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Biomedical subjects

S Ben-Haim

Publications and source records attributed to S Ben-Haim.

At least 37 records · Page 2Linked to original sources
PubMed1994

The safety and pharmacokinetics in adult subjects of an intravenously administered 99mTc-labeled 17 amino acid peptide (CYT-379).

A phase I study was designed to evaluate the safety and pharmacokinetics of a novel platelet reactive peptide, peptide acetyl-SYGRGDVRGDFKCTCCA-amide (CYT-379), which binds to the fibrinogen receptor of activated platelets and also binds to 99mTc. Eleven subjects with suspected deep venous thrombosis had 0.1, 0.5 or 1.0 mg of the peptide infused intravenously. Pharmacokinetics were determined by assaying blood samples in 6 of the 11 subjects and by urine sampling in 5 of these 6 subjects. Plasma and whole blood time-activity curves demonstrated an initial fast component with half-time clearance of 0.2 +/- 0.01 and 0.2 +/- 0.02 h and a slow component with half-time clearance of 2.8 +/- 0.3 and 2.7 +/- 0.2 h (mean +/- SEM for plasma and whole blood, respectively). Urine clearance was 22.6 +/- 3.3 and 10.8 +/- 1.6 mL/min when normalized to body surface area. The cumulative excretion of 99mTc-CYT-379 in the urine was 16.6 +/- 3.6, 45.6 +/- 16.9 and 45.6 +/- 1.8% of the administered dose over 0-2, 0-12 and 0-24 h after radiopharmaceutical injection, respectively. Images obtained in 11 subjects immediately, at 1-2, and 4-6 h after injection were evaluated for abnormalities and were compared with duplex Doppler ultrasonography. 99mTc-CYT-379 images were positive in only 3 of 7 subjects who had a positive duplex Doppler examination in at least one lower extremity. One subject with negative duplex Doppler had also negative 99mTc-CYT-379 scintigraphy. One subject with negative scintigraphy and two other subjects with positive scintigraphy had no other imaging studies of the deep venous system performed. No adverse reactions were observed during or after the infusion of 99mTc-CYT-379. 99mTc-CYT-379 appears to be a safe radiopharmaceutical and demonstrates rapid clearance from plasma in human subjects.

Adult↗
PubMed1994

Captopril-enhanced 99Tcm-MAG3 renal scintigraphy in subjects with suspected renovascular hypertension.

This pilot study was undertaken to generate preliminary data on the accuracy of captopril-enhanced renal scintigraphy with a relatively new radiopharmaceutical, 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) for detecting significant renal artery stenosis. Truth data was based either on arteriographic or outcome criteria (blood pressure response to therapy). Twenty-seven subjects with suspected renovascular hypertension were studied with baseline and captopril-enhanced 99Tcm-MAG3 renal scintigraphy and renal arteriography. Scan interpretations were expressed as a probability of a significant renal artery stenosis. Scan interpretations were compared with renal arteriographic results, renal vein renin levels, blood pressure values after renal artery repair, and blood pressure control after 4-26 months of clinical follow-up. Using > or = 50% luminal obstruction on arteriography as the reference standard for renal artery stenosis and a high probability scan representing a positive test, the test sensitivity and specificity were 33 and 97%, respectively (using high or indeterminate probability to represent a positive scan, the test sensitivity and specificity were 67 and 83%, respectively). The negative predictive value of a low probability scan for renal artery stenosis was 80%. However, including a measure of renovascular hypertension (blood pressure response to renal artery repair) as the reference standard, the accuracy of the scan improves, with the negative predictive value of a low probability scan for renovascular hypertension increasing to 97%. Scintigraphic results were also positively correlated with renal vein renin values in a statistically significant fashion (two-tailed Fisher exact test statistic = 6.43, P = 0.0219). Captopril-enhanced 99Tcm-MAG3 renal scintigraphy is a moderately accurate technique for detecting renal artery stenosis. More importantly, our preliminary findings suggest that the scintigraphic technique using 99Tcm-MAG3 appears to predict the blood pressure response to renal artery repair in subjects with suspected renovascular hypertension, thereby separating subjects with haemodynamically insignificant renal artery stenosis from those with renovascular hypertension.

Angiography↗
PubMed1994

SPECT quantitation of cobalt-57-bleomycin to predict treatment response and outcome of patients with lung cancer.

UNLABELLED: Our hypothesis is that the concentration of 57Co-bleomycin (Co-bleo) in lung tumors reflects tumor cell kinetics and thus, prognosis. The relationship between the tumor concentration of Co-bleo measured in vivo by quantitative SPECT, response to chemotherapy and survival was investigated. METHODS: Twenty patients with small-cell lung carcinoma (SCLC) and 49 patients with non-small-cell lung carcinoma (NSCLC) were studied. The concentration of Co-bleo was measured by SPECT in vivo in the tumor. The correlation between Co-bleo concentration in the tumor and the fraction of Co-bleo bound to DNA was investigated in an EMT6 murine tumor model and in samples of eight human tumors. RESULTS: Tumors that did not respond to treatment showed a significantly higher Co-bleo concentration 8 hr after injection than tumors that responded (5.83% +/- 1.97% ID/cc * 10(-3) versus 2.55% +/- 1.23% ID/cc * 10(-3), p < 0.001). Values of Co-bleo concentration of 2.97% ID/cc * 10(-3) for SCLC and 2.72% ID/cc * 10(-3) for NSCLC were found to best separate patients into short- and long-term survival groups. In the EMT6 murine tumor model, a good correlation was found between the concentration of Co-bleo in the tumor and the fraction of Co-bleo bound to DNA (r = 0.75). In human tumor samples, a good correlation was found between DNA-bound Co-bleo measured in vitro and the concentration measured in vivo by SPECT (r = 0.85). CONCLUSIONS: SPECT-measured Co-bleo concentration predicts the response to treatment and the outcome in patients with lung tumor by showing Co-bleo binding to DNA and tumor cell kinetics.

Aged↗
PubMed1993

Power spectrum analysis and heart rate variability in Stage 4 and REM sleep: evidence for state-specific changes in autonomic dominance.

The present study investigated autonomic activity during NREM and REM sleep stages and wakefulness by spectral analysis of heart rate variability. The results demonstrated that NREM sleep in humans was characterized by a widely different autonomic activation pattern than REM sleep: high parasympathetic activity was found in NREM, while REM was characterized by attenuated vagal tone, and augmented sympathetic activity. The overall pattern during wakefulness showed an intermediate position between NREM and REM patterns; parasympathetic activity was lower than in NREM and higher than in REM, with an opposite trend for sympathetic activity.

Journal Article↗
PubMed1993

Diuretic-enhanced I-131 clearance after ablation therapy for differentiated thyroid cancer.

The authors assessed whether the whole-body radiation burden can be reduced with diuretic enhancement of iodine-131 excretion in patients with thyroid cancer and slow clearance. Whole-body imaging and quantitative I-131 clearance data obtained before and after ablation therapy were evaluated in 56 patients. Fourteen patients with slow pre-ablation therapy clearance (> 50% retention at 24 hours) received oral diuretics after I-131 therapy. Nine patients began taking furosemide 24 hours after I-131 treatment. Five patients had been receiving thiazide diuretics and were continued on the same dose after treatment. The mean half-time of I-131 clearance for the patients treated with furosemide decreased by 12 hours (P < .05) but was not significantly decreased for those who received thiazides or for the patients who did not receive diuretics. Administration of diuretics can improve I-131 clearance in patients with thyroid cancer and slow clearance, reducing the radiation burden and shortening the hospital stay.

Adolescent↗
PubMed1993

Cardiac function and responsiveness to beta-adrenoceptor agonists in rats with obstructive jaundice.

The function and role of the heart and the contribution of cardiac beta-adrenoceptors in the pathogenesis of circulatory failure in obstructive jaundice were studied in the 3-day bile duct-ligated (BDL) rat using three different techniques to measure cardiac function and beta-adrenoceptor activity, number, and affinity. The techniques were the pithed rat preparation, the isolated working heart preparation, and a competitive radioligand binding assay for beta-adrenoceptors. The results of these experiments were compared with those obtained in 3-day bile duct-manipulated (sham operated; SO) rats. Impaired indexes of basal cardiac contractility were observed in the BDL pithed rats and isolated working hearts. In these two preparations, responsiveness to norepinephrine and the beta-adrenoceptor agonists, isoproterenol and dobutamine, was unaffected by bile duct ligation. The affinity and number of cardiac beta-adrenoceptors in membranes from the hearts of SO and BDL rats were not significantly different from each other. These experiments have established for the first time that the 3-day BDL rat has a cardiac myopathy associated with intact responsiveness to beta-adrenoceptor agonists, a normal unchanged affinity and number of cardiac beta-adrenoceptors.

Adrenergic beta-Agonists↗
PubMed1992

Dynamic properties of cardiovascular systems.

A recently derived mathematical model of an isolated heart is extended here to a closed-loop cardiovascular system. Taking the end-diastolic volume as state variable, the authors show that the closed-loop cardiovascular system can be described by a one-dimensional nonlinear discrete dynamical system that depends on parameters describing the systolic and diastolic properties of the heart, heart rate, total peripheral resistance, and arterial capacitance. Studies of this model show that the system possesses a rich spectrum of dynamical behavior, from stable points through stable cycles to a "chaotic" behavior. It is shown that such an analysis of dynamic behavior yields those domains in the parameter space that correspond to a normal and abnormal beating heart, when the heart ejects time-invariant and time-variant (periodic or aperiodic) stable stroke volumes, respectively. Determination of such domains may lead to better understanding of the specific pathologic mechanism involved in the evolution of an abnormal beating heart.

Cardiovascular Physiological Phenomena↗
PubMed1992

Ga-67 uptake unsuppressed by leukopenia and intense antibiotic therapy.

The authors describe a patient with myelofibrosis who showed intense Ga-67 uptake in spite of being severely leukopenic and receiving large amounts of antibiotics. They conclude that false-negative results associated with leukopenia or intensive antibiotic treatment may not always be correct.

Abscess↗
PubMed1992

Spectrum of scintigraphic appearance of liver hemangiomas.

Two hundred and twenty five liver hemangiomas in 166 patients were studied with Tc-99m labeled RBC and are the basis for this atlas. All hemangiomas showed various presentations of the perfusion blood pool mismatch, which is the basis for diagnosis. The size of the hemangiomas was the factor that determined the mixing of the Tc-99m RBC with the blood and, hence, the sequence of visualization of the lesion. Hemangiomas may appear as multiple lesions on liver scan and imitate metastases. Ninety-five hemangiomas appeared in 36 patients as multiple focal abnormalities. Hemangiomas are extremely variable in size. They may be huge (31 hemangiomas) and sometimes occupy most of the abdomen. Or they can be very small and are then detected only by SPECT (two cases). Thrombosed large hemangiomas appear as focal defects on Tc-99m RBC.

Erythrocytes↗
PubMed1992

Lymphoma: predictive value of Ga-67 scintigraphy after treatment.

The negative predictive value (PV-) and positive predictive value (PV+) of gallium-67 scintigraphy and computed tomography (CT) were compared after treatment in 43 patients with Hodgkin disease and in 56 patients with non-Hodgkin lymphoma. The usefulness of these studies in predicting survival was also evaluated. In patients with Hodgkin disease, the PV- of Ga-67 scintigraphy was 0.84 and of CT was 0.88. The PV+ was 0.80 for Ga-67 studies and only 0.29 for CT. In patients with non-Hodgkin lymphoma, the PV- of Ga-67 scintigraphy was 0.84 and of CT was 0.80. The PV+ was 0.73 and 0.35, respectively. For both groups, the differences in disease-free survival between patients with negative and positive Ga-67 studies were significant (P less than .05 in Hodgkin disease and P less than .001 in non-Hodgkin lymphoma), but the differences were not significant for CT. These data show that, after treatment of patients with lymphoma, Ga-67 scintigraphy is a good predictor of clinical outcome and can be used beneficially in patient treatment.

Adolescent↗
PubMed1992

Leukocyte scintigraphy in the diagnosis of mycotic aneurysm.

Early diagnosis of a mycotic aneurysm is critical, but often unsuspected, due to the insidious onset of symptoms related to occult infection. This study was undertaken to assess the role of leukocyte scintigraphy in establishing the diagnosis of mycotic aneurysm. The records of all patients with possible mycotic aneurysm between 1985 and 1991 were reviewed. Seven patients had leukocyte scintigraphy and computed tomography (CT), three also had magnetic resonance imaging (MRI) and three had angiography as part of the diagnostic workup. CT and MRI detected aneurysms in five of the seven patients, but CT scans were misinterpreted in two patients as indicative of abscess only. In six patients, infection could not be differentiated from thrombosis, seroma or hemorrhage by CT or MRI. Leukocyte scintigraphy was positive in all four patients with infected aneurysms; it was negative in two of the three noninfected aneurysms and equivocal in the third. Leukocyte scintigraphy provided a useful early survey that demonstrated evidence of infected aneurysms in four patients and identified other sites of infection in two patients. Leukocyte uptake complemented CT, MRI and angiographic findings distinguishing between seroma/hematoma and adjacent infection to establish a preoperative diagnosis of infected aneurysms.

Aged↗
PubMed1991

Stability analysis of one-dimensional dynamical systems applied to an isolated beating heart.

In this paper we propose a new model of an isolated beating heart. The model is described by a one-dimensional non-linear discrete dynamical system which depends on several parameters. Applying stability analysis we investigate the dynamic properties of the non-linear system. We find those domains in the parameter space in which the equilibrium point of the system (the fixed point) and the periodic orbits are attractors and in which they are unstable. These domains correspond to a normal and abnormal beating heart, i.e. when the end diastolic volumes are stable time invariant and time variant, respectively. On transition between these domains there is a bifurcation which gives rise to a pair of attracting points of period 2. This case corresponds to the simplest type of period doubling behavior of an abnormal beating heart, called mechanical alternans. Our results provide qualitative and quantitative predictions which can be used for comprehensive experimental design.

Blood Pressure↗
PubMed1991

[Adult respiratory distress syndrome complicating acute pyelonephritis in pregnancy].

On the fifth day of a course of antibiotic therapy for acute Klebsiella pyelonephritis, a 21-year-old pregnant woman developed adult respiratory distress syndrome. She improved rapidly on fluid restriction and intravenous furosemide and did not require mechanical ventilation. 17 weeks later, after 40 weeks of pregnancy, she spontaneously delivered a healthy male infant weighing 3280 g.

Adult↗
PubMed1990

Normal and abnormal Ga-67 SPECT anatomy in patients with lymphoma.

The appearance of normal Ga-67 SPECT images in the coronal, sagittal and transaxial planes is described. The normal tomographic appearance of bone, liver, spleen, and gut is shown and compared with disease involvement above and below the diaphragm.

Gallium Radioisotopes↗
PubMed1990

Administered dose and tumor dose of bleomycin labeled with cobalt-57 in mice and men.

Tumor concentrations of the chemotherapeutic drug, bleomycin, labeled with cobalt-57 (Co-bleo) were compared in mouse tumor models and in human lung tumors using quantitative single-photon emission computed tomography. Drug concentrations in histologically similar human tumors showed marked variability for the same injected dose (ID). Small cell carcinomas showed concentrations between 1.09 and 8.85 %ID/cc x 10(-3) while non-small cell lung tumors showed a concentration variation between 0.36 and 6.75 %ID/cc x 10(-3). In contrast to the situation in human tumors, uptake in mouse tumors showed only slight variability in animals with the same tumor model. EMT-6 tumors in mice showed at 6 hr significantly higher uptake of Co-bleo (p less than 0.001) and significantly higher tumor-to-lung ratio (p less than 0.001) when compared to murine fibrosarcomas. The EMT-6 tumors in contrast to the fibrosarcomas responded to bleomycin treatment in a dose dependent manner. The results indicate that while in mice the tumor dose closely follows the administered dose, in humans, the tumor dose and the tumor-to-lung ratio in the individual patient cannot be predicted from the administered dose.

Aged↗
PubMed1990

Residual mass and negative gallium scintigraphy in treated lymphoma.

Two patients with treated lymphoma demonstrated a residual mass on CT following treatment. In both cases gallium-67 (67Ga) scintigraphy demonstrated increased uptake in the original tumor mass and no uptake in the mass after treatment. In both cases the entire residual tumor mass was resected and found to contain no cancer tissue. This is further evidence of the role 67Ga scintigraphy may play in monitoring response of lymphoma patients to treatment. In contrast, other imaging modalities such as ultrasound, plain film x-rays, or CT only show the presence of a mass but not its nature.

Abdominal Neoplasms↗
PubMed1989

The concentration of bleomycin labeled with Co-57 in primary and metastatic tumors.

The concentration over time of bleomycin labeled with Co-57 was measured in 39 primary and metastatic tumor sites in 16 patients using a newly developed and validated single photon emission computed tomography (SPECT) method. There were nine primary tumors, 15 metastatic tumors, and five multifocal lymphomas. Co-bleomycin concentrations also were measured in primary and metastatic B-16 melanoma tumors in mice. In humans, metastases to lymph nodes (1.58 +/- 0.51 %ID/ml X minutes) showed significantly higher (P less than 0.01) tumor cumulative concentrations of Co-bleomycin than metastases to liver, bone, lung, and brain (0.76 +/- 0.20 %ID/ml X minutes). The cumulative concentrations of Co-bleomycin in human lymphomas (1.1 +/- 0.25 %ID/ml X minutes) also were significantly higher (P less than 0.01) than the concentrations in human metastases other than lymph nodes. The cumulative concentration in cerebral metastases (0.65 +/- 0.18 %ID/ml X minutes) was significantly lower (P less than 0.05) than in noncerebral metastases (1.22 +/- 0.53 %ID/ml X minutes). Primary tumors in humans showed higher concentrations of Co-bleomycin than metastases, except for lymph nodes. In contrast with humans, murine metastases showed higher concentrations of Co-bleomycin (6.20 +/- 2.65 %ID/g) than primary tumors (2.94 +/- 0.90 %ID/g) (P less than 0.001). The concentrations of Co-bleomycin in murine tumors that were affected by bleomycin were about three orders of magnitude higher than in human tumors. The results of this in vivo study document the differences in drug delivery of Co-57-labeled bleomycin to human primary and metastatic tumors and show differences in drug delivery between human and murine tumors.

Adolescent↗