A rapid and efficient method for the radiosynthesis and purification of [125I]SCH23982

The radiosynthesis of (1R)-(+)-1-phenyl-3-methyl-7-[125I]iodo-8-hydroxy- 2,3,4,5-tetrahydro-1H-3-benzazepine (commonly referred to as SCH23982) and its use as a high affinity D1 dopamine antagonist ligand have been reported previously. We now provide a simple and inexpensive protocol for the rapid and efficient synthesis of this radioligand based on the Cloramine-T-catalyzed reaction between the commercially available precursor (R)-(+)-1-phenyl-3-methyl- 8-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine and carrier-free sodium [125I]iodide. [125I]SCH23982 is separated rapidly (within 20 min) from the precursor and reaction byproducts (e.g., chlorinated precursor, SCH23390) by reverse-phase HPLC on a C-8 column. The major iodinated product has been identified as SCH23982 based on co-chromatography with authentic SCH23982, UV spectral characteristics, and biological activity. The chromatographic effluent containing the active product is adsorbed on a C-18 Sep-Pak cartridge to remove mobile-phase constituents and permit it to be eluted and diluted to the desired concentration; this technique is used also for periodic repurification. Our synthesis protocol results in final purified product that incorporates ca. 50% of the initial 125I (tested using starting quantities of 1-10 mCi Na125I); the final product has a specific activity of ca. 2500 +/- 350 Ci/mmol. Data from in vitro receptor autoradiographic and homogenate studies with this radioligand are consistent with previously reported values in terms of expected receptor distribution, affinity, and density (KD of 1.0 nM, Bmax of 1400 fmol/mg protein in rat striatal membranes).     

The effect of percutaneous oestrogen replacement therapy on Lp(a) and other lipoproteins

OBJECTIVES: To determine the effect of percutaneous oestrogen replacement therapy on lipoprotein (a) and other plasma lipoproteins. METHODS: Open longitudinal prospective study conducted at the hormone replacement clinic of the Prince of Wales Hospital, New Territories, Hong Kong. Thirty women who had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign gynaecological conditions were treated with 1.5 mg of percutaneous 17 beta-oestradiol gel applied daily for a period of 12 consecutive months. Measurements of plasma lipoproteins were made before the commencement of treatment and repeated at 6- and 12-month intervals. RESULTS: There was a significant reduction in the concentrations of Lp(a) during the first 6 months of treatment, with median values falling from 7.87 mg dL-1 to 6.16 mg dL-1 (P = 0.004, 0-6 months). During the second 6 months, the median concentration increased to 9.38 mg dL-1, (P = 0.072, 6-12 months), which did not significantly differ from the baseline level (P = 0.545, 0-12 months). Significant reductions in the concentrations of apoprotein A-I (apo A-I), apoprotein B (apo B), high density lipoprotein cholesterol (HDL-C), and HDL3-C were also present after 6 months (P = 0.043, 0.049, 0.028, 0.013, respectively), but there were no differences between the baseline values of these lipoproteins and those at the completion of the study (P = 0.948, 0.244, 0.839, 0.117 respectively). Drug compliance was maintained throughout the study, with similar mean oestradiol concentrations at 6 and 12 months. CONCLUSIONS: The percutaneous administration of 17 beta-oestradiol has variable short term effects on plasma lipoproteins which are not maintained over a longer duration of treatment. By avoiding the 'first pass' effect on the liver, this method of delivery does not appear to produce the sustained changes in lipoproteins seen with oral treatment.     

Supraceliac, but not infrarenal, aortic cross-clamping upregulates neutrophil integrin CD11b

OBJECTIVE: To evaluate the effects of supraceliac and infrarenal aortic cross-clamping on the expression of neutrophil integrin in CD11b (a marker of systemic cytokine release). DESIGN: Two groups, determined by anatomic placement of aortic cross-clamp. Laboratory personnel were blinded as to group assignment. SETTING: University teaching and community hospitals. Laboratory facilities used were university and Veteran's Affairs medical centers. PARTICIPANTS: Patients scheduled for aortic surgery. INTERVENTIONS: Blood sampling was performed at baseline, after 30 minutes of aortic cross-clamp duration, 30 and 90 minutes after reperfusion (for tumor necrosis factor-alpha plasma levels in infrarenal cross-clamp group), and at baseline and 90 minutes reperfusion (for neutrophil CD11b expression quantification) in both groups. MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor-alpha measured by ELISA technique did not change at any time period in the infrarenal clamping group. Neutrophil CD11b expression, measured by double antibody staining and FACScan analysis, did not change significantly at 90 minutes of reperfusion in the infrarenal group, but increased significantly (p < 0.05) in the supraceliac aortic cross-clamp group. CONCLUSION: Neutrophil integrin CD11b has been demonstrated to be the primary adhesive glycoprotein responsible for neutrophil organ entrapment and subsequent neutrophil-mediated reperfusion injury. These results suggest that upregulation of neutrophil integrin CD11b after supraceliac aortic clamping may in part be responsible for the higher incidence of acute lung injury after thoracic aortic aneurysm repair requiring supraceliac clamping when compared with infrarenal aneurysm surgery.     

Curative potential of combined modality therapy for advanced Hodgkin's disease

During the period from 1969 through 1977, 124 patients with advanced Hodgkin's disease underwent treatment with combination chemotherapy and radiotherapy. Sixty-three cases were previously untreated, and 61 were relapses following radical radiotherapy for localized Hodgkin's disease. No patient in this series had received prior chemotherapy. Of 102 patients (84%) who have entered complete remission, 92 remain in complete remission with a median follow up time of five years, 10 patients having relapsed, and acute leukemia having developed in 2. The cumulative survival rate for all 124 patients is 80% at five years; the relapse-free survival rate is 74%. In many, if not most cases, the Hodgkin's disease appears to be cured. We have also identified two subgroups of patients for whom the prognosis is worse than for patients with advanced-stage disease as a whole. Patients over the age of 40 years have a five-year survival rate of only 45%, compared with 89% for all other patients. Those Stage IV patients with multiple extranodal sites of involvement have a five-year survival rate of 48%, compared with 81% for other Stage IV patients with only a single extranodal site involved.     

Episodes of psychiatric utilization

The continued growth of outpatient psychiatric care has been accompanied by a large number of research studies concerning the determinants of psychiatric utilization. One of the major limitations of these efforts has been the inability to go beyond distributional data on the use of services. This article describes a methodology for generating episodes of psychiatric care given a data set with a small amount of routinely collected data present in many medical information systems. Both demographic and medical characteristics are significantly associated with health services resource use as defined by the number of visits in an episode. A model predicting recurrent episodes of care is also described. The general utility of this approach and the substantive implications of the specific results are discussed.     

Monolithic demodulator for 40-gb/s DQPSK using a star coupler

A novel device that demodulates both quadratures of the optical differential quadrature phase-shift keying (DQPSK) format in a single interferometer by using a 4 /spl times/ 4 star coupler was demonstrated. Simultaneous measurements of both DQPSK quadratures at 42.7 Gb/s are also presented.