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Biomedical subjects

J D Tobin

Publications and source records attributed to J D Tobin.

At least 19 recordsLinked to original sources
PubMed1992

Biochemical parameters associated with low bone density in healthy men and women.

A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.

Adult↗
PubMed1992

Sex differences in geometry of the femoral neck with aging: a structural analysis of bone mineral data.

The greater hip fracture rate among elderly women is generally ascribed to differences in femoral neck strength between the sexes. Strength of a given bone is a function of both its material properties and the magnitudes of mechanical stresses within it. This study examined the hypothesis that these apparent strength differences between the sexes are due to dissimilarities in the restructuring of the femoral neck with age, which result in higher stresses in elderly women. Using Hip Strength Analysis, a computer program developed by the authors, femoral neck cross-sectional geometric properties for stress analyses were derived from bone mineral image data of 409 community living, white subjects ranging from 19 to 93 years of age. Though both sexes show declines in femoral neck bone mineral density (BMD) and cross-sectional area with age, only females show a decline in the cross-sectional moment of inertia (CSMI, a geometric index of bone rigidity). The lack of decline in male CSMI appears to be a result of a small but significant increase in femoral neck girth. Similar age-related changes have been observed in the femoral shaft by others. The net effect of these observed changes is that mechanical stresses in the femoral neck of females appear to increase at three times the rate per decade of those of males. These results lend support to the hypothesis that the higher fracture rate in elderly women is due, at least in part, to elevated levels of mechanical stress, resulting from a combination of greater bone loss and less compensatory geometric restructuring with age.

Adult↗
PubMed1992

Glucose tolerance in women: the effects of age, body composition, and sex hormones.

OBJECTIVE: To determine the separate and interactive effects of age, phase of the menstrual cycle, menopausal hormone status, body fat mass, and regional fat distribution on glucose tolerance in healthy women. DESIGN: Retrospective study. SETTING: The Baltimore Longitudinal Study of Aging. PATIENTS: Two hundred sixty healthy women aged 22-89 years. MEASUREMENTS: Plasma levels of estradiol and progesterone, body mass index (BMI), waist-to-hip ratio (WHR), and plasma glucose values in the fasting state (FPG) as well as 120 minutes after 40 gm/m2 of oral glucose (G120) were measured for each participant. RESULTS: We found a progressive decline in oral glucose tolerance of 0.4 mM (6.7 mg/dL)/decade at G120) in women from early to late adult years, with no relationship to phase of the menstrual cycle and no abrupt change associated with the menopause. Multiple regression analysis revealed significant, independent effects of BMI and WHR on FPG and G120. The influence of age (P less than 0.01) on G120 was stronger than that of the BMI or WHR (P less than 0.05). There was no significant relationship between the levels of endogenous sex hormones and glucose tolerance after adjustments for age, BMI, and WHR. However, women taking oral contraceptives, but not those receiving postmenopausal replacement therapy, did exhibit mildly elevated G120 values. CONCLUSIONS: Age per se, and to a lesser extent BMI and WHR, but not levels of endogenous sex steroids, contribute to the physiological decline in glucose tolerance in older women.

Activities of Daily Living↗
PubMed1992

Factor structure of morphometric variables measured on six metacarpal bones.

Morphometry of the second, third and fourth metacarpal bone was performed on hand-wrist radiograms of both hands in a sample of 434 male and 549 female adult subjects. Morphometric data (bone length-L, total diaphysis width-T and medullary canal width-M) and age were processed using principal factor analysis with oblique rotation, separately for males and females. In both sexes three factors accounting for 74.7% of the total variance were extracted, but their patterns of variation differed. Factors-"cumulative environmental-genetic factor", "longitudinal factor", and "transversal factor"-are discussed within the context of their biological meaning affecting the phenotypic formation of metacarpal skeleton in a given population.

Adult↗
PubMed1992

Alcohol consumption in the guinea pig is associated with reduced megakaryocyte deformability and platelet size.

Mild thrombocytopenia is common in alcoholic individuals. Ethanol appears to impair platelet production primarily by affecting the maturing megakaryocyte compartment. We recently showed that guinea pigs have an unusually large number of elongated platelet forms even under conditions of steady-state thrombopoiesis, and a portion of their mature (stage IV) megakaryocytes yield extremely long extensions on micropipette aspiration. This study evaluates the effect of a moderately low level of ethanol consumption by guinea pigs on platelet size and form and megakaryocyte deformability. Adult Duncan Hartley guinea pigs took ethanol 2.5% (vol/vol) ad libitum for 4 weeks under environmentally controlled conditions, never reaching detectable blood ethanol levels (< 0.01%); the platelet count fell 16%. Elongated platelet forms constituted 29% of the cardiac puncture platelets of control animals, but only 3% of the cardiac puncture platelets of animals given ethanol; discocytic platelets of ethanol-treated animals were also significantly smaller. Individual stage III and IV megakaryocytes were aspirated into 5 microns diameter micropipettes by stepwise increment in pressure from 10 to 200 cm water. The extensions drawn from megakaryocytes of ethanol-exposed animals were significantly shorter than the extensions from control megakaryocytes. Extremely long extensions over 50 microns in length were drawn from 21% of the control megakaryocytes but less than 1% of ethanol-exposed megakaryocytes. Moderately low level ethanol consumption was associated with reduced platelet count and size, along with rigidity of mature megakaryocytes in guinea pigs. Few ethanol-exposed megakaryocytes yielded extremely long cell extensions, nor were elongated platelet forms prevalent in the circulation of animals given ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗
PubMed1991

Factors associated with osteoarthritis of the hand in males: data from the Baltimore Longitudinal Study of Aging.

The association of metabolic and physiologic factors with hand osteoarthritis was studied in 888 Caucasian male subjects aged 17-102 years in the Baltimore Longitudinal Study of Aging. Left-hand radiographs taken between 1958 and 1975 were read by one investigator for grade of osteoarthritis using Kellgren-Lawrence scales. Possible risk factors, assessed at the same visit as the last radiograph during this interval, included age and measures of bone mass, body composition, muscle mass, and muscle strength. Results of bivariate analyses of these cross-sectional data showed that increasing grade of hand osteoarthritis was associated with increasing age; greater mean levels of waist/hip ratio and percentage of body fat; and lower mean levels of percentage of cortical area, grip strength, and forearm circumference. After adjustment for age using residuals from best-fit quadratic regression models, none of these independent variables remained significantly associated with grade of hand osteoarthritis. These data fail to support hypotheses that metabolic and physiologic factors are associated with hand osteoarthritis independent of their known age-related changes.

Adolescent↗
PubMed1991

Reversible effects of ethanol in utero on cardiac sarcoplasmic reticulum of guinea pig offspring.

STUDY OBJECTIVE: The aim was to investigate the effects of chronic ethanol exposure in utero on the sarcoplasmic reticulum of the developing heart. DESIGN: Pregnant guinea pigs were given 2.5% ethanol in their drinking water and guinea pig lab chow from day 30 to the end of pregnancy. Control pregnant guinea pigs received regular drinking water and lab chow. Ethanol was discontinued at delivery. Cardiac calcium transport function was evaluated in isolated sarcoplasmic reticulum from offspring of ethanol treated and control guinea pigs killed at 1-3 d and 3-5 months of age. EXPERIMENTAL SUBJECTS: The study group consisted of 28 Camm-Hartley guinea pigs. There were 24 controls of the same species. MEASUREMENTS AND MAIN RESULTS: Maternal deaths, litter size, number of stillborns, newborn body weight, and heart weight were not different in ethanol treated and control guinea pigs and their offspring. Ca2+ uptake, Ca2+ binding, and Ca2+ stimulated ATPase activity in isolated sarcoplasmic reticulum were all reduced in 1-3 d old offspring from ethanol treated mothers when compared to age matched control offspring (p less than 0.05). By 3-5 months, calcium transport in cardiac sarcoplasmic reticulum of ethanol treated offspring was similar to that of age matched control offspring. CONCLUSIONS: Moderate ethanol exposure in utero produced functional cardiac alterations in the newborn which were slowly reversible with abstinence from ethanol.

Adenosine Triphosphatases↗
PubMed1991

Is the recommended daily allowance for vitamin D too low for the homebound elderly?

A population of sunlight-deprived elderly was studied to determine the daily intake of vitamin D and whether dietary intake was sufficient to maintain a normal vitamin D status. Twenty-two subjects over 65 years old with serum creatinine less than 180 mumols/L and confined indoors for more than 6 months were chosen from the community and a nursing home in Southeast Baltimore. Three-day food records were obtained along with serum levels of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2 D), and intact parathyroid hormone (PTH). The mean daily vitamin D intake was over twofold greater than the adult Recommended Daily Allowance (RDA) of 200 IU. The mean 25-OHD level was 40 nmol/L (normal 25-138 nmol/L) with seven patients less than 25 nmol/L. Of these participants with 25-OHD values less than 25 nmol/L, the mean vitamin D intake was 467 IU (range 36-1096 IU). We conclude that the current RDA seems inadequate for many older individuals who do not get sun exposure. This particular population of elderly is at risk to develop vitamin D deficiency and the associated complications.

Aged↗
PubMed1990

The age-associated decline in glomerular filtration in healthy normotensive volunteers. Lack of relationship to cardiovascular performance.

Whether the well-documented age-associated decline in the glomerular filtration rate, manifest as a decline in creatinine clearance, is secondary to an age-related change in cardiovascular performance is at present unknown. To answer this question, we measured arterial blood pressure, 24-hour creatinine clearance, and cardiac output determined from gated cardiac blood pool scans in the sitting position in healthy normotensive men (n = 75) and women (n = 42) (ages 25 to 82 years), from the Baltimore Longitudinal Study on Aging. These subjects were selected for the absence of cardiovascular disease, renal disease, and confounding medications. By linear regression analysis, creatinine clearance, expressed in mL/min/m2, declined cross-sectionally with age (creatinine clearance = 90 -0.33[age], r = .31, P less than .001), whereas systolic blood pressure in mm Hg increased with age (systolic blood pressure = 111 + 0.27[age], r = .30, P less than .001); cardiac output in L/min/m2 did not vary with age (r = .03, P = .74). In stepwise multiple regression analysis with age, cardiac index, and systolic blood pressure as independent variables and creatinine clearance as the dependent variable, only age was a significant predictor of creatinine clearance. (F = 11.31, DF + 116, r = .30, P less than .001). Thus, the age-associated decline in creatinine clearance is not modulated by changes in cardiac index or systolic blood pressure in healthy normotensive subjects.

Adult↗
PubMed1979

Glucose clamp technique: a method for quantifying insulin secretion and resistance.

Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.

Glucose↗
PubMed1979

Kinetics of native insulin in diabetic, obese, and aged men.

The kinetics of unlabeled porcine insulin were studied in 69 nondiabetic male subjects aged 18-83 yr with obesity indexes of 0.93 - 1.51 and in 12 maturity-onset diabetics age 46-78 yr with obesity indexes of 0.95-1.56 by using the euglycemic clamp technique. Analysis of the insulin kinetic data by using a mathematical model permitted the determination, for each individual, of steady state distribution masses and degradation rate constants. The individuals were grouped to allow comparison of the results on the basis of age, obesity index, or diabetes. The responses over a period of 120 min to an infusion and wash out of insulin show some transient as well as steady state differences with age, obesity, or diabetes. Analysis of these data by use of compartmental models leads to the conclusion that in the steady state the ratio of insulin in extravascular spaces to that in plasma (T/P) is decreased in the moderately obese group (26%) and in the diabetic group (17%) but increased in the older group (13%) when each is compared with the appropriate control. Since extravascular insulin includes both insulin bound to receptors and insulin in the interstitial fluid, the observed changes in the extravascular to plasma mass ratio most likely reflect changes in in vivo binding to receptors, although the magnitude of the change would be modified somewhat by changes in the size of the interstitial spaces relative to plasma. In addition, the rate of entry of new insulin into plasma (BSDR) was increased in the diabetic population (45%; P less than 0.02) as well as in the moderately obese group (27%) but was decreased somewhat in the older group (11%). The following general conclusions can be drawn from the results: The pattern of parameter changes seen with obesity is similar to that seen with maturity-onset diabetes. The decrease in T/P seen with obesity and with maturity-onset diabetes cannot be accounted for solely by changes in fasting plasma insulin levels in these populations. The pattern of changes seen in the older subjects is opposite that seen in the maturity-onset diabetics, which suggests that diabetes is a perturbation distinct from the normal aging process. Finally, the changes in the metabolism of insulin are not large, making it unlikely that they are the sole cause of the major alterations in glucose tolerance seen with aging, obesity, or diabetes.

Adolescent↗
PubMed1978

The response of arginine vasopressin to intravenous ethanol and hypertonic saline in man: the impact of aging.

The effect of age on the hypothalamic-hypophyseal-renal axis in normal man was determined by assaying plasma arginine vasopressin (AVP) responses to inhibitory and to secretory stimuli. Nine young (21-49 years) and 13 old (54-92 years) subjects received IV ethanol (375 mg/m2 per min). AVP levels fell progressively during the infusion in the young group, but fell for only 30 min in the old group and then rose paradoxically despite the continuing increase in blood ethanol. Eight young (22-48 years) and 8 old (52-66 years) men were provided identical osmolal loads by a 2-hour IV infusion of 3% NaCl at 0.1 ml/kg per min. Serum AVP rose 2.5 times the baseline in the young and 4.5 times the baseline in the old men despite identical free water clearances. Osmoreceptor sensitivity (the slope of AVP on osmolality) was greater in the old subjects. The heightened sensitivity to hyperosomolality helps examine the paradoxical response to ethanol, since osmolality increased during that time. This increased AVP response may severe to compensate for the reduced renal ability to conserve salt and water in aging man.

Adult↗
PubMed1978

Oral glucose augmentation of insulin secretion. Interactions of gastric inhibitory polypeptide with ambient glucose and insulin levels.

Gastric inhibitory polypeptide, or GIP, has been postulated as the major enteric hormonal mediator of insulin release. The release of immuno-reactive GIP (IR-GIP) after oral glucose and its role in insulin release was studied in normal men by the glucose clamp technique. In 24 subjects studied with the hyperglycemic clamp, blood glucose was maintained at 125 mg/dl above basal for 2 h via a primed-continuous IV glucose infusion coupled to a servo-controlled negative feedback system. 40 g glucose per m(2) surface area was ingested at 60 min, and the blood glucose was maintained at the steady-state hyperglycemic level. Plasma IR-GIP and insulin (IRI) levels were measured throughout the 2-h period. IR-GIP levels changed little when IV glucose alone was given; the mean basal value was 305+/-34 (SEM) pg/ml. After oral glucose, IR-GIP levels began to rise within 10 min and reached a peak within 40 min of 752+/-105 pg/ml. Plasma IRI responded initially to the square wave of hyperglycemia in the typical biphasic pattern. After oral glucose, plasma IRI levels rose strikingly above the elevated levels produced by hyperglycemia alone, reaching a peak of 170+/-15 muU/ml within 45 min. The time course of the rise in IR-GIP and IRI was nearly identical. To assess whether the maintenance of euglycemia would affect this process, the euglycemic clamp was employed in 11 subjects to maintain basal blood glucose levels during a similar 2-h study. A primed-continuous insulin infusion, with a constant rate of 120 mU/m(2) per min was given together with a servo-controlled glucose infusion. This resulted in hyper-insulinemia of approximately 300 muU/ml. Glucose was ingested by six subjects at 60 min. Plasma IR-GIP responded to oral glucose similarly to the effect seen in the hyperglycemic studies. No increase in endogenous insulin release was seen despite the increase in IR-GIP when euglycemia was maintained. However, in five of seven subjects given insulin whose blood glucose concentration rose by 20 mg/dl or more after oral glucose, there was an increase in plasma insulin concentration associated with the elevation in IR-GIP. Thus, the effect of glucose-released IR-GIP on insulin secretion is dependent upon the presence of some degree of hyper-glycemia and is not inhibited in the presence of marked hyperinsulinemia.

Adolescent↗
PubMed1978

Glucose intolerance in uremia. Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin.

The relative contributions of impaired insulin secretion and of tissue insensitivity to insulin to the carbohydrate intolerance of uremia were investigated in 10 chronically uremic subjects. Two types of glucose-clamp experiments were performed in each patient before and after 10 wk of thrice weekly hemodialysis. In both types the blood glucose concentration was maintained at a constant level by the periodic adjustment of a variable glucose infusion with a negative feedback formula.Hyperglycemic clamp. The blood glucose concentration was acutely raised and maintained 125 mg/dl above basal levels for 2 h. Since the glucose concentration was held constant, the glucose infusion rate is an index of glucose metabolism (M). After dialysis M increased in all patients from an average of 4.23 to 6.30 mg/kg body wt per min (P < 0.001). The plasma insulin responses (I) both pre- and postdialysis were biphasic with an early burst within the first 2-5 min, followed by a phase of gradually increasing insulin concentration. After dialysis the plasma insulin response diminished slightly. Consequently, the M/I ratio, an index of tissue sensitivity to endogenous insulin, increased postdialysis in all subjects by an average of 92% (P < 0.01). Euglycemic clamp. The plasma insulin concentration was acutely raised and maintained by a primecontinuous insulin infusion. The blood glucose concentration was held constant at the basal level by a variable glucose infusion as above. M/I again is a measure of tissue sensitivity to insulin (exogenous) and increased in all patients postdialysis by an average of 57% (P < 0.01). In two patients hepatic glucose production was measured with tritiated glucose during the euglycemic clamp and declined by 84% predialysis. A similar decrease (82%) was observed postdialysis. Thus, both the hyperglycemic and euglycemic clamp techniques demonstrated tissue insensitivity to insulin to be the dominant carbohydrate defect in uremia. The surprising apparent lack of consistency in the change in beta cell response postdialysis is explained by the strong inverse correlation between beta cell sensitivity to glucose and tissue sensitivity to insulin (r = -0.920; P < 0.001). Those individuals who showed the most striking improvement in tissue sensitivity to insulin actually decreased their serum insulin response to hyperglycemia; those whose improvement in tissue sensitivity was more modest showed increases in beta cell responses.

Administration, Oral↗
PubMed1978

Loss of insulin response to ingested amino acids after jejunoileal bypass surgery for morbid obesity.

Amino acid tolerance tests were performed before and after jejunoileal bypass surgery for morbid obesity to determine whether an enteric factor(s) originating in the bypassed jejunum and/or ileum potentiates the insulin response to oral nitrogen loading. Preoperatively a 30-gm. mixture of amino acids given orally evoked a larger peak insulin than an intravenous load yielding comparable plasma amino acid elevations (82 +/- 17 muU./ml versus 38 +/- 8 muU./ml., p less than 0.05). Four months after operation, basal insulin concentrations were 46 per cent (p less than 0.001) of preoperative values. After surgery the response to intravenous amino acids was preserved when expressed as percentage increase above basal. In contrast, the peak increment and the percentage increase in insulin secretion after 30-gm. oral amino acid loading was significantly blunted (p less than 0.005). A smaller amino acid load (16.5 gm.) was given preoperatively to duplicate the plasma amino acid elevations seen postoperatively with the 30-gm. mixture given by mouth. The insulin response postoperatively was still significantly lower (167 +/- 33 per cent versus 98 +/- 16 per cent, p less than 0.05). After various explanations for the diminished postoperative insulin release following oral amino acid ingestion are considered, the results are best explained by the loss of an enteric insulinotrophic factor(s) normally released by the bypassed portions of jejunum or ileum in response to ingested protein.

Amino Acids↗
PubMed1977

Aging and ethanol metabolism.

The effect of aging on the distribution and elimination of ethanol was studied in a group of 50 healthy subjects ranging in age from 21 to 81 yr (mean, 53.3). Ethanol was administered in a continuous 1-hr infusion at a mean rate of 375 mg/m2 body surface area/min (equivalent to a mean dose of 0.57 gm/kg body weight). Serial blood samples for the determination of ethanol concentration was obtained at 15- to 30-min intervals for up to 4 hr post infusion. Ethanol elimination and distribution were evaluated with the aid of a two-compartment model. Rates of ethanol elimination were not affected by age. Peak ethanol concentration in blood water at the end of the infusion period was correlated with age (r= 0.55, p less than 0.001). Lean body mass and total volume of distirbution fo the ethanol were negatively correlated with age. The smaller volume of distirbution, in association with the decreased lean body mass, most likely explains the higher peak ethanol concentration found in the blood after administration of an ethanol does on the basis of surface area in the old as compared with the young subjects. This study demonstrates that age-related changes in body composition are important factors in the study of ethanol metabolism and its pharmacologic effects.

Adult↗
PubMed1977

A test of the hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses in man.

The hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses was tested in five subjects following one hour of sustained hyperglycemia. Despite a rapidly falling blood glucose concentration, no increase in plasma growth hormone, cortisol, glucagon, or catecholamines occurred as long as the blood glucose concentration remained above fasting levels. Plasma growth hormone, cortisol, and catecholamines were not released until the mean blood glucose reached 28 mg./100 ml., 39 mg./100 ml., and 39 mg./100 ml., respectively, below the fasting level. Plasma glucagon was suppressed during the period of hyperglycemia. As the blood glucose concentration fell below basal levels, a progressive increase in glucagon occurred. Plasma glucagon returned to fasting values when the nadir in blood glucose was attained. During the period of rapidly falling blood glucose, only plasma insulin showed any change; its response lagged behind the decline in blood glucose. By the time the fasting glucose level was attained, the plasma insulin was still almost three times the basal level. We concluded that under our experimental conditions the rate of fall in blood glucose and the degree of hypoglycemia achieved is primarily determined by the plasma insulin concentration.

Blood Glucose↗