Postural Control in Elderly Persons with Osteoporosis: Efficacy of an Intervention Program to Improve Balance and Muscle Strength A Randomized Controlled Trial

Burke TN, Franc, a FJR, de Meneses SRF, Cardoso VI, Marques AP: Postural control in elderly persons with osteoporosis: Efficacy of an intervention program to improve balance and muscle strength: A randomized controlled trial. Am J Phys Med Rehabil 2010; 89: 549-556. Objective: To assess the efficacy of an exercise program aiming to improve balance and muscular strength, for postural control and muscular strength of women with osteoporosis. Design: Sample consisted of 33 women with osteoporosis, randomized into one of two groups: intervention group, in which exercises for balance and improvement of muscular strength of the inferior members were performed for 8 wks (n = 17, age 72.8 +/- 3.6 yrs); control group, which was women not practicing exercises (n = 16, age 74.4 +/- 3.7 yrs). At baseline and after 8 wks of treatment, postural control was assessed using a force plate (Balance Master, Neurocom), and muscular strength during ankle dorsiflexion, knee extension, and flexion was assessed by dynamometry. Results: Adherence to the program was 82%. When compared with the control group, individuals in the intervention group significantly improved the center of pressure velocity (P = 0.02) in the modified clinical test of sensory interaction for balance test, center of pressure velocity (P < 0.01), and directional control (P < 0.01) in limits of stability test, isometric force during ankle dorsiflexion (P = 0.01), knee extension (P < 0.01), and knee flexion (P < 0.01). Conclusions: Balance and strength exercises are effective in improving postural control and lower-limb strength in elderly women with osteoporosis.

E-cadherin and beta-catenin Loss of Expression Related to Bone Metastasis in Prostate Cancer

Objectives: E-cadherin and beta-catenin are adhesion molecules responsible for the maintenance of normal epithelial cell phenotype. A disturbance in epithelial cell adhesion, which leads to a more invasive and metastatic phenotype, is a hallmark of tumor progression. Several immunohistochemical studies have reported a strong correlation between loss of their expression to higher stage and grade in prostate carcinoma, but their influence in metastatic process is not yet known. The aim of this study is to verify the role of adhesion molecules in the progression of prostate cancer (PC), assessing the expression of E-cadherin and beta-catenin in bone metastasis. Materials and Methods: Twenty-eight bone metastases of prostate carcinoma were submitted to immunohistochemistry analysis for E-cadherin and beta-catenin expression. In 6 patients, we were able to assess the expression of the adhesion molecules in the primary tumors and their respective metastases. The definition of normal expression for both antibodies was strong and diffuse expression in more than 70% of tumor cells. Results: In bone metastases, there was loss of expression of E-cadherin and beta-catenin in 86% and 82%, respectively. Among the primary tumors, E-cadherin and beta-catenin expression was normal in 83% and 50% cases, respectively. Considering the 6 patients with paired primary and bone metastasis, we found loss of expression for both E-cadherin and beta-catenin in most of the cases. Conclusions: Comparing primary PC and its metastasis, we showed persistent loss of E-cadherin and beta-catenin expression. This phenomenon may be related to metastatic potential in PC, because we have shown underexpression for E-cadherin and beta-catenin in 86% and 82% of bone metastases.

Biopsy-Proven Pulmonary Determinants of Heart Disease

Heart disease (HD) can stress the alveolar blood-gas barrier, resulting in parenchymal inflammation and remodeling. Patients with HD may therefore display any of the symptoms commonly attributed to primary pulmonary disease, although tissue documentation of corresponding changes through surgical lung biopsy (SLB) is rarely done. Intent on exploring the basis of HD-related alveolar-capillary barrier dysfunction, a retrospective analysis of SLB histopathology was conducted in patients with clinically diagnosed HD, diffuse pulmonary infiltrates, and no evidence of primary pulmonary disease. Patients eligible for the study had a clinical diagnosis of heart disease, acute or chronic, and presented with diffuse infiltrates on chest X-ray. All qualified subjects (N = 23) who underwent diagnostic SLB between January 1982 and December 2005 were subsequently examined. Specific biopsy parameters investigated included demonstrable edema, siderophage influx, hemorrhage, venous and lymphatic ectasia, vascular sclerosis, capillary congestion, and fibroblast proliferation. Based on observed alveolar-capillary barrier (ACB) alterations, three main morphologic groups emerged: one group (6 patients) with alveolar edema; a second group (11 patients) characterized by pulmonary congestion; and a final group (6 patients) showing microscopic foci of acute ACB lung injury. Alveolar-capillary stress due to acute high-pressure or volume overload often manifests as diffuse pulmonary infiltrates with variable but generally predictable histopathology. In patients with biopsy-proven alveolar edema, pulmonary congestion, or acute microscopic lung injury, the clinician must be alert for the possibility of primary heart disease, particularly if the patient is elderly or when a history of myocardial, valvular, or coronary vascular disease exists.

Fundus-Based and Electroretinographic Strategies for Stratification of Late-Stage Vogt-Koyanagi-Harada Disease Patients

PURPOSE: To propose an analytic framework for ocular fundus alterations in late-stage Vogt,Koyanagi-Harada (VKH) disease, to describe the characteristics of overall retinal function as measured with full field electroretinography (ERG), and to correlate the intensity of the fundus changes with full-field ERG alterations and to stratify patients accordingly. DESIGN: Cross-sectional case series. METHODS: Forty-seven eyes of 26 patients with late, stage VKH disease (> 6 months past disease onset) followed-up at the University of Sao Paulo School of Medicine underwent fundus photography within 2 months of a full,field ERG examination, both according to pre-defined protocols. Fundus pictures were evaluated by two observers regarding diffuse fundus depigmentation, nummular lesions, pigment clumps, and subretinal fibrosis, and an overall analysis classified the fundus changes as mild, moderate, or severe. Full field ERG results were analyzed according to fundus-based stratification and also were stratified into 3 groups solely on the basis of decreasing amplitudes (ERG based or cluster stratification). The concordance between fundus-based and full-field ERG-based stratification strategies was estimated. RESULTS: Overall fundus grading showed substantial interobserver concordance (kappa = 0.78). Comparison of full field ERG parameters of the three fundus based stratified groups showed diffusely diminished amplitudes with preservation of implicit times (P < .05). Fundus-based and full-field ERG-based stratification strategies also showed substantial concordance (kappa = 0.68). CONCLUSIONS: The analytic framework for fundus findings proposed in this study seems reproducible and useful, because the severity categories do correlate with retinal function as measured by full-field ERG. This system may allow more precise exchange of information between practitioners as well as researchers with regard to identifying patients with greater retinal compromise rapidly as well as in comparison of outcomes of different treatment regimens. (Am J Ophthalmol 2009;148: 939-945. (C) 2009 by Elsevier Inc. All rights reserved.)

Pentoxyphylline in association with vitamin E reduces cutaneous fibrosis in systemic sclerosis

Systemic sclerosis (SSc) is a disorder characterized by skin thickness and vasculopathy. The objective of the study was to evaluate the therapeutic effect and safety of the association of pentoxyphylline and vitamin E in SSc patients. Twelve SSc patients (American College of Rheumatology criteria) enrolled this 24-week open-label study. Patients received daily 800 mg of pentoxyphylline and 800 UI of vitamin E and were evaluated at 4-week interval. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at week 24. Nine diffuse SSc patients treated 6 months with cyclophosphamide were used as a historical control group. The mean age of the treated group was 43.6 years, and ten of 12 (84%) patients were women. Their mean MRSS reduced from 25.7 to 18.7 (p = 0.03) at 16th week and remained significantly reduced throughout the study. In contrast, only a trend of MRSS reduction was observed in the historical control group (p = 0.06). Two patients started the study with active ischemic ulcers and ended with a complete healing of them. No serious side effects were reported. Pentoxyphylline and vitamin E might be an alternative therapeutic approach in SSc patients.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

Aims We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). Methods and results Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and A beta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (0). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and A beta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and A beta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and A beta reserves, respectively. Conclusion Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Active tuberculosis and Mycobacterium tuberculosis latent infection in patients with HIV/AIDS

Objectives Tuberculosis (TB) remains an important disease associated with HIV infection and AIDS in Brazil, even in a setting of free access to antiretroviral therapy (ART) and TB treatment. In previous studies, isoniazid therapy (IT) for latent infection with Mycobacterium tuberculosis (LIMTb) was found to reduce the risk of TB by 62% in patients with a tuberculin test (TT)> 5 mm. The objectives of this study were to investigate the occurrence of TB, the prevalence of LIMTb and the coverage of the TT and IT, and to estimate the number of missed opportunities to prevent TB in patients with HIV/AIDS. Methods A random sample of patients with HIV/AIDS was selected; data from the medical files were obtained, and a TT was performed in consenting subjects. Results In the 203 subjects included in the study, TB occurrence was 13.3%, LIMTb prevalence was 20% and the coverage of the TT and IT was 59.2 and 55%, respectively. Patients with TB had a lower nadir CD4 cell count, but their CD4 recovery was comparable to that of non-TB patients. Patients with LIMTb always had a higher CD4 cell count. Conclusions By expanding the coverage of the TT and IT to nearly 100%, we could more than double the number of prevented cases of TB. TB prevention programmes must be reinforced to reduce the number of missed opportunities for diagnosis, and IT must be improved to reduce TB among patients with HIV/AIDS. Empowering patients with knowledge about TB, the preventive role of IT and the need for an annual TT may be the best way of lowing rates of TB in patients with HIV/AIDS.

Evolution of Laparoscopic Colorectal Surgery in Brazil Results of 4744 Patients From the National Registry

Background: Since its introduction, laparoscopic colorectal surgery has raised intense debate and controversies regarding its safety and effectiveness. Methods: This multicentric registry reports the experience of 28 Brazilian surgical teams specializing in laparoscopic colorectal surgery. Results: Between 1992 and 2007, 4744 patients (1994 men-42% and 2750 women-58%) were operated upon, with ages ranging from 13 to 94 years (average 57.5y). Benign diseases were diagnosed in 2356 patients (49.6%). Most diseases were located in 50.7% of the left and sigmoid colon, 28.2% in the rectum and anal canal. 8.0% in the right colon, and diffuse 7.0%. There were 181 (3.8%) intraoperative complications (from 0% to 14%). There were 261 (5.5%) reported conversions to laparotomy (from 0% to 16.5%), mainly during the early experience (n = 119 - 59.8%). Postoperative complications were registered in 683 (14.5%) patients (from 5.0% to 50%). Mortality occurred in 43 patients (0.8%). Surgeons who performed less than 50 cases reported similar rates of intraoperative (4.2% vs. 3.8%,- P = 0.7), postoperative complications (20.8% vs. 14.3%; P = 0.07), and mortality (1.0% vs. 0.9%; P = 0.5) but the conversion rate was higher (10.4% vs. 5.4%; P = 0.04). Two thousand three hundred and eighty-nine (50.4%) malignant tumors were operated upon, and histologic classification showed 2347 (98%) adenocarcinomas, 30 (0.6%) spinocelular carcinomas, and 12 (0.2%) other histologic types. Tumor recurrence rate was 16.3% among patients followed more than I year. After an average follow-Lip of 52 months, 19 (0.8%) parietal recurrences were reported, 18 of which were in port sites and I in a patient with disseminated disease. There was no incisional recurrence in the ports used to withdraw the pathologic specimen. Compared with other registries, there was a 75% increase in the number of groups pet-forming laparoscopic colorectal surgery and a decrease in conversions (from 10.5%. to 5.5%) and mortality (from 1.5% to 0.9%) rates. Conclusions: (1) The number of patients operated upon increased expressively during the last years; (2) operative indications for benign and malignant diseases were similar, and diverticular disease of the colon comprised 40% of the benign ones; (3) conversion and mortality rates decreased over time; (4) Surgeon`s experience did not influence the complication rates, but was associated with a lower conversion; and (5) oncologic outcome expressed by recurrence rates showed results similar to those reported in conventional surgery.

A study of actinic cheilitis treatment by two low-morbidity CO(2) laser vaporization one-pass protocols

Therapeutic approaches to chronic actinic cheilitis focus on the removal or destruction of diseased epithelium. The CO(2) laser has become an important therapeutic alternative, achieving clinical resolution in around 90% of patients. Although many laser physical parameters have been reported, some are known for their low potential for scar induction without compromising the success of the results. The aim of this clinicohistological study was to compare the therapeutic responses to two low-morbidity protocols involving a single laser pass. A total of 40 patients with chronic multicentric and microscopically proven disease were randomly submitted to two conservative CO(2) laser protocols using a bilateral comparative model. The degree of histological atypia of the epithelium was determined in 26 patients both pre- and postoperatively for both protocols. Other histological phenomena were assessed in addition to this central analysis parameter. Clinical recurrence occurred in 12.5% of patients for each protocol, together with a significant reduction in the degree of epithelial atypia (p < 0.001), which was occasionally complete. However, no difference was found between the protocols (p > 0.05). Using these morphological parameters it was not possible to determine whether postoperative epithelial atypias in part of the sample were reactive or residual in nature. A few patients may show minor postoperative lesions. Due to their potential to achieve clinical and importantly microscopic resolution, the studied protocols may be used for mild through moderate dysplastic epithelium and clinically diffuse disease.

Preliminary findings from a new animal model for Peyronie`s disease involving extracorporeal shock waves

To develop an experimental model in rabbits to analyse the efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie`s disease. We used 15 adult male rabbits divided into three equal groups. In group 1 (no penile ESWT) rabbits had three sessions of ESWT with 2000 shocks each (15 kV), but a rubber mat was placed between the shock head and rabbit to protect the penis; the rabbits were killed at 7 days after the last session of ESWT. In group 2 the rabbits had three sessions of ESWT using the same parameters, and were killed immediately after the last session to analyse the penis. In group 3 the rabbits had three sessions of ESWT as before but were killed at 7 days after the last session, and the penile tissue analysed macroscopically and histologically. The results showed clearly that the model was efficient, creating a similar situation to that when applying ESWT in the human penis. All of the rabbits in groups 2 and 3 had haematomas and diffuse petechiae after ESWT, and only four had urethral and penile bleeding. Almost all macroscopic changes disappeared after 48 h and only one rabbit in group 3 after 7 days had a haematoma on the dorsal penile surface. The histology (assessed using haematoxylin and eosin staining) of the cavernous body of the penis showed: unchanged histology in group 1; in group 2 there was a dilated and congested vascular space in the cavernous body, with interstitial extensive bleeding in the dermis; and in group 3 there was an increase in interstitial fibrous tissue in the cavernous septum, with deposition of collagen fibres and thickening of the tunica albuginea. The present model was efficient in producing tissue injury in the normal penis when treated with ESWT, suggesting that this promising model should be considered for use future studies of Peyronie`s disease.

Interferon and Alternative Activation of Monocyte/Macrophages in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

Objective. To explore the relationship between biomarkers of pulmonary arterial hypertension (PAH), interferon (IFN)-regulated gene expression, and the alternative activation pathway in systemic sclerosis (SSc). Methods. Peripheral blood mononuclear cells (PBMCs) were purified from healthy controls, patients with idiopathic PAH, and SSc patients (classified as having diffuse cutaneous SSc, limited cutaneous SSc [lcSSc] without PAH, and lcSSc with PAH). IFN-regulated and ""PAH biomarker"" genes were compared after supervised hierarchical clustering. Messenger RNA levels of selected IFN-regulated genes (Siglec1 and MX1), biomarker genes (IL13RA1, CCR1, and JAK2), and the alternative activation marker gene (MRC1) were analyzed on PBMCs and on CD14- and CD14+ cell populations. Interleukin-13 (IL-13) and IL-4 concentrations were measured in plasma by immunoassay. CD14, MRC1, and IL13RA1 surface expression was analyzed by flow cytometry. Results. Increased PBMC expression of both IFN-regulated and biomarker genes distinguished SSc patients from healthy controls. Expression of genes in the biomarker cluster, but not in the IFN-regulated cluster, distinguished lcSSc with PAH from lcSSc without PAH. The genes CCR1 (P < 0.001) and JAK2 (P < 0.001) were expressed more highly in lcSSc patients with PAH compared with controls and mainly by CD14+ cells. MRC1 expression was increased exclusively in lcSSc patients with PAH (P < 0.001) and correlated strongly with pulmonary artery pressure (r = 0.52, P = 0.03) and higher mortality (P = 0.02). MRC1 expression was higher in CD14+ cells and was greatly increased by stimulation with IL-13. IL-13 concentrations in plasma were most highly increased in lcSSc patients with PAH (P < 0.001). Conclusion. IFN-regulated and biomarker genes represent distinct, although related, clusters in lcSSc patients with PAH. MRC1, a marker for the effect of IL-13 on alternative monocyte/macrophage activation, is associated with this severe complication and is related to mortality.

Study into the use of continuous positive airway pressure in obstructive sleep apnoea-hypopnoea syndrome patients with daytime drowsiness

Background: Obstructive sleep apnoea-hypopnoea syndrome (OSAHS) is a respiratory disorder with high morbidity and mortality. Continuous positive airway pressure (CPAP) is the most commonly prescribed conservative treatment for adults with OSAHS. CPAP therapy normalises or decreases OSAHS symptoms and can reduce and prevent OSAHS complications. Aims: To evaluate adherence to nasal CPAP treatment and CPAP impact on daytime drowsiness. Method: A sample of 20 patients evaluated for daytime drowsiness using the Epworth sleepiness scale and interviewed for adherence to nasal CPAP use. Results: There was a significant decrease in the level of daytime sleepiness of the patients users of nasal CPAP (p=0.017); patients not using nasal CPAP experienced a decrease without statistical significance (p=0.162). 100% of CPAP users reported benefits and 50% of these reported related discomforts. Conclusions: Patients with OSAHS that use CPAP have a greater reduced level of sleepiness than those who do not use it.

Targeted Mutagenesis in Pathogenic Leptospira Species: Disruption of the LigB Gene Does Not Affect Virulence in Animal Models of Leptospirosis

The pathogenic mechanisms of Leptospira interrogans, the causal agent of leptospirosis, remain largely unknown. This is mainly due to the lack of tools for genetically manipulating pathogenic Leptospira species. Thus, homologous recombination between introduced DNA and the corresponding chromosomal locus has never been demonstrated for this pathogen. Leptospiral immunoglobulin-like repeat (Lig) proteins were previously identified as putative Leptospira virulence factors. In this study, a ligB mutant was constructed by allelic exchange in L. interrogans; in this mutant a spectinomycin resistance (Spc(r)) gene replaced a portion of the ligB coding sequence. Gene disruption was confirmed by PCR, immunoblot analysis, and immunofluorescence studies. The ligB mutant did not show decrease virulence compared to the wild-type strain in the hamster model of leptospirosis. In addition, inoculation of rats with the ligB mutant induced persistent colonization of the kidneys. Finally, LigB was not required to mediate bacterial adherence to cultured cells. Taken together, our data provide the first evidence of site-directed homologous recombination in pathogenic Leptospira species. Furthermore, our data suggest that LigB does not play a major role in dissemination of the pathogen in the host and in the development of acute disease manifestations or persistent renal colonization.

Current management practices for acromegaly: an international survey

To determine whether peer-reviewed consensus statements have changed clinical practice, we surveyed acromegaly care in specialist centers across the globe, and determined the degree of adherence to published consensus guidelines on acromegaly management. Sixty-five acromegaly experts who participated in the 7th Acromegaly Consensus Workshop in March 2009 responded. Results indicated that the most common referring sources for acromegaly patients were other endocrinologists (in 26% of centers), neurosurgeons (25%) and primary care physicians (21%). In sixty-nine percent of patients, biochemical diagnoses were made by evaluating results of a combination of growth hormone (GH) nadir/basal GH and elevated insulin like growth factor-I (IGF-I) levels. In both Europe and the USA, neurosurgery was the treatment of choice for GH-secreting microadenomas and for macroadenomas with compromised visual function. The most widely used criteria for neurosurgical outcome assessment were combined measurements of IGF-I and GH levels after oral glucose tolerance test (OGTT) 3 months after surgery. Ninety-eight percent of respondents stated that primary treatment with somatostatin receptor ligands (SRLs) was indicated at least sometime during the management of acromegaly patients. In nearly all centers (96%), the use of pegvisomant monotherapy was restricted to patients who had failed to achieve biochemical control with SRL therapy. The observation that most centers followed consensus statement recommendations encourages the future utility of these workshops aimed to create uniform management standards for acromegaly.

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.