Aberrant expression of the polarity complex atypical PKC and non-muscle myosin IIA in active and inactive inflammatory bowel disease

Epithelial barrier function is contingent on appropriate polarization of key protein components. Work in intestinal epithelial cell cultures and animal models of bowel inflammation suggested that atypical PKC (aPKC), the kinase component of the Par3–Par6 polarity complex, is downregulated by pro-inflammatory signaling. Data from other laboratories showed the participation of myosin light chain kinase in intestinal inflammation, but there is paucity of evidence for assembly of its major target, non-muscle myosin II, in inflammatory bowel disease (IBD). In addition, we showed before that non-muscle myosin IIA (nmMyoIIA) is upregulated in intestinal inflammation in mice and TNFα-treated Caco-2 cells. Thus far, it is unknown if a similar phenomena occur in patients with IBD. Moreover, it is unclear whether aPKC downregulation is directly correlated with local mucosal inflammation or occurs in uninvolved areas. Frozen sections from colonoscopy material were stained for immunofluorescence with extensively validated specific antibodies against phosphorylated aPKC turn motif (active form) and nmMyoIIA. Inflammation was scored for the local area from where the material was obtained. We found a significant negative correlation between the expression of active aPKC and local inflammation, and a significant increase in the apical expression of nmMyoIIA in surface colon epithelia in inflamed areas, but not in non-inflamed mucosa even in the same patients. Changes in aPKC and nmMyoIIA expression are likely to participate in the pathogenesis of epithelial barrier function in response to local pro-inflammatory signals. These results provide a rationale for pursuing mechanistic studies on the regulation of these proteins.     

Intensive treatment models and coercion

Little evidence exists concerning the optimal treatment for patients with first-episode schizophrenia-spectrum disorders and the effect on traditional outcomes. The aim was to investigate whether optimal treatment models have an effect on the level of use of coercion and on traditional outcomes. Hospital-based Rehabilitation, an intensified inpatient treatment model, Integrated Treatment, an intensified model of Assertive Community Treatment, and standard treatment were compared for patients with first-episode schizophrenia-spectrum disorders. Ninety-four patients with first-episode schizophrenia-spectrum disorders estimated to benefit from long-term hospitalization were included consecutively from the Copenhagen OPUS-trial and randomized to the three treatment models. At 1-year follow-up, Hospital-based Rehabilitation and Integrated Treatment had better scores on symptoms in the negative dimension and on client satisfaction. Integrated Treatment had fewer bed-days, more patients living in non-supervised accommodation, and better score on quality of life. No differences were found as to the use of coercion. This study adds to the evidence that intensified treatment models are superior to standard treatment. A higher number of bed-days in Hospital-based Rehabilitation did not influence the effect on the outcomes measured.     

BMP signaling through BMPRIA in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier

Bone morphogenetic protein (BMP) signaling is involved in differentiation of neural precursor cells into astrocytes, but its contribution to angiogenesis is not well characterized. This study examines the role of BMP signaling through BMP type IA receptor (BMPRIA) in early neural development using a conditional knockout mouse model, in which Bmpr1a is selectively disrupted in telencephalic neural stem cells. The conditional mutant mice show a significant increase in the number of cerebral blood vessels and the level of vascular endothelial growth factor (VEGF) is significantly upregulated in the mutant astrocytes. The mutant mice also show leakage of immunoglobulin around cerebral microvessels in neonatal mice, suggesting a defect in formation of the blood–brain-barrier. In addition, astrocytic endfeet fail to encircle cortical blood vessels in the mutant mice. These results suggest that BMPRIA signaling in astrocytes regulates the expression of VEGF for proper cerebrovascular angiogenesis and has a role on in the formation of the blood–brain-barrier.     

A study of prophylactic use of 15-methyl prostalglandin F2alpha in the active management of third stage of labour

To compare active management of third stage of labour with 15-methyl prostaglandin F2alpha (PGF2alpha) and conventional management with methylergometrine as prophylaxis for postpartum hemorrhage, a randomised comparative study was carried out at Calcutta National Medical College and Hospital, Kolkata on 100 women. They were randomly allotted to one of the two groups. Group A included 50 women who received 15-methyl PGF2alpha (125 microg) intramusculary at the time of delivery of the anterior shoulder and group B included 50 women who underwent conventional management of the third stage of labour where methylergometrine 0.2 mg was given after delivery of placenta. Main outcome measured were duration of third stage, amount of bleeding and side-effects. The present study showed that there were significent reduction of the duration of third stage as well as reduction of amount of bleeding particularly when 125 microg of 15-methyl PGF2alpha was given intramuscularly at the time of delivery of the anterior shoulder in comparison to coventional method of management of third stage of labour with methylergometrine. Placental expulsion occurred within 4 minutes in group A and 16.5 minutes in group B. The amount of bleeding following delivery was 95.6 ml in average in group A and 249.6 ml in average in group B. 15-methyl PGF2alpha (125 microg) is certainly effective in prevention of postpartum haemorrhage particularly in developing country like India where this complication contributes a major factor for maternal mortality.     

Genital fistula--our experience

Genital fistulas cause immense physical and psychosocial problem in women's life. The present study was conducted to note the varieties of genital fistula as well as their causative factors and the results of the operative corrections. Altogether 42 patients with different varieties of genital fistula were enrolled in the study. The causative factors of the genital fistulas, specially, that of vesicovaginal fistulas were thoroughly enquired. After confirming the diagnosis, the operative corrections were undertaken. Among the varieties of genital fistula, 76.19% were vesicovaginal fistula, 11.90% were rectovaginal fistula and 4.76%, 4.76% and 2.38% cases of ureterovaginal, urethrovaginal and vesicocervical fistulas respectively. The primipara women were the major sufferers of genital fistulas due to obstetric grounds. Regarding aetiologies of vesicovaginal fistulas, 71.87% patients had obstetric reasons, after prolonged labour, instrumental delivery and after caesarean section due to obstructed labour. Abdominal hysterectomy (44.44%) topped the list of the gynaecological causes of vesicovaginal fistulas. The cases of ureterovaginal fistulas were after abdominal hysterectomy. One case of urethrovaginal fistula was due to some chemical application for correction of genital prolapses. The rectovaginal fistulas were mostly due to obstetric reasons. The success rate after the first attempt of repair of vesicovaginal fistula was 82.75% and overall failure was 10.34%. The other varieties of fistulas were repaired with 100% success rate. The incidence of genital fistulas can be reduced by vigilant obstetric care and meticulous surgery.     

1例CRRT枸橼酸抗凝管道连接错误事件的根本原因分析及对策

应用根本原因分析法,对1例持续肾脏替代治疗（CRRT）枸橼酸抗凝管道连接错误的护理不良事件进行分析。根据根本原因分析的步骤,应用事件序列表、鱼骨图、五问法等管理工具,分析CRRT枸橼酸抗凝管道连接错误的根本原因并制定对策。转变管理者的管理理念,从系统层面剖析护理不良事件的根本原因,并提出改善对策与防范措施,并与大家分享,以达到更好地改进工作质量的目的。     

Optimizing lithium dosing in hemodialysis

We studied a 62-year-old female hemodialysis patient during initiation and maintenance of lithium carbonate therapy. Three different methods were applied to estimate the regimen: a scenario based on volume of distribution (V(d)), a scenario based on glomerular filtration rate (GFR), and a scenario in which we developed an algorithm based on a 2-compartment distribution without elimination. The GFR estimate led to plasma concentrations 3-4 times lower than those anticipated. In contrast, the estimates based on V(d) and the algorithm derived from pharmacokinetic modeling led to comparable loading dose estimates. Furthermore, the maintenance dose estimated from the central compartment (V1) led to plasma concentrations within the therapeutic range. Thus, a regimen where 12.2 mmol lithium was given after each hemodialysis session resulted in stable between-dialysis plasma lithium concentrations in this patient with no residual kidney function. We did not observe adverse effects related to this regimen, which was monitored from 18 days to 8 months of therapy, and the patient experienced relief from her severe depressive disorder. In conclusion, dialysis patients may be treated with lithium administrated immediately postdialysis. Further observations are necessary to obtain robust long-term safety data and to optimize the monitoring schedule.