Diffuse-regressive alterations and apoptosis of myocytes: Possible causes of myocardial dysfunction in HIV-related cardiomyopathy

Objective: To determine the frequency of cardiac alterations in necropsies of AIDS patients in pre-HAART era and better understand the pathogenesis of HIV-related cardiomyopathy. Design: Retrospective study of 94 complete necropsies. Method: Macroscopic, histopathologic (histochemical,immunohistochemical and in situ hybridization techniques) and ultra structural myocardial evaluation (23 cases). Results: Cardiac alterations were observed in 94.4%; 74% showed variable degrees of cardiac dilation not related to known cardiovascular diseases. Eighty-two percent (81.8%) of patients with biventricular dilation showed diffuse-regressive alterations (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules). Myocarditis was diagnosed in 27 cases (28.7%), 16 (59.3%) of known etiology. The ultra structural study has revealed cardiomyocytes alterations (mitochondriosis, loss of myofibrils, increase in the amount of perinuclear-lipofuscin pigment granules) associated to activation signals of capillary-endothelial cells (enhancement of pseudopodia and transcellular channels). Cardiomyocytes` apoptosis was demonstrated at structural level in 10 (43.5%) patients; tumor necrosis factor alpha (TNF alpha) was detected in 17/18 cases. Conclusions: This pioneer study described the association of histopathological and ultra structural findings (thinning and waving cardiomyocytes with increase of lipofuscin pigment granules, mitochondriosis and loss of myofibrils) with different degrees of cardiac-chamber dilation probably representing a spectrum of alterations that would lead to myocardial dysfunction and development of HIV-related cardiomyopathy. Cardiomyocytes` apoptosis observed at ultra structural level and demonstration of TNF alpha associated to described alterations suggest that this cytokine plays an important role in both negative-inotropic effect and capacity to induce apoptosis through death receptor-controlled pathway. (C) 2008 Published by Elsevier Ireland Ltd.

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

Background: Up to 60% of chronic obstructive pulmonary disease ( COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. Methods: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of alpha-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p <= 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = -0.451, p < 0.05). Conclusions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test. Copyright (C) 2011 S. Karger AG, Basel

Bariatric Surgery in Adolescents: Preliminary 1-year Results with a Novel Technique (Santoro III)

Background Bariatric surgery (BS) was recognized as the only treatment for morbid obesity in adolescents. Classic surgical procedures are based on mechanical restriction and/or malabsorption, resulting in a large number of possible complications and demanding lifelong medical attention. A novel BS design, the Santoro III procedure, relies on modifying secretion of the satiogenic hormones GLP-1 and PYY. This approach avoids common BS complications such as prostheses, narrow anastomoses, excluded segments, and malabsorption. This study describes the 1-year follow-up of the first ten adolescents operated on using the Santoro III technique in a pediatric surgical service. Methods Ten adolescents, mean age 16.1 +/- 1.7 years with body mass index (BMI) greater than 40 kg/m(2) (range 44 to 72 kg/m(2)), refractory to at least 2 years of medical weight loss treatment were selected by a multidisciplinary team to undergo BS. This operation consists of a sleeve gastrectomy with enteroomentectomy and partial gastro-ileal derivation. Results After 1 year, mean body weight decreased from 140.3 to 88.6 kg, and BMI decreased from 52.8 +/- 9.5 kg/m(2) to 33.4 +/- 7.7 kg/m(2), with percent of excess BMI lost as 83.9 +/- 17.1%. Glucose, insulin, total cholesterol, LDL-cholesterol, and triglyceride levels decreased significantly, while HDL-cholesterol, hemoglobin, and albumin levels remained unchanged. There were no mortalities or reoperations. The two complications that presented during the trial (intraperitoneal abscess and polyneuritis) resolved with medical treatment without sequelae. All the patients returned to their normal activities and their BMI began to stabilize approximately 2 years following surgery. Conclusions The Santoro III procedure is an attractive option for adolescent BS, with promising 1-year follow-up results. These initial studies should be monitored for long-term outcomes and confirmed on a larger group of patients.

Program for Prostate Cancer Screening Using a Mobile Unit: Results From Brazil

OBJECTIVES To evaluate the initial results of a prostate cancer screening program using mobile units in Brazil. METHODS Since 2004, we have conducted a program of prostate cancer screening using mobile units across 231 municipalities from 6 Brazilian states. RESULTS A total of 17 571 men were evaluated by clinical history, digital rectal examination (DRE), and serum free and total prostate-specific antigen (PSA) levels. The recommendations for biopsy were a PSA level of >= 4.0 ng/mL, DRE findings suspicious for cancer, or a PSA level of 2.5-4.0 ng/mL with a percent-free PSA level <15%. The biopsy protocol included 12 biopsy cores from the peripheral zone, 2 from the transition zone, and additional sampling of suspicious areas. The cumulative cancer detection rate was 3.7%. The main indication for biopsy was a PSA level of >= 4.0 ng/mL (51.2%), with a positive predictive value (PPV) of 44.1%. Another 19.7% of biopsied men had suspicious DRE findings with a normal PSA level (PPV 23.5%). A percent-free PSA level of <15% in men with a PSA level of 2.5-4.0 ng/mL and normal DRE findings yielded a PPV of 31.1%. The PPV was greater (70.9%) for the 7.1% of men with both suspicious DRE findings and a PSA level of >4.0 ng/mL. Most cancers were Stage T1-T2 (93.4%), and the percentage of Gleason score of >= 7 was 32.5%. The proportion of insignificant cancers according to Epstein`s criteria was 13.5%. CONCLUSIONS A mobile prostate cancer screening unit enabled an underserved population to gain access to specialized care through the public healthcare system. The cancer detection rate in this population was similar to those from international studies. UROLOGY 76: 1052-1057, 2010. (C) 2010 Published by Elsevier Inc.

Current Patient Management of Chronic Myeloid Leukemia in Latin America A Study by the Latin American Leukemia Net (LALNET)

BACKGROUND: Treatment recommendations have been developed for management of patients with chronic myeloid leukemia (CML). METHODS: A 30-item multiple-choice questionnaire was administered to 435 hematologists and oncohematologists in 16 Latin American countries. Physicians self-reported their diagnostic, therapeutic, and disease management strategies. RESULTS: Imatinib is available as initial therapy to 92% of physicians, and 42% of physicians have access to both second-generation tyrosine kinase inhibitors. Standard-dose imatinib is the preferred initial therapy for most patients, but 20% would manage a young patient initially with an allogeneic stem cell transplant from a sibling donor, and 10% would only offer hydroxyurea to an elderly patient. Seventy-two percent of responders perform routine cytogenetic analysis for monitoring patients on therapy, and 59% routinely use quantitative polymerase chain reaction. For patients who fail imatinib therapy, 61% would increase the dose of imatinib before considering change to a second-generation tyrosine kinase inhibitor, except for patients aged 60 years, for whom a switch to a second-generation tyrosine kinase inhibitor was the preferred choice. CONCLUSIONS: The answers to this survey provide insight into the management of patients with CML in Latin America. Some deviations from current recommendations were identified. Understanding the treatment patterns of patients with CML in broad population studies is important to identify needs and improve patient care. Cancer 2010;116:4991-5000. (C) 2070 American Cancer Society.

Submucosal Injection of 0.4% Hydroxypropyl Methylcellulose Facilitates Endoscopic Mucosal Resection of Early Gastrointestinal Tumors

Background and Aims: Submucosal injection of a viscoelastic solution prolongs submucosal lift, thus, facilitating endoscopic mucosal resection. Our objective was to assess the safety and clinical effectiveness of 0.4% hydroxypropyl methylcellulose (HPMC) as a submucosal injectant for endoscopic mucosal resection. Patients and Methods: A prospective, open-label, multicenter, phase 2 study was conducted at 2 academic institutions in Brazil. Eligible participants included patients with early gastrointestinal tumors larger than 10 mm. Outcomes evaluated included complete resection rates, volume of HPMC injected, duration of the submucosal cushion as assessed visually, histology of the resected leisons, and complication rates. Results: Over a 12-month period, 36 eligible patients with superficial neoplastic lesions (stomach 14, colon 11, rectum 5, esophagus 3, duodenum 3) were prospectively enrolled in the study. The mean size of the resected specimen was 20.4 mm (10 to 60 mm). The mean volume of 0.4% HPMC injected was 10.7 mL (range 4 to 35 mL). The mean duration of the submucosal fluid cushion was 27 minutes (range 9 to 70 min). Complete resection was successfully completed in 89%. Five patients (14%) developed immediate bleeding requiring endoclip and APC application. Esophageal perforation occurred in 1 patient requiring surgical intervention. There were no local or systemic adverse events related to HPMC use over the follow-up period (mean 2.2 mo). Conclusion: HPMC solution (0.4%) provides an effective submucosal fluid cushion and is safe for endoscopic resection of early gastrointestinal neoplastic lesions.

HEMODYNAMIC AND PERFUSION END POINTS FOR VOLEMIC RESUSCITATION IN SEPSIS

Sepsis is the systemic inflammatory response syndrome secondary to a local infection, and severe sepsis and septic shock are the more devastating scenarios of this disease. In the last decade, considerable achievements were obtained in sepsis knowledge, and an international campaign was developed to improve the treatment of this condition. However, sepsis is still one of the most important causes of death in intensive care units. The early stages of sepsis are characterized by a variety of hemodynamic derangements that induce a systemic imbalance between tissue oxygen supply and demand, leading to global tissue hypoxia. This dysfunction, which may occur in patients presenting normal vital signs, can be accompanied by a significant increase in both morbidity and mortality. The early identification of high-risk sepsis patients through tissue perfusion markers such as lactate and venous oxygen saturation is crucial for prompt initiation of therapeutic support, which includes early goal-directed therapy as necessary. The purpose of this article was to review the most commonly used hemodynamic and perfusion parameters for hemodynamic optimization in sepsis, emphasizing the physiological background for their use and the studies that demonstrated their effectiveness as goals of volemic resuscitation.

EARLY GOAL-DIRECTED THERAPY IN TREATMENT OF PEDIATRIC SEPTIC SHOCK

In the whole world, around 29,000 children younger than 5 years die every day, and sepsis is the most common cause of death. Whereas in adult patients vasomotor paralysis represents the predominant cause of mortality, death in pediatric sepsis is associated with severe hypovolemia and low cardiac output. The purpose of this article was to review the recent evidence on early treatment of pediatric severe sepsis and septic shock. Although current American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines represent best practice, stronger evidences are lacking to confirm the components of these recommendations. Retrospective studies showed, at the same time, the positive effects arising from the utilization of American College of Critical Care Medicine-Pediatric Advanced Life Support guidelines and the existing barriers to its implementation. And one randomized control trial paralleled the results observed in adult patients and revealed that early goal-directed therapy in children is one of the few therapeutic interventions that proved to be beneficial in septic shock treatment. Early goal-directed therapy in pediatric septic shock is a successful method to optimize and parameterize treatment, but there is still a long way to turn septic shock resuscitation simpler and more widely spread.

Consequences of Comorbid Sleep Apnea in the Metabolic Syndrome-Implications for Cardiovascular Risk

Study Objectives: Metabolic syndrome (MetSyn) increases overall cardiovascular risk. MetSyn is also strongly associated with obstructive sleep apnea (OSA), and these 2 conditions share similar comorbidities. Whether OSA increases cardiovascular risk in patients with the MetSyn has not been investigated. We examined how the presence of USA in patients with MetSyn affected hemodynamic and autonomic variables associated with poor cardiovascular outcome. Design: Prospective clinical study. Participants: We studied 36 patients with MetSyn (ATP-III) divided into 2 groups matched for age and sex: (1) MetSyn+OSA (n = 18) and (2) MetSyn-OSA (n = 18). Measurements: USA was defined by an apnea-hypopnea index (AHI) > 15 events/hour by polysomnography. We recorded muscle sympathetic nerve activity (MSNA - microneurography), heart rate (HR), and blood pressure (BP - Finapres). Baroreflex sensitivity (BRS) was analyzed by spontaneous BP and HR fluctuations. Results: MSNA (34 +/- 2 vs 28 +/- 1 bursts/min, P = 0.02) and mean BP (111 +/- 3 vs. 99 +/- 2 mm Hg, P = 0.003) were higher in patients with MetSyn+OSA versus patients with MetSyn-USA. Patients with MetSyn+OSA had lower spontaneous BRS for increases (7.6 +/- 0.6 vs 12.2 +/- 1.2 msec/mm Hg, P = 0.003) and decreases (7.2 +/- 0.6 vs 11.9 +/- 1.6 msec/mm Hg, P = 0.01) in BP. MSNA was correlated with AHI (r = 0.48; P = 0.009) and minimum nocturnal oxygen saturation (r = -0.38, P = 0.04). Conclusion: Patients with MetSyn and comorbid USA have higher BP, higher sympathetic drive, and diminished BRS, compared with patients with MetSyn without USA. These adverse cardiovascular and autonomic consequences of USA may be associated with poorer outcomes in these patients. Moreover, increased BP and sympathetic drive in patients with MetSyn+OSA may be linked, in part, to impairment of baroreflex gain.

Comparison between videofluoroscopy and endoscopic evaluation of swallowing for the diagnosis of dysphagia in children

OBJECTIVE: To compare videofluoroscopy swallowing study (VFSS) with the fiberoptic endoscopic evaluation of swallowing (FEES) in children and to determine the accuracy of FEES in the diagnosis of specific swallowing disorders. STUDY DESIGN: Cross-sectional study. SETTING: Hospital da Crianca Santo Antonio, affiliated with Santa Casa de Misericordia Hospital Complex, Porto Alegre, RS, Brazil. SUBJECTS AND METHODS: FEES findings were compared to those of VFSS in 30 children. Kappa coefficients for interobserver agreement were calculated. Thereafter, these coefficients were evaluated in terms of agreement between FEES and VFSS. In addition, the sensitivity, specificity, positive predictive value, and negative predictive value of FEES were calculated for four swallowing parameters (posterior spillover, pharyngeal residues, laryngeal penetration, and laryngotracheal aspiration). RESULTS: Interobserver agreement rates greater than 70 percent were obtained for all FEES parameters analyzed, except for pharyngeal residues with puree consistency (agreement = 66.7%, K = 0.296, P = 0.091). Laryngeal aspiration and penetration yielded the best level of agreement (100%, K = 1) for the laryngeal aspiration of puree residues. CONCLUSION: The diagnostic agreement between FEES (both observers) and VFSS was low. Regarding the analyzed parameters, laryngeal penetration and aspiration yielded the highest interobserver agreement in terms of FEES, and also showed the highest specificity and positive predictive value when compared to VFSS. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.

Tuberculous meningitis in HIV-infected patients in Brazil: clinical and laboratory characteristics and factors associated with mortality

Background: Tuberculous meningitis (TBM) is a growing problem in HIV-infected patients in developing countries, where there is scarce data about this co-infection. Our objectives were to analyze the main features and outcomes of HIV-infected patients with TBM. Methods: This was a retrospective study of HIV-infected Brazilian patients admitted consecutively for TBM. All patients had Mycobacterium tuberculosis isolated from the cerebrospinal fluid (CSF). Presenting clinical and laboratory features were studied. Multivariate analysis was used to identify variables associated with death during hospitalization and at 9 months after diagnosis. Survival was estimated using the Kaplan-Meier method. Results: We included 108 cases (median age 36 years, 72% male). Only 15% had fever, headache, and meningeal signs simultaneously. Forty-eight percent had extrameningeal tuberculosis. The median CD4+ cell count was 65 cells/mu l. Among 90 cases, 7% had primary resistance to isoniazid and 9% presented multidrug-resistant strains. The overall mortality during hospitalization was 29% and at 9 months was 41%. Tachycardia and prior highly active antiretroviral therapy (HAART) were associated with 9-month mortality. The 9-month survival rate was 22% (95% confidence interval 12-43%). Conclusions: Clinical and laboratory manifestations were unspecific. Disseminated tuberculosis and severe immunosuppression were common. Mortality was high and the 9-month survival rate was low. Tachycardia and prior HAART were associated with death within 9 months of diagnosis. (C) 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The Prognosis of the Traumatic Subarachnoid Hemorrhage: A Prospective Report of 121 Patients

Recent investigations have shown the significance of subarachnoid bleeding on computed tomography scans first taken after admission for head injuries. In our study, we describe a prospective follow-up of 121 patients with traumatic subarachnoid hemorrhage (tSAH). From January 2004 to January 2007 we collected data prospectively from 121 patients admitted with diagnosis of tSAH to our trauma intensive care unit, on the basis of admission with a computed tomography scan. The classification of tSAH was performed using the Fisher scale with modification, and the follow-up was performed using the Glasgow Outcome Scale (GOS). The minimum period for a follow-up was established 6 months after the injury. Traffic accident was the main cause of head injuries (72% in total; 48% involving cars and 24% involving motorcycles), followed by falls (23%) and aggression (5%). Twenty-eight percent of patients sustained major multiple injuries, with spinal injury as the main associated trauma. The outcome was favorable (GOS score 4 or 5) in 54 patients (45%) and unfavorable (GOS score 1, 2, or 3) in 67 patients (55%). The mortality rate was proportionally greater in patients who had cisternal clots >1 mm (P < 0.001), assessed by the Fisher scale with modification. When functional recovery was evaluated using the GOS, the recovery rate and the daily life activities were lower in patients with intraventricular bleeding (P = 0.001). Our results showed that patients with severe tSAH had the worst prognosis.

Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS-II study, 2007 to 2008

BACKGROUND: The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics. STUDY DESIGN AND METHODS: Data were extracted from the blood center, compiled in a data warehouse, and analyzed. Population data were obtained from the Brazilian census. RESULTS: During 2007 to 2008, there were 615,379 blood donations from 410,423 donors. A total of 426,142 (69.2%) were from repeat (Rpt) donors and 189,237 (30.8%) were from first-time (FT) donors. Twenty percent of FT donors returned to donate in the period. FT donors were more likely to be younger, and Rpt donors were more likely to be community donors. All were predominantly male. Replacement donors still represent 50% of FT and 30% of Rpt donors. The mean percentage of the potentially general population who were donors was approximately 1.2% for the three centers (0.7, 1.5, and 3.1%). Adjusting for the catchment`s area, the first two were 2.1 and 1.6%. CONCLUSIONS: Donors in the three Brazilian centers tended to be younger with a higher proportion of males than in the general population. Donation rates were lower than desirable. There were substantial differences in sex, age, and community/replacement status by center. Studies on the safety, donation frequencies, and motivations of donors are in progress to orient efforts to enhance the availability of blood.

Obstructive Sleep Apnea, Masked Hypertension, and Arterial Stiffness in Men

BACKGROUND Obstructive sleep apnea (OSA) is an established cause of hypertension However, it is not clear whether the frequency of masked hypertension in patients with OSA and whether OSA have an independent role on arterial stiffness taking into account ambulatory blood pressure (BP) monitoring (ABPM) METHODS We evaluated 61 male normotensive participants as determined by casual clinic BP level <140/90 mm Hg without clinical evidence of cardiovascular disease and on no medications (43 patients with moderate-to-severe OSA (apnea-hypopnea index (AHI) >= 15 events/hour by polysomnography) and 18 age- and body mass index-matched controls without OSA (AHl <5 events/hour)) Pulse wave velocity (PWV), an index of arterial stiffness, and 24-h ABPM were performed in a blinded fashion Masked hypertension was defined when abnormal daytime ABPM was >= 135 or >= 85 mm Hg RESULTS The AHI and lowest oxygen saturation were 26 +/- 16 and 90 +/- 2 vs 528 +/- 210 events/hour and 75 +/- 10% for controls and OSA patients, respectively, P < 0 001. Compared with controls, patients with OSA had higher office systolic BP (113 +/- 9 vs 118 +/- 10 mm Hg, P=0 05) and a higher unadjusted proportion of masked hypertension (2 controls (11.1%)vs 13 patients (30 2%), P < 005) PWV was 87 +/- 0.7, 9.4 +/- 1.0, and 10.6 +/- 1.1 m/s in the control, OSA without and with masked hypertension groups, respectively (P < 0 01 for each comparison) Multiple regression showed that systolic daytime ABPM and the lowest oxygen saturation were independently related to PWV (adjusted R(2) = 0 34, P < 0 01) CONCLUSIONS Patients with OSA presented a higher unadjusted rate of masked hypertension than matched controls. Lowest oxygen saturation has an independent association with arterial stiffness

Treatment of obstructive sleep apnea syndrome in patients from a teaching hospital in Brazil: is it possible?

The aim of this study was to evaluate the efficacy of a cost-effective intra-oral appliance for obstructive sleep apnea syndrome built into a large teaching hospital. Out of 20 evaluated and treated patients, 14 concluded the study: eight men and six women, with a mean age of 42-46 (mean + SD) years and mean body mass index of 27.66. Inclusion criteria were mild or moderate apnea-hypopnea index (AHI) according to a polysomnographic study. All patients were treated with the monobloco intra-oral appliance. They were then submitted to a follow-up polysomnographic study after 60 days using the appliance. An orofacial clinical evaluation was carried out with the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) questionnaire and with clinical evaluation questionnaire devised by the Orofacial Pain Team before and 60 days after fitting the intra-oral appliance. The AHI showed a statistically meaningful (p = 0.002) reduction from 15.53 to 7.82 events per hour, a non-statistically significant oxygen saturation increase from 83.36 to 84.86 (p = 0.09), and Epworth`s sleepiness scale reduction from 9.14 to 6.36 (p = 0.001). Three patients did not show any improvement. The most common side effect during the use of the appliance/device was pain and facial discomfort (28.57%), without myofascial or temporomandibular joint pain as evaluated by the RDC/TMD questionnaire. The intra-oral device produced a significant reduction of the apnea-hypopnea index during the study period with the use of the monobloco intra-oral appliance. Patients did not show prior myofascial pain or 60 days after use of the intra-oral appliance.