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Background: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants.Methods: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes.Results: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester).Conclusions: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.). [ABSTRACT FROM AUTHOR]

Mucopolysaccharidoses (MPS) are genetically determined diseases, leading to a deficiency of enzymes in the glycosaminoglycan (GAG) degradation pathway. The accumulation of GAG occurs in connective tissue in various organs and systems of the body, including the larynx, trachea, and bronchi. Respiratory symptoms are common and severe in these patients, and respiratory disease is a frequent cause of death. A cross-sectional study with flexible bronchoscopy was conducted in 30 MPS patients (6 MPS I, 8 MPS II, 2 MPS III, 3 MPS IV-A, and 11 MPS VI). Only four patients (13.33%) had a normal airway; nine (30%) had mild to moderate disease, 12 (40%) moderate to severe, and five patients (16.67%) had severe disease. Of particular interest, neuronopathic MPS II had the largest proportion of tracheostomized patients who died due to respiratory complications; in MPS IV-A, all patients had significant tracheobronchial deformity with associated tracheomalacia, despite lacking laryngeal involvement. Laryngotracheobronchial disease (LTBD) was associated to longer disease history and was significantly more severe in older patients. Longer use of enzyme replacement therapy did not prevent the progression of LTBD, although the age of therapy introduction may be a crucial factor in lower airway involvement.

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder caused by pathogenic variants of the RMRP gene and characterized by metaphyseal bone dysplasia associated with hypotrichosis, immunodeficiency, and predisposition to malignancy. However, the genotype-phenotype correlation in CHH is not well understood. Here, we report a single country cohort of 23 Brazilian patients with clinical and radiological features consistent with CHH. We found 23 different pathogenic variants in the RMRP gene - 12 novel and 11 previously described in the literature. Interestingly, the most frequent Finnish pathogenic variant related to CHH (g.71A>G) was not found in our cohort. In contrast, more than 50% of the patients carried the rare g.196C>T variant suggesting a possible founder effect in the Brazilian population. In silico analysis showed that pathogenic variants occurred either in the regions conserved in mammalian species or within essential domains for the ribonucleoprotein complex. Pathogenicity prediction studies can improve the understanding of how these variants affect RNA., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2019 by S. Karger AG, Basel.)

Robot-assisted radical prostatectomy (RARP) may be performed via an extraperitoneal (eRARP) or transperitoneal (tRARP) approach. There are no published studies comparing these two methods in patients with a history of prior inguinal hernia repair with mesh (IHRm), but the latter is often advocated in this setting. A retrospective review of patients who underwent RARP with prior IHRm who had a minimum follow-up of 3 months from July 1, 2003 to December 31, 2014 was undertaken. Of 2927 patients who underwent RARP for primary treatment of adenocarcinoma of the prostate, 286 patients had a clear history of IHRm. Of these, 116 patients underwent eRARP and 170 patients underwent tRARP. No differences were noted between the groups with respect to age, body mass index or American Society of Anesthesiology score. Patients in the tRARP group had higher D'Amico risk classification scores (p < 0.0001) and as such, underwent less nerve-sparing procedures (p < 0.0001) and had a higher rate of concomitant pelvic lymph node dissections (p < 0.0001). The tRARP group had a higher incidence of laparoscopic and bilateral IHRm. On univariate analysis, EBL was lower in the tRARP group (172.41 vs. 201.98, p = 0.05) but all other parameters were similar. After controlling for covariates using regression analysis with model selection, a trend was noted towards lower operating room time in the tRARP group (p = 0.0624) but no other differences were noted. The presence of prior IHRm does not seem to be a contraindication to eRARP. OR time may be lower with tRARP (trend) but all other quality indicators studied were similar.

Introduction and Objective: With the peritoneum acting as a natural surface for lymphatic reabsorption, transperitoneal robot-assisted radical prostatectomy (tRARP) is thought to be associated with a lower incidence of symptomatic lymphoceles (SLs) compared with its extraperitoneal counterpart (eRARP) when bilateral pelvic lymph node dissection (BPLND) is performed. In this study, we aim to determine if there is a difference in SL formation and characteristics between the two approaches., Materials and Methods: We retrospectively reviewed the records of patients who underwent eRARP or tRARP and BPLND by a single surgeon at a tertiary care academic center from July 1, 2003, to May 31, 2016. Patients with a history of prior pelvic radiotherapy, concomitant inguinal hernia repair, RARP without BPLND, or nonadenocarcinoma of the prostate were excluded. The resulting eRARP and tRARP groups were propensity matched for age, body mass index (BMI), American Association of Anesthesiologists (ASA) score, D'Amico risk classification, and pathological lymph node (LN) count., Results: A total of 3183 RARPs were performed during this time period. After applying exclusion criteria and propensity score matching, 671 patients remained in each group. No statistically significant differences were noted between the groups with regard to age, BMI, ASA, pre-RARP prostate-specific antigen, D'Amico risk classification, biopsy and pathological Gleason sum score, pathological T stage, or margin status. The tRARP group had a higher clinical T stage (p = 0.0015), length of stay (LOS; p = 0.005), pathological N stage (4.92% vs 1.36%, p = 0.0002), and high total LN count (7.22 ± 5.54 vs 5.78 ± 4.18 LNs, p < 0.0001). The eRARP group had higher operating room times (197.4 ± 48.96 minutes vs 192.2 ± 44.12 minutes, p = 0.04) and estimated blood loss (218.4 ± 152.0 mL vs 179.9 ± 119.4 mL, p < 0.0001). No differences were noted in the frequency of SL formation [eRARP: 19/671 (2.83%) vs tRARP: 10/671 (1.49%), p = 0.09] or any clinical characteristics of the SL. Logistic regression analysis showed no effect of LN count (p = 0.071), pathological N stage (p = 0.111), or both combined (p = 0.085) on SL formation., Conclusions: In this cohort, the rate and clinical characteristics of SL were similar among patients treated with eRARP or tRARP and BPLND. The low event rate of SL in each group and trends favoring higher SL with LN yield and pN1 disease in the tRAPR group may deem the study underpowered to make definitive conclusions.

Introduction: We sought to determine the value of obtaining preoperative urinary cytology when diagnostic workup of an upper tract mass is suspicious for upper tract urothelial carcinoma (UTUC), but biopsy fails to confirm the diagnosis., Methods: Using billing code data, 239 patients were identified as having undergone radical nephroureterectomy (RNU) by 16 urologists from September 29, 1998 to July 31, 2015. Of this group, 19 adult patients had a presumed preoperative diagnosis of UTUC in a native kidney, at least three months of followup, no history of concurrent radical cystectomy with RNU, and negative/non-diagnostic tissue biopsy. These patients were divided into three groups: Group A had no urinary cytology taken (n=6); Group B had upper and/or lower tract cytology performed with neither positive nor atypical (n=7); Group C had upper and/or lower tract cytology performed with at least one positive or atypical (n=6)., Results: Demographic information and diagnostic workup was similar between the groups, although Group A had more patients with a history of prior radical cystectomy for bladder cancer (p=0.02). One patient in Group B had benign tissue on final pathology. All patients in Groups A and C had malignancy on final pathology and overall, the three groups had similar rates of malignancy., Conclusions: When a composite of clinical findings suggest UTUC, performing urinary cytology may not be necessary. A negative result in this setting should not be used to rule out UTUC, as this is often discordant with final pathology. A positive cytology result may help solidify the diagnosis when other findings are less clear., Competing Interests: Competing interests: The authors report no competing personal or financial interests.

Introduction: During robot-assisted radical prostatectomy (RARP), the prostate may be approached extraperiteoneally (extraperitoneal robot-assisted radical prostatectomy [eRARP]) or transperitoneally (transperitoneal robot-assisted radical prostatectomy [tRARP]). The former avoids the abdominal cavity, which might be of benefit in patients who have had prior abdominal or pelvic surgery (PAPS). Our objective was to compare the outcomes of patients with PAPS undergoing either technique., Methods: A retrospective review of patients treated with RARP from July 1, 2003 to December 31, 2014 with a minimum follow-up of 3 months was undertaken. Of 2927 patients, 620 were identified as having undergone RARP (without concomitant unrelated procedures) and PAPS (excluding patients with prior inguinal hernia repair with mesh or unclear surgical histories) for prostate adenocarcinoma without prior pelvic radiotherapy. Of these, 340 patients underwent eRARP and 280 patients underwent tRARP., Results: Patients in the eRARP group were younger (61.04 years vs 62.32, p = 0.02), had a higher body mass index (29.65 vs 28.98, p = 0.09), lower American Society of Anesthesiologists scores (p = 0.03), and lower D'Amico risk classification disease (p < 0.0001). The two groups had similar rates of 1, 2, and >2 PAPS. On univariate analysis, the eRARP group had lower operative time (188.96 minutes vs 197.92 minutes, p = 0.003), extensive lysis of adhesions (0.9% vs 14.3%, p < 0.0001), length of hospital stay (LOS) (1.13 days ±0.45 vs 1.33 day ±1.08, p = 0.003), and higher estimated blood loss (210.74 mL vs 190.79 mL, p = 0.06). The eRARP group had a lower rate of gastrointestinal complications (0% vs 3.21%, p = 0.0007), a trend toward lower early post-operative complications (8.53% vs 12.86%, p = 0.08), and lower overall complications (9.41% vs 15%, p = 0.03). In regression analysis with model selection, only LOS was lower in the eRARP group (p = 0.02)., Conclusions: Both methods are safe in patients with prior abdominal surgeries. A lower incidence of gastrointestinal complications and a shorter length of stay were noted in the extraperitoneal cohort.

Unlabelled: What's known on the subject? and What does the study add? Elderly patients have more years to compound comorbidities and it has previously been shown that comorbidity is an important predictor of overall survival in patients with bladder cancer, including those treated with radical cystectomy (RC). Other studies have also demonstrated higher stage at diagnosis, higher rate of upstaging on final pathology and a longer delay to definitive therapy for older patients. Because of these findings, elderly patients are being offered RC less often than younger patients. Whether or not this practice is justified has come under recent scrutiny and there has been much conflicting data in the literature. While some studies have shown worse outcomes for elderly patients, others have shown similar results for both elderly and younger patients. Large population-based databases have recently been used to try to determine whether age effects outcome after RC but their conclusions may not be as generalizable as ours for several reasons: billing code data was used to build patient cohorts, patients were generally recipients of Medicare, lack of pathological review, and lack of available and accurate clinical data. Our series is unique in that it comprises a large group of patients from two major tertiary care academic institutions using a very robust dataset. Pathological specimens were reviewed by dedicated genitourinary pathologists, including those recovered from peripheral hospitals. Our sample size is one of the largest single- or multi-institutional studies., Objective: • To analyse the impact of patient age on survival after radical cystectomy (RC)., Patients and Methods: • After ethics review board approval, two databases of patients with bladder cancer (BC) undergoing RC at the University Heath Network, Toronto, Canada (1992-2008) and the University of Turku, Turku, Finland (1986-2005) were retrospectively analysed. • A total of 605 patients who underwent this procedure between June 1985 and March 2010 were included. • Patients were divided into four age groups: ≤ 59, 60-69, 70-79 and ≥ 80 years. • Demographic, clinical and pathological data were compared, as well as recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OAS) rates., Results: • Compared with younger patients (age ≤ 79 years), elderly patients (age ≥ 80 years) had higher American Society of Anesthesiologists scores (P < 0.001), a greater number of lymph nodes removed during surgical dissection (P < 0.001), and underwent less adjuvant treatment (P < 0.001). • Choice of urinary diversion differed among the groups, with ileal conduit being used for all patients ≥ 80 years (P < 0.001). • No differences were noted between age groups with respect to RFS (P= 0.3), DSS (P= 0.4) or OAS (P= 0.4)., Conclusion: • Although RC is an operation with significant morbidity, it is a viable treatment option for carefully selected elderly patients. Senior patients (≥ 80 years) should not be denied RC if they are deemed fit to undergo surgery. • Senior adults do not suffer from adverse histopathological features as compared with younger patients., (© 2012 BJU INTERNATIONAL.)

Unlabelled: Study Type - Prognosis (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Surgical volume has been well established as a predictor of outcomes for several complex surgical procedures, yet few studies have evaluated this relationship with regards to radical nephrectomy with either renal vein or inferior vena cava thrombectomy. In addition, most published literature consists of single-institution series from centres of excellence. We performed a population-level analysis and identified surgeon volume as a significant predictor of short-term mortality for this procedure. Such findings have potential implications regarding future policy and regionalization of care., Objective: • To study the short-term mortality associated with radical nephrectomy with renal vein or inferior vena cava thrombectomy and the variables associated with this adverse outcome., Methods: • Using the Ontario Cancer Registry, we identified 433 patients in the province of Ontario, Canada undergoing radical nephrectomy with venous thrombectomy between 1995 and 2004. • We determined mortality rates at postoperative days 30 and 90. • Other variables analysed include pathological tumour characteristics, surgeon graduation year, hospital/surgeon academic status, surgery year and hospital/surgeon volume. • We used multivariable logistic regression to assess outcomes., Results: • Overall mortality was 2.8% (30-day) and 5.8% (90-day). • Surgeons performing a single nephrectomy with venous thrombectomy performed 14% of the cases and had the highest 30-day (6.7%) and 90-day (10%) mortality. The mortality rate for surgeons performing more than one surgery was 2.1% (30-day) and 5.1% (90-day). • In recent years, this procedure was performed more commonly by the highest volume surgeons - 67% of cases in 2004 vs 40% in 1995. • Significant predictors of 30-day mortality included procedure year and low surgeon volume. • Significant predictors of 90-day mortality included procedure year, low surgeon volume, left-sided tumour and increasing hospital volume., Conclusions: • For radical nephrectomy with venous thrombectomy, surgeon volume predicts short-term mortality, emphasizing the importance of experience in patient outcome. • Despite a shift towards high-volume surgeons, 13.8% of cases continued to be performed by low-volume providers. • If these results are confirmed in other jurisdictions, radical nephrectomy with venous thrombectomy should be regionalized and performed by surgeons who manage these cases regularly., (© 2012 BJU INTERNATIONAL.)

Background: Holoprosencephaly (HPE), the most common malformation of the human forebrain, may result from mutations in over 12 genes. Sonic Hedgehog (SHH) was the first such gene discovered; mutations in SHH remain the most common cause of non-chromosomal HPE. The severity spectrum is wide, ranging from incompatibility with extrauterine life to isolated midline facial differences., Objective: To characterise genetic and clinical findings in individuals with SHH mutations., Methods: Through the National Institutes of Health and collaborating centres, DNA from approximately 2000 individuals with HPE spectrum disorders were analysed for SHH variations. Clinical details were examined and combined with published cases., Results: This study describes 396 individuals, representing 157 unrelated kindreds, with SHH mutations; 141 (36%) have not been previously reported. SHH mutations more commonly resulted in non-HPE (64%) than frank HPE (36%), and non-HPE was significantly more common in patients with SHH than in those with mutations in the other common HPE related genes (p<0.0001 compared to ZIC2 or SIX3). Individuals with truncating mutations were significantly more likely to have frank HPE than those with non-truncating mutations (49% vs 35%, respectively; p=0.012). While mutations were significantly more common in the N-terminus than in the C-terminus (including accounting for the relative size of the coding regions, p=0.00010), no specific genotype-phenotype correlations could be established regarding mutation location., Conclusions: SHH mutations overall result in milder disease than mutations in other common HPE related genes. HPE is more frequent in individuals with truncating mutations, but clinical predictions at the individual level remain elusive.

Purpose: The post-vasectomy pain syndrome is a rare but serious and debilitating complication of vasectomy. For men with the post-vasectomy pain syndrome vasectomy reversal is a surgical option after medical management has failed. However, there is a paucity of data in the literature defining its therapeutic efficacy. In this study we better define the role and effect of vasectomy reversal in the treatment of men with the post-vasectomy pain syndrome., Materials and Methods: Three urologists in Toronto, Ontario performed 149 publically funded vasectomy reversals between January 2000 and September 2010. The electronic health records were reviewed and 23 of the 149 (15%) procedures were performed for the post-vasectomy pain syndrome. Of these men who underwent 14 vasovasostomies 13 completed a telephone conducted questionnaire (response rate 56%). Patient demographics, preoperative and postoperative pain scores, and quality of life were retrospectively assessed., Results: Orchialgia occurred a mean ± SD of 19 ± 42.5 months after vasectomy and the men (mean age 43.8 ± 5.2 years) experienced pain for 50.3 ± 34.9 months before vasovasostomy. After vasovasostomy improvement of pain occurred in 93% (13 of 14) and 50% were rendered pain-free with an average improvement in pain intensity scores of 65% (p <0.005). Of the men 15% (2 of 13) had a recurrence of pain to baseline but overall 79% (11 of 14) had a durable positive response. Quality of life was significantly improved after vasovasostomy (p <0.005) and 93% (13 of 14) of the patients said they would undergo the same operation again., Conclusions: Vasovasostomy is an effective treatment modality for the post-vasectomy pain syndrome, and it can achieve robust and durable long-term improvement in pain intensity and quality of life., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

We analyzed placental tissue in one fetus with MPS II (iduronate sulphatase deficiency) and another with MPS VI (arylsulfatase B deficiency). Both were diagnosed prenatally, but families decided to continue pregnancies and placentas were collected at birth. We were able to demonstrate early storage of GAGs in both diseases by GAG measurement and microscopy analysis. Our results suggest that some alterations related to MPS storage, although not pronounced, may be observed in placental tissue of patients affected by MPS II and MPS VI., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT) was proposed and in the 90's, enzyme replacement therapy (ERT),began to be developed and was approved for clinical use in MPS I, II and VI in the first decade of the 21st century. The authors of this paper are convinced that a better future for patients affected by mucopolysaccharidoses depends upon identifying, understanding and appropriately managing the multisystemic manifestations of these diseases. This includes the provision of support measures (which should be part of regular multidisciplinary care of these patients) and of specific therapies. Although inhibition of synthesis of GAG and the recovery of enzyme activity with small molecules also may play a role in the management of MPS, the breakthrough is the currently available intravenous ERT. ERT radically changed the setting for treatment of mucopolysaccharidosis I, II and VI in the last decade., Benefits can even be extended soon to MPS IV A (ERT for this condition is already in clinical development), with prediction for treatment of MPS III A and the cognitive deficit in MPS II by administration of the enzyme directly into the central nervous system (CNS). A large number of Brazilian services, from all regions of the country, already have experience with ERT for MPS I, II and VI. This experience was gained not only by treating patients but also with the participation of some groups in clinical trials involving ERT for these conditions. Summing up the three types of MPS, more than 250 patients have already been treated with ERT in Brazil. The experience of professionals coupled to the data available in international literature, allowed us to elaborate this document, produced with the goal of bringing together and harmonize the information available for the treatment of these severe and progressive diseases, which, fortunately, are now treatable, a situation which bring new perspectives for Brazilian patients, affected by these conditions.

Pompe disease (glycogen storage disease type II or acid maltase deficiency) is an inherited autosomal recessive deficiency of acid alpha-glucosidase (GAA), with predominant manifestations of skeletal muscle weakness. A broad range of studies have been published focusing on Pompe patients from different countries, but none from Brazil. We investigated 41 patients with either infantile-onset (21 cases) or late-onset (20 cases) disease by muscle pathology, enzyme activity and GAA gene mutation screening. Molecular analyses identified 71 mutant alleles from the probands, nine of which are novel (five missense mutations c.136T > G, c.650C > T, c.1456G > C, c.1834C > T, and c.1905C > A, a splice-site mutation c.1195-2A > G, two deletions c.18&#95;25del and c.2185delC, and one nonsense mutation c.643G > T). Interestingly, the c.1905C > A variant was detected in four unrelated patients and may represent a common Brazilian Pompe mutation. The c.2560C > T severe mutation was frequent in our population suggesting a high prevalence in Brazil. Also, eight out of the 21 infantile-onset patients have two truncating mutations predicted to abrogate protein expression. Of the ten late-onset patients who do not carry the common late-onset intronic mutation c.-32-13T > G, five (from three separate families) carry the recently described intronic mutation, c.-32-3C > A, and one sibpair carries the novel missense mutation c.1781G > C in combination with known severe mutation c.1941C > G. The association of these variants (c.1781G > C and c.-32-3C > A) with late-onset disease suggests that they allow for some residual activity in these patients. Our findings help to characterize Pompe disease in Brazil and support the need for additional studies to define the wide clinical and pathological spectrum observed in this disease.

Background: Third kidney retransplants have technical and immunologic hurdles that may preclude success, which is of particular importance in the contemporary context of discrepancy between organ supply and demand., Methods: The outcomes of third renal transplant recipients (TRTR) were compared with those receiving a first transplant from paired donor kidneys to assess transplant success and complication rates. The Ontario-based Trillium Gift of Life Network database was used to identify deceased donors (n=28) who donated one kidney to a TRTR and the mate kidney to a primary renal transplant recipient (PRTR) from June 1977 to August 2006., Results: As anticipated, TRTR were sensitized versus PRTR based on % panel reactive antibodies (24%+/-34% vs. 7%+/-14%, P=0.03). Delayed graft function (46% vs. 22%, P=0.05) and biopsy-proven rejection episodes (50% vs. 29%, P=0.01) occurred more frequently with TRTR despite greater frequency of induction therapy (74% vs. 35%, P=0.004). However, 1- and 5-year patient survival were similar at 93%, 83% and 96%, 87% for TRTR and PRTR, respectively. Accordingly, 1- and 5-year allograft survival censored for mortality, were comparable at 78%, 66% and 78%, 75%. Renal function was similar in both groups. Bacterial infections (43% vs. 18%, P=0.001) and wound problems (28% vs. 11%, P=0.09) were the only postoperative complications to occur more frequently in the TRTR., Conclusion: We conclude that third renal transplantation should not be discouraged based on functional outcomes alone.

The 3M syndrome is a rare autosomal recessive disorder recently ascribed to mutations in the CUL7 gene and characterized by severe pre- and postnatal growth retardation. Studying a series of 33 novel cases of 3M syndrome, we have identified deleterious CUL7 mutations in 23/33 patients, including 19 novel mutations and one paternal isodisomy of chromosome 6 encompassing a CUL7 mutation. Lack of mutations in 10/33 cases and exclusion of the CUL7 locus on chromosome 6p21.1 in six consanguineous families strongly support the genetic heterogeneity of the 3M syndrome.

Introduction: To assess the efficacy of calcineurin inhibitor (CNI)-free immunosuppression vs. calcineurin-based immunosuppression in patients receiving expanded criteria donor (ECD) kidneys., Patient and Methods: Thirteen recipients of ECD kidneys were enrolled in this pilot study and treated with induction therapy and maintained on sirolimus, mycophenolate mofetil (MMF) and prednisone. A contemporaneous control group was randomly selected comprised of 13 recipients of ECD kidneys who had been maintained on CNI plus MMF and prednisone., Results: For the study group vs. the control group, two-yr graft survival was 92.3% vs. 84.6% (p = NS), two-yr patient survival was 100% vs. 92.3% (p = NS) and the acute rejection rates were 23% vs. 31% (p = NS), respectively. Renal function was significantly better in the study group compared with control up to the six-month mark, after which, it remained numerically but not statistically significant. Complications were more common in the study group, but serious adverse events requiring discontinuation were rare., Conclusion: This pilot study demonstrates that CNI-free regimens can be safely implemented in patients receiving ECD kidneys with excellent two-yr patient and graft survival and good renal allograft function. Longer follow-up in larger randomized controlled trials are necessary to establish these findings.

Objectives: To evaluate the functional outcomes and quality of life of adult patients with neurogenic bladders who had undergone Casale Spiral Monti vesicostomy., Methods: Twelve patients who underwent Casale Spiral Monti vesicostomy from May 1999 to December 2004 were evaluated with the Medical Outcomes Study 36-item short-form health survey to assess for postoperative quality of life. Complications and patient reported continence were also documented., Results: The 12 patients (mean age 27.4 years) were followed up for a mean of 2.8 years. All 12 reported excellent urinary continence after the procedure, with only 7 patients who had the capacity to self-catheterize. Two patients reported wearing one light pad per day over the stoma. Two patients required one endoscopic dilation each for stomal stenosis, and one patient was readmitted 3 weeks postoperatively for the management of paralytic ileus. Eight patients reported no urinary tract infection since the operation. All 12 patients reported being very satisfied with the procedure., Conclusions: The results of this study have demonstrated that Casale Spiral Monti vesicostomy can have dramatic positive effects on the quality of life in adults with a neurogenic bladder by granting them social independence, convenient bladder management, and excellent continence rates.

Aim: This study aims to assess the clinical features of 77 South American patients (73 Brazilian) with mucopolysaccharidosis type II (MPS II)., Methods: Details of the patients and their disease manifestations were obtained from a review of medical records, interviews with the patients and/or their families, and physical examination of the patients., Results: Mean birth weight was 3360 g, median age at onset of symptoms was 18 months and median age at diagnosis was 6 years. For the whole sample (median age, 8.2 years; range, 2.8-53.0 years), neurological degeneration, typical pebbly skin lesions, seizures and extensive dermal melanocytosis were found in 23.3, 13.0, 13.0 and 1.3% of the cases, respectively. The most frequently reported echocardiogram abnormality was mitral valve regurgitation. Refraction errors were the most common ophthalmological manifestation. The following characteristics were found to be associated with the severe form of MPS II: earlier age at biochemical diagnosis, higher levels of urinary glycosaminoglycans, language development delay, behavioural disturbances, poor school performance and mental retardation., Conclusion: Our results suggest that there is a considerable delay between the onset of signs and symptoms and the diagnosis of MPS II in Brazil (and probably in South America as well), and that many complications of this disease are underdiagnosed and undertreated. Therefore, the implementation of programmes aiming to increase the awareness of the disease, the availability of biochemical diagnostic tests and the provision of better support to affected patients is urgently needed.

During air travel, the length of time spent in a sitting position and the absence of muscular activity in the calves severely slow the rate of blood flow in the lower limbs. The aim of this randomized, cross-over, double-blind study was to evaluate local application of Hydroxyethyl-rutosides (O-Beta-Hydroxyethylrutosides) in the treatment of symptoms of venous insufficiency including stasis-induced edema during extended air travel on flights exceeding 6 hours. Hydroxyethyl-rutosides or placebo was applied every 3 or 4 hours throughout the flight. In the 51 subjects evaluated (both males and females) the results show statistically significant differences favoring treatment with Hydroxyethyl-rutosides both with regard to objective signs of edema: change in minimum ankle circumference was less during trips in which Hydroxyethyl-rutosides was applied, whether compared with the maximum measurement (p = 0.04) or the last measurement made during the flights, and with regard to subjective signs: several symptoms occurred significantly less frequently when the subject applied Hydroxyethyl-rutosides during the flight [pain (p = 0.03), sensation of heavy and tired legs (p = 0.04) and sensation of swelling (p = 0.02)]. the patient's overall assessment of the treatment was also favorable after using Hydroxyethyl-rutosides Gel (p = 0.01). the number of subjects complaining of edema (pitting edema, marks of shoes, difficulties putting shoes back on) was significantly lower during periods of treatment with Hydroxyethyl-rutosides Gel (p = 0.001). Local application of Hydroxyethyl-rutosides, 3 to 4 times during 6 to 14 hours is thus effective in treating the main symptoms of venous insufficiency including stasis-induced edema caused by extended periods in the sitting position during long air flights.

Blood samples from 44 unrelated cystic fibrosis (CF) patients from Rio de Janeiro, Brazil, were analyzed for the 8 European CF mutations. Six homozygous and 15 heterozygous carriers of the DF508 mutation were found, corresponding to 47.7% of CF patients (allele frequency 0.3068). The G542X and G551D mutations were also observed with allele frequencies of 0.0227 and 0.0114, respectively. An analysis of the DF508 mutation in 291 randomly chosen, healthy individuals was performed, and only 3 heterozygous carriers were identified. These results show that the frequency of the DF508 allele in Rio de Janeiro is much lower than the world average; this may be due to the extremely heterogeneous ethnic admixture of the study population. By combining the results of these 2 different samples (CF patients and random population) and admixture data from Rio de Janeiro, we can estimate the CF incidence in this population to be 1:3542 individuals. However, taking into account the Rio de Janeiro ethnic admixture, we can find an estimate of 1:6902 individuals.

We describe a family with Stanescu osteosclerosis. The propositus and his mother were short and had cortical sclerosis of the long bones, deficient facial sinus development, cranial bone malformations, and normal intelligence. To the best of our knowledge, only two such families have been described previously. The autosomal dominant pattern of inheritance of this skeletal dysplasia is reinforced, as there are many other reportedly affected relatives, including the maternal grandfather, uncles, and aunts of the propositus. The findings of wormian bones and calcification of the falx, not previously described, may be added to the phenotype.

The fungicidal class I endochitinases (E.C.3.3.1.14, chitinase) are associated with the biochemical defense of plants against potential pathogens. We isolated and sequenced a genomic clone, DAH53, corresponding to a class I basic endochitinase gene in pea, Chi1. The predicted amino acid sequence of this chitinase contains a hydrophobic C-terminal domain similar to the vacuole targeting sequences of class I chitinases isolated from other plants. The pea genome contains one gene corresponding to the chitinase DAH53 probe. Chitinase RNA accumulation was observed in pea pods within 2 to 4 h after inoculation with the incompatible fungal strain Fusarium solani f. sp. phaseoli, the compatible strain F. solani f.sp. pisi, or the elicitor chitosan. The RNA accumulation was high in the basal region (lower stem and root) of both fungus challenged and wounded pea seedlings. The sustained high levels of chitinase mRNA expression may contribute to later stages of pea's non-host resistance.

beta-glucanases are prominent proteins in pea endocarp tissue responding to fungal infection. We have cloned and sequenced a partial pea cDNA clone, pPIG312, corresponding to a beta-1,3-glucanase in pea pods challenged with the incompatible pathogen Fusarium solani f. sp. phaseoli. The insert from the partial pea cDNA was used to probe a genomic library derived from pea leaves of the same cultivar. One of the genomic clones, pPIG4-3, contained the complete coding sequence for a mature beta-1,3-glucanase protein. The predicted amino acid sequence of the pea beta-1,3-glucanase has 78% identity to bean beta-1,3-glucanase, 62% and 60% to two tobacco beta-1,3-glucanases, 57% to soybean beta-1,3-glucanase, 51% to barley beta-1,3-glucanase, and 48% to barley beta-1,3-1,4-glucanase. Genomic Southern analysis indicates that the pea genome contains only one beta-1,3-glucanase gene corresponding to the probe used in this study. Accumulation of beta-1,3-glucanase mRNA homologous with the pPIG312 probe was detected in pea pods within 4 to 8 h after challenge with F. solani f. sp. phaseoli, f. sp. pisi, a compatible strain, or the elicitor, chitosan. In the incompatible reaction, mRNA accumulation remained high for 48h, whereas it rapidly decreased in the compatible reaction. After fungal inoculation of whole pea seedlings, the enhanced mRNA accumulation occurred mainly in the basal region (lower stem and root). This beta-1,3-glucanase mRNA was constitutively expressed in the roots of pea seedlings.(ABSTRACT TRUNCATED AT 250 WORDS)