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Biomedical subjects

J J Cunningham

Publications and source records attributed to J J Cunningham.

At least 55 records · Page 3Linked to original sources

Hypercorticosteronuria and diminished pituitary responsiveness to corticotropin-releasing factor in obese Zucker rats.

Metabolic defects in obese (fa/fa) Zucker rats have previously been shown to be reversed by adrenalectomy; however, hypercorticosteronemia has not been demonstrated. We now report that the total daily excretion of corticosterone and urea nitrogen are significantly greater (P less than 0.01) in obese Zucker rats than in age-matched lean Zucker rats. This excessive excretion of corticosterone is not of autonomous adrenal origin, since dexamethasone treatment (20 micrograms/kg X day) for 2 days induced a proportionate reduction in corticosterone excretion (approximately 50%) in both obese and lean Zucker rats. Corticosterone excretion was further suppressed to levels not different from those in lean rats after 2 days of dexamethasone (40 micrograms/kg X day). Both the peak and total pituitary beta-endorphin secretion in response to an iv bolus of corticotropin-releasing factor (CRF) were diminished in obese Zuckers. The response to CRF in obese Zucker rats was dampened and superimposable on that of dexamethasone-treated lean Zucker rats, suggesting the existence of chronic hypercorticosteronemia as a component of this genetic obesity. These observations provide evidence for a compensatory alteration of the pituitary-adrenal axis. We suggest that corticosterone turnover may be increased in obese Zucker rats.

Animals↗

The analysis of glucose kinetics using a single jugular catheter in awake rats.

The rates of glucose production and utilization can be estimated by a primed-constant infusion technique using separate catheters for the infusion of radiolabelled glucose and periodic blood withdrawal. In rats, a carotid artery catheter is most often combined with a jugular or femoral venous catheter in such studies. We presently describe a method which utilizes a single jugular catheter for both infusion and sampling in the awake rat. This method is directly compared with simultaneous carotid artery sampling during both the dynamic steady state and a nonsteady state induced by a constant infusion of insulin. Our results demonstrate the validity of a single vein design for the analysis of glucose kinetics in either state. Rapid sampling and complete flushing prevent disruption of infusate equilibrium and sample contamination respectively. This single catheter method requires less technical skill for placement, reduces surgical intervention and enhances the comfort of the awake rat.

Animals↗

Enhanced hepatic insulin sensitivity and peripheral glucose uptake in cold acclimating rats.

Cold-exposed rats exhibit hypermetabolism, hyperphagia, and increased glucose oxidation. Their counterregulatory hormone secretion is markedly elevated, while insulin levels fall acutely, gradually returning to basal during acclimation. We assessed both hepatic and peripheral sensitivity to insulin in rats in the basal state and after 5 days of cold (5 C) exposure. The contribution of gluconeogenesis to total glucose turnover was measured and compared to daily urinary corticosterone excretion. Hepatic glucose production was equally suppressed by the infusion of insulin at 1.2 mU/kg X min in both control and cold-acclimated rats, but enhanced hepatic sensitivity to low dose (0.6 mU/kg X min) insulin infusion was only observed after cold exposure. The metabolic clearance of glucose was elevated with cold stress and was insensitive to the infusion of insulin at either level. Insulin resistance was not observed. Urinary excretion of corticosterone and urea nitrogen were markedly increased, but creatinine excretion was unchanged, suggesting that the concurrent increase in gluconeogenesis resulted from increased protein intake rather than increased catabolism of muscle protein.

Adaptation, Physiological↗

Sonographic measurement of the extrahepatic bile duct before and after retrograde cholangiography.

The maximum diameter of the extrahepatic bile duct visible on cholesonograms was measured immediately before and immediately after endoscopic retrograde cannulation and injection of the biliary and pancreatic ducts (ERCP) in 24 patients. Sonographic bile duct diameter increased by 3 mm or more in nine patients, all of whom had had a previous cholecystectomy. Bile duct diameter was unchanged in the remaining 15 patients, six of whom had had cholecystectomy. The technical performance of ERCP alone will alter bile duct diameter in a significant proportion of patients having endoscopic cannulation of the biliary tree. This is particularly so for patients who have had their gallbladders removed. The true diameter of the extrahepatic bile duct cannot be determined in many patients by simple measurement of images obtained at ERCP, even when corrections are made for radiographic magnification.

Bile Ducts↗

Lean body mass is a predictor of the daily requirement for thyroid hormone in older men and women.

Levothyroxine (T4) replacement need in adults with primary hypothyroidism has recently been reported to fall with age. Previous studies have demonstrated that the resting metabolic rate falls with age in euthyroid adults and that this fall is proportional to a reduction in lean body mass (LBM). Since LBM is correlated also with 24-hour energy expenditure, this study examined the possibility that LBM might be an accurate predictor of T4 requirement. Seventy-five hypothyroid adults receiving full replacement therapy, ranging in age from 24 to 88 years, were studied retrospectively. Lean body mass was found to be a better predictor of T4 requirement than age or weight for the entire group as well as for subgroups of men and women 51 years old and older. The age-related reduction in LBM may be responsible for the reported decrease in the rate of fractional thyroxine degradation with age.

Age Factors↗

Influence of exercise on urea, creatinine, and 3-methylhistidine excretion in normal human subjects.

To evaluate the effects of exercise on net protein catabolism, the losses of urea in sweat and urine and urinary creatinine and 3-methylhistidine (3MH) excretion were determined in eight healthy subjects during cycle ergometer exercise performed at approximately 45% of VO2max for 90 min. The subjects ingested a meat-free diet for 5 days starting 3 days before and continuing for 1 day after the day of exercise. During exercise, total urea excretion (urine + sweat losses) increased 100% above pre- and postexercise values. Thirty percent of the total urea excretion during exercise was in the form of sweat losses. Total protein breakdown (as reflected by urea excretion), however, could account for less than 5% (21 +/- 4 kcal) of total calorie expenditure during the exercise (567 +/- 83 kcal). Urinary creatinine excretion increased by 50% during exercise. Urinary excretion of 3MH also tended to rise, but the ratio of urinary 3MH to creatinine showed no change in response to exercise. We conclude that 1) light to moderate exercise results in an increase in net protein catabolism and an increase in creatinine excretion; 2) sweat losses are an important route for urea excretion during exercise; 3) there is no evidence of a disproportionate increase in breakdown of myofibrillar contractile proteins; and 4) in spite of the increase in the rate of protein catabolism, protein is only a minor source of energy during light to moderate exercise.

Adolescent↗

Effect of examination time of day on the quality of real-time cholesonograms.

Real-time sector scans of the gallbladder and common hepatic duct were performed at 7:00 a.m., 1:00 p.m., and 5:00 p.m. on 16 volunteers eating a regular diet. Technically satisfactory but not ideal scans of the common duct could be obtained irrespective of dietary status or time of day. As the day progressed, about one-half of subjects having gallbladder scans showed a significant decrease in bile volume, spurious gallbladder wall thickening, or compromised images from excessive intestinal gas. The data suggest that, if possible, gallbladder imaging should be performed early in the morning after overnight fasting, even when high-resolution sector scanners are used. However, because nearly one-half of patients can have satisfactory scans under any circumstances, cholesonograms should be performed in emergency situations or in those instances where patients would suffer inconvenience or financial hardship by delay of the study for an additional day.

Adult↗

Sonographic findings in clinically unsuspected acute and chronic scrotal hematoceles.

Three patients with scrotal swelling for 2 days, a year, and many years, respectively, were shown ultimately to have hematoceles even though their clinical history and physical findings were atypical. Contact B-scans of these lesions all showed a basically anechoic mass traversed by thick irregular septations. The septations in one acute case decreased in size and number over 10 days. Hematocele should be considered in the differential diagnosis when sonographic ultrasound studies of a scrotal swelling reveal a multicystic mass even if the history and physical findings are more compatible with neoplasm.

Diagnosis, Differential↗

Sonographic diameter of the common hepatic duct in sickle cell anemia.

The maximum diameter of the common hepatic duct was measured from the cholecystosonograms of 95 children and young adults with proven sickle cell anemia. Four mm was considered the upper limit of normal. Half the patients were male, half were female; 40% had gallstones and 25% had signs and symptoms of acute biliary diseases. The diameter of the common hepatic duct was normal in all but six patients. In five of these, the degree of enlargement was minor (1-3 mm). Three of the six patients with enlarged ducts had acute cholangitis without obstruction, two had clinically "silent" enlargements, and one had symptomatic biliary obstruction by calculi. Simple measurement of common hepatic duct diameter is not a sensitive or specific indicator of biliary disease in patients with sickle cell anemia.

Adolescent↗

Strong acoustical shadowing from the gallbladder bed: ultrasonic-pathologic correlation.

We reviewed a series of 25 patients whose cholecystosonograms showed ultrasonic nonvisualization of the gallbladder, high-amplitude echoes in the region of the gallbladder bed, and strong acoustical shadowing. These 3 findings have previously been thought to be a reliable indication of a small contracted gallbladder filled with stones. In our series, all 25 such patients did not have gallstones, but the size and number of the calculi were highly variable. Only a small minority of our patients had a contracted gallbladder in most, the volume of the gallbladder was either normal or greater than normal. Ultrasonic nonvisualization of the gallbladder accompanied by acoustical shadowing was not a reliable indicator of gallbladder wall thickness in our series. Of 25 patients, 20 had either a normal gallbladder wall or only slight thickening. When we reviewed our images to determine how many fit the "WES" criteria thought to be a specific manifestation of a contracted gallbladder filled with stones, we found that 14 of 25 individuals clearly showed this group of ultrasonic findings. We could not, however, correlate the presence or absence of the 'WES' triad with the number and size of stones, the gallbladder volume, or thickness of the gallbladder wall.

Cholelithiasis↗

Body composition and resting metabolic rate: the myth of feminine metabolism.

Resting metabolic rate (RMR) in adults can be viewed from two perspectives. Body surface area is used to index RMR in the clinical perspective. Normal values of RMR are thus sex-specific and appear to be lower in women. However, the physiological perspective is one of an asexual metabolism that differs in the mass of active cells. The body cell mass is relatively reduced in women due to a smaller skeletal muscle mass in tandem with a greater fat mass. RMR is proportionately reduced and thus highly correlated with body cell mass or lean body mass in mixed sex data. Athletic training can negate the differences in body composition and RMR per unit weight. The body mass index is another nonphysiological and sex-specific parameter currently being applied to obesity research. The clinical utility of body surface area for the prediction of RMR results from its correlation with body composition within either sex. The clinical and physiological perspectives of RMR must be clearly distinguished and treated as distinct.

Adult↗