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Biomedical subjects

H Freund

Publications and source records attributed to H Freund.

At least 73 records · Page 4Linked to original sources
PubMed1983

Progestagenic and antigonadotrophic activities of STS 557.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) was tested for progestagenic activity in rabbits and for ovulation-inhibiting activities in rabbits and rats in comparison with levonorgestrel and, in some cases, with norethisterone acetate or chlormadinone acetate. In the immature rabbit, the endometrium transformation-inducing activity of STS 557 was about 5 times higher than levonorgestrel for both oral and subcutaneous administration. The ovulation-inhibiting effect of STS 557 was 3.5 times higher than that of levonorgestrel in the rabbit after oral administration, and about 7 times higher in the rat. After subcutaneous injection, however, the antiovulatory activity of STS 557 in rats was only about 4% of that of levonorgestrel when the ED 50 were compared.

Administration, Oral↗
PubMed1983

Interceptive activities of STS 557 in rabbits, mice and rats.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) is a interceptive agent in rabbits, mice and rats. In rats, it also shows post-implantational pregnancyterminating activity. In rabbits treated orally before mating or after ovulation for three consecutive days, it inhibited pregnancy largely at total doses of 0.08 mg/kg in the former and completely with 8.0 mg/kg in the latter case. A single subcutaneous dose of 40 mg/kg given on day 1 of pregnancy inhibited completely nidation in rats. In inhibition of pregnancy in rats could also be realized when the dose of 40 mg/kg was distributed on several days and given subcutaneously at daily doses of 5.0 mg/kg on days 1--8 of pregnancy, and even only daily doses of 2 mg STS 557/kg were needed in this respect, if animals which showed no living conceptuses were scored as "non-pregnant". STS 557 was effective in terminating pregnancy in rats, too, when given subcutaneously after implantation for 4 days at daily doses of 50 mg/kg, beginning on day 5 or on day 8 of pregnancy. The nidation inhibiting effects of STS 557 in rabbits treated pre-coitally, and in mice as well as in rats treated post-coitally were more marked than those of levonorgestrel. The interceptive and post-implantational inhibiting activity of STS 557 may be based on its antiprogestagenic properties. Luteolysis in the nidation phase can be excluded as shown by radioimmunoassay of progesterone in rats. The antigestagenic effects on the endometrium in rats were evident in the diamine oxidase assay. The acceleration of tubal egg transport, the morphological changes of the endometrium shown by scanning electron microscopy, and the effects on blastocyst transfer, all investigated in rats, suggest peripheral mechanisms of action.

Amine Oxidase (Copper-Containing)↗
PubMed1983

Inhibition of male fertility by STS 557.

To ascertain the effects of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) on the reproductive and endocrine functions, male rabbits were given the substance orally daily over 8 weeks. In doses of 10 and 20 mg STS 557 per animal per day fertility inhibition was accompanied by a decrease of spermatogenesis and sexual activity. At the chosen dose of 5 mg per day, STS 557 caused a decrease of sperm motility, semen fructose content and sterility of the bucks. On the other hand, libido, semen volume, sperm number, sialic acid content in semen, serum LH and testosterone remained unaffected. Concomitant injection of testosterone did not reverse the suppressive effect of STS 557 on fertility. Motility of human sperm was lowered markedly by STS 557 in vitro. The human sperm penetration and pronuclear formation were significantly reduced in the vitro fertilization assay with zona-free hamster eggs. Findings are discussed in view of the development of male contraceptives.

Animals↗
PubMed1983

Maintenance of colloid osmotic pressure in critically ill surgical patients on total parenteral nutrition.

The effect of total parenteral nutrition (TPN) on plasma colloid osmotic pressure (COP) was investigated in critically ill and stable surgical patients. Normal COP ranged from 22 to 26 mm Hg (mean +/- SD 24 +/- 2). In critically ill patients COP levels dropped as low as 14 mm Hg (mean 17 +/- 2.4), and remained at these low levels despite aggressive nutritional support with 2,500 to 4,000 kcal and 100 to 170 g protein/day given as central vein parenteral nutrition. A group of stable surgical patients receiving TPN as supportive therapy was investigated as a comparison with the critically ill group. The mean COP level in this stable group was 21.8 +/- 0.6 mm Hg, at the low-normal level. Only when the critically ill patients became less catabolic, sometimes coincident with the resumption of oral intake, did COP levels rise toward normal. As long as a patient is critically ill, the low COP levels should be corrected by the addition of plasma and albumin, as TPN seems to be inadequate for this task in these surgical patients.

Colloids↗
PubMed1982

Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy.

Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group and 47% in the acute hepatitis group. Encephalopathy appeared to correlate with individual amino acids differentially in the various groups and with the ratio between the aromatic and the branched-chain amino acids. Ammonia did not correlate with either the degree of encephalopathy or improvement therefrom. In 24 Patients therapy for hepatic encephalopathy was limited to infusion of the branched-chain enriched amino acid solution only, with wake-up in 66% of this group. The results strongly suggest that in protein intolerant patients requiring nutritional support, infusion with branchedchain enriched amino acid solutions is well tolerated with either no worsening of or improvement in hepatic encephalopathy coincident with the achievement of nitrogen equilibrium and adequate nutritional support.

2-Hydroxyphenethylamine↗
PubMed1982

Surgical correction of ectropion of the anal mucosa.

A method to correct an ectropion of the anal mucosa, using the triangular flap technique, has been described. The operation is simple and physiologically sound, with special attention being paid to skin tension lines. The results are excellent, and the patient is relieved of discomfort, bleeding tenesmus and pruritus which accompany ectropion of the anal mucosa.

Anal Canal↗
PubMed1981

Lactate after exercise in man: I. Evolution kinetics in arterial blood.

Arterial and venous blood lactate concentrations were measured at 10 or 30 s time intervals before, during, and after several types of muscular exercise on an ergocycle in a sitting or supine position. Arterial blood lactate concentration curves over the recovery period were found to fit a biexponential time function including a rapidly increasing and a slowly decreasing component, even during active recovery at approximately 40% VO2 max exercise. The velocity constants were dependent on the exercise load. They were also linearly related to each other. The time of lactate disappearance during recovery increased with the work load.

Arm↗
PubMed1981

Lactate after exercise in Man: II. Mathematical model.

A mathematical model of lactate kinetics after exercise has been constructed from the application of the mass conservation law and the following assumptions: 1. The total lactate distribution space is composed of two compartments, i.e., (M) the previously working muscles and (S) the remaining lactate space; 2. The rates of lactate release and utilization in (M) and (S) are proportional to the lactate contents of these compartments; 3. The post-exercise lactate production rates in (M) and (S) are constants; 4. Arterial lactate concentration can represent the average lactate concentration in (S). Consideration of experimental facts reported in the literature shows these assumptions to be reasonable. The relationships obtained express the compatibility of parameters and time functions concerning lactate concentrations, as well as rates of production, uptake, release, and utilization. They open the way to various applications, especially those involving numerical fits to observed time courses of lactate concentrations.

Humans↗
PubMed1981

Lactate after exercise in man: III. Properties of the compartment model.

Lactate movements during recovery following muscular exercise in man were studied by means of a two-compartment model. Mathematical discussion of the literal expressions obtained allows one to represent parameters concerning lactate exchange, utilization, and production in the previously working muscles and in the remaining lactate distribution space. It also shows that bi-exponential time courses predicted for muscular and blood lactate concentrations as well as for rates of lactate uptake, release, and utilization can denote several morphologies. All of the time evolutions for muscular and blood lactate concentrations found in the literature are consistent with these theoretical possibilities in the model. A numerical application confirms this concordance. Thus, this simple model, for which the basic assumption were previously justified, appears to be qualitatively able to describe lactate exchanges and disappearance after exercise. A practical algorithm is put forward to display its possibilities and to test further its quantitative validity.

Humans↗
PubMed1981

Lactate after exercise in man: IV. Physiological observations and model predictions.

Following earlier papers that established the mathematical form of the time dependence of lactate concentrations during recovery from several types of exercise, and that set up a two-compartment model predicting the same time dependences, the present work applies the model to obtain parameters of specific physiological processes. Satisfactory agreement between predictions of the model and our experiment and literature data is obtained in the cases were comparisons can be made, as in the muscular lactate time evolution measured from biopsy samples, in blood flows through the active muscle at the end of exercise or at rest and their evolution during recovery, as well as in the volume of the active muscle compartment. The model prediction that lactate efflux from the muscles to the blood can reduce to zero during recovery is verified experimentally.

Arteries↗
PubMed1981

Choledochoduodenostomy in the treatment of benign biliary tract disease.

During the 15 year period 1965 through 1979, sixty patients underwent choledochoduodenostomy for benign obstructive lesions of the biliary tract. Patients with traumatic and iatrogenic common duct strictures were excluded. Eighty-two percent of the patients were in the seventh to ninth decades of life. Twenty-seven patients (45 percent) had undergone a total of 40 previous biliary tract surgical interventions. Thirty-three patients (55 percent) in the older age group (average age 75 years) were subjected to choledochoduodenostomy as a primary procedure during the first surgical intervention on the biliary system. Cholangitis recurred in only one patient (in whom the sump syndrome was the culprit), while all other patients have been free of abdominal complaints, cholangitis and pancreatitis during follow-up of 1 to 15 years. There was no operative mortality; morbidity was 26 percent. Hospital stay averaged 15 days. These favorable results mark choledochoduodenostomy as a safe, simple and effective procedure in the treatment of benign biliary tract disease, particularly in aged and high risk patients.

Adolescent↗
PubMed1981

An increase in vasoactive intestinal peptide levels in canine endotoxin shock.

Some of the many metabolic and cardiovascular activities and effects of vasoactive intestinal peptide are quite similar to the changes observed in endotoxin shock. The changes occurring in plasma vasoactive intestinal peptide levels during canine endotoxin shock were studied. Vasoactive intestinal peptide levels were markedly and significantly elevated following the administration of endotoxin, corresponding well with the drop in systemic blood pressure. In the dogs surviving the experiment, plasma vasoactive intestinal peptide levels returned to normal levels after 24 hours, corresponding well with the restoration of normal hemodynamic values. Surviving dogs exhibited significantly lower vasoactive intestinal peptide levels than did nonsurvivors. Many of the biologic activities of vasoactive intestinal peptide make it suitable for counteracting endotoxemia, thus acting as the defense of the body against endotoxin. However, the lower vasoactive intestinal peptide levels in the surviving dogs rather points to vasoactive intestinal peptide as a causative factor in canine endotoxemia.

Animals↗
PubMed1980

Protecting the high-risk rectal anastomosis.

Anastomotic leakage is a serious complication of colonic surgery, and contributes significantly to morbidity and mortality. A new technique has been developed to reduce the danger from such leaks, which involves exteriorizing a loop of transverse colon without opeining it. Should a leak develop, this loop can be transformed into a colostomy; otherwise, it can be easily remimplanted into the abdomen once the bowel is healed.

Colon↗
PubMed1980

Induction of pituitary tumours and hyperprolactinemia in female rats by estrogens. The effect of apomorphine, reserpine and L-dopa.

Prolonged estrogen treatment induced an enlargement of the anterior pituitary gland and finally resulted in irreversible pituitary tumours. Using continuous estrogen delivery [subcutaneous (s.c.) cholesterol-estrogen implants], the effects of ethinyl estradiol and the likewise synthetic estrogens STS 153 and STS 456 have been studied with or without concomitant administration of a progestogen without anti-estrogenic activities (STS 557). There was a dose-dependent prolactin cell-stimulating effect of all these estrogens. Ethinyl estradiol (EE2) had the most marked effect followed by STS 456 which coincides with the relative uterotrophic activity found in rats and mice. The elevated serum prolactin levels in rats with an EE2 implant for 6 months could be reduced slightly but not significantly by apomorphine and reserpine at a daily dose of 100 micrograms/animal and 5 micrograms/animal, respectively. Daily administration of 300 micrograms L-dopa led to a slight but insignificant increase of serum prolactin. The high pituitary weight and serum prolactin levels induced by long-term EE2 treatment were partially reversible after implant withdrawal.

Animals↗
PubMed1980

Blood pyruvate recovery curves after short heavy submaximal exercise in man.

Arterial pyruvate and lactate concentrations were measured after short heavy submaximal exercise on a bicycle ergometer, at 10 or 30 s time intervals, on six male subjects. During most of the first 2 min of recovery pyruvate concentration decreased. Thereafter, it increased and reached its maximum within the 5th to 9th min of recovery. Finally, it decreased gradually as a function of time. Recovery curves could be accurately described after a short delay time following the end of the exercise, by a sum of three exponential terms according to the equation: (Formula: see text), where the time origin (to) is fixed at about 1-1.5 min(delay time) after the end of exercise, t is the time after to, Y(O) and Y(t) are the concentrations of pyruvate respectively at times zero and T, and Ai and zi are constants. The velocity constant of the final arterial blood pyruvate decrease was similar to that of the simultaneously measured lactate, indicating that the rate of lactate removal is closely related to that of pyruvate. This is consistent with the fact that pyruvate is a necessary intermediate in the lactate metabolism.

Adult↗
PubMed1980

Does intravenous fat spare nitrogen in the injured rat?

The role of glucose versus fat as a source of energy in parenteral nutrition is controversial, particularly when administered after trauma, injury or in sepsis. In the present series of experiments, rats undergoing laparotomy and jugular vein cannulation were infused with hypertonic glucose or Intralipid with and without amino acids. The results demonstrate that the combination of amino acids and glucose has a better nitrogen-conserving ability than amino acids and fat, lasting at least 4 days after injury. However, when infused without amino acids, fat had the same nitrogen-conserving quality as glucose. The authors attribute the improved nitrogen-conserving quality of amino acids and glucose to the specific carbohydrate influence on amino acid metabolism, an action which is specific in both protein-free and protein-containing meals but has only very limited effect in the absence of simultaneously infused or fed amino acids. In the moderately to severely injured rat, a glucose calorie is significantly more effective in sparing nitrogen than a fat calorie.

Amino Acids↗
PubMed1980

Plasma amino acid analysis in the differential diagnosis of jaundice.

Distinguishing between obstructive (surgical) and hepatocellular (medical) jaundice is sometimes impossible using the relatively simple diagnostic means of history, physical examination and liver function tests. In an attempt to reduce the number of jaundiced patients in need of complex and expensive diagnostic procedures, we investigated the use of the plasma amino acid pattern in the diagnosis of jaundice. Jaundiced rats with galactosamine-induced hepatitis and seven patients with acute onset hepatitis presented a plasma amino acid pattern in which most all amino acid levels were elevated except for arginine in the rat and branched chain amino acids in the patients. Rats jaundiced due to common bile duct ligation and seven patients with obstructive jaundice proved at surgery exhibited a near-normal amino acid pattern. These experimental and clinical data demonstrate very clear qualitative and quantitative differences in plasma amino acid patterns of hepatocellular and obstructive jaundice, with the latter exhibiting an almost-normal pattern. We suggest the use of the plasma amino acid pattern as a useful adjunct in the differential diagnosis of medical and surgical jaundice.

Adult↗