PubMed Health⌕ Search

Biomedical subjects

D Rudman

Publications and source records attributed to D Rudman.

At least 127 records · Page 7Linked to original sources

Accumulation of urinary cancer-related glycoprotein, EDCl, in psoriasis.

EDCl is a novel glycoprotein, mol wt 27,000, isolated in 1976 from leukemic urine. It inhibits the serine proteases trypsin and chymotrypsin and is antigenically related to interalpha trypsin inhibitor (IATI), mol wt 170,000, a normal plasma antiprotease. Since psoriasis is a non neoplastic hyperproliferative state, we have now measured EDCl by a specific radioimmunoassay (RIA) in plasma and urine of 24 untreated psoriatic patients. EDCl was not detectable in normal urine (less than 1 mg/gm creatinine) or plasma (less than 1 mg/L). 55% of psoriatic urine specimens were positive by RIA, containing 8 to 110 mg/gm creatinine. 75% of plasmas were positive, containing 12 to 32 mg/L. Plasma and urine contents of EDCl were significantly (P less than .05) correlated with severity of clinical disease (% skin involved) but not with age, sex, distribution or type of lesion, family history or arthritis.

Adult↗

Tyramine kinetics and metabolism in cirrhosis.

Hypertyraminemia is common in hepatic cirrhosis and correlates in severity with encephalopathy. The mechanism of cirrhotic hypertyraminemia has not been established. The alternative possibilities are increased production from tyrosine and impaired degradation by monoamine oxidase. This investigation determined the pharmacokinetics of tyramine after an intravenous bolus injections of [3H]-tyramine (180--200 muCi 12 Ci/mmol sp act) in 13 cirrhotics and 9 controls. In normals, [3H]tyramine levels initially declined rapidly (alpha-phase) followed by a slower decline (beta-phase) with an average t 1/2 of 20.8 min. Average normal metabolic clearance rate and production rate were 13.2 liters/min and 15.4 microgram/min, respectively. In cirrhotic patients, the plasma disappearance curve for [3H]tyramine was qualitatively similar to that of the control subjects with no apparent different in beta-t 1/2 (17.2 min). The hypertyraminemia of cirrhosis resulted primarily from overproduction of tyramine, as the production rate (32.0 microgram/min) in these patients was significantly greater (P less than 0.05) than in controls, whereas the metabolic clearance rate remained normal (average 12.2 liters/min). A difference in ratio of tyramine metabolic products was noted as well. Cirrhotics had a high ratio of plasma 4-hydroxyphenylethanol:4-hydroxyphenylacetic acid (60:40 vs. 30:70) as compared with normals. Although the tyramine clearance rates are similar in normals and cirrhotics, different mechanisms may be responsible for catabolism.

Adult↗

Serum and urine polyamines in normal and in short children.

The serum and urine polyamines putrescine, spermidine, and spermine were measured in 112 normal subjects from 0 to 70 yr of age, and in three groups of short children from 7 to 20 yr: 21 growth hormone (GH) deficient patients, 20 normal variant short stature children, and 9 girls with 45, X Turner's syndrome. Urine polyamines were expressed as micromoles per gram of creatinine or per kilogram body weight, and serum polyamines were expressed as nanomoles per milliliter. In normals, the three polyamines were highest in urine and serum at birth. The mean levels declined progressively with age, the rate of change decreasing with age. The mean for the normal subjects, and its 95% confidence and prediction intervals, were estimated from birth to age 70 for each serum and urine polyamine. In GH-deficient children, serum and urine values were significantly lower (P < 0.05) than the age-specific normal values (with the exception of serum spermidine and spermine), averaging 25-55% below normal. This abnormality was corrected during 1 wk of treatment with human GH. In Turner's syndrome, serum and urine values were significantly reduced (P < 0.05), averaging 35-80% below age-specific normals. GH treatment had no corrective effect. In 6 of 20 normal variant short stature children, polyamine levels were significantly (P < 0.01) subnormal, averaging 50-80% below age-specific normals in both serum and urine. Treatment with GH had no corrective effect. These data show that levels of polyamines in serum and urine are correlated with linear growth primarily during the first decade of life. Subnormal polyamine levels are generally associated with growth retardation.

Adolescent↗

Predicting the response of growth hormone-deficient children to long term treatment with human growth hormone.

A previous study showed that when GH-deficient children below the third percentile in height are treated with 0.168 U human GH (hGH)/kg BW3/4 for 10 days, their height increases by 0.3--1.9 cm during the next 8 weeks. The present study determined whether this acute response would predict the child's long term response to 1 yr of treatment with the same dose of hGH given three times a week. Eighteen GH-deficient children and adolescents, aged 8--16 yr, were measured every 2 weeks over 108 weeks. After a control period of 12 weeks (period 1), the patient received hGH for 10 days. During the remainder of the 12 weeks of period 2 and during the next 12 weeks (period 3), hGH was not given. Patients recieved hGH three times a week during periods 4 and 5 (24 weeks each). Periods 6 and 7 (12 weeks each) were posttreatment control periods. During periods 1, 3, 6, and 7, rate of growth was less than 0.2 cm/month. During period 2, the rate ranged between 0.1--0.8 cm/month. During periods 4 and 5, the growth rate ranged from 0.2--1.0 cm/month. Rate of growth during periods 4 and 5 (y) was related to rate during period 2 (x) by the equation y = 0.027 + 1.17 x. The correlation coefficient between y and x was 0.91 (P less than 0.001). The increment in height which will occur during 48 weeks of treatment can be predicted from the response to 10 days of treatment by this equation. The SE of the prediction averages +/- 1.2 cm/yr.

Adolescent↗

Enteral hyperalimentation: an alternative to central venous hyperalimentation.

Severe protein-energy undernutrition is a frequent finding among chronically ill patients. Its causes are anorexia, hypermetabolism, and malabsorption. Adverse consequences include impaired cell-mediated immunity increased susceptibility to infection, poor wound healing, weakness, and death. Spontaneous oral intake is inadequate in patients with this disorder, and therapeutic maintenance or repletion alimentation is needed. Enteral hyperalimentation is the method of choice, if tolerated. A successful treatment program usually requires a small-bore, flexible nasoenteral tube, appropriate feeding solution, and constant flow delivery of nutrient. If only partial dietary requirements are tolerated enterally, peripheral intravenous nutrient solutions can often supply the deficit. Although not suitable for all patients, enteral hyperalimentation is more physiologic, safer, easier, and more economical than central venous hyperalimentation. It would be well tolerated by many patients who now receive nutritional repletion by the latter method.

Humans↗

Plasma and urine cyclic guanosine 3':5'-monophosphate in disseminated cancer.

Plasma and 24-h urinary adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclic GMP) were measured by radioimmunoassay in 12 normal subjects, 33 patients with six types of non-neoplastic disease (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 34 patients with five types of disseminated neoplastic disease (acute myelocytic leukemia; Hodgkin's disease; and metastatic cancer of the lung, colon, and breast). In patients with non-neoplastic disease, cyclic nucleotide values in plasma and urine did not differ significantly (P greater than 0.05) from those in normal subjects. In patients with disseminated cancer, cyclic AMP values in plasma and urine likewise did not differ significantly from those in normal subjects. Plasma cyclic GMP, in contrast, was significantly elevated in all five types of cancer patients, and urinary cyclic GMP was significantly elevated (five times the normal mean) in patients with acute myelogenous leukemia and Hodgkin's disease.

Adult↗

Hyperalimentation in alcoholic hepatitis.

Enteral hyperalimentation in four patients with severe alcoholic hepatitis and anorexia increased spontaneous food intake, increased their nitrogen balance and the patients improved clinically. Seven patients with alcoholic hepatitis, who were clinically ill and able to eat only 410-1,100 calories per day, were given a 900 mosM/l. parenteral "hyperalimentation" solution by a peripheral vein (P-900). The intravenous nutrition provided daily 51.6-77.4 gm. amino acids in addition to oral intake. All patients improved. None developed detectable encephalopathy after 16-42 days of P-900 therapy. Five additional patients had ascites and alcoholic hepatitis. The daily infusion of 2,000 ml. P-900 was not associated with hyponatremia, renal failure or encephalopathy in four of these five patients who improved and continued their diuresis. P-900 therapy was discontinued in one because of progressive hyponatremia. The observations indicate that over and above the maximum tolerable oral nutrition, intravenous nutrition can be effectively utilized by clinically ill, jaundiced patients with alcoholic hepatitis without precipitating encephalopathy or interference with standard therapy of ascites.

Hepatitis, Alcoholic↗

Tyrosine metabolism in cirrhosis.

The aim of this study was to define the enzyme defect responsible for tyrosinemia in cirrhotic patients. The principal hepatic degradation pathway for tyrosine, tyrosine leads to p-hydroxyphenylpyruvic acid equilibrium homogentisic acid leads to CO2 was studied in 18 cirrhotic patients and eight controls. The classic method employed in elucidation of hereditary tyrosinosis was sued. Metabolic intermediates on the pathway were measured in the basal state, and following oral loading doses (50 mg/kg BW) of tyrosine, PHPA, and homogentisic acid. Cirrhotic patients showed a significant increase (p = 0.005) in fasting plasma tyrosine and in basal PHPA excretion and impaired tolerance to all three metabolites when compared to normals. Fifteen of the 18 cirrhotic patients showed tyrosine intolerance which was not accompanied by change in distal metabolites compared to their basal levels. Nevertheless 13 of the 18 did exhibit intolerance of either PHPA or homogentisic acid. We conclude that in contrast to the single complete defect in hereditary disorders of tyrosine metabolism, cirrhotic patients have partial defects at tyrosine transaminase, PHPA oxidase, and homogentisic acid oxidase, the initial step being rate-limiting.

Adult↗

Prostaglandins in blood of diabetic versus non-diabetic humans.

We have found a higher concentration of prostaglandins in blood from the diabetic patient under long-term indomethacin therapy as compared with blood from non-diabetics. These findings are generally (qualitatively) similar to previous reports with studies of blood serum from diabetic patients, not on indomethacin treatment, compared with non-diabetics. Certain rationale are presented in an effort to explain the reason why blood prostaglandins in the diabetic are not lowered when the patients are treated with a drug which is clearly established as a blocker of prostaglandin synthesis.

Diabetes Mellitus↗

Prevalence of growth hormone deficiency in children with cleft lip or palate.

Two hundred children 7 to 14 years of age with isolated cleft defects of the lip, palate, or both were surveyed for stature. Twelve percent were less than the third percentile in height and were designated "short." All of the short children received an endocrine evaluation. Endogenous growth hormone was examined after two days' pretreatment with stilbesteral. Four of the 25 short children with CLP had total, and four had partial, GH deficiency. Three of the GH-deficient patients were also deficient in ACTH or TSH. In contrast, in a series of 75 short (less than third percentile) children 7 to 14 years of age without cleft defect or other apparent congenital abnormality, only two had total and two had partial GH deficiency. The data suggest that children with isolated CLP have short stature about four times more often, and GH-deficiency about 40 times more often, than children without CLP. The increased prevalence of GH-deficiency may stem from the embryologic relation of adenohypophysis and oral ectoderm.

Adolescent↗

A randomized, controlled trial of the distal splenorenal shunt.

In 1971 a prospective, randomized trial was initiated to determine efficacy of the distal splenorenal shunt in the management of cirrhotic patients who had previously bled from esophageal varices. When entry into the trial was terminated in 1976, 26 patients had received the distal splenorenal shunt (selective) and 29 had undergone a nonselective shunting procedure (18 interposition mesorenal, six interposition mesocaval, and five other nonselective shunts). Three operative deaths occurred in each group. Early postoperative angiography revealed preservation of hepatic portal perfusion in 14 of 16 selective patients (88%), but in only one of 20 nonselective patients (5%; p < .001). Quantitative measures of hepatic function (maximal rate of urea synthesis or MRUS and Child's score) were similar to preoperative values in the selective group but were significantly decreased in nonselective patients on the first postoperative evaluation (p < .001 for MRUS; p < .05 for Child's score). Eighty-seven per cent of selective and 81% of nonselective patients have now been followed for three to six years since surgery. Late postoperative evaluation of 29 survivors (12 selective, 17 nonselective) still shows an advantage to the selective group with respect to MRUS, Child's score, and incidence of hepatopetal portal blood flow, but differences are no longer statistically significant. However, if the seven patients with portal flow (five selective; two nonselective) are compared to the 20 with absent portal flow (seven selective; 13 nonselective), the former group has significantly higher values for MRUS (p < .05) and Child's score (p < .025). No patient with continuing portal perfusion has developed encephalopathy as compared to a 45% incidence of this complication in individuals without portal flow (p < .05). No significant differences between selective and nonselective groups have appeared with respect to total cumulative mortality (ten selective; 38%; eight nonselective, 28%), shunt occlusion (two selective, 10%; five nonselective, 18%), or recurrent variceal hemorrhage (one selective, 4%; two nonselective, 8%). Overall, significantly fewer selective patients have developed postoperative encephalopathy (three selective, 12%; 15 nonselective, 52%; p < .001). Therefore, we conclude that the distal splenorenal shunt, especially when its objective of maintaining hepatic portal perfusion is achieved, results in significantly less morbidity than nonselective shunting procedures.

Alcoholism↗