Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase

We tested the hypothesis that nitric oxide (NO) arising from the action of inducible nitric oxide synthase (iNOS) is responsible for the deficiency in vasopressin (AVP) release and consequent hypotension during endotoxaemic shock. Wild-type (WT) and iNOS knockout mice (iNOS^–/–) were given either saline or Escherichia coli lipopolysaccharide (LPS, 1.0 mg/kg i.v., final volume 0.03 ml). Mean arterial blood pressure (MAP) was measured and plasma AVP levels determined before and after LPS or saline injection. In WT mice, MAP was significantly lower 2 h after LPS administration and remained low for the remainder of the 6-h observation period. AVP plasma levels were increased at the 2nd and 4th h of the experiment, returning thereafter to basal levels. Conversely, LPS injection in iNOS iNOS^–/– mice elicited a sustained increase in plasma AVP concentration and attenuated the fall in blood pressure. These data indicate that NO arising from the iNOS plays an important inhibitory role in AVP release during endotoxaemia and may be responsible for the hypotension occurring during this vasodilatory shock.     

Assessment of a Simulation Training Exercise to Teach Intrauterine Tamponade for the Treatment of Postpartum Hemorrhage

Introduction: Postpartum hemorrhage is a common complication of vaginal birth. Few midwives have experience in the performance of procedures to manage hemorrhage that fails to respond to initial management with medications and bimanual compression. Methods: A simulation model was constructed by using a half‐pelvis birth simulator and a hollowed out cantaloupe. Practicing midwives and students participated in a simulation exercise by using uterine packing and placement of a uterine tamponade balloon. Pre‐exercise and post‐exercise self‐assessments were performed. Data were analyzed by using the Wilcoxon matched pairs signed rank test. Results: A total of 25 learners participated in the training session. All 25 participants showed improvement in their self‐assessed competency level for the placement of the Bakri Postpartum Balloon (P < .001), and 24 of 25 showed improvement in self‐assessed competency levels for uterine packing (P < .001). Discussion: An inexpensive simulation model can be used to effectively train midwives to treat postpartum hemorrhage by using methods of exerting direct pressure to the uterine cavity.     

Dengue Control Program in São José do Rio Preto, São Paulo State, Brazil: problems with health agents' work and population adherence

This study aimed to identify the aspects that interfere with the performance of vector control agents and community health workers and population adherence to dengue control programs. The focal group methodology was applied to discuss the relations between the program, health agents, and population. According to the results, dengue control and prevention were considered relatively unimportant activities, i.e., ideal community health workers would be capable of solving other (supposedly more important) problems. Vector control agents emphasized the population's lack of adherence and the fact that they (the control agents) were confused with garbage collectors (considered less important than community health workers, and with a focus more on productivity than quality). Women frequently blamed neighbors for the dengue problem and associated the disease with lack of hygiene. These aspects have a negative impact on dengue control agents' work and result from the program's vertical structure. Possible solutions would be to incorporate the agents into community health clinics, encourage cooperation between departments, and provide the conditions for them to intervene in the environment.     

Intestinal Mucosa-Associated Microflora in Ulcerative Colitis Patients Before and After Restorative Proctocolectomy with an Ileoanal Pouch

Purpose  This study was designed to identify the mucosa-associated microflora in patients with severe ulcerative colitis before and after restorative proctocolectomy with ileoanal pouch construction in comparison with historic controls. Methods  Ten patients with a diagnosis of ulcerative colitis were evaluated. Mucus was collected during colonoscopy from all segments of the colon and terminal ileum before surgery, and from the ileal pouch two and eight months after ileostomy closure. The prevalence and mean concentration of the mucosa-associated microflora were compared over time and with historic controls. Results   Veillonella sp was the most prevalent bacterium in patients and controls. Klebsiella sp was significantly more prevalent in the ileum of controls, was not found in patients with ulcerative colitis, and after proctocolectomy returned to values found in controls. Some bacteria such as Enterobacter sp, Staphylococcus sp (coag-), Bacteroides sp (npg), Lactobacillus sp, and Veillonella sp had higher mean concentrations in the ileal pouch of patients after surgery than in controls. Conclusion  No bacterium was identified that could be exclusively responsible for the maintenance of the inflammatory process. The mucosa-associated microflora of patients with ulcerative colitis underwent significant changes after proctocolectomy with ileal pouch construction and returned to almost normal values for some bacteria. Presented at the meeting of the International Society of University Colon & Rectal Surgeons, Budapest, Hungary, June 6 to 10, 2004.     

DNA Ploidy Status and Prognosis in Colorectal Cancer: A Meta-Analysis of Published Data

Purpose In colorectal cancer, the negative effect of aneuploidy has been a controversy for more than 20 years. Studies to determine a survival-deoxyribonucleic acid content relationship have conflicting results. A systematic literature search followed by a meta-analysis of published studies addressing prognostic effect of aneuploidy for patients who underwent surgical treatment of colon and rectal cancer was conducted. Methods The main outcome measure was the five-year overall mortality rate after surgical resection. For the selected studies, we estimated this outcome for three subsets of patients through separate meta-analyses: 1) for all patients with colorectal cancer; 2) only between patients with Stage II colon cancer; and 3) only for studies in which follow-up losses were declared. The presence of publication bias was assessed with a funnel plot for asymmetry. Results A total of 5,478 patients with colorectal cancer were represented in 32 studies (Group 1), we estimated a reduction in the five-year overall mortality from 43.2 percent for aneuploid tumors to 29.2 percent for diploid tumors (combined relative risk = 1.44; 95 percent confidence interval = 1.34–1.55; P < 0.001). In addition, 357 patients with Stage II colon cancer (Group 2) extracted from three studies had an absolute reduction of 14.3 percent in five-year overall mortality favoring diploid tumors (combined relative risk = 1.93; 95 percent confidence interval = 1.29–2.89; P = 0.001). Lastly, of 14 studies in which follow-up losses were declared (Group 3), 2,221 patients were represented and a 15.7 percent mortality reduction was measured favoring patients with diploid tumors (combined relative risk = 1.44; 95 percent confidence interval = 1.3–1.61; P < 0.001). Conclusions Patients who undergo an aneuploid colorectal cancer surgical resection have a higher risk of death after five years. This finding may ultimately impact survival of patients with node-negative colon cancer through adjuvant therapy. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 3 to 7, 2006.     

Modulating apoptosis as a target for effective therapy

Alterations in cell proliferation and cell death are essential determinants in the pathogenesis and progression of several diseases such as cancer, neurodegenerative disorders or autoimmune diseases among others. Complex networks of regulatory factors determine whether cells proliferate or die. Recent progress in understanding the molecular changes offer the possibility of specifically targeting molecules and pathways to achieve more effective and rational therapies. Drugs that target molecules involved in apoptosis are used as treatment against several diseases. Candidates such as TNF death receptor family, caspase inhibitors, antagonists of the p53-MDM2 interaction, NF-kappaB and PI3K pathways and Bcl-2 family members have been targeted as cancer cell killing agents. Moreover, apoptosis of tumor cells can also be achieved by targeting the inhibitor of apoptosis proteins, IAPs, in addition to the classical antiproliferative approach. Disruption of STAT activation and interferon beta therapy have been used as a treatment to prevent the progression of some autoimmune diseases. In models of Parkinson's, Alzheimer's and amyotrophic lateral sclerosis, blocking of Par-4 expression or function, as well as caspase activation, prevents neuronal cell death. Finally, it has been shown that gene therapy may be an encouraging approach for treatment of neurodegenerative disorders.     

Effects of ritanserin on aversive classical conditioning in humans

According to one formulation of the behavioural functions of 5HT, aversive conditioned stimuli mediate their behavioural and emotional effects through activation of 5HT projections from dorsal raphe nucleus to receptors of the 5HT2 family in amygdala and elsewhere. To test this theory in humans, groups of ten normal volunteers received placebo, the 5HT2/1c antagonist ritanserin (10 mg PO) and no pill. Ritanserin had no effect on skin conductance level, variability (spontaneous fluctuations) or habituation to a sequence of ten neutral tones. After a conditioning trial in which tone 11 was followed by an aversive white noise, skin conductance responses to a further ten tones were enhanced. This effect was abolished by ritanserin. The results indicate a selective involvement of 5HT2/1c receptors in modulating aversively conditioned skin conductance responses.     

Combined resection of the duodenum and pancreas for locally advanced colon cancer

Colorectal cancer invading adjacent organs is a frequent event occurring in 5.5% to 12% of all colorectal malignancies. Colon cancer directly invading the duodenum and pancreas is rare and may require combined resection of the colon, pancreas, and duodenum, which represents a complex operation with significant morbidity and mortality rates. In this article, a case of a 41-year-old patient with a right colon cancer directly infiltrating the duodenum and head of the pancreas is presented. The patient was treated by radical combined resection of the colon, duodenum, and pancreas. Pathological examination confirmed neoplastic invasion of the adjacent organs and absence of lymph node metastasis (T4N0). The patient recovered uneventfully. Patients with colorectal cancer infiltrating adjacent organs such as the duodenum and the pancreas should be treated by radical en bloc resection of the tumor. This procedure is the preferred treatment strategy because it seems to be associated with improved overall survival rates.