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Biomedical subjects

D Rudman

Publications and source records attributed to D Rudman.

At least 199 records · Page 11Linked to original sources
PubMed1973

Maximal rates of excretion and synthesis of urea in normal and cirrhotic subjects.

When normal individuals eat 0.33 g protein N/kg body weight (BW)((3/4)) per day, they excrete 10-15 mg urea N/h per kg BW((3/4)). If they now ingest (at 0 h) 0.27 (dose A), 0.40 (dose B), 0.53 (dose C), 0.94 (dose D), or 1.33 (dose E) g protein N/kg BW((3/4)) (in the form of casein, ovalbumin, or lactalbumin), the rate of urea N excretion accelerates within 4 h. At dose C a maximal rate of urinary urea N excretion (MRUE) is reached, which averages 55 mg urea N/h per kg BW((3/4)) and which persists for 16 h. Higher doses of protein do not further accelerate urea excretion, but prolong the duration of MRUE to 28 h (after dose E). Blood urea N (BUN) rises by 7-20 mg/100 ml during the first 8 h after dose C to E, and remains stable within +/-5 mg/100 ml during the ensuing 8-28 h of MRUE. Each increment of protein above dose C causes a further increment in plasma alpha-amino N. During infusion of free amino acids at a rate of 110 or 165 mg amino acid N/h per kg BW((3/4)) for 12 h, rate of urea excretion increases to the MRUE value produced by dose C-E of oral protein.These findings indicate that MRUE corresponds to a period of maximal rate of urea synthesis (MRUS). MRUS is greater than MRUE because one fraction of newly formed urea is hydrolyzed in the gastrointestinal tract, and another fraction may accumulate temporarily in body water during the MRUE period. Oral neomycin reduces the proportion of urea hydrolyzed in the gut to less than 20%; its extent is measured by recovery in the urine of a tracer dose of [(14)C]urea injected intramuscularly during determination of MRUE. Accumulation of urea in body water is estimated from increment in BUN during the period of MRUE measurement (8-24 h after dose E of casein) and from body water measured with (3)H(2)O. Then MRUS is calculated as: ([mg urea N excreted between 8 and 24 h after dose E] + [BUN at 24 h - BUN at 8 h] x [body water]) x (100/% recovery [(14)C]urea) x (1/kg BW((3/4))) x (1/16 h).MRUS in 10 normal subjects averaged 65 mg urea N/h per kg BW((3/4)) (range 55-76), and in 34 cirrhotics 27 mg urea N/h per kg BW((3/4)) (range 6-64). Among 19 cirrhotic patients fed 40, 60, 80, or 100 g protein daily for successive 10 day periods, the occurrences of hyperammonemia, hyperaminoacidemia, and encephalopathy at each level of protein intake were inversely related to MRUS value.

Administration, Oral↗
PubMed1973

Metabolic effects of plasmin digests of human growth hormone in the rat and man.

As a first step in our study of structure-function relationships among primate and non-primate growth hormones, human growth hormone (hGH) was subjected to the limited digestive activity of human plasmin. The lyophilized whole digest, containing less than 2% of unchanged hormone, had an average of 2.3 new amino-terminal groups per mole. The digest had the same potency as the native hormone (a) in causing weight gain in hypophysectomized rats; (b) in stimulating somatomedin production in hypophysectomized rats; (c) in stimulating upake of [(3)H]leucine into isolated diaphragm of hypophysectomized rats; (d) in accelerating transport of [(14)C]alpha-aminoisobutyric acid into isolated diaphragm of hypophysectomized rats; (e) in stimulating uptake of [3-0-methyl-(14)C]glucose by isolated adipose tissue of hypophysectomized rats; (f) in accelerating conversion of [(14)C]glucose to (14)CO(2) by isolated epididymal adipose tissue of hypophysectomized rats. The digest also caused glucosuria in partially pancreatectomized rats treated with dexamethasone. These metabolic actions of plasmin-digested hGH in the array of animal tests were confirmed by comparable effects elicited in 11 human subjects (nine pituitary-deficient children and adolescents and two nondeficient adults). A single injection of the plasmin digest caused an increase in plasma free fatty acids and a fall in plasma amino acids. Seven daily injections caused positive balances of nitrogen, phosphorous, sodium, and potassium, gain in body weight, and in two of three subjects impairment of glucose tolerance. The potency of the plasmin digest in producing these metabolic effects in man was comparable to that of native hGH.Thus, 2-3 bonds in the hGH molecule can be cleaved by plasmin without impairing the hormone's growthpromoting, anabolic, diabetogenic, and adipokinetic actions for rat and man.

Adipose Tissue↗
PubMed1972

Metabolic effects of human growth hormone and of estrogens in boys with Duchenne muscular dystrophy.

Metabolic balance studies were conducted in seven boys with Duchenne-type muscular dystrophy, and in six normal boys of similar age, during a 12 day control period and during a 12 day period of treatment with human growth hormone (HGH) at the following doses: 0.0168, 0.0532, and 0.168 U/kg body weight (BW)((3/4)) per day (doses A, B, and C, respectively). In five of the six normals, dose C caused positive balances in N, P, Na, and K; doses B and A had anabolic effects in two and one normal subjects, respectively. In six of the seven Duchenne cases, dose C caused negative balances of N and K, and sometimes of P. Negative balances were produced in three of the Duchenne subjects by dose B, and in one by dose A. None of the dystrophy cases exhibited an anabolic response to any dosage of HGH tested. The release of endogenous HGH in response to insulin, after 2 days' pretreatment with diethylstilbestrol, was similar in both groups of subjects. In the course of these tests, a marked anabolic effect of diethylstilbestrol in the Duchenne patients was apparent. Therefore metabolic balance studies were repeated, in both Duchenne and normal cases, during a 12 day control period and during 12 days of treatment with diethylstilbestrol (0.106 mg/kg BW((3/4)) per day). In three of the normal children, diethylstilbestrol had no effect on the elemental balances; in two cases, a retention of Na was observed. In all seven Duchenne cases, diethylstilbestrol caused positive balances in N, P, Na, and K. Ethinyl estradiol (0.0106 mg/kg BW((3/4)) per day) produced positive N, P, Na, and K balances in all three Duchenne cases tested with this agent. The data show that exogenous HGH causes a catabolic effect in boys with Duchenne dystrophy. These patients are hyperresponsive to the anabolic effect of diethylstilbestrol. The latter phenomenon may reflect the inhibitory effect of estrogen upon the peripheral actions of these boys' endogenous HGH.

Adolescent↗
PubMed1971

Capacity of human subjects to utilize keto analogues of valine and phenylalanine.

Three adult human subjects were maintained for 7 days (period I) on a protein-free formula diet containing the minimum daily requirements of the eight essential amino acids plus 40 g glycine. During the last 5 days of this period, the average daily nitrogen balances for the three subjects were +0.52, +0.71, and +0.30 g, respectively. During the next 7 days (period II), valine was withdrawn from the diet, and the glycine ration increased by an equimolar amount. During the last 5 days of period II, average daily nitrogen balances declined to -1.82, -1.61, and -1.87 g, respectively. In the final period of 7 days (period III), the keto analogue of valine, alpha-ketoisovaleric acid, was added to the diet in a quantity equimolar to the minimum daily requirement of valine. During the last 5 days of this period, average daily nitrogen balances improved to -0.02, -0.18, and -0.83 g, respectively. Analogous experiments in three subjects involved the withdrawal from the diet of phenylalanine (period II) and replacement by its keto analogue, phenylpyruvic acid (period III). The average daily nitrogen balances were as follows: period I: +1.04, +0.96, and +0.53 g; period II: -1.45, -1.83, and -1.94 g; period III: +0.07, +0.11, and -0.52 g. The data demonstrate that man can convert alpha-ketoisovaleric acid and phenylpyruvic acid to the corresponding essential amino acids, valine and phenylalanine. The efficiency of these conversions is considerably less than 100%.

Adult↗
PubMed1971

Observations on the responsiveness of human subjects to human growth hormone. Effects of endogenous growth hormone deficiency and myotinic dystrophy.

The effect of human growth hormone (HGH) on the N, P, Na, and K balance, and on the body weight (BW) of three groups of subjects was measured. In group I were nine cases (age 6-69) with HGH deficiency; in group II, eight cases (age 9-79) with normal endogenous HGH; in group III, four cases with myotonic dystrophy (age 45-51). After a 7 day control period, the hormone was administered for 7 days. Each subject was tested with three doses of HGH: dose A, 0.0168 U/kg BW(3/4) per day; dose B, 0.0532 U/kg BW(3/4) per day; dose C, 0.168 U/kg BW(3/4) per day. In group I, the responsiveness to HGH declined with age. Two subjects aged 6 yr responded to all three doses of HGH with positive balances in N, P, Na, and K and increases in BW. At ages 15-17, responses were obtained only to doses B and C in three cases, and only to dose C in two cases. Two subjects, aged 42 and 69, responded only to dose C. Not only did the threshold dose increase with age in group I, but the magnitude of the responses declined with age as well.Patients of group II were less responsive to all doses of HGH than were patients of group I at comparable age. None responded to dose A or dose B. All responded to dose C, but the increments in balances and in BW stimulated by this dose were only one-third to one-half as great as in HGH-deficient subjects of similar age. Three patients of group III responded to all three doses of HGH, and one responded to doses B and C. The responses were similar in magnitude to those in the 6-yr old HGH-deficient children, and greater than those in all other subjects studied. These data show that responsiveness to exogenous HGH rises with deficiency of endogenous HGH, and that individuals with myotonic dystrophy are hyperresponsive to exogenous HGH.

Adolescent↗