The prednisolone suppression test in depression: Dose-response and changes with antidepressant treatment

Depressed patients have reduced glucocorticoid receptor (GR) function, as demonstrated by resistance to the suppressive effects of the synthetic glucocorticoid hormone, and GR agonist, dexamethasone. We have developed a suppressive test with prednisolone, a synthetic glucocorticoid that is similar to cortisol in its pharmacodynamics and pharmacokinetics, and binds to both the GR and the mineralocorticoid receptor (MR). We have found that depressed patients suppress normally to prednisolone, unless they are particularly non-responsive to treatment. In the present study, we evaluated 28 inpatients with treatment-resistant depression (TRD), and compared salivary cortisol secretion (at 0900 h, 1200 h and 1700 h) after placebo or after prednisolone (5 mg), before and after an inpatient treatment admission. Half of the patients (n = 14) reached treatment response. When comparing the assessment between admission and discharge, cortisol output after placebo fell (-26% of area under the curve; p = 0.024) while the output after prednisolone did not change. Moreover, there was no change in the response to prednisolone (percentage suppression) between admission at discharge, and this was not influenced by treatment response. Finally, we could confirm and extend our previously published data with prednisolone (5 mg), showing that depressed patients (n = 12) and controls (n = 12) suppressed equally to both 5 and 10 mg doses of prednisolone. This study suggests that the response to prednisolone is similar in depressed patients and controls at different doses of prednisolone, and does not change with symptomatic improvement. This is in contrast with findings, from us and others, using other measures of hypothalamic-pituitary-adrenal axis function, such as basal cortisol levels or the response to dexamethasone. Thus, we propose that the prednisolone suppression test may offer specific biological and clinical information, related to its action at both the GR and the MR. (C) 2010 Elsevier Ltd. All rights reserved.

Huntington`s Disease-Like 2 in Brazil-Report of 4 Patients

Huntington`s disease-like 2 (HDL2) is a neurodegenerative disorder found in people of African ancestry with clinical, radiological, and neuropathological manifestations similar to Huntington`s disease (HD). HDL2 is caused by a pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. We describe four cases of HDL2 from four unrelated families, and discuss their clinical findings. HDL2 should be considered in every patient with an HD-like phenotype who tests negative for the HD mutation, even if African ancestry is not immediately apparent. (C) 2008 Movement Disorder Society

Neurophysiological findings of the late-onset, dominant, proximal spinal muscular atrophies with dysautonomia because of the VAPB PR056SER mutation

The vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) Pro56Ser Mutation has been identified in Brazilian families showing various motor neuron syndromes. However, the neurophysiological characteristics of these patients have not been detailed, and some questions Still need to be solved, such as the possible presence of myotonia and the origin of the abdominal protrusion seen in most patients. The eventual finding of suggestive electrophysiological characteristics would be helpful not only for clinical diagnosis but also to selection of the appropriate DNA test. To clarify these questions we carried out sensory and motor conduction Studies, including symphatetic skin response, and needle examination in six genetically proven affected members. The electromyographic findings were those of a slowly progressive motor neuron disorder. Topographically, the abdominal muscles were severely affected, but the facial and laryngeal muscles were preserved or very mildly involved. Sensory conduction studies and sympathetic Skin responses were normal. No myotonic discharge was recorded. These findings are indistinguishable from those of other motor neuron disorders, although the predominant involvement of the proximal limbs and of the abdominal muscles may be of some help in the appropriate clinical setting.

OCT findings in macular hole formation in eyes with complete vitreofoveal separation

The current study describes the morphologic macular features in two eyes that developed full-thickness macular holes in the setting of documented vitreofoveal separation. Using third-generation optical coherence tomography, complete vitreofoveal separation associated with the disruption of the inner foveal retina was documented in both cases. Five months after presentation, decreased vision and epiretinal membrane formation associated with development of a full-thickness macular hole were observed in the first patient. In the second patient, a full-thickness macular hole was demonstrated by optical coherence tomography 6 weeks after presentation. These findings suggest that full-thickness macular holes may develop in eyes with vitreofoveal separation. Evidence of the disturbance of the inner foveal architecture on optical coherence tomography indicates the potential role of factors other than anteroposterior or oblique vitreoretinal tractional forces in the genesis of some full-thickness macular holes.

Nasal allergies in the Latin American population: Results from the Allergies in Latin America survey

Allergies in Latin America is the first cross-national survey that describes the symptoms, impact, and treatment of nasal allergies (NAs) in individuals >= 4 years old in Latin America (LA). In total, 22,012 households across the Latin American countries of Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela were screened for children, adolescents, and adults with a diagnosis of NA and either symptoms or treatment in the past 12 months. A total of 1088 adults and 457 children and adolescents were included and the sample was probability based to ensure valid statistical inference to the population. Approximately 7% of the LA population was diagnosed with NAs with two of three respondents stating that their allergies were seasonal or intermittent in nature. A general practice physician or otolaryngologist diagnosed the majority of individuals surveyed. Nasal congestion was the most common and bothersome symptom of NAs. Sufferers indicated that their symptoms affected productivity and sleep and had a negative impact on quality of life. Two-thirds of patients reported taking some type of medication for their NAs, with a roughly equal percentage of patients reporting taking over-the-counter versus prescription medications. Changing medications was most commonly done in those reporting inadequate efficacy. The most common reasons cited for dissatisfaction with current medications were related to inadequate effectiveness, effectiveness wearing off with chronic use, failure to provide 24-hour relief, and bothersome side effects (e.g., unpleasant taste and retrograde drainage into the esophagus). Findings from this cross-national survey on NAs have confirmed a high prevalence of physician-diagnosed NAs and a considerable negative impact on daily quality of life and work productivity as well as substantial disease management challenges in LA. Through identification of disease impact on the LA population and further defining treatment gaps, clinicians in LA may better understand and treat NAs, thus leading to improvements in overall patient satisfaction and quality of life. (Allergy Asthma Proc 31:S9-S27, 2010; doi: 10.2500/aap.2010.31.3347)

Pain and distress reactivity and recovery as early predictors of temperament in toddlers born preterm

Background: Pain reactivity may reflect underlying mechanisms of constitutional aspects of temperament. Aim: To examine whether the neonatal biobehavioral reactivity and recovery responses from pain and distress, as well as the gestational age, the illness severity and the amount of painful procedures undergone the Neonatal Intensive Care Unit (NICU) stay, predict temperament later in toddlerhood, in vulnerable children born preterm. Study design: Prospective-longitudinal study. Subjects: Twenty-six preterm and very low birth weight infants followed from birth to toddlerhood. Outcome measures: Illness severity was assessed with the Clinical Risk Index for Babies (CRIB) score. The medical charts were reviewed prospectively for obtaining the amount of pain exposure in NICU. For assessing the behavioral and cardiac reactivity and recovery from pain and distress, the neonates were evaluated during routine blood collection in the NICU in the first 10 days of life. Pain and distress reactivity and recovery was measured using the Neonatal Facial Coding System score, the duration of crying. and the magnitude of average heart rate. At toddlerhood, mothers answered the Early Childhood Behavior Questionnaire. Results: Higher biobehavioral reactivity to pain and distress predicted higher temperamental Negative Affect, above and beyond gestational age, illness severity and amount of pain exposure in NICU. However, we did not find a predictive relation between gestational age, CRIB score and number of painful procedures undergone NICU and toddler`s temperament. Conclusions: The findings highlight the relevance of the neonatal individual characteristics of reactivity for identifying more vulnerable infants for future problems in biobehavioral regulation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.

Mesial temporal lobe epilepsy: Clinical and neuropathologic findings of familial and sporadic forms

Purpose: To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms. Methods: Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of Sao Paulo School of Medicine at Ribeirao Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm`s stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining. Results: There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm`s staining in the fascia dentata-inner molecular layer (p < 0.05). Discussion: Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures.

Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM-1)

Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process to the negative selection of autoreactive thymocytes. This phenomenon was termed ""promiscuous gene expression"" (PGE), which is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of autoimmune diseases are largely unknown, though it may be a result of a chronological effect. Although the effect of Aire mutations in pathogenic autoimmunity is well know, it could not be a unique cause for autoimmunity. Independently of mutations, temporal deregulation of Aire expression may imbalance Aire-dependent PTAs and/or wide PGE. This deregulation may be an early warning sign for autoimmune diseases as it guarantees autoantigen representation in the thymus. To assess this hypothesis, we studied the expression levels of Aire, Aire-dependent (Ins2) and Aire-independent (Gad67 and Col2a1) PTAs using real-time-PCR of the thymic stromal cells of NOD mice during the development of autoimmune type 1 diabetes mellitus (DM-1). Wide PGE was studied by microarrays in which the PTA genes were identified through parallel CD80(+) mTEC 3.10 cell line expression profiling. The results show that Aire gene was down-regulated in young pre-autoimmune (pre-diabetic) NOD mice. PGE and specific PTA genes were down-regulated in adult autoimmune diabetic animals. These findings represent evidence indicating that chronological deregulation of genes important to negative selection may be associated with the development of an autoimmune disease (DM-1) in mice.

Audiological findings in pacients treated with radiotherapy for head and neck tumors

Radiotherapy has been widely used given its increase in the successful outcomes and cure of some cancers. Aim: To evaluate the functionality of the auditory system in patients who underwent radiotherapy treatment for head and neck tumors. Materials and Methods: From May 2007 to May 2008, otorhinolaryngological and audiological evaluation (Pure Tone Audiometry (air and bone conduction), Speech Audiometry, Tympanometry, Acoustic Reflex testing and Distortion Product Otoacoustic Emissions) were performed in 19 patients diagnosed with head and neck neoplasia and treated with radiotherapy. Prospective case series study. Results: 10.5% left ears and 26.3% right ears had bilateral hearing loss soon after radiotherapy according to ASHA criteria. Conclusions: Radiotherapy treatment for head and neck cancer has ototoxic effects. Early programs of auditory rehabilitation should be offered to these patients.

Comparison of MB fraction of creatine kinase mass and troponin I serum levels with necropsy findings in acute myocardial infarction

Serum levels of troponin and heart-related fraction of creatine kinase (CK-MB) mass are used as diagnostic and prognostic criteria in myocardial infarction, but the relation between those levels and-the necropsy-determined size of necrosis has not been tested in human beings. In this retrospective study, 1-cm-thick transverse sections of the ventricles were cut from the base to the apex in the necropsy hearts of 27 patients aged 47 to 86 years (mean 66, median 69; 19 men). Total and necrotic areas were measured using a computer-linked image analysis system. The weights of the necrotic areas were also calculated. The correlations of the areas and weights of necrotic myocardium with the highest serum values of CK-MB mass and troponin 1, which had been quantified during life by chemiluminescence immunoassays, were verified by Pearson`s test; results were considered significant at p <= 50.05. Significant correlations were detected between CK-MB mass peak and infarct size (r = 0.63, p < 0.01) and weight (r = 0.69, p < 0.01) and between CK-MB mass and highest troponin level (r = 0.73, p < 0.01); however, the correlations between highest troponin level and myocardial infarct size (r = 0.31, p = 0.11) and weight (r = 0.35, p = 0.07) were small and nonsignificant. In conclusion, despite the well-established role of serum levels of troponin as a diagnostic tool for myocardial infarction, their highest values showed poor correlations with the extent of infarct. In contrast, the highest serum level of CK-MB mass was well correlated with myocardial infarct size. (c) 2008 Elsevier Inc. All rights reserved.