Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Gastric secretory and hormonal patterns in end-stage chagasic achalasia

P>Achalasia surgical treatment alters the esophagogastric junction anatomy (cardiomyotomy plus fundoplication or esophagectomy and gastric pull-up), thus favoring a certain degree of gastroesophageal reflux. Gastric secretory and hormonal functioning is not completely known in chagasic patients. The aim of this study was to evaluate the gastric secretory and hormonal response in patients with end-stage chagasic achalasia compared with normal subjects. Gastric secretion and hormonal response were assessed by estimation of gastric acid secretion (GAS) in basal condition and after pentagastrin stimulation, basal serum gastrin, and serum pepsinogen (SP) in basal condition and after betazole hydrochloride (Histalog (R); Eli Lilly and Company, Indianapolis, IN, USA) stimulation in 27 patients with chagasic achalasia. The results were then compared with those of 24 normal subjects. In the chagasic group, the mean basal and stimulated GAS were significantly lower than in the control group (basal: 1.277 vs. 3.13, P = 0.002; stimulated: 15.9 vs. 35.8, P = 0.0001). Chagasic patients` SG levels showed a significantly higher basal value than the control group (83.3 vs. 36.8, P = 0.0001). There was a significant increase of SP after stimulation compared with the basal levels in both chagasic and control groups. Although the chagasic patients` SP values were higher than the controls, this difference was not statistically significant, either in basal and stimulated conditions (basal: 122.0 vs. 108.9, stimulated 120 min: 177.1 vs. 158.9). In patients with chronic Chagas` disease (ChD), although autonomic denervation does not suppress the strength of the gastric mucosal cells` secretory response to stimulation, it reduces GAS (parietal cell) without, however, affecting SP production (chief cells). On the other hand, the gastrin-producing cells have continuously been stimulated by low GAS.

Small Bowel Endoscopy Using the Double-Balloon Technique: Four-Year Results in a Tertiary Referral Hospital in Brazil

Background: Double-balloon enteroscopy (DBE) allows evaluation and therapy for various small bowel diseases. In this series the outcome of a 4-year experience in a tertiary hospital school in Brazil is reported. Methods: A total of 457 consecutive DBE were performed in 418 patients from August 2004 to August 2008. 93 patients with several indications, whose aim was not the evaluation of suspected diseases of the small bowel mucosa, were excluded, therefore leaving 364 DBE in 325 patients for analysis. Data were retrospectively collected with regard to clinical, endoscopic findings, therapy and complications. Results: Among the 364 DBE performed in 325 patients, 143/325 were males (44%) and 182/325 females (56%) with a mean age of 48.6 +/- 15.7 years (range 17-89). Mean investigation time was 64 +/- 22 min (range 35-135). The depth of insertion beyond the ligament of Treitz was 230 +/- 85 cm (range 30-500) by the antegrade approach and 140 +/- 75 cm (range 0-320) by the retrograde approach. Total enteroscopy was achieved in 41.66% of the attempts (30 of 72 patients). Overall diagnostic yield was 54.95% (200 of 364 procedures) ranging from 0 to 100% in this series, depending on the indication. Angiodysplasia was the main diagnosis in 24.5% (49 of 200 procedures) and endoscopic treatment, including biopsies, hemostasis, tattooing and polypectomy were performed in 65.38% (238 of 364 procedures). No major complications were reported. Conclusions: DBE is a feasible, safe and well-tolerated procedure allowing endoscopic therapy. Selection of indications increases its diagnostic yield. Copyright (C) 2009 S. Karger AG, Basel

Transanal Endoscopic Microsurgery for Residual Rectal Cancer After Neoadjuvant Chemoradiation Therapy Is Associated With Significant Immediate Pain and Hospital Readmission Rates

BACKGROUND: Transanal endoscopic microsurgery may represent appropriate diagnostic and therapeutic procedure in selected patients with distal rectal cancer following neoadjuvant chemoradiation. Even though this procedure has been associated with low rates of postoperative complications, patients undergoing neoadjuvant chemoradiation seem to be at increased risk for suture line dehiscence. In this setting, we compared the clinical outcomes of patients undergoing transanal endoscopic microsurgery with and without neoadjuvant chemoradiation. METHODS: Thirty-six consecutive patients were treated by transanal endoscopic microsurgery at a single institution. Twenty-three patients underwent local excision after neoadjuvant chemoradiation therapy for rectal adenocarcinoma, and 13 patients underwent local excision without any neoadjuvant treatment for benign and malignant rectal tumors. Chemoradiation therapy included 50.4 to 54Gy and 5-fluorouracil-based chemotherapy. All patients underwent transanal endoscopic microsurgery with primary closure of the rectal defect. Complications (immediate and late) and readmission rates were compared between groups. RESULTS: Overall, median hospital stay was 2 days. Immediate (30-d) complication rate was 44% for grade II/III complications. Patients undergoing neoadjuvant chemoradiation therapy were more likely to develop grade II/III immediate complications (56% vs 23%; P = .05). Overall, the 30-day readmission rate was 30%. Wound dehiscence was significantly more frequent among patients undergoing neoadjuvant chemoradiation therapy (70% vs 23%; P = .03). Patients undergoing neoadjuvant chemoradiation therapy were at significantly higher risk of requiring readmission (43% vs 7%; P = .02). CONCLUSION: Transanal local excision with the use of endoscopic microsurgical approach may result in significant postoperative morbidity, wound dehiscence, and readmission rates, in particular, because of rectal pain secondary to wound dehiscence. In this setting, the benefits of this minimally invasive approach either for diagnostic or therapeutic purposes become significantly restricted to highly selected patients that can potentially avoid a major operation but will still face a significantly morbid and painful procedure.

Avaliação radiográfica da cobertura acetabular à cabeça femoral, após osteotomia tripla e aplicação de cunha sacroilíaca, em pelve de cadáveres de cães

Na tentativa de evitar algumas das dificuldades associadas à osteotomia pélvica tripla (OPT), foi desenvolvido experimentalmente o método de aplicação de cunha na junção sacroilíaca para aumentar a ventroversão acetabular. O objetivo deste estudo foi aplicar as técnicas de cunha sacroilíaca e OPT em cadáveres e avaliar radiograficamente a eficácia da ventroversão acetabular. Para tal, foram utilizados 10 cadáveres de cães, adultos, com 15-25 kg. Em cada hemipelve direita foi realizada OPT com placas de 20° e 40°. Na hemipelve esquerda foram aplicadas cunhas nas articulações sacroilíacas de 20° e 40°. Avaliações radiográficas em projeções ventrodorsais foram realizadas para mensuração da cobertura acetabular à cabeça femoral nas duas técnicas. De acordo com os dados obtidos pode-se observar que não houve diferença entre a técnica de OPT e o uso de cunha sacroilíaca utilizando implantes de 20° e 40°, mas ocorreu diferença significativa (p<0,05) entre os cães antes e após a aplicação dos implantes de 20° e 40°, e também entre os que receberam implantes de 20° e os de 40°. A aplicação de cunha sacroilíaca produziu resultados semelhantes à OPT, e também se mostrou como de mais fácil aplicação.

Acidentes e doenças do trabalho notificadas, de motoristas profissionais do Estado de São Paulo

São descritos os acidentes do trabalho para motoristas profissionais residentes no Estado de São Paulo. Os dados tiveram origem em base específica elaborada nas CATs e processos notificados na Previdência Social do Estado de São Paulo, entre 1997 e 1999. Apresentam-se as características dos motoristas acidentados e dos acidentes do trabalho. São analisadas taxas de incidência, mortalidade e letalidade dos motoristas para o Estado, Região Metropolitana de São Paulo e Município de São Paulo

Cardiomyopathy, adult valve disease and heart failure in South America

Continued assessment of temporal trends in mortality and epidemiology of specific cardiovascular diseases in South America is needed to provide a scientific basis for rational allocation of the limited healthcare resources and introduction of strategies to reduce risk and predict the future burden of cardiovascular disease. The epidemiology of cardiomyopathies, adult valve disease and heart failure (HF) in South America is reviewed here. Diseases of the circulatory system are the main cause of death based on data from about 50% of the South American population. Among the cardiovascular causes of death, cerebrovascular disease is predominant followed by ischaemic heart disease, other heart diseases and hypertensive disease. Of note, cerebrovascular disease is the main cause of death in women, and race also influenced cardiovascular mortality rates. HF is the most important cardiovascular reason for admission to hospital due to cardiovascular disease of ischaemic, idiopathic dilated cardiomyopathic, valvular, hypertensive and chagasic aetiologies. Also, mortality due to HF is high, especially owing to Chagas' disease. HF and aetiologies associated with HF are responsible for 6.3% of deaths. Rheumatic fever is the leading cause of valvular heart disease. The findings have important public health implications because the allocation of healthcare resources, and strategies to reduce the risk of HF should also consider controlling Chagas' disease and rheumatic fever in South American countries.

Charcot`s arthropathy secondary to herpetic encephalitis sequelae: an unusual presentation

Neuropathic arthropathy (Charcot`s arthropathy) is a progressive articular disease associated with a reduced sensorial and protector proprioceptive reflex. Its etiology includes many different conditions such as syringomyelia, traumatic lesion causing medullary deformity, spina bifida, diabetic neuropathy, leprosy neuropathy, neurofibromatosis, amyloid neuropathy, alcohol, and repetitive injection of hydrocortisone into joints, among others. However, the relationship between Charcot`s arthropathy and herpetic encephalitis has not yet been described. Herpes encephalitis causes acute and chronic diseases of the peripheral or central nervous system. It can manifest as subacute encephalitis, recurrent meningitis, or myelitis. It can also resemble psychiatric syndromes, diplopia, sensory changes in the face and limbs, personality changes, frontal dysexecutive syndrome, stiff neck, subclinical alterations of the vestibular function, intracranial hypertension, convulsion, hemiparesis, and generally includes motor components, among others. On the other hand, pure peripheral sensory disturbance has not been described. In this article, we report the clinical case of a patient with Charcot`s arthropathy secondary to pure peripheral sensory polyneuropathy as a consequence of progressive herpetic encephalitis sequelae. In this article, the authors report the first case of Charcot`s arthropathy secondary to herpetic encephalitis.

Should patients with esophageal atresia be submitted to esophageal substitution before they start walking?

P>Esophagocoloplasty and gastric transposition are two major methods for esophageal substitution in children with esophageal atresia, and there is broad agreement that these operations should not be performed before the children start walking. However, there are some reported advantages of performing such operations in the first months of life or in the neonatal period. In this study, we compared our experience with esophageal substitution procedures performed in walking children with esophageal atresia, with the outcomes of children who had the operation before the third month of life reported in the literature. The purpose of this study was to establish if we have to wait until the children start walking before indicating the esophageal replacement procedure. From February 1978 to October 2009, 129 children with esophageal atresia underwent esophageal replacement in our hospital (99 colonic interpositions and 30 gastric transpositions). The records of these patients were reviewed for data regarding demographics, complications (leaks, graft failures, strictures, and graft torsion), and mortality and compared with those reported in the two main articles on esophageal replacement in the neonatal period or in patients less than 3 months of age. The main complication of our casuistic was cervical anastomosis leakage, which sealed spontaneously in all except in four patients. One patient of the esophagocoloplasty group developed graft necrosis and three patients in the gastric transposition group had gastric outlet obstruction, secondary to axial torsion of the stomach placed in the retrosternal space. The long-term outcome of the patients in both groups was considered good to excellent in terms of normal weight gain, absence of dysphagia, and other gastrointestinal symptoms. The comparisons of the main complications and mortality rates in walking children with esophageal substitutions performed in the first months of life showed that the incidences of cervical anastomotic leaks and graft failures were similar, but mortality rate in the first few months of life was significantly greater than that observed in our group of patients (P = 0.001). Based on the comparison of our results with those of published series, we conclude that the recommendation of performing esophagocoloplasty or total gastric transposition in children with esophageal atresia after they start walking is still valid.

Screening Anal Dysplasia in HIV-Infected Patients: Is There an Agreement Between Anal Pap Smear and High-Resolution Anoscopy-Guided Biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system (""without dysplasia"" and ""with dysplasia of any grade""). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

Lymph Node Size in Rectal Cancer Following Neoadjuvant Chemoradiation-Can We Rely on Radiologic Nodal Staging After Chemoradiation?

OBJECTIVES: Local excision is currently being considered as an alternative strategy for ypT0-2 rectal cancer. However, patient selection is crucial to rule out nodal disease and is performed by radiologic studies that consider size as a surrogate marker for positive nodes. The purpose of this study was to determine the difference in size between metastatic and nonmetastatic nodes and the critical lymph node size after neoadjuvant chemoradiation therapy. METHODS: The 201 lymph nodes available from 31 patients with ypT0-2 rectal cancer were reviewed and measured. Lymph nodes were compared according to the presence of metastases and size. RESULTS: There was a mean of 6.5 lymph nodes per patient and 12 positive nodes of the 201 recovered (6%). Ninety-five percent of all lymph nodes were <5 mm, whereas 50% of positive lymph nodes were <3 mm. Metastatic lymph nodes were significantly greater in size (5.0 vs. 2.5mm; P = 0.02). Lymph nodes >4.5 mm had a greater risk of harboring metastases (P = 0.009). CONCLUSIONS: Patients with ypT0-2 rectal cancer following neoadjuvant chemoradiation have very small perirectal nodes. Individual metastatic lymph nodes are significantly larger. However, a significant number of lymph nodes after neoadjuvant chemoradiation (negative and positive) are <3 mm. Individual lymph node size is not a good predictor of nodal metastases and may lead to inaccurate radiologic staging.

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.

Total gastric transposition is better than partial gastric tube esophagoplasty for esophageal replacement in children

Whenever the surgeon uses the stomach as an esophageal substitute, either one of two techniques is generally performed: total gastric transposition or gastric tube esophagoplasty. No existing reports compare the complications associated with these two surgical procedures. The purpose of this study is to review the authors` experience with total gastric transposition and verify whether this technique is superior to gastric tube esophagoplasty in children by comparing the main complications with those reported in the publications of gastric tubes esophagoplasties in the English language literature published in the last 38 years. A total of 35 children underwent total gastric transposition according to the classical technique. Most of these patients (27, or 77.1%) had long gap esophageal atresia. The most frequently observed complications were compared to those reported in nine studies of gastric tube esophagoplasty comprising 184 patients. Mortality and graft failure rates were also compared. Seven patients (20.0%) presented with leaks, all of which closed spontaneously. Six children were reoperated, three experienced gastric outlet obstruction secondary to axial torsion of the stomach placed in the retrosternal space and the other three experienced delayed gastric emptying that required revision of the piloroplasty. There were two deaths (5.7%) and no graft failure. Strictures were observed in five patients (14.2%) and all of these were resolved with endoscopic dilatations. Six patients had diarrhea that spontaneously resolved. In the late follow-up period, all patients were on full feed and thriving well. The comparisons with gastric tube patients demonstrated that the total gastric transposition group presented with significantly less leaks and strictures (P = 0.0001 and 0.001, respectively). The incidence of death and graft failure was not statistically different. In conclusion, gastric transposition is as a simple technical procedure for esophageal replacement in children with satisfactory results, and is superior to gastric tube esophagoplasty.

Wild canids, domestic dogs and their pathogens in Southeast Brazil: disease threats for canid conservation

Wild canids are under many pressures, including habitat loss, fragmentation and disease. The current lack of information on the status of wildlife health may hamper conservation efforts in Brazil. In this paper, we examined the prevalence of canine pathogens in 21 free-ranging wild canids, comprising 12 Cerdocyon thous (crab-eating fox), 7 Chrysocyon brachyurus (maned wolf), 2 Lycalopex vetulus (hoary fox), and 70 non-vaccinated domestic dogs from the Serra do Cip National Park area, Southeast Brazil. For wild canids, seroprevalence of antibodies to canine parvovirus, canine adenovirus, canine coronavirus and Toxoplasma gondii was 100 (21/21), 33 (7/21), 5 (1/19) and 68 (13/19) percent, respectively. Antibodies against canine distemper virus, Neospora caninum or Babesia spp. were not found. We tested domestic dogs for antibodies to canine parvovirus, canine distemper virus and Babesia spp., and seroprevalences were 59 (41/70), 66 (46/70), and 42 (40/70) percent, respectively, with significantly higher prevalence in domestic dogs for CDV (P < 0.001) and Babesia spp. (P = 0.002), and in wild canids for CPV (P < 0.001). We report for the first time evidence of exposure to canine coronavirus in wild hoary foxes, and Platynossomun sp. infection in wild maned wolves. Maned wolves are more exposed to helminths than crab-eating foxes, with a higher prevalence of Trichuridae and Ancylostomidae in the area. The most common ectoparasites were Amblyomma cajennense, A. tigrinum, and Pulex irritans. Such data is useful information on infectious diseases of Brazilian wild canids, revealing pathogens as a threat to wild canids in the area. Control measures are discussed.

Divergence Involving Global Regulatory Gene Mutations in an Escherichia coli Population Evolving under Phosphate Limitation

Many of the important changes in evolution are regulatory in nature. Sequenced bacterial genomes point to flexibility in regulatory circuits but we do not know how regulation is remodeled in evolving bacteria. Here, we study the regulatory changes that emerge in populations evolving under controlled conditions during experimental evolution of Escherichia coli in a phosphate-limited chemostat culture. Genomes were sequenced from five clones with different combinations of phenotypic properties that coexisted in a population after 37 days. Each of the distinct isolates contained a different mutation in 1 of 3 highly pleiotropic regulatory genes (hfq, spoT, or rpoS). The mutations resulted in dissimilar proteomic changes, consistent with the documented effects of hfq, spoT, and rpoS mutations. The different mutations do share a common benefit, however, in that the mutations each redirect cellular resources away from stress responses that are redundant in a constant selection environment. The hfq mutation lowers several individual stress responses as well the small RNA-dependent activation of rpoS translation and hence general stress resistance. The spoT mutation reduces ppGpp levels, decreasing the stringent response as well as rpoS expression. The mutations in and upstream of rpoS resulted in partial or complete loss of general stress resistance. Our observations suggest that the degeneracy at the core of bacterial stress regulation provides alternative solutions to a common evolutionary challenge. These results can explain phenotypic divergence in a constant environment and also how evolutionary jumps and adaptive radiations involve altered gene regulation.