A new strategy of delayed long-term prophylaxis could prevent cytomegalovirus disease in (D+/R−) solid organ transplant recipients

Abstract:  Long-term prophylaxis against cytomegalovirus (CMV) started immediately after transplantation in (D+/R−) poses a higher risk of late-onset CMV disease. Delayed CMV prophylaxis could allow a transitory exposure of the immune system to CMV, which would let the immune system mount an adequate CMV-specific cytotoxic response in (D+/R−) patients and confer protection against CMV disease. We included all (D+/R−) solid organ transplant recipients (SOT) performed at our institution (January 3/October 6) who received CMV prophylaxis (mainly with oral valganciclovir) during 100 d. In the first period (until December 4), prophylaxis was initiated immediately after transplantation (conventional prophylaxis: CP). Since January 5, it was initiated after 14 d (delayed prophylaxis: DP). Incidence and severity of CMV disease was compared between both groups. A total of 44 SOT recipients were included (CP: 26 and DP: 18). CMV disease was diagnosed in eight patients (18%), seven of 26 (27%) in the CP group, and one of 18 (5.5%) in the DP group (p = 0.07). CMV colitis was reported in five of 26 patients in the CP group (19%), whereas there were no cases of visceral CMV disease in the DP group (p = 0.048). A 14-d delay in the beginning of long-term prophylaxis against CMV in (D+/R−) is safe and could prevent the onset of late-CMV disease.     

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

济川煎加味治疗老年糖尿病合并便秘24例

便秘是老年糖尿病患者的常见合并症之一.笔者自2006年6月～2007年6月以济川煎为基础方加味治疗老年糖尿病患者合并便秘24例,现报道如下. 　　……     

In vivo Regulation of Prolactin Gene Expression in the Male Rat: Role of Sex Steroids and Dopamine

The influence of sex steroids and the dopaminergic system on the in vivo modulation of prolactin (PRL) mRNA levels was investigated by quantitative in situ hybridization in the male rat anterior pituitary gland. In situ hybridization was performed using a [³⁵S]-labeled cDNA probe encoding PRL. Orchiectomy performed 14 days earlier did not modify PRL mRNA levels. In orchiectomized rats treatment with the dopaminergic agonist bromocriptine for 14 days decreased PRL mRNA levels by 30%, while in intact animals the same treatment did not induce any changes in PRL mRNA levels. Administration of the dopamine D₂ receptor antagonist haloperidol in both intact and orchiectomized rats induced a 4-fold increase in mRNA levels. Administration of dihydrotestosterone to orchiectomized animals which had been treated or not with haloperidol or bromocriptine did not modify PRL mRNA levels. In orchiectomized animals administration of 17ß-estradiol (0.25 μg twice daily) for 14 days caused a 4-fold increase in amounts of PRL mRNA. Administration of bromocriptine to 17ß-estradiol-treated animals induced a 15% decrease of PRL mRNA levels compared to those obtained by 17ß-estradiol administered alone. The concomitant administration of 17ß-estradiol and haloperidol resulted in a 50% increase in PRL mRNA levels compared to those measured in animals treated with haloperidol alone. The present results clearly demonstrate that in vivo estrogen as well as dopamine-mediated mechanisms play a regulatory role in PRL mRNA levels in the male rat.     

Liver and lung resection for colorectal metastasis

Aim: To examine the survival benefit of liver and lung resection for colorectal metastasis and the potential prognostic factors that affect patient survival. Methods: All patients who had resection of lung or liver metastasis for colorectal metastasis in Queen Elizabeth Hospital, Hong Kong from 1995 to 2004 were retrospectively reviewed. The overall and disease‐free survival was analysed, in particularly between liver and lung metastasis. All factors that may have affected the survival were entered into Cox's proportional hazards regression model to identify significant variables associated with survival. Results: At 5 years, the overall survival of patients who had resection of lung and liver metastasis was 44% and 38%, respectively; the disease‐free survival was 26% and 24%, respectively. Overall and disease‐free survival of patients with resection of lung metastasis was comparable to those with resection of liver metastasis. The differentiations of primary tumour and time to metastasis were shown to be significant prognostic factors influencing overall survival. Those patients with systemic chemotherapy after resection of colorectal metastasis demonstrated a significantly higher probability of overall survival. Conclusion: Resection of lung and liver metastases from colorectal origin was safe and both procedures improved survival. The use of chemotherapy after resection of metastasis significantly improved the overall survival.     

Chemical warfare agents

The first 150 words of the full text of this article appear below. Key points

• Chemical personal protective equipment must be wornwhen in contact with contaminated casualties.
• Recognizing theclinical features of chemical warfare agent poisoning allowssupportive treatment and appropriate antidotes to be promptlyadministered.
• The mnemonic DUMBELS describes the muscarinicfeatures of the nerve agent poisoning toxidrome.
• There areeffective antidotes for poisoning with nerve agents, blood agents(metabolic poisons), botulinum toxin and kolokol-1.
• There areno specific antidotes for blistering agents (vesicants) andchoking agents.

  Chemical warfare (CW) agents are chemical substances that havea direct toxic effect on plants, animals and humans. Classifiedaccording to their physiological effects, agents effective againsthumans include nerve agents, blistering agents (vesicants),blood agents, choking agents and toxins. Incapacitating, vomiting,psychoactive and riot control agents (e.g. CS gas) also exist.¹ All personnel in contact with contaminated casualties must wearthe appropriate level of chemical personal protective equipment(CPPE) until adequate decontamination is . . . [Full Text of this Article]