Pilot therapeutic education program in multiple system atrophy: Safety, quality of life and satisfaction from a national registry based longitudinal study.

BACKGROUND: Therapeutic education programs are effective in several chronic conditions. However, evidence is lacking in multiple system atrophy (MSA). We aimed to assess efficacy and safety of a comprehensive therapeutic education program in people with MSA (PwMSA) and their caregivers. METHODS: In this prospective longitudinal study we included 16 PwMSA and their main caregivers in 4 groups of 4 dyads each. The program consisted of eight 60-min interdisciplinary sessions: introduction, orthostatic hypotension, speech therapy, gait and respiratory physiotherapy, psychological support, urinary dysfunction, occupational therapy/social work. UMSARS, NMSS, PDQ39, EQ5 and Zarit scales were administered at baseline and 6 months later. After each session participants filled-out a modified EduPark satisfaction questionnaire and a Likert scale. Educational material was generated for each session after suggestions by participants. RESULTS: At baseline PwMSA and caregivers were comparable in age and sex, with significant correlation between UMSARS-IV (disability) and PDQ39 (quality of life). Adherence to sessions was of 94,92 %. Total modified EduPark scores and Likert scales did not differ in PwMSA vs. caregivers, mild-moderate vs. severe-advanced cases or between genders. The significant difference in satisfaction across sessions (p = 0.03) was driven by higher scores in speech, respiratory and occupational therapy sessions. Longitudinally there was no significant worsening in any scale, nor a significant increase post-vs. pre-program in the number of consultations. CONCLUSIONS: The healthcare education program in MSA was feasible, satisfactory, and safe for patients and caregivers. The educational material of the program is being forwarded to incident MSA cases attending our clinic.

Water vapor thermal therapy: Technical variations among spanish hospitals and efficacy at 2-year follow-up.

AIM: The aim of this work is to evaluate the initial experience with water vapor thermal therapy (WVTT) for benign prostatic hyperplasia (BPH) in Spanish university hospitals, as well as to describe the differences in technique and follow-up between centers. MATERIALS AND METHODS: This retrospective observational multicenter study collected baseline characteristics, surgical, postoperative and follow-up data at 1, 3, 6, 12 and 24 months, including validated questionnaires, flowmetric variations, complications, and the need for pharmacological or surgical treatment following the procedure. Possible triggers for postoperative acute urinary retention (AUR) were also analyzed. RESULTS: A total of 105 patients were included. No differences were observed between the groups with and without AUR with respect to catheterization time (5 and 4.3 days respectively, P=.178), or prostate volume (47.9g and 41.4g respectively, P=.147). The mean improvement at 3, 6, 12 and 24 months in terms of peak flow was 5.3, 5.2, 4.2 and 3.8ml/s, respectively. As for ejaculation, an improvement was observed after 3 months of follow-up and was maintained over time. CONCLUSIONS: Minimally invasive treatment for BPH with WVTT shows good functional outcomes at 24 months follow-up, without significant impairment of sexual function and a low incidence of complications. There are minor inter-hospital variations, mainly in the immediate postoperative period.

Functional outcomes after prostatic cryosurgery. / Resultados funcionales después de crioterapia prostática.

OBJECTIVE: To assess the functional effects of prostatic cryosurgery on micturition. MATERIAL AND METHODS: Prospective study of men who underwent cryosurgery (CS) for prostate cancer between 2013 - 2015. Low urinary tract symptoms (LUTS) and quality of life (QoL) were assessed 1 month before surgery using IPSS questionnaire, a three-day voiding diary (3DVD) and uroflowmetry with ultrasound-measured postvoid residual volume. Need of medical treatment for LUTS was also recorded. The same assessment was performed at 3, 6 and 12 months after CS. Outcomes after surgery were compared to those prior to surgery. RESULTS: Forty-five patients underwent a CS during the study period, of whom 25 patients could be recruited in the study. Mean age was 73.5 years (range 66-84). Nineteen CS (76%) were performed as a primary procedure, while 6 CS (24%) as a salvage procedure. No statistical differences were found comparing results of IPSS, QoL, D3vd or uroflowmetry and PVR at 3, 6 or 12 months after CS compared to before surgery. Before CS, 8 (32%) patients were on medical treatment for LUTS, while at 6 and 12 months after surgery, 3 (13.6%) and 2 (9.5%) patients required some medication, respectively. CONCLUSION: According to the punctuation of IPSS, QoL questionnaire, and a 3-day voiding diary, LUTS does not worsen after CS. Prostatic cryosurgery does not seem to impact uroflowmetry results.

Recommendations for the Diagnosis and Management of Bladder Pain Syndrome. Spanish Urological Association Consensus Document.

INTRODUCTION: Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and other bladder pathologies share common manifestations, such as the presence of mictional symptoms and a negative impact on the patient's quality of life. To be properly diagnosed and clinically managed, it is important to distinguish between its clinical modalities and diagnostic criteria for adequate exclusion. OBJECTIVE: The purpose of this study was to standardize criteria for making decisions in BPS management, for its diagnosis, initial treatment and follow-up. MATERIAL AND METHOD: A nominal group methodology was employed, using scientific evidence on BPS taken from a systematic (non-exhaustive) literature review for developing recommendations along with specialist expert opinions. RESULTS: The diagnosis of BPS should be made based on the patient's clinical history, with emphasis on pain and mictional symptoms as well as excluding other pathologies with similar symptomatology. BPS treatment should be directed towards restoring normal bladder function, preventing symptom relapse and improving patients' quality of life. It is therefore advisable to start with conservative treatment and to adopt less conservative treatments as the level of clinical severity increases. It is also recommended to abandon ineffective treatments and reconsider other therapeutic options. CONCLUSIONS: Quickly identifying the pathology is important when trying to positively influence morbidity and care quality for these patients.

Consensus document of the Spanish Urological Association on the management of uncomplicated recurrent urinary tract infections.

INTRODUCTION: The clinical manifestations of urinary infections, commonly mild and uncomplicated, have resulted in a generally empirical therapeutic decision-making process, which does not help fight resistances to antibacterial agents, thus causing a high rate of recurrence. OBJECTIVE: This study seeks to reduce the clinical variability in the diagnosis and treatment of uncomplicated recurrent urinary tract infections (RUTIs). MATERIAL AND METHOD: The consensus document was developed using a nominal group methodology, using scientific evidence on RUTIs extracted from a systematic (noncomprehensive) literature review, along with the expert judgment of specialists and their experience in clinical practice. RESULTS: RUTIs are considered the manifestation of at least 3 episodes of uncomplicated infection, with a positive culture in the past 12 months, in addition to (for men) the absence of structural or functional abnormalities. We maintain that the treatment should be empiric when suspecting RUTIs (prior to obtaining a urine sample for culture) in those patients who have a high probability of recurrence, associated risk factors and/or urinary or general symptoms, such as fever and chills. Homogeneous criteria are recommended for the diagnosis and treatment in order to fight the increased rates of resistance that the microorganisms develop against antimicrobial agents. CONCLUSION: Imprecision in the identification of the infection requires a search for agreements on homogenized criteria and decision algorithms that guide the management of these patients.

Nitrergic neuromuscular transmission in the mouse internal anal sphincter is accomplished by multiple pathways and postjunctional effector cells.

The effector cells and second messengers participating in nitrergic neuromuscular transmission (NMT) were investigated in the mouse internal anal sphincter (IAS). Protein expression of guanylate cyclase (GCα, GCß) and cyclic GMP-dependent protein kinase I (cGKI) were examined in cryostat sections with dual-labeling immunohistochemical techniques in PDGFRα(+) cells, interstitial cells of Cajal (ICC), and smooth muscle cells (SMC). Gene expression levels were determined with quantitative PCR of dispersed cells from Pdgfrα(egfp/+), Kit(copGFP/+), and smMHC(Cre-egfp) mice sorted with FACS. The relative gene and protein expression levels of GCα and GCß were PDGFRα(+) cells > ICC ≫ SMC. In contrast, cGKI gene expression sequence was SMC = ICC > PDGFRα(+) cells whereas cGKI protein expression sequence was neurons > SMC ≫ ICC = PDGFRα(+) cells. The functional role of cGKI was investigated in cGKI(-/-) mice. Relaxation with 8-bromo (8-Br)-cGMP was greatly reduced in cGKI(-/-) mice whereas responses to sodium nitroprusside (SNP) were partially reduced and forskolin responses were unchanged. A nitrergic relaxation occurred with nerve stimulation (NS, 5 Hz, 60 s) in cGKI(+/+) and cGKI(-/-) mice although there was a small reduction in the cGKI(-/-) mouse. N(ω)-nitro-l-arginine (l-NNA) abolished responses during the first 20-30 s of NS in both animals. The GC inhibitor ODQ greatly reduced or abolished SNP and nitrergic NS responses in both animals. These data confirm an essential role for GC in NO-induced relaxation in the IAS. However, the expression of GC and cGKI by all three cell types suggests that each may participate in coordinating muscular responses to NO. The persistence of nitrergic NMT in the cGKI(-/-) mouse suggests the presence of a significant GC-dependent, cGKI-independent pathway.

[Kidney transplantation in children weighing 11 kg or less]. / Trasplante renal en el paciente con peso igual o menor a 11 kg.

AIMS OF THE STUDY: To evaluate the outcome of kidney transplantation in children with low weight. METHODS: Retrospective review of the medical records of patients weighing 11 kg or less that received kidney transplantation between 2001 and 2013 were retrospectively reviewed. RESULTS: Fifty-nine kidney transplantations were performed in pediatric patients in our center, 12 of them were performed in patients weighing 11 kg or less (20%). The mean age of the recipient at the time of transplantation was 2 years (1-3.5); the mean weight was 9.4 ± 1.1 kg (8.3-11). The etiology of kidney failure was malformative in 42% of patients, inherited in 33%, glomerular in 8% and oiler etiologies in 17% of the patients. Two patients did not receive replacement therapy before transplantation (16.7%), nine received peritoneal dialysis (75%) and one of them hemodialysis (8.3%). Eleven of the grafts were from cadaveric donor (91.7%) and one of them from a living donor (8.3%). The mean donor age was 10 years (0.5-29). There was one case of acute graft thrombosis (8.3%) and one case of eventration requiring reoperation; there were no other major complications. Mean follow-up was 59 months (4-130). Overall survival (OS) was 100% at 1 year and 91.7% at 5 years. There was one death in a patient with mitochondrial disease with a functioning graft. Graft survival (GS) was 92% at 1 year and 75% at 5 years. CONCLUSION: Kidney transplantation is the treatment of choice for end-stage kidney failure in the young child. It provides good results in terms of patient and graft survival.

Differential expression of genes related to purinergic signaling in smooth muscle cells, PDGFRα-positive cells, and interstitial cells of Cajal in the murine colon.

BACKGROUND: Purinergic signaling provides regulation of colonic motility. Smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and platelet-derived growth factor receptor α-positive (PDGFRα(+) ) cells are electrically coupled and form a functional (SIP) syncytium that constitutes the receptive field for motor neurotransmitters in the tunica muscularis. Each cell type in the SIP syncytium has specialized functions in mediating motor neurotransmission. We compared gene transcripts for purinergic receptors and membrane-bound enzymes for purine degradation expressed by each cell type of the SIP syncytium. METHODS: Fluorescence-activated cell sorting (FACS) was used to purify SMC, ICC, and PDGFRα(+) cells from mixed cell populations of colonic muscles dispersed from reporter strains of mice with constitutive expression of green fluorescent proteins. Differential expression of functional groups of genes related to purinergic signaling was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). KEY RESULTS: We detected marked phenotypic differences among SMC, ICC, and PDGFRα(+) cells. Substantial numbers of genes of importance in purinergic neurotransmission were enriched in PDGFRα(+) cells in relation to SMC and ICC. Notably, genes related to mediating effects and extracellular biotransformation of enteric purinergic inhibitory neurotransmitters were strongly expressed by PDGFRα(+) cells. CONCLUSIONS & INFERENCES: Our results demonstrate differential expression of genes for proteins involved in purinergic signaling in the SIP syncytium. These results may further clarify the specific functions of each cell type, identify novel biomarkers for postjunctional cells, and provide hypotheses for further studies to understand the physiological roles of cells of the SIP syncytium.

Transposition of iliac vessels in implantation of right living donor kidneys.

BACKGROUND: The rate of right laparoscopic living-donor nephrectomy (RLLDN) is low among kidney transplantations due to the short renal vein and presumed higher risk of thrombosis. Our objective was to describe a surgical technique to compensate for the shorter veins of these grafts. METHODS: Between January 2004 and July 2010, we prospectively collected data from all transplantations using RLLDN-harvested kidneys at our center. Recipient iliac vein transposition was performed in all patients. We reviewed the indications, surgical techniques, and postoperative courses. RESULTS: The 43 included cases showed a 2.1 +/- 0.6 cm, average length of the right renal vein as measured on abdominal computed tomography (CT). The mean extraction and implantation times were 109 +/- 33 and 124 +/- 31 minutes, respectively; the mean warm ischemia time was 151 +/- 29 seconds. Two recipients required postsurgical blood transfusions. In 97.6% of cases, there was immediate urine flow. Postoperative echo-Doppler revealed good arterial and venous flows in all patients. No venous thromboses were detected. The recipients' average hospital stay was 8 +/- 5 days. With a mean follow-up of 57 months, 86% of recipients maintain a glomerular filtration rate (GFR) >50 mL/min and creatinine levels <1.5 mg/dL. CONCLUSIONS: Transposition of the recipient iliac vein during implantation is a good technical solution to compensate for the short length of the right renal vein. The use of iliac vein transposition allowed us to perform safe implants of RLLDN-harvested kidneys with good short-term and long-term results.

Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies.

Cortical gray matter deficits have been found in patients with schizophrenia, with evidence of progression over time. The aim of this study was to determine the extent of progressive cortical gray matter volume changes over time in schizophrenia, their site and time of occurrence, and the role of potential moderators of brain changes. English language articles published between 1 January 1983 and 31 March 2012 in the MEDLINE and EMBASE databases were searched. Longitudinal magnetic resonance imaging studies comparing changes in cortical gray matter volume over time between patients with schizophrenia and healthy controls were included. Hedges g was calculated for each study. Analyses were performed using fixed- and random-effects models. A subgroup analysis was run to explore the pattern of brain changes in patients with first-episode schizophrenia. A meta-regression statistic was adopted to investigate the role of potential moderators of the effect sizes (ESs). A total of 19 studies, analyzing 813 patients with schizophrenia and 718 healthy controls, were included. Over time, patients with schizophrenia showed a significantly higher volume loss of total cortical gray matter, left superior temporal gyrus (STG), left anterior STG, left Heschl gyrus, left planum temporale and posterior STG bilaterally. Meta-analysis of first-episode schizophrenic patients showed a more significant pattern of progressive loss of whole cerebral gray matter volume involving the frontal, temporal and parietal lobes, and left Heschl gyrus compared with healthy controls. Clinical, pharmacologic and neuroradiological variables were found to be significant moderators of brain volume changes in patients with schizophrenia. The meta-analysis demonstrates that progressive cortical gray matter changes in schizophrenia occur with regional and temporal specificity. The underlying pathological process appears to be especially active in the first stages of the disease, affects the left hemisphere and the superior temporal structures more and is at least partly moderated by the type of pharmacological treatment received.

The DRG shift: a new twist for ICD-10 preparation.

Analysis of your specific business is a key component of ICD-10 implementation. An understanding of your organization's current reimbursement trends will go a long way to assessing and preparing for the impact of ICD-10 in your environment. If you cannot be prepared for each detailed scenario, remember that much of the analysis and resolution requires familiar coding, DRG analysis, and claims processing best practices. Now, they simply have the new twist of researching new codes and some new concepts. The news of a delay in the implementation compliance date, along with the release of grouper Version 29, should encourage your educational and business analysis efforts. This is a great opportunity to maintain open communication with the Centers for Medicare & Medicaid Services, Department of Health and Human Services, and Centers for Disease Control. This is also a key time to report any unusual or discrepant findings in order to provide input to the final rule.

Hypertension, dyslipidemia and overweight are related to lower testosterone levels in a cohort of men undergoing prostate biopsy.

Testosterone deficiency syndrome (TDS) is a clinical and biochemical entity related to sexual and cardiovascular health. Hypertension, diabetes mellitus (DM), dyslipidemia and overweight are four clinical factors strongly related to cardiovascular illnesses. The aim of our study was to determine if the presence and number of cardiovascular risk factors was related to total testosterone levels and the presence of biochemical TDS. We retrospectively analyzed 384 patients referred to our center for prostate biopsy between September 2007 and December 2009. Variables age, height, weight, body mass index (BMI), tobacco use, alcohol intake, hypertension, DM, dyslipidemia (hypercholesterolemia/hypertriglyceridemia) and overweight (BMI>25) were recorded prospectively. Hormonal profile was determined as part of our clinical protocol. We used 231 and 346 ng dl(-1) as total testosterone cut-points (8-12 nmol l(-1)) for diagnosis of biochemical TDS, following ISA-ISSAM-EAU Guidelines. We analyzed the relationship between testosterone levels and the presence of hypertension, DM, dyslipidemia and overweight, and with the number of these cardiovascular risk factors. Mean age was 66 ± 8 years. Prevalence of TDS was 6.5% within the 231 ng ml(-1) cutoff point and 28.4% for the 346 ng dl(-1) cutoff point. Levels of testosterone were related to hypertension (P=0.007), dyslipidemia (P=0.013), overweight (P=0.036) and the number of cardiovascular risk factors (P=0.018). The prevalence of TDS in our population is comparable to data from international studies. Testosterone levels decrease as the number of cardiovascular risk factors rise.

Identification of histamine receptors and effects of histamine on murine and simian colonic excitability.

BACKGROUND: Inflammatory responses can include recruitment of cells of hematopoietic origin to the tunica muscularis. These cells can secrete a variety of factors which can reset the gain of smooth muscle cells (SMC) and influence motor patterns. Histamine (H), a major mediator in inflammation, is released by mast cells and exerts diverse effects in SMC by binding to H receptors. The profiles of H receptor expression in animal models used to study inflammatory diseases are unknown. METHODS: Histamine receptor expression and electro-mechanical responses to H were tested in simian and murine colonic smooth muscle using qualitative and quantitative PCR, isometric force measurements, microelectrode recordings and patch clamp techniques. KEY RESULTS: H1, H2, and H4 receptor transcripts were expressed at similar levels in simian colonic tissue whereas only the H2 receptor transcript was detected in murine colonic tissue. Stimulation of simian colonic muscles with H caused depolarization and contraction in the presence of tetrodotoxin. Histamine activated non-selective cation channels in simian SMC. In contrast, H caused hyperpolarization and inhibited contractions of murine colon. The hyperpolarization was inhibited by the K(ATP) channel blocker, glibenclamide. Histamine-activated K(+) currents were inhibited by glibenclamide in murine colonic SMC. CONCLUSIONS & INFERENCES: Histamine receptor expression in simian SMC was similar to that reported in humans. However, H receptor profile and responses to H were considerably different in mice. Thus, monkey colon may be a more suitable model to study how inflammatory mediators affect the gain of smooth muscle excitability.

[Pioneer experience in Spain with LSSS nephrectomy in living donor]. / Experiencia pionera en España con nefrectomía LESS de donante vivo.

INTRODUCTION: LESS surgery (Laparoendoscopic single site surgery) is a surgical technique that aims to perform intraabdominal surgery using a single site entry, allowing for reduction in the number and size of the incisions, achieving better esthetic results with at least the same functional outcomes as with the conventional laparoscopic surgery. MATERIAL AND METHODS: We present the first experience of LESS living donor nephrectomy carried out by a totally European team. To perform it, a Quadport® device was placed through a 4 cm long paraumbilical incision. RESULTS: The nephrectomy was performed using the standards of conventional laparoscopic surgery, with the use of a precurved instrument in the left hand and straight instruments in the right. After bagging the kidney, the artery and vein were sectioned after clipping, allowing for rapid extraction of the organ through the same incision, with warm ischemia of 3.30" and 2.47," respectively. CONCLUSION: Living donor nephrectomy using the LESS technique is feasible and can be considered a good option for obtaining live donor kidney grafts in males. The application of said surgical in living kidney donor can increase the rate of donation, by reducing morbidity and improving the esthetic results with the same outcome for the donor as for the recipient.

Psychopathologic, neuropsychological and functional outcome measures during cognitive rehabilitation in schizophrenia: a prospective controlled study in a real-world setting.

BACKGROUND: Cognitive dysfunction has been demonstrated in patients with schizophrenia, and this may affect patients' functional outcome. The improvement of such dysfunction by means of cognitive remediation interventions has become a relevant target in the care of schizophrenia. OBJECTIVE: To assess the effectiveness of the cognitive subprograms of Integrated Psychological Therapy (IPT) on symptomatological, neuropsychological and functional outcome variables and to analyze the relationships between cognitive and functional outcome changes in schizophrenia. METHODS: Thirty-two patients with schizophrenia were assigned to cognitive remediation (IPT-cog) or usual rehabilitative interventions in a naturalistic setting of care. Clinical, neuropsychological and functional outcome variables were assessed at baseline and after 24 weeks of treatment. RESULTS: The IPT-cog group improved significantly more than the comparison group with respect to psychopathological and functional outcome variables. Moreover, only the IPT-cog group improved significantly in the neuropsychological domains of verbal and working memory, with specific significant correlations between neurocognitive performance and functional outcome changes. CONCLUSIONS: The results of the study confirm the effectiveness of the cognitive remediation component of IPT in schizophrenia, and indicate that some of the changes in functional outcome may be mediated by improvement in specific cognitive domains.

Accuracy of contrast-enhanced ultrasound in the detection of bladder cancer.

OBJECTIVE: To assess the accuracy contrast-enhanced ultrasound (CEUS) in bladder cancer detection using transurethral biopsy in conventional cystoscopy as the reference standard and to determine whether CEUS improves the bladder cancer detection rate of baseline ultrasound. METHODS: 43 patients with suspected bladder cancer underwent conventional cystoscopy with transurethral biopsy of the suspicious lesions. 64 bladder cancers were confirmed in 33 out of 43 patients. Baseline ultrasound and CEUS were performed the day before surgery and the accuracy of both techniques for bladder cancer detection and number of detected tumours were analysed and compared with the final diagnosis. RESULTS: CEUS was significantly more accurate than ultrasound in determining presence or absence of bladder cancer: 88.37% vs 72.09%. Seven of eight uncertain baseline ultrasound results were correctly diagnosed using CEUS. CEUS sensitivity was also better than that of baseline ultrasound per number of tumours: 65.62% vs 60.93%. CEUS sensitivity for bladder cancer detection was very high for tumours larger than 5 mm (94.7%) but very low for tumours <5 mm (20%) and also had a very low negative predictive value (28.57%) in tumours <5 mm. CONCLUSION: CEUS provided higher accuracy than baseline ultrasound for bladder cancer detection, being especially useful in non-conclusive baseline ultrasound studies.

Audit of an initial 100 cases of laparoscopic live donor nephrectomy.

BACKGROUND: The objective of this study was to analyze variables related to the surgical technique and postoperative evolution of kidney donors. MATERIALS AND METHODS: This retrospective analysis describes 100 laparoscopic nephrectomies from living donors performed in our hospital between February 2002 and July 2007. The variables were age, family relationship, surgical time, warm ischemia time, hospital stay, oral feeding resumption, morphine use, return to work, and complications. RESULTS: The average age of the donors was 49.5 years and their male:female ratio was 1:2. The left kidney was extracted from 82% of patients. The warm ischemia time was 2.5 minutes (range = 1.09-5.10). There was only one case of multiple vessels. The surgical time was 149.5 minutes (range = 80-255). The mean hospital stay was 4.8 days (range = 1-18). Food intake was resumed after 24 hours, with morphine needed for 0.9 days. The time to return to work was 39 days (range = 7-120). The complications included kidney rupture (n = 1), liver tear (n = 1), hematoma (n = 6), including four requiring blood transfusions; fever and leukocytosis (n = 5) and one collection. No patients died as a result of the surgery. CONCLUSIONS: Living-donor laparoscopic nephrectomy constitutes the gold standard among surgical options.

Third and fourth kidney transplant: still a reasonable option.

INTRODUCTION: At present, a second kidney transplant is considered an established therapeutic option for patients who have lost a previous graft. Second transplants show similar graft survival as first transplants. A debate exists about the benefit of submitting the patient to a third or fourth renal transplant, or to maintain dialysis. OBJECTIVE: We sought to analyze graft and patient survivals as well as associated variables and surgical complications of third and fourth transplantations. MATERIAL AND METHODS: From July 1985 to December 2008, we performed 74 third and 8 fourth transplantations among 2763 cases. We prospectively collected the variables of age, gender, graft origin, hyperimmunization, time on dialysis, location, bench surgery, acute rejection episodes, graft survival, and operative complications. RESULTS: Third and fourth trasplantations were performed in 49 men and 33 women, with an overall mean age of 40.26 years who were on dialysis for an average of 126.89 months before transplantation. Mean graft survivals of their first and second grafts were 35.6 and 50.1 months, respectively. Acute or chronic rejection was reason for renal failure in 71% and 75% of cases, respectively. Patient survivals at 1 and 5 years were 92.7% and 90.6%, for third and both 85.7% for the fourth transplantation. The third and fourth transplantations showed 1- and 5-year graft survivals of 88% and 76.4% and 71.4% and 42.9%, respectively. Sixty-eight cases underwent cadaveric donor and 14 living donor (mean age, 42.1 years) transplantations. Nine patients were hyperimmunized. In 60 cases, we used the left kidney. Orthotopic kidney transplantation was performed in 15 cases; heterotopic transplant to the right iliac fossa in 40 and in the left iliac fossa in 17 cases. Arterial bench surgery was necessary in 6 cases and venous in 3. We performed 3 hepatorenal and 1 cardiorenal transplantation. The complications included 29 cases (35.4%) of postoperative acute tubular necrosis, 14 of acute rejection episodes (17.1%); 12 of perirenal hematoma (14.6%); 1 urinary fistula (1.2%); 4 lymphocele (4.9%); 2 ureteral stenosis (2.4%); variables arterial kink requiring surgery (1.2%), and 1 venous thrombosis with graft loss (1.2%). The 4 patients who died in the perioperative period succumbed to intravascular disseminated coagulation (n = 1) cardiac failure (n = 2), and septic shock (n = 1). Induction antibody therapy, hyperimmunized status, or operative complications were not independent prognostic factors for patient or graft survival. CONCLUSIONS: Third or fourth renal transplantations constitute a valid therapeutic option with reasonable short- and long-term patient and graft survivals. Although orthotopic kidney transplantation was used in selected patients, we preferred an iliac fossa approach for most.

Formation of an adduct by clenbuterol, a beta-adrenoceptor agonist drug, and serum albumin in human saliva at the acidic pH of the stomach: evidence for an aryl radical-based process.

Clenbuterol (CLB) is an antiasthmatic drug used also illegally as a lean muscle mass enhancer in both humans and animals. CLB and amine-related drugs in general are nitrosatable, thus raising concerns regarding possible genotoxic/carcinogenic activity. Oral administration of CLB raises the issue of its possible transformation by salivary nitrite at the acidic pH of gastric juice. In acidic human saliva CLB was rapidly transformed to the CLB arenediazonium ion. This suggests a reaction of CLB with salivary nitrite, as confirmed in aerobic HNO(2) solution by a drastic decrease in nitric oxide, nitrite, and nitrate. In human saliva, both glutathione and ascorbic acid were able to inhibit CLB arenediazonium formation and to react with preformed CLB arenediazonium. The effect of ascorbic acid is particularly pertinent because this vitamin is actively concentrated within the gastric juice. EPR spin trapping experiments showed that preformed CLB arenediazonium ion was reduced to the aryl radical by ascorbic acid, glutathione, and serum albumin, the major protein of saliva. As demonstrated by anti-CLB antibodies and MS, the CLB-albumin interaction leads to the formation of a covalent drug-protein adduct, with a preference for Tyr-rich regions. This study highlights the possible hazards associated with the use/abuse of this drug.