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Biomedical subjects

R B Shafer

Publications and source records attributed to R B Shafer.

At least 37 records · Page 2Linked to original sources
PubMed1984

The role of the endogenous opiates in zinc deficiency anorexia.

Anorexia is a major symptom of zinc deficiency, but the mechanism(s) for this anorexia are poorly defined. Recent studies have suggested an integral role for endogenous opiate peptides in appetite regulation. Dynorphin, a leucine-enkephalin containing opiate peptide, is a potent inducer of spontaneous feeding. In this study we showed that zinc deficient animals were relatively resistant to dynorphin-induced feeding. Measurement of dynorphin levels using a highly sensitive radioimmunoassay showed that zinc deficient animals had lower levels of dynorphin in the hypothalamus than did ad lib fed animals, with weight restricted animals having intermediate values. [3H]-naloxone binding was significantly increased to isolated brain membranes from zinc deficient animals using 1 nM unlabeled naloxone when compared to ad lib fed controls with the weight restricted animals again having intermediate values. These data suggest that abnormalities in endogenous opiate regulation of appetite may well play a role in the anorexia of zinc deficiency. The effects of zinc deficiency on endogenous opiate action appear to include alterations in receptor affinity, a post-receptor defect and alterations in the synthesis and/or release of dynorphin.

Animals↗
PubMed1984

Adrenocortical hyperactivity in newly admitted alcoholics: prevalence, course and associated variables.

After initial screening of 269 consecutive Psychiatry Service admissions suggested adrenal stimulation in alcoholics, 52 consecutive newly-admitted alcoholics were intensively studied in order to determine the extent of adrenal hyperactivity, how quickly it resolved and the factors associated with it. While 21% failed to show suppression of cortisol at either 0800 or 1600 hr the day following administration of dexamethasone (1 mg) at 2300 hr, no patient showed both clinical and biochemical evidence of alcoholic pseudo-Cushing's syndrome, and all patients suppressed normally eight days later. Analysis of a variety of variables, including several measures of recent alcohol consumption, alcohol withdrawal and depression failed to show significant association with nonsuppression. The DST should be interpreted cautiously in alcohol abusers during the first 10-14 days following admission. Persistent nonsuppression, however, is probably not due to alcohol abuse.

Adrenocortical Hyperfunction↗
PubMed1984

Can the three-phase bone scan differentiate osteomyelitis from metabolic or metastatic bone disease?

The three-phase bone scan has been reported of value in the diagnosis of osteomyelitis. The use of a radionuclide angiogram, an immediate postinjection "blood pool" image, and 2 to 3 hour delayed image have been useful in separating nonosseous inflammatory disease from osteomyelitis. However, dependence on increased blood flow and focal hyperemia for this diagnosis may limit the use of the study if other processes are shown to produce similar results. To identify limitations of the three-phase bone scan we studied 14 patients with metastatic bone disease and nine patients with Paget's disease. Blood flow results showed no increase in three of 14 patients with metastases, intermediate increase in seven of 14 patients with metastases and two of nine patients with Paget's, and intense increase in four of 14 patients with metastases and seven of nine patients with Paget's. All patients showed increased focal activity in the immediate "blood pool" and delayed images. We conclude that because of increased flow Paget's disease may be difficult to separate from osteomyelitis. However, metastatic disease can often be differentiated on the basis of quantitative focal hyperemia. The three-phase bone scan remains of value in the diagnosis of osteomyelitis, but other diseases of bone must be included in the differential diagnosis.

Aged↗
PubMed1984

Effect of cholestasis on hepatic transport of 99mtechnetium p-isopropyl-iminodiacetic acid.

Hepatobiliary imaging with 99mTc-p-isopropyl-iminodiacetic acid (PIPIDA) and other acetanilidoiminodiacetic acid derivatives is a frequently used clinical tool in evaluating patients with jaundice. However, there has been little objective assessment of the effects of cholestasis on hepatic transport of acetanilioiminodiacetic acid derivatives. In our studies, transport of 99mTc-PIPIDA by isolated rat hepatocytes obtained from animals with extrahepatic obstruction secondary to bile duct ligation or intrahepatic cholestasis induced by ethinyl estradiol therapy was determined. Uptake constants for 99mTc-PIPIDA by hepatocytes isolated from livers of animals with ligated bile ducts were significantly decreased compared with uptake by liver cells from sham-operated controls (0.0030 +/- 0.0003 vs. 0.0089 +/- 0.0010 femtomole X 10(6) cells-1 X min-1 X pmol/L-1; p less than 0.001). Hepatocytes isolated from livers of animals given ethinyl estradiol also demonstrated significantly reduced 99mTc-PIPIDA uptake compared with controls given propylene glycol (0.0034 +/- 0.0002 vs. 0.0060 +/- 0.0004 fmol X 10(6) cells-1 X min-1 X pmol/L-1; p less than 0.001). Fractional rates of efflux of the study compound from hepatocytes preincubated with 99mTc-PIPIDA were significantly decreased in experiments using ethinyl estradiol (p less than 0.005) but did not differ significantly from controls in studies of bile duct ligation. 99mTc-PIPIDA uptake was significantly decreased in the presence of high bile salt concentrations (100 to 200 mumol/L), but unconjugated bilirubin concentrations as high as 200 mumol/L (approximately 12 mg/dl) had no effect on hepatocyte uptake of the ligand. The finding that cholestasis significantly impairs hepatocyte uptake of 99mTc-PIPIDA provides a possible explanation for the clinical observation that a patent biliary tree and normal serum bilirubin level are not always sufficient to ensure normal hepatobiliary imaging. These data also suggest that elevation of bile acid levels during cholestasis may either contribute to impaired uptake of hepatobiliary imaging agents or serve as a marker of cholestasis-induced abnormalities in the liver functions responsible for hepatic transport of these compounds.

Alkaline Phosphatase↗
PubMed1984

Gastrointestinal transit in thyroid disease.

Diarrhea and malabsorption are common manifestations of hyperthyroidism, whereas constipation or obstipation frequently occur in hypothyroidism. Abnormalities of gastrointestinal motility have been proposed as the primary cause of these complaints, but documentation has been conflicting and largely limited to observations of the transit time of a barium meal. We studied gastrointestinal transit time in fasting patients with thyroid dysfunction using the pulmonary excretion of H2 after the ingestion of a nonabsorbable carbohydrate, lactulose, as an indicator of the rate of transit to the colon. Mean transit time of 10 hyperthyroid patients (29 +/- 4.0 min) was significantly less than that of 42 healthy controls (72 +/- 3.7 min, p less than 0.001), and of 6 hyperthyroid patients when they became hypothyroid after treatment (80 +/- 11.0 min, p less than 0.05). Transit time decreased significantly when hypothyroid patients were given thyroid replacement (p less than 0.01). These findings support the hypothesis that abnormal gut motility may be the primary cause of the diarrhea and malabsorption of hyperthyroidism, and the constipation and obstipation commonly seen in hypothyroidism.

Adult↗
PubMed1983

Impotence in medical clinic outpatients.

One thousand one hundred eighty men in a medical outpatient clinic were screened as to the presence of impotence. Four hundred one men (34%) were impotent, and of those, 188 (47%) chose to be examined for their problem. After a comprehensive evaluation the following diagnoses were obtained: medication effect, 25%; psychogenic, 14%; neurological, 7%; urologic, 6%; primary hypogonadism, 10%; secondary hypogonadism, 9%; diabetes mellitus, 9%; hypothyroidism, 5%; hyperthyroidism, 1%; hyperprolactinemia, 4%; miscellaneous, 4%; and unknown causes, 7%. The mean age of the impotent patients was 59.4 years, and the prevalence of alcoholism was 7%. Luteinizing hormone, follicle-stimulating hormone, testosterone, thyroxine, triiodothyronine (T3), T3 resin uptake, and prolactin studies were necessary to diagnose individual cases. We conclude that erectile dysfunction is a common and often overlooked problem in middle-aged men followed in a medical clinic.

Alcoholism↗
PubMed1983

Acute effects of nicotinic acid on hepatic transport of 99mTc-PIPIDA.

Hepatic injury has been associated with nicotinic acid treatment of schizophrenia and hypercholesterolemia. This association was implicated when the liver and biliary tract were not visualized after 99mTc-HIDA in a patient taking 3 g daily of nicotinic acid. We studied hepatic transport of 99mTc-PIPIDA both in vitro in isolated hepatocytes and in vivo in rabbits pretreated with nicotinic acid to further examine this association. Nicotinic acid increased uptake of PIPIDA by isolated hepatocytes and 7 days of nicotinic acid treatment in rabbits produced no abnormalities in hepatic uptake, gallbladder visualization, or biliary excretion of PIPIDA. We conclude that nicotinic acid does not have an inhibitory effect on uptake of biliary imaging agents and actually may be useful in enhancing hepatic imaging in patients with reduced liver function.

Animals↗
PubMed1983

Iodine trapping and organification in patients with chronic renal failure.

In vitro thyroid function tests were studied in 30 patients on regular hemodialysis. In addition, 8 patients (one not yet dialyzed) underwent perchlorate discharge testing and the salivary to plasma ratio of 131I was measured to identify defects in iodine uptake or organification. When compared with 35 healthy controls, uremic patients had lower total T4 (5.8 +/- 0.4 vs 8.6 +/- 0.3 micrograms/100 ml) and total T3 (81 +/- 6 vs 124 +/- 5 ng/100 ml) but T3RU was higher in dialysis patients (35.5 +/- 0.9 vs 28 +/- 0.5%, P less than 0.01). The TSH levels were not different from those of controls. The RAI uptake 1 h after perchlorate was significantly higher than the control valve (0.6 +/- 0.14 vs 0.06 +/- 0.04, P less than 0.05). Similarly, the salivary to plasma ratio of 131I was higher in patients with chronic renal failure (70 +/- 10:1 vs 40 +/- 4:1). It is concluded that there is altered iodine trapping in CRF patients but iodine organification appears to be normal.

Adult↗
PubMed1983

Effect of fasting and parenteral alimentation on PIPIDA scintigraphy.

Ten patients were prospectively studied using 99mTc-PIPIDA imaging to evaluate the effects of fasting and parenteral alimentation on gallbladder function. Three of ten patients had initial nonvisualization of the gallbladder for up to 2 hr, yet had normal visualization on repeat imaging performed after resumption of oral intake or after parenteral alimentation was discontinued. 99mTc-PIPIDA imaging should be interpreted with caution in patients fitting into either of these groups.

Adult↗
PubMed1983

Return of fertility after treatment for nonseminomatous testicular cancer: changing concepts.

We studied the return of ejaculation in 31 patients who had undergone retroperitoneal lymphadenectomy for stage I or II nonseminomatous germ cell testicular cancer. Ejaculation returned spontaneously in 13 patients and was restored by sympathomimetic drugs in 5 of 8 patients treated. Both patients known to have tried to father a child succeeded. We also studied the effects of chemotherapy (vinblastine and bleomycin with or without cisplatin) in 34 patients, 24 of whom also had undergone retroperitoneal lymphadenectomy. Although chemotherapy profoundly depressed spermatogenesis during treatment 75 per cent of the patients tested 18 months or more after completion of treatment had some return of function, as evidenced by normal follicle-stimulating hormone levels and/or the presence of live sperm in the ejaculate. We concluded that it is possible to perform a therapeutically sound retroperitoneal lymphadenectomy for low stage nonseminomatous testicular cancer that permits return of ejaculation in many patients and that spermatogenesis recovers in a significant number of patients treated for this cancer with modern chemotherapy. Thus, traditional beliefs that operative and drug treatment of nonseminomatous testicular cancer invariably causes infertility must be revised.

Antineoplastic Agents↗
PubMed1983

The effects of Lipomul, CCK, and TRH on gallbladder emptying.

Tc-99m IDA compounds have been used in the quantitative analysis of motor function of the gallbladder. However, stimuli to provoke emptying have been variable and frequently nonphysiologic. To determine the utility and dependability of provocative agents for gallbladder emptying, we studied the effects of Lipomul, CCK, and TRH after the intravenous administration of Tc-99m disofenin. Computer processing of region-of-interest over the gallbladder permitted time/activity analysis of each study and computation of the ejection fraction (EF). Results showed that Lipomul consistently produced an effect on gallbladder emptying (EF 16-42%). CCK, while more dramatic in response, was less predictable (EF 8-100%). TRH favored accumulation of activity and did not cause gallbladder emptying. The combination of CCK and TRH decreased the rate of gallbladder emptying produced by CCK alone. We conclude that the availability, low cost, and dependable effect on gallbladder emptying make Lipomul the gallbladder stimulant of choice for clinical use.

Cholecystokinin↗
PubMed1983

Normal gallbladder scintigraphy in acute cholecystitis.

Normal gallbladder scintigraphy occurs in 2 to 5% of reported patients with acute cholecystitis. Gallbladder visualization is found in patients with acalculous cholecystitis and in those with recent relief of cystic duct obstruction but persistence of inflammation. A patient is reported who had clinical and pathologic findings of acute cholecystitis but normal gallbladder visualization. This reemphasizes that the diagnosis of acute cholecystitis cannot be excluded by normal gallbladder scintigraphy.

Acute Disease↗
PubMed1983

Propranolol-induced hyperthyroxinemia.

A patient on a regimen of 400 mg/day of propranolol hydrochloride was observed to have elevated thyroxine (T4) and free T4 levels with a normal thyrotropin response to protirelin. This led us to study the prevalence of hyperthyroxinemia in 14 consecutively treated patients with hypertension on daily doses of propranolol of 320 mg or more. Four of 14 patients had elevated serum T4 levels. As a group, the patients on propranolol therapy had higher serum T4 levels, free T4 indices, and triiodothyronine levels than did healthy controls. The use of high-dosage propranolol may be associated with euthyroid hyperthyroxinemia and be a source of diagnostic confusion. All patients receiving therapy with high-dosage propranolol should undergo protirelin testing before one can conclude that their elevated thyroid hormone levels are due to hyperthyroidism.

Humans↗
PubMed1983

Effect of exorphins on gastrointestinal function, hormonal release, and appetite.

Peptic digestion of gluten results in the production of substances having opiatelike activity in bio- and receptor assays. These substances have been termed exorphins. In this study, we determined the effect of gluten, hydrolyzed gluten, and hydrolyzed gluten plus the opiate blocker naloxone on a variety of hormonal parameters, gastrointestinal transit time, small bowel mucosal integrity, and satiety. Hydrolyzed gluten prolonged intestinal transit time, and this effect was reversed by concomitant administration of naloxone. Hydrolyzed gluten also produced a naloxone-reversible increase in plasma somatostatinlike activity, which may have been responsible for the delayed transit time. No effects of the "exorphins" could be demonstrated on serum gastrin, cortisol, carbohydrate metabolism, or small bowel mucosal integrity. Although a number of studies have suggested a role for endogenous opiates in appetite regulation, we could not demonstrate any effect of "exorphins" on the amount of calories ingested nor on the perception of satiety. This study defines a potential role for small opiatelike peptides in foodstuffs in the regulation of intestinal function.

Adult↗
PubMed1983

Salivary thyroxine as an estimate of free thyroxine: concise communication.

To test the hypothesis that the levels of salivary thyroxine (T4) reflect those of circulating free T4, we developed a radioimmunoassay (RIA) sensitive to low levels of T4. Concurrent saliva and serum samples were obtained from 32 euthyroid volunteers, ages 19-64. Salivary and serum T4 and cortisol levels were measured by RIA. Salivary albumin was measured by nephelometry. Salivary T4 levels were higher than predicted, 4.2-35 ng/dl (normal range 0.6-2.0). No correlation was found between salivary T4 and serum levels of free T4 and total T4 but there was a significant correlation between salivary T4 and albumin (r = 0.82). Salivary cortisol levels agreed with reported results and showed no correlation with salivary albumin. We conclude that salivary levels of drugs and hormones may be strongly affected by protein binding, and caution must be exercised in using salivary levels as an estimate of circulating free levels.

Adult↗
PubMed1982

An atlas of salivary gland disorders.

In the initial evaluation of a possible salivary gland disorder, salivary scintigraphy is a diagnostic and non-invasive examination of function (7). Further definition of anatomical abnormalities may require a panoramic radiograph of teeth and mandible, contrast sialogram, ultrasound, or computerized tomography. However, these latter methods contribute primarily anatomical information, and scintigraphy remains the best assessment of function. Our clinical experience with salivary scintigraphy is summarized in Table 1.

Abscess↗