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Biomedical subjects

P B Hoffer

Publications and source records attributed to P B Hoffer.

At least 19 recordsLinked to original sources
PubMed1992

Amphetamine-stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates.

We used the reversibly binding D2 dopamine receptor radioligand [123I]IBZM (iodobenzamide) to test whether the endogenous neurotransmitter dopamine competes in vivo for radiotracer binding measured with single photon emission computed tomography (SPECT). In a series of nonhuman primate experiments (n = 27), the effects of temperature, amphetamine, haloperidol, and reserpine on brain uptake of [123I]IBZM were measured. Specific brain uptake of [123I]IBZM reached a peak by 100 min postinjection of radioligand and demonstrated a gradual, apparent "steady-state" washout over the next 2 hr. Brain uptake was temperature dependent, with rates of washout of specifically bound radioligand greater under normothermic conditions (26%/hr: core body temperature 35-37 degrees C) than under conditions of controlled hypothermia (11%/hr; 32-34 degrees C). Given the greater retention of radioactivity, low-temperature conditions were used in all other experiments. Administration of haloperidol (0.02 mg/kg IV) during the period of apparent steady state resulted in a dramatic increase in washout (60%/hr; p less than 0.0001), consistent with its potent D2 receptor antagonist properties. d-Amphetamine (1.0 mg/kg IV), which has negligible affinity for the D2 receptor but mediates the release of endogenous stores of dopamine, also enhanced washout (34%/hr; p less than 0.0005). Reserpine pretreatment at doses (1.0 mg/kg) sufficient to cause greater than 90% depletion of striatal dopamine levels blocked this amphetamine-enhanced washout (10%/hr; p less than 0.05). Reserpine did not block the increased washout induced by the direct-acting D2 receptor antagonist haloperidol. These results are consistent with the hypothesis that endogenous dopamine may effectively compete for radioligand binding in vivo in neuroreceptor imaging studies using PET and SPECT.

Animals↗
PubMed1992

"Central" and "peripheral" benzodiazepine receptors: opposite changes in human epileptogenic tissue.

We measured the density of two benzodiazepine (BZ) receptor subtypes in neurosurgically obtained hippocampal tissue from the seizure focus of patients with temporal lobe epilepsy (TLE) showing mesial temporal sclerosis, the most common pathologic finding in TLE. We performed quantitative in vitro receptor autoradiography with [125I]Ro 16-0154, a probe for the central-type BZ receptor and with [3H]PK 11195, a probe for the peripheral-type BZ receptor. In comparison with autopsy and neurosurgical control groups, patients with mesial temporal sclerosis had regionally selective decreased central-type and increased peripheral-type BZ receptors. These changes paralleled regional losses of neurons and proliferation of glia. Decreases of the inhibitory central-type BZ receptor may be a component of the enhanced excitability of the seizure focus and also may allow localization of the focus by in vivo neuroreceptor imaging. Single photon emission computed tomography (SPECT) imaging of two TLE patients with [123I]Ro 16-0154 suggests that this technique may provide a more sensitive means of localizing the seizure focus than current imaging methods relying on changes in blood flow or glucose metabolism.

Adult↗
PubMed1991

SPECT regional cerebral blood flow and neuropsychological testing in non-demented HIV-positive drug abusers: preliminary results.

1. Non-demented HIV seropositive and seronegative methadone maintained patients and healthy volunteers (n = 10 each) participated. 2. All subjects underwent SPECT regional cerebral blood flow scanning following injection of Tc-99m HMPAO. All patients underwent neuropsychologic (NP) testing. 3. The left striatum/whole brain blood flow ratio was elevated in the HIV positive group compared to the healthy subjects. Two HIV positive patients had clearly abnormal striatal ratios. Both groups were impaired on NP testing; HIV+ patients were somewhat more impaired on tests of sustained attention and verbal memory. 4. SPECT scanning with Tc-99 HMPAO may identify a subgroup of HIV positive patients with evidence of CNS involvement prior to onset of dementia symptoms.

AIDS Dementia Complex↗
PubMed1991

Captopril renography in the diagnosis of renal artery stenosis and the prediction of improvement with revascularization. The Yale Vascular Center experience.

To enhance diagnosis and predict improvement in blood pressure control following surgery or renal angioplasty in patients with hypertension and renal artery stenosis (RAS), we employed captopril renography in 113 clinically selected patients, all of whom had renal angiography to verify the diagnosis. Criteria for normal captopril renograms were established from an initial cohort of 23 hypertensive patients with normal angiograms who had been judged to be at high risk for RAS using the same clinical criteria. Renal revascularization or nephrectomy was performed in 45 patients and the success of the procedure was determined in the 40 patients for whom 3-month follow-up was available. In these 113 patients, 58 (51%) had RAS. Captopril renography was 91% sensitive and 87% specific in identifying or excluding RAS. Diagnostic utility was preserved in those patients with renal insufficiency (serum creatinine equal to or greater than 1.5 mg/dL) (n = 46). Scintigraphic abnormalities induced by captopril were strongly associated with cure or improvement in blood pressure control following revascularization or nephrectomy (16 of 19), while the lack of captopril-induced change was associated with failure of such intervention (17 of 21) (P = .0001). We conclude that captopril renography is sensitive and specific for the diagnosis of RAS in a clinically selected high-risk group of hypertensives, and that the test accurately predicts the success or failure of therapeutic intervention.

Adolescent↗
PubMed1991

Simplified captopril renography in diagnosis and treatment of renal artery stenosis.

To improve the diagnosis and forecast the response to surgery or renal angioplasty in patients with hypertension and renal artery stenosis, we employed a simplified captopril renography protocol in conjunction with renal arteriography in 94 clinically selected patients. Fifty hypertensive patients (group 1) with a high clinical likelihood of renovascular hypertension were evaluated using a simplified captopril renography protocol and renal angiography on the arterial side. Criteria for normal captopril renal scintigrams were established based on this original cohort and validated in an additional 44 clinically comparable patients (group 2). Renal revascularization or nephrectomy was performed in 39 patients, and success of the procedure was determined in the 34 patients for whom 3-month follow-up was available. In the 94 patients, 44 (47%) had renal artery stenosis. Simplified captopril renography was 91% sensitive and 94% specific in identifying or excluding renal artery stenosis in the combined group, with no difference in the diagnostic utility between groups 1 and 2, or in those with renal insufficiency (n = 38) or those with bilateral disease (n = 17). Scintigraphic abnormalities induced by captopril were strongly associated with cure or improvement in blood pressure control following revascularization or nephrectomy (15 of 18), while the lack of captopril-induced changes was associated with failure of such intervention (13 of 16) (p = 0.0004). We conclude that simplified captopril renography is highly sensitive and specific in the diagnosis of renal artery stenosis in a clinically selected high-risk population and that the test accurately predicts the success or failure of therapeutic intervention.

Aged↗
PubMed1991

Visual stimulation increases technetium-99m-HMPAO distribution in human visual cortex.

The ability of changes in the distribution of technetium-99m-hexamethylpropylene amine oxime (99mTc-HMPAO) to reflect physiologic changes in regional cerebral blood flow (rCBF) was evaluated using photic stimulation, a procedure known to increase rCBF in the striate cortex. Seven healthy subjects were injected with 740 MBq 99mTc-HMPAO on two separate days. On one day, the injection was performed following closure of the eyes and patching for 5 min. On the other day, subjects were exposed to a stroboscopic light to produce photic simulation. Images of distribution of 99mTc-HMPAO were obtained using a Strichman 810X single-photon emission computed tomogram (SPECT) brain scanner. Comparison of images obtained during light occluded versus stimulation conditions revealed a significant increase in distribution of radiopharmaceutical in visual cortex relative to whole brain (peak increase corrected for radiopharmaceutical backdiffusion 36.7% +/- 6.6%). HMPAO appears to provide a useful method for detecting relative rCBF increases with SPECT.

Adult↗
PubMed1990

Patients at high risk for renal artery stenosis: a simple method of renal scintigraphic analysis with Tc-99m DTPA and captopril.

Fifty patients with suspected renal artery stenosis (RAS) were studied with renal scintigraphy before and after administration of captopril. Twenty-three patients had RAS (greater than or equal to 75% RAS or greater than or equal to 50% RAS with poststenotic dilatation) and 27 had normal renal arteries at angiography. Angiotensin-converting enzyme inhibitors were discontinued 24 hours prior to renal scintigraphy; all other medications were continued. Each patient was evaluated with a simplified captopril renal scintigraphic protocol: renal imaging after administration of 12 mCi (444 MBq) of technetium-99m diethylenetriaminepentaacetic acid (DTPA), a 3-hour wait, oral administration of 50 mg of captopril, a 1-hour wait, and another scintigram obtained after administration of 12 mCi (444 MBq) of Tc-99m DTPA. Times of peak renal activity (Tmax) were determined from renal time-activity curves, and glomerular filtration rates (GFRs) were calculated with the Gates technique. A Tmax greater than or equal to 11 minutes after injection or a GFR ratio (larger GFR/smaller GFR) greater than 1.5 enabled detection of RAS with 91% sensitivity, 93% specificity, and 92% accuracy. Renal scintigraphy without captopril had only 43%-68% sensitivity in detecting RAS, depending on the criteria used.

Captopril↗
PubMed1990

Noninvasive staging of lung cancer. Indications and limitations of gallium-67 citrate imaging.

The results of evaluation of the hila and mediastinum with 67Ga scans are contradictory, as are the recommendations by different investigators on the use of 67Ga scintigraphy in the clinical evaluation of patients with primary lung carcinoma. Nevertheless, the economy and logistic simplicity of evaluating local and distant metastases with a single imaging procedure are attractive, especially because the symptoms may not enable the physician to make a correct identification of the organ systems affected by metastases. Neumann and Hoffer state that "at present conventional Ga-67 scanning techniques cannot be recommended for preoperative staging of mediastinal lymph node metastases in lung cancer patients." According to Waxman, 67Ga scintigraphy, relative to other imaging modalities, is a sensitive indicator of hilar spread of a tumor. However, because of the normally high background activity within the sternum and spine, mediastinal abnormalities may be poorly detected. Since most pulmonary tumors metastasize via regional nodes to the pulmonary hilum and then to the mediastinum, the high sensitivity for the detection of pulmonary hilar abnormalities and the high specificity for detection of mediastinal lesions suggest that gallium scintigraphy is a valuable adjunctive test when used appropriately. The results obtained locally are probably the best guide for individual physicians in the selection of diagnostic tests for their patients. Gallium scans may thus be helpful in the clinical evaluation of patients with lung cancer. Although gallium scans identify mediastinal node involvement, there is considerable controversy over the relationship between the sensitivity and specificity of the method. By detecting distant extrathoracic metastases, the 67Ga scan may identify a small group of patients who can be spared a needless operation. Gallium scanning fails specifically for metastases within the brain; thus, it does not supplant CT scans of the brain and it is less sensitive than bone scans in detecting osseous metastases. Gallium scanning of patients with small-cell lung cancer is not useful in the selection of therapy but does become important from a prognostic standpoint. Patients with extrathoracic involvement by small-cell carcinoma of the lung are known to have limited survival times compared with those of patients with thoracic involvement alone. In identifying patients with extensive disease, the oncologist is thus provided with prognostic information that may be useful in the counseling of the patient and the patient's family.

Citrates↗
PubMed1989

Hypermedia in radiology: computer-assisted education.

Hypertext is a new computer-based method of presenting information that provides greater flexibility than conventional methods of continuing education. With a hypertext system, an individual using the computer can acquire more information on a word or concept that needs to be pursued in depth. Hypermedia is an expanded concept which uses the computer's ability to incorporate images, sounds, and video images in addition to text. This interactive, multimedia approach customizes information for more effective learning. The authors devised a prototype hypermedia textbook of nuclear medicine using a personal computer with hypermedia software that contains text, graphs, tables, figures, literature citations, and an easily persuable image database. All the information is organized with multiple cross-references, allowing instant branching to relevant facts, in different levels of detail. The system's applications and the ease of expansion or modification by the user are described.

Computer-Assisted Instruction↗
PubMed1989

The synthesis of 11 beta-methoxy-[16 alpha-123I] iodoestradiol and its interaction with the estrogen receptor in vivo and in vitro.

In order to produce an estrogen receptor mediated imaging agent, we have synthesized 11 beta-methoxy-16 alpha-iodoestradiol labeled with 123I, and have studied its interaction with the estrogen receptor and its distribution in rats and rabbits. This 123I-labeled steroid, 11 beta-methoxy-16 alpha-[123I]iodoestradiol, binds with high affinity, Ka = 6 x 10(9) M-1, and specificity to the estrogen receptor in uterine cytosol. When tested in vivo, this radiolabeled steroid concentrates by a receptor mediated mechanism, in the estrogen target tissue, the uterus, producing very high target to nontarget tissue ratios. The results of these experiments indicate that 11 beta-methoxy-16 alpha-[123I]iodoestradiol may be a useful imaging agent for clinically monitoring and detecting estrogen receptor containing tumors.

Animals↗
PubMed1988

Correlative imaging in abdominal infection: an algorithmic approach using nuclear medicine, ultrasound, and computed tomography.

A wide variety of focal and diffuse infectious processes involve the abdomen. At one extreme are diseases such as pyelonephritis, cystitis, and pelvic inflammatory disease, conditions usually diagnosed without imaging studies and treated without complications. At the other extreme are abdominal abscesses, which may defy clinical diagnosis, are associated with significant morbidity and mortality, and may remain undetected or insufficiently characterized in spite of multiple imaging studies. The limited diagnostic value of clinical evaluation and plain film radiography in abscess detection has lead to widespread use of sophisticated imaging techniques including Gallium-67 (67Ga) scintigraphy, Indium-111 WBC (111In-WBC) scintigraphy, computed tomography (CT), and ultrasonography (US). Abdominal abscesses occur in a wide variety of anatomic sites, may involve any abdominal organ system, and have a number of different causes. The heterogeneity of the disease process and the varying capabilities of the different imaging techniques (with respect to site and organ system) make reliance on a single technique undesirable. An algorithmic approach using 67Ga or 111In-WBC scintigraphy, CT, and US provides a logical and clinically practical approach to complicated abdominal infection. By recognizing differences in clinical presentation and by appreciating the diagnostic strengths and weaknesses of nuclear medicine, CT, and US, the algorithm provides a reliable and direct route to accurate diagnosis while minimizing unnecessary examinations.

Abdomen↗
PubMed1988

Radiolabeled porphyrin vs gallium-67 citrate for the detection of human melanoma in athymic mice.

We performed the biodistribution and imaging studies of 111In and 67Ga labeled tetra(4-N-methylpyridyl)porphine, (T4NMPYP), and compared it to that of 67Ga-citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both 111In and 67Ga labeled T4NMPYP (3, 6, 24 and 48 h) were similar but differed from that of 67Ga-citrate (48 h). The optimum tumor uptake of both radiolabeled porphyrins was at 6 h post-injection and was lower than the tumor uptake of 67Ga-citrate at 48 h post-injection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of 67Ga-citrate. The imaging studies performed with 111In-T4NMPYP and 67Ga-citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of 111In-T4NMPYP.

Animals↗