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Biomedical subjects

J D Tobin

Publications and source records attributed to J D Tobin.

At least 91 records · Page 5Linked to original sources
PubMed1977

Management of anticoagulation in outpatients: experience with an anticoagulation service in a municipal hospital setting.

In 66 months, a general hospital's outpatient Anticoagulation Service (ACS) monitored 263 patients who received 280 courses of warfarin sodium totalling 254 patient treatment years. Major hemorrhagic morbidity was 4% of courses and there was no mortality attributable to warfarin therapy. Major hemorrhage occurred in patients with increased anatomic risk of bleeding (diverticulosis, hemorrhoids, cystitis), and was not a function of patient age, sex, anticoagulation control, or medications administered concurrently with warfarin. Control of anticoagulation was not correlated with age or other medications, but was worsened significantly by the presence of congestive heart failure. We attribute a favorable experience with outpatient ACS to careful patient selection, patient education and monitoring, attention to duration of anticoagulation, and continuing communication with primary physicians who retained responsibility for medical care. An ACS offers safety, consistency, efficiency, and a unified approach to outpatient anticoagulation in the general hospital setting.

Aged↗
PubMed1976

The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study.

Standard true 24-hour creatinine clearance determinations were performed on 884 subjects of the Baltimore Longitudinal Study. On the basis of clinical data, subjects were placed in categories indicating the presence of specific diseases or medications which might alter glomerular filtration rate. Subjects not included in these categories were considered normal (N=548). In the normals, cross-sectional analysis by 10-year age groups showed a progressive linear decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80. Three or more serial clearances were obtained at 12- to 18-mo. intervals on 293 normal subjects. These longitudinal data showed an acceleration of the rate of decline in creatinine clearance with advancing age. The decrease in creatinine clearance with age seen in this study represents true renal aging and is not secondary to diseases which become increasingly prevalent in the elderly. A nomogram constructed from these data provides normative age-corrected standards for creatinine clearance.

Adolescent↗
PubMed1976

Effects of arterial versus venous sampling on analysis of glucose kinetics in man.

A compartmental model is presented to account for transient and steady-state changes in blood glucose concentration which result from transit through the forearm and hand in man. This model permits the inter-conversion of arterial and venous data and the derivation of arterial equivalent total body glucose models from venous data. Data were obtained from subjects in the basal state following a pulse injection of [1-14C]glucose tracer. An artery, an antecubital vein, and a dorsal vein of a heated hand (68 degrees C environment) were sampled. Blood transit time is shorter 0.3 vs. 1.0 min) and irreversible glucose loss is reduced (1.9 vs. 2.9%) in the heated hand preparation when compared to the antecubital vein preparation. Because of the smaller correction required and the smaller variation among individuals when heated hand rather than antecubital vein data are obtained, we suggest that for analysis of whole-body kinetics such data should be used along with the compartmental model correction when arterial data cannot be obtained.

Adult↗
PubMed1976

Effects of brief starvation on muscle amino acid metabolism in nonobese man.

A reduction in the release of substrate amino acids from skeletal muscle largely explains the decrease in gluconeogenesis characterizing prolonged starvation. Brief starvation is associated with an increase in gluconeogenesis, suggesting increased release of amino acids from muscle. In the present studies, accelerated amino acid release from skeletal muscle induced by brief starvation was sought to account for the accompanying augmentation of gluconeogenesis. To do this amino acid balance across forearm muscles was quantified in 15 postabsorptive (overnight fasted) subjects and in 7 subjects fasted for 60 h. Fasting significantly reduced basal insulin (11.3-7.5 muU/ml) and increased glucagon (116-134 pg/ml). Muscle release of the principal glycogenic amino acids increased. Alanine release increased 59.4%. The increase in release for all amino acids averaged 69.4% and was statistically significant for threonine, serine, glycine, alanine, alpha-aminobutyrate, methionine, tyrosine, and lysine. Thus, with brief starvation, muscle release of glycogenic amino acids increases strikingly. This contrasts with the reduction of amino acid release characterizing prolonged starvation. The adaptation of peripheral tissue metabolism to brief starvation is best explained by the decrease in insulin.

Adult↗
PubMed1976

Metabolism of forearm tissues in man. Studies with glucagon.

The role of glucagon in regulating peripheral tissue metabolism in man was assessed in the present studies. To do this, glucagon was infused for two hours into the brachial artery to produce a high but physiologic increment in the glucagon content of arterial blood supplying ipsilateral tissues. Metabolic effects on muscle and on subcutaneous adipose tissue plus skin were sought in seven overnight-fasting subjects and seven subjects starved briefly (60 hours). In the overnight-fasted group the infusion increased bassl glucagon concentration by 1,216 pg./ml. but was without effect on forearm tissue metabolism of glucose, lactate,glycerol, or amino acids. Starvation significantly reduced basal insulin (11.0 to 7.4 muU./ml.) and increased endogenous glucagon (116 to 134 pg./ml.). Basally, there was substantial ketone utilization and a decrease in glucose consumption by both muscle and subcutaneous adipose tissue plus skin. The glucagon infusion increased basal glucagon by 784 pg./ml. Muscle balances of glucose, lactate, acetoacetate, amino acids, and glycerol were unaffected. The metabolism of glucose, lactate, acetoacetate, glycerol, and free fatty acids by subcutaneous adipose tissue plus skin was also unchanged. It is concluded that physiologic increments of glucagon lasting two hours are without effect on forearm tissues in overnight-fasted and briefly starved man.

Acetoacetates↗
PubMed1975

Antipyrine metabolism in man: influence of age, alcohol, caffeine, and smoking.

Age has been shown to influence drug metabolism but effects of aging could be due to other variables that influence metabolism and differ with age. Plasma half-life and metabolic clearance rate of antipyrine were studied in 307 healthy male subjects, aged 18 to 92. Half-life was 16.5% longer and metabolic clearance rate was 18.5% less in a group of the older than in the younger subjects. Both caffeine and cigarette use were positively correlated with the rate of antipyrine metabolism. Multiple regression analysis showed that the effect of smoking was partially responsible for the age differences in antipyrine metabolism. Smoking explained 12% of the variance in metabolic clearance rate and age explained 3%. Our results suggest that studies attempting to quantify the effects of aging on drug metabolism must also take into account other factors that differ with age.

Adolescent↗
PubMed1975

Insulin control of glucose metabolism in man: a new kinetic analysis.

Analyses of the control of glucose metabolism by insulin have been hampered by changes in bloog glucose concentration induced by insulin administration with resultant activation of hypoglycemic counterregulatory mechanisms. To eliminate such mechanisms, we have employed the glucose clamp technique which allows maintenance of fasting blood glucose concentration during and after the administration of insulin. Analyses of six studies performed in young healthy men in the postabsorptive state utilizing the concurrent administration of [14C]glucose and 1 mU/kg per min (40 mU/m2 per min) porcine insulin led to the development of kinetic models for insulin and for glucose. These models account quantitatively for the control of insulin on glucose utilization and on endogenous glucose production during nonsteady states. The glucose model, a parallel three-compartment model, has a central compartment (mass = 68 +/- 7 mg/kg; space of distribution = blood water volume) in rapid equilibrium with a smaller compartment (50 +/- 17 mg/kg) and in slow equilibrium with a larger compartment (96 +/-21 mg/kg). The total plasma equivalent space for the glucose system averaged 15.8 liters or 20.3% body weight. Two modes of glucose loss are introduced in the model. One is a zero-order loss (insulin and glucose independent) from blood to the central nervous system; its magnitude was estimated from published data. The other is an insulin-dependent loss, occurring from the rapidly equilibrating compartment and, in the basal period, is smaller than the insulin-independent loss. Endogenous glucose production averaged 1.74 mg/kg per min in the basal state and enters the central compartment directly. During the glucose clamp experiments plasma insulin levels reached a plateau of 95 +/-8 microU/ml. Over the entire range of insulin levels studied, glucose losses were best correlated with levels of insulin in a slowly equilibrating insulin compartment of a three-compartment insulin model. A proportional control by this compartment on glucose utilization was adequate to satisfy the observed data. Insulin also rapidly decreased the endogenous glucose production to 33% of its basal level (0.58 mg/kg per min), this suppression being maintained for at least 40 min after exogenous insulin infusion was terminated and after plasma insulin concentrations had returned to basal levels. The change in glucose utilization per unit change in insulin in the slowly equilibrating insulin compartment is proposed as a new measure for insulin sensitivity. This defines insulin effects more precisely than previously used measures, such as plasma glucose/plasma insulin concentration ratios. Glucose clamp studies and the modeling of the coupled kinetics of glucose and insulin offers a new and potentially valuable tool to the study of altered states of carbohydrate metabolism.

Adolescent↗
PubMed1975

Outpatient management of anticoagulation.

The Anticoagulation Service insures uniformity of approach to the regulation of anticoagulation for patients of hospital-based primary physicians. There has been no anticoagulant-related mortality in 254 patient treatment-years, and the major complication rate is 4% of treatment courses. There is a relatively low complication rate because of the systematic approach to anticoagulation therapy, recognition of the importance of patient education, communication with the primary physician, and flexibility of drug dosage and patient visit regimens. Achieving the therapeutic range of the prothrombin time with minimum complications is the goal of this Service. The hallmark of adequate control is predictable response of the prothrombin time to adjustments in drug dosage. Statistical analysis of six years' experience has provided support for the thesis that control of anticoagulation and incidence of complications are not significantly altered by patient age, sex, or the presence of concurrent nonthromboembolic medical illness.

Administration, Oral↗
PubMed1974

A model of the kinetics of insulin in man.

The design of the present study of the kinetics of insulin in man combines experimental features which obviate two of the major problems in previous insulin studies. (a) The use of radioiodinated insulin as a tracer has been shown to be inappropriate since its metabolism differs markedly from that of the native hormone. Therefore porcine insulin was administered by procedures which raised insulin levels in arterial plasma into the upper physiologic range. Hypoglycemia was prevented by adjusting the rate of an intravenous infusion of glucose in order to control the blood glucose concentration (the glucose-clamp technique). (b) Estimation of a single biological half-time of insulin after pulse injection of the hormone has been shown to be inappropriate since plasma insulin disappearance curves are multiexponential. Therefore the SAAM 25 computer program was used in order to define the parameters of a three compartment insulin model. The combined insulin mass of the three compartments (expressed as plasma equivalent volume) is equal to inulin space (15.7% body wt). Compartment 1 is apparently the plasma space (4.5%). The other two compartments are extra-vascular; compartment 2 is small (1.7%) and equilibrates rapidly with plasma, and compartment 3 is large (9.5%) and equilibrates slowly with plasma. The SAAM 25 program can simulate the buildup and decay of insulin in compartments 2 and 3 which cannot be assayed directly. Insulin in compartment 3 was found to correlate remarkably with the time-course of the servo-controlled glucose infusion. Under conditions of a steady-state arterial glucose level, glucose infusion is a measure of glucose utilization. We conclude that compartment 3 insulin (rather than plasma insulin) is a more direct determinant of glucose utilization. We suggest that the combined use of glucose-clamp and kinetic-modeling techniques should aid in the delineation of pathophysiologic states affecting glucose and insulin metabolism.

Adolescent↗
PubMed1969

Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels.

Amino acid balance across skeletal muscle and across subcutaneous adipose tissue plus skin of the forearm has been quantified in postabsorptive man before and after insulin infusion into the brachial artery. Skeletal muscle released significant amounts of alpha amino nitrogen after an overnight fast. Most individual amino acids were released. Alanine output was by far the greatest. The pattern of release probably reflects both the composition of muscle protein undergoing degradation and de novo synthesis of alanine by transamination. A significant correlation was observed between the extent of release of each amino acid and its ambient arterial concentration. Elevation of forearm insulin in eight subjects from postabsorptive (12 muU/ml) to high physiologic levels (157 muU/ml) in addition to stimulating muscle glucose uptake blocked muscle alpha amino nitrogen release by 74%. Consistent declines in output were seen for leucine, isoleucine, tyrosine, phenylalanine, threonine, glycine, and alpha-aminobutyric acid. Alanine output was insignificantly affected. Doubling forearm insulin levels (from 10 to 20 muU/ml) in eight subjects increased muscle glucose uptake in three and blocked alpha amino nitrogen output in two although both effects were seen concurrently in only one subject. Changes in net amino acid balance after insulin could be accounted for by increased transport of amino acids into muscle cells or retardation of their exit. It is likely that ambient arterial amino acid concentrations are established and maintained primarily by the extent of muscle amino acid release. The individual amino acids whose outputs from forearm muscle decline after forearm insulinization correspond well with those whose levels fall systematically after systemic insulinization. This suggests that declines in amino acid levels after systemic insulinization are due to inhibition of muscle release. Doubling basal insulin approaches the threshold both for blockade of muscle amino acid output and stimulation of glucose uptake, effects which appear to occur independently.

Adipose Tissue↗