Beneficial Effect of Creatine Supplementation in Knee Osteoarthritis

NEVES JR., M., B. GUALANO, H. ROSCHEL, R. FULLER, F. B. BENATTI, A. L. DE SA PINTO, F. R. LIMA, R. M. PEREIRA, A. H. LANCHA JR., E. BONFA. Beneficial Effect of Creatine Supplementation in Knee Osteoarthritis. Med. Sci. Sports Exerc., Vol. 43, No. 8, pp. 1538-1543, 2011. Introduction: The aim of this study was to investigate the efficacy of creatine (CR) supplementation combined with strengthening exercises in knee osteoarthritis (OA). Methods: A randomized, double-blind, placebo-controlled trial was performed. Postmenopausal women with knee OA were allocated to receive either CR (20 g.d(-1) for 1 wk and 5 g.d(-1) thereafter) or placebo (PL) and were enrolled in a lower limb resistance training program. They were assessed at baseline (PRE) and after 12 wk (POST). The primary outcome was the physical function as measured by the timed-stands test. Secondary outcomes included lean mass, quality of life, pain, stiffness, and muscle strength. Results: Physical function was significantly improved only in the CR group (P = 0.006). In addition, a significant between-group difference was observed (CR: PRE = 15.7 +/- 1.4, POST = 18.1 +/- 1.8; PL: PRE = 15.0 +/- 1.8, POST = 15.2 +/- 1.2; P = 0.004). The CR group also presented improvements in physical function and stiffness subscales as evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (P = 0.005 and P = 0.024, respectively), whereas the PL group did not show any significant changes in these parameters (P > 0.05). In addition, only the CR group presented a significant improvement in lower limb lean mass (P = 0.04) as well as in quality of life (P = 0.01). Both CR and PL groups demonstrated significant reductions in pain (P G 0.05). Similarly, a main effect for time revealed an increase in leg-press one-repetition maximum (P = 0.005) with no significant differences between groups (P = 0.81). Conclusions: CR supplementation improves physical function, lower limb lean mass, and quality of life in postmenopausal women with knee OA undergoing strengthening exercises.

Evaluation of the cytogenetic effects of I-131 preceded by recombinant human thyrotropin (rhTSH) in peripheral lymphocytes of Wistar rats

The present study was carried out to investigate the cytogenetic effects of therapeutic exposure to radioiodine preceded by rhTSH in an animal model. Three groups of Wistar rats (n = 6) were used: one group was treated only with I-131 (11.1 MBq/animal); the other two groups received rhTSH (1.2 mu g/rat of either Thyrogen or rhTSH-IPEN, respectively) 24 h before administration of radioiodine. The percentage of lymphocytes with chromosome aberrations and the average number of aberrations and of dicentrics per cell were determined on blood samples collected 24 h, 7 and 30 days after administration of I-131. The data show that the treatment with radioiodine alone or associated with rhTSH resulted in a greater quantity of chromosome alterations in relation to basal values after 24 h, with a gradual decline after 7 and 30 days of treatment. An increase in chromosome alterations was also seen after rhTSH treatment alone. Neither of the treatments, i.e., with I-131 alone or associated with hormone, resulted in an aneugenic effect or influenced the kinetics of cellular proliferation in rat blood lymphocytes. There was no significant difference between the cytogenetic effects of Thyrogen and rhTSH-IPEN treatment. These data suggest that the treatment with radioiodine, associated or not with rhTSH, affects to a limited extent a relatively small number of cells although the occurrence of late stochastic effects could not be discarded.

Visuospatial attention disturbance in Duchenne muscular dystrophy

AIM The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to investigate attentional function in individuals with DMD. METHOD Twenty-five males (mean age 12y; SD 2y 2mo) with DMD and 25 healthy males (mean age 12y; SD 2y) were tested in a visuospatial task (Posner computerized test). They were instructed to respond as quickly as possible to a lateralized visual target stimulus with the ipsilateral hand. Their attention was automatically orientated by a peripheral prime stimulus or, alternatively, voluntarily orientated by a central spatially informative cue. RESULTS The main result obtained was that the attentional effect (sum of the benefit and the cost of attention) did not differ between the two groups in the case of automatic attention (p=0.846) but was much larger for individuals with DMD than for comparison individuals in the case of voluntary attention (p < 0.001). INTERPRETATION The large voluntary attentional effect exhibited by the participants with DMD seems similar to that of younger children, suggesting that the disease is associated with delayed maturation of voluntary attention mechanisms.

Long-term follow up of abdominal rectosigmoidectomy with posterior end-to-side stapled anastomosis for Chagas megacolon

Aim Chagas` disease is an endemic parasitosis found in Latin America. The disease affects different organs, such as heart, oesophagus, colon and rectum. Megacolon is the most frequent long-term complication, caused by damage to the myoenteric and submucous plexus, ultimately leading to a functional barrier to the faeces. Patients with severe constipation are managed surgically. The study aimed to analyse the 10-year minimum functional outcome after rectosigmoidectomy with posterior end-to-side anastomosis (RPESA). Method A total of 21 of 46 patients were available for follow up. Patients underwent clinical, radiological and manometric evaluation, and the results were compared with preoperative parameters. Results Of the 21 patients evaluated, 81% (17) were female, with a mean age of 60.6 years. Good function was achieved in all patients, with significant improvement in defaecatory frequency (P < 0.0001), usage of enemas (P < 0.0001) and patient satisfaction. Barium enema also showed resolution of the colonic and rectal dilatation in 19 cases evaluated postoperatively. Conclusion Minimal 10-year follow up of RPESA showed excellent functional results, with no recurrence of constipation.

Synchronous collision malignant melanoma and adenocarcinoma of the rectum

Collision tumors consist of two independent but coexisting tumors. This uncommon situation might be easily mistaken for a composite tumor where one histogenetic event originates from two apparently distinct neoplasms. Colorectal collisions are particularly unusual; here, we report the exceedingly rare case of a 61-year-old man with malignant melanoma and adenocarcinoma colliding in the rectum. Collision tumors have an idiopathic pathophysiology and in fact ""accidental meeting"" is accepted by many authors. This article discusses the concepts about cancer development, which are overlooked by this hypothesis, another theory to explain that this rare occurrence involves microenvironment changes.

Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease

Background and Aims: Although the metabolic risk factors for non-alcoholic fatty liver disease (NAFLD) progression have been recognized, the role of genetic susceptibility remains a field to be explored. The aim of this study was to examine the frequency of two polymorphisms in Brazilian patients with biopsy-proven simple steatosis or non-alcoholic steatohepatitis (NASH): -493 G/T in the MTP gene, which codes the protein responsible for transferring triglycerides to nascent apolipoprotein B, and -129 C/T in the GCLC gene, which codes the catalytic subunit of glutamate-cystein ligase in the formation of glutathione. Methods: One hundred and thirty-one biopsy-proven NAFLD patients (n = 45, simple steatosis; n = 86, NASH) and 141 unrelated healthy volunteers were evaluated. Genomic DNA was extracted from peripheral blood cells, and the -129 C/T polymorphism of the GCLC gene was determined by restriction fragment length polymorphism (RFLP). The -493 G/T polymorphism of the MTP gene was determined by direct sequencing of the polymerase chain reaction products. Results: The presence of at least one T allele in the -129 C/T polymorphism of the GCLC gene was independently associated with NASH (odds ratio 12.14, 95% confidence interval 2.01-73.35; P = 0.007), whereas, the presence of at least one G allele in the -493 G/T polymorphism of the MTP gene differed slightly between biopsy-proven NASH and simple steatosis. Conclusion: This difference clearly warrants further investigation in larger samples. These two polymorphisms could represent an additional factor for consideration in evaluating the risk of NAFLD progression. Further studies involving a larger population are necessary to confirm this notion.

Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis

Aim: There is no proven medical therapy for the treatment of non-alcoholic steatohepatitis (NASH). Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. The aim of our study was to evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) in improving the aminotransferases and histological parameters (steatosis, inflammation, hepatocellular ballooning, and fibrosis) after 12 months of treatment. Methods: Twenty consecutive patients (mean age 53 +/- 2 years [36-68] and body mass index [BMI] 29 [25-35]) with biopsy-proven NASH were enrolled in the study. NAC (1.2 g/day) and MTF (850-1000 mg/day) were given orally for 12 months. All patients underwent evaluation of serum aminotransferases, fasting lipid profile and serum glucose, anthropometric parameters, and nutritional status at 0 and 12 months. A low calorie diet was prescribed for all patients. Results: Serum alanine aminotransferase, high-density lipoprotein, insulin, and glucose concentrations and thehomeostasis model assessment-insulin resistance (HOMA-IR) index were reduced significantly at the end of study (P < 0.05). The BMI declined, but without statistical significance. Aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, cholesterol, and triglycerides levels were not altered with the treatment. Liver steatosis and fibrosis decreased (P < 0.05), but no improvement was noted in lobular inflammation or hepatocellular ballooning. The NASH activity score was significantly improved after treatment. Conclusion: Based on the biochemical and histological evidence in this pilot study, NAC in combination with MTF appears to ameliorate several aspects of NASH, including fibrosis. Further studies of this form of combination therapy are warranted to assess its potential efficacy.

Applicability of the university of pennsylvania smell identification test (SIT) in brazilians: pilot study

The University of Pennsylvania Smell Identification Test (SIT) is the most cited olfactory test in the literature because it is easy to perform and there is high test-retest reliability. There were no standardized olfaction values in a normal Brazilian population. Aim: To measure the SIT score in a group of Brazilians, and to assess the level of difficulty when implementing the test. Study design: A cross-sectional study. Materials and Methods: The SIT was applied in 25 Brazilian volunteers of various income levels who presented no olfactory complaints. Following the test, subjects answered a questionnaire with a visual analog scale (VAS) for the level of difficulty. Results: The mean in the sample of Brazilians was 32.5 (SD: 3.48) our of 40; this is below what is considered normal for US citizens. The level of difficulty was on average 26 mm (SD: 24.68) in the VAS, but it trended towards easy; 4(16%) participants did not recognize some of the odors under `alternatives`. Conclusion: In this pilot study, there was evidence of good test applicability; the score of the sample of Brazilians was just below normosmia. Further studies are needed to confirm the existence of differences between people of different income levels.

The impact of gender, age and hearing loss on tinnitus severity

Tinnitus is a symptom present in approximately 15% of the world population. Most patients are between 40 and 80 years of age; the prevalence above 60 reaches 33%. About 20% have moderate to severe impact in the quality of life but the factors associated with the tinnitus annoyance are not completely known. Aim: The objective of this study is to evaluate the relationship between age, gender and hearing loss on tinnitus annoyance. Materials and methods: 68 patients were evaluated at the tinnitus center at our hospital, from March 2007 to march 2008, with a detailed interview, complete otolaryngological examination, the Portuguese version of the Tinnitus Handicap Inventory and pure tone audiometry. Results: Age varied from 24 to 83 (mean=59); the mean THI value was 39 (females: 36; males: 44). THI grades were: slight: 32.3%; mild: 19.1%; moderate: 20.6%; severe: 13.2% and catastrophic: 14.7%. No significant correlation was found between gender (p=0.30), age (p=0.77) hearing loss (p>0.05 for all averages analyzed) and tinnitus severity. Conclusion: Gender, age and hearing loss do not influence tinnitus annoyance, using the THI.

Surgical Treatment of Myelomeningocele Carried Out at `Time Zero` Immediately after Birth

Background/Aims: To present a protocol of immediate surgical repair of myelomeningocele (MMC) after birth (`time zero`) and compare this surgical outcome with the surgery performed after the newborn`s admission to the nursery before the operation. Methods: Data from the medical files of 31 patients with MMC that underwent surgery after birth and after admission at the nursery ( group I) were compared with a group of 23 patients with MMC admitted and prospectively followed, who underwent surgery immediately after birth - `at time zero` ( group II). Results: The preoperative rupture of the MMC occurred more frequently in group I (67 vs. 39%, p < 0.05). The need for ventriculoperitoneal shunt was 84% in group I and 65% in group II and 4 of them were performed during the same anesthetic time as the immediate MMC repair, with no statistically significant difference. Group I had a higher incidence of small dehiscences when compared to group II ( 29 vs. 13%, p < 0.05); however, there was no statistically significant difference regarding infections. After 1 year of follow-up, 61% of group I showed neurodevelopmental delay, whereas only 35% of group II showed it. Conclusions: The surgical intervention carried out immediately after the birth showed benefits regarding a lower incidence of preoperative rupture of the MMC, postoperative dehiscences and lower incidence of neurodevelopmental delay 1 year after birth. Copyright (C) 2009 S. Karger AG, Basel

Muscle sympathetic nervous activity in depressed patients before and after treatment with sertraline

Background Sympathetic hyperactivity is one of the mechanisms involved in the increased cardiovascular risk associated with depression, and there is evidence that antidepressants decrease sympathetic activity. Objectives We tested the following two hypotheses: patients with major depressive disorder with high scores of depressive symptoms (HMDD) have augmented muscle sympathetic nervous system activity (MSNA) at rest and during mental stress compared with patients with major depressive disorder with low scores of depressive symptoms (LMDD) and controls; sertraline decreases MSNA in depressed patients. Methods Ten HMDD, nine LMDD and 11 body weight-matched controls were studied. MSNA was directly measured from the peroneal nerve using microneurography for 3 min at rest and 4 min during the Stroop color word test. For the LMDD and HMDD groups, the tests were repeated after treatment with sertraline (103.3 +/- 40 mg). Results Resting MSNA was significantly higher in the HMDD [29.1 bursts/min (SE 2.9)] compared with LMDD [19.9 (1.6)] and controls [22.2 (2.0)] groups (P=0.026 and 0.046, respectively). There was a significant positive correlation between resting MSNA and severity of depression. MSNA increased significantly and similarly during stress in all the studied groups. Sertraline significantly decreased resting MSNA in the LMDD group and MSNA during mental stress in LMDD and HMDD groups. Sertraline significantly decreased resting heart rate and heart rate response to mental stress in the HMDD group. Conclusion Moderate-to-severe depression is associated with increased MSNA. Sertraline treatment reduces MSNA at rest and during mental challenge in depressed patients, which may have prognostic implications in this group. J Hypertens 27:2429-2436 (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Biofilms in Chronic Rhinosinusitis with Nasal Polyps

Objective. (1) Evaluate the presence of biofilms in patients with chronic sinusitis with nasal polyps (CRSwNP) and (2) investigate the association of biofilm presence and CRSwNP. Study Design. Cross-sectional study. Setting. University-based tertiary care center. Subjects and Methods. The study group consisted of 33 consecutive patients undergoing functional endoscopic sinus surgery for CRSwNP. The control group consisted of 27 control patients undergoing septoplasty for nasal obstruction without diagnosis of chronic sinusitis. Mucosal samples were harvested intraoperatively for scanning electron microscopic examination to determine biofilm presence. Statistical analysis was performed. For all statistical tests, P = .05 was considered significant. Results. Biofilms were found in 24 (72.7%) of the 33 patients with CRSwNP and in 13 (48.1%) of the 27 septoplasty patients (odds ratio = 2.87; 95% confidence interval, 0.98-8.42; P = .051). Conclusion. (1) Biofilms were present in patients undergoing functional endoscopic sinus surgery for CRSwNP and also in controls without chronic sinusitis. This suggests that biofilms may not be sufficient to cause chronic sinusitis without other cofactors. Host factors could be the responsible for the pathogenesis of biofilms. (2) Although the prevalence of biofilms in patients with CRSwNP was not significantly different from that in the controls, the extremely wide 95% confidence interval, which is just below unity, suggests that a meaningful clinical difference may have been missed because of low statistical power. Further studies are necessary.

Acromegaly: correlation between expression of somatostatin receptor subtypes and response to octreotide-lar treatment

About one-third of acromegalics are resistant to the clinically available somatostatin analogs (SA). The resistance is related to density reduction or different expression of somatostatin receptor subtypes (SSTR). This study analyzes SSTR`s expression in somatotrophinomas, comparing to SA response, hormonal levels, and tumor volume. We analyzed 39 somatotrophinomas; 49% were treated with SA. The most expressed SSTR was SSTR5, SSTR3, SSTR2, SSTR1, and SSTR4, respectively. SSTR1 and SSTR2 had higher expression in patients that had normalized GH and IGF-I. SSTR3 was more expressed in patients with tumor reduction. There was a positive correlation between the percentage of tumor reduction and SSTR1, SSTR2 and SSTR3 expression. Also, a positive correlation between SSTR2 mRNA expression and the immunohistochemical reactivity of SSTR2 was found. Our study confirmed the association between the SA response to GH and IGF-I and the SSTR2. Additionally, this finding was also demonstrated in relation to SSTR1.

Effects of Salivary Gland Homogenate from Wild-Caught and Laboratory-Reared Lutzomyia longipalpis on the Evolution and Immunomodulation of Leishmania (Leishmania) amazonensis Infection

We investigated the effects of Lutzomyia longipalpis salivary glands homogenate of wild-caught and laboratory-reared vectors on the lesion evolution and immunomodulation of the infection caused by Leishmania (Leishmania) amazonensis. To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were inoculated Subcutaneously into the hind footpads or into the ear dermis with 10(6) promastigotes in the presence or not of SGH from wild-caught and laboratory-colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co-inoculated with wild-caught SGH, as the parasitism and the infiltration of macrophages at the inoculation site. Wild-caught SGH also determined lower production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory-reared SGH. Our findings address a probable bias by using SGH from laboratory-colonized sand flies instead of wild-caught vector SGH in studies concerning saliva effects. A possible mild influence of sand fly saliva in natural infections caused by Leishmania is also speculated, as infection is transmitted by wild and not by laboratory-reared vectors.

Children with Cushing`s syndrome: primary pigmented nodular adrenocortical disease should always be suspected

Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare form of bilateral adrenocortical hyperplasia that is inherited in an autosomal dominant manner and leads to ACTH-independent Cushing`s syndrome (CS). PPNAD may be isolated or associated with Carney Complex (CNC). For the diagnosis of PPNAD and CNC, in addition to the hormonal and imaging tests, searching for PRKAR1A mutations may be recommended. The aims of the present study are to discuss the clinical and molecular findings of two Brazilian patients with ACTH-independent CS due to PPNAD and to show the diagnostic challenge CS represents in childhood. Description of two patients with CS and the many sequential steps for the diagnosis of PPNAD is provided. Sequencing analysis of all coding exons of PRKAR1A in the blood, frozen adrenal nodules (patients 1 and 2) and testicular tumor (patient 1) is performed. After several clinical and laboratory drawbacks that misled the diagnostic investigation in both patients, the diagnosis of PPNAD was finally established and confirmed through pathology and molecular studies. In patient 1, sequencing of PRKAR1A gene revealed a novel heterozygous 10-bp deletion in exon 3, present in his blood, adrenal gland and testicular tumor. The etiologic diagnosis of endogenous CS in children is a challenge that requires expertise and a multidisciplinary collaboration for its prompt and correct management. Although rare, PPNAD should always be considered among the possible etiologies of CS, due to the high prevalence of this disease in this age group.