Design, synthesis, and unraveling the antibacterial and antibiofilm potential of 2-azidobenzothiazoles: insights from a comprehensive in vitro study.

The present study reports the synthesis of 2-azidobenzothiazoles from substituted 2-aminobenzothiazoles using sodium nitrite and sodium azide under mild conditions. All the synthesized compounds were examined for their antibacterial activity against Gram (+) bacteria, Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 51299), Bacillus cereus (ATCC 10876) and Gram (-) bacteria, Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 10145), Klebsiella pneumonia (ATCC BAA-2146)and clinical isolates of Gram (+) Methicillin Resistant S. aureus (MRSA) and Multi Drug Resistant E. coli. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values by broth dilution method revealed that compound 2d exhibited significant antibacterial potential against E. faecalis and S. aureus with MIC of 8 µg/mL, while other synthesized compounds had only moderate effects against all the tested species. The compound significantly inhibited the biofilm formation of the bacterial strains below its MIC. The selective cytotoxicity of Compound 2d towards bacterial cells was evidenced on extended exposure of Human Embryonic Kidney-293 cell line to higher concentrations of the compound. Hence, the present study confirmed that compound 2d can be a potential drug candidate for future development as an antibacterial drug.

Neurodegeneration and epigenetics: A review / Neurodegeneracion y epigenética: una revisión

Neuronal function and differentiation are tightly regulated by both genome and epigenome. Based on the environmental information the epigenetic changes occur. Neurodegeneration is the consequence of dysregulation of both the genome and epigenome. In this study, we saw different types of alterations of epigenome present in neuronal cells of different model organisms for neurodegenerative disorders. The epigenetic modifications including chromatin modification, DNA methylation, and changes in regulatory RNAs (miRNA) are having a great impact on neurodegenerative disorders as well as memory. The effects of these re-editing in the neuronal cells cause Alzheimer's disease, Parkinson's disease, Huntington's disease but an unusual form of neuroepigenetics has been seen in Prion Disease. Subsequently, for the development of treatment of these diseases, epigenetic modifications should be kept in mind. Although until now many reports came on drug discovery inhibiting histone deacetylases and DNA methyltransferases to reverse the epigenetic change but they lack targeted delivery and sometimes cause a cytotoxic effect on neuronal cells. In future, advancement in targeted and non-cytotoxic drugs should be the main focus for therapeutic treatment of the neurodegenerative disorders.(AU)

La función y diferenciación neuronales están reguladas en gran medida por el genoma y el epigenoma. Los estímulos ambientales producen cambios epigenéticos. La neurodegeneración es consecuencia de una alteración en el genoma y el epigenoma. Hemos analizado diferentes tipos de alteraciones del epigenoma presentes en células neuronales de diferentes modelos animales de enfermedad neurodegenerativa. Los cambios epigenéticos (modificación de la cromatina, metilación del ADN, cambios en los ARN reguladores [miARN]) tienen un impacto importante en las enfermedades neurodegenerativas y en la memoria. Dichos cambios en células neuronales causan diferentes enfermedades, como las de Alzheimer, Parkinson, y Huntington; sin embargo, las enfermedades priónicas muestran formas epigenéticas inusuales. Por tanto, el desarrollo de tratamientos para estas enfermedades debe considerar los cambios epigenéticos. Se han desarrollado diversos fármacos inhibidores de la histona deacetilasa y la ADN metiltransferasa, que revierten los cambios epigenéticos, pero no utilizan sistemas de liberación inteligente, por lo que a veces pueden producir efectos citotóxicos en las células neuronales. La investigación sobre tratamientos para las enfermedades neurodegenerativas debe centrarse en el desarrollo de fármacos no citotóxicos con sistemas de liberación inteligente.(AU)

Neurodegeneration and epigenetics: A review.

Neuronal function and differentiation are tightly regulated by both genome and epigenome. Based on the environmental information the epigenetic changes occur. Neurodegeneration is the consequence of dysregulation of both the genome and epigenome. In this study, we saw different types of alterations of epigenome present in neuronal cells of different model organisms for neurodegenerative disorders. The epigenetic modifications including chromatin modification, DNA methylation, and changes in regulatory RNAs (miRNA) are having a great impact on neurodegenerative disorders as well as memory. The effects of these re-editing in the neuronal cells cause Alzheimer's disease, Parkinson's disease, Huntington's disease but an unusual form of neuroepigenetics has been seen in Prion Disease. Subsequently, for the development of treatment of these diseases, epigenetic modifications should be kept in mind. Although until now many reports came on drug discovery inhibiting histone deacetylases and DNA methyltransferases to reverse the epigenetic change but they lack targeted delivery and sometimes cause a cytotoxic effect on neuronal cells. In future, advancement in targeted and non-cytotoxic drugs should be the main focus for therapeutic treatment of the neurodegenerative disorders.

OUTpatient intravenous LASix Trial in reducing hospitalization for acute decompensated heart failure (OUTLAST).

BACKGROUND: Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF. METHODS: In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization. Patients in Groups 2/3 also received a comprehensive HF-care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Echocardiography, quality of life and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. RESULTS: Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American). There were a total of 14 (15%) hospitalizations for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p = 0.11; p = 0.037 comparing Groups 2 and 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. CONCLUSION: The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

Neurodegeneration and epigenetics: A review.

Neuronal function and differentiation are tightly regulated by both genome and epigenome. Based on the environmental information the epigenetic changes occur. Neurodegeneration is the consequence of dysregulation of both the genome and epigenome. In this study, we saw different types of alterations of epigenome present in neuronal cells of different model organisms for neurodegenerative disorders. The epigenetic modifications including chromatin modification, DNA methylation, and changes in regulatory RNAs (miRNA) are having a great impact on neurodegenerative disorders as well as memory. The effects of these re-editing in the neuronal cells cause Alzheimer's disease, Parkinson's disease, Huntington's disease but an unusual form of neuroepigenetics has been seen in Prion Disease. Subsequently, for the development of treatment of these diseases, epigenetic modifications should be kept in mind. Although until now many reports came on drug discovery inhibiting histone deacetylases and DNA methyltransferases to reverse the epigenetic change but they lack targeted delivery and sometimes cause a cytotoxic effect on neuronal cells. In future, advancement in targeted and non-cytotoxic drugs should be the main focus for therapeutic treatment of the neurodegenerative disorders.

Prevalence and Prognostic Significance of Left Ventricular Noncompaction in Patients Referred for Cardiac Magnetic Resonance Imaging.

BACKGROUND: Presence of prominent left ventricular trabeculation satisfying criteria for left ventricular noncompaction (LVNC) on routine cardiac magnetic resonance examination is frequently encountered; however, the clinical and prognostic significance of these findings remain elusive. This registry aimed to assess LVNC prevalence by 4 current criteria and to prospectively evaluate an association between diagnosis of LVNC by these criteria and adverse events. METHODS AND RESULTS: There were 700 patients referred for cardiac magnetic resonance: 42% were women, median age was 70 years (range, 45-71 years), mean left ventricular ejection fraction was 51% (±17%), and 32% had late gadolinium enhancement on cardiac magnetic resonance. The cohort underwent diagnostic assessment for LVNC by 4 separate imaging criteria-referenced by their authors as Petersen, Stacey, Jacquier, and Captur, with LVNC prevalence of 39%, 23%, 25% and 3%, respectively. Primary clinical outcome was combined end point of time to death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, and heart failure hospitalization. Secondary clinical outcomes were (1) all-cause mortality and (2) time to the first occurrence of any of the following events: cardiac death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, or heart failure hospitalization. During a median follow-up of 7 years, there were no statistically significant differences in assessed outcomes noted between patients with and without LVNC irrespective of the applied criteria. CONCLUSIONS: Current criteria for the diagnosis of LVNC leads to highly variable disease prevalence in patients referred for cardiac magnetic resonance. The diagnosis of LVNC, by any current criteria, was not associated with adverse clinical events on nearly 7 years of follow-up. Limited conclusions can be made for Captur criteria due to low observed prevalence.

Right atrial volume by cardiovascular magnetic resonance predicts mortality in patients with heart failure with reduced ejection fraction.

BACKGROUND: Right Atrial Volume Index (RAVI) measured by echocardiography is an independent predictor of morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). The aim of this study is to evaluate the predictive value of RAVI assessed by cardiac magnetic resonance (CMR) for all-cause mortality in patients with HFrEF and to assess its additive contribution to the validated Meta-Analysis Global Group in Chronic heart failure (MAGGIC) score. METHODS AND RESULTS: We identified 243 patients (mean age 60 ± 15; 33% women) with left ventricular ejection fraction (LVEF) ≤ 35% measured by CMR. Right atrial volume was calculated based on area in two- and four -chamber views using validated equation, followed by indexing to body surface area. MAGGIC score was calculated using online calculator. During mean period of 2.4 years 33 patients (14%) died. The mean RAVI was 53 ± 26 ml/m2; significantly larger in patients with than without an event (78.7±29 ml/m2 vs. 48±22 ml/m2, p<0.001). RAVI (per ml/m2) was an independent predictor of mortality [HR = 1.03 (1.01-1.04), p = 0.001]. RAVI has a greater discriminatory ability than LVEF, left atrial volume index and right ventricular ejection fraction (RVEF) (C-statistic 0.8±0.08 vs 0.55±0.1, 0.62±0.11, 0.68±0.11, respectively, all p<0.02). The addition of RAVI to the MAGGIC score significantly improves risk stratification (integrated discrimination improvement 13%, and category-free net reclassification improvement 73%, both p<0.001). CONCLUSION: RAVI by CMR is an independent predictor of mortality in patients with HFrEF. The addition of RAVI to MAGGIC score improves mortality risk stratification.

Review and Analysis of Publication Trends over Three Decades in Three High Impact Medicine Journals.

CONTEXT: Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. OBJECTIVE: We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. DATA SOURCES AND STUDY SELECTION: Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. DATA EXTRACTION: Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. RESULTS: 1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). CONCLUSION: Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

"Second" Primary Cardiac Sarcoma in a Patient With Ewing Sarcoma. Always Expect The Unexpected.

A high suspicion for relapsed metastatic disease must arise when an intracardiac mass is detected in a patient with a recent history of Ewing sarcoma. Nevertheless, the scenario may eventually turn out to be much more complex than expected, and the possibility that the intracardiac tumor may instead be a "second" primary sarcoma, although extremely rare, should also be considered. We describe the first case of concomitant diagnosis of Ewing sarcoma and low-grade myxoid spindle cell sarcoma in the same young patient.

Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular Function Among Patients Undergoing Exercise Stress Myocardial Perfusion Imaging.

BACKGROUND: Right ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors, including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown. METHODS AND RESULTS: The population comprised 2051 patients who underwent exercise stress myocardial perfusion imaging and echo (5.5±7.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores were ≈3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion defects (all P≤0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both P<0.01), without difference in corresponding anterior defects (P=0.13). In multivariable analysis, inducible inferior and lateral wall perfusion defects increased the likelihood of RV dysfunction (both P<0.05) independent of LV function, fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance whether measured by exercise duration (6.7±2.8 versus 7.9±2.9 minutes; P<0.001) or peak treadmill stage (2.6±0.9 versus 3.1±1.0; P<0.001), paralleling results among patients with LV dysfunction (7.0±2.9 versus 8.0±2.9; P<0.001|2.7±1.0 versus 3.1±1.0; P<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction (P<0.001) and was associated with each parameter independent of age or medication regimen. CONCLUSIONS: Among patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent of LV dysfunction.

Influence of moderate to severe chronic periodontitis on dental pulp.

BACKGROUND: The relationship between periodontal disease and dental pulp changes is controversial and has been debated for many years. This human study was performed to evaluate the possible effects of moderate to advanced periodontal disease on the different aspect of dental pulp structure. MATERIALS AND METHODS: Twenty hopeless permanent teeth were extracted from systemically healthy adults because of moderate to advanced chronic periodontitis, with a bone loss of >6 mm and a mobility of grade 2 or 3. Upon extraction, the apical 2 to 3 mm of the roots were immediately sectioned. Four to five sections were mounted on each slide, and every third slide was stained with hematoxylin and eosin. The specimens were histologically processed and examined by an oral pathologist. RESULTS: Non-inflamed pulp, with partial or complete necrosis in some sections and several non-necrotic sections, was found in only 6.3% of teeth. Most teeth (58.3%) displayed edematous pulps. Slightly fibrotic pulps were seen in 52.1% of sections. Odontoblastic integrity was seen in 31.3% of teeth. Most teeth (77.1%) displayed no pulp stones. In 43.8% of teeth, the pulp vessels displayed dilatation. CONCLUSIONS: Moderate to advanced periodontal disease can affect the dental pulp. Careful consideration of diagnostic and treatment planing in patients with endodontic-periodontal involvement is therefore recommended.

A randomized, double-blind, placebo-controlled trial on the efficacy and tolerability of sertraline in Iranian veterans with post-traumatic stress disorder.

BACKGROUND: Unlike civilian post-traumatic stress disorder (PTSD), the efficacy of sertraline for the treatment of combat-related PTSD has not yet been proven. The present study aimed to evaluate the clinical efficacy of sertraline against combat-related PTSD in a randomized, double-blind, placebo-controlled trial. METHOD: Seventy Iranian veterans of the Iran-Iraq war who met the DSM-IV criteria for diagnosis of PTSD were randomized to receive either flexibly dosed sertraline (50-200 mg/day) (n=35, completers=32) or placebo (n=35, completers=30) for 10 weeks. Efficacy was evaluated by the Impact of Event Scale--Revised (IES-R) and the Clinical Global Impression scale--Severity (CGI-S) and Improvement (CGI-I) ratings. Responder criteria were defined as a ≥30% reduction in the IES-R total score plus a CGI-I rating of 'much' or 'very much' improved. RESULTS: On both intention-to-treat (ITT) and per protocol (completer) methods of analysis, the mean reductions in the IES-R total and subscale (re-experiencing/intrusion, avoidance/numbing and hyperarousal) scores (p<0.001) and also in the CGI-S score (p<0.01) were significantly greater in the sertraline group than in the placebo group. For the CGI-I, the mean endpoint score was significantly lower in the sertraline group than in the placebo group (p≤0.001). The number of responders in the sertraline group was significantly higher than in the placebo group (44% v. 3%, p≤0.001). Sertraline was well tolerated, with a 6% discontinuation rate as a result of adverse reactions. CONCLUSIONS: The results of this study suggest that sertraline can be an effective, safe and tolerable treatment for combat-related PTSD in Iranian veterans.

Association of diabetes mellitus and dyslipidaemias in the Tehran population.

The aim of this survey was to evaluate the role of diabetes in the lipid profiles of the Tehran population. Measurements were carried out on 10 136 people aged 20-69 years for blood sugar, triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and data were collected on medical history, physical activity, smoking and obesity. The prevalence of any type of dyslipidaemia in the whole group was 68.5% and of diabetes mellitus was 11.0% (10.6% in men and 11.3% in women). The prevalence of dyslipidaemia in diabetics was 88.9%. There was strong association between diabetes mellitus and dyslipidaemia (P < 0.05). In regression analysis, diabetes was the second most important factor after obesity in secondary dyslipidaemia.

Association of diabetes mellitus and dyslipidaemias in the Tehran population

The aim of this survey was to evaluate the role of diabetes in the lipid profiles of the Tehran population. Measurements were carried out on 10 136 people aged 20-69 years for blood sugar, triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and data were collected on medical history, physical activity, smoking and obesity. The prevalence of any type of dyslipidaemia in the whole group was 68.5% and of diabetes mellitus was 11.0% [10.6% in men and 11.3% in women]. The prevalence of dyslipidaemia in diabetics was 88.9%. There was strong association between diabetes mellitus and dyslipidaemia [P < 0.05]. In regression analysis, diabetes was the second most important factor after obesity in secondary dyslipidaemia

Causes of rehospitalization after renal transplantation; does age of recipient matter?

BACKGROUND: This study assessed the causes and related factors of rehospitalization following renal transplantation among elderly compared with younger patients. METHODS: We reviewed the charts of 567 patients rehospitalized after kidney transplantation from 2000 to 2006. According to age at the time of transplantation, hospitalizations were divided into two groups: group 1 (age >or=50 years) and group II (age 20 to 50 years). Demographics, clinical findings, causes for rehospitalization, patient outcomes (recovery, graft loss, death), intensive care unit (ICU) admission, length of hospital stay, time interval from transplantation to rehospitalization, as well as hospital costs were compared between the two groups. RESULTS: One hundred eighty-five (32.6%) rehospitalizations were charted for group I, who showed a higher proportion of admissions due to infection (42.2% vs 29.8%, P=.004) and macrovascular disease (3.8% vs 1.0%, P=.027) compared with group II. ICU admission (8.8% vs 2.4%, P=.001), mortality (10.2% vs 3.6%, P=.008), and hospital charges (1610 +/- 933 vs 931 +/- 850 purchase power parity dollars, P=.001) were also seen more frequently in group I but displayed a lower frequency of admissions due to graft rejection (20% vs 34.3%, P=.001). CONCLUSION: Recipient age at the time of transplantation was a main factor affecting rehospitalization among our patients.

Cytomegalovirus disease after kidney transplantation: clues to accurate diagnosis.

BACKGROUND: The clinical diagnosis of cytomegalovirus (CMV) disease after kidney transplantation is often not accurate. We evaluated the factors associated with a correct diagnosis of CMV disease in these patients. MATERIALS AND METHODS: This retrospective study of all renal transplant patients between 2004 and 2005 with a clinical diagnosis of CMV disease included both donors and recipients who were seropositive for CMV at transplantation. We assessed the rate and correlated factors with a correct diagnosis. RESULTS: Among 127 cases, the 30 (23.6%) patients who had a correct diagnosis of CMV disease. Showed higher ages at transplantation (48.8 +/- 15.3 vs. 39.8 +/- 14.4 years; P=.004) and a shorter interval between transplantation and symptom presentation (9.7 +/- 20.7 vs. 25.6 +/- 33.6 days; P=.048). Diabetes mellitus (DM) was the cause of end-stage renal disease (ESRD) in 41% of patients with a correct diagnosis, whereas it was the cause in 11% of CMV disease-negative patients (P<.001). A multiple logistic regression model showed that DM as the cause of ESRD (P=.001; odds ratio [OR] 16.331), >5 months duration between transplantation and the presence of symptoms (P=.001; OR, 0.060), and age at transplantation >55 years (P=.022; OR, 3.833) were predictors of a correct diagnosis of CMV disease (chi(2)=46.45; P<.001). CONCLUSION: The results herein showed that considering some variables significantly improved the accuracy of a correct diagnosis of CMV disease after kidney transplantation.

Posttransplantation lymphoproliferative disorders in renal transplant recipients: report of over 20 years of experience.

INTRODUCTION: Despite the benefits of immunosuppressive medications to improve graft function, they have several adverse effects, such as development of neoplasms in renal transplant recipients. Posttransplantation lymphoproliferative disorders (PTLDs) are not uncommon complications, so we conducted a study to evaluate the characteristics of affected patients. METHODS: We enrolled 2117 kidney recipients from June 1984 to March 2004 in order to find pathological and clinical evidence of neoplasms. We collected and analyzed all data on PTLD patients. RESULTS: Overall there were 46 recipients with different types of neoplasms, among which the most common types were diseases of the skin (24 cases, 52.2%), Kaposi's sarcoma (15 cases, 32.6%), and PTLD (14 cases, 30.4%). The mean (+/- SD) age of PTLD patients at the time of transplantation was 37.86 +/- 9.67 years and 42.8% were women. Median and mean (+/- SD) time interval to PTLD diagnosis were 38.5 and 50.35 +/- 41.7 months, respectively (range 1 to 146 months). Types of PTLD in these patients were kidney lymphoma (14.3%); gastrointestinal (14.3%); brain lymphoma; tonsils; palatine; Hodgkin's lymphoma, large cell lymphoma, and acute lymphoblastic lymphoma (each 7.1%), with 28.6% unspecified types. The 1-, 5-, and 10-year patient survival rates after transplantation were 71.4%, 51.4%, and 44.3%, respectively. Despite discontinuing immunosuppressive therapy in PTLD patients, five of six surviving had graft function up to a mean time of 105.4 +/- 57.6 months after transplantation. CONCLUSION: Our findings showed that the prevalence of PTLD was 0.66%, which was less than reports from Western countries. The fact that there were surviving grafts for a considerable time despite discontinuing immunosuppressive therapy is of great importance.

Sleep quality and its correlates in renal transplant patients.

BACKGROUND: The aim of this study was to evaluate correlated morbidity measures with poor sleep quality among kidney transplanted patients. METHODS: In a cross-sectional study of 125 Iranian kidney transplant patients in 2006, we employed self-administered questionnaires to evaluate the quality of sleep (PSQI), quality of life (SF-36), anxiety and depression, sexual activity, marital relationship, and medical comorbidity. Patients with PSQI score of >5 were considered to be "poor sleepers." Students t-test was used to compare the morbidity measures between the two groups: "poor sleeper" versus "good sleepers." RESULTS: Seventy-eight (62%) patients were poor sleepers. This group showed a higher total medical comorbidity score (P=.009), more bodily pain, poorer general mental health, and less physical function on SF- 36 (P=.02), less sexual function, and more severe anxiety (P=.02). There was no significant difference between poor sleepers and good sleepers in the mean of other subscores of the SF-36, marital status, and depressive symptoms. CONCLUSIONS: A poor quality of sleep is common after kidney transplantation. This problem is associated with higher medical comorbidity and poorer emotional state. Therefore, more attention should be paid to evaluation of sleep quality in this patient population.

Cyclosporine trough (C0) and 2-hour postdose (C2) levels: which one is a predictor of graft loss?

BACKGROUND: Compared with conventionally measured trough level (C0), cyclosporine 2-hour postdose (C2) concentrations show a better correlation with the area under the curve and acute graft rejection. OBJECTIVES: We evaluated the relationships of C0 and C2 with long-term graft survival among kidney transplant recipients. METHODS: In a case-control design, we selected 215 adult kidney recipients. Inclusion criteria were more than 18 years of age at transplantation and at least 6 months of follow-up. The case group consisted of patients with graft loss (n=17) and a control group, patients with functioning grafts (n=198). The C0 and C2 levels for the first 6 months posttransplantation, along with demographic and clinical data, were compared between the two groups using univariate analysis. P<.05 was considered to be significant. RESULTS: The mean age at transplantation was 40.5 +/- 16.5 years. The mean follow-up duration was 18 +/- 14 months. The mean C0 values for the case and control groups were 257.8 +/- 126.5 and 248.5 +/- 104.4 mumol/L, respectively (P>.05). The values for C2 were 712.7 +/- 273.2 and 886.2 +/- 266.9 mumol/L, respectively (P=.01). CONCLUSIONS: We observed that C2, but not C0, in the first 6 months posttransplantation were a predictor of long-term graft survival. The findings here in supported the results of other studies that have proposed cyclosporine concentration monitoring by C2 rather than C0 measurements.

Vaccination with cell immunoglobulin mucin-1 antibodies and inactivated influenza enhances vaccine-specific lymphocyte proliferation, interferon-gamma production and cross-strain reactivity.

Influenza virus causes a contagious and potentially serious infection of the upper respiratory tract. While neutralizing antibodies are protective against infection, the problem of antigenic drift remains, requiring the constant monitoring and development of new vaccines. The magnitude of this situation is underscored by the emergence of new potentially human pathogenic influenza strains, avian H5N1 being the most recent example. We present evidence that antibodies against T cell immunoglobulin mucin-1 (TIM-1), a recently identified immunomodulatory molecule, stimulate cellular immunity against influenza viruses and cross-strain immune reactivity. To determine potential immunostimulatory properties of anti-TIM-1, mice were vaccinated with inactivated influenza virus in the presence or absence of TIM-1-specific monoclonal antibodies. Development of cellular immunity against both the influenza strain used for immunization and serotypically distinct virus strains was monitored 3 weeks after vaccination by determining antigen-specific lymphocyte proliferation and cytokine production. Results show that TIM-1 antibodies enhance antigen-specific cellular proliferation (P < 0.05) and interferon (IFN)-gamma production (P < 0.01). Using blocking anti-CD4 and CD8 antibodies, it was observed that antigen-specific cellular proliferation is CD4-dependent and that the majority of proliferating cells are CD4+. Finally, vaccination with inactivated influenza virus with TIM-1 antibody results in the significant (P < 0.001) induction of proliferation and IFN-gamma production upon stimulation with one of three serologically distinct strains. TIM-1 antibodies demonstrate an adjuvant effect promoting antigen-specific cellular proliferation and IFN-gamma production, which are important for the promotion of cell-mediated immunity. These results are the first to suggest that TIM-1 antibody may serve as a potent adjuvant in the development of new influenza virus vaccines.