Clinical electrophysiologic effects of a single high oral dose of amiodarone

Summary— Several recent reports have described the antiarrhythmic effects of a single high oral dose of amiodarone but clinical electrophysiologic effects have not been reported. The present study was performed to assess electrophysiologic effects in 12 patients. After baseline electrophysiologic studies (EPS) patients were administered a single oral dose of 30 mg/kg of amiodarone. EPS was repeated 7.5 ± 0.5 hours later. Plasma levels of amiodarone and its metabolite desethylamiodarone were determined at the time of the second EPS. Holter monitoring was performed for 24 hours after amiodarone administration. Amiodarone significantly increased the following parameters: corrected QT interval (+4.5%), functional refractory period of the right atrium (+7%); AH interval (+12.3%), effective refractory period of the atrioventricular node (+18.5%), and cycle length of Wenckebach block (+8.4%). These effects were not correlated with plasma levels of amiodarone and desethylamiodarone. Holter monitoring detected no significant bradycardia or arrhythmia. These findings indicate that the effects of a single high oral dose of amiodarone are the same as those known to be induced by acute intravenous administration.     

Modified sperm stress test: a simple assay that predicts sperm-related abnormal in-vitro fertilization

Loss of sperm motility is associated with the process of sperm senescence and occurs at different rates within a given normal or abnormal sperm population. Reactive oxygen species attack cell membrane phospholipids, generating fatty acid peroxides and other degradation products, that also have deleterious effects on sperm motility and fertilizing ability. The objective of this investigation was to study a modification of the original sperm stress test (MOST), changing the culture medium to one offering transitional metals and shortening the total test time, to ascertain whether it can predict fertilization under these laboratory conditions. A total of 41 semen samples was obtained from patients undergoing in-vitro fertilization (IVF) at our institution. Semen samples were grouped into those producing total fertilization rates (FR) within normal limits (>50%) and those showing low total FR (<50%). The normal FR group had a significantly greater MOST mean value than the low FR group (0.71 versus 0.44). Furthermore, there was a statistically significant correlation between the MOST score and ungrouped fertilization rates (r = 0.53, P = 0.0004). Diagnostic statistics for MOST ratio values predicting <50% FR showed an optimal threshold of 0.39. Collectively, sensitivity, specificity, positive predictive value and negative predictive value have their largest values at this threshold. Taking into account the above mentioned threshold figures, there is a significant association between MOST and FR categories (P = 0.0009). In conclusion, MOST is a simple assay that has significant predictive value for sperm related IVF abnormalities.      

Methotrexate for the treatment of refractory Crohn's disease.

BACKGROUND: Previous studies suggested that methotrexate has beneficial effects in patients with Crohn's disease. We report our experience with this agent in patients with chronic active Crohn's disease who previously failed to improve with conventional treatment, including azathioprine in most cases. METHODS: Between June 1988 and June 1992, 39 patients with refractory Crohn's disease were treated with methotrexate. In patients with active disease, clinical remission was defined by a Harvey-Bradshaw index of less than 4. For patients also taking corticosteroids, the dates of remission and complete steroid withdrawal were recorded. For patients who achieved clinical remission, and those in clinical remission when methotrexate was started, the relapse rate on methotrexate therapy was noted. RESULTS: In the 37 patients with active disease at methotrexate initiation, the probability of remission was 72% at 3 months. The probability of remission and steroid withdrawal was 42% at 12 months. In patients on clinical remission, the probability of relapse on methotrexate was 58% at 12 months. Twenty-two patients experienced side-effects, but these only warranted methotrexate discontinuation in four cases. CONCLUSIONS: Methotrexate appears effective in most patients with refractory Crohn's disease and its short-term toxicity is acceptable, but the long-term benefit seems more limited.     

乙酰丹酚酸A对大鼠大脑中动脉血栓所致局部脑缺血性损伤的保护作用

乙酰丹酚酸A(ASAA)是丹参有效成分的衍生物。用三氯化铁局部涂抹损伤血管形成大鼠大脑中动脉血栓模型。以脑梗塞范围、行为障碍、脑组织病理改变为观察指标,研究ASAA对大脑中动脉血栓所致局部脑缺血的预防作用。结果表明,ASAA50及100 mg·kg^-1iv可显著降低大鼠脑梗塞范围,改善行为障碍。脑组织检查中,ASAA100 mg·kg^-1组动物大脑中动脉内血栓形成极少或未形成,脑组织缺血病变较轻。以上结果提示,ASAA可能通过抑制脑血栓形成,从而减轻血栓形成所致的局部脑缺血性损伤。     

Carcinogenesis induced by UVA (365-nm) radiation: the dose-time dependence of tumor formation in hairless mice

Although ultraviolet B (UVB wavelengths 280-315 nm) dominates the carcinogenic effect of sunlight, ultraviolet A (UVA 315-400 nm) is estimated to contribute 10-20% to the carcinogenic dose; a substantial background that is not affected by a depletion of the ozone layer. Furthermore, certain high-power modern tanning lamps emit mainly long wave UVA (UVA1; 340-400 nm). For a proper risk estimate of UVA exposure its carcinogenicity relative to that of UVB exposure needs to be determined more accurately. To this end we determined the dose-time relationship for skin tumor induction in hairless mice that were irradiated daily with custom-made Philips 365-nm sources. Irradiation of the group exposed to the highest of the four daily doses (430, 240, 140 and 75 kJ/m2) had to be discontinued because severe scratching set in after 3 months (no tumors). In the lower dose-groups the prevalence curves for skin carcinomas (percentage of tumor-bearing mice versus logarithm of time) ran virtually parallel, and were similar to those found with daily UVB exposure. However, the relationship between the daily dose (D) and the median tumor induction time (t50) appeared to differ: with UVB we found that t50 D(r) = constant, with r = 0.6, whereas with UVA1 we found r approximately 0.4. This would imply that 365-nm carcinogenesis shows less of a dose-dependency than UVB carcinogenesis, and that 365-nm radiation becomes more carcinogenic, relative to UVB, as the daily doses are lowered. This relative shift at low doses complicates extrapolation of UVB to UVA risks in humans. Based on the t50 from the lowest dose-group we found that the carcinogenicity at 365 nm (per J/m2) is 0.9 x 10(-4) times that at 293 nm, the wavelength of maximum carcinogenicity in hairless mice. This result for 365-nm carcinogenicity falls well within the margins of error of the wavelength dependency that was estimated earlier from experiments with broadband UV sources.      

Fluid pressure may cause periprosthetic osteolysis: Particles are not the only thing

Early prosthesis migration predicts late clinical failure, as also does the shape or position of, e.g., a femoral stem. These factors appear unrelated to wear particles. Thus, the initiation of the loosening process has other causes. After this process has started (i.e., the prosthesis migrates), particles may play a role, at least by inhibiting new bone formation at the membrane, but the hypothesis of pressure-induced bone resorption appears easier to support by animal experiments and accords with mechanical risk factors.     

Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG).

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information.