P Hoffer | PubMed Health

PubMed1997

Preclinical evaluation of [123I]R93274 as a SPECT radiotracer for imaging 5-HT2A receptors.

Studies in rodents have suggested that the radioiodinated 5-HT2A receptor antagonist [123I]R93274 (123-iodine-N-[(3-p-fluorophenyl-1-propyl)-4-methyl-4-piperidinyl]-4-ami no- 5-iodo-2-methoxybenzamide) (Kd = 0.1 nM) might be a promising single photon emission computerized tomography (SPECT) radiotracer to image 5-HT2A receptors in the living human brain. In this study, we characterized the brain uptake of [123I]R93274 in baboons. Highest brain uptake was observed in cortical areas, while lower uptake was observed in the striatum and the cerebellum. Injection of pharmacological doses of the 5-HT2A receptor antagonist ketanserin resulted in reduction of cortical and striatal radioactivities to the level observed in the cerebellum. Injection of the selective dopamine D2 receptor antagonist raclopride did not affect [123I]R93274 brain uptake. Quantification of 5-HT2A receptors was achieved by measuring the binding potential of 5-HT2A receptors for [123I]R93274 (the binding potential is the product of the density and affinity of available receptors). Regional binding potential values were derived with a three-compartmental kinetic analysis of the time-activity curves in the brain and plasma. Binding potential values of 93 +/- 34 ml/g, 71 +/- 35 ml/g and 31 +/- 11 ml/g were measured in the occipital, temporal and striatal regions, respectively. Similar values were derived using a noncompartmental graphical analysis. These values were in accordance with the in vitro regional distribution of 5-HT2A receptors in primate brain. In conclusion, [123I]R93274 allows visualization and quantification of 5-HT2A receptors in the baboon brain with SPECT.

Animals↗

PubMed1996

Comparison of nifedipine GITS and hydrochlorothiazide in the management of elderly patients with stage I-III diastolic hypertension.

A randomized, double blind, parallel study was performed to compare the effects of nifedipine gastrointestinal therapeutic system (GITS) to hydrochlorothiazide (HCTZ) in the management of the elderly hypertensive. Eighteen patients, mean age 65 +/- 5 years, with Stage I-III diastolic hypertension (sitting diastolic BP between 90 and 115 mm HG) were included in each treatment group. Following a 2 to 8 week placebo washout phase, patients received either nifedipine GITS or HCTZ and were titrated over 5 weeks to achieve a goal diastolic blood pressure less than 90 mm Hg. Patients were then continued on medication during an 8 week maintenance phase. Treatment effect on systolic and diastolic blood pressure was assessed. Serum electrolytes, lipids, blood urea nitrogen, and creatinine were measured before and after treatment. Posttreatment changes in renal and cardiovascular function, as well as left ventricular mass were evaluated. The results showed significant reductions in systolic and diastolic blood pressure with both drugs; no treatment difference was found, although goal blood pressure was achieved more rapidly with nifedipine GITS (28 v 34 days, P < .05). BUN was significantly increased only after diuretic therapy (P < .01) and serum potassium fell to a greater degree with HCTZ (0.3 mEq/L v 0.1 mEq/L) than with nifedipine GITS. No statistically significant changes in left ventricular mass, ejection fraction, glomerular filtration rate, or renal blood flow were seen after therapy with either drug. However, the time peak LV diastolic filling rate decreased with nifedipine GITS (197 to 164 msec) and increased with HCTZ (172 to 198 msec). This treatment difference approached statistical significance (P = .07). Adverse side effects of treatment were reported by 50% of nifedipine GITS patients and 28% of patients treated with HCTZ. This treatment difference was not statistically significant. We conclude that both nifedipine GITS and HCTZ monotherapy provide significant blood pressure reduction in older hypertensives with Stage I-III diastolic hypertension. Both drugs are well tolerated with no significant adverse effect on renal or cardiovascular function after short term therapy.

Aged↗

PubMed1992

Localization of extratemporal epileptic foci during ictal single photon emission computed tomography.

We obtained single photon emission computed tomography (SPECT) scans with technetium-99M-hexamethyl-propylene-amine-oxime in 11 patients during 12 extratemporal partial seizures (9 simple partial, 3 complex partial). Ten ictal SPECT studies in 9 patients showed a focal region of hyperperfusion, which agreed with electrical seizure onset in 5 and with clinical seizure localization in 4 in whom ictal electroencephalography was not localized. Contralateral cerebellar and ipsilateral basal ganglia hyperperfusion was seen in 3 patients with a frontal lobe seizure focus. Ictal hyperperfusion was well circumscribed, unlike the diffuse hyperperfusion changes reported during temporal lobe seizures. This observation may indicate a different degree of seizure spread in temporal as opposed to extratemporal epilepsy. Because electroencephalographic localization is often elusive in extratemporal seizures, ictal SPECT may be very helpful for the localization of extratemporal foci.

Adolescent↗

PubMed1983

Tomographic gallium-67 citrate scanning. Useful new surveillance for metastatic melanoma.

Conventional gallium scans are not useful to evaluate patients with metastatic melanoma. We evaluated a new method of tomographic gallium imaging. One hundred fourteen tomographic scans were obtained in a prospective surveillance study of 67 patients over a 3-year period. Scans were evaluated and compared to findings of independent clinical evaluations. Sensitivity of gallium identification of tumor involving peripheral lymph nodes and soft tissues, abdomen, mediastinum, and osseous sites was 68% to 100%; overall sensitivity of this technique is 82% with specificity of 99% in 570 organ system assessments. Analysis of discordant findings when a site was clinically occult but gallium-positive showed gallium uptake to be true-positive in six of seven lymphatic sites, three of three lung and mediastinal sites, six of six abdominal sites, but in no brain or bone sites. Gallium lesions identified by computed tomographic scans proved to be false-positive at one lymphatic and one bone site, and false-negative at four otherwise clinically evident lymph node and soft tissue sites, seven pulmonary sites, and four brain sites. Gallium tomographic scanning provides a composite assessment of melanoma and may eliminate the need for other studies.

Adult↗

PubMed1982

Relationship of 99mTc-MDP uptake to regional osseous circulation in skeletally immature and mature dogs.

Uptake of intravenously injected 99mTc-MDP in multiple regions of healthy skeletally immature and mature dogs was correlated with regional chondro-osseous blood flow determined by radioactively labeled microspheres. Compared to the microsphere distribution, the distribution of 99mTc-MDP indicated that blood flow is an important, but not exclusive, factor in the uptake of bone-seeking tracers. Other factors such as the affinity of the tracer for the various types of chondro-osseous tissues must also affect tracer uptake. A measure of the relative affinity of 99mTc-MDP for bone was derived by the ratio of the percentage of tracer uptake to the percentage of blood flow. The juxta-ephyseal region demonstrated the greatest affinity for the tracer, followed in decreasing affinity, by the cortical bone, epiphyseal cartilage, trabecular bone of the metaphysis and secondary ossification center, and marrow space. Within the spongiosa, affinity generally increased as the proportion of osseous trabeculae relative to marrow space increased. 99mTc-MDP uptake is disproportionately increased in areas of active bone growth and remodeling where the surface area of hydroxyapatite crystals available for adsorption is probably highest.

Animals↗

PubMed1982

Tomographic gallium-67 citrate scanning: useful new surveillance for metastatic melanoma.

Conventional gallium scans are not useful to evaluate patients with metastatic melanoma. We evaluated a new method of tomographic gallium imaging. One hundred fourteen tomographic scans were obtained in a prospective surveillance study of 67 patients over a 3-year period. Scans were evaluated and compared to findings of independent clinical evaluations. Sensitivity of gallium identification of tumor involving peripheral lymph nodes and soft tissues, abdomen, mediastinum, and osseous sites was 68% to 100%; overall sensitivity of this technique is 82% with specificity of 99% in 570 organ system assessments. Analysis of discordant findings when a site was clinically occult but gallium-positive showed gallium uptake to be true-positive in six of seven lymphatic sites, three of three lung and mediastinal sites, six of six abdominal sites, but in no brain or bone sites. Gallium lesions identified by computed tomographic scans proved to be false-positive at one lymphatic and one bone site, and false-negative at four otherwise clinically evident lymph node and soft tissue sites, seven pulmonary sites, and four brain sites. Gallium tomographic scanning provides a composite assessment of melanoma and may eliminate the need for other studies.

Adult↗

PubMed1981

Scintigraphic diagnosis of cirrhosis: a receiver operator characteristic analysis of the common interpretative criteria.

Receiver operator characteristic (ROC) techniques were used to determine relative importance of heterogeneity, bone marrow uptake, hepatomegaly, splenomegaly, and focal lesions in the scintigraphic diagnosis of cirrhosis, as well as to determine whether each of the criteria should be used as an identifier (high sensitivity) or as a discriminator (high specificity). Heterogeneity, splenomegaly, and bone marrow uptake were found to be good identifiers of hepatic disease. However, heterogeneity was found to be a poor discriminator for cirrhosis, splenomegaly showed some value as a discriminator, and bone marrow uptake was found to be a reliable discriminator for alcoholic liver disease. The presence of focal lesions was a good discriminator for metastatic disease, and was not specific for cirrhosis. Hepatomegaly also was not specific for cirrhosis. This method of analysis provides a relatively simple method for assembling a hierarchical guide to diagnostic criteria for the interpreting physician.

False Negative Reactions↗

PubMed1980