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Biomedical subjects

H Freund

Publications and source records attributed to H Freund.

At least 19 recordsLinked to original sources

Lactate exchange and removal abilities in sickle cell patients and in untrained and trained healthy humans.

Arterial blood lactate concentrations obtained on seven black males with hemoglobin sickle cell disease (SC) before, during, and after graded bicycle exercise up to exhaustion were compared with those of seven untrained (HU) and seven trained (HT) healthy males of the same ethnic origin. Lactate recovery curves were fitted by a biexponential time function consisting of a rapidly increasing and a slowly decreasing component. Higher work rates were reached by the HU and HT than by the SC group. Blood lactate rose distinctly over the corresponding preexercise resting values after the 25-, 50-, and 100-W exercise steps for the SC, HU, and HT groups, respectively. The arterial oxygen content was significantly lower for the SC than for the HU group at rest and at the end of exercise. The velocity constants of the slowly decreasing component of the lactate recovery curves were similar for the SC, HU, and HT groups despite the fact that they cycled up to different absolute work rates. The velocity constant of the rapidly increasing component was significantly higher for the HT. In terms of the functional meaning given to these constants and in view of their inverse relationship with absolute work rate (Freund et al. J. Appl. Physiol. 61: 932-939, 1986), these results indicate that, relative to the HU, the HT and the SC display improved and impaired abilities, respectively, to exchange and to remove lactate.

Adult

[Physiologic blood coagulation studies in idiopathic arterial thrombosis].

QUESTIONING: The prevalence of inherited thrombotic syndromes in the general population appears to be higher than that of inherited bleeding disorders. However, the most important candidates for screening are patients with unexplained thromboembolism at ages of less than 40 years: In 19 children suffering from "idiopathic" arterial thrombosis laboratory screening has been performed. METHODS: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand-factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin have been investigated. RESULTS: Compared to an age matched healthy control group we could demonstrate in children with arterial thrombosis in vitro platelet activation with significant enhanced platelet aggregation, elevated levels of von Willebrand-factor and alpha-1-antichymotrypsin at the onset of disease. Protein C and alpha-2-antiplasmin were significantly decreased. These changes turned back to normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, c1-inactivator and alpha-2-macroglobulin showed no alterations compared to controls. CONCLUSIONS: Platelet activation and alteration of platelet function have been shown in vivo and in vitro to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The lowering of protein C levels at the onset of thrombotic diseases is discussed to be due to an increased turnover, whereas the decreased levels of alpha-2-antiplasmin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.

Adolescent

[The effect of supramaximal exercise on the recovery kinetics of lactate].

Blood lactate recovery curves from muscular exercise can be described by a sum of two exponential terms consisting in a rapidly increasing and a slowly decreasing component. A two-compartment model consisting of the previously working muscles and the remainder of the lactate space furnishes the simplest but nevertheless realistic explanation of this evolution pattern. The velocity constants of the rapidly increasing (gamma 1) and the slowly decreasing (gamma 2) components inform respectively on the abilities of the body to exchange and remove lactate. However the blood lactate recovery curves observed in three untrained subjects after 3-min 107-115% VO2max cycling display a transitory plateauing of the lactate concentration between the increasing and decreasing phases of the curves. This levelling off of the concentrations at their highest value was not observed in an endurance trained subject after a 3-min 107% VO2max exercise. Despite the plateauing and consequent less good fit than to the usual evolution curves, the recovery curves could still be accurately fitted by the biexponential time function. After supramaximal exercise the abilities to exchange and to remove lactate are severely impaired. These impairments in the functional properties of the organism are very likely associated with and/or linked to physico-chemical modifications which have been observed as much at the cellular level as in the body fluids during and after supramaximal exercise.

Acidosis

Blood lactate during constant-load exercise at aerobic and anaerobic thresholds.

Venous blood lactate concentrations [1ab] were measured every 30 s in five athletes performing prolonged exercise at three constant intensities: the aerobic threshold (Thaer), the anaerobic threshold (Than) and at a work rate (IWR) intermediate between Thaer and Than. Measurements of oxygen consumption (VO2) and heart rate (HR) were made every min. Most of the subjects maintained constant intensity exercise for 45 min at Thaer and IWR, but at Than none could exercise for more than 30 min. Relationships between variations in [1ab] and concomitant changes in VO2 or HR were not statistically significant. Depending on the exercise intensity (Thaer, IWR, or Than) several different patterns of change in [1ab] have been identified. Subjects did not necessarily show the same pattern at comparable exercise intensities. Averaging [1ab] as a function of relative exercise intensity masked spatial and temporal characteristics of individual curves so that a common pattern could not be discerned at any of the three exercise levels studied. The differences among the subjects are better described on individual [1ab] curves when sampling has been made at time intervals sufficiently small to resolve individual characteristics.

Aerobiosis

Comparative lactate kinetics after short and prolonged submaximal exercise.

Arterial blood lactate concentrations were determined in two groups of eleven males before, during and after near 2 W.kg body mass-1 bicycle exercise. One group of subjects cycled for 3 min, whereas the second group exercised for 60 min. All the lactate curves during recovery could be fitted to a bi-exponential time function consisting of a rapidly increasing and a slowly decreasing component. This typical evolution pattern indicates that the two-compartment model which has been proposed to represent the movements of lactate after short exercise applies also to recovery from prolonged exercise. Lengthening exercise duration decreased (respectively 10% and 28%) the value of both velocity constants of the fits to the lactate recovery curves, with the difference (28%) being statistically significant for the velocity constant describing the slowly decreasing part of the curves. This result indicates that extending exercise from 3 to 60 min impairs the ability to remove lactate after the exercise.

Adult

Lactate removal ability and graded exercise in humans.

Venous lactate concentrations of nine athletes were recorded every 5 s before, during, and after graded exercise beginning at a work rate of 0 W with an increase of 50 W every 4th min. The continuous model proposed by Hughson et al. (J. Appl. Physiol. 62: 1975-1981, 1987) was well fitted with the individual blood lactate concentration vs. work rate curves obtained during exercise. Time courses of lactate concentrations during recovery were accurately described by a sum of two exponential functions. Significant direct linear relationships were found between the velocity constant (gamma 2 nu) of the slowly decreasing exponential term of the recovery curves and the times into the exercise when a lactate concentration of 2.5 mmol/l was reached. There was a significant inverse correlation between gamma 2 nu and the rate of lactate increase during the last step of the exercise. In terms of the functional meaning given to gamma 2 nu, these relationships indicate that the shift to higher work rates of the increase of the blood lactate concentration during graded exercise in fit or trained athletes, when compared with less fit or untrained ones, is associated with a higher ability to remove lactate during the recovery. The results suggest that the lactate removal ability plays an important role in the evolution pattern of blood lactate concentrations during graded exercise.

Adolescent

Effect of exercise duration on lactate kinetics after short muscular exercise.

Arterial blood lactate concentrations were measured in six normal males before, during and after 3- and 6-min bicycle exercises performed at three different work rates. The lactate recovery curves were fitted to a bi-exponential time function consisting of a rapidly increasing and a slowly decreasing component, which supplied an accurate representation of the changes in lactate concentration. Variations in the parameters of this mathematical model have been studied as a function of the duration of exercise and of the work rate, showing a clear dependence on exercise duration such that increasing exercise length decreases the velocity constants of the fitted curves. In terms of the functional meaning which can be given to these constants, this result indicates that extending exercise duration from 3 to 6 min reduces the ability of the whole body to exchange and remove lactate. This effect did not qualitatively modify the one already described, which is due to increased work rates, but it shifted the ability to exchange and remove lactate towards lower values. The main conclusion of the study is that lactate kinetic data vary as a function of time during exercise. This inference must be accounted for in the interpretation of lactate data obtained during muscular exercise.

Adult

Comparison of arterial and venous blood lactate kinetics after short exercise.

Seventeen healthy male volunteers participated in this study designed to compare arterial with both arterialized venous and venous lactate kinetics after short exercise. Blood samples drawn before, during, and after bicycle exercise were analyzed continuously for lactate. A mathematical function incorporating two exponential terms was fitted to the arterial, arterialized venous, and venous lactate recovery curves, and the parameters of the mathematical function were compared using a linear regression. All parameters measured on or fitted to the arterialized venous curves correlated well with the respective arterial data (correlation coefficient R = 0.82 to 0.99, P less than 0.001). Among the parameters obtained from the fit to the venous curves, only those describing lactate removal correlated closely with the arterial results. It is concluded that for lactate kinetic studies during recovery following short-term muscular exercise, the information obtained from arterialized venous blood is comparable to arterial blood, whereas the use of venous blood, from the sampling site in this study, appears suitable for determining only the parameters for lactate disappearance. These conclusions are illustrated by the comparison between arterial, arterialized venous, and venous parameters as a function of the work rate of the previously performed exercise.

Adult

Prolonged submaximal exercise and L-carnitine in humans.

Changes in the main physiological parameters and circulating indicators of carbohydrate, protein, lipid (and ketone body) metabolism were measured in ten exercising subjects before L-carnitine (L-carn) loading, after 4 weeks of daily loading with 2 g L-carn, and 6-8 weeks after terminating L-carn administration. Measurements were made on venous blood samples collected during each experiment at fixed time intervals over an initial rest of 45 min, 60 min bicycle exercise performed near 50% VO2max and 120 min recovery. Free and total plasma carnitine levels reached a plateau corresponding to an average rise of 25% for both fractions, 9-10 days after the beginning of the L-carn diet. These levels returned to their initial values 6-8 weeks after cessation of the supply. Generally L-carn supplementation did not significantly modify the physiological parameters and circulating metabolites. No distinct increase of the relative participation of endogenous lipids in the fuel supply of prolonged submaximal exercise was observed. In normal human subjects the increased demand for fatty acid oxidation resulting from exercise seems to be adequately supported by endogenous levels of carnitine.

Adult

Managing the granulocytopenic patient with acute perianal inflammatory disease.

Acute perianal inflammation concomitant with a decrease in the number of circulating granulocytes developed in 15 patients with various hematologic disorders. The treatment included antibiotic coverage alone (11 patients) or combined with surgical drainage of the inflamed area (7 patients). Our study shows that surgical drainage during agranulocytosis resulted in slow healing of the wound, prolonged hospitalization, and a higher mortality rate, when compared with the group that received antibiotics alone (28 percent versus 18 percent). The preferred treatment for these patients is the administration of broad spectrum antibiotics without attempting drainage of the infected area.

Acute Disease

Work rate-dependent lactate kinetics after exercise in humans.

Arterial blood lactate concentrations were measured on 19 subjects before, during, and after a 3-min bicycle exercise at several work rates, and the concentrations during the recovery phases were fitted to a biexponential time function consisting of a rapidly increasing and a slowly decreasing component. Highly significant correlations with the work rate of the exercise preceding the recovery were found for all the parameters of the fitted equation. The two velocity constants show inverse linear relationships, whereas the other parameters vary according to a definite power function. A functional meaning has been given to the two velocity constants, namely the ability of the tissues to exchange and to remove lactate. For the group of subjects studied, after exercises at work rates below about 3.5 W/kg, the tissue's ability to utilize, and possibly to exchange lactate, increases over values generally reported for resting conditions, whereas after exercises at higher work rates the inverse occurs. Lactate kinetics during recovery appear to be the result of two underlying processes, one enhancing the ability of the tissues to exchange and remove lactate and the other restraining it.

Adult

Further report on the endocrinological profile of two synthetic estrogens with antifertility properties, STS 456 and STS 593.

Two synthetic estrogens, STS 456 and STS 593, with noteworthy post-coital antifertility properties in the rat were studied for their estrogenic, antiestrogenic, progestagenic, antiprogestagenic, antigonadotrophic, androgenic and antiandrogenic effects in laboratory animals. Beside their weak estrogenic activity which corresponds to their slight affinity to the uterine estrogen receptor in the rat, both steroids show remarkable antiestrogenic effects. No progestagenic, androgenic and antiandrogenic effects were found but STS 593 showed some antiprogestagenic activity. The antigonadotrophic efficacy of STS 456 was relatively high while STS 593 was scarcely active. The results are discussed with respect to possible application of these drugs for interceptive purposes.

Anabolic Agents

Chronic hepatic encephalopathy. Long-term therapy with a branched-chain amino-acid-enriched elemental diet.

Therapy of chronic hepatic encephalopathy is often frustrating, limited as it is by the ability to adequately nourish such patients. Protein is needed for repair, but such patients are intolerant of protein. Previous work from this and other laboratories has suggested that the distorted plasma amino acid pattern may be causally related to hepatic encephalopathy. A single, well-studied, long-term patient received therapy with a branched-chain amino-acid-enriched elemental diet that not only enabled adequate nutrition with protein but resulted in improvement in hepatic function as well as reversal of some aspects of hepatic encephalopathy that heretofore have been deemed irreversible. The results confirm that branched-chain-enriched amino acid diets previously successful in the intravenous mode may be successfully used in chronic long-term support of patients with protein intolerance, with improvement in hepatic function secondary to improvement in nutrition.

Administration, Oral

Effects of adenosine diphosphate, colchicine and temperature on size of human platelets.

An improved measuring system based on the Coulter principle and developed in our laboratory is used to size human blood platelets. The mean volume of platelets in 24 healthy subjects is found to be 8.45 micron 3 with a standard deviation of 1.07 micron 3; the typical size-distribution curve is unimodal and asymmetrical, with a marked skew to the right. The effects of different reagents on platelet size (shape factor x volume) are evaluated. Platelets increase in size by 23% following suspension in isotonic, phosphate-buffered saline and incubation with 10 microM adenosine diphosphate; no change is observed when the suspending medium is autologous plasma. Cooling the platelets to 0-4 degrees C results in a size increase of 25%; rewarming to 37 degrees C restores them to their initial size within 2 hr. A similar increase occurs when the platelets are incubated with 1-10 mM colchicine. It is proposed that these reagents, which are known to produce changes in the orientation of the marginal bundle of microtubules, cause platelets to undergo disc-sphere transformations. Calculations are made which show that such transformations increase platelet size by 27% as measured electrically, and we conclude that the so-called volume changes reported in the literature reflect shape changes only and that no true volume increase actually takes place.

Adenosine Diphosphate

Chromium deficiency during total parenteral nutrition.

Chromium is required for maintenance of normal glucose tolerance. After complete bowel resection and five months of total parenteral nutrition, severe glucose intolerance, weight loss, and a metabolic encephalopathy-like confusional state developed in a patient. Serum chromium levels were at the lowest normal level. Supplementation of 150 microgram of chromium per day reversed the glucose intolerance, reduced insulin requirements, and resulted in weight gain and the disappearance of encephalopathy. The low levels of chromium and response to chromium supplementation suggest that chromium deficiency can arise in long-term total parenteral nutrition.

Blood Glucose