拉米夫定抗乙型肝炎病毒治疗中耐药突变的后续治疗

拉米夫定(lamivudine)抗乙型肝炎病毒治疗中耐药突变发生率高,文献报道在拉米夫定治疗1,2,3,4,5a时分别为14%,38%,49%,66%,69%.耐药突变可导致血清HBVDNA水平阳转或明显上升,肝功能严重受损,甚至病情恶化死亡.关于拉米夫定抗乙型肝炎病毒治疗中耐药突变的后续治疗目前国内外尚无统一用药方案,单药治疗(如:继续使用拉米夫定、阿德福韦、恩替卡韦)在临床使用中已经取得了一定疗效,联合抗病毒治疗和中医药治疗是今后研究的方向.     

Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype‐4 chronic hepatitis C patients

The therapeutic effect of pegylated interferon (peg‐IFN) alfa‐2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa‐2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa‐2a (160 μg) subcutaneous once weekly and oral weight‐based ribavirin (1000–1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P < 0.001; respectively]. Along the study, the observed adverse events were mild and similar across treatment groups. Addition of hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170–2178, 2016. © 2016 Wiley Periodicals, Inc.

     

Disrupted muscarinic M1 receptor signaling correlates with loss of protein kinase C activity and glutamatergic deficit in Alzheimer's disease

There are few studies on the clinical and neurochemical correlates of postsynaptic cholinergic dysfunction in Alzheimer's disease (AD). We have previously found that attenuation of guanine nucleotide-binding (G-) protein coupling to muscarinic M(1) receptors in the neocortex was associated with dementia severity. The present study aims to study whether this loss of M(1)/G-protein coupling is related to alterations in signaling kinases and NMDA receptors. Postmortem frontal cortices of 22 AD subjects and 12 elderly controls were obtained to measure M(1) receptors, M(1)/G-protein coupling, NMDA receptors as well as protein kinase C (PKC) and Src kinase activities. We found that the extent of M(1)/G-protein coupling loss was correlated with reductions in PKC activity and NMDA receptor density. In contrast, Src kinase activity was neither altered nor associated with M(1)/G-protein coupling. Given the well established roles of neuronal PKC signaling and NMDA receptor function in cognitive processes, our results lend further insight into the mechanisms by which postsynaptic cholinergic dysfunction may underlie the cognitive features of AD, and suggest alternative therapeutic targets to cholinergic replacement.     

Serum prolactin response to embryo transfer during human in vitro fertilization and embryo transfer

Serum prolactin (PRL) concentrations around the time of embryo transfer (ET) have not been studied, despite the fact that transient hyperprolactinemia regularly occurs in response to laparoscopy for oocyte recovery and ET itself may be stressful enough to induce a PRL rise. Hyperprolactinemia might compromise luteal support for implantation and contribute to the limited success of ET. We measured serum PRL concentrations in 10 normoprolactinemic women immediately before, during, and after ET and compared the PRL response around ET to that induced by laparoscopy as a measure of the competency of the stress-prolactin axis. Nine of ten patients demonstrated a significant PRL response to surgery. The mean (±SEM) intraoperative PRL concentration (124.0±19.6 ng/ml) was significantly higher than the preoperative level (12.3±2.4 ng/ml) (P<0.01). Three hours after surgery PRL levels had decreased (44.8±11.5 ng/ml) but remained above baseline. All subjects were normoprolactinemic 48 hr after laparoscopy. Serum PRL concentration did not change significantly in response to ET, with levels of 10.4±1.7, 12.4±1.1, and 10.6±1.8 ng/ml immediately before, during, and 3 hr after ET, respectively. While laparoscopy for in vitro fertilizationembryo transfer commonly induces hyperprolactinemia, the PRL rise is transient, with no carryover to the time of ET. Embryo transfer itself does not induce a significant PRL rise.     

Transvaginal and transabdominal ultrasound for monitoring of follicular development in an in vitro fertilization and embryo transfer program: Patient response

Summary Patients' response to daily ultrasound scanning by either a transvaginal or a transabdominal method for the purpose of monitoring the ovarian response to gonadotropin therapy in an in vitro fertilization and embryo transfer program has been evaluated. A questionnaire was used to determine various aspects of these two procedures, sources of discontent, and the patients' preference. The vast majority of patients reported less discomfort and generally preferred the transvaginal over the transabdominal scanning method. The transvaginal method is easy to perform, affords excellent visualization of the pelvic organs, and in addition, is clearly preferred by patients over the transabdominal technique. We recommend its use in patients monitored for IVF-ET and for a variety of other clinical conditions requiring detailed evaluation of the pelvic organs.     

Potential association between male infertility and occupational psychological stress

The purpose of this work was to investigate the influence of working conditions, occupational exposures to potential reproductive toxic agents, and psychological stress on male fertility. The study population consisted of 202 consecutive male patients attending a fertility clinic. Of those, 106 patients had attended the clinic because of a male infertility problem (case group), 66 patients had attended the clinic because of a female infertility problem (control group), and 30 patients had a combined infertility problem (male and female). Male infertility was associated with working in industry and construction as compared with other occupations (78.6% vs 58.3%, P = 0.044). Industry and construction workers were of lower educational level than the other workers (mean: 12.1 vs 13.4 years, P = 0.021). These patients also tended to smoke more than the other workers (OR = 2.53, 95% CI = 1.08 to 5.98), more often worked in shifts (OR = 3.12, 95% CI = 1.19 to 8.13), reported physical exertion in work (OR = 3.35, 95% CI = 1.44 to 7.80), and were more exposed to noise and welding (OR = 3.84, 95% CI = 1.63 to 9.14, OR = 4.40, 95% CI = 1.11 to 1.76, respectively). Male infertility (case group) was found to be statistically related to higher marks in all four measures of burnout as compared with the controls. The largest difference was obtained in the measure of cognitive weariness (mean: 2.9 vs 2.1, P < 0.001). In a multiple logistic regression analysis, industry and construction jobs (adjusted OR = 2.2, 95% CI 1.2 to 2.7) and cognitive weariness (adjusted OR = 1.8, 95% CI = 1.03 to 4.6) were found to be independent risk factors for male infertility problems. Male infertility was independently associated with industry and construction jobs as well as job burnout.     

Chronic disease prevalence in immigrants to Israel from the former USSR

The purpose of this study was to evaluate the prevalence of chronic health conditions in the Russian population who immigrated to Israel during 1989–1992. Interviewer-supported self-administered questionnaires were distributed to a 50% random sample of 1710 immigrants residing in the city of Nazareth-Ilit in Northern Israel. The final study group included 897 adults after a 3.5% of noncompliance. The study participants were asked to report all chronic diseases from a list of 11 disease states. The data were coupled with their demographic data and are presented as age/sex-specific prevalence rates. Self-reported disease prevalence rates among the Russian immigrants to Israel were found to be very high (62.2% of the males and 68.7% of the females reported a mean 3–3.5 diseases per person). These reported rates were significantly higher for immigrants from the European republics (67.1%) than for those from Asian republics (55.6%). The highest reported age-specific disease prevalence rates were for musculoskeletal diseases (389/1000), ischemic heart disease (340/1000), gastrointestinal diseases (269/1000), and hypertension (226/1000). A higher rate among females was found for almost all disease states. The prevalence rates reported by the Russian Jews in this study are much higher than commonly observed in Western countries. This is in accordance with a similar difference in reported mortality rates between Western countries and the former USSR. The etiologic explanation of this finding is yet to be studied. In addition, and in light of the mass immigration of Eastern European residents to the West it is of major importance for local health authorities to respond appropriately to the differences in health status of these immigrating populations.     

Short-term treatment of post-traumatic stress disorder with naltrexone: an open-label preliminary study

Eight patients (6 men and 2 women) with chronic post-traumatic stress disorder (PTSD) were treated with naltrexone 100-200 mg/day. Seven patients completed 2 weeks of treatment. A subtle and clinically insignificant improvement was noted in intrusive and hyperarousal symptoms (p < 0.05 for both), but not in avoidance symptoms. All patients demonstrated side effects which limited the targeted dose. It is suggested that the subtle positive effect of naltrexone and the hypersensitivity of these patients to its side effects do not encourage the use of naltrexone in the treatment of PTSD patients.