Effect of lipids on growth hormone secretion in humans.

To determine the effect of elevations of plasma lipids on growth hormone secretion in humans, paired insulin hypoglycemia tests and paired arginine infusion tests were performed on eight and six normal female volunteers respectively. On 1 of the 2 test days for each growth hormone stimulus, subjects were given 60 g corn oil (Lipomul) 3 hr before testing followed by intravenous heparin (5000 U) at the time of insulin or arginine administration. Lipomul plus heparin administration inhibited both insulin- and arginine-induced plasma HGH elevations with almost complete suppression of the response to arginine. The plasma HGH (human growth hormone) inhibition was associated with elevation in plasma triglycerides and inhibition of plasma FFA (free fatty acid) depression after insulin or arginine. Neither the hypoglycemic response to insulin nor the blood glucose and plasma immunoreactive-insulin responses to arginine were altered by Lipomul plus heparin administration. In four additional subjects in whom Lipomul was given without heparin, the elevated plasma triglyceride values were not associated with suppression of arginine-induced plasma HGH elevations. In the same four subjects, heparin administration without Lipomul neither suppressed arginine-induced plasma HGH elevations nor prevented the depression in plasma FFA after arginine as much as when Lipomul plus heparin had been given. These latter observations suggest that the elevation in plasma FFA was responsible for suppression of growth hormone secretion by Lipomul plus heparin. These studies indicate a possible role of plasma FFA in regulation of growth hormone secretion.

A reappraisal of staging and therapy for patients with cancer of the rectum. I. Development of two new systems of staging.

Existing systems of staging for patients with rectal cancer depend almost exclusively on anatomic evidence. Consequently, the stages cannot be determined in advance of therapeutic decisions and cannot be used for patients treated without surgery. Furthermore, the stages contain no provision for important prognostic distinctions, that cannot be discerned from anatomic data. After preparing a taxonomy for hiterto unclassified medical data, we developed and tested two new systems of staging in a cohort if 318 patients. The first system which can be applied before treatment, is divided into four composite stages that contain elements of symptomatic, chronometric, co-morbid, and para-morbid data, as well as information obtained from physical examination, sigmoidoscopy, and roentgenography. The second system, applicable to patients with resected tumors, is based on a combination of pre-therapeutic clinical information and post-surgical anatomic evidence. The two systems produce prognostic gradients that are clinically distinctive and statistically efficacious.

A reappraisal of staging and therapy for patients with cancer of the rectum. II. Patterns of presentation and outcome of treatment.

Two new biologically composite systems of staging were used to analyze the patterns of presentation, therapy, and outcome for 318 patients with rectal cancer. Selectional bias was evident in therapeutic decisions. The patients chosen for surgical exploration and possible resection came mainly from prognostically favorable stages and had higher survival rates than the "inoperable" patients wven when the tumor was not resected. In patients with tumors located 8 cm or higher above the anus, survival rates in each composite symptom-anatomic (S-A) stage were essentially similar with radical and simple resections. Radical surgery gave better survival rates than simple surgery for tumors at 5 to 7 cm and was an anatomic necessity to remove tumors at 0 to 4 cm. Regardless of the extensiveness of surgery, the S-A stages were directly related to rates of postoperative infection, postoperative death, subsequent quality of life, and deaths due either to cancer or to noncancer causes.

Ethanol-host interactions determined by radiorespirometry of 14C glucoses.

1. Theoretical considerations in continuous flow analysis by Walker, Shepherdson and McGowan have been applied to continuous flow radiorespirometry of 14C-glucoses to demonstrate ethanol response differences between water- and ethanol preferring mice. 2. Ethanol dosages in the n mols/kg range stimulated glucose utilization rates more in ethanol-than in water-preferring mice, while intermediate dosages (micron and low mmol/kg) produced equal stimulation but at different dosages. Pharmacological dosages (20-88 mmols/kg) inhibited glucose rates in water-preferring mice. The inhibition was released at 44 mmols/kg in ethanol-preferring mice. 3. Inhibition release was shown to be associated more with glucose carbons other than one, and considered consistent with a sodium-plus potassium-activated ATPase mechanism. 4. Intermediate ethanol dosage changes could be assigned to differences induced in glucose carbon one metabolism with H2O2-catalase and/or microsomal-ethanol-oxidizing systems (MEOS) mechanisms. 5. Our studies suggest that measurements of adenylate deaminase activities might clarify shifts in transaminations (human) and shifts in mononucleotides seen following chronic ethanol ingestion.

A noninvasive technique for monitoring response to chemotherapy in human acute leukemia.

To see whether urine enzyme activities could be used as an index in evaluating the disease status of leukemia patients, we examined the activities of four enzymes: arylsulfatases A(AS-A) and B(AS-B), alkaline phosphatase (AP), and lactate dehydrogenase (LDH). AP and LDH showed no consistent patterns. The activities of AS-A and AS-B correlated well with the patient's clinical status, increasing during progression of disease and decreasing toward normal activities during responses to therapy, as judged from bone marrow cellularity and differential. Among 23 untreated patients with a histologic diagnosis of acute leukemia we found increased activities of the urine enzymes in these proportions: AS-A in 23 patients (100%), AS-B in 22 (95.7%), AP in 7 (30.4%), and LDH in 10 (43.5%). Five patients in remission from acute leukemia had normal activities for all four enzymes. In one patient in remission for more than one year, a rise in urinary arylsulfatase activity preceded observable bone marrow relapse by 4 months. Unlike that of serum of urine lysozyme and serum copper, the determination of urine arylsulfatase activities appears to be a consistent, useful indicator of response to antileukemic therapy. In contrast to the determination of polyamines, the quantitation of arylsulfatase activity is achieved with greater ease and with instrumentation available in most clinical laboratories.