Cervical exploration for primary hyperparathyroidism--A 25 year experience

Parathyroidectomy should be considered in every patient with hypercalcaemia and primary hyperparathyroidism even if the symptoms are vague. Cervical exploration is a safe operation with very satisfactory results. Our experience in 214 patients over 25 years shows permanent postoperative normocalcaemia in 95% of cases with a complication rate of 2.8%. All patients with primary HPT, regardless of age or the severity of symptoms should be candidates for cervical exploration.     

A peptide interaction in the major groove of RNA resembles protein interactions in the minor groove of DNA

A 17-amino acid arginine-rich peptide from the bovine immunodeficiency virus Tat protein has been shown to bind with high affinity and specificity to bovine immunodeficiency virus transactivation response element (TAR) RNA, making contacts in the RNA major groove near a bulge. We show that, as in other peptide-RNA complexes, arginine and threonine side chains make important contributions to binding but, unexpectedly, that one isoleucine and three glycine residues also are critical. The isoleucine side chain may intercalate into a hydrophobic pocket in the RNA. Glycine residues may allow the peptide to bind deeply within the RNA major groove and may help determine the conformation of the peptide. Similar features have been observed in protein-DNA and drug-DNA complexes in the DNA minor groove, including hydrophobic interactions and binding deep within the groove, suggesting that the major groove of RNA and minor groove of DNA may share some common recognition features.     

Prostatic cryosurgery: use of MR imaging in evaluation of success and technical modifications

PURPOSE: To evaluate the usefulness of contrast material-enhanced magnetic resonance (MR) imaging in objective assessment of prostatic cryosurgery and the role of MR imaging in the modification of prostatic cryosurgical technique. MATERIALS AND METHODS: Thirty-eight consecutive patients with localized (T1-3, N0, M0) prostatic adenocarcinoma treated with prostatic cryosurgery underwent MR imaging without contrast enhancement before cryosurgery and unenhanced and gadolinium-enhanced MR imaging within 1-3 weeks after cryosurgery. The first 20 patients also underwent MR imaging at 3 months after cryosurgery. MR imaging findings were correlated with those from transrectal ultrasound-directed prostatic staging biopsy. RESULTS: Cryonecrotic prostate was identified as avascular regions characterized by absolute signal void on contrast-enhanced images. With progressive modification of cryosurgical technique, complete cryoablation of the prostate was achieved in the latter nine of the 38 patients. When cryoablation was considered complete according to MR imaging criteria, findings invariably correlated with those at biopsy, with no residual prostate tissue or tumor. CONCLUSION: Gadolinium-enhanced MR imaging of the prostate after cryosurgery provides a highly accurate means of monitoring success. Objective MR imaging findings allow modifications to the technology and technique, resulting in optimal therapeutic results with prostatic cryosurgery.     

Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin

The effectiveness and safety of warfarin were compared with those of a low-molecular-weight heparin (dalteparin) for the prevention of deep-vein thrombosis after total hip arthroplasty in a prospective, randomized, multi-institutional trial. Patients who were older than eighteen years of age and were scheduled to have an elective primary or revision total hip arthroplasty were eligible; 580 patients were randomized, 550 had the operation and received prophylaxis, and 382 had evaluable venograms. Prophylaxis was provided either with warfarin beginning the night before the operation or with dalteparin beginning two hours before the operation and was continued until venography was performed. Bleeding was assessed on the basis of intraoperative blood loss, transfusion requirements, a decrease in hematocrit, and clinically identified bleeding complications. The prevalence of deep-vein thrombosis was found to be significantly lower in the patients who had received dalteparin than in those who had received warfarin (twenty-eight [15 per cent] of 192 patients compared with forty-nine [26 per cent] of 190 patients; p = 0.006). Deep-vein thrombosis occurred in the calf veins of twenty-one patients (11 per cent) who had received dalteparin and of forty-three patients (23 per cent) who had received warfarin; this difference was significant (p = 0.003). Proximal deep-vein thrombosis occurred in ten patients (5 per cent) who had received dalteparin and in sixteen patients (8 per cent) who had received warfarin; however, with the numbers available, no significant difference could be detected (p = 0.185). We also could not detect a significant difference with regard to the intraoperative and postoperative blood loss, the decrease in hematocrit, and the prevalence of major bleeding complications between the two groups; however, the patients who had received dalteparin had a significantly higher prevalence of bleeding complications involving the operative site (p = 0.03), and a significantly greater percentage required postoperative transfusions (p = 0.001). We concluded that preoperative prophylaxis with dalteparin is significantly more effective than that with warfarin in preventing deep-vein thrombosis after total hip arthroplasty. The greater effectiveness of dalteparin must be considered, however, in light of an increased need for postoperative transfusions and an increase in the prevalence of wound-related bleeding complications.     

Evaluation of triple quantum-filtered 23Na NMR spectroscopy in the in situ rat liver

Expression of intermediate filaments (IFs) has been suggested to be a reliable marker for differentiating epithelial and non-epithelial tumors. Moreover, the c-erbB-2 and p53 genes are considered to be involved relatively early in the process of human carcinogenesis. In order to elucidate the origin of uterine carcinosarcomas, we analyzed IF, c-erbB-2 and p53 expression in and the ultrastructural characteristics of clones derived from a human uterine-carcinosarcoma cell line, EMTOKA. The expression of IFs and other proteins in the EMTOKA clones was identical to that in the EMTOKA cell line. It and its 7 clones all expressed cytokeratins 8, 17, 18 and 19, vimentin, epithelial membrane antigen, S-100, myoglobin, type-II collagen, alpha-smooth-muscle actin, placental alkaline phosphatase and epidermal-growth-factor receptor. The c-erbB-2 and p53 expression levels of all the cell types of the EMTOKA cell line and its clones were the same. Interestingly, an ultrastructural study showed that the EMTOKA cell line and its clones at early and late passages possessed the characteristics of epithelial cell types without either transitional forms between the epithelial and stromal components or differentiation into sarcomatous components. The results of this study lend particular support to the combination tumor hypothesis that a precursor (stem) cell gives rise both to epithelial and to mesenchymal components during the histogenesis of uterine carcinosarcoma, the epithelial component of which appears to be dominant, suggesting that the established cell lines derived from a common stem cell.     

Probability and strategy: an event-related potential study of processing syntactic anomalies

Syntactic ambiguities requiring additional processing usually elicit positive going waveforms with onset latencies between 300 and 600 ms in the event-related potential (ERP). It is still unclear to what extent these components can be viewed either (a) as language specific in nature or (b) as members of the domain-unspecific P300 family of components. The present study investigates this question by means of probability manipulations applied to German sentences with subject-object ambiguities. Non-preferred object-subject (OS) word order requires structural revisions whereas the initially preferred subject-object (SO) word order does not. In the present experiment, the proportions of OS and SO structures were varied across experimental blocks (i.e., .25/.75 vs. .75/.25). The data of 20 participants reveal that ERP components were predominantly influenced when the subjects were explicitly informed about the actual proportions before each single block. In this case an early frontal positive component at about 400 ms and a subsequent posterior positivity were elicited by rare sentence structures irrespective of word order, suggesting that sentence processing was under strategic control. Conversely, participants that were not informed about sentence proportions showed larger positivities to the unpreferred OS sentences. Probability manipulations did not affect this pattern significantly. The data suggest that positivities evoked by syntactic ambiguities respond differently to probability manipulations than the P300 component.     

Molecular dynamics simulations of the docking of substituted N5- deazapterins to dihydrofolate reductase

Orientations of the deazapterin ring and the conformational preferences of groups appended to the deazapterin ring in a set of 8-substituted deazapterin cations docked into the dihydrofolate reductase (DHFR) binding site have been investigated using a methodology based on the simulated annealing technique within molecular dynamics (MD) simulations. Of five possible binding pockets for the 8-substituents, identified from a preliminary manual docking study, one has been definitively eliminated after an analysis of MD trajectories, while another remains uncertain. Using a new method based on standard thermodynamic cycles and a linear approximation of polar and non-polar free energy contributions from MD averages, binding affinities of the different ligands in each binding site have been correlated with experimental dissociation constants. The study has provided insights into structure-activity relationships for use in the design of modified inhibitors of DHFR.