Inappropriateness of statistical methods used in evaluating postanesthetic hepatic injury.
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Anesthetics↗
Biomedical subjects
M H Kutner
Publications and source records attributed to M H Kutner.
First-order clearance of plasma galactose: the effect of liver disease.
Galactose clearance kinetics at plasma concentrations of 0.01-0.1 mg/ml were studied during continuous infusion of 25-100 mg D-galactose per minute. In 10 subjects, plasma galactose vs. time curves during 140-min infusion, and 60 min thereafter, showed the data to fit a single-compartment model and attain 95% of plasma steady state by 80 min. Doubling the infusion rate in 14 subjects resulted in an 8% reduction in clearance at the higher rate. Hepatic extraction in normal subjects was 94%, while in cirrhotics it was 79%. Day-to-day reproducibility in 11 subjects gave a coefficient of variation of 4.5%. Extrahepatic clearance showed 2% of the total to occur in the urine, and 2.3% to occur by erythrocyte metabolism. The overall mean (+/-SD) clearance in the normal subjects of 1378 +/- 218 ml/min was significantly (p less than 0.05) greater than for the stable cirrhotics at 918 +/- 279 ml/min, but not significantly different from patients with acute hepatocellular damage at 1186 +/- 300 ml/min. This index gives flow-dependent hepatic clearance, and provides a noninvasive measure of effective liver blood flow.
Erythrocytes↗
Children with normal-variant short stature: treatment with human growth hormone for six months.
Children with normal-variant short stature can be classified into four subgroups by measuring their anabolic and growth reactions to a 10-day course of human growth hormone. In Subgroup 1 there is no anabolic or growth reaction; in Subgroup 2 there is a weak anabolic reaction but no growth; Subgroups 3 and 4 have both reactions but Subgroup 4 is more responsive than Subgroup 3. We monitored growth rate and plasma immunoreactive somatomedin C concentrations in four to six children from each subgroup (age range, eight to 11 years) before, during, and after six months of injections of growth hormone (0.08 unit per kilogram of body weight per day). In children in Subgroups 3 and 4, the average somatomedin C level, which was subnormal before treatment, was restored to normal. Simultaneously, the average growth rate accelerated fivefold. In children in Subgroups 1 and 2, whose average pretreatment somatomedin C was normal, growth hormone had little effect on somatomedin level of growth rate. The somatomedin response in Subgroups 3 and 4 was apparent by the 10th day of treatment. This response provides a rapid method for identifying affected children who will benefit from longterm administration of human growth hormone.
Body Height↗
Gluconate calcium therapy and neonatal hypercalciuria.
Nephrolithiasis was present in a 2-month-old premature infant with bronchopulmonary dysplasia who had been receiving furosemide and intravenous (IV) gluconate calcium therapy. This infant was found to be hypercalciuric. Furosemide therapy is known to increase calcium excretion. In the present study, we examined sick infants who were receiving gluconate calcium without furosemide to evaluate the effect of gluconate calcium therapy on urinary calcium excretion. The sick infants receiving gluconate calcium had higher values of urinary calcium than did the well infants taking regular formula feedings. Moreover, the calciuria appeared to increase progressively with continued gluconate calcium therapy. It appears that prolonged use of either furosemide or IV gluconate calcium leads to hypercalciuria, which, in turn, may predispose the premature infant to nephrolithiasis.
Calcium↗
Radionuclide angiography of the liver and spleen. Noninvasive method for assessing the ratio of portal venous to total hepatic blood flow and portasystemic shunt patency.
Radioactivity verus time curves were generated for the first pass of technetium-99m pertechnetate through the left ventricle, kidneys, spleen and liver, after a 20 mCi peripheral intravenous bolus injection. The rate of change of radioactivity in these organs before recirculation is proportional to blood flow through the organ. The hepatic perfusion index, defined as the ratio of portal flow to total hepatic blood flow, was correlated with the angiographic grade of portal perfusion. The hepatic perfusion index in seven normal subjects was 66.0 +/- 3.4 percent (mean +/- standard error of the mean), and in 22 cirrhotic patients with decreasing angiographic perfusion of grades 1 to 4 the index was 54 +/- 4.6, 37 +/- 2.6, 17 +/- 4.7 and 3 +/- 1.1 percent, respectively. The correlation between the calculated perfusion index and the angiographic grade of portal flow was highly significant (p less than 0.001). The passage of radionuclide through the spleen differed before and after shunt surgery in patients with portal hypertension. The slope to height ratio, based on the downslope of the splenic curve, was significantly greater (p less than 0.01) in the shunted patients and provided a simple index for assessing shunt patency.
Adult↗
A method of screening for growth hormone deficiency using anthropometrics.
Among children less than 3rd percentile in height, less than 1% are deficient in endogenous growth hormone, while 80% have no recognizable organic cause for short stature, and are termed normal variants. This study investigated whether anthropometric evaluation can distinguish growth hormone-deficient from normal variant children. Height, weight, midarm circumference and 10 skinfold thicknesses were measured in 24 growth hormone-deficient and 26 normal variant children; indices of linear growth, adiposity, and lean body mass were derived from these. All these variables were analyzed statistically by discriminant analysis. This led to a screening formula, here called a "Z-function," based only on height and five skinfolds (abdomen, back, chest, knee, and calf). The Z-function classified correctly all but two growth hormone-deficients and two normal variants. Because of the small and possibly inhomogeneous sample, the particular formula developed here is not recommended for general use, but these preliminary findings show that a simple anthropometric screening test is indeed feasible, and could be useful in pediatric practice.
Adipose Tissue↗
Measurement of liver and spleen volume by computed tomography. Assessment of reproducibility and changes found following a selective distal splenorenal shunt.
Liver and spleen size were measured in 11 normal subjects and 12 patients with cirrhosis. Volume was calculated by adding together the area measurements obtained from successive transverse abdominal scans. The normal mean volume of the liver (+/- S.D.) was 1,493 +/- 230 cm3 and that of the spleen was 219 +/- 76 cm3; interobserver variability was 4-8% and the day-to-day coefficient of variation was 6-10%. In cirrhotic patients studied prior to and 7-10 days after a distal splenorenal shunt, the mean liver volume fell from 1,642 to 1,529 cm3 (p less than 0.06) and the mean spleen volume from 660 to 507 cm3 (p less than 0.006), supporting the use of such a shunt in selective decompression of varices and maintenance of portal hypertension. This is a clinically useful method of measuring organ volume with the required sensitivity.
Adult↗
Impaired growth hormone secretion in the adult population: relation to age and adiposity.
Growth hormone (GH) release was studied in adults of normal stature, ages 21-86 yr. The subjects were 85-115% of ideal body weight, between the 5th and 95th percentiles in height, and free of active or progressive disease. 9 to 12 individuals in each decade from thirds to ninth were evaluated. The following criteria of GH status were measured: serum GH concentration, analyzed by radioimmunoassay at half-hour intervals for 4 h after onset of sleep, and at 1-h intervals from 8 a.m. to 4 p.m. in 52 subjects; daily retention of N, P, and K in response to 0.168 U human (h)GH/kg body wt3/4/day in 18 subjects; and plasma somatomedin C (SmC) level before and during exogenous hGH treatment in 18 subjects. All 10 individuals, 20-29 yr old, released substantial amounts of endogenous GH during both day and night (average peak serum GH obtained during day and night was 7.3 and 20.3 ng/ml, respectively); average plasma SmC was 1.43 U/ml (95% tolerance limits, 0.64-2.22 U/ml). There was no significant effect of exogenous hGH on elemental balances or on plasma SmC. In contrast, 6 of 12 individuals 60-79 yr old showed the following evidences of impaired GH release; peak waking and sleeping serum GH less than 4 ng/ml; plasma SmC less than 0.38 U/ml; a significant retention in N, P, and K; and a significant rise in plasma SmC, in response to exogenous hGH. Plasma SmC, serum GH during sleep, serum GH during the day, retentions of N, P, and K in response to exogenous hGH, and rise in plasma SmC in response to hGH were all intercorrelated (P less than 0.05). Plasma SmC less than 0.38 U/ml corresponded to peak nocturnal serum GH less than 4 ng/ml. The prevalence of plasma SmC less than 0.38 U/ml increased progressively from age 20 to 90: third decade, 0%; fourth, 11%; fifth, 20%; sixth, 22%; seventh, 42%; eight, 55%; and ninth, 55%. Within each decade, plasma SmC was inversely related to adiposity.
Adult↗
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↗
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↗
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↗
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↗
Sources of variability in echocardiographic measurements.
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Adult↗
Protein-calorie undernutrition in hospitalized cancer patients.
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Adult↗
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↗
Further observations on four subgroups of normal variant short stature.
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Body Height↗
A radiographic method of quantifying protein-calorie undernutrition.
Estimation of midarm adipose tissue and muscle by the anthropometric technique is based on the idealized assumption that the arm and its muscle compartments are circular, and that fat is distributed evenly around the arm. We examined the validity of these assumptions by computerized axial tomography of the midarm in 21 subjects ranging from 65 to 255% of ideal body weight. Computerized axial tomography identified three errors inherent in the anthropometric method: 1) The arm and its muscle compartment were rarely circular, but resembled instead an ellipse and "cloverleaf", respectively; 2) fat was distributed asymmetrically around the arm, and furthermore when triceps skinfold was less than 5 mm, no fat was radiographically detectable, and 3) muscle are calculated by the anthropometric method includes bone area. Since bone area was not influenced by nutritional status, anthropometric "muscle area" underestimated the degree of muscle atrophy in undernutrition. Despite these limitations, in subjects 60 to 120% of ideal body weight anthropometric estimates of midarm muscle area (MAMA) and fat area did not differ greatly from the radiographic values. Anthropometric MAMA was consistently greater than the radiographic value by 15 to 25%, while midarm fat area agreed within +/- 10%. The error in the anthropometric MAMA could be nearly eliminated by two types of correction: expressing MAMA as a percentage of normal, and correcting for bone content by subtracting midarm bone area (6.3 and 4.7 cm2 for men and women). In subjects greater than 150% ideal body weight, however, anthropometric estimates of MAMA and midarm fat area differed from the radiographic values by greater than 50% even after the above two types of correction. Midarm computerized axial tomography scan provides an accurate alternative to the anthropometric method for estimating midarm muscle and fat in these obese individuals.
Adipose Tissue↗
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↗