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Biomedical subjects

D Rudman

Publications and source records attributed to D Rudman.

At least 91 records · Page 5Linked to original sources
PubMed1983

Effects of allopurinol in Duchenne's muscular dystrophy.

There is no effective treatment at present for Duchenne's muscular dystrophy (DMD). Recently, clinical improvement and increased muscle strength have been reported after 100 mg of allopurinol was administered daily to 21 boys with DMD in a double-blind crossover study. Its effectiveness was determined by an extensive battery of muscle function, cardiac, and laboratory tests. The ten-month study was divided into four periods; (1) one month of baseline observation; (2) three months of therapy to allopurinol and placebo control groups; (3) three months of therapy to crossed over groups; and (4) three months of therapy to all patients. No statistically significant changes between the allopurinol and control periods occurred in the muscle function tests. The earlier report of clinical improvement during allopurinol treatment was not confirmed.

Adolescent↗
PubMed1983

Comparison of the effects of Hepatic-Aid and a Casein modular diet on encephalopathy, plasma amino acids, and nitrogen balance in cirrhotic patients.

Hepatic-Aid is purported to ameliorate encephalopathy and promote positive nitrogen balance in protein-intolerant, cirrhotic patients by correcting their imbalanced amino acid profile. This study evaluated Hepatic-Acid by comparing a 50-g Casein diet with an identical diet with 20-g Casein/30-g Hepatic-Aid per day in a cross-over study. Four patients with biopsy-proven stable cirrhosis, encephalopathy, and under-nutrition were studied. Each study period included three days of equilibration and eight days of metabolic balance, with the following measured at baseline and on balance days 5 and 8: routine biochemistry, fasting ammonia, psychometric tests, EEG, and plasma amino acid profiles. There was no significant change in clinical status, routine biochemistry, fasting ammonia, psychometrics or EEG between the two study periods. Mean (+/-SD) nitrogen balance on the Casein diet at 1.5 +/- 1.5 g/day was not significantly different from that on the Hepatic-Aid diet at 1.5 +/- 1.2 g/day. Plasma amino acid profiles showed a significant fall (p less than 0.05) in fasting and intraprandial tyrosine (tyr) and phenylalanine (phe) on Hepatic-Aid, but only intraprandial leucine (leu), isoleucine (ile), and valine (val) were significantly increased (p less than 0.05) on Hepatic-Aid. The ratio leu + ile + val to tyr + phe was significantly increased (p less than 0.05) on Hepatic-Aid. It is concluded that Hepatic-Aid, as given in this study, maintains N balance similar to Casein, alters the amino acid profile towards normal, but does not ameliorate encephalopathy.

Aged↗
PubMed1983

Structural variants of human growth hormone: biochemical, genetic, and clinical aspects.

Human growth hormone (hGH) is a mixture of peptides in which the major physiologic component is a single chain polypeptide of 191 residues with a molecular weight of 22,000 ("22K" form). The minor components differ from the 22K form in terms of mass (e.g. the 20K form, a single-chain peptide synthesized by deletion of residues 32-46 of the 22K isomer, and the 45K variant formed by aggregation of the 22K molecule), or of charge (e.g. the more acidic two-chain forms alpha 2 and alpha 3 which are generated by proteolytic deletion of residues 135-140 and 135-146 from the 22K variant). The minor components also differ from the 22K molecule in (a) their metabolic effects; (b) their capacity to bind to antiserum raised against the 22K form in a radioimmunoassay (RIA); and (c) their ability to bind to membrane receptors for the 22K hGH in a radioreceptor assay (RRA). Two genes, N and V, involved in the biosynthesis of hGH, are located on human chromosome 17. Heritable alterations of the N gene may cause deficiency of immunoreactive hGH and growth failure. A pathologic variant of hGH has also been identified which is indistinguishable from the 22K form on RIA, but which has low reactivity on hGH-RRA and low somatomedogenic activity. Several mechanisms to account for this bioinactive variant are discussed.

Child↗
PubMed1983

Three types of alpha-melanocyte-stimulating hormone: bioactivities and half-lives.

Three types of alpha-melanocyte-stimulating hormone (alpha MSH) that differ in the acetyl status of the N-terminal serine have been found in the neurointermediate lobe of the pituitary gland and in the brain: desacetyl alpha MSH, which lacks an acetyl group; monoacetyl alpha MSH, in which the amino group of the serine is acetylated; and diacetyl alpha MSH, in which both amino and hydroxy groups of the serine are acetylated. We compared the lipolytic and melanotropic actions of these three peptides, and their rates of disappearance from plasma, both in vitro and in vivo. The following differences were found. a) For in vitro lipolytic actions on rabbit adipose tissue slices, the potencies differed according to the order diacetyl = monoacetyl greater than desacetyl. On rabbit isolated adipocytes, however, the three peptides were equipotent. b) For in vivo lipolytic action in the rabbit, not only potency but also kinetics differed. Diacetyl alpha MSH had the slowest onset, longest duration, and greatest potency. The desacetyl variant had the quickest onset, shortest duration, and least potency. c) The half-life for elimination from rabbit plasma both in vitro and in vivo was shortest for the desacetyl form and longest for the diacetyl peptide. d) For in vitro melanotropic effect on frog skin, kinetics of action were the same for all three peptides, but potency differed according to the order diacetyl = monoacetyl greater than desacetyl. Thus acetylation of alpha MSH alters lipolytic and melanotropic potencies in vitro and lipolytic potency and kinetics in vivo. These differences result in part from the fact that acetylation slows the degradation of the tridecapeptide both inside and outside the circulation.

Adipose Tissue↗
PubMed1983

Effects of opioid peptides and opiate alkaloids on insulin secretion in the rabbit.

In pentobarbital-anesthetized rabbits, iv injection of 9 nmol (31 micrograms) human beta-endorphin (beta h-endorphin)/kg BW caused a significant (P less than 0.05) increase in serum glucose and a significant decline in serum insulin during the subsequent 60 min. When 9 nmol/kg BW beta h-endorphin were injected simultaneously with 0.7 g glucose/kg BW, the clearance of serum glucose and the expected glucose-stimulated rise in serum insulin were both inhibited. The threshold dose for the insulinopenic effect of beta h-endorphin in the anesthetized, glucose-loaded rabbit was 0.09 nmol/kg BW. Threshold doses/kg BW were determined for six structurally related peptides found to possess insulinopenic activity: camel beta-endorphin, 0.09 nmol; N-arg-beta h-endorphin, 0.09 nmol; D-ala2-beta h-endorphin, 0.09 nmol; leu5-beta h-endorphin, 0.09 nmol; met-(O)5-beta h-endorphin, 0.9 nmol; and beta h-endorphin1-27, 0.9 nmol. Threshold dose/kg BW for somatostatin was 9 nmol. The following compounds were inactive at 9 nmol/kg BW: N-acetyl-beta h-endorphin; N-acetyl-arg-beta h-endorphin; beta h-endorphin2-31; beta h-endorphin6-31; beta h-endorphin(((1-5 + 6-31))); beta h-endorphin1-18 (gamma-endorphin); beta h-endorphin1-17 (alpha-endorphin); beta h-endorphin1-5 (met-enkephalin); leu5-beta h-endorphin (leu-enkephalin); met-NH2(5)-beta h-endorphin1-5 (met-enkephalinamide); D-ala2-leu5-beta h-endorphin1-5; D-ala2-N-me-phe4, met-(O)5-ol-beta h-endorphin1-5; and D-ala2-D-leu5-beta h-endorphin1-5. Ninety nmoles per kg BW of naloxone did not alter the insulinopenic effect of 0.9 nmol/kg BW beta h-endorphin. As little as 2.9 X 10(-10) molar beta h-endorphin inhibited glucose-stimulated release of insulin by rabbit pancreas slices in vitro. The capacities of the peptides and alkaloids to inhibit insulin secretion in vitro followed the same general order as the in vivo insulinopenic capacities. Naloxone at 2.9 X 10(-6) M did not reduce the antisecretagogue effect of 2.9 X 10(-8) M beta h-endorphin. These findings, when compared with previously described structure-activity relationships for opioid receptors, indicate the presence of a novel receptor for beta-endorphin in rabbit pancreas, the activation of which inhibits glucose-stimulated secretion of insulin.

Amino Acids↗
PubMed1982

Hypocitraturia in calcium nephrolithiasis.

Several investigators have reported that hypocitraturia is frequent in patients with idiopathic kidney stones. In these studies, however, glomerular filtration rate, urinary tract infection, sex, diet, time of day, and medications, all potentially influential variables, were uncontrolled. Fifteen men, aged 30-52 yr, with recurrent idiopathic calcium oxalate stones and 15 normal age-matched men were studied. Patients with hyperparathyroidism, renal tubular acidosis, reduced creatinine clearance (less than 80 ml . min/1.73 M2), or urinary infection were excluded. Medications were stopped 2 weeks before the study began. A standard constant diet, furnishing 800 mg calcium and free of citrate, was fed for 20 days. During the last 10 days, 4.5 g sodium citrate were given orally. Eight-hour collections of urine were analyzed for calcium and citrate. Filtered load and net tubular reabsorption of citrate were also calculated. The 24-h urinary excretion of calcium was elevated in eight stone formers, and citrate excretion was depressed in seven. Five patients were both hypercalciuric anc hypocitraturic. The hypocitraturia resulted from excessive net tubular reabsorption of a normal filtered load of citrate. Urinary citrate was highest between 0800-1600 h, whereas calcium was highest between 1600-2400 h; both components were lowest between 2400-0800 h. The diurnal profiles of urinary calcium and citrate were similar in the stone formers and in the normal men. Oral sodium citrate did not influence urinary citrate in either group. These data suggest that in adult men, hypocitraturia may be a common predisposing factor for calcific nephrolithiasis.

Adult↗
PubMed1981

Children with normal-variant short stature: treatment with human growth hormone for six months.

Children with normal-variant short stature can be classified into four subgroups by measuring their anabolic and growth reactions to a 10-day course of human growth hormone. In Subgroup 1 there is no anabolic or growth reaction; in Subgroup 2 there is a weak anabolic reaction but no growth; Subgroups 3 and 4 have both reactions but Subgroup 4 is more responsive than Subgroup 3. We monitored growth rate and plasma immunoreactive somatomedin C concentrations in four to six children from each subgroup (age range, eight to 11 years) before, during, and after six months of injections of growth hormone (0.08 unit per kilogram of body weight per day). In children in Subgroups 3 and 4, the average somatomedin C level, which was subnormal before treatment, was restored to normal. Simultaneously, the average growth rate accelerated fivefold. In children in Subgroups 1 and 2, whose average pretreatment somatomedin C was normal, growth hormone had little effect on somatomedin level of growth rate. The somatomedin response in Subgroups 3 and 4 was apparent by the 10th day of treatment. This response provides a rapid method for identifying affected children who will benefit from longterm administration of human growth hormone.

Body Height↗
PubMed1981

Gluconate calcium therapy and neonatal hypercalciuria.

Nephrolithiasis was present in a 2-month-old premature infant with bronchopulmonary dysplasia who had been receiving furosemide and intravenous (IV) gluconate calcium therapy. This infant was found to be hypercalciuric. Furosemide therapy is known to increase calcium excretion. In the present study, we examined sick infants who were receiving gluconate calcium without furosemide to evaluate the effect of gluconate calcium therapy on urinary calcium excretion. The sick infants receiving gluconate calcium had higher values of urinary calcium than did the well infants taking regular formula feedings. Moreover, the calciuria appeared to increase progressively with continued gluconate calcium therapy. It appears that prolonged use of either furosemide or IV gluconate calcium leads to hypercalciuria, which, in turn, may predispose the premature infant to nephrolithiasis.

Calcium↗
PubMed1981

Tyrosine transaminase activity in normal and cirrhotic liver.

Most cirrhotics have tyrosinemia and subnormal tyrosine tolerance; in some the ability to metabolize p-hydroxyphenylpyruvic and homogentisic acids is impaired. In previous studies, the initial transamination appeared to be the rate-limiting step. In this study, hepatic tyrosine transaminase activity was compared in liver biopsies from eight noncirrhotic and ten cirrhotic subjects to determine whether the subnormal tyrosine tolerance was related to decreased maximal activity of this enzyme. Fasting plasma tyrosine in the cirrhotics (133 +/- 43 micromol/liter) was significantly higher (P less than 0.005) than in the noncirrhotic subjects (64 +/- 25 micromol/liter). Tyrosine transaminase activity in the cirrhotic livers (42 +/- 11 micromol PHPA/g liver/hr, or 0.47 +/- 0.1 micromol PHPA/mg protein/hr) was not significantly different from the enzyme activity in the noncirrhotic liver (43 +/- 7 micromol PHPA/g liver/hr, or 0.39 +/- .12 micromol PHPA/mg protein/hr.) Thus elevated tyrosine levels in cirrhotics cannot be explained by decreased tyrosine transaminase activity in the liver, and other explanations must be sought.

Aged↗
PubMed1981

A method of screening for growth hormone deficiency using anthropometrics.

Among children less than 3rd percentile in height, less than 1% are deficient in endogenous growth hormone, while 80% have no recognizable organic cause for short stature, and are termed normal variants. This study investigated whether anthropometric evaluation can distinguish growth hormone-deficient from normal variant children. Height, weight, midarm circumference and 10 skinfold thicknesses were measured in 24 growth hormone-deficient and 26 normal variant children; indices of linear growth, adiposity, and lean body mass were derived from these. All these variables were analyzed statistically by discriminant analysis. This led to a screening formula, here called a "Z-function," based only on height and five skinfolds (abdomen, back, chest, knee, and calf). The Z-function classified correctly all but two growth hormone-deficients and two normal variants. Because of the small and possibly inhomogeneous sample, the particular formula developed here is not recommended for general use, but these preliminary findings show that a simple anthropometric screening test is indeed feasible, and could be useful in pediatric practice.

Adipose Tissue↗
PubMed1981

Impaired growth hormone secretion in the adult population: relation to age and adiposity.

Growth hormone (GH) release was studied in adults of normal stature, ages 21-86 yr. The subjects were 85-115% of ideal body weight, between the 5th and 95th percentiles in height, and free of active or progressive disease. 9 to 12 individuals in each decade from thirds to ninth were evaluated. The following criteria of GH status were measured: serum GH concentration, analyzed by radioimmunoassay at half-hour intervals for 4 h after onset of sleep, and at 1-h intervals from 8 a.m. to 4 p.m. in 52 subjects; daily retention of N, P, and K in response to 0.168 U human (h)GH/kg body wt3/4/day in 18 subjects; and plasma somatomedin C (SmC) level before and during exogenous hGH treatment in 18 subjects. All 10 individuals, 20-29 yr old, released substantial amounts of endogenous GH during both day and night (average peak serum GH obtained during day and night was 7.3 and 20.3 ng/ml, respectively); average plasma SmC was 1.43 U/ml (95% tolerance limits, 0.64-2.22 U/ml). There was no significant effect of exogenous hGH on elemental balances or on plasma SmC. In contrast, 6 of 12 individuals 60-79 yr old showed the following evidences of impaired GH release; peak waking and sleeping serum GH less than 4 ng/ml; plasma SmC less than 0.38 U/ml; a significant retention in N, P, and K; and a significant rise in plasma SmC, in response to exogenous hGH. Plasma SmC, serum GH during sleep, serum GH during the day, retentions of N, P, and K in response to exogenous hGH, and rise in plasma SmC in response to hGH were all intercorrelated (P less than 0.05). Plasma SmC less than 0.38 U/ml corresponded to peak nocturnal serum GH less than 4 ng/ml. The prevalence of plasma SmC less than 0.38 U/ml increased progressively from age 20 to 90: third decade, 0%; fourth, 11%; fifth, 20%; sixth, 22%; seventh, 42%; eight, 55%; and ninth, 55%. Within each decade, plasma SmC was inversely related to adiposity.

Adult↗
PubMed1981

Epinephrine deficiency in hypocorticotropic hypopituitary children.

In rats, adrenal medullary synthesis of epinephrine is impaired by ACTH deficiency and is not improved by replacement doses of glucocorticoid. We have evaluated plasma epinephrine and norepinephrine concentrations in 43 children, 8-15 yr old. These children were divided into 5 groups, with 6-10 per group: normals; children with isolated GH deficiency; hypopituitary children deficient in both GH and TSH; hypopituitary children deficient in GH, TSH, and ACTH; and short children without known organic disease. The deficiencies of ACTH and TSH were being treated with replacement doses of cortisol and T4. Plasma catecholamines were measured in the supine position at rest every other hour from 0800-1600 h, and after exercise in the standing position at 1000 h. Plasma norepinephrine levels, both at rest and after exercise, were normal in all four groups of short children. Resting and postexercise plasma epinephrine levels were reduced to 10-20% of normal in the hypocorticotropic hypopituitary patients, and were normal in the other three groups of short children.

Adipose Tissue↗
PubMed1981

Hyperalimentation of the cancer patient with protein-calorie undernutrition.

Because protein-calorie undernutrition is common in patients with neoplastic disease, nutritional support is often recommended. It is uncertain, however, that methods of supplemental alimentation successful in noncancerous subjects are suitable in cancer patients. We measured elemental balances, serum proteins, anthropometrics (triceps skinfold and mid-arm muscle area), and creatinine/height ratio in 15 undernourished patients with advanced cancer and in 10 noncancer undernourished controls during central venous or enteral hyperalimentation and found the following. (a) During central venous hyperalimentation, cancer patients showed significantly less improvement than the noncancerous controls in body weight (median increment, 5 kg in cancer patients and 8.5 kg in noncancerous), albumin (0.1 g/dl in cancer patients and 0.5 g/dl in noncancerous patients), creatinine/height ratio (4% of standard in cancer and 10% of standard in noncancer), and mid-arm muscle area (4% of standard in cancer and 11% of standard in noncancer). During enteral hyperalimentation, gains in body weight and albumin by cancer patients were significantly inferior to those in noncancerous subjects. Triceps skinfold increments, in contrast, were similar during both central venous and enteral hyperalimentation for cancer and noncancerous patients. (b) While nitrogen retention was similar in cancer and noncancer patients, the cancer group retained significantly less magnesium and phosphorus (delta Mg in cancer patients, 3.2 mEq/day central, -2.7 mEq/day enteral; delta Mg in noncancer patients, 11.9 mEq/day central, 10.1 mEq/day enteral; delta P in cancer patients, 0.13 g/day central, 0.07 g/day enteral; delta P in noncancer patients, 0.27 g/day central, 0.33 g/day enteral). The poorer balances of cancer patients were caused by increased urinary, not fecal, loss. These findings indicate a partial block in repletion of lean body mass or abnormal composition of newly deposited lean body mass when undernourished patients with advanced cancer receive hyperalimentation.

Adult↗