Mechanism of improvement in mitral regurgitation after cardiac resynchronization therapy.

AIMS: The aim of the current study was to evaluate the relationship between the presence of left ventricular (LV) dyssynchrony at baseline and acute vs. late improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Sixty eight patients consecutive (LV ejection fraction 23 +/- 8%) with at least moderate MR (>or=grade 2+) were included. Echocardiography was performed at baseline, 1 day after CRT initiation and at 6 months follow-up. Speckle tracking radial strain was used to assess LV dyssynchrony at baseline. The majority of patients improved in MR after CRT, with 43% improving immediately after CRT, and 20% improving late (after 6 months) after CRT. Early and late responders had similar extent of LV dyssynchrony (209 +/- 115 ms vs. 190 +/- 118 ms, P = NS); however, the site of latest activation in early responders was mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas the lateral wall was the latest activated segment in late responders. CONCLUSION: Current data suggest that the presence of baseline LV dyssynchrony is related to improvement in MR after CRT. LV dyssynchrony involving the posterior papillary muscle may lead to an immediate reduction in MR, whereas LV dyssynchrony in the lateral wall resulted in late response to CRT.     

The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity

The integrity of sperm DNA is crucial for the maintenance of genetic health. A major source of damage is reactive oxygen species (ROS) generation; therefore, antioxidants may afford protection to sperm DNA. The objectives of the study were, first, to measure the effects of antioxidant supplementation in vitro on endogenous DNA damage in spermatozoa using the single cell gel electrophoresis (comet) assay and, second, to assess the effect of antioxidant supplementation given prior to X-ray irradiation on induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll centrifugation in the presence of ascorbic acid (300, 600 microM), alpha tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5, 10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand breakage was measured using the comet assay. Sperm DNA was protected from DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60 microM) and urate (400 microM). These antioxidants provided protection from subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or ascorbate and alpha tocopherol together induced further DNA damage. Supplementation in vitro with the antioxidants ascorbate, urate and alpha tocopherol separately has beneficial effects for sperm DNA integrity.      

氯沙坦减少高血压患者终点事件的研究(LIFE STUDY)

标　　题　应用ＡＴⅡ受体拮抗剂抗高血压治疗作　　者　ＫｊｅｌｄｓｅｎＳＥ,ＯｍｖｉｋＰ.　　参考文献　ＴｉｄｓｓｋｒＮｏｒＬａｅｇｅｆｏｒｅｎ,1996,116:504～507研究疾病　高血压病。目　　的　评估氯沙坦对心血管死亡率及非致死性心肌梗死和非脑卒中发生率的影响,同时评估该药对充血性心力衰竭或心绞痛所致的总死亡率和住院率的影响,以及长期应用氯沙坦对发生新诊断糖尿病的影响。设　　计　随机、三盲、对照研究。病人资料　8300例年龄55～80岁、收缩压在160～200ｍｍＨｇ、舒张压在95～115ｍｍＨｇ的高血压患者,ＥＣＧ上有左室…     

Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect.

Recently, it has been postulated that the beneficial effect of intravenous immunoglobulins (IVIGs) in antibody-mediated autoimmune disorders is based on accelerated catabolism of autoantibodies. In the current study, in vivo experiments were performed with mice in which autoantibody production was mimicked by continuous infusion of monoclonal antibodies. In this model, a single dose of IVIG reduced the plasma concentrations of the infused immunoglobulin (Ig)G1 monoclonal antibody (mAb) by approximately 40% after 3 days, whereas the concentration of an IgA mAb was not affected. To extrapolate these findings to humans, a computational model for IgG clearance was established that accurately predicted the time course and magnitude of the decrease in IgG plasma levels observed in mice. Adapted for humans, this model predicted a gradually occurring decrease in autoantibody levels after IVIG administration (2 g/kg), with a maximum reduction of approximately 25% after 3 to 4 weeks and a continued decrease of several months. In conclusion, a single high dose of IVIG induces a relatively small but long-lasting reduction of autoantibody levels by accelerated IgG clearance. This mechanism has clinical relevance in the sense that it can fully explain, as the sole mechanism, the gradual decrease in autoantibody levels observed in several patient studies. However, in some clinical studies, larger or more rapid effects have been observed that cannot be explained by accelerated clearance. Hence, IVIG can also reduce autoantibody levels through mechanisms such as down-regulation of antibody production or neutralization by anti-idiotypic antibodies.     

An Animal Model for the Detection of Hypotensive Side Effects of Immunoglobulin Preparations

Intravenous administration of certain immunoglobulin preparations may cause severe adverse reactions, especially in immunodeficient patients. These reactions are generally assumed to be related to the anticomplementary activity of the preparations, caused by IgG aggregates. Because the exact mechanism of the adverse reaction is unknown, we investigated the reactions induced in anesthetized rats on rapid intravenous administration of different human immunoglobulin preparations. The most conspicuous observation was a severe, long-lasting hypotension, induced by standard immunoglobulin preparations (for intramuscular use), which appeared to be independent from the concomitant complement and neutrophil activation. The long-lasting hypotension was not related to the presence of prekallikrein activator, which induced a transient hypotensive reaction only after sensitizing the rats to bradykinin. The reactions appeared to be associated with IgG aggregates. It was found that certain aggregates induced mainly complement activation, whereas others had mainly a hypotensive effect or no effect at all. It was concluded that the rat model provides a sensitive and reproducible test system for vasoactive properties of immunoglobulin preparations for intravenous administration that cannot be predicted from in vitro measurements, such as anticomplementary activity, aggregate content or prekallikrein activator activity. It is suggested that the test may also be used for other plasma products for intravenous administration.     

Interobserver variation in the interpretation of abdominal radiographs

A total of 140 sets of abdominal radiographs were reviewed independently by four qualified diagnostic radiologists. The degree of interobserver agreement was determined by calculating kappa values for 19 commonly used radiographic signs and diagnoses. There was fair to excellent interobserver agreement for 11 signs and diagnoses and poor agreement for the remaining eight. The signs and diagnoses for which agreement is poor cannot be considered reliable and include particularly large bowel obstruction and nonspecific gas pattern.     

Prolonged vascular retention of a hemoglobin solution modified by cross-linking with 2-nor-2-formylpyridoxal 5'-phosphate

The usefulness of hemoglobin solutions as plasma expanders with oxygen-carrying capacity is limited by a high oxygen affinity and a rapid clearance from the circulation. A large amount of the hemoglobin is cleared by the kidneys, because the hemoglobin can pass the glomeruli after dissociation into dimers. This dissociation can be prevented by cross-linking the beta chains with 2-nor-2-formylpyridoxal 5'-phosphate (NFPLP), a modification that also diminishes the oxygen affinity. In the present study, the vascular retention of modified hemoglobin (HbNFPLP) compared with unmodified hemoglobin (Hb) was investigated in rats and rabbits by replacing half the blood volume with a mixture of Hb and HbNFPLP (7 gm/100 ml). The amount of free hemoglobin in the circulation was determined from the plasma concentration, corrected for the decrease in plasma volume. The decrease in plasma volume was calculated from the increase in hematocrit (in the rats, 30% to 40% in 3 hours). The ratio Hb/HbNFPLP was determined by high-performance anion-exchange chromatography. The half-disappearance times for HbNFPLP and Hb were found to be 3 hours and 1 hour in rats and 7 hours and 2.5 hours in rabbits, respectively. In the rats, one third of the unmodified Hb was found in the urine 5 hours after the exchange, against only 5% of the HbNFPLP. In rats without kidneys, the ratio of Hb/HbNFPLP in the circulation remained constant. The results demonstrate that intramolecular cross-linking of hemoglobin with NFPLP prevents excretion by the kidneys, but does not influence other clearance mechanisms.