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To evaluate the efficacy and safety of vindesine in patients with metastatic melanoma after complete metastasectomy. One hundred and forty-two patients with metastatic spread to regional sites, lymph nodes, and distant sites after complete metastasectomy were randomized to receive either treatment with vindesine for 2 years or observation alone. Vindesine 3 mg/m intravenously was administered biweekly for the first 26 weeks following 3-week intervals for an additional 26 weeks and thereafter every 4 weeks for 52 weeks. One hundred and thirty-nine patients were eligible for intent-to-treat analysis. Median follow-up time was 46 months. Median recurrence free survival was 7.9 months in the vindesine group and 7.6 months in the observational group (P=0.40). Three-year overall survival rate was 54.9% (37 patients) for patients receiving vindesine in comparison to 43.6% (31 patients) in the observation arm (P=0.07). No grade IV toxicity was observed. The two major side effects in the vindesine group were alopecia and peripheral neuropathy. Ten patients went off treatment because of grade III toxicity. Adjuvant treatment with vindesine did not significantly prolong disease free or overall survival in high-risk melanoma patients. Thus, this randomized trial did not confirm earlier reports of beneficial effects of adjuvant vindesine and can therefore not be recommended.

Spontaneous regression of primary melanoma lesions is regarded as the result of the recognition of melanoma-associated antigen (MAA)-derived peptides by cytotoxic T-lymphocytes and destruction of melanoma cells. The transporter associated with antigen processing (TAP1/2) is likely to play a crucial role in this process since it loads antigen peptides onto MHC class I molecules. To determine the impact of TAP defects on the spontaneous regression of melanoma lesions, we have compared the expression of TAP1 and TAP2 in 39 primary melanoma lesions exhibiting clinical and histological signs of tumour regression and in 35 primary melanoma lesions without regression phenomena. TAP1 expression was significantly associated with regression of melanoma lesions, since the staining pattern with anti-TAP1 antibody was positive in 38 of the 39 lesions exhibiting regression phenomena and in only 24 of the 35 lesions without histopathological signs of tumour regression. In the latter group, six lesions were stained with a heterogeneous pattern and five with a negative pattern. Furthermore, in lesions with a heterogeneous staining pattern, a clear association was found between TAP1 expression in melanoma cells and the presence of tumour-infiltrating lymphocytes. These results suggest that TAP1 plays an important role in the MAA-specific cytotoxic T-lymphocyte response, which has been suggested to underlie the spontaneous regression of primary melanoma.

Liposarcomas are a heterogeneous group of tumors with variable histopathology and clinical behavior. Accurate diagnosis, subtyping, and grading are essential to select appropriate treatment. Well-differentiated tumors are slow-growing and may reach large sizes without symptoms. They are considered l

OBJECTIVE Reliability of assessment is important in any kind of neuropsychiatric study, but is particularly pivotal in schizophrenia research where symptom instability is common. MATERIALS AND METHODS Two fluorodeoxyglucose PET scans, 1 week apart, were carried out in schizophrenic patients while they were performing a simple visual discrimination task. Subject and scan conditions were held constant. Regional metabolic rates of glucose utilization were calculated as absolute and scaled; they were compared using correlational statistics. RESULTS Average differences between scans were 5-9% for the parietal and occipital cortices, but 1-3% for other cortical areas, differences comparable with reported variances in normal controls. CONCLUSION These results suggest that test-retest variance in metabolic imaging in schizophrenia is relatively low and that task performance increases metabolic stability in brain areas unrelated to task performance.

Eleven visual parameters of Tc-99m DTPA imaging studies were evaluated to identify scintigraphic findings that best detect changes in renal function, to determine at which GFR levels they appear, and to establish criteria for visual estimation of renal function. Visual parameters were compared to in vitro GFR determinations in 41 patients. Three visual parameters offered best discrimination. The first one appeared at GFR values below 70 mL/min (sensitivity: 76%). The renal peak activity on the flow study (normally equal or greater than aortic) no longer reached the intensity of the aortic peak (pKpA). The second parameter appeared at GFR values below 50 mL/min (sensitivity: 85%). The estimated kidney-to-liver ratio in the 2-minute image (usually 3 or greater) decreased to values less than 3. The third scintigraphic finding, pelvicalyceal system nonvisualization, appeared at GFR levels below 20 mL/min (sensitivity 100%). Use of these 3 scintigraphic findings allows categorization of patients into four functional groups: 1) severe dysfunction (GFR: 0-20 mL/min), 2) moderate to severe dysfunction (GFR: 21-50 mL/min), 3) moderate dysfunction (GFR: 50-70 mL/min), and 4) Normal study (GFR70 mL/min). Visual analysis of Tc-99m DTPA images does not identify patients with mildly decreased renal function (GFR: 70-90 mL/min).

The potential use of single photon emission CT (SPECT) for quantification depends on its physical performance characteristics. We investigated the performance of a high resolution four-head brain SPECT scanner (Neuro-Spect; Summit/Hitachi). With an attenuation coefficient of 0.11 cm-1 and the Chang correction method, the calibration factor of the scanner was 515 (cpm/ml)/(microCi/ml) and showed only a minimal but systematic dependence on object size. Without scatter, the resolution was 4.7 mm (full width at half-maximum); in a scatter medium, the resolution was 5.3-10.0 mm with high resolution collimation and 7.7-18.8 mm with general purpose collimation, depending on filtering. A recovery coefficient of close to 100% was measured in the center of spheres with a size of at least 20 mm placed in a cylindrical water-filled phantom. In lesions of this size, scatter was 20%. We conclude from our measurements that the investigated high resolution SPECT offers significant improvements in resolution, scatter, and recovery, which will improve both the quality of brain studies and the measurement of quantitative parameters such as the cortex/white matter ratio.

In basal cell carcinoma, release of proteolytic activity is implicated in extracellular matrix degradation and tumor infiltration. The stromelysin metalloproteinase family is a major candidate for the matrix proteolytic activity in infiltrative tumors. However, in murine models of basal cell carcinoma, neither stromelysin 1 nor 2 appears to play a role in tumor infiltration. We have analyzed the expression of the newly described stromelysin 3 in human basal cell carcinoma using Northern blot analysis and in situ hybridization. In 12 of 14 cases, levels of stromelysin 3 expression were more than tenfold above those observed in normal skin. In one of five cases of squamous cell carcinoma, stromelysin 3 expression was tenfold above levels seen in normal skin. Stromelysin 3 expression was either undetectable or extremely weak in all five cases of infiltrative malignant melanoma. In basal cell carcinoma, stromelysin 3 transcripts were localized by in situ hybridization to the stromal tissue immediately adjacent to basal cell carcinoma, the tumor cells themselves being negative. Therefore, expression of stromelysin 3 in stromal cells may be expected to play a significant role in destruction of the basal membrane zone and extracellular matrix in basal cell carcinoma invasion.

Accurate localization of an imaging plane of interest is often needed prior to a positron emission tomographic (PET) study. We have developed a simple method for accurate and reproducible selection of an imaging plane for PET using magnetic resonance (MR) imaging. This method is useful when optimal sampling of specific brain structures, such as small subcortical nuclei, or when a specific imaging angle is required for the PET study. An external localizing device, consisting of a series of tubes visible on MR, is affixed to an individually fitted thermoplastic mask. This mask system is worn by the patient during both the MR and PET studies. A plane of interest is planned from the sagittal MR image and defined by its relation to the localizing device and to the MR scanner's "landmark" or reference position. This plane is transferred to the mask by means of a calibrated alignment laser. The coplanar acquisition of MR and PET images allows individualized analysis of brain structure-function relationships. Phantom studies demonstrated the accuracy and reproducibility of imaging plane selection by this method to be within 1 mm and 1 degree. Application of the localization protocol in a human subject is also presented.

To assess the precision of gated equilibrium radioventriculography in measuring changes in left ventricular stroke volume (LVSV), we studied five dogs each with a chronically implanted electromagnetic flowmeter on the ascending aorta. Per cent changes in left ventricular stroke counts (LVSC) were compared to those in LVSV following acute changes induced by positive end respiratory pressure. We have compared LVSCs calculated in five different ways: (1) Manual outlining of LV region of interest (LVROI), either single fixed enddiastolic (ED) ROI or ED and endsystolic (ES) ROIs with the aid of functional images (first harmonic of Fourier analysis); (2-5) automatic outlining of LV ROI (the algorithm generated 30 profiles on which the maximum of second derivative delineated the LV edges) was performed either on ED image or both ED and ES images. For these four methods a crescent-shaped ROI for background correction was manually drawn at the border of the LV ROI. The fifth method used an automatically drawn single fixed LVED ROI with interpolative background substraction (IBS) between LV and RV edges. LVSC changes, calculated with the IBS method correlated better with LVSV changes than the other four methods. Thus assessment of small LVSC changes is highly processing-dependent.

Radionuclide gated cardiac blood pool (GBP) imaging was used to quantitatively assess the severity of acute aortic valvular regurgitation produced experimentally in 10 anesthetized dogs. Right ventricular (RV) and left ventricular (LV) stroke counts (end-diastolic minus end-systolic counts in RV and LV regions of interest) were used as indices of the stroke volumes of the two ventricles. Regurgitant fraction (RFGBP) was derived by assuming that an excess of LV stroke counts compared to RV stroke counts was due to regurgitant flow: RFGBP = LV stroke counts - RV stroke counts/LV stroke counts X 100. Regurgitant fraction (RFEMF) was also estimated directly from an electromagnetic flowmeter (EMF) on the ascending aorta. Mean RFEMF was 55.8 +/- 17.9% (+/-SD). Close agreement was found between regurgitant fractions measured by GBP and EMF (RFGBP = 1.09, RFEMF - 4.7%, r = 0.88, p less than 0.001, SEE = 9.98%). The severity of regurgitation from blood pool images also correlated closely with aortic pulse pressure (r = 0.89) and the length of the tear in the aortic valve (r = 0.84). These results suggest that blood pool imaging may be sueful for noninvasive quantification of regurgitant flow in patients with valvular insufficiency.

Summary Several new lipophilic 99Tcm complexes have recently been described as alternatives to N-isopropyl (123I) iodoamphetamine (123IAMP) for measurement of regional cerebral blood flow (RCBF). In this study we have compared brain uptake and blood clearance of 99Tcm-N-ethylpiperidine-diamino dithiol (99Tcm-NEP DADT), its 4-methylated derivative (99Tcm-Me-NEP-DADT) and 99Tcm-hexamethyl-propylene-amine-oxime (99Tcm-HMPAO) with that of 123IAMPin two dogs. Single photon emission tomography (SPECT) was employed to measure brain accumulation and retention of the four radiopharmaceuticals. Cerebral uptake of the 99Tcm complexes (0.8–1.1%) was lower than that of 123IAMP (1.6% of the injected dose). There was consider-able extracerebral activity in the dog's head, especially in the olfactory and snout regions. Because of slow blood clearance 99Tcm-HMPAO showed high uptake in these regions. Brain uptake of 99Tcm-HMPAO reached a plateau 5 to 10 min after intravenous injection and remained constant for the entire study period (1 h). 99Tcm-NEP-DADT, on the other hand, showed significant clearance from the brain after reaching maximal uptake at 10 to 15 min after injection. However, brain imaging with these agents was possible during the first 20 min. The mechanism of brain uptake, as well as the relationship between brain uptake and RCBF need to be evaluated for each of the four radiopharmaceuticals.

Radionuclide ventriculography was performed in 15 healthy subjects during quiet breathing and during inspiration against a 24 cm H2O threshold load with a respiratory gating technique. Inspiratory threshold loading caused an inspiratory decrease in ejection fraction from 64% to 59% (p less than .001). Stroke counts proportional to stroke volume decreased by 9.6% (p less than .02) due to an increase in end-systolic counts of 15.9% (p less than .05). End-diastolic counts decreased in four subjects and increased in three subjects, but the mean counts did not change significantly. These findings suggest that negative pleural pressure causes an impediment to left ventricular ejection comparable to an increase in arterial pressure. Respiratory gating of radionuclide ventriculography during loaded breathing is suggested as a controlled stress on the ventricle for diagnostic purposes.

Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricle to administer microspheres and in a peripheral artery to determine cardiac output. Each dog received two microsphere injections: (1) while normally oxygenated (room air), and (2) under hypoxia (10% oxygen-90% nitrogen in 10 dogs and 5% oxygen-95% nitrogen in 11 dogs). Absolute cardiac output increased from 87 +/- 15 ml/min per kg to 101 +/- 14 ml/min per kg during mild hypoxia (10% oxygen) (P less than 0.05), and from 73 +/- 17 ml/min per kg to 120 +/- 24 ml/min per kg during severe hypoxia (5% oxygen) (P less than 0.01). Absolute blood flows increased to all organs except skin and muscle during hypoxia, although there were decreases in the fractional distribution of cardiac output to the splanchnic bed and kidney. Striking changes were found in coronary, hepatic, and cerebral circulation, and the organ with, greatest response to hypoxia was the heart, with increased coronary flow of 37% and 285% during exposure to 10% and 5% oxygen, respectively. Hence, low oxygen levels in blood cause redistribution of cardiac output and arterial content plays an important role in blood flow regulation.

This study was done to determine the value of thallium-201 myocardial scintigraphic imaging (MSI) for identifying disease in the individual coronary arteries. Segmental analysis of rest and stress MSI was performed in 133 patients with ateriographically proved coronary artery disease (CAD). Certain scintigraphic segments were highly specific (97 to 100%) for the three major coronary arteries: anterior wall and septum for the left anterior descending (LAD) coronary artery; the inferior wall for the right coronary artery (RCA); and the proximal lateral wall for the circumflex (LCX) artery. Perfusion defects located in the anterolateral wall in the anterior view were highly specific for proximal disease in the LAD involving the major diagonal branches, but this was not true for septal defects. The apical segments were not specific for any of the three major vessels. Although MSI was abnormal in 89% of these patients with CAD, it was less sensitive for identifying individual vessel disease: 63% for LAD, 50% for RCA, and 21% for LCX disease (narrowings > = 50%). Sensitivity increased with the severity of stenosis, but even for 100% occlusions was only 87% for LAD, 58% for RCA and 38% for LCX. Sensitivity diminished as the number of vessels involvedmore » increased: with single-vessel disease, 80% of LAD, 54% of RAC and 33% of LCX lesions were detected, but in patients with triple-vessel disease, only 50% of LAD, 50% of RCA and 16% of LCX lesions were identified. Thus, although segmented analysis of MSI can identify disease in the individual coronary arteries with high specificity, only moderate sensitivity is achieved, reflecting the tendency of MSI to identify only the most severely ischemic area among several that may be present in a heart. Perfusion scintigrams display relative distributions rather than absolute values for myocardial blood flow.« less

A simple, noninvasive radionuclide technique which measures the severity of valvular regurgitation has been developed. The technique compares right and left ventricular stroke volume indices (change in counts between diastole and systole over the left and right ventricles) from 45 degrees LAO gated cardiac blood pool scans. In 14 control subjects, the left-to-right ventricular stroke index ratio was near unity (1.15 +/- 0.15 [SD]). In 26 patients with mitral and/or aortic regurgitation it was larger (range 1.36--5.30, mean 2.44). Comparison between the stroke index ratio and qualitative angiographic estimates of regurgitation revealed good agreement (F = 45.5, p less than 0.001). Gated cardiac blood pool scans permit noninvasive assessment of the severity of valvular regurgitation.

Precordial scanning of the distribution of radioiodine (I 131 -labeled iodide) in patients with myocardial infarction has been suggested by others as a means of delineating the infarcted area. Attempts to localize radioiodine in 14 precordial scans of 12 patients with myocardial infarction resulted in the demonstration of localized areas of radioactivity in seven scans. This collection of radioactivity was found to be within the stomach, resulting from the normal concentration of radioiodine that occurs in gastric secretions.

Nuclear angiocardiography with a gamma camera, a pinhole collimator, and 99m Tc pertechnetate was performed on 43 children aged 3 years or less, including 10 neonates. Twenty-six children had congenital heart disease, which was confirmed at cardiac catheterization; the rest had no structural cardiac anomaly. Use of the pinhole collimator allowed magnification of cardiac images, with enhancement of resolution. Sensitivity was improved by positioning the pinhole 14 cm rather than 19 cm from the crystal of the gamma camera. Anterior and left lateral angiocardiograms were obtained with both 35-mm images at 0.3-sec intervals and cine-images at 18 frames/sec. Abnormalities in origin, size, and position of the great arteries, in chamber configurations, and in the time and course of activity in right and left heart, lungs, and great vessels were used to assist in identification of anomalies such as transposition of the great arteries, pulmonary atresia with intact ventricular septum, truncus arteriosus, and aortic atresia. 99m Tc in a dose of 18.5 mCi/M 2 of body area was used and produced whole-body and gonadal radiation doses less than 1 rad. The low risk and simplicity of the technic make it promising as a screening procedure and as an adjunct to cardiac catheterization for cyanosed infants.

The temperature records of 30 patients were examined for a febrile response after the injection of 111 ln-DTPA for cisternography. All lots of the material were tested and found to be negative by the U.S. Pharmacopeia rabbit test for pyrogens. The material also was tested for reactivity with the amebocyte lysate of Limulus. Six of the seven patients who received material strongly reactive with the Limulus lysate had temperature increases greater than 1°F within eight hours of the injection. No febrile response was observed in the remaining patients, who received material weakly reactive or nonreactive with the Limulus lysate. In two of the seven patients who received the strongly reactive material, aseptic meningitis also developed. This observation supports the hypothesis that bacterial endotoxin contamination of radiopharmaceuticals used in cisternography may cause aseptic meningitis.

Nineteen mothers of premature infants were interviewed in an attempt to determine a possible relationship between prematurity and orgasmic coitus during pregnancy. Although the limited number of subjects precludes tests of statistical significance and definitive conclusions, the findings do suggest possible associations. While there appeared to be no relationship between prematurity and coitus per se during pregnancy, the association of frequent or intense orgasm with prematurity does raise some questions that further investigation might answer. Because of the hazard of prematurity to the subsequent development of the child, further exploration of the possible relationship of prematurity to orgasmic coitus during pregnancy appears warranted.

Neurotransmitter receptors may be involved in a number of neuropsychiatric disease states. The ligand 3-N-[11C]methylspiperone, which preferentially binds to dopamine receptors in vivo, was used to image the receptors by positron emission tomography scanning in baboons and in humans. This technique holds promise for noninvasive clinical studies of dopamine receptors in humans.