Michael Kutner

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.

Associations of Demographic, Functional, and Behavioral Characteristics with Activity‐Related Fear of Falling Among Older Adults Transitioning to Frailty

OBJECTIVES: To determine, in a cohort of older individuals transitioning to frailty (defined by Speechley and Tinetti, 1991) who have previously fallen, whether there are significant associations between demographic, functional, and behavioral characteristics and activity‐related fear of falling, using both the Falls Efficacy Scale (FES) and the Activities‐Specific Balance Confidence Scale (ABC).

Protein-calorie undernutrition in hospitalized cancer patients.

Abstract A survey of the nutritional status of hospitalized cancer patients was conducted in two phases. In phase 1, protein-calorie nutrition was evaluated in 54 ward patients by anthropometries, creatinine excretion and serum albumin. In phase two, 30 cancer patients with protein-calorie undernutrition were transferred to the Clinical Research Unit for study of the underlying mechanisms. Evaluation in this group included anthropometries, serum albumin, creatinine excretion, vitamin levels, caloric intake, basal metabolic rate and stool fat content. Duration of survival from study was recorded in both phases. We found a nearly universal prevalence of protein-calorie undernutrition in advanced cancer, with loss of adipose tissue, visceral protein and skeletal muscle varying unpredictably from patient to patient. The creatinine to height ratio was the most sensitive indicator of protein-calorie undernutrition; 88 per cent of the patients in both phases had a creatinine to height ratio less than 80 per cent of standard, whereas only 42 per cent and 23 per cent of these patients had values less than 80 per cent of standard for triceps skin fold and mid-arm muscle area, respectively. In phase 2, plasma folate, ascorbic acid and vitamin A levels were low in 20 to 45 per cent. Steatorrhea was rare. Neither the basal metabolic rate nor caloric intake differed from expected values for normal sedentary subjects of comparable size. The degree of malnutrition significantly correlated with survival. Patients who died within 70 days of study generally had a creatinine to height ratio We conclude that protein-calorie undernutrition is present in most hospitalized cancer patients but that it varies widely in degree between subjects and is often obscured at the bedside by residual obesity. The creatinine to height ratio, however, is a sensitive quantitative indicator of this condition. There appear to be nutritional thresholds below which survival is decreased. Survival might be enhanced if nutrition could be maintained above these critical levels.

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.

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 Childs A/B (56%) and Childs C (44%). Sixty-one per cent had alcoholic and 39% nonalcoholic cirrhosis. No patients have been lost to follow-up, which currently stands at a median of 26 months. Rebleeding occurred significantly (p < 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 < 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 < 0.05) better maintained in the sclerosis (95%) compared to the DSRS (53%) group. Galactose elimination capacity improved significantly (p < 0.05) in 21 patients successfully managed by sclerosis at 1 year and was significantly (p < 0.01) better maintained in the sclerosis compared to DSRS group. The authors conclude that endoscopic sclerosis: (1) has a higher rebleeding rate than DSRS, with one third of patients failing therapy from rebleeding; (2) allows significant improvement in liver function when successful; and (3) gives significantly improved survival in the management of variceal bleeding when backed up by surgical therapy for patients with uncontrolled rebleeding.

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.

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 non-selective patients (5%; p <.001). Quantitative measures of hepatic function (maximal rate of urea synthesis or MRUS and Childs 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 Childs 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 non-selective) still shows an advantage to the selective group with respect to MRUS, Childs 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 Childs 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 non-selective, 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.

Regression Analysis of Poisson-Distributed Data

Abstract The principle of maximum likelihood is used to obtain estimates of the parameters in a regression model when the experimental observations are assumed to follow the Poisson distribution. The maximum likelihood estimates are shown to be equivalent to those obtained by minimization of a quadratic form which reduces to a modified chi square under the Poisson assumption. Computationally, both of these estimation procedures are equivalent to a properly weighted least squares analysis. Approximate tests of the assumed Poisson variation and “goodness of fit” of the data to the model are proposed. Applications of the estimation procedure to linear and nonlinear regression models are discussed, and numerical examples are presented.

Endoscopic Variceal Sclerosis Compared with Distal Splenorenal Shunt To Prevent Recurrent Variceal Bleeding in Cirrhosis: A Prospective, Randomized Trial

STUDY OBJECTIVE To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis. DESIGN A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months. SETTING A private, tertiary-referral university hospital. PATIENTS Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval. TREATMENTS Endoscopic variceal sclerosis or distal splenorenal shunt. MEASUREMENTS AND MAIN RESULTS Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively). CONCLUSIONS Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study Five Years after Surgery

In the Prospective Evaluation of Radial Keratotomy (PERK) Study, 793 eyes of 435 patients with 2 to 8 diopters (D) of myopia received a standardized surgery consisting of 8 incisions with a diamond-bladed knife set at 100% of the thinnest paracentral ultrasonic corneal thickness measurement and a diameter of the clear zone of 3.0 to 4.5 mm; 97 eyes (12%) received an additional 8 incisions. There were 757 eyes (95%) followed for 3 to 6.3 years. After surgery, uncorrected visual acuity was 20/40 or better in 88% of eyes. The refractive error was within 1 D of emmetropia for 64% of eyes; 19% were myopic and 17% were hyperopic by more than 1 D. Between 6 months and 5 years after surgery, 22% of the eyes had a refractive change of 1 D or more in the hyperopic direction. For 25 eyes (3%) there was a loss of 2 or more lines of best spectacle-corrected visual acuity.