18 months. Thirty-two percent of the patients successfully attained goal weight; the holding rate of this group has been considerably greater, with 30 percent of women and 58 percent of men maintaining weight loss (within 10 lbs) for a minimum of 18 months. Complications of obesity i.e. hypertension, type II diabetes mellitus, and hyperlipidemias were remarkably improved after weight loss. Complications of the VLCD including cardiac abnormalities, were minimal. Our 8-year experience strongly suggests that the VLCD approach using high quality protein supplement and multi-disciplinary counselling provides a reasonable success rate for achieving and maintaining weight loss in the morbidity obese population.

Adult

The coexistence of male pseudohermaphrodites with 17-ketosteroid reductase deficiency and 5 alpha-reductase deficiency within a Turkish kindred.

Two distinct enzyme defects affecting androgen production and resulting in male pseudohermaphroditism were found in a Turkish kindred from a small isolated village in the Taurus mountains of southern Turkey. Pedigree analysis revealed the inter-relationships of 9 male pseudohermaphrodites. Six affected subjects had adequate steroid hormone analysis. Two adult male pseudohermaphrodites had 17-ketosteroid reductase deficiency with elevated concentrations of plasma androstenedione relative to testosterone, and elevated concentrations of urinary androsterone (A) and etiocholanolone (E) relative to tetrahydrocortisol (THF), 5 alpha-tetrahydrocortisol (5 alpha-THF) and tetrahydrocortisone (THE). Four affected males (three adults, one child) had 5 alpha-reductase deficiency (elevated ratios of plasma testosterone/dihydrotestosterone and urinary 5 beta/5 alpha C19 and C21 steroid metabolites). The homozygous state for both enzyme deficiencies was not demonstrable in the same affected subject, suggesting that the enzyme deficiencies are segregating separately within this kindred. Whether the mutant genes are segregating on allelic chromosomes or other autosomes cannot be determined from this study.

17-Hydroxysteroid Dehydrogenases

Possible differences in potency of purified pork insulins: confirmation by the euglycemic clamp technique.

A 33-year-old female with insulin-dependent diabetes mellitus (IDDM) for 14 yr had been taking a constant insulin dose for 2 yr. She experienced frequent hypoglycemic reactions when switched from purified pork insulin Iletin II NPH (LILLY) to Protophane (NOVO) which could not be explained by a change in either diet or body wt. A 75% reduction in dose led to a restoration of prior control. The euglycemic clamp technique was utilized to determine whether a difference in potency existed between the 2 commercially available purified pork insulins in this patient and 4 additional subjects, one of whom was not diabetic. There was an 18% difference in potency between insulins in the patient leading to these studies. A difference of more than 10% was noted in 3 of the 5 paired tests, suggesting increased potency (18, 29, 55.1%) of Actrapid (NOVO) compared with Iletin II Regular (LILLY). Until these preliminary observations are confirmed or denied, it is prudent to observe patients closely when switching from one brand of insulin to another even when the species of origin and purity are the same.

Adult

Familial male pseudohermaphroditism due to 5-alpha-reductase deficiency in a Turkish village.

Twelve persons with sexual ambiguity were identified in an isolated village in southern Turkey. Eleven were examined and had pseudovaginal perineoscrotal hypospadias; eight were studied. Serum and urine samples from five affected males and urine samples from three affected children were analyzed. Urine samples from another 26 villagers, mostly parents and siblings, were also analyzed. In all but one of the affected adult subjects, serum testosterone levels were either normal or increased, and in all adults, the dihydrotestosterone levels were low (8 to 20 ng/dl) and the testosterone/dihydrotestosterone ratios were elevated (to 36 or more); the levels of 4-androstenedione were normal. Thirty-four urine samples were analyzed for etiocholanolone/androsterone, 11-beta-hydroxyetiocholanolone/11-beta-hydroxyandrosterone, tetrahydrocorticosterone/5-alpha-tetrahydrocorticosterone and tetrahydrocortisol/5-alpha-tetrahydrocortisol ratios. In affected persons, all 5-beta/5-alpha urinary C19 and C21 steroid metabolite ratios measured were elevated. These findings are compatible with the diagnosis of male pseudohermaphroditism due to 5-alpha-reductase deficiency. In parents and some of the siblings of the affected subjects, the 5-beta/5-alpha urinary ratios were between affected and normal levels. The intermediate 5-beta/5-alpha ratios of the parents who were phenotypically normal, together with documented consanguinity, confirm an autosomal recessive mode of inheritance and are useful in identification of the carrier state. The urinary tetrahydrocortisol/5-alpha-tetrahydrocortisol ratios provided the highest index of discrimination between homozygotes (mean +/- SD, adults: 35.80 +/- 20.10; children: 15.48 +/- 7.91), heterozygotes (parents: 4.56 +/- 1.61; siblings and other relatives: 5.97 +/- 3.68), and normal subjects (1.07 +/- 0.36). Thus, this study identified a second community with inherited male pseudohermaphroditism due to 5-alpha-reductase deficiency, confirming the autosomal recessive inheritance of this condition and the generalized abnormality in both C19 and C21 steroid 5-alpha metabolism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Red cell sorbitol and diabetic control.

There is a disagreement about the value of red cell sorbitol as an indicator of diabetic control. We studied 7 insulin requiring diabetics, one for 10 days and 6 for 24 hours. In the 10-day study, blood samples were obtained every 4-6 hours. Sequential analysis of plasma glucose and red cell sorbitol levels showed that simultaneous levels had the best correlation r = 0.534, P less than .001. In the 24-hour studies, blood samples were obtained at 1 to 4-hour intervals. Three of the 6 patients showed the best correlation between simultaneous plasma glucose and red cell sorbitol, with r = 0.727 to 0.957 and P less than .001 to P less than .07. When plasma glucose values were compared to red cell sorbitol levels 1, 2, 4, 8 and 12 h later, correlation coefficients were not as good as the simultaneous comparison. We conclude that the measurement of red cell sorbitol correlates well with simultaneous plasma glucose in some but not all diabetic subjects and provides no additional information to the clinician.

Adult

Elevated prolactin levels in bronchogenic carcinoma.

The frequency and significance of hyperprolactinemia was studied in 21 consecutive, untreated male patients with bronchogenic carcinoma. Seven patients (33%) were found to have elevated serum prolactin (hPRL) levels. No correlation was demonstrated between increased hPRL levels, tissue histology, or tumor burden. L-dopa suppression and/or TRH stimulation tests were obtained in three untreated patients with hyperprolactinemia. The results of these tests were considered normal suggesting hypothalamic control.

Adenocarcinoma

Enkephalins and pituitary hormone release: modification of responsiveness to LHRH.

An intraperitoneal injection of leucine-enkephalin into rats stimulates gonadotropin and prolactin release. To elucidate the mechanism of this releasing property of leucine-enkephalin, rat hemipituitaries were incubated with either enkephalin alone or enkephalin in combination with OHRH. Enkephalin alone had no effect on LH or prolactin release in vitro but potentiated the LH response to LHRH. Neither leucine-enkephalin nor LHRH alone had an effect on GH release; however, when combined, a GH response to LHRH occurred. These results suggest that leucine-enkephalin can modify the pituitary responsiveness to certain hypothalamic releasing hormones by a direct pituitary action.

Animals

The hypothalamic-pituitary-gonadal axis during hyperthyroidism in the rat.

The rat, an animal without testosterone-estrogen-binding-globulin, was treated with L-T4 to the point of hyperthyroidism in order to study the hypothalamic-pituitary-testicular axis during this condition. Hyperthyroidism led to a significant decline in serum FSH, a fall in serum LH which was not satistically significant, and no change in serum levels of testosterone or estradiol. Testes of hyperthyroid rats produced significantly more testosterone during in vitro incubations than did the testes of control animals. We conclude that hyperthyroidism in the rat leads to a fall in FSH levels either via direct pituitary suppression or via accelerated FSH metabolism. In addition, in vitro studies suggest that excess thyroid hormone may stimulate intratesticular 17 beta-hydroxysteroid dehydrogenase.

Animals

Increased estrogen production in obese men.

Serum estrone (E1) and 17beta-estradiol (E2) were noted to be 2-fold elevated in a group of morbidly obese men. Urinary E1 and E2 production rates were elevated in proportion to the degree of obesity, with values as high as 127 and 157 micrograms/day, respectively. Although serum testosterone (T) concentrations were reduced in obese men, averaging 348 +/- 35 vs. 519 +/- 42 ng/dl in lean controls, the dialyzable T fractions were elevated and, hence, the calculated free T concentrations were normal in obese men. Further, the obese men exhibited normal serum LH, FSH, and T responses to clomiphene citrate, indicating intact hypothalamic-pituitary-Leydig cell axes. MCRs of T and peripheral conversion of T to E2 and androstenedione (delta) to E1 were all increased in obese men in proportion to the percentage above ideal weight. Although the obese mean exhibited increased blood levels and production rates of estrogens, there were no signs of feminization, increased T-estrogen-binding, globulin levels, or suppressed basal gonadotropin levels, suggesting a lack of biological effect. We postulate that obese men exhibit defective estrogen receptors, leading to decreased T-estrogen-binding globulin, increased clearance of androgenic hormones, and elevated estrogen production rates.

Body Weight

Hyperparathyroidism and coexisting diabetes mellitus. Altered carbohydrate metabolism.

Hyperparathyroidism was diagnosed in a 67-year-old diabetic man treated for 20 years with isophane insulin suspension, 40 to 45 units/day. It was also diagnosed in a 64-year-old diabetic with severe retinopathy and vascular disease, who was not dependent on insulin. In the first case, removal of a parathyroid adenoma resulted in frequent hypoglycemic attacks, which led to a reduction of the administration of insulin isophane suspension to 20 units/day. In the second case, there was a notable improvement in the glucose tolerance testing that followed surgery, accompanied by a decrease in total plasma insulin response from 17,838 to 5,605 units, by planimetry. These observations suggest that hyperparathyroidism worsens coexisting diabetes mellitus and that one must be aware of increased insulin sensitivity and the possibility of severe hypoglycemia in cases that require insulin after surgical correction of the hypercalcemic state.

Aged

Radioimmunoassay for colchicine in plasma and urine.

A radioimmunoassay for the measurement of colchicine (in quantities as small as 0.05 nanogram) in plasma and urine was developed with the use of an antibody from immunized rabbits. After the intravenous injection of 2 milligrams of colchicine in seven subjects, the calculated zero-time concentration in the plasma was 2.9 +/- 1.5 micrograms per deciliter, and the mean half-time in the plasma was 58 +/- 20 minutes. Declining, but measurable, amounts of colchicine could be detected in urine up to day 9 after the drug was administered.

Aged

The circadian rhythm of renin.

The circadian rhythm of plasma renin activity during continuous recumbency was determined fifty-one times in thirty subjects who either slept at night or remained awake for 24 h. Both groups had maximum values between 2400 and 0800 h, despite absence of the expected early morning fall in blood pressure, pulse, and glomerular filtration rate in the awake subjects. Infusion of normal saline between 2300 and 0300 h initially suppressed renin, but did not prevent its subsequent rise regardless of the amount of sodium appearing in the urine. Of thirteen patients tested two to five times, twelve had recurrence of the zenith within a single 4 h period on retesting, despite differences in sodium intake, basal blood pressure, and mean plasma renin activity. Peaks of lesser magnitude were also frequently noted, most commonly at 1000 h and 1800-2000 h. Minimum PRA values were not restricted to a particular time of day and did not generally recur at the same time upon retesting. The mean ratio of maximum to minimum PRA in each study was 246% +/- 18.3% (+/- 1 SEM). The circadian rhythm of renin appears to be independent of known renal mechanisms responsible for regulating renin release. It is possible that this rhythm is controlled by the central nervous system.

Adult

The starved kidney: a defect in renal concentrating ability.

The renal tubular responsiveness to antidiuretic hormone was assessed in seven obese patients during starvation and feeding by an overnight dehydration test followed by exogenous vasopressin. All seven subjects showed a mean reduction of one-third in their maximum urinary osmolality on day 4 of starvation. Thes- data show that the renal tubule is partially insensitive to antidiuretic hormone at a time when it is also insensitive to mineralocorticoids.?Author

Adult