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Biomedical subjects

R B Shafer

Publications and source records attributed to R B Shafer.

At least 19 recordsLinked to original sources

Thyrotropin and prolactin response to thyrotropin-releasing hormone in depressed and nondepressed alcoholic men.

Thyrotropin-releasing hormone (TRH) stimulation tests were performed on 81 alcoholic men after at least 3 weeks of abstinence. Subjects were given 500 micrograms of TRH intravenously, and thyroid-stimulating hormone (TSH) and prolactin (PRL) were measured at baseline, and then 15 and 30 min later. Comparisons were made among alcoholics with (n = 27) and without (n = 54) a lifetime history of depression as determined by the Diagnostic Interview Schedule. Nine nondepressed, nonalcoholic subjects served as controls. Alcoholics with or without a depression history did not differ from each other or from control in TSH or PRL response area under the curve. Blunted TSH responses were present in 10 (12%) of the alcoholics and none of the controls when blunting was defined as a delta max TSH less than 5 microU/ml. When blunting was defined as a delta max TSH less than 7 microU/ml, 18 (22%) of the alcoholics and 1 (1%) of the controls were blunted. Conversely, 2 (2.5%) of the alcoholics had a delta max TSH greater than 32 microU/ml. All subjects were clinically euthyroid. Contrary to expectation, depressed subjects were slightly less likely to show blunted responses than nondepressed subjects. No relationship was found between neuroendocrine measurements and several measurements of alcoholism or depression. Some alcoholic subjects show a blunted TSH response to TRH injection, which may be a function primarily of the alcoholism itself. The precise mechanism remains unknown.

Adult

Effects of opioid blockade with nalmefene in older impotent men.

We evaluated the effect of the opioid antagonist nalmefene on the HPG axis and on food consumption in 14 older impotent men. These patients had low to low normal mean serum testosterone values and normal gonadotrophin levels on screening evaluation. Normal response to GnRH was demonstrated in all the men. The protocol called for 24 hours of evaluation before and during administration of nalmefene 2.0 mg IV every 8 hours for 3 doses. During each 24 hour period, the following determinations were made: serum testosterone, FSH, and LH by five separate determinations between 8 AM and noon; 8 AM and 11 PM serum cortisols; 24 hour urine collections for free cortisol; and nocturnal penile tumescence (NPT). Food consumption was measured from 4 PM to 10 AM during the two periods. Nalmefene resulted in significant rises in testosterone, LH, and FSH. Nalmefene significantly elevated morning and evening cortisol measurements in all the patients. Nalmefene decreased total calorie consumption, principally by decreasing fat consumption. There was no effect on NPT. We conclude that in older impotent men, nalmefene acutely increases activity of the HPG axis and decreases calorie intake predominantly by decreasing fat consumption.

Erectile Dysfunction

Effects of biliary obstruction on hepatic clearance of bacteria.

High surgical mortality in patients with obstructive jaundice and sepsis have been attributed to reticuloendothelial system (RES) depression. The purpose of this study was to clarify the effects of mechanical biliary obstruction on RES clearance of pathogenic bacteria by comparing the phagocytic index (K) with the directly measured hepatic uptake of indium 111-labeled bacteria injected into the portal vein of normal dogs and dogs with partial (PBO) or complete biliary obstruction (CBO). No significant difference was observed between the K in normal dogs (0.19 +/- 0.08; n = 6) and that in dogs with PBO (0.24 +/- 0.06; n = 5) or CBO (0.21 +/- 0.03; n = 4). There was no significant difference in uptake of radiolabel by the liver among the three groups of dogs. In our model, biliary obstruction had no effect on hepatic RES function and may not represent a significant determinant of mortality in patients with obstructive jaundice.

Alkaline Phosphatase

Monoclonal antibody-targeted radiotherapy of renal cell carcinoma using a nude mouse model.

Radiation dosimetry and monoclonal antibody (MAB)-targeted radiotherapy studies were performed to evaluate the feasibility of using tumor-preferential MAB as targeting agents for internal radiotherapy of renal cell carcinoma (RCC). Two human RCC xenograft lines, TK-177G and TK-82, were established in nude mice and studied using MAB A6H as a targeting agent. This MAB has previously demonstrated excellent in vivo localization to RCC xenografts. Two doses of A6H (13 to 19 micrograms) labeled with iodine 131 (110 to 130 microCi) caused the tumor to regress or arrested the tumor growth in both xenografts. Similar doses (18 to 43 micrograms; 120 microCi) of 131I-labeled control MAB AFP-22 or of unlabeled A6H did not inhibit tumor growth. While most mice in the control groups had tumors greater than 250 mg in weight by day 43, none of the tumors in mice treated with 131I-labeled A6H grew to that size during the 3-month observation period. Sequential computerized scintigraphy was used to calculate the amount of radioisotope localized in tumor versus normal mouse tissue. Therapeutic doses of 131I-labeled A6H delivered a median calculated radiation dose of 38 cGy/microCi (range, 28 to 57) injected dose to RCC xenografts, and a median of 0.9 cGy/microCi to normal mouse tissues. These findings suggest that A6H is able to target radioisotopes highly specifically to RCC and achieve a therapeutic effect in the experimental setting.

Animals

Localization of human renal cell carcinoma xenografts with a tumor-preferential monoclonal antibody.

We previously described an immunoglobulin G1 monoclonal antibody (UMVA-RCC-A6H) that is highly reactive with human renal cell carcinoma (RCC) and has little cross-reactivity to other cell types both normal and malignant. In efforts detailed herein, radiolabeled A6H selectively localized to RCC xenografts and provided high resolution images of the xenografts. Also, A6H clearly discriminated between RCC xenografts and other human tumor xenografts. Consistent images of RCC xenografts (greater than 60 mg) were obtained without background subtraction. The amount of radiolabeled A6H in the tumor usually ranged from five to twenty times that of the blood. Normal mouse tissues, abscesses, and other human tumor xenografts contained less radiolabel per mg than did blood. A control monoclonal antibody of the same isotype failed to exhibit any localization in xenografts or normal tissues. Approximately 40% of the radiolabeled A6H dose per g was localized in the RCC xenograft 2 days after injection, although at the time of imaging about 60% of the radiolabel remaining in the mouse was associated with the xenograft. These results demonstrate that a RCC restrictive monoclonal antibody does specifically localize to RCC xenografts and supports the hope that this approach may have clinical value for diagnosis, staging, or treatment.

Animals

Assessment of left ventricular function in aortic insufficiency using echocardiography, gated scintigraphy and contrast angiography.

Echocardiography, gated scintigraphy and contrast angiography were used to measure left ventricular ejection fractions in 20 patients with varying degrees of aortic insufficiency. There was good correlation between the radionuclide and the angiographic ejection fractions. Echocardiographic ejection fraction correlated less well with the angiographic ejection fraction. The radionuclide left ventricular ejection fraction may prove valuable in the noninvasive serial evaluation of left ventricular function in patients with chronic aortic insufficiency.

Adult

Abnormal images of right heart disorders.

Increasing attention is being given to radioisotopic studies of the right heart. Measurement of right ventricular ejection fraction has become more common. We present examples of cardiac images which were obtained during the scintigraphic assessment of right sided cardiac disorders. Images of the first pass, of the gated cardiac study, and of the nongated cardiac blood pools offer complementary information to the overall radionuclide evaluation of right heart disease.

Blood Pressure

Radionuclide left ventricular dV/dt for the assessment of cardiac function in patients with coronary disease.

To investigate potential uses of left-ventricular (LV) systolic ejection rate (LV dV/dt) in the evaluation of LV function, we examined the effect of exercise, angiotensin, and leg raising on LV ejection fraction and LV dV/dt in patients with coronary-artery disease. The following observations were made: a) LV ejection fraction and dV/dt changed proportionately, but in opposite directions, during supine exercise; b) LV ejection fraction and dV/dt decreased to a similar extent during angiotensin infusions; and c) LV ejection fraction and dV/dt were unchanged by leg raising. The changes in peak and mean LV dV/dt were similar. Regardless of the physiologic state, peak LV dV/dt occurred during the first third of systole. These data imply that in this population there were no specific advantages of LV dV/dt over LV ejection fraction in the evaluation of LV performance.

Angiotensin II

Comparison of two radioimmunoassays and a microbiologic assay for bleomycin.

Recently two radioimmunoassays have been independently developed for determination of bleomycin levels. In this study these assays are compared with each other and with a standard microbiologic assay for bleomycin. Bleomycin levels were determined in serum and urine samples obtained at varying intervals following intramuscular bleomycin injection. There were systematic differences between the assays. One radioimmunoassay indicated bleomycin levels lower than the levels indicated by the microbiologic assay with serum samples. With urine samples, both radioimmunoassays indicated bleomycin levels greater than the microbiologic assay.

Antibody Specificity

A review of carotid cavernous fistula including diagnosis and evaluation by nuclear medicine angiography.

The various causes and differential diagnosis of carotid cavernous fistula are discussed as well as the description of the use of radionuclide angiography in the diagnosis and evaluation of patients with carotid cavernous fistulas. Radionuclide angiography has proven extremely useful in the diagnosis and follow-up of patients with carotid cavernous fistulas. The procedure is of maximum benefit in situations where repeat studies are required at frequent intervals. Five cases are described in which the nuclear medicine technique was instrumental in primary diagnosis and follow-up.

Adult

Implications of liver activity associated with 133Xe ventilation lung scans.

A series of 35 xenon-133 (133Xe) ventilation studies yielded nine cases demonstrating accumulation of activity in the liver. Maximum intrahepatic deposition of radioxenon occurred during the washout phase of the study. In addition to those clinical instances which make this phenomenon possible, i.e., obesity, alcoholic-induced liver steatosis and diabetes mellitus, we found that hyperlipidemia and coronary artery disease also favor xenon-133 localization into the hepatic parenchyma. It is concluded that the lipid avidity of 133Xe facilitates its liver accumulation hyperlipidemic patients and in patients with coronary artery disease, and that this action may be explored to further understand deranged metabolic pathways in the liver of these patients. Hepatic accumulation of 133Xe during ventilation studies must be considered when assessing regional ventilation/perfusion relationships.

Adult

Fenestrated sagittal sinus mimicking posterior cerebral infarction.

Two patients who presented with abnormal neurological findings and focal abnormalities on static brain imaging, were felt to have infarction in the distribution of the posterior cerebral artery. However, the posterior flow study delineated the cause of the abnormality as being a fenestrated anomaly of the sagittal sinus. The incidence of occlusive disease of the posterior cerebral artery, its clinical and scintigraphic presentation and the potential pitfalls for misinterpretation are reviewed.

Brain