Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Coccygectomy has a favorable effect on the intensity, manifestation, and characteristics of pain caused by coccygodynia: a retrospective evaluation of 34 patients followed for 3–18 years

Background  Coccygodynia can cause severe pain and disability in patients. There are contradictions in the literature regarding the final results of coccygectomy for coccygodynia. We evaluated the long-term effects of coccygectomy on the intensity, characteristics, and manifestation of pain caused by coccygodynia to determine the adequacy of operation among treatment modalities. Materials and methods  Thirty-four patients with coccygodynia were treated by coccygectomy. In 22 cases, trauma, and in one case childbirth was the cause. 11 cases were regarded as idiopathic. The intensity, characteristics of pain, and the most painful activities were evaluated at an average of 7.6 (3–18) years of follow-up time. Results  Before the operation, all 34 patients had pain while sitting, moreover, 26 of them had pain during standing, walking, at night or a combination of these. 21 patients had intolerable or very intensive, mainly acute, sharp or burning pain. 11 patients had dyschesia, 2 had dysuria and 6 had dyspareunia. At follow-up, 7 patients were completely free of pain, 15 others had moderate, 11 medium, and only one patient had severe, but none had intolerable pain. Only seven patients had acute, sharp or burning pain postoperatively. The decrease of average pain score from 8.0 to 3.2 was significant (P < 10⁻¹²). The number of the patients with dyschesia and dyspareunia decreased from 11 to 7 and from 6 to 3, respectively. Two patients had dysuria, but their complaints did not change after the operation. One of the two patients who needed reoperation had an excellent final result, while the other remained unchanged. 12 and 16 patients (together 82%) regarded the final result of the operation excellent and good, respectively. The condition of five others did not change, while one became worse. The patients with younger age, smaller body mass index, and less co-morbidities had better final result. There were no serious complications. Conclusion  Coccygectomy for coccygodynia is a safe method to decrease the intensity of pain and other complaints of the patients. The operation can be the choice of treatment if conservative measures fail.     

Intracarotid histamine administration results in dose-dependent vasogenic brain oedema formation in new-born pigs

Inflammation Research -     

微血管密度和p16基因表达对判定肾癌生物学行为的意义

目的 :探讨肿瘤内的微血管密度 (IMD)和 p1 6基因表达与肾细胞癌 (RCC)生物学行为的关系。 方法 :采用免疫组织化学方法 ,对 76例RCC患者的根治性肾切除标本 ,检测第Ⅷ因子相关抗原和 p1 6基因表达 ,分析IMD、p1 6基因表达与RCC分期、分级及预后的相关性。 结果 :IMD随临床分期升高而增加 (P <0 .0 5 ) ,而与分级无明显相关性 (P >0 .0 5 ) ,随访 5年内死亡者IMD明显升高 (P <0 .0 1 ) ;癌旁组织中 p1 6阳性率 (75 .0 % )显著高于RCC组织 (4 8.7% ) ,p1 6阳性表达随临床分期、病理分级升高而降低 (P <0 .0 5 ) ,而与IMD呈负相关性。结论 :IMD是预测RCC恶性行为的一个有用指标 ,IMD和p1 6基因表达可为RCC的疗效和预后判定提供重要的资料。     

Sinoatrial Node Electrogram Studies in Patients with Sick Sinus Syndrome

Sinoatrial node electrogram (SNE) was recorded successfully in recent years, using transvenous electrode catheter. Via SNE and intratrialelectrogram (IEG), one could measure sinoatrial conduction time(SACT) directly, observe sinoatrial node (SN) potential changes in cadiac cycles, diagnose some sinus arrhythmias which couldn't be confirmed by surface ECG. All these could offer accurate evidence for differential diagnosis of sick sinus syndrome (SSS). The authors recommend a modified method for the location of the electrode catheter, by which one can increase success rate of obtaining stable SNE. Using this method, the authors recorded SNE in 10 cases with SSS successfully.     

Intraperitoneal injection of cholecystokinin elicits sleep in rabbits

Cholecystokinin (CCK) reduces food intake and promotes non-rapid-eye-movement sleep (NREMS) in rats. The purpose of present experiments was to determine if CCK is somnogenic in rabbits; another species in which CCK suppresses feeding. White New Zealand rabbits were treated intracerebroventricularly (ICV; 0.05, 0.5 and 2 μg) or intraperitoneally (IP; 2.5, 10 and 40 μg/kg) with CCK or saline, and sleep-wake activity and brain temperature (T_br) were recorded for 6 h. Injections of 10 and 40 μg/kg CCK IP elicited a decrease in wakefulness and an increase in NREMS during the first hour postinjection. The hypnogenic effects were accompanied by a decrease in T_br. After the IP injection of a lower dose (2.5 μg/kg) a slight, nonsignificant increase in NREMS during the first hour postinjection was followed by a decrease in NREMS. ICV injections of CCK had relatively small inhibitory effects on sleep. We conclude that circulating, hormone CCK might be a hypnogenic signal with a peripheral site of action.     

Inhibition of tumor necrosis factor in the brain suppresses rabbit sleep

Tumor necrosis factor (TNF) is a cytokine that possesses many biological activities, including enhancement of non-rapid-eye-movement sleep (NREMS). The role of endogenous TNF in the regulation of spontaneous sleep is unknown. If TNF is involved in sleep regulation, then reduction of endogenous TNF should suppress spontaneous sleep. A soluble TNF-binding protein I (TNF-BP I) and a synthetic fragment of TNF-BP I, TNF-R-(159–178), that contains the biologically active region of TNF-BP I, were used. These substances bind TNF and possess TNF-inhibitory activity; their effects on rabbit sleep after intracerebroventricular injection were determined across a 6-h recording period. Two doses of TNF-BP I (0.05 g and 0.5 g) were administered; the higher dose of TNF-BP I significantly decreased NREMS. Four doses of TNF-R-(159–178) (0.25 g, 2.5 g, 25 g and 50 g) were used. The 25 g and 50 g doses significantly suppressed NREMS. The highest dose (50 g) also decreased REM sleep. These results are consistent with the hypothesis that endogenous brain TNF is involved in the regulation of normal sleep.     

Occurrence of hlyA and sheA genes in extraintestinal Escherichia coli strains

The association of a hemolytic phenotype with the carriage of the alpha-hemolysin gene (hlyA) and/or the silent hemolysin gene (sheA or clyA) among 540 extraintestinal clinical isolates of Escherichia coli and 110 fecal isolates from healthy individuals was investigated. Though HlyA is an important virulence factor in extraintestinal E. coli infection, the role of SheA is not completely clarified. Two hemolytic sheA+ E. coli strains that lacked hlyA and possessed no other hemolysin genes were identified. No hlyA+ sheA+ strains were identified, suggesting that there is possible incompatibility between hlyA and sheA in the chromosome of E. coli.     

N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine increases the permeability of primary mouse cerebral endothelial cell monolayers

Inflammation Research -     

Ribosomal DNA internal transcribed spacer sequences do not support the species status of Ampelomyces quisqualis, a hyperparasite of powdery mildew fungi

Phylogenetic relationships among Ampelomyces isolates, pycnidial hyperparasites and biological control agents of powdery mildews, were inferred from internal transcribed spacer (ITS) sequences of the ribosomal DNA (rDNA). Currently, these hyperparasites are considered to be a single species, A. quisqualis, despite observed morphological and cultural differences. Ten Ampelomyces isolates, representing seven previously defined ITS RFLP groups, were sequenced and analyzed. Sequence-divergence values among isolates belonging to different RFLP groups ranged from 4.3 to 22.4%, suggesting that these isolates may represent different taxa. When Ampelomyces ITS sequences were analyzed by cladistic methods with the sequences of other ascomycetous fungi, they formed two lineages in the Dothideales. Slow-growing Ampelomyces isolates formed a clade with Leptosphaeria microscopica and L. nodorum, whereas fast-growing Ampelomyces isolates formed a clade with Epicoccum nigrum. Sequence-divergence values between these two clades ranged from 17.3 to 22.4%, suggesting that the taxa in the two clades are not closely related and possibly not congeneric. The data presented here indicate that the identification of `A. quisqualis' isolates used in biological control experiments should be re-evaluated. Received: 10 March 1997 / Accepted: 13 February 1998