Upper gastrointestinal bleeding in children with haemophilia: a clinical significance of Helicobacter pylori infection

Summary. For patients with haemophilia, gastrointestinal (GI) bleeding is a life‐threatening complication and can be caused by the Helicobacter pylori infection. Among children with haemophilia who had visited with GI bleeding, the prevalence of H. pylori infection and the recurrence rate after H. pylori eradication was investigated. Seven children with haemophilia A with hematemesis (age: 5.3–17.0 years) were evaluated for the causes of GI bleeding and the detection of H. pylori. Gastroendoscopy was done to find the bleeding focus and for further evaluation including rapid urease test and mucosal biopsy. Four patients had dyspepsia and abdominal pain for several weeks or months prior to hematemesis. Three patients did not show any symptoms of bleeding. From gastroendoscopy, four patients were diagnosed as duodenal ulcer, one as H. pylori associated chronic gastritis and one as haemorrhagic gastritis. One patient showing a normal finding was diagnosed with adenoid haemorrhage after nasopharyngoscopy. Helicobacter pylori infection was found in four of six patients with GI bleeding (3, duodenal ulcer; 1, H. pylori associated chronic gastritis). The patients with H. pylori infection had an eradication treatment of triple therapy and no recurrence happened. In children with haemophilia, H. pylori should also be considered as an important cause of GI bleeding. The recurrence of the infection and GI bleeding can be prevented with eradication of H. pylori. Screening test for H. pylori would be needed in children with haemophilia in endemic area.     

Calpain‐dependent cleavage of SHP‐1 and SHP‐2 is involved in the dephosphorylation of Jurkat T cells induced by Entamoeba histolytica

Host cell death induced by Entamoeba histolytica is an important mechanism for both host defence and microbial immune evasion during human amoebiasis. However, the signalling pathways underlying cell death induced by E. histolytica are not fully understood. This study investigated the involvement of the protein tyrosine phosphatases (PTPs) SHP‐1 and SHP‐2 in the dephosphorylation associated with E. histolytica‐induced host cell death. Incubation with E. histolytica resulted in a marked decrease in protein tyrosine phosphorylation levels and degradation of SHP‐1 or SHP‐2 in Jurkat cells. Pre‐treatment of cells with a calpain inhibitor, calpeptin, impeded the amoeba‐induced dephosporylation and cleavage of SHP‐1 or SHP‐2. Additionally, inhibition of PTPs with phenylarsine oxide (PAO) attenuated Entamoeba‐induced dephosphorylation and DNA fragmentation in Jurkat T cells. These results suggest that calpain‐dependent cleavage of SHP‐1 and SHP‐2 may contribute to protein tyrosine dephosphorylation in Jurkat T cell death induced by E. histolytica.     

Reactive oxygen species in rats with chronic post-ischemia pain

Background: An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw.
Methods: Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague–Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N -nitro- l -arginine methyl ester ( l -NAME, 10 mg/kg), or SOD (4000 U/kg)+ l -NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats.
Results: Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and l -NAME, which were used to investigate the roles of superoxide (O_2 ˙⁻) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks.
Conclusions: Our findings suggest that O_2 ˙⁻ and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects.     

Association between central venous pressure and blood loss during hepatic resection in 984 living donors

Background: Although low central venous pressure (CVP) anesthesia has been used to minimize blood loss during hepatectomy, the efficacy of this technique remains controversial. We therefore assessed the association between blood loss and CVP during hepatic resection, and examined significant determinants associated with intraoperative hemorrhage during hepatectomy in living donors.
Methods: Between April 2004 and April 2008, 984 living donors who underwent a hepatic resection were assessed retrospectively. Univariate and multivariate analyses were performed to explore the relationships between intraoperative blood loss and several variables including CVP.
Results: The mean intraoperative blood loss was 691.3 ± 365.5 ml. Only four donors required packed red blood cell transfusions (mean, 1.5 U). The mean duration of hepatic resection was 92.1 ± 26.3 min. The mean, maximum, and minimum values of CVP measured during hepatectomy were 4.6 ± 1.7, 5.3 ± 1.8, and 4.0 ± 1.8 mmHg, respectively, and were not significantly correlated with intraoperative blood loss. On multivariate analysis, predictors of hemorrhage were liver fatty change, gender, and body weight, but none of the mean CVP, surgeons, anesthesiologists, anesthesia duration, resected liver volume, hepatectomy type, systolic blood pressure, heart rate, or body temperature were significant.
Conclusions: CVP during hepatic resection was not associated with intraoperative blood loss in living liver donors, suggesting that CVP may not be an important factor in predicting blood loss during hepatectomy in healthy subjects.     

Anaesthetic requirement and stress hormone responses in patients undergoing lumbar spine surgery: anterior vs. posterior approach

Background: The intensity of nociceptive stimuli reflects the severity of tissue injury. The anaesthetic requirement and stress hormonal responses were determined to learn whether they differ according to different surgical approaches (anterior vs. posterior) during the spinal surgery.
Methods: Patients undergoing lumbar spine surgery without neurological deficits were divided into two groups: one having posterior ( n =13) and the other having anterior fusion ( n =13). The end-tidal sevoflurane concentrations (ET_SEVO) required to maintain the bispectral index score at 40–50 were determined. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum osmolality and plasma concentrations of catecholamines, cortisol and vasopressin (AVP) were measured.
Results: There were no differences in MAP, HR, CVP and serum osmolality between the groups. ET_SEVO was higher in the anterior than in the posterior group ( P <0.05). The plasma concentrations of norepinephrine and cortisol increased in both groups during the surgery, whereas those of epinephrine remained unchanged. AVP concentrations increased during the surgery in the anterior group, and remained unaltered in the posterior group. The anterior group needed more analgesics ( P <0.01) during the first 1 h after the operation.
Conclusions: The anterior approach required a deeper level of anaesthesia while undergoing spinal surgery and more use of post-operative analgesics than the posterior approach. It was also associated with a more pronounced AVP release during the surgery.     

Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers

Park SW, Chung NG, Hur SY, Kim HS, Yoo NJ, Lee SH. Mutational analysis of hypoxia‐related genes HIF1α and CUL2 in common human cancers. APMIS 2009; 117: 880–5. Hypoxia is a general feature of solid cancer tissues. Hypoxia upregulates hypoxia‐inducible factor 1α (HIF1α) that transactivates downstream genes and contributes to cancer pathogenesis. HIF1α is upregulated not only by hypoxia but also by genetic alterations in HIF1α‐related genes, including VHL. Cullin 2 (CUL2) interacts with the trimeric VHL‐elongin B‐elongin C complex and plays an essential role in the ubiquitinated degradation of HIF1α. The aim of this study was to explore whether HIF1α and CUL2 genes are somatically mutated, and contribute to HIF1α activation in common human cancers. For this, we have analyzed the coding region of oxygen‐dependent degradation domain of HIF1α in 47 colon, 47 gastric, 47 breast, 47 lung, and 47 hepatocellular carcinomas, and 47 acute leukemias by a single‐strand conformation polymorphism assay. In addition, we analyzed mononucleotide repeat sequences (A8) in CUL2 in 55 colorectal and 45 gastric carcinomas with microsatellite instability (MSI). We found one HIF1α mutation (p.Ala593Pro) in the hepatocellular carcinomas (1/47; 2.1%), but none in other cancers. We found two CUL2 frameshift mutations in colon cancers (p.Asn292MetfsX20), which were exclusively detected in high MSI cancers (4.9%; 2/41). Our data indicate that somatic mutation of HIF1α is rare in common cancers, and somatic mutation of CUL2 occurs in a fraction of colorectal cancers (colorectal cancers with high MSI). The data suggest that neither HIF1α nor CUL2 mutation may play a central role in HIF1α activation in gastric, colorectal, breast, lung and hepatocellular carcinomas, and acute leukemias.     

Persistence of heroin use despite methadone treatment: Poor coping self‐efficacy predicts continued heroin use

Aim. To evaluate the association between coping self‐efficacy and persistent use of heroin by patients enrolled in a methadone treatment program. Design and Methods. Cross‐sectional survey. One hundred and ninety‐one patients attending outpatient methadone clinics in South‐East England, United Kingdom. Validated questionnaires were used to assess drug use (Maudsley Addiction Profile), alcohol use (Alcohol Use Disorders Identification Test), mental health (Hospital Anxiety and Depression Scale) and coping self‐efficacy (brief 8‐item Drug Taking Confidence Questionnaire). Results. Half of the participants (95/191) reported heroin use in the preceding 14‐day period. Heroin use during methadone treatment was associated with financial problems (P = 0.008), spending time with other drug users (P < 0.001), cocaine use (P = 0.002), low mood (P = 0.002) and dissatisfaction with the daily methadone dose (P = 0.014). Compared with ‘Heroin‐abstinent’ patients, the ‘Heroin’ group reported significantly lower mean coping self‐efficacy scores (t = 9.8, d.f. = 182, P < 0.001, effect size 1.17). After correcting for the effects of co‐variants in a logistic regression model, the main determinants of persistent heroin use were ‘coping self‐efficacy’[B ?0.05; standard error (SE) 0.008; Wald 36.6; odds ratio (OR) 0.95, 95% confidence interval (CI) 0.94, 0.97; P < 0.001] and ‘dissatisfaction with methadone dose’ (B 0.93; SE 0.46; Wald 4.1; OR 2.5, 95% CI 1.03, 6.25; P = 0.042). Satisfaction with methadone dose showed no association with self‐efficacy. Discussion and Conclusions. While heroin use during methadone treatment can partly be explained by inadequate dosing, our data suggest a more complex picture with significant contribution from poor coping self‐efficacy. Efforts aimed at enhancing and maintaining the patients' self‐efficacy and social skills are likely to improve heroin and other drug use outcomes with added benefits for treatment completion rates and the throughput of methadone programs.[Senbanjo R, Wolff K, Marshall EJ, Strang J. Persistence of heroin use despite methadone treatment: Poor coping self‐efficacy predicts continued heroin use. Drug Alcohol Rev 2009]     

Control of Palmar Hyperhidrosis with a New "Dry-Type" Iontophoretic Device

BACKGROUND: Palmar hyperhidrosis is characterized by excessive sweating on the palm, and among the various treatment modalities, tap water iontophoresis has been widely used. OBJECTIVE: The objective of this study was to assess the effect of a new "dry-type" iontophoretic device that was locally manufactured and did not use tap water to control sweating. METHODS: Ten subjects with palmar hyperhidrosis were enrolled in this study. To be treated the patients were instructed that they only have to grasp the device. Only one palm was treated for 2 weeks, and then the treatment was discontinued the following next 2 weeks. The other palm was not treated as a control. At the end of second week, biopsy specimens were obtained from untreated and treated palm, respectively, and examined histologically. RESULTS: Nine of 10 patients were satisfied with this therapy reducing their sweat outputs from 33% to 51% of baseline at the end of 2 weeks' treatment, and after 2 weeks of discontinuation of treatment sweat productions returned to near baseline. The pathologic examinations showed some occlusions and destruction of intraepithelial eccrine ducts only in the treated palm. CONCLUSION: We suggest that dry-type iontophoresis could reduce palmar sweating more conveniently than other conventional methods.     

某农村地区高血压家族聚集性和遗传度的研究

目的探讨高血压家族聚集性及遗传度。方法采用遗传流行病学方法,对718名（286名先证者和432名对照）家系进行了家族聚集性、遗传方式及遗传度分析。结果先证者一级亲属高血压患病率为2.68%,与对照组的1.87%相比差异有显著性;2项分布显示,高血压家族中实际发病数超过其2项分布的理论概率范围,即高血压分布呈明显家族聚集现象;高血压的遗传度为14.31%（男5.04%,女22.44%）。结论遗传因素在韩国人高血压的发病中起一定的作用,但环境因素的作用可能比遗传因素更为重要。     

补肾中药对骨质疏松症大鼠下丘脑BMP-4、Smad6 mRNA及蛋白表达的影响

目的探索肾虚骨质疏松症的病理机制,研究补肾中药对肾虚骨质疏松大鼠防治作用的机理。方法实验采用去双侧卵巢的方法,建立肾虚骨质疏松症模型。补肾中药复方（高、中、低）剂量对实验大鼠治疗12周,以骨疏康颗粒、盖天力牡蛎钙作为阳性对照药,并设正常对照组和模型空白组。用RT-PCR法、Western印迹法检测肾虚骨质疏松症大鼠下丘脑组织中BMP-4、Smad6 mRNA和蛋白表达。结果①与正常组比较,模型空白组大鼠下丘脑组织中的BMP-4 mRNA和蛋白表达水平明显增强;Smad6 mRNA和蛋白表达水平明显降低。②与模型空白组比较,补肾中药组对模型大鼠下丘脑组织中的BMP-4 mRNA和蛋白表达明显降低;而Smad6 mRNA和蛋白表达明显增强。结论肾虚骨质疏松症的病理机制为肾精不足,骨髓、脑髓失养,表现在下丘脑-垂体-靶腺轴的调控失常,包括下丘脑组织的细胞因子及其信号传导通路的异常。