Estradiol in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune polymorphous disease that primarily affects women of reproductive age. This gender disparity has suggested the importance of investigating the role of reproductive hormones in the pathogenesis of the disease. Estradiol, the most potent form of estrogen, plays a key role in shaping the immune system including the production of lymphocytes, the peripheral differentiation of regulatory T cells (T-regs), antibody production, and the complement and interferon systems, and has been studied in the pathogenesis of systemic lupus erythematosus (SLE). It operates by binding to estrogen receptors (ERs) α and ß, initiating cellular responses including alterations in gene expression. Regulatory T cells are instrumental in preserving immunological self-tolerance and moderating immune responses. Estradiol's serum levels correlate with the expansion of CD4+CD25+ and FoxP3+ in healthy females. However, this response is reduced in lupus patients. Estradiol also interacts with microRNAs (miRNAs) in gene regulation. Hsa-miR-10b-5p, a miRNA targeting SRSF1, is overexpressed in SLE patients and its levels increase with exposure to estrogens. Other miRNAs also show correlation with plasma Estradiol levels. The precise role of Estradiol in the pathogenesis of SLE remains complex and multifaceted and is a topic for further research.

Risk of hepatitis B virus reactivation in hepatitis B virus + hepatitis C virus-co-infected patients with compensated liver cirrhosis treated with ombitasvir, paritaprevir/r + dasabuvir + ribavirin.

Hepatitis B virus may reactivate in patients with chronic hepatitis C treated with direct-acting antivirals. The aim of this study was to investigate the risk of hepatitis B virus (HBV) reactivation in HBV + hepatitis C virus (HCV)-co-infected patients with compensated liver cirrhosis treated with paritaprevir/ombitasvir/ritonavir, dasabuvir with ribavirin. We reviewed prospectively gathered data from a national cohort of 2070 hepatitis C virus patients with compensated liver cirrhosis who received reimbursed paritaprevir/ombitasvir/r, dasabuvir with ribavirin for 12 weeks from the Romanian National Health Agency during 2015-2016. Twenty-five patients in this cohort were HBs antigen positive (1.2%); 15 untreated with nucleotide analogues agreed to enter the study. These patients were followed up: ALT monthly, serology for HBV and DNA viral load at baseline, EOT and SVR at 12 weeks. Hepatitis B virus (HBV)-co-infected patients were all genotype 1b and 52% females, with a median age of 60 years (51 ÷ 74); 76% were pretreated with peginterferon + ribavirin; 72% were with severe necroinflammatory activity on FibroMax assessment; 40% presented comorbidities; and all were HBe antigen negative. Hepatitis C virus (HCV) SVR response rate was 100%. Hepatitis B virus (HBV)-DNA viral load was undetectable in 7/15 (47%) before therapy, and for the other 8 patients, it varied between below 20 and 867 IU/mL. Five patients (33%) presented virological reactivation (>2 log increase in HBV-DNA levels) during therapy. One patient presented with hepatitis associated with HBV reactivation, and two started anti-HBV therapy with entecavir. Hepatitis B virus (HBV) virological reactivation was present in 33% in our patients. Generally, HBV-DNA elevations were mild (<20 000 IU/mL); however, we report one case of hepatitis associated with HBV reactivation.

Different effects of anti-TNF-alpha biologic drugs on the small bowel macroscopic inflammation in patients with ankylosing spondylitis.

BACKGROUND & AIMS: Considering the ability of anti-TNF alpha drugs to lower the burden intestinal inflammation in patients with inflammatory bowel disease (IBD), and the similarity between IBD and ankylosing spondylitis (AS) regarding inflammatory intestinal involvement, we aimed to investigate the impact of anti-TNF alpha biologic therapy on subclinical intestinal inflammation in AS patients. METHODS: Between January 2008 and December 2013, 38 AS patients and 23 controls were enrolled in the study and investigated with small bowel videocapsule endoscopy examination and ileocolonoscopy. Each tertile of the small bowel (proximal, mid and distal) was assessed by calculating the Lewis score based on the image stream. RESULTS: The Lewis scores were significantly higher in the AS group compared to controls (580.9 ± 818 vs. 81 ± 121, p<0.001). 16 patients (42.1%) were on anti-TNF alpha therapy (Adalimumab (n = 5), Infliximab (n = 5) or Etanercept (n = 6)).31.3% of them used NSAIDs simultaneously, compared with 77.3% of the other patients (p<0.01). Their Lewis scores were lower compared to the other patients for the entire small bowel (306 ± 164 vs. 790 ± 1038, p = 0.015), its proximal and distal tertiles (238 ± 154 vs. 560 ± 543, p = 0.021, and 140 ± 189 vs. 300 ± 220, p = 0.027, respectively). The Lewis score was also lower in patients receiving Adalimumab/Infliximab compared to those on Etanercept for the entire bowel and its distal tertile (262 ± 165 vs. 380 ± 148, p = 0.069 and 62 ± 101 vs. 273 ± 236, p = 0.060, respectively). CONCLUSION: Anti-TNF alpha therapy in patients with AS reduces the subclinical intestinal inflammation, but the magnitude seems to depend upon the class anti-TNF alpha agent used (Clinical Trials. gov NCT00768950).

Preparation regimen is more important than patient-related factors: a randomized trial comparing a standard bowel preparation before colonoscopy with an individualized approach.

BACKGROUND: Optimal bowel preparation is one of the most important factors affecting the quality of colonoscopy. Several patient-related factors are known to influence the quality of bowel cleansing but randomized trials in this area are lacking. We aimed to compare an individualized bowel prep strategy based on patient characteristics to a standard preparation regimen. MATERIAL AND METHODS: We conducted an endoscopist-blinded multicenter randomized control-trial. The Boston Bowel Prep Score (BBPS) was used to assess quality of bowel preparation and a 10 point visual analogue scale to assess patient comfort during bowel prep. Patients were randomised to either the standard regimens of split-dose 4L polyethylene-glycol (group A), split-dose sodium picosulphate/magnesium citrate (group B) or to either of the two depending on their responses to a 3-item questionnaire (individualized preparation, group C). RESULTS: 185 patients were randomized during the study period and 143 patients were included in the final analysis. Patients in the individualized group had a median BBPS of 7 compared to a median of 6 in the standard group (p = 0.7). Also, there was no significant difference in patients' comfort scores, irrespective of study group or laxative regimen. However, on multivariable analysis, a split-dose 4L polyethylene-glycol was an independent predictor for achieving a BBPS>6 (OR 3.7, 95% CI 1.4-9.8), regardless of patient-related factors. CONCLUSION: The choice of laxative seems to be more important than patient-related factors in predicting bowel cleansing. Comfort during bowel prep is not influenced by the type of strategy used.

Is there still a place for erythrocyte sedimentation rate and C-reactive protein in systemic lupus erythematosus?

The inflammatory response during systemic lupus erythematosus (SLE) flares is known to be atypical, characterized by a disproportionately lower C-reactive protein (CRP) elevation when compared with erythrocyte sedimentation rate (ESR). Thus, in these patients, the analysis of inflammatory markers might be challenging in daily clinical practice. Clinicians need frequently to distinguish lupus reactivations and infectious conditions, and the significance of ESR and CRP seems to be different. Even though a non-specific marker of inflammation, ESR utility in SLE should not be neglected and it appears to be a useful biomarker for SLE activity assessment. Describing a specific cut-off for ESR in SLE is important for patients' follow-up, and levels up to 25-30 mm/h have been proposed as an upper limit of the normal range. Regarding CRP, even though higher baseline levels are described in SLE when compared with controls, including in remission periods, its response during flares seems to be incomplete and not always correlated with disease activity; while CRP values greater than 10 mg/l could be indicative for severe flares, when there is no serositis or arthritis, higher CRP levels above 50-60 mg/l may be associated with infection.

Rapid Fecal Calprotectin Testing Predicts Mucosal Healing Better than C-reactive Protein and Serum Tumor Necrosis Factor α in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Serum and fecal biomarkers have been used as noninvasive methods for assessing disease activity in ulcerative colitis. C-reactive protein, serum tumor necrosis factor-α and fecal calprotectin are among the most promising such biomarkers. However, their role in the management of ulcerative colitis patients remains to be clarified. We aimed to evaluate the accuracy of C-reactive protein, fecal calprotectin and tumor necrosis factor-α in detecting clinical and endoscopic activity and predicting disease outcome. METHODS: A cohort of ulcerative colitis patients was prospectively evaluated for clinical and endoscopic disease activity using the Mayo score. Serum C-reactive protein and tumor necrosis factor-α levels were measured and a point-of-care method was used for determining Calprotectin levels. RESULTS: Fifty-three patients with ulcerative colitis were followed for a median of 12 months. Fecal calprotectin and C-reactive protein levels were significantly higher in patients with clinically active disease at baseline, but only calprotectin levels correlated with endoscopic activity. Calprotectin values over 300 µg/g had 60% sensitivity and 90% specificity for detecting active endoscopic disease and 61% sensitivity and 89% specificity for predicting mucosal healing. CONCLUSION: Rapid calprotectin testing is a better predictor of mucosal healing than serum biomarkers and it could improve the management of ulcerative colitis patients by decreasing the need for invasive investigations.

IL-17, IL-6 and IFN-γ in Systemic Sclerosis Patients.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease characterized by cutaneous and visceral fibrosis and its pathogenesis is incompletely understood. T helper cells are key regulators of the immune response and they seem to be involved in Ssc clinical manifestations. The aim of the study is to determine key cytokines secreted by Th1 (IFN-γ), Th2 (IL-6) and Th17 (IL-17) in Ssc patients and correlate them with specific manifestations of Ssc patients. MATERIAL AND METHODS: 35 consecutive Ssc patients and 20 age and sex matched controls were recruited. Serum IL-17, IFN-γ and IL-6 were determined using ELISA method. RESULTS: Serum IL-17 and IL-6 levels were not significantly different in Ssc patients and controls. Serum IFN-γ levels were higher in Ssc patients when compared to controls. Higher serum IFN-γ levels associated with pulmonary hypertension. After adjusting for gender and age, IL-17 levels remained independently associated with some clinical manifestations of Ssc patients (telangiectasia and high activity score of Ssc). CONCLUSION: Th17 and Th1 cell responses are active in Ssc patients as their cytokines associated with higher disease activity scores and pulmonary manifestations. Th17 and Th1 specific activity and homing within Ssc patients still needs to be defined and determined in order to target them as potential future therapeutic targets in Ssc patients.

Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients.

BACKGROUND: The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate. AIM: To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients. METHODS: 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE's criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS's criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive "criteria" APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-P2 glycoprotein I antibodies (aß2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT). Results. Only the aß2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/ without positive APLAs): median (min; max) 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p<0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aß2 GPI (IgG and IgM ) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the "non-criteria" APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels. CONCLUSIONS: IgG aß2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the "non-criteria" APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the "non-criteria" APLAs with the antiDNA and complement C3 levels were also observed.

Factors affecting colonoscopy comfort and compliance: a questionnaire based multicenter study.

AIMS: Colonoscopy screening reduces colorectal cancer-related mortality and incidence. However, many patients are reluctant to undergo colonoscopy or return for follow-up because of the investigation's cumbersome and unpleasant nature. We aimed to identify patient-related factors significantly influencing comfort and quality of colonoscopy analyzing responses to a self-administered validated questionnaire. METHODS: Patients undergoing colonoscopy under sedation in two high-volume endoscopy units were invited to answer a short prevalidated questionnaire regarding preprocedure anxiety, satisfaction with information provided, most worrisome aspect of the procedure and knowledge of the benefits of colonoscopy. Self-reported comfort during colonoscopy as graded on a 10 point visual analog scale was the main variable considered. Univariate analysis identified factors possibly associated with a higher degree of comfort during colonoscopy that were then tested through multivariate logistical regression. RESULTS: 452 questionnaires were returned. Most patients reported an acceptable degree of discomfort during colonoscopy but 70.2% of the respondents considered the information provided prior to the procedure to be insufficient. On multivariate analysis older age, higher degree of satisfaction with information provided (p = 0.04), lower preprocedure anxiety levels (p < 0.01) and endoscopy center (p < 0.01) were shown to correlate with increased comfort during colonoscopy. Education level, previous colonoscopy, gender and bowel prep quality did not influence patient comfort. CONCLUSIONS: Patient comfort during colonoscopy is dependent on satisfaction with the information provided before the procedure. Higher availability of the physician and better interaction with the patient might decrease patient perceived burden of colonoscopy and lead to higher return rates in the screening and surveillance setting.

Pharmacological treatment in calcinosis cutis associated with connective-tissue diseases.

BACKGROUND: Dystrophic calcinosis cutis is a common manifestation in connective tissue diseases, but there's still no consensus on treatment. OBJECTIVES: The purpose of this review is to discuss the current pharmacological options of treatment in calcinosis cutis related to rheumatic diseases. METHOD: We performed an extensive MEDLINE search of articles from 1970 to January 2014 using the index word "calcinosis" and the co-indexing terms "treatment", "calcium channel blocker", "diltiazem", "nifedipine", "verapamil", "amlodipine", "anticoagulant", "warfarin", "bisphosphonate", "etidronate", "pamidronate", "alendronate", "risedronate", "aluminum hydroxide", "probenecid", "antibiotic", "tetracycline", "minocycline", "ceftriaxone", "colchicine", "intravenous immunoglobulin", "sodium thiosulfate", "TNF-alpha inhibitors", "infliximab", "rituximab", "thalidomide", "corticosteroids", "stem cell transplantation". RESULTS: Diltiazem is recommended by some authors as first-line approach in calcinosis cutis and is also the therapeutic principal referred by the largest number of available publications. It seems to be efficient in more than half of the reported cases. There remain, however, a significant number of patients in which another solution must be found. The general trends observed over time are of switching the search of solutions in dystrophic calcinosis cutis related to connective tissue diseases, from therapies on calcium metabolism to therapies for the underlying disease. The new options available in the management of calcinosis cutis, like biological therapies or intravenous immunoglobulin, seem to be promising, but not universally successful. In children with severe forms, hematopoietic stem cell transplantation can also be taken into consideration. CONCLUSIONS: Data for all therapies proposed in calcinosis cutis is generally reported in single cases and small case series and so, the existent data is all yielding a low level of evidence.

Novel predictors of intrapulmonary vascular dilatations in cirrhosis: extending the role of pulse oximetry and echocardiography.

BACKGROUND AND STUDY AIMS: Intrapulmonary vascular dilatations (IPVDs) are a criterion for the diagnosis of hepatopulmonary syndrome in patients with liver cirrhosis. We aimed to show that IPVDs are more common than suspected in a heterogenous cirrhotic population and to identify new diagnostic parameters. PATIENTS AND METHODS: Forty-three consecutive patients with cirrhosis admitted to our Gastroenterology department were included in this prospective study. History, physical examination, ECG and, when warranted, pulmonary function tests and chest radiograph were used to exclude patients with significant cardiac or pulmonary disease. Contrast enhanced transthoracic echocardiography (CEE) was used to determine the presence of IPVDs. Pulse oximetry readings were taken in the supine and standing positions. RESULTS: We found 12 patients with IPVDs. Statistical analysis proved the correlation between IPVDs and systolic pulmonary artery pressure (sPAP) (p= .049), right ventricle wall width (RVW) (p = .013) and E/A ratio (p = .034) but not left atrial or ventricular diameter. Orthodeoxia was also present more frequently in patients with positive CEE. The difference between supine and standing oxygen saturation (changeSat) proved a fair diagnostic test for detecting IPVDs, with an area under the receiver operated curve (AUROC) of 0.823. CONCLUSIONS: Our study shows that RVW, sPAP, E/A and orthodeoxia determined by pulse oximetry are valuable novel predictors of IPVDs, encouraging the routine use of pulse oximetry and echocardiography in cirrhotic patients.

Clinical prediction rule for differentiating tuberculous from viral meningitis.

SETTING: The Professor Dr Matei Bals National Institute of Infectious Diseases, Bucharest, Romania. OBJECTIVE: To create a prediction rule to enable clinicians to differentiate patients with tuberculous meningitis (TBM) from those with viral meningitis. DESIGN: We retrospectively analysed patients admitted to a tertiary care facility between 2001 and 2011 with viral meningitis and TBM. Patients were defined as having TBM according to a recently published consensus definition, and as viral meningitis if a viral aetiology was confirmed, or after ruling out bacterial, fungal and non-infectious causes of meningitis. RESULTS: We identified 433 patients with viral meningitis and 101 TBM patients and compared their clinical and laboratory features. Multivariable analysis showed a statistically significant association between TBM and the following variables: duration of symptoms before admission of ≥5 days, presence of neurological impairment (altered consciousness, seizures, mild focal signs, multiple cranial nerve palsies, dense hemiplegia or paraparesis), cerebrospinal fluid/blood glucose ratio < 0.5 and cerebrospinal fluid protein level > 100 mg/dl. We propose a diagnostic score based on the coefficients derived from the logistic regression model with a sensitivity and specificity for TBM of respectively 92% and 94%. CONCLUSIONS: Our study suggests that easily available clinical and laboratory data are very useful for differentiating TBM from other causes of meningitis.

Detection of Mycobacterium tuberculosis resistance mutations to rifampin and isoniazid by real-time PCR.

OBJECTIVE: The objective of our study was to evaluate the use of a real-time polymerase chain reaction (PCR)-based technique for the prediction of phenotypic resistance of Mycobacterium tuberculosis. MATERIALS AND METHODS: We tested 67 M tuberculosis strains (26 drug resistant and 41 drug susceptible) using a method recommended for the LightCycler platform. The susceptibility testing was performed by the absolute concentration method. For rifampin resistance, two regions of the rpoB gene were targeted, while for identification of isoniazid resistance, we searched for mutations in katG and inhA genes. RESULTS: The sensitivity and specificity of this method for rapid detection of mutations for isoniazid resistance were 96% (95% CI: 88% to 100%) and 95% (95% CI: 89% to 100%), respectively. For detection of rifampin resistance, the sensitivity and specificity were 92% (95% CI: 81% to 100%) and 74% (95% CI: 61% to 87%), respectively. The main isoniazid resistance mechanism identified in our isolates is related to changes in the katG gene that encodes catalase. We found that for rifampin resistance the concordance between the predicted and observed phenotype was less than satisfactory. CONCLUSIONS: Using this method, the best accuracy for genotyping compared with phenotypic resistance testing was obtained for detecting isoniazid resistance mutations. Although real-time PCR assay may be a valuable diagnostic tool, it is not yet completely satisfactory for detection of drug resistance mutations in M tuberculosis.

Preliminary data on the involvement of B, C and D hepatitis viruses in the etiopathogenesis of chronic lymphoproliferative syndromes in Romania.

UNLABELLED: THE AIMS OF THE STUDY: Evaluation of the prevalence of HBV, HCV, HDV infection in patients with chronic lymphoproliferative diseases (CL), identification of the most involved viral genotypes, correlation between viremia dynamics and CL evolution, detection of molecular mechanisms implicated in CL pathogenesis, identification of lymphocytic receptors for viral antigens and biologic markers for early diagnosis of CL. METHODS: We present preliminary results of the first year of our research grant. This is a prospective, analytic, observational study in patients diagnosed with CL and HBV, HCV, HDV chronic infection. We included the following forms of CL: non-Hodgkin malignant lymphoma (NHL), Hodgkin lymphoma (HL) and chronic lymphocytic leukemia (CLL). We used the following commercial test kits: HCV RNA Real time PCR on a COBAS TaqMan (Roche Diagnostics) analyzer with 28 to 140.000.000 UI/ml detection range for HCV viremia, HBV DNA Real time PCR on a COBAS TaqMan (Roche Diagnostics) analyzer with 6 to 110.000.000 UI/ml detection range for HBV and the Roboscreen-RoboGene AJ kit with 10-10.000.000 replica/ml detection range for HDV. RESULTS: We have included 20 patients with CL and chronic hepatitis infection so far. Median age of the patients was 61 years. The identified CL forms were: B cell NHL (15 cases), T cell NHL (1 case), CLL (3 cases), Hodgkin lymphoma (1 case), equally distributed in aggressive and indolent forms of CL. HCV infection was diagnosed in 10 patients with CL, HBV infection was found in 10 patients with CL, 3 of them having co-infection HBV + HDV. In 4 patients with HBV infection viremia was over 20.000 IU/ml and the pattern of the CL was the aggressive form of the disease. The feature of the co-infection HBV + HDV was the predominance of indolent forms of CL. Among patients with HCV infection, only 3 cases were detected with viremia over 600.000 IU/ml and CL was represented by aggressive forms of the disease. We also have immunohistochemical data available in 19 cases, which seem to confirm the role of hepatitis viruses in lymphoproliferative disease etiopathogenesis. CONCLUSIONS: We ascertained an almost equally represented prevalence of HCV and HBV infection in patients with CL. The levels of HBV, HCV and HDV viremia were low in most of the cases. The most frequent form of CL was B cell NHL. We found an equal distribution between indolent and aggressive forms of NHL associated to hepatitis virus infection.

Involuntary weight loss: case series, etiology and diagnostic.

Involuntary weight loss is an important clinical condition that has not been extensively covered in the medical literature. Searching MEDLINE, we identified twelve case series in different regions of the world, mostly in developed countries. Three series included ambulatory patients, while nine studied patients from secondary care hospitals. A quarter of patients with involuntary weight loss had a cancer, and many had psychiatric diseases. Organic causes of involuntary weight loss are usually revealed by a basic evaluation, and a normal result is generally reassuring. In this case it is recommended a watchful surveillance instead of blind investigations, because the prognosis of IWL of undetermined cause is good. On the contrary, patients with involuntary weight loss caused by cancers have a severe prognostic due to the advanced stage of the disease. On the other way, these patients are easy to diagnose.

Otoacoustic emissions analysers for monitoring aminoglycosides ototoxicity.

OBJECTIVES: Aminoglycosides (AG) are widely prescribed despite their notorious toxicity. These antibiotics cause irreversible hearing loss, starting with high frequencies and progressing toward conversational frequencies (0.5-2 kHz), by destroying the acoustic hair cells in the inner ear. The integrity of these cells could be analysed by recording faint sounds that they produce otoacoustic emissions (OAE). The aim of the present study was to monitor and to characterise the acoustic toxicity of the AG using an OAE analyser. METHOD: We performed a prospective study of 49 patients receiving gentamicin (G), during 2007-2008. We made serial OAE recordings with an ILO 92 analyser (1-8 kHz) on at least 3 occasions: at the start, during treatment and after the cessation of G therapy (1-6 months). The recordings were performed at the patient's bedside and did not require the active participation of the patient. The method is fast, non-invasive, accurate and does not request an ENT specialist. We included patients presenting OAE. Ototoxicity was defined using adapted ASHA (American Speech Hearing Association) criteria. RESULTS: We studied 49 patients (24/25 female/male), mean age of 37.24 (3-70 years old), who received G for 4-42 days: less than 10 days--24 patients and more than 10 days--25 patients. Hearing impairment was observed in 10 patients (20.4%) and appeared during the therapy or in the next 3 months, with a loss of one or 2 high frequencies that occurred unilaterally in 9 out of 10 cases. The acoustic damage correlates with the length of G treatment. We did not find a statistical correlation between the degree of impairment and the age, regimen or addition of another ototoxic drug, although the hearing loss was slightly higher in those with concomitant exposure. CONCLUSION: OAE monitoring of AG treatment is a very useful way for detecting and preventing acoustic toxicity, because it could warn about hearing loss before damage of the conversational frequencies. The accuracy is similar to the classical methods, but it is faster and easier to perform.

Impact of highly active antiretroviral therapy on cytomegalovirus viraemia in the absence of specific anti-cytomegalovirus therapy.

OBJECTIVES: (1) to evaluate the effect of HAART on CMV viraemia in co-infected patients, in the absence of specific anti-CMV therapy; (2) to compare 2 molecular biology techniques for the detection and quantification of CMV-DNA in these patients. METHODS: We present the preliminary data of an ongoing prospective research grant on newly diagnosed HIV seropositives, in a tertiary care hospital, during June 2006- June 2008. Clinical, virological (HIV and CMV viraemia) and immunological (CD4) screening was performed every 3 months. The CMV viraemia was performed by RoboGene Human Cytomegalovirus Quantification kit (aj Roboscreen). We retested all undetectable CMV viremia found in patients with CD4 <50/mmc, by CMV PCR kit (Qiagen Diagnostics). Both PCR reactions were performed on ABI Prism 7000 (Applied Biosystems). RESULTS: Up to date, our study has included 105 HIV-infected subjects, who were seropositive for anti-CMV IgG antibodies. Average follow-up was 18 months. CMV viraemia was found detectable in 21 cases at first visit and in other 5 at the second visit. 22 cases had CD4 <50/mmc, among which 14 had undetectable CMV viraemia. The results of both molecular biology techniques were widely the same. HAART was prescribed to 86% of the patients; all the patients having detectable CMV viraemia received HAART, but not any specific anti-CMV therapy. Under HAART, all the detectable CMV loads which were retested in time became undetectable at next visits, after a median of 16.5 weeks from the introduction of therapy. CONCLUSIONS: CMV viraemia detection was useful in early diagnosis of asymptomatic CMV infection. As opposed to transplant cases, molecular biology techniques for the detection and quantification of CMV-DNA in HIV-patients have not been standardized yet. In our study, the two kits RoboGene Human Cytomegalovirus (HCMV) Quantification kit (aj Roboscreen) and CMV PCR kit (Qiagen Diagnostics) were comparable. HAART made the reduction of CMV viral load, without any specific anti-CMV therapy. As in the case of other opportunistic infections, undetectable natural history of CMV infection seemed to have been improved by controlling HIV infection.

An immunological approach to cerebral ischemia (I). Immune cells and adhesion molecules.

Ischemic stoke is a major cause of death and an important source of disability in industrialized countries. Since there is no ideal treatment for cerebral ischemia, any approach aiming to limit the devastating consequences of the ischemic process is justified. Concerning immune responses, it has become clear in the latest years that actors of the immune system are involved in multiple and various neurobiological processes such as cerebral ischemia, neurodegeneration, neuroprotection and neuroregeneration. An immunological approach to cerebral ischemia can distinguish, besides the implication of inflammation in the developing of atherothrombosis thus leading to stroke, the clear involvement of immune cells and mediators in processes continuing the initial stage of ischemia, having consequences on recovery or lesion extent. Cerebral infarctions develop within minutes to hours of cessation of the cerebral blood flow, but may expand over subsequent days. There is increasing evidence that leukocytes, cytokines, cell adhesion molecules, and other immune mediators contribute to secondary infarction growth, but inflammatory cytokines are also involved in signaling pathways leading to neuroprotection related to ischemic pre-conditioning. The aim of this review is to show some aspects concerning the complex and diverse functions of immune modifications occurring in cerebral ischemia. This first part will focus on the involvement of immune cells, adhesion molecules and immunological transcription factors in the development of ischemic lesion.