Modification and abolition of re-entry within the His-Purkinje system in man by diphenylhydantoin

The phenomenon of macrore-entry (Re) within the His-Purkinje system (HPS) was consistently observed in 10 of 19 patients during retrograde refractory period studies. Effects of intravenous infusion of diphenylhydantoin (DPH) on Re were studied in these 10 patients 10 minutes after completion of infusion (mean plasma level equal to 17.0 microgram/ml). Diphenylhydantoin modified determinants of Re in seven patients (group I) and abolished Re in the remaining three patients (group II). In group I, DPH shortened the critical V1 V2 from 310.0 +/- 30.5 to 292.9 +/- 25.6 msec (P less than 0.025) and critical V2 H2 intervals for Re from 201.4 +/- 18.4 to 185.0 +/- 13.8 msec (P greater than 0.05). In group II, DPH abolished Re in two of three patients by precluding attainment of critical V2 H2 intervals whereas Re was abolished in the remaining one patient despite attainment of critical V2 H2 intervals (vs control). For both groups, DPH significantly shortened functional and effective refractory periods of the HPS (P less than 0.001 and less than 0.01, respectively) without significantly affecting the effective refractory period of the ventricular muscle. Diphenylhydantoin either completely abolished or significantly shortened the retrograde gap zones in the HPS. It is concluded that diphenylhydantoin significantly shortens His-Purkinje system refractoriness, abolishing Re in the patients with higher degree of improvement in refractoriness.     

Serum and urinary zinc levels in urolithiasis

Zinc has an important place amongst inhibitors of crystallisation and crystal growth. These views are supported by in vivo and in vitro studies which suggest that the urinary zinc level is a significant factor in urolithiasis. Some recent studies have given contradictory results. Blood serum and urinary zinc levels were measured in 30 normal healthy controls and 42 stone forming patients (renal, ureteric and vesical). Statistically significant levels were found in all groups, varying according to the number of calculi. Increased urinary zinc levels and decreased serum zinc levels appear to be secondary to the process of stone formation. The role of zinc as an inhibitor of urolithiasis is questionable.     

Follow-up of asbestosis patients and predictors for radiographic progression

OBJECTIVE: We followed a group of 85 Finnish asbestosis patients radiographically for an average of 6.5 (range 2-10) years to examine the progression of the disease and to assess possible explanations for the progression. METHODS: The examinations included full-size chest radiographs and a blood specimen analysis. The radiographs were classified according to the 1980 International Labor Office (ILO) classification. Progression was accepted if the second or third radiography was estimated (in a side-by-side comparison) to have more profusion of small opacities qualitatively than the first, even if the radiographs were classified into the same profusion category. RESULTS: In all, 38% of the patients showed progression during the follow-up period. The average progression of small opacities ranged from ILO 1/1 to ILO 2/2 (0.4 minor ILO categories/year). The asbestosis was progressive more often among the sprayers than among the insulators and asbestos factory workers [cross-tabulation, odds ratio (OR) 5.0, 95% confidence interval (95% CI) 1.2-20]. In the logistic regression model the ILO classification category at the beginning of the follow-up (OR 1.54; 95% CI 0.96-2.47), the fibronectin (OR 1.01; 95% CI 1.00-1.01) and angiotensin-converting enzyme (ACE; OR 1.10; 95% CI 1.00-1.20) levels, and the erythrocyte sedimentation rate (ESR; OR 1.05; 95% CI 1.00-1.10) were statistically associated with the radiographic progression of small opacities. Abnormalities of the pleura were found to progress more often among the patients with progressive parenchymal opacities. CONCLUSION: For the progression of small-opacity profusion the significant predictors in the logistic regression model were the ILO profusion category at the beginning of the follow-up period, the fibronectin level, the ACE value, and the ESR. The model correctly classified 94% of the patients with progression and 65% of those without progression. The differences in the mean values recorded for the biomarkers between the progressors and nonprogressors, however, were small and may therefore not be of any importance to the clinician.     

Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment

BACKGROUND: Combined treatment of allograft recipients with anti-CD40 ligand and CTLA-4Ig (costimulation blockade) is a powerful promising albeit not consistently tolerizing therapy. It would be desirable to use an effective conventional immunosuppressive regimen in low doses or for a short course as an adjunct; however, cyclosporine treatment drastically blunts the ability of costimulation blockade to produce long-term engraftment. METHODS: Short courses of cyclosporine or rapamycin were compared as adjuncts to costimulation blockade in the murine BALB/c to C3H/He heterotopic cardiac allograft model. RESULTS: Although cyclosporine therapy blocked the capacity of costimulation blockade to produce permanent engraftment, combined rapamycin and costimulation blockade treatment produced permanent engraftment. CONCLUSION: A theoretical basis for the differing effects of cyclosporine and rapamycin upon the outcome of costimulation blockade is forwarded. Combined use of costimulation blockade and rapamycin may provide a means to bring costimulation blockade into the clinic.     

Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.