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Biomedical subjects

M Kutner

Publications and source records attributed to M Kutner.

At least 37 records · Page 2Linked to original sources

Hypercatecholaminemia in Reye's syndrome.

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's syndrome as compared with concentrations in a control population. Hypercatecholaminemia may contribute to the encephalopathy of Reye's syndrome.

Adolescent

Isolation and characterization of Streptomyces erythreus plasmids.

Streptomyces erythreus strains were found to carry several plasmids of molecular weights ranging from about 2 X 10(6) Mr to 40 X 10(6) Mr. Restriction enzyme maps for the streptomycete plasmids pPC7 and pPC8 were constructed for the enzymes Bg/II, EcoRI, XbaI, HindIII, BamHI and SalI. The smaller, pPC8, plasmid appears to be a naturally occurring deletion variant of pPC7. These plasmids belong to the group of conjugative streptomycete plasmids.

Culture Media

Abnormal regulation of pyridoxal 5'-phosphate in Reye's syndrome.

Seeking to determine the effect of liver disease associated with Reye's syndrome on the regulation of plasma pyridoxal 5'-phosphate, we measured this compound in plasma from 11 patients with biopsy-proven Reye's syndrome. Its concentrations in plasma are significantly higher [37.5 (SD 6.13) micrograms/L] at the onset of the disease than after treatment [8.50 (SD 2.9) micrograms/L] or in a group of hospitalized patients with no evidence of liver disease [8.4 (SD 1.5) micrograms/L]. The concentration of pyridoxal 5'-phosphate in plasma at the time the patients entered the hospital correlated significantly with their activities of serum alanine aminotransferase.

Adolescent

Reliability in evaluating passive intervertebral motion.

Reliable measurements are prerequisite to the successful conduct of outcome studies. In a study of the performance of physical therapists (n = 5) in evaluating passive mobility of the vertebral column with normal subjects (n = 5), several sources of measurement variability were assessed: the reliability within and between therapists, the criteria for grading, and the subjects themselves. Intratherapist reliability was found to be dependable; intertherapist reliability was not. Problems that merit further study were identified as idiosyncratic behaviors that may develop with experience, subject characteristics, and the instrument itself. Periodic assessment of the reliability of therapists in performing evaluations is recommended because of its importance to therapeutic programming.

Clinical Competence

Ten years portal hypertensive surgery at Emory. Results and new perspectives.

Five hundred four Shunt procedures have been done at Emory University Hospitals between 1971 and 1981 to decompress bleeding esophageal varices. This paper reviews how far the experiences of a prospective randomized study (55 patients) of distal splenorenal shunts against total shunts is supported by the nonrandomized experience (449 patients), and outlines our current methods of management dictated by this experience. The overall operative mortality for 348 selective shunts is 4.1% and for 156 nonselective shunts, 14.1%. The five-year survival following Selective shunt is 59%, and following nonselective shunt is 49%: more than half the selective shunt patients are alive, in contrast to the median survival of 44.5 months for patients having nonselective shunts. Following Selective shunt, the survival in nonalcoholic patients is significantly better than the median survival of alcoholic patients of 57 months. Encephalopathy, reported at three years after surgery in the randomized patients was significantly (p < 0.001) lower after selective shunt (12%) compared to nonselective shunt (52%): in the same population at seven years, all patients with patent nonselective shunts have clinical or subclinical encephalopathy, but only 30% of the selective shunt patients have subclinical encephalopathy. Shunt patency, immediately after surgery, is 93% following selective shunt, with only two documented late thromboses: nine of nine patients, at a mean of seven years, retain patency in the randomized study. Shunt occlusion increases with time after interposition nonselective shunts: seven of 13 are occluded at a mean follow-up of seven years in the randomized study. Portal venous perfusion is retained in 93% of patients seven to ten days after selective shunt, but in no patient with a patent nonselective shunt. Late portal perfusion is maintained in nine of the eleven patients in the randomized group studied at a mean of seven years after selective shunt. Restoration of portal perfusion has led to clearing of encephalopathy and improvement in hepatic function in six patients. The following conclusions are made: (1) selective shunts can be done with low operative mortality, and long-term patency with excellent control of bleeding; (2) hepatic portal venous perfusion has been maintained after selective shunt for ten years, and this is vital for preventing encephalopathy and maintaining hepatic function; (3) long-term survival after selective shunt is better than any reported series for nonselective shunt; and (4) selective shunts are the operative procedure of choice for variceal decompression and nonselective shunts should rarely be performed for elective decompression.

Analysis of Variance

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

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

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

Dacron interposition shunts for portal hypertension. An analysis of morbidity correlates.

Analysis of 79 Dacron interposition shunts performed at Emory University from 1971 to 1977 identified a number of preoperative characteristics that correlate with short-term and long-term morbidity. Initial hospital mortality was related to the degree of elevation of the bilirubin and serum glutamic oxaloacetic transaminase (SGOT), to the presence of encephalopathy and to the urgency of the shunt procedure. Cumulative survival correlated best with the preoperative SGOT and bilirubin values, but other variables, including the Child's classification, preoperative encephalopathy, serum albumin, and the age of the patient at the time of operation, also exhibited significant associations. The hospital mortality of 13% and cumulative mortality of 48% in this series are in substantial agreement with similar reports in the literature. This experience differs widely from that described by most authors, however, in two other important respects: 1) significant hepatic encephalopathy has been observed in 45% of these hospital survivors, and 2) almost one-quarter of these patients have experienced spontaneous shunt closure. Thus, major shunt related complications have occurred in 70% of the patients to date. This incidence of undesirable consequences raises a serious question concerning the continued use of the Dacron interposition shunt for elective portal decompression.

Adult

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

Relationship between survival and histologic type in small cell anaplastic carcinoma of the lung.

Survival and histologic subtype were compared in 61 patients with small cell anaplastic lung cancer. Patients with lymphocyte-like (oat cell) and fusiform histologies treated with chemotherapy had longer median survivals than the polygonal and other varieties on the same treatment. Likewise, when detectable disease was confined to the chest and supraclavicular nodes, the patients with lymphocyte-like and fusiform types lived longer. The improved survival in the lymphocyte-like and fusiform categories accounted for most of our improved overall median survival rates with the COPP regimen in small cell lung cancer. Survival in the polygonal and other types was not appreciably different from that seen in non-small cell lung cancer (squamous and adenocarcinoma). It may be possible to refine treatment plans on the basis of cell type so as to further increase survival in small cell anaplastic lung carcinoma.

Antineoplastic Agents

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

Accurate measurement of liver, kidney, and spleen volume and mass by computerized axial tomography.

Computerized axial tomography permits accurate cross-sectional radiographic visualization of visceral organs. Thus, "radiographic area" of an organ slice can be calculated and converted to actual area from a standard grid printed on the roentgenogram. Because the width between slices is known, the volume of an organ slice can be calculated as area times width. Mass of the organ slice is then the product of slice volume and organ density, and entire mass of the organ is the sum of the masses of all the organ slices. The validity of this method was examined in four water-filled balloons, in 12 excised human cadaver organs (six kidneys, three livers, and three spleens), and in two human cadavers while the organs (four kidneys, one liver, and two spleens) remained in situ. Radiographic volume and mass agreed with actual volume and mass within +/- 3% to 5%, thus confirming the accuracy of this method.

Humans

Normative data on low back mobility and activity levels. Implications for neuromuscular reeducation.

Low back mobility and electromyographic movements were performed in 121 normal subjects, grouped by age and sex. Women tended to show greater ranges of motion for straight leg raising, trunk rotation and lateral bending while vertebral separation (forward flexion) was greater in men. A sex-age interaction was observed only in lateral bending, thus implying that for other mobility measurements, data within the age groupings employed in this study can be combined for men and women. Electromyographic data were integrated and quantified using EMG biofeedback equipment for unilateral or bilateral recordings made primarily from the erector spinae muscle between lumbar 3-4 and lumbar 4-5 levels, three centimeters lateral to the spinous processes. Dynamic (trunk flexion-extension, lateral rotation-standing, stooping) and static (quiet sitting, rotation-sitting) movements were performed over a ten second interval. Data analyses verified previous electromyographic studies by demonstrating the trunk extensor function of the erector spinae and the relatively greater unilateral activity when turning to the opposite direction in the erect posture. EMG silence was seen during full trunk flexion. Noticeable sex-age interaction were observed for all dynamic movements but not for static activities. Therefore, it is suggested that EMG data during dynamic movements in a normal population cannot be grouped for men and women within a specified age distribution. These data represent one series of baselines to which mobility and movement patterns in a back pain patient group can be compared. Suggestions are offered for the use of EMG biofeedback during dynamic lower back movements as a possible method of alleviating the pain state, perhaps by altering the patient's posture.

Adolescent

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