Dobutamine Stress Echocardiography in Heart Transplant Recipients` Evaluation: The Role of Reinnervation

Introduction. Orthotopic heart transplantation renders the recipient denervated. This remodeling of the intrinsic cardiac nervous system should be taken in account during functional evaluation for allograft coronary artery disease. Dobutamine stress echocardiography (DSE) has been used to detect patients at greater risk. The aim of this study was to determine whether patients with various autonomic response levels, and supposed reinnervation patterns, show the same response to DSE. Methods. We studied 20 patients who had survived more than 5 years after orthotopic heart transplantation. All patients underwent a Holter evaluation. We considered patients with low variability to be those with less than a 40-bpm variation from the lowest to highest heart rate, so-called ""noninnenervated"" (group NI). Patients who had 40-bpm or more variation were considered to show high variability and called ""reinnervated"" (group RI). After that, all patients performed an ergometric test and DSE. Results. Groups were defined as NI (n = 9) and RI (n = 11). Ergometric tests confirmed this response with NI patients showing less variability when compared to RI patients (P = .0401). During DSE, patients showed similar median heart rate responses according to the dobutamine dose. Spearmen correlation showed r = 1.0 (P = .016). Conclusions: DES was effective to reach higher heart rates, probably related to catecholamine infusion. These findings may justify a better response when evaluating cardiac allograft vasculopathy in heart transplant patients.

Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

Background. Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. Methods. The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance <50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 +/- 12.3 years and time since transplantation 8.7 +/- 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 +/- 0.9 to 1.69 +/- 0.5 mg/dL, P = .01) and CrCl (24.9 +/- 6.5 to 45.7 +/- 17.2 mL/min, P = .005) at 6 months follow-up. Conclusion. The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

The impact of trauma and post-traumatic stress disorder on the treatment response of patients with obsessive-compulsive disorder

Few case series studies have addressed the issue of treatment response in patients with obsessive-compulsive disorder (OCD) and comorbid post-traumatic stress disorder (PTSD), and there are no prospective studies addressing response to conventional treatment in OCD patients with a history of trauma (HT). The present study aimed to investigate, prospectively, the impact of HT or PTSD on two systematic, first-line treatments for OCD. Two hundred and nineteen non-treatment-resistant OCD outpatients were treated with either group cognitive-behavioral therapy (GCBT n = 147) or monotherapy with a selective serotonin reuptake inhibitor (SSRI n = 72). Presence of HT and PTSD were assessed at intake, as part of a broader clinical and demographical baseline characterization of the sample. Severity and types of OCD symptoms were assessed with the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and the Dimensional YBOCS (DYBOCS), respectively. Depression and anxiety symptoms were measured with the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Both treatments had 12-week duration. Treatment response was considered as a categorical [35% or greater reduction in baseline YBOCS scores plus a Clinical Global Impression-Improvement rating of better (2) or much better (1)] and continuous variable (absolute number reduction in baseline YBOCS scores). Treatment response was compared between the OCD + HT group versus the OCD without HT group and between the OCD + PTSD group versus the OCD without PTSD group. Parametric and non-parametric tests were used when indicated. Data on HT and PTSD were available for 215 subjects. Thirty-eight subjects (17.67% of the whole sample) had a positive HT (OCD + HT group) and 22 subjects (57.89% of the OCD + HT group and 10.23% of the whole sample) met full DSM-IV criteria for PTSD. The OCD + HT and OCD without HT groups presented similar response to GCBT (60% of responders in the first group and 63% of responders in the second group, p = 1.00). Regarding SSRI treatment, the difference between the response of the OCD + HT (47.4%) and OCD without HT (22.2%) groups was marginally significant (p = 0.07). In addition, the OCD + PTSD group presented a greater treatment response than the OCD without PTSD group when treatment response was considered as a continuous variable (p = 0.01). The age when the first trauma occurred had no impact on treatment response. In terms of specific OCD symptom dimensions, as measured by the DYBOCS, OCD treatment fostered greater reductions for the OCD + PTSD group than for the OCD without PTSD group in the scores of contamination obsessions and cleaning compulsions, collecting and hoarding and miscellaneous obsessions and related compulsions (including illness concerns and mental rituals, among others). The OCD + PTSD group also presented a greater reduction in anxiety scores than the OCD without PTSD group (p = 0.003). The presence of HT or PTSD was not related to a poorer treatment response in this sample of non-treatment-resistant OCD patients. Unexpectedly, OCD patients with PTSD presented a greater magnitude of response when compared with OCD without PTSD patients in specific OCD symptom dimensions. Future studies are needed to clarify if trauma and PTSD have a more significant impact on the onset and clinical expression of OCD than on the conventional treatment for this condition, and whether OCD stemming from trauma would constitute a subtype of OCD with a distinct response to conventional treatment.

The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients

Introduction: The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients. Purpose: To assess the behavior of C-reactive protein (CRP) in renal transplant recipients with a diagnosis of cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI). Methods: A retrospective analysis of 129 patients admitted at our hospital, from 2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical analysis was done and values were expressed as medians, range. Results: When CRP levels were compared among the groups with CMV disease, TB or BI, the group with CMV disease presented lower levels of CRP (18.4 mg/L, 0.28-44 mg/L) than the TB and BI (p < 0.05) groups. The area under the receiver-operating characteristics curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in 100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5 mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease subgroups, respectively (p < 0.05). Conclusion: The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.

Sirolimus in Pediatric Liver Transplantation: A Single-Center Experience

Background and Aims. Liver transplantation (OLT) in children has seen significant improvements in recent years. Long-term immunosuppressive strategies have focused on avoiding the risks of long-term immunosuppression, particularly nephrotoxicity, de novo malignancy and late infections. Since its introduction in renal transplantation in 1999, sirolimus (SRL) has been used by an increasing number of liver transplant centers. The aim of this study was to review the experience using SRL in pediatric liver transplant recipients at a single center. Methods. Between 1989 and 2006, 318 children underwent OLT including 13 who were converted to SRL therapy because of tacrolimus-related side effects. The indications were posttransplant lymphoproliferative disease (PTLD; n = 11), nephrotoxicity (n = 1), and de novo autoimmune hepatitis (n = 1). One patient with PTLD previously concurrently displayed chronic rejection. SRL dosages ranged between 0.4 and 5 mg/d. The median duration of follow-up was 18 months. Results. PTLD recurred in 1 patient. There were no episodes of acute rejection. One child developed hyperlipidemia that resolved with diet and medication. Conclusions. Conversion from tacrolimus to SRL in selected pediatric liver transplant recipients is safe. Children with PTLD may benefit from immunosuppression with SRL after liver transplantation.

Obesity Decreases Time to Claudication and Delays Post-Exercise Hemodynamic Recovery in Elderly Peripheral Arterial Disease Patients

Background: Although obesity is usually observed in peripheral arterial disease (PAD) patients, the effects of the association between these diseases on walking capacity are not well documented. Objective: The main objectives of this study were to determine the effects of obesity on exercise tolerance and post-exercise hemodynamic recovery in elderly PAD patients. Methods: 46 patients with stable symptoms of intermittent claudication were classified according to their body mass index (BMI) into normal group (NOR) = BMI < 28.0 and obese or in risk of obesity group (OBE) = BMI >= 28.0. All patients performed a progressive graded treadmill test. During exercise, ventilatory responses were evaluated and pre- and post-exercise ankle and arm blood pressures were measured. Results: Exercise tolerance and oxygen consumption at total walking time were similar between OBE and NOR. However, OBE showed a lower claudication time (309 +/- 151 vs. 459 +/- 272 s, p = 0.02) with a similar oxygen consumption at this time. In addition, OBE presented a longer time for ankle brachial index recovery after exercise (7.8 +/- 2.8 vs. 6.3 +/- 2.6 min, p = 0.02). Conclusion: Obesity in elderly PAD patients decreased time to claudication, and delayed post-exercise hemodynamic recovery. These results suggest that muscle metabolic demand, and not total workload, is responsible for the start of the claudication and maximal exercise tolerance in PAD patients. Moreover, claudication duration might be responsible for the time needed to a complete hemodynamic recovery after exercise. Copyright (c) 2008 S. Karger AG, Basel

Automatic versus manual pressure support reduction in the weaning of post-operative patients: a randomised controlled trial

Introduction Reduction of automatic pressure support based on a target respiratory frequency or mandatory rate ventilation (MRV) is available in the Taema-Horus ventilator for the weaning process in the intensive care unit (ICU) setting. We hypothesised that MRV is as effective as manual weaning in post-operative ICU patients. Methods There were 106 patients selected in the postoperative period in a prospective, randomised, controlled protocol. When the patients arrived at the ICU after surgery, they were randomly assigned to either: traditional weaning, consisting of the manual reduction of pressure support every 30 minutes, keeping the respiratory rate/tidal volume (RR/TV) below 80 L until 5 to 7 cmH(2)O of pressure support ventilation (PSV); or automatic weaning, referring to MRV set with a respiratory frequency target of 15 breaths per minute (the ventilator automatically decreased the PSV level by 1 cmH(2)O every four respiratory cycles, if the patient`s RR was less than 15 per minute). The primary endpoint of the study was the duration of the weaning process. Secondary endpoints were levels of pressure support, RR, TV (mL), RR/TV, positive end expiratory pressure levels, FiO(2) and SpO(2) required during the weaning process, the need for reintubation and the need for non-invasive ventilation in the 48 hours after extubation. Results In the intention to treat analysis there were no statistically significant differences between the 53 patients selected for each group regarding gender (p = 0.541), age (p = 0.585) and type of surgery (p = 0.172). Nineteen patients presented complications during the trial (4 in the PSV manual group and 15 in the MRV automatic group, p < 0.05). Nine patients in the automatic group did not adapt to the MRV mode. The mean +/- sd (standard deviation) duration of the weaning process was 221 +/- 192 for the manual group, and 271 +/- 369 minutes for the automatic group (p = 0.375). PSV levels were significantly higher in MRV compared with that of the PSV manual reduction (p < 0.05). Reintubation was not required in either group. Non-invasive ventilation was necessary for two patients, in the manual group after cardiac surgery (p = 0.51). Conclusions The duration of the automatic reduction of pressure support was similar to the manual one in the postoperative period in the ICU, but presented more complications, especially no adaptation to the MRV algorithm. Trial Registration Trial registration number: ISRCTN37456640

Radical Retropubic Prostatectomy for Localized Prostate Cancer in Renal Transplant Patients

OBJECTIVE To investigate the feasibility of radical retropubic prostatectomy (RRP) in renal transplant recipients with clinically localized prostate cancer. METHODS A prospective protocol was established between August 2004 and November 2007. In that period, 8 patients diagnosed with localized prostate cancer were submitted to RRP, and their clinicopathologic data were reviewed. RESULTS The mean age (standard deviation) at surgery was 59.6 +/- 6.7 years (range, 49-67 years). All patients had TIC tumors, except for 1 with a T2A tumor. The mean preoperative prostate-specific antigen value was 4.5 +/- 1.8 ng/mL (range, 1.6-7.0 ng/mL). The mean interval between renal transplantation and RRP was 89.9 +/- 65.1 months (range, 40-209 months). The procedure was well tolerated without major complications, and all patients were discharged on the fifth postoperative day. There was no impairment to bladder descent caused by the presence of the allograft or the ureteroneocystostomy. Urethrovesical anastomosis was easily performed in all cases in the standard manner. Blood transfusion was needed in 2 patients (1 received 2 U and another 5 U of blood). The mean operative duration was 183 +/- 29.7minutes (range, 150-240 minutes), the mean estimated blood loss was 656 +/- 576 mL (range, 100-2000 mL), and no deterioration of graft function was observed. All patients were followed, and the mean follow-up was 10.5 months (range, 2-30 months). Prostate-specific antigen was undetectable in all cases during this time frame. CONCLUSIONS Radical retropubic prostatectomy in renal transplant patients is safe, effective, and can be easily performed in the same manner as described by Walsh, regardless of the presence of the allograft. The only necessary technical modification is the avoidance of ipsilateral lymphadenectomy to prevent damage to the transplanted organ. UROLOGY 72: 1362-1365, 2008. (C) 2008 Elsevier Inc.

Molecular Characterization of Strains of Respiratory Syncytial Virus Identified in a Hematopoietic Stem Cell Transplant Outpatient Unit Over 2 Years: Community or Nosocomial Infection?

Respiratory syncytial virus (RSV) is recognized as the leading cause of nosocomial respiratory infection among hematopoietic stem cell transplant (HSCT) recipients, causing considerable morbidity and mortality. RSV is easily transmitted by contact with contaminated surfaces, and in HSCT units, more than 50% of RSV infections have been characterized as of nosocomial origin. From April 2001 to October 2002, RSV was identified by direct immunofluorescent assay in 42 symptomatic HSCT recipients. Seven RSV strains from 2001 and 12 RSV strains from 2002 were sequenced. RNA extraction, cDNA synthesis, and seminested polymerase chain reaction (PCR) with primers complementary to RSV genes G and F were pet-formed. PCR products were analyzed by nucleotide sequencing of the C-terminal region of gene G for typing (in group A or B). Of the 7 strains analyzed in 2001, only 2 belonged to group B; the other 5 belonged to group A. Of these 7 strains, 3 were identical and were from recipients receiving outpatient care. In 2002, of the 12 strains analyzed, 3 belonged to group A and the other 9 belonged to group B. Of these 9 strains, 7 were genetically identical and were also from recipients receiving outpatient care. Therefore, multiple strains of RSV cocirculated in the hematopoietic stem cell transplant units (ward and outpatient units) between 2001 and 2002. Nosocomial transmission was more likely to occur at the HSCT outpatient unit than in the HSCT ward. Infection control practices should also be implemented in the outpatient setting.

Post-craniotomy headache: characteristics, behaviour and effect on quality of life in patients operated for treatment of supratentorial intracranial aneurysms

We prospectively studied headache characteristics during 6 months after craniotomy performed for treatment of cerebral aneurysms in 79 patients. Semistructured interviews, headache diaries, the Hospital Anxiety and Depression Scale and the Epworth Sleepiness Scales, the Short Form-36 Health Survey (SF-36) and McGill Pain Questionnaire were used. Seventy-two patients had headaches, half before the fifth day after surgery. Changes were observed in headache diagnosis, side and site in the postoperative period. Headache frequency increased immediately after surgery and then decreased over time. Headache frequency was associated with depressive and anxiety symptoms. Pain intensity was higher in women and in patients with more anxiety symptoms. An incidence of post-craniotomy headache of 40% was observed according to International Headache Society classification criteria, 10.7% of the acute and 29.3% of the chronic type. The bodily pain domain of the SF-36 was worse in patients with more anxiety symptoms. Greater frequencies of headache were associated with lower scores on bodily pain and social functioning.

Effect of academic psychological stress in post-graduate students: The modulatory role of cortisol on superoxide release by neutrophils

Experimental and clinical evidence shows that neutrophils play an important role in the mechanism of tissue injury in immune complex diseases through the generation of reactive oxygen species. In this study, we examined the influence of academic psychological stress in post-graduate students on the capacity of their blood neutrophils to release superoxide when stimulated by immune complexes bound to nonphagocytosable surfaces and investigated the modulatory effect of cortisol on this immune function. The tests were performed on the day before the final examination. The state-trait anxiety inventory questionnaire was used to examine whether this stressful event caused emotional distress. In our study, the psychological stress not only increased plasma cortisol concentration, but it also provoked a reduction in superoxide release by neutrophils. This decrease in superoxide release was accompanied by diminished mRNA expression for subunit p47(phox) of the phagocyte superoxide-generating nicotinamide adenine dinucleotide phosphate-oxidase. These inhibitory effects were also observed by in vitro exposure of neutrophils from control volunteers to 10(-7) M hydrocortisone, and could be prevented by the glucocorticoid receptor antagonist RU-486. These results show that in a situation of psychological stress, the increased levels of cortisol could inhibit superoxide release by neutrophils stimulated by IgG immune complexes bound to nonphagocytosable surfaces, which could attenuate the inflammatory state.

Schistosoma mansoni encodes SMT3B and SMT3C molecules responsible for post-translational modification of cellular proteins

The sumoylation pathway is a post-translational modification of nuclear proteins widespread among several organisms. SMT3C is the main protein involved in this process and it is covalently conjugated to a diverse assortment of nuclear protein targets. To date, 3 SUMO paralogues (SMT3C, A/B) have been characterized in mammals and plants. In this work we characterized two SUMO related genes, named SMT3B and SMT3C throughout Schistosoma mansoni life cycle. The SmSMTB/C encodes for proteins sharing significant amino acid homology with SMT3. Phylogenetical analyses revealed that both SmSMT3B/C are distinct proteins. Additionally, SmSMT3B and C are expressed in cercariae, adult worms, eggs and schistosomula however SinSMT3C gene showed an expression level 7 to 9 fold higher than SmSMT3B in eggs, schistosomula and adult worms. The comparison between the SmSMT3C genomic and cDNA sequences established that the encoding sequence is interrupted by 3 introns of 70, 37 and 36 bp. Western Blot has shown SMT3 conjugates are present in nuclear and total protein fractions of adults and cercariae. Therefore our results suggest a functional sumoylation pathway, and the presence of two paralogues also suggests the specificity of substrates for SMT3 in S. mansoni. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Perceived Self-Efficacy Among Liver Transplant Candidates and Recipients

Self-efficacy is defined as one`s belief that one can perform the necessary behaviors to achieve one`s goals. This belief is one of the most powerful motivational predictors of how well a person will perform at almost any endeavor. Limited information is available, however, about self-efficacy in the organ transplantation population. This study aimed to identify the self-efficacy belief among liver transplant candidates and recipients and compare these results with demographic characteristics. The authors analyzed 100 patients who were candidates and recipients for liver transplantation in a Brazilian center. The average self-efficacy score for the candidates was significantly lower than for the recipients. Future investigation is necessary to explore possible interventions to be taken before and after liver transplantation that could influence self-efficacy of the organ transplantation patients.

Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas

We have performed cDNA microarray analyses to identify gene expression differences between highly invasive glioblastoma multiforme (GBM) and typically benign pilocytic astrocytomas (PA). Despite the significant clinical and pathological differences between the 2 tumor types, only 63 genes were found to exhibit 2-fold or greater overexpression in GBM as compared to PA. Forty percent of these genes are related to the regulation of the cell cycle and mitosis. QT-PCR validation of 6 overexpressed genes: MELK, AUKB, ASPM, PRC1, IL13RA2 and KIAA0101 confirmed at least a 5-fold increase in the average expression levels in GBM. Maternal embryonic leucine zipper kinase (MELK) exhibited the most statistically significant difference. A more detailed investigation of MELK expression was undertaken to study its oncogenic relevance. In the examination of more than 100 tumors of the central nervous system, we found progressively higher expression of MELK with astrocytoma grade and a noteworthy uniformity of high level expression in GBM. Similar level of overexpression was also observed in medulloblastoma. We found neither gene promoter hypomethylation nor amplification to be a factor in MELK expression, but were able to demonstrate that MELK knockdown in malignant astrocytoma cell lines caused a reduction in proliferation and anchorage-independent growth in in vitro assays. Our results indicate that GBM and PA differ by the expression of surprisingly few genes. Among them, MELK correlated with malignancy grade in astrocytomas and represents a therapeutic target for the management of the most frequent brain tumors in adult and children. (C) 2007 Wiley-Liss, Inc.

HLA polymorphisms as incidence factor in the progression to end-stage renal disease in Brazilian patients awaiting kidney transplant

Chronic renal failure (CRF) leads in the majority of instances to end-stage renal disease (ESRD) requiring renal replacement therapy. Age, gender, genetics, race, hypertension, and smoking among others are factors associated with ESRD. Our interest was to evaluate the possible associations of class I and II HLA antigens with ESRD renal disease independent of other factors, among patients with CRF, having various diagnoses in the Brazilian population of the Sao Paulo state. So 21 HLA-A, 31 HLA-B, and 13 HLA-DR were detected in 105 patients who were compared with 160 healthy controls of both sexes who were not related to the patients evaluated until 2005. We calculated allelic frequencies, haplotypes frequencies, etiological fractions (EF), preventive fractions, and relative risks (RR). We compared demographic data of patients and controls. The antigens positively associated with ESRD were: HLA-A78 (RR = 30.31 and EF = 0.96) and HLA-DR11 (RR = 18.87 and EF = 0.65). The antigens HLAB14 (RR = 29.90 and EF = 0.75) was present at a significantly lower frequency among patients compared with controls. In contrast, no haplotype frequency showed statically significant associations. Further molecular studies may clarify types and subtypes of alleles involved with ESRD progression.