Comparative epidemiology of chronic fatigue syndrome in Brazilian and British primary care: prevalence and recognition

Background Although fatigue is a ubiquitous symptom across countries, clinical descriptions of chronic fatigue syndrome have arisen from a limited number of high-income countries. This might reflect differences in true prevalence or clinical recognition influenced by sociocultural factors. Aims To compare the prevalence, physician recognition and diagnosis of chronic fatigue syndrome in London and Sao Paulo. Method Primary care patients in London (n=2459) and Sao Paulo n=3914) were surveyed for the prevalence of chronic fatigue syndrome. Medical records were reviewed for the physician recognition and diagnosis. Results The prevalence of chronic fatigue syndrome according to Centers for Disease Control 1994 criteria was comparable in Britain and Brazil, 2.1% v. 1.6% (P=0.20). Medical records review identified 11 diagnosed cases of chronic fatigue syndrome in Britain, but none in Brazil (P<0.001). Conclusions The primary care prevalence of chronic fatigue syndrome was similar in two Culturally and economically distinct nations. However, doctors are unlikely to recognise and label chronic fatigue syndrome as a discrete disorder in Brazil. The recognition of this illness rather than the illness itself may be culturally induced.

Exploring the knowledge contained in neuroimages: Statistical discriminant analysis and automatic segmentation of the most significant changes

Objective: The aim of this article is to propose an integrated framework for extracting and describing patterns of disorders from medical images using a combination of linear discriminant analysis and active contour models. Methods: A multivariate statistical methodology was first used to identify the most discriminating hyperplane separating two groups of images (from healthy controls and patients with schizophrenia) contained in the input data. After this, the present work makes explicit the differences found by the multivariate statistical method by subtracting the discriminant models of controls and patients, weighted by the pooled variance between the two groups. A variational level-set technique was used to segment clusters of these differences. We obtain a label of each anatomical change using the Talairach atlas. Results: In this work all the data was analysed simultaneously rather than assuming a priori regions of interest. As a consequence of this, by using active contour models, we were able to obtain regions of interest that were emergent from the data. The results were evaluated using, as gold standard, well-known facts about the neuroanatomical changes related to schizophrenia. Most of the items in the gold standard was covered in our result set. Conclusions: We argue that such investigation provides a suitable framework for characterising the high complexity of magnetic resonance images in schizophrenia as the results obtained indicate a high sensitivity rate with respect to the gold standard. (C) 2010 Elsevier B.V. All rights reserved.

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.

Photodynamic therapy for acne vulgaris: A critical review from basics to clinical practice Part II. Understanding parameters for acne treatment with photodynamic therapy

Photodynamic therapy requires a photosensitizer, oxygen, and activating light. For acne, pilosebaceous units are ""target"" structures. Porphyrins are synthesized in vivo from 5-aminolevulinic acid (ALA), particularly in pilosebaceous units. Different photosensitizers and drug delivery methods have been reported for acne treatment. There are a variety of porphyrin precursors with different pharmacokinetic properties. Among them, ALA and methyl-ester of ALA (MAT.) are available for possible off-label treatment of acne vulgaris. In addition, various light sources, light dosimetry, drug incubation time, and pre- and posttreatment care also change efficacy and side effects. None of these variables has been optimized for acne treatment, but a number of clinical trials provide helpful guidance. In this paper, we critically analyze clinical trials, case reports, and series of cases published through 2009. (J Am Acad Dermatol 2010;63:195-211.)

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.

DETERMINATION OF ENERGY VALUE OF HAMBURGERS AND MEATBALLS BY DIRECT CALORIMETRY AND FOOD ANALYSIS COMPOSITION. COMPARISON WITH NUTRITION INFORMATION DISPLAYED ON PACKAGES

The nutritional composition found in the laboratory and those present on labels of manufactured foods can differ significantly. The purpose of this study was to determine the nutritional composition of hamburgers and meatballs and compare them with your labels. The food analysis was performed following the Analytical Standards Institute`s Adolfo Lutz and energy content was determined by bomb calorimetry. Regarding the energy value, all the samples had values less than informed on the label. The content of lipids of hamburgers and meatballs ( except the beef) were lower than those reported on the label. The values of protein for the meatballs and chicken hamburger had lower values than those labels. Thus, the labels may overestimate as underestimate some nutritional values, leading to population erroneous information.

Cannabidiol inhibitory effect on marble-burying behaviour: involvement of CB1 receptors

Cannabidiol (CBD) is a major nonpsychotomimetic component of Cannabis sativa that has been shown to have an anxiolytic effect in human and animal models. Earlier studies suggest that these effects involve facilitation of serotonin, a neurotransmitter that has also been related to obsessive-compulsive disorder. On the basis of this evidence, this study investigated the effects of CBD in C57BL/6J mice submitted to the marble-burying test (MBT), an animal model proposed to reflect compulsive behaviour. CBD (15, 30 and 60 mg/kg) induced a significant decrease in the number of buried marbles compared with controls (34, 41 and 48%, respectively). A similar, although larger, decrease was also found after the serotonin selective reuptake inhibitor paroxetine (10 mg/kg, 77% decrease) and the benzodiazepine diazepam (2.5 mg/kg, 84% decrease). The effect of CBD (30 mg/kg) was still significant after 7 days of daily repeated administration, whereas the effect of diazepam disappeared. Pretreatment with WAY100635 (3 mg/kg), a 5HT1A receptor antagonist, prevented the effects of paroxetine but failed to alter those of CBD. These latter effects, however, were prevented by pretreatment with the CB1 receptor antagonist AM251 (1 mg/kg). These results indicated that CBD and paroxetine decrease the number of buried marbles in the MBT through distinct pharmacological mechanisms. They also suggest a potential role of drugs acting on the cannabinoid system in modulating compulsive behaviour. Behavioural Pharmacology 21: 353-358 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Ovarian hyperstimulation syndrome: pathophysiology and prevention

To review and discuss the pathophysiology and prevention strategies for ovarian hyperstimulation syndrome (OHSS), which is a condition that may occur in up to 20% of the high risk women submitted to assisted reproductive technology cycles. The English language literature on these topics were reviewed through PubMed and discussed with emphasis on recent data. The role of estradiol, luteinizing hormone, human chorionic gonadotropin (hCG), inflammatory mediators, the renin-angiotensin system and vascular endothelial growth factor is discussed in the pathophysiology of OHSS. In addition we consider the prevention strategies, including coasting, administration of albumin, renin-angiotensin system blockage, dopamine agonist administration, non-steroidal anti-inflammatory administration, GnRH antagonist protocols, reducing hCG dosage, replacement of hCG and in vitro maturation of oocytes (IVM). Among the many prevention strategies that have been discussed, the current evidence points to the replacement of hCG by GnRH agonists in antagonist cycles and the performance of IVM procedures as the safest approaches.

Leuprolide acetate reduces both in vivo and in vitro ovarian steroidogenesis in infertile women undergoing assisted reproduction

Despite the probable inhibitory effects of GnRH analogues on ovarian steroidogenesis in vitro, their association with assisted reproduction protocols shows favorable results. This suggests that there are important differences in the behaviors of these drugs when administered in vivo versus in vitro. To clarify these differences, this study was designed to analyze the effect of leuprolide acetate (LA) on ovarian steroidogenesis in women undergoing In Vitro Fertilization (IVF). A prospective, randomized open label study was conducted on 14 women (26-35 years): seven receiving only gonadotrophins (Group 1) and seven receiving gonadotrophin plus LA at 1mg/day (Group 2). The LA in vivo effect was determined with serum and follicular fluid (FF) samples and via luteinized granulosa cell cultivation (GCC), where cells were obtained during oocyte retrieval after ovarian hyperstimulation. In vitro analysis was performed via addition of LA to GCC only for Group 1 (without LA) at progressively higher concentrations (0, 10(-12), 10(-9) and 10(-6) M). In vivo, the main observation was a reduction in androgen production in Group 2, represented by lower androstenedione production in FF (G1 = 6479 +/- 3458; G2 = 3021 +/- 1119 ng/ml; p = 0.04) and a lower testosterone peak in GC at 96 h (G1 = 0.64 +/- 0.12 ng/ml; G2 = 0.50 +/- 0.19ng/ml; P = 0.02), but a higher fertilization rate (G1 = 67%; G2 = 83%; p = 0.009). in vitro, testosterone, estradiol and progesterone were also reduced by LA, even though this reduction occurred for progesterone only at the highest LA dosage (10(-6) M; 606.0 +/- 114.3 ng/ml versus 1524.0 +/- 246.5 ng/ml; p=0.02). Results show that LA reduces ovarian steroidogenesis in vivo by essentially inhibiting androgen synthesis; whereas, in vitro, ovarian steroidogenesis is reduced overall. (C) 2008 Elsevier Inc. All rights reserved.

Cannabidiol for the treatment of psychosis in Parkinson`s disease

The management of psychosis in Parkinson`s disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson`s Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.

Intravitreal Bevacizumab for Diabetic Macular Edema Associated With Severe Capillary Loss: One-Year Results of a Pilot Study

PURPOSE: To evaluate the effects of intravitreal bevacizumab in patients with diabetic macular edema (DME) associated with severe capillary loss. DESIGN: Multicenter, open-label, nonrandomized study. METHODS: SETTING: Two tertiary ophthalmic referral centers in Brazil. STUDY POPULATION: Ten consecutive patients with DME and ""severe"" capillary loss. OBSERVATION PROCEDURES: Intravitreal injection(s) of bevacizumab (1.5 mg). Standardized ophthalmic evaluation was performed at baseline and at weeks 8, 16, 24, and 54. MAIN OUTCOME MEASURES: Changes in best-corrected visual acuity (BCVA) and in optical coherence tomography variables (central macular thickness [CMT] and total macular volume [TMV]). RESULTS: Significant changes in BCVA and in CMT/TMV were noted throughout the study (P<.001, P=.009, and P<.001, respectively). The mean logarithm of the minimal angle of resolution Early Treatment Diabetic Retinopathy Study BCVA was 0.786 (similar to 20/125(+1)) at baseline, 0.646 (similar to 20/80(-2)) at week 8, 0.580 (20/80(+1)) at week 16, 0.574 (similar to 20/80(+1)) at week 24, and 0.558 (similar to 20/80(+2)) at week 54. Compared with baseline, a significant change in BCVA was noted at all follow-up visits (P <=.008). The mean CMT/TMV values were, respectively, 472.6/10.9 at baseline, 371.4/9.9 at week 8, 359.5/9.8 at week 16, 323.9/9-4 at week 24, and 274.6/8.7 at week 54. Compared with baseline, a significant change in both CMT and TMV was noted only at 24 and 54 weeks (P <=.007). At 54 weeks, fluorescein angiography demonstrated no change in the extent of macular capillary loss and reduced dye leakage as compared with baseline in all patients. CONCLUSIONS: Favorable changes in BCVA and in CMT/TMV observed throughout 1 year suggest that intra-vitreal bevacizumab may be a viable alternative treatment for the management of patients with DME and severe capillary loss. (Am J Ophthalmol 2009;147:1022-1030. (C) 2009 by Elsevier Inc. All rights reserved.)

Regeneration of the Corneal Epithelium after Debridement of its Central Region: An Autoradiographic Study on Rabbits

Purpose: To investigate the proliferative behavior of the corneal and limbal epithelia after debridement on the central region of the rabbit cornea. Methods: After scraping a circular epithelial area, 5 mm in diameter, in the center of the cornea, (3)H-thymidine ((3)H-TdR) was injected intravitreally, and the rabbits killed from 1 to 49 days afterward. The cornea, together with the adjacent conjunctiva, was processed for autoradiography. Results: The regenerating epithelium at the center of the cornea exhibited high frequencies of labeled nuclei when compared to controls. The mitotic indexes for the limbus were comparable in experimental and control eyes. The unique basal stratum of the limbal epithelium exhibited quick proliferation and vertical migration in all eyes. Cells that remained labeled for four weeks or more were observed throughout the corneal epithelium, including its basal stratum, and this did not depend on epithelial damage. Conclusion: Corneal epithelium wounds are healed by sliding and proliferation of cells surrounding the epithelial gap without any evidence for the participation of the limbal epithelium. Daughter cells labeled with (3)H-TdR were visualized in all layers of the corneal epithelium up to 7 weeks after the DNA precursor injection. However, at this long interval, the only labeled cells in the limbus were in the suprabasal layers.

Morphological and autoradiographic studies on the corneal and limbal epithelium of rabbits

The investigation was centered on the morphological features of the conjunctiva-cornea transition (limbus) of the rabbit eye and the proliferative behavior of its epithelium. The eyes were processed for examination with light and electron microscopy, as well as for autoradiography after intravitreal injection of [H-3]thymidine ([H-3]TdR). At the sites of extraocular muscle insertion, the vascularization of the stroma extended to the peripheral cornea, and the limbal epithelium was thin with its basal stratum made up by clear cuboidal cells. In between the muscle insertions, the cuboidal clear cells, as well as the stroma blood vessels; were scarce. At the light microscope level, the basement membrane was distinct in the cornea but not in the limbus or the conjunctiva. Autoradiographs demonstrated that, at the limbus, the basal cells migrated very quickly to the suprabasal region and remained there up to the 28-day interval. Labeled cells were identified in all epithelial layers of the cornea, including the basal one, at 21 and 28 days but not in the limbal basal clear cells. The rate of renewal of conjunctival epithelium was similar to that observed for the transition with scarce clear cells. The high-resolution autoradiographs demonstrated that the basal cuboidal clear limbal cells exhibit a quick renewal and that they are not label-retaining cells. These latter ones were detected all over the corneal epithelium and in the suprabasal layers of the limbus up to 28 days, in physiological conditions, without the need of stimulation by damage to the corneal epithelium.

INTRAVITREAL INJECTION OF AUTOLOGOUS BONE MARROW-DERIVED MONONUCLEAR CELLS FOR HEREDITARY RETINAL DYSTROPHY A Phase I Trial

Purpose: To evaluate the short-term (10 months) safety of a single intravitreal injection of autologous bone marrow-derived mononuclear cells in patients with retinitis pigmentosa or cone-rod dystrophy. Methods: A prospective, Phase I, nonrandomized, open-label study including 3 patients with retinitis pigmentosa and 2 patients with cone-rod dystrophy and an Early Treatment Diabetic Retinopathy Study best-corrected visual acuity of 20/200 or worse. Evaluations including best-corrected visual acuity, full-field electroretinography, kinetic visual field (Goldman), fluorescein and indocyanine green angiography, and optical coherence tomography were performed at baseline and 1, 7, 13, 18, 22, and 40 weeks after intravitreal injection of 10 X 10(6) autologous bone marrow-derived mononuclear cells (0.1 mL) into 1 study eye of each patient. Results: No adverse event associated with the injection was observed. A 1-line improvement in best-corrected visual acuity was measured in 4 patients 1 week after injection and was maintained throughout follow-up. Three patients showed undetectable electroretinography responses at all study visits, while 1 patient demonstrated residual responses for dark-adapted standard flash stimulus (a wave amplitude approximately 35 mu V), which remained recordable throughout follow-up, and 1 patient showed a small response (a wave amplitude approximately 20 mu V) recordable only at Weeks 7, 13, 22, and 40. Visual fields showed no reduction (with a Goldman Standard V5e stimulus) for any patient at any visit. No other changes were observed on optical coherence tomography or fluorescein and indocyanine green angiograms. Conclusion: Intravitreal injection of autologous bone marrow-derived mononuclear cells in eyes with advanced retinitis pigmentosa or cone-rod dystrophy was associated with no detectable structural or functional toxicity over a period of 10 months. Further studies are required to investigate the role, if any, of autologous bone marrow-derived mononuclear cell therapy in the management of retinal dystrophies. RETINA 31: 1207-1214, 2011

Imipramine enhances cell proliferation and decreases neurodegeneration in the hippocampus after transient global cerebral ischemia in rats

This study was aimed to determine whether imipramine chronic treatment promotes neurogenesis in the dentate gyrus (DG) and interferes with neuronal death in the CA1 subfield of the hippocampus after transient global cerebral ischemia (TGCI) in rats. After TGCI, animals were treated with imipramine (20 mg/kg, i.p.) or saline during 14 days. 5-Bromo-2`-deoxyuridine-5`-monophosphate (BrdU) was injected 24 h after the last imipramine or saline injection to label proliferating cells. In order to confirm the effect of TGCI on neuronal death and cell proliferation, a group of animals was sacrificed 7 days after TGCI. Neurogenesis and neurodegeneration were evaluated by doublecortin (DCX)-immunohistochemistry and Fluoro-Jade C (FJC)- staining, respectively. The rate of cell proliferation increases 7 days but returns to basal levels 14 days after TGCI. There was a significant increase in the number of FJC-positive neurons in the CA1 of animals 7 and 14 days after TGCI. Chronic imipramine treatment increased cell proliferation in the SGZ of DG and reduced the neurodegeneration in the CA] of the hippocampus 14 days after TGCI. Immunohistochemistry for DCX detected an increased number of newly generated neurons in the hippocampal DG 14 days after TGCI, which was not affected by imipramine treatment. Further studies are needed to evaluate whether imipramine treatment for longer time would be able to promote survival of newly generated neurons as well as to improve functional recovery after TGCI. (C) 2009 Elsevier Ireland Ltd. All rights reserved.