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Biomedical subjects

M H Kutner

Publications and source records attributed to M H Kutner.

At least 37 records · Page 2Linked to original sources

Model of spontaneous obesity in aging male Wistar rats.

We analyzed retrospectively data from 148 chow-fed male Wistar rats killed between the age of 6 wk and 2 yr while varying in body weight from 136 to 917 g. The purpose of this study was to clarify the relationship of body weight and body lipid content with the composition and cellularity of the epididymal and retroperitoneal fat depots. A positive linear association was found between body weight and body water or fat-free dry residue, whereas total body lipid exhibited a curvilinear relationship with body weight. The weight of the epididymal pads was linearly related to body weight but not to body lipid. In contrast, retroperitoneal pad weight was exponentially related to body weight and paralleled total body lipid. A strong linear correlation was found between total body lipid and weight (r = 0.959) or depot lipid content (r = 0.967) of the retroperitoneal fat pads. In this rat model of aging and spontaneous obesity, significant regional differences exist in adipose depot composition and cellularity. A practical outcome of this study is a simple and accurate prediction of body lipid content from the gravimetric determination of the retroperitoneal fat depots.

Adipose Tissue↗

Kinetics of system A amino acid uptake by muscle: effects of insulin and acute uremia.

We found that acute renal failure (ARF) depresses maximal responsiveness to insulin of system A amino acid transport in muscle [Maroni, Karapanos, and Mitch. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F74-F80, 1986]. To examine mechanisms for this change, we measured the kinetics of system A in response to insulin and ARF in epitrochlearis muscle. Insulin stimulation increased the diffusion constant (KD) approximately twofold in muscles from both ARF and control rats, suggesting that insulin can modulate nonsaturable alpha-(methylamino)isobutyrate uptake. Compared with basal values, insulin did not significantly change maximal transport velocity (Vmax) in ARF or control rats; however, insulin decreased Michaelis constant (Km) by 79 and 63%, respectively. Inhibition of protein synthesis with cycloheximide did not prevent stimulation of system A by insulin. Acute uremia had no effect on nonsaturable uptake or basal system A kinetics. However, ARF produced opposing effects on insulin-stimulated system A kinetics. There was a approximately 47% decrease in Vmax, which was partially offset by a 66% reduction in Km. In summary, both insulin and ARF modulate system A kinetics by mechanisms that are independent of protein synthesis.

Acute Disease↗

Natural killer cells in children with malignant solid tumors. Effect of recombinant interferon-alpha and interleukin-2 on natural killer cell function against tumor cell lines.

Natural killer (NK) cells and NK cell activity were determined in three groups (newly diagnosed [n = 21], on therapy [n = 21], and off therapy [n = 18]) of children with various types of malignant solid tumors and in a control group (n = 26) by means of Leu-7 and Leu-11b monoclonal antibodies and a 4-hour 51Cr-release assay, respectively. The erythroleukemia cell line K562 was used as a target cell. The newly diagnosed group included eight patients with localized disease (Stage I-II), ten with bulky but nonmetastatic disease (Stage III), and three with metastases (Stage IV). The mean percent of NK cell activity in the newly diagnosed group was significantly higher than that of the control group. Children with Stage III tumors at diagnosis had higher mean NK cell function than those with Stage I-II and Stage IV. On therapy patients had significantly fewer NK cells and lower NK cell cytotoxicity than those in the other groups studied. We also studied the following: (1) the in vitro effect of recombinant interferon-alpha (rIFN-alpha) and recombinant interleukin-2 (rIL-2) on NK cell function of peripheral blood lymphocytes (PBL) from children with solid malignancies; and (2) the susceptibility of neuroblastoma-derived (CHP-126 and SKNSH) and rhabdomyosarcoma-derived (A-204) cell lines to NK cell lysis. Both rIFN-alpha and rIL-2 enhanced NK cell activity of PBL from children with malignancies and healthy children against K562 and solid tumor cell lines. The enhancing effect or rIL-2 was greater than that of rIFN-alpha. CHP-126 and SKNSH cell lines were susceptible to NK cell lysis mediated by the PBL of children with neuroblastoma and the control group. The A-204 cell line was less sensitive than K562 to NK cell cytotoxicity. Our results suggest a potential therapeutic role for both cytokines in the treatment of malignant solid tumors of childhood.

Adolescent↗

Vitamin B6 repletion in cirrhosis with oral pyridoxine: failure to improve amino acid metabolism.

This study evaluated the effect of daily oral pyridoxine supplementation in patients with cirrhosis. Eight subjects were treated with 25 mg of pyridoxine for 28 days. Before and after the supplementation period, B6 status was assessed by measuring fasting plasma vitamer levels and response to a 25 mg oral pyridoxine load. In addition, a 24-hr urine collection was analyzed during each load study for B6 metabolites. The data indicated that supplementation achieved repletion of peripheral B6 stores, as evidenced by: (i) a significant (p less than 0.005) rise in fasting plasma pyridoxal phosphate after supplementation (mean +/- S.D. = 56.8 +/- 30.5 nmoles per liter) as compared to initial levels (17.0 +/- 17.8 nmoles per liter); (ii) a higher (p less than 0.05) percentage excretion of the pyridoxine load as urinary 4-pyridoxic acid (31.0 +/- 9.3%) compared to the initial load (19.6 +/- 5.8%), and (iii) a postsupplementation area under the plasma concentration vs. time curve for pyridoxal phosphate (377 +/- 529 nmoles.hr per liter), which was decreased (p less than 0.005) from the presupplementation value (934 +/- 756 nmoles.hr per liter). The postsupplementation fasting plasma pyridoxal phosphate concentrations were within the normal range. The consequences of B6 repletion on amino acid metabolism were measured by oral protein loads (n = 4) or oral methionine loads (n = 4). No significant changes were observed for methionine or any other amino acid in regard to plasma fasting concentration, peak concentration or AUC. Although the vitamin B6 deficiency of cirrhosis was corrected by daily oral pyridoxine supplementation, there was apparently no improvement in the deranged amino acid metabolism.

Amino Acids↗

Increased galactose clearance after liver transplantation: a measure of increased blood flow through the denervated liver?

This study measured the liver blood flow-dependent index of galactose clearance in patients after liver transplantation, to test the hypothesis that liver blood flow is increased in the denervated liver. Eight normal subjects and 16 patients 1 to 8 months after liver transplant were studied. All patients were stable with no evidence of severe rejection at the time of study. Galactose clearance was measured at steady state during continuous infusion of 75 mg per min of 5% galactose. The results show a statistically significant (p less than 0.01) higher average galactose clearance in the transplant patients (1,187 +/- 316 ml per min per m2) compared to the control group (709 +/- 121 ml per min per m2). The major limiting factor in galactose clearance at low concentrations is liver blood flow, and we interpret these data as evidence for increased blood flow in the transplanted liver. Possible mechanisms for the increased galactose clearance are (i) loss of normal vasomotor tone in the denervated liver, or (ii) persistence of abnormal systemic hemodynamics after transplantation. Elucidation of these mechanisms awaits further study.

Adult↗

EEG mean frequencies are sensitive indices of phenylalanine effects on normal brain.

We previously reported that changes in plasma phenylalanine (PHE) concentrations of 1000 microM or more adversely affected cognitive function and reduced mean frequency of the EEG power spectrum. In the present study, we characterized EEG effects of changes in plasma PHE from physiological to supraphysiological concentrations. Subjects were mentally normal children and adult volunteers with 3 different genotypes for phenylalanine hydroxylase (PHY): homozygous deficient, heterozygous, and homozygous normal. Double-blinded crossover studies were performed at equilibrium during PHE restriction and supplementation. The mean frequency of the power spectrum and the mean across a set of alpha-theta factors showed highly significant, reversible, generalized EEG slowing during PHE supplementation in subjects homozygous for PHY deficiency. Smaller but significant changes in EEG mean frequencies occurred in the heterozygous and normal subjects. Spectral profiles of EEG change were similar in both groups; the mean alpha-theta was more sensitive in the second group. Demonstration of EEG changes with PHE supplementation in normal individuals has important dietary implications.

Adult↗

Choline may be an essential nutrient in malnourished patients with cirrhosis.

Elemental diets designed for nutritional support in protein-calorie malnutrition are often deficient in choline, a nonessential nutrient. Previously, malnourished patients on these diets were found to be at risk of developing plasma choline deficiency. We have now estimated the prevalence of this deficiency by determining fasting plasma levels of choline among cirrhotic and noncirrhotic malnourished male subjects maintained on regular hospital mixed food or elemental parenteral and enteral formulas. Plasma choline concentrations (microM, average +/- SD) were as follows: (i) mixed foods, 11.3 +/- 4.3 for cirrhotic (n = 22) and 9.3 +/- 2.4 for noncirrhotic (n = 12) patients; (ii) parenteral formula, 5.3 +/- 1.6 for cirrhotic (n = 5) and 8.6 +/- 5.2 for noncirrhotic (n = 16) subjects; and (iii) enteral formula, 6.1 +/- 1.2 for cirrhotic (n = 5) and 11.7 +/- 1.9 for noncirrhotic (n = 4) subjects. The level for healthy normal subjects eating mixed foods was 12.0 +/- 2.2. The prevalence of plasma choline deficiency, i.e., plasma levels greater than or equal to 2 SD below the normal average, was as follows: parenteral formula, all cirrhotic and 10 of 16 noncirrhotic subjects; enteral formula, all cirrhotic and none of the noncirrhotic subjects. The reversibility of choline deficiency was examined in a longitudinal study of three phases involving 10 patients--5 with alcoholic cirrhosis (all on enteral formula); 5 noncirrhotic (1 on enteral and 4 on parenteral formula). During phase 1 (3-day equilibration period; ad libitum regular hospital diet), plasma choline levels were within the normal range for all subjects. During phase 2 (2 wk, choline depletion phase, elemental formulas), choline levels were subnormal in all cirrhotic subjects (5.1 +/- 2.0 microM) on enteral formula and all noncirrhotic patients on parenteral formula (5.9 +/- 1.3 microM). During phase 3 (2 wk, choline repletion phase, elemental formula + 6 g choline/day), the levels normalized in all patients (cirrhotic 11.4 +/- 3.1 microM and noncirrhotic 11.9 +/- 3.2 microM). Analyses of abdominal computed tomographic scans and plasma liver chemistries in the cirrhotic subjects during the three phases suggested a correlation between plasma choline deficiency and hepatic steatosis and abnormal liver enzyme levels in some patients. Therefore, choline may be an essential nutrient in malnourished cirrhotic patients and its deficiency may be associated with adverse hepatic effects.

Adult↗

Bedside cerebrospinal fluid glucose analysis.

We studied the reliability and accuracy of a two-minute reagent strip (Chemstrip bG) and hand-held autoanalyzer (Accu-Chek IIR) for determining cerebrospinal fluid glucose. We found that both bedside methods were highly reliable (r = 0.93, Chemstrip bG: r = 0.95, Accu-Chek II) and were very accurate (89.7% and 96.6% accurate at +/- 15 and 20 mg/dL, respectively, for the Chemstrip bG: 91.7% and 95.8% accurate at +/- 15 and 20 mg/dL, respectively, for the Accu-Chek II) over a wide range of glucose values in 237 determinations. There was no significant difference between the two bedside methods. We conclude that these two methods of bedside glucose estimation are both highly reliable and accurate and could be used to quickly determine patients' cerebrospinal fluid glucose values.

Autoanalysis↗

Distal splenorenal shunt with splenopancreatic disconnection. A 4-year assessment.

The aims of distal splenorenal shunt with splenopancreatic disconnection (DSRS-SPD) were to improve maintenance of portal flow and prevent siphoning of hepatotrophic factors from the pancreas, as occurs after standard DSRS. The main patient population targeted for improvement were alcoholic cirrhotics, who have poorer survival than nonalcoholic cirrhotics and greater loss of portal flow (60%) after standard DSRS. Seventy-eight patients had DSRS-SPD during the study period 1983 to 1987: thirty-two patients were Child's A, 25 were Child's B, and 21 were Child's C. The 35 patients with alcoholic cirrhosis were a significantly poorer risk group by Child's class and galactose elimination capacity (GEC) than the 39 patients with nonalcoholic cirrhosis. Four patients had portal vein thrombosis. At 4-year follow-up, portal perfusion is maintained in 84% alcoholic and 90% nonalcoholic patients, with hepatic and systemic hemodynamics showing identical patterns for both groups. Hepatic function measured by GEC was maintained in alcoholic patients (290 +/- 68 mg/min to 303 +/- 74 mg/min) and nonalcoholics patients (342 +/- 92 to 320 +/- 118 mg/min). Gastric variceal rebleeding occurred in 10 patients--4 early (less than 2 months) and 6 late (18 to 54 months), leading to operation in 4 and transhepatic embolization in 4 patients: 2 of these patients died from this complication. Survival data show an operative mortality rate of 6.4% and overall mortality rate of 30%, with no significant difference between alcoholic and nonalcoholic cirrhotics. DSRS-SPD has significantly improved maintenance of portal perfusion and survival in patients with alcoholic cirrhosis requiring selective shunt for variceal bleeding when compared to standard DSRS. In this population DSRS-SPD is the operation of choice. In patients with nonalcoholic cirrhosis, the current data have not shown DSRS-SPD to have advantage over standard DSRS.

Angiography↗

Acquired renal cystic disease in end-stage renal disease: an autopsy study of 155 cases.

Autopsy reports on 155 successive end-stage renal disease (ESRD) patients and 147 control patients without ESRD, matched for age, race and gender, were collected. Cystic transformation of the kidneys was noted in 58% of the ESRD patients and 13.6% of the control patients. There were 25 ESRD patients with renal adenoma and 3 with renal cell carcinoma. The single best predictor of cystic transformation or tumorous degeneration was patient's age. A statistically significant association between cystic transformation and gender, as well as the cause of ESRD, was also found. In contrast to previous reports we were unable to document a strong association between the incidence of either cystic transformation or tumorous degeneration with the duration of dialysis, nor did these two parameters correlate with mode of dialysis. We suggest that cystic transformation of the kidneys in ESRD is related to age and renal failure per se, is not strongly associated with duration of dialysis and is independent of mode of dialysis. Concomitant tumorous degeneration was frequent, but this was usually an incidental autopsy finding. Renal malignancy was uncommon and metastases were absent.

Adenoma↗

Effect of beta h-endorphin on release of insulin by rabbit pancreas in response to four secretagogues: comparison with somatostatin and epinephrine.

Previous work showed beta h-endorphin inhibits glucose-stimulated secretion of insulin by rabbit pancreas slices. This study, also conducted with rabbit pancreas slices, compared the antisecretagogue actions of beta h-endorphin, somatostatin 1-14, and epinephrine versus four secretagogues, glucose, mannose, leucine and potassium chloride. All three antisecretagogues inhibited all four secretagogues. The order of potency of the antisecretagogues varied according to secretagogue. Naloxone antagonized only beta h-endorphin among the three antisecretagogues, and phentolamine antagonized only epinephrine.

Animals↗

Distal splenorenal shunt versus endoscopic sclerotherapy for long-term management of variceal bleeding. Preliminary report of a prospective, randomized trial.

This paper reports the preliminary results of a prospective randomized trial comparing endoscopic variceal sclerosis and distal splenorenal shunt (DSRS) in the management of patients with cirrhosis and variceal bleeding. Seventy-one patients have been entered; 36 have received sclerosis and 35 DSRS. Randomization of the study population was stratified on Child's A/B (56%) and Child's C (44%). Sixty-one per cent had alcoholic and 39% non-alcoholic cirrhosis. No patients have been lost to follow-up, which currently stands at a median of 26 months. Rebleeding occurred significantly (p less than 0.05) more frequently in patients in the sclerosis group (19 of 36: 53%) compared to DSRS (1 of 35: 3%), but only 11 of 36 (31%) were not controlled by further sclerosis and failed that therapy. Patients in whom sclerosis failed underwent surgery. Survival was significantly (p less than 0.01) improved in the sclerosis group (+ surgery in 31%), with an 84% 2-year survival compared to a 59% 2-year survival in the DSRS group. Portal perfusion was significantly (p less than 0.05) better maintained in the sclerosis (95%) compared to the DSRS (53%) group. Galactose elimination capacity improved significantly (p less than 0.05) in 21 patients successfully managed by sclerosis at 1 year and was significantly (p less than 0.01) better maintained in the sclerosis compared to DSRS group. The authors conclude that endoscopic sclerosis: has a higher rebleeding rate than DSRS, with one third of patients failing therapy from rebleeding; allows significant improvement in liver function when successful; and gives significantly improved survival in the management of variceal bleeding when backed up by surgical therapy for patients with uncontrolled rebleeding.

Acute Disease↗

Splenopancreatic disconnection. Improved selectivity of distal splenorenal shunt.

UNLABELLED: Distal splenorenal shunt (DSRS) improves survival from variceal bleeding in nonalcoholic cirrhotics but not in alcoholic subjects. The metabolic response after DSRS is also different in alcoholic and nonalcoholic cirrhotics. Portal perfusion, quality of blood perfusing the liver, cardiac output, and liver blood flow do not change in nonalcoholics. In alcoholics, portal perfusion is frequently lost (60%), quality of blood perfusing the liver decreases, and cardiac output and liver blood flow increase. It is proposed that portal flow is lost in alcoholics via pancreatic and colonic collaterals after surgery. Elimination of this sump by adding complete dissection of the splenic vein and division of the splenocolic ligament to DSRS (splenopancreatic disconnection, SPD) could preserve portal perfusion, decrease shunt loss of hepatotrophic factor, and improve survival in alcoholic cirrhotics. This report compares data 1 year after surgery in two groups of cirrhotics: group I (8 nonalcoholic; 16 alcoholic) had DSRS without SPD; group II (17 nonalcoholic; 11 alcoholic) received DSRS + SPD. METHODS: Portal perfusion grade, cardiac output (CO), liver blood flow (f), hepatic function (GEC), and hepatic volume (vol) were measured before and 1 year after surgery. Shunt loss of hepatotrophic factor was estimated by insulin response (change in plasma concentration over 10 minutes: AUC) after arginine stimulation. RESULTS: Groups I and II were similar before surgery. Metabolically, nonalcoholics remained stable after both DSRS and DSRS + SPD. After standard DSRS, alcoholics lost portal perfusion (75%, p less than 0.05), CO, and f increased (p less than 0.05), and quality of blood perfusing the liver was decreased (GEC/f: p less than 0.05). DSRS + SPD preserved portal perfusion better (p less than 0.05) in alcoholic cirrhotics than did DSRS alone. After DSRS + SPD, the metabolic response in alcoholics resembled that of nonalcoholics. CO, f, and GEC/f remained stable. These data show: DSRS + SPD preserves postoperative portal perfusion in alcoholic cirrhotics better than DSRS alone. Metabolic response to DSRS + SPD is similar in alcoholic and nonalcoholic cirrhotics. Because portal perfusion and metabolic integrity are preserved after DSRS + SPD, its use in alcoholic cirrhotics should improve survival.

Cardiac Output↗