Treatment of achalasia: lessons learned with Chagas` disease

Chagas` disease (CD) is highly prevalent in South America. Brazilian surgeons and gastroenterologists gained valuable experience in the treatment of CD esophagopathy (chagasic achalasia) due to the high number of cases treated. The authors reviewed the lessons learned with the treatment of achalasia by different centers experienced in the treatment of Chagas` disease. Preoperative evaluation, endoscopic treatment (forceful dilatation and botulinum toxin injection), Heller`s myotomy, esophagectomy, conservative techniques other than myotomy, and reoperations are discussed in the light of personal experiences and review of International and Brazilian literature. Aspects not frequently adopted by North American and European surgeons are emphasized. The review shows that nonadvanced achalasia is frequently treated by Heller`s myotomy. Endoscopic treatment is reserved to limited cases. Treatment for end-stage achalasia is not unanimous. Esophagectomy was a popular treatment in advanced disease; however, the morbidity/mortality associated to the procedure made some authors seek different alternatives, such as Heller`s myotomy and cardioplasties. Minimally invasive approach to esophageal resection may change this concept, although few centers perform the procedure routinely.

Frequency and clinical profile of patients with polycystic kidney disease in Southern Brazil

Background. Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic nephropathies, affecting one in every 800-1000 individuals in the worldwide general population and 5-10% of hemodialysis patients. Little data concerning the prevalence of ADPKD in Brazil are available. Thus, the aim of the present study was to investigate both the frequency and clinical profile of ADPKD among hemodialysis patients in south of Brazil. Methods. This cross-sectional study consisted of patients from 24 hemodialysis centers. Patients were screened for ADPKD by clinical, laboratorial, and image examination in medical records. Results. Of 1326 patients on hemodialysis in the south of Brazil that composed this study, 99 (7.5%) had polycystic kidney as primary cause for chronic renal failure. Comparisons between ADPKD and non-ADPKD patients revealed no differences regarding mean age, gender, and ethnicity. Conclusions. Our data revealed that ADPKD is prevalent among patients on hemodialysis in the south of Brazil. In addition, the clinical profile of ADPKD is similar to reported data from North America and Europe, putatively due to the similar ethnic composition mainly based on European descents.

Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial

Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer`s disease, although no benefits were obtained from short-term treatment. Aims To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5mmol/l) (n=24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (A beta(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392. Results Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P=0.03) and better perform-ance on the cognitive subscale of the Alzheimer`s Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer`s disease.

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.

Immunoendocrinology of the Thymus in Chagas Disease

During immune response to infectious agents, the host develops an inflammatory response which could fail to eliminate the pathogen or may become dysregulated. In this case, the ongoing response acquires a new status and turns out to be detrimental. The same elements taking part in the establishment and regulation of the inflammatory response (cytokines, chemokines, regulatory T cells and counteracting compounds like glucocorticoids) may also mediate harmful effects. Thymic disturbances seen during Trypanosoma cruzi (T. cruzi) infection fit well with this conceptual framework. After infection, this organ suffers a severe atrophy due to apoptosis-induced thymocyte exhaustion, mainly affecting the immature double-positive (DP) CD4+CD8+ population. Thymus cellularity depletion, which occurs in the absence of main immunological mediators involved in anti-T. cruzi defense, seems to be linked to a systemic cytokine/hormonal imbalance, involving a dysregulated increase in Tumor Necrosis Factor alpha (TNF-alpha) and corticosterone hormone levels. Additionally, we have found an anomalous exit of potentially autoimmune DP cells to the periphery, in parallel to a shrinkage in the compartment of natural regulatory T cells. In this context, our data clearly point to the view that the thymus is a target organ of T. cruzi infection. Preserved thymus may be essential for the development of an effective immune response against T. cruzi, but this organ is severely affected by a dysregulated circuit of proinflammatory cytokines and glucocorticoids. Also, the alterations observed in the DP population might have potential implications for the autoimmune component of human Chagas disease. Copyright (C) 2011 S. Karger AG, Basel

Evaluation of the respiratory muscle strength of cirrhotic patients: Relationship with Child-Turcotte-Pugh scoring system

Pulmonary abnormalities are observed in chronic hepatopathy. The measurement of the maximum inspiratory and expiratory pressure may evaluate lung function and the risks associated with hepatic transplantation. Thus, the present work sought to evaluate the respiratory muscle strength of 29 patients between 17 and 63 years old who were enrolled for liver transplantation. The patients were classified according to Child-Turcotte-Pugh score as A, B, or C, and also according to a physiotherapeutic evaluation, which included measurement of respiratory muscle strength by means of a digital manovactrometer, which determines the maximum inspiratory pressure (MaxIP) and the maximum expiratory pressure (MaxEP). The tests were performed with seated individuals having their nostrils obstructed by a nasal clip. The MaxIP was measured during the effort initiated in the residual volume, whereas the MaxEP was measured during the effort initiated in the total pulmonary capacity, keeping pressures stable for at least 1 second. The statistical analysis was performed through using the Mann-Whitney test with a 5% level of significance. The MaxIP values of Child A 95.5 +/- 40.507 cm H2O (average +/- DP) and Child B 87.2 +/- 35.02 patients were higher than those for Child C patients (34.83 +/- 3.68; P <.05). Similar results were observed for the MaxEP of Child A and B groups (116.25 +/- 31.98 and 97.28 +/- 31.08, respectively; P <.05), versus the Child C group (48.16 +/- 22.60). Between groups A and B, the MaxEP were similar (P >.05). We concluded that Child C patients display muscle weakness significantly greater than that of subjects classified as Child A or B.

Evaluation of Adult Chronic Chagas` Heart Disease Diagnosis by Molecular and Serological Methods

Chagas` disease caused by Trypanosoma cruzi is endemic in Latin America. T. cruzi presents heterogeneous populations and comprises two main genetic lineages, named T. cruzi I and T. cruzi II. Diagnosis in the chronic phase is based on conventional serological tests, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA), and diagnosis in the acute phase based on parasitological methods, including hemoculture. The objective of this study was to evaluate the diagnostic procedures of Chagas` disease in adult patients in the chronic phase by using a PCR assay and conventional serological tests, including TESA-blot as the gold standard. Samples were obtained from 240 clinical chronic chagasic patients. The sensitivities, compared to that of TESA-blot, were 70% for PCR using the kinetoplast region, 75% for PCR using the nuclear repetitive region, 99% for IIF, and 95% for ELISA. According to the serological tests results, we recommend that researchers assess the reliability and sensitivity of the commercial kit Chagatest ELISA recombinant, version 3.0 (Chagatest Rec v3.0; Wiener Lab, Rosario, Argentina), due to the lack of sensitivity. Based on our analysis, we concluded that PCR cannot be validated as a conventional diagnostic technique for Chagas` disease. These data have been corroborated by low levels of concordance with serology test results. It is recommended that PCR be used only for alternative diagnostic support. Using the nuclear repetitive region of T. cruzi, PCR could also be applicable for monitoring patients receiving etiologic treatment.

Quantitative and qualitative comparison of 3.0 T and 1.5 T MR imaging of the liver in patients with diffuse parenchymal liver disease

Purpose: The purpose of our study was to compare signal characteristics and image qualities of MR imaging at 3.0 T and 1.5 T in patients with diffuse parenchymal liver disease. Materials and methods: 25 consecutive patients with diffuse parenchymal liver disease underwent abdominal MR imaging at both 3.0 T and 1.5 T within a 6-month interval. A retrospective study was conducted to obtain quantitative and qualitative data from both 3.0 T and 1.5 T MRI. Quantitative image analysis was performed by measuring the signal-to-noise ratios (SNRs) and the contrast-to-noise ratios (CNRs) by the Students t-test. Qualitative image analysis was assessed by grading each sequence on a 3- and 4-point scale, regarding the presence of artifacts and image quality, respectively. Statistical analysis consisted of the Wilcoxon signed-rank test. Results: the mean SNRs and CNRs of the liver parenchyma and the portal vein were significantly higher at 3.0 T than at 1.5 T on portal and equilibrium phases of volumetric interpolated breath-hold examination (VIBE) images (P < 0.05). The mean SNRs were significantly higher at 3.0 T than at 1.5 T on T1-weighted spoiled gradient echo (SGE) images (P < 0.05). However, there were no significantly differences on T2-weighted short-inversion-time inversion recovery (STIR) images. Overall image qualities of the 1.5 T noncontrast T1- and T2-weighted sequences were significantly better than 3.0 T (P < 0.01). In contrast, overall image quality of the 3.0 T post-gadolinium VIBE sequence was significantly better than 1.5 T (P< 0.01). Conclusions: MR imaging of post-gadolinium VIBE sequence at 3.0 T has quantitative and qualitative advantages of evaluating for diffuse parenchymal liver disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Ultrasonographic Evaluation of Achilles Tendon Repair After Percutaneous Sectioning for the Correction of Congenital Clubfoot Residual Equinus

Background: Most cases of congenital clubfoot treated with the Ponseti technique require percutaneous Achilles tenotomy to correct the residual equinus. Clinical evidence suggests that complete healing occurs between the cut tendon stumps, but there have not yet been any detailed studies investigating this reparative process. This study was performed to assess Achilles tendon repair after percutaneous section to correct the residual equinus of clubfoot treated with the Ponseti method. Method: A prospective study analyzed 37 tenotomies in 26 patients with congenital clubfoot treated with the Ponseti technique, with a minimum follow-up of 1 year after the section. The tenotomy was performed percutaneously with a large-bore needle bevel with patient sedation and local anesthesia. Ultrasonographic scanning was performed after section to ascertain that the tenotomy had been completed and to measure the stump separation. In the follow-up period, the reparative process was followed ultrasonographically and assessed at 3 weeks, 6 months, and 1 year posttenotomy. Results: The ultrasonography performed immediately after the procedure showed that in some cases, residual strands between the tendon ends persisted, and these were completely sectioned under ultrasound control. A mean retraction of 5.65 mm +/- 2.26 mm (range, 2.3 to 11.0 mm) between tendon stumps after section was observed. Unusual bleeding occurred in one case and was controlled by digital pressure, with no interference with the final treatment. After 3 weeks, ultrasonography showed tendon repair with the tendon gap filled with irregular hypoechoic tissue, and also with transmission of muscle motion to the heel. Six months after tenotomy, there was structural filling with a fibrillar aspect, mild or moderate hypoechogenicity, and tendon scar thickening when compared with a normal tendon. One year after tenotomy, ultrasound showed a fibrillar structure and echogenicity at the repair site that was similar to a normal tendon, but with persistent tendon scarring thickness. Conclusions: There is a fast reparative process after Achilles tendon percutaneous section that reestablishes continuity between stumps. The reparative tissue evolved to tendon tissue with a normal ultrasonographic appearance except for mild thickening, suggesting a predominantly intrinsic repair mechanism.

Heart failure disease management program experience in 4,545 heart failure admissions to a community hospital

Background Disease management programs (DMPs) are developed to address the high morbi-mortality and costs of congestive heart failure (CHF). Most studies have focused on intensive programs in academic centers. Washington County Hospital (WCH) in Hagerstown, MD, the primary reference to a semirural county, established a CHF DMP in 2001 with standardized documentation of screening and participation. Linkage to electronic records and state vital statistics enabled examination of the CHF population including individuals participating and those ineligible for the program. Methods All WCH inpatients with CHF International Classification of Diseases, Ninth Revision code in any position of the hospital list discharged alive. Results Of 4,545 consecutive CHF admissions, only 10% enrolled and of those only 52.2% made a call. Enrollment in the program was related to: age (OR 0.64 per decade older, 95% CI 0.58-0.70), CHF as the main reason for admission (OR 3.58, 95% CI 2.4-4.8), previous admission for CHF (OR 1.14, 95% CI 1.09-1.2), and shorter hospital stay (OR 0.94 per day longer, 95% CI 0.87-0.99). Among DMP participants mortality rates were lowest in the first month (80/1000 person-years) and increased subsequently. The opposite mortality trend occurred in nonenrolled groups with mortality in the first month of 814 per 1000 person-years in refusers and even higher in ineligible (1569/1000 person-years). This difference remained significant after adjustment. Re-admission rates were lower among participants who called consistently (adjusted incidence rate ratio 0.62, 95% CI 0.52-0.77). Conclusion Only a small and highly select group participated in a low-intensity DMP for CHF in a community-based hospital. Design of DMPs should incorporate these strong selective factors to maximize program impact. (Am Heart J 2009; 15 8:459-66.)

Etiopathogenesis of Hepatic Osteodystrophy in Wistar Rats with Cholestatic Liver Disease

The pathophysiology of hepatic osteodystrophy (HO) remains poorly understood. Our aim was to evaluate bone histomorphometry, biomechanical properties, and the role of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) system in the onset of this disorder. Forty-six male Wistar rats were divided into two groups: sham-operated (SO, n = 23) and bile duct-ligated (BDL, n = 23). Rats were killed on day 30 postoperatively. Immunohistochemical expression of IGF-I and GH receptor was determined in liver tissue and in the proximal growth plate cartilage of the left tibia. Histomorphometric analysis was performed in the right tibia, and the right femur was used for biomechanical analysis. The maximal force at fracture and the stiffness of the mid-shaft femur were, respectively, 53% and 24% lower in BDL compared to SO. Histomorphometric measurements showed low cancellous bone volume and decreased cancellous bone connectivity in BDL, compatible with osteoporosis. This group also showed increased mineralization lag time, indicating disturbance in bone mineralization. Serum levels of IGF-I were lower in BDL (basal 1,816 +/- A 336 vs. 30 days 1,062 +/- A 191 ng/ml, P < 0.0001). BDL also showed higher IGF-I expression in the liver tissue but lower IGF-I and GH receptor expression in growth plate cartilage than SO. Osteoporosis is the most important feature of HO; BDL rats show striking signs of reduced bone volume and decreased bone strength, as early as after 1 month of cholestasis. The endocrine and autocrine-paracrine IGF-I systems are deeply affected by cholestasis. Further studies will be necessary to establish their role in the pathogenesis of HO.

Relationship between changes in insulin sensitivity and associated cardiovascular disease risk factors in thiazolidinedione-treated, insulin-resistant, nondiabetic individuals: pioglitazone versus rosiglitazone

This study compared the effects of administering rosiglitazone (RSG) vs pioglitazone (PIO) oil cardiovascular disease risk factors in insulin-resistant. nondiabetic individuals with no apparent disease. Twenty-two nondiabetic, apparently healthy individuals, classified as being insulin resistant oil the basis of a steady-state plasma glucose concentration of at least 10 mmol/L during the insulin suppression test, were treated with either RSG or 1110 for 3 months. Measurements were made before and after drug treatment of weight; blood pressure; fasting and daylong glucose, insulin, and free fatty acid (FFA) levels; and lipid and lipoprotein concentrations. Insulin sensitivity (steady-state plasma glucose concentration) significantly improved in both treatment groups, associated with significant decreases in daylong plasma concentrations of glucose, insulin, and FFA. Diastolic blood pressure fell somewhat in both groups, and this change reached significance in those receiving PIO. Improvement in lipid metabolism was confined to the PIO-treated group, signified by a significant decrease in plasma triglyceride concentration, whereas triglyceride concentration did not decline in the RSG-treated group, and these individuals also had increases in total (P = .047) and low-density lipoprotein cholesterol (P = .07). In conclusion, RSG and PIO appear to have comparable abilities to improve insulin sensitivity and lower daylong glucose, insulin, and FFA concentrations in nondiabetic, insulin-resistant individuals. However, despite these similarities, their effects on lipoprotein metabolism seem to be quite different, with beneficial effects confined to PIO-treated individuals. (C) 2009 Elsevier Inc. All rights reserved.

Anti-nucleosome and anti-chromatin antibodies are present in active systemic lupus erythematosus but not in the cutaneous form of the disease

The objective of this study is to investigate the presence of anti-nucleosome (anti-NCS) and anti-chromatin (anti-CRT) antibodies in patients with cutaneous lupus erythematosus (CLE) compared with active and inactive systemic lupus erythematosus (SLE). A total of 154 subjects were evaluated: 54 patients presenting CLE, 66 patients with active SLE and 34 with inactive SLE. Lupus activity was assessed using the disease activity index (SLEDAI). Anti-NCS and anti-CRT antibodies were detected by enzyme-linked immunosorbent assay ( ELISA). Only one of 54 patients with CLE tested positive for both anti-NCS and anti-CRT antibodies. The prevalence of anti-CRT antibodies was significantly higher in active SLE (84.8%) when compared with inactive SLE (26.4%) and CLE (1.8%) ( P < 0.001). Anti-NCS antibodies were also more prevalent in active SLE patients (74.2%) than inactive SLE (11.7%) and CLE patients ( 1.8%) ( P < 0.001). The presence of anti-CRT and anti-NCS antibodies was correlated to disease activity in patients with SLE (r = 0.4937, r = 0.5621, respectively). Furthermore, the detection of both antibodies was correlated with disease activity in patients with SLE who tested negative for anti-dsDNA antibodies ( r = 0.4754 for anti-NCS and r = 0.4281 for anti-CRT). The presence of these two auto-antibodies was strongly associated with renal damage in patients with SLE ( OR = 13.1, for anti-CRT antibodies and OR = 25.83, for anti-NCS antibodies). The anti-NCS and anti-CRT antibodies were not found in CLE. In patients with SLE, there is a correlation of these antibodies with disease activity and active nephritis. When compared with anti-dsDNA antibodies, anti-NCS and anti-CRT antibodies were more sensitive in detecting disease activity and kidney damage in lupus patients. Lupus (2009) 18, 223-229.

Prevalence of Insulin Resistance and Related Risk Factors for Cardiovascular Disease in Patients With Essential Hypertension

BACKGROUND There is evidence that the subgroup of patients with essential hypertension who are also insulin resistant is at increased risk of cardiovascular disease (CVD). We are unaware of the frequency of insulin resistance in patients with essential hypertension as well as the CVD risk in this subgroup of patients. This analysis was aimed at providing the prevalence of insulin resistance and associated CVD risk factors in treated and untreated patients with essential hypertension. METHODS The study population consisted of 126 patients with hypertension: 56 untreated and 70 in a stable treatment program. Body mass index (BMI), blood pressure, plasma glucose and insulin responses to an oral glucose challenge, lipid and lipoprotein concentrations, and steady-state plasma glucose (SSPG) concentration during the insulin suppression test were measured. Insulin resistance was defined operationally as a SSPG concentration >180 mg/dl. RESULTS Demographic characteristics and metabolic CVD risk factors were comparable in both groups, with 30-50% of both treated and untreated patients having abnormalities of all risk factors measured. Approximately 50% of patients met the criteria for insulin resistance in both groups, and the prevalence of abnormal CVD risk factors in this group was increased two to threefold as compared to the other half of the subjects. CONCLUSIONS Approximately 50% of patients with essential hypertension, both treated and untreated, appear to be insulin resistant, and CVD risk factors are greatly accentuated in this subset of patients.