hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Background The aim of this study was to search for mutations in the humanmutS homolog 2 (hMSH2) and humanmutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC). Methods The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing. Results Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. ThehMLH1 gene had a higher mutation detection rate thanhMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in thehMLH1 gene and four in thehMSH2 gene. Conclusions ThehMLH1 gene had a higher mutation detection rate thanhMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.     

Epidural analgesia with 0.15% ropivacaine plus sufentanil 0.5 microgram ml-1 versus 0.10% bupivacaine plus sufentanil 0.5 microgram ml-1: a double-blind comparison during labour

Background. Ropivacaine has been claimed to produce less motorblock than bupivacaine during epidural analgesia. However, thisadvantage has not been clearly confirmed in obstetric studiesusing low analgesic concentrations in a ratio close to thatsuggested to be equianalgesic. Methods. This double-blind, randomized, prospective study wasperformed in 140 parturients who requested epidural analgesia.After a lumbar epidural catheter had been placed, patients receivedeither 0.10% bupivacaine plus sufentanil 0.5 µg ml^–1or 0.15% ropivacaine plus sufentanil 0.5 µg ml^–1followed by a continuous infusion. Additional boluses were usedfor inadequate levels of analgesia. Visual analogue pain scores,motor block, level of sensory block, supplementary boluses andmain characteristics of labour were recorded. Results. No differences were observed between the two groupsfor pain scores, total volume of anaesthetic solution used [59(23) and 57 (24) ml in the bupivacaine and ropivacaine groupsrespectively], duration of labour, mode of delivery, side-effectsor satisfaction score. The incidence of motor block was notstatistically different between the groups (54 and 69% in thebupivacaine and ropivacaine groups respectively, P=0.07). However,when motor block occurred, survival analysis showed that itoccurred sooner in the course of labour with ropivacaine comparedwith bupivacaine (log rank test, P=0.012). Conclusion. Combined with sufentanil 0.5 µg ml^–1,0.10% bupivacaine and 0.15% ropivacaine produce effective andequivalent analgesia during labour, with similar incidencesof motor block. Br J Anaesth 2002; 88: 809–13     

The Strongest Correlates of PTSD for Firefighters: Number,Recency, Frequency,or Perceived Threat of Traumatic Events?

Firefighters experience a wide range of traumatic events while on duty and are at risk to develop psychopathology and posttraumatic stress disorder (PTSD). According to cognitive models, the person's interpretation of the traumatic event is responsible for the development of PTSD rather than the traumatic event itself. This cross‐sectional study aimed to explore the contribution of perceived threat to explain PTSD symptoms in Portuguese firefighters, after adjusting for potential confounding factors. A sample of 397 firefighters completed self‐report measures of exposure to traumatic events, psychopathology, and PTSD. Perceived threat explained unique variance in PTSD symptoms, R² = .40, ΔR² = .02, F(10, 367) = 24.55, p < .001, Cohen's f² =.03, after adjusting for psychopathology, number, recency, and frequency of the events, and other potential confounding variables. The association between psychopathology and PTSD was also moderated by perceived threat, R² = .43, ΔR² = .03, F(11, 366) = 25.33, p < .001, Cohen's f² =.05. Firefighters may benefit from interventions that focus on perceived threat to prevent PTSD symptoms.     

Postgranulomatous anetoderma associated with Takayasu's arteritis in a child

Takayasu's arteritis (TA) is a rare chronic inflammatory arteriopathy affecting mainly the aorta and its branches. Many skin manifestations have been reported in association with this disease. Pyoderma gangrenosum and subcutaneous inflammatory lesions of the leg are the most frequent. We studied a boy with TA in whom a papular rash of the trunk preceded the onset of vascular symptoms by many years. Histologically, the lesions were superficial and consisted of middermal noncaseating tuberculoid granulomas, which progressed to atrophy and anetoderma because of elastic network disruption. Granulomas were also found in synovial tissue but not in a temporal artery biopsy specimen, which showed only intimal hyperplasia. Our observations suggest that vascular and skin lesions with elastic tissue may both result from a common granulomatous hypersensitivity process.     

Is facial pattern a predisposing factor for otitis media with effusion in children?

Abnormalities in craniofacial morphology are associated with Eustachian tube dysfunction and otitis media with effusion (OME).Aim: to evaluate the relationship between facial pattern and craniofacial growth direction, and OME in children with enlarged tonsils and adenoids (ETA).Methods: Clinical prospective survey in 79 children (41 male and 38 female), ranging from 4 to 10 years of age, with tonsil and adenoid enlargement (Brodsky's grades III and IV). Forty children presented with OME (study group) and 39 did not (control group). Cephalometric analysis was used to determine the facial pattern.Results: There was no correlation observed between facial pattern and OME (c 2 = 0.25 p = 0.88). Facial Axis was larger in the OME group (F(1.75) = 3.68 p = 0.05) and the Lower Anterior Facial height was smaller (F(1. 75) = 3.99 p = 0.05) in children with otitis media with effusion.Conclusions: There was no correlation between OME and facial pattern in children with ETA although a more horizontal facial growth direction, and a smaller lower anterior facial height was observed consistently among subjects in this group. This suggests that abnormal positioning of the eustachian tube influences the development of OME in children with ETA.     

Hypertension impairs postnatal vasculogenesis: role of antihypertensive agents

We analyzed the effect of hypertension on postischemic vasculogenesis. Ischemia was induced by right femoral artery ligature in Wistar Kyoto rats (WKY) or spontaneously hypertensive rats (SHR) treated with or without angiotensin-converting enzyme inhibitor (Perindopril, 0.76 mg/kg/d) and angiotensin type 1 receptor blocker (losartan, 30 mg/kg/d). Basal postischemic neovascularization was reduced in SHR compared to WKY (P<0.05, n=8). Treatment with ACE inhibitor or angiotensin type 1 receptor blocker decreased blood pressure levels by 1.4- and 1.3-fold (P<0.001), respectively and restored vessel growth in SHR to WKY levels. Interestingly, 14 days after bone-marrow mononuclear cell (BM-MNC) transfusion, angiographic scores, capillary density, and foot perfusion were decreased by 1.4-, 1.5-, and 1.2-fold, respectively in SHR transfused with BM-MNCs isolated from SHR compared to those receiving BM-MNCs of WKY (P<0.05, n=6). Alteration in BM-MNCs proangiogenic potential was likely related to the reduction in their ability to mobilize into peripheral circulation, as revealed by the 2.9-fold decrease in number of circulating CD34+/CD117+ cells (P<0.001) and to differentiate into cells with endothelial phenotype, as revealed by the 2.1-fold reduction in percentages of DilLDL/BS-1 lectin positive cells (P<0.001). In addition, reactive oxygen species (ROS) levels were increased by 2.2-fold in SHR BM-MNCs compared to WKY BM-MNCs (P<0.01), as assessed by L-012 luminescence. Cotreatment with ACE inhibitor, angiotensin type 1 receptor blocker, or antioxidants (NAC 3 mmol/L, Apocynin 200 micromol/L) reduced ROS levels, improved the number of DilLDL/BS-1 lectin-positive cells by around 1.5-fold, and restored BM-MNCs proangiogenic effects in ischemic hindlimb. In conclusion, alteration in progenitor cell proangiogenic function may participate to the hypertension-induced impairment in postischemic revascularization.