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Biomedical subjects

D Rudman

Publications and source records attributed to D Rudman.

At least 109 records · Page 6Linked to original sources
PubMed1981

Hypotyrosinemia, hypocystinemia, and failure to retain nitrogen during total parenteral nutrition of cirrhotic patients.

Six patients with gastrointestinal malabsorption and 12 with alcoholic cirrhosis received total parenteral nutrition for 4 wk. Freamine II, the source of the amino acids, is nearly devoid of cystine and tyrosine. We monitored daily nitrogen balance and other nutritional parameters and 22 plasma amino acids. Malabsorbers had a strongly positive nitrogen balance and improvements in nutritional parameters. Plasma amino acids were maintained within or above their normal fasting ranges. Eight of 12 cirrhotics resembled malabsorbing patients in terms of positive nitrogen balance, improved nutritional parameters, and plasma amino acids. In 4 cirrhotics, nitrogen balance remained negative and nutritional repletion failed to occur. Plasma cystine and tyrosine fell to below 30% of their normal fasting means. In 2 of these patients, oral supplements of cystine and tyrosine were given during the fifth week of parenteral nutrition. Plasma cystine and tyrosine were normalized, nitrogen balance became positive, and other repletion indicators demonstrated recovery. We conclude that in 4 cirrhotics, repletion was blocked by deficiencies of cystine and tyrosine, resulting from hepatic inability to synthesize cystine from methionine and tyrosine from phenylalanine.

Amino Acids↗
PubMed1981

Enteral versus parenteral nutritional support in cancer patients.

There are many theoretical and practical advantages to enteral rather than parenteral administration of nutrients. However, it is unlikely that enteral supplementation of nutritional intake as presently practiced will be successful as a primary therapy for most patients with the cancer cachexia syndrome. The most likely role of enteral nutritional support (ENS) is in conjunction with other therapies. This modality deserves evaluation in surgery with curative intent. Changes in diet are effective in reducing the gastrointestinal symptoms of abdominopelvic irradiation, but the effect of ENS on the hematologic toxicity of radiation therapy and on response rates and survival is unclear. Elemental diets can reduce the gastrointestinal toxicity of conventional doses of 5-FU, but they worsen the mortality and hematologic toxicity of higher doses. Factors such as protein, fat, and carbohydrate sources, degree of hydrolysis of protein, lactose content, and timing of dietary manipulations are important in evaluating the response to ENS.

Animals↗
PubMed1981

Total parenteral nutrition as an adjunct to chemotherapy of metastatic colorectal cancer.

A randomized study was performed in advanced cancer to test the effectiveness of total parenteral nutrition (TPN) in maintaining and improving nutrition, to examine the effects of TPN on tumor growth, and to determine if TPN altered chemotherapy response rates, treatment tolerance, and survival. Forty-five patients on identical chemotherapy were randomized to TPN versus ad libitum feeding. TPN was well tolerated. No clinical or tumor marker evidence suggesting neoplastic growth stimulation was obtained. Chemotherapy-related complications and chemotherapy responses did not differ between the two groups. TPN had little effect on performance status. TPN patients gained an average of 2.8 kg before chemotherapy, but triceps skinfold and mid-arm muscle area did not change significantly during TPN. Survival did not improve with TPN. We conclude that current techniques of TPN are of limited benefit in advanced colon cancer. A small subset of patients with short-gut malabsorption may be helped. Further study is needed to determine the mechanisms of cancer undernutrition and to refine nutritional supplementation techniques on the basis of these mechanisms.

Adenocarcinoma↗
PubMed1981

Effect of total parenteral nutrition on survival in advanced colon cancer.

To determine if total parenteral nutrition (TPN) with constant infusion of hypertonic glucose and amino acids by central vein (35 kcal/kg/day) would influence survival in advanced colorectal carcinoma, 50 patients were randomized to receive either chemotherapy alone or the same drugs plus TPN for 14 days before treatment and a variable period thereafter. Overall median survival was significantly decreased in the TPN patients (79 vs 305 days, P = 0.03). Survival was significantly decreased in the TPN patients who had lost the least percentage of premorbid weight (0-6%) (66 vs 398 days, P = 0.02), and in all TPN males (61 vs 209 days, P = 0.03), when compared to similar controls. TPN did not increase survival in any patient subcategory. Catheter-related and metabolic complications were uncommon. We conclude that TPN as used in this study did not prolong median survival in the group as a whole, and may have shortened survival in males and in patients with little or no prior weight loss.

Adolescent↗
PubMed1980

Hypocitraturia in patients with gastrointestinal malabsorption.

We measured serum and urinary citrate, oxalate, calcium, and magnesium in 22 normal subjects and in 16 patients with malabsorption. The patients had subnormal levels of serum citrate and magnesium during fasting, subnormal 24-hour levels of urinary citrate, magnesium, and calcium, and excessive levels of urinary oxalate. Daily citrate excretion averaged only 15 per cent of normal. The hypocitraturia in the patients resulted from a subnormal filtered load of citrate and abnormally high net tubular reabsorption of the anion. An oral citrate supplement raised both the serum concentration and the filtered load of citrate to normal fasting values, but net tubular reabsorption remained abnormally high and urinary excretion abnormally low. Intramuscular magnesium sulfate, which corrected the hypomagnesemia and hypomagnesuria, had no effect on serum citrate or its filtered load. Nevertheless the injection restored net tubular reabsorption of citrate to normal and partially improved the hypocitraturia. Full correction of the hypocitraturia was achieved by combined treatment with oral citrate and intramuscular magnesium sulfate. Hypocitraturia may contribute to the formation of oxalate stones in these patients, and therefore our treatment may help to prevent this complication.

Administration, Oral↗
PubMed1980

Effect of growth hormone and oxandrolone singly and together on growth rate in girls with X chromosome abnormalities.

The linear growth effects of oxandrolone, human growth hormone, and Ox + hGH were compared in six girls, age 11 to 15 years, with X chromosome abnormalities (three with X,O karyotype, three with Turner syndrome variants). Over six successive three-month periods, the patient received either no treatment, Ox, hGH, or Ox + hGH. The data demonstrate a significant (P less than 0.001) synergistic effect between Ox and hGH in stimulating linear growth in Turner syndrome and its variants.

Adolescent↗
PubMed1980

Decarboxylation of alpha-ketoisovaleric acid after oral administration in man.

The keto analogues of essential amino acids represent a promising therapeutic modality in hereditary and acquired disorders of nitrogen metabolism. The utilization of these substances in humans has been assayed primarily by nitrogen balance studies. A simple and accurate breath excretion test for 14CO2 enabled us to measure the decarboxylation of 1-14C-alpha-ketoisovaleric acid (KIV, the keto analogue of valine) in two normal and six diseased subjects. Normal volunteers as well as patients with gastrectomy, hepatic failure, renal failure, and myotonic dystrophy were tested in 5-g protein diets supplemented with essential amino acids and KIV (in place of valine). The normal volunteers and the gastrectomy patient were then restudied on 120 g protein/day. With low protein intake, 13 to 32% of ingeted KIV underwent rapid decarboxylation, and this proportion appeared to correlate inversely with damage to organ systems containing the branched-chain keto acid dehydrogenase. With high protein intake, the proportion decarboxylated rose to 44 to 53%. Thse results confirm that the decarboxylation of KIV in man varies under different conditions of dietary intake and metabolic disease. The 14CO2 brewth excretion test is applicable to other related analyses of carboxylic acid metabolism in human subjects.

Adult↗
PubMed1980

Analysis of Twenty-three plasma proteins in ascites. The depletion of fibrinogen and plasminogen.

The concentrations of 23 plasma proteins were measured by radial immunodiffusion in the plasma and ascites of 17 patients with cirrhosis and four patients with intraperitoneal malignancies, to learn whether there is a selectivity in the movement of proteins from plasma into ascites, analogous to that of proteinuria. Additionally, since some of the proteins are involved in coagulation, we hoped to clarify the coagulopathy frequently seen following peritoneovenous shunting of ascites. Analysis was by groups: group 1 consisted of nine patients with cirrhosis with an ascites-total protein content less than 2.5 g/dl; group 2 consisted of eight patients with cirrhosis with ascites-total protein content greater than or equal to 2.5 g/dl; and group 3 consisted of four patients with malignant ascites. The ratio of the plasma concentration/ascites concentration ([P]/[A]) for each protein was calculated for each patient. In each group the median [P]/[A] for each protein was plotted against the natural logarithm of its molecular weight (In MW). For 21 of the 23 proteins, [P]/[A] showed a close linear relationship to In MW. Fibrogen and plasminogen showed significant (p < 0.0002) elevation above the regression line relating [P]/[A] to In MW. This indicates depletion of fibrinogen and plasminogen in ascites. The ascites in group 1 showed moderate selectivity, defined as the slope of the regression line (1.59), while groups 2 and 3 were essentialy nonselective (0.35 and 0.50). Fibrin-split products were elevated in all ascites but not in plasma, indicating either fibrinolysis or fibrinogenolysis within the ascites. A normal ratio for prothrombin suggests fibrinogenolysis may be the dominant mechanism. Thus the coagulopathy induced by LeVeen valve insertion may be in part secondary to the infusion of plasmin or a plasminogen activator into the circulation.

Afibrinogenemia↗
PubMed1980

Abnormal polyamine metabolism in hereditary muscular dystrophies: effect of human growth hormone.

Previous studies showed hyperre-sponsiveness to human growth hormone (hGH) in men with myotonic or limb girdle dystrophies (MMD or LGD). Because polyamines may mediate some actions of hGH, we have now investigated polyamine metabolism in these and other dystrophies. Under metabolic balance study conditions, serum and urine levels of putrescine (Pu), spermidine (Sd), spermine (Sm), and cadaverine (Cd) were measured in six normal men (36-44 yr), four men with MMD (38-44 yr), and three men with LGD (30-36 yr), before and during treatment with 0.532 U/kg body wt ((3/4)/d) of hGH. Daily balances of N, P, and K were also monitored. In the normal subjects, hGH did not influence elemental balances or serum and urine polyamines. In MMD, hGH caused significant retention of N, P, and K (P < 0.005). Basal levels of Sm and Cd were significantly elevated above normal (P < 0.005), and Pu, Sm, and Cd increased two- to fourfold above basal during hGH treatment (P < 0.005). In LGD, hGH also caused retention of N, P, and K. Basal levels of nearly all the polyamines (not serum Pu) were significantly above normal in serum and urine (P < 0.05). During hGH treatment, all four polyamines rose significantly above basal (P < 0.005). Serum and urine polyamine levels in five boys with Duchenne muscular dystrophy, age 8-13, did not differ from those in five age-matched normal boys. Skeletal muscle polyamines were measured in five men (31-40 yr) without muscle disease and in three men with LGD (30-38 yr). Average concentrations of Pu, Sd, Sm, and Cd were 46, 306, 548, and 61 nmol/g wet wt in LGD and 1, 121, 245, and 14 in the normal subjects, respectively (P < 0.05 in each instance). Polyamines were determined in skeletal muscle, liver, kidney, and brain of male mice with hereditary muscular dystrophy and in age- and sex-matched normal controls. Pu, Sd, Sm, and Cd levels were two to three times higher than normal in muscle, but did not differ in liver, kidney, and brain. Similar findings were made in male hamsters with hereditary dystrophy and in their controls. The abnormality in hamster muscle polyamines appeared between 1 and 6 wk of age and persisted or intensified until 30 wk. These data reveal abnormalities of polyamine metabolism in men with MMD, in men with LGD, and in mice or hamsters with hereditary muscular dystrophy. The polyamine disorder could be related to dystrophic patients' hyperresponsiveness to hGH.

Adolescent↗
PubMed1980

Effects of melanotropic peptides on fetal adrenal gland.

Adrenal glands from early, mid, and late fetuses of rabbit, guinea pig, and rat, and from newborn animals of each species, were incubated for 1-4 h with and without 0.1 nM-1 microM ACTH, alpha- or beta-melanocyte-stimulating hormone (alpha MSH or beta MSH). The effects of the peptides were measured on production of glucocorticoids, and on incorporation of labeled thymidine or leucine into DNA or protein, respectively. The findings were similar in all three species. ACTH stimulated synthesis of glucocorticoids throughout fetal life. Potency increased progressively, as reflected by declining minimal effective dose and rising maximal response. In early and mid fetus alpha MSH and beta MSH caused a modest glucocorticoid steroidogenic effect. ACTH and alpha MSH stimulated DNA and protein synthesis in the early and mid fetal gland. alpha MSH was more potent than ACTH in these respects, minimal effective dose being generally 10 times less and maximal response 25-200% greater. The effects diminished or disappeared in the late fetal and newborn gland. These data indicate that alpha- and beta MSH possess steroidogenic or growth-promoting properties, or both, for the fetal adrenal gland.

Adrenal Glands↗
PubMed1980

Effect of plasma inter-alpha trypsin inhibitor and cancer-related glycoprotein EDC1 on phytohemagglutinin-induced thymidine uptake in lymphocytes.

EDC1, a glycoprotein with a molecular weight of 27,500, was purified from the urine of a leukemic patient, and a radioimmunoassay was developed to use as an immunodiagnostic tool for cancer. Previous studies showed that up to 60% of patients with disseminated neoplastic diseases excreted 100 to 500 mg of EDC1 per day. This protein was immunologically related to inter-alpha-trypsin inhibitor (IATI; M.W. 170,000), a glycoprotein normally present in plasma. EDC1, like IATI, inhibited trypsin and chymotrypsin. EDC1 and IATI have now been found to inhibit the incorporation of thymidine into DNA of normal lymphocytes transformed by phytohemagglutinin. In the presence of 1000 micrograms of EDC1 or 300 micrograms of IATI, incorporation of thymidine by cells was totally inhibited. These proteins were not cytotoxic, did not affect transport of thymidine across the membrane, formed no complex with phytohemagglutinin, and did not compete with phytohemagglutinin for its binding sites. It is proposed that EDC1 and IATI may exert this effect by inhibiting a protease required for blastogenesis.

Alpha-Globulins↗
PubMed1980

Elevated plasma and urinary guanosine 3':5'-monophosphate and increased production rate in patients with neoplastic diseases.

The plasma and 24-hr urinary levels of cyclic adenosine 3':5'-monophosphate and of cyclic guanosine 3':5'-monophosphate (cGMP) were determined for 19 healthy normal patients, 54 patients with six types of nonneoplastic diseases (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 54 patients with five types of neoplastic disease (cancers of the lung, colon, and breast, acute myelocyte leukemia, and Hodgkin's disease). The cyclic adenosine 3':5'-monophosphate levels of urine and plasma in normal subjects, in noncancer subjects, and in cancer subjects did not differ significantly. The cGMP levels in the noncancer group were similarly unchanged from those in the normal group. However, mean cGMP levels in the urine and plasma of patients with neoplastic diseases were, respectively, 2- and 3-fold greater than the normal values (p less than 0.005 for urine and p less than 0.05 for plasma). Pharmacokinetic studies with [3H]cGMP in nine healthy controls and 15 patients with neoplasia showed that the mean production rate of this nucleotide in patients with metastatic cancer was elevated when compared to normal patients, but many values fell within the normal range. In acute leukemia, the production rate was seven times normal, with four of five patients having values clearly outside the normal range. The plasma clearance rate in patients with neoplasia was not decreased when compared to that in normal patients. It is proposed that an increased production rate, rather than any change in plasma clearance, accounts for the increased levels of cGMP in the plasma and urine of some patients with neoplastic disease.

Cyclic AMP↗
PubMed1979

Nasogastric hyperalimentation through a polyethylene catheter: an alternative to central venous hyperalimentation.

We performed nasogastric hyperalimentation with polyethylene catheters and appropriate feeding solutions in 12 cachectic patients who had been referred as candidates for central venous hyperalimentation. Most patients had primary gastrointestinal disease. The duration of hyperalimentation averaged 31 days. Seven patients obtained rapid weight gain (average 0.3 kg/day) with the nasogastric hyperalimentation alone. An additional two were successfully repleted with the addition of parenteral fluids via peripheral veins. In the nine repleted patients, serum albumin rose by average 19%, 24-hr urine creatinine by average 21%, and triceps skinfold by average 46%. The nature of the weight gain in the nine successful cases was analyzed by the metabolic balance study technique. Average composition of the increment in weight was: 50% protoplasm, 48% extracellular fluid, 19% adipose tissue, and less than 1% bone. We conclude that nasogastric hyperalimentation can replace central venous hyperalimentation in a substantial proportion of patients now receiving the latter type of treatment.

Adult↗