Incidence and prognosis implications of long term left ventricular reverse remodeling in patients with dilated cardiomyopathy.

BACKGROUND: Left ventricular reverse remodeling (LVRR) in dilated cardiomyopathy is poorly known within the context of current therapeutic approach. Our goal is to describe the present incidence of LVRR, the factors able to predict it and the long term prognosis of these patients. METHODS AND RESULTS: We performed a retrospective analysis of a cohort or 387 consecutive outpatients. Mean follow-up was 50.4 ± 28.4 months. Sustained LVRR occurred in 57.6% of patients. The number of coronary arteries with severe stenosis (HR 0.69, 95% CI 0.55-0.86; p=0.001), New York Heart Association Functional Class (NYHA FC) (HR 0.39, 95% CI 0.27-0.54; p<0.001) as well as the severity of mitral regurgitation (MR) at the end of follow-up (HR 0.42, 95% CI 0.30-0.58; p<0.001) and the time until first event (HR 1.02, 95% CI 1.01-1.03; p<0.001) were independent predictors of left ventricular ejection fraction improvement. LVRR was tightly related to prognosis due to the fact that both improvement in cardiac function achieving normal or slightly impaired LVEF (HR 0.31, 95% CI 0.17-0.56; p<0.001) and shorter time to achieve LVRR (HR 0.99, 95% CI 0.98-0.99; p=0.017) formed part of the best model for predicting events in DCM. CONCLUSION: More than half of the patients showed sustained LVRR associated with a significantly better prognosis. Fewer numbers of coronary arteries with severe stenosis, milder NYHA FC and the absence of significant MR at the end of follow-up as well as longer event free period formed a simple model to prognosticate LVRR. LVRR and the time to achieve it were strongly related to long term prognosis in patients with DCM.

Disnea laringea en recién nacido por quiste branquial / Branchial cyst causing laryngeal dyspnoea in a newborn

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Granulomatosis de Wegener causante de parálisis facial y cofosis bilaterales / Wegener’s granulomatosis causing bilateral facial paralysis and deafness

La parálisis facial bilateral (PFB) es una entidad infrecuente, que habitualmente se presenta como manifestación de una enfermedad sistémica. Presentamos el caso de una mujer afecta de granulomatosis de Wegener (GW), con especial afectación de las vías respiratorias altas y ótica, que desarrolló hipoacusia y PFB resistente a tratamientos inmunosupresores y bolos de corticoides, con pruebas de imagen que no muestran afectación del nervio facial en las estructuras óticas. Finalmente, la paciente mejoró de la PFB, pero la cofosis es permanente y se ha realizado un implante coclear. Las series publicadas sobre PFB son escasas, y no hacen referencia a la GW como posible etiología (AU)

Bilateral facial paralysis (BFP) is an uncommon condition that typically occurs as a manifestation of systemic disease. We present a female patient with Wegener's granulomatosis (WG), particularly upper respiratory and ear impairment who develops hypoacusis and BFP, resistant to immunosuppressive therapy and steroid boluses. Her imaging tests showed no involvement of the facial nerve as it passed through the ear structures. The patient finally improved the BFP; however, deafness is permanent and she has entered into a cochlear implant program. Published papers on BFP are rare and they make no reference to WG as a possible aetiology (AU)

Wegener's granulomatosis causing bilateral facial paralysis and deafness.

Bilateral facial paralysis (BFP) is an uncommon condition that typically occurs as a manifestation of systemic disease. We present a female patient with Wegener's granulomatosis (WG), particularly upper respiratory and ear impairment who develops hypoacusis and BFP, resistant to immunosuppressive therapy and steroid boluses. Her imaging tests showed no involvement of the facial nerve as it passed through the ear structures. The patient finally improved the BFP; however, deafness is permanent and she has entered into a cochlear implant program. Published papers on BFP are rare and they make no reference to WG as a possible aetiology.

Miotomía del cricofaríngeo en el tratamiento de la distrofia muscular oculofaríngea / Cricopharyngeal myotomy in the treatment of oculopharyngeal muscular dystrophy

La distrofia muscular oculofaríngea (DMOF) es una enfermedad hereditaria autosómica dominante que causa disfagia orofaríngea, ptosis palpebral y debilidad muscular proximal. Es causada por una expresión anormal del triplete GCG del gen PABPN1, situado en el cromosoma 14. El estudio de la disfagia orofaríngea que sufren estos pacientes se basa en la historia clínica, la endoscopia digestiva alta, la radiología con contraste baritado y la manometría esofágica. El diagnóstico definitivo se confirma con el estudio genético. Presentamos 6 casos, 3 de ellos de una misma familia, remitidos a nuestro departamento con el diagnóstico confirmado de DMOF, los cuales se sometieron a una miotomía del cricofaríngeo para conseguir una deglución normal(AU)

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathic disease which provokes oropharyngeal dysphagia, palpabral ptosis and proximal limb weakness. It is the abnormal expression of the GCG triplet in the PABPN1 gene on chromosome 14 that causes this disease. The study of the oropharyngeal dysphagia that these patients suffer from should include upper gastrointestinal endoscopy, barium video-radiology and oesophageal manometry. Genetic study confirms the diagnosis. We report 6 patients (3 of whom were siblings) referred to our department with a confirmed diagnosis of OPMD, who underwent cricopharyngeal myotomy to achieve normal swallowing(AU)

Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria.

The long-term outcome of patients with IgA nephropathy who present with normal renal function, microscopic hematuria, and minimal or no proteinuria is not well described. Here, we studied 141 Caucasian patients with biopsy-proven IgA nephropathy who had minor abnormalities at presentation and a median follow-up of 108 months. None of the patients received corticosteroids or immunosuppressants. We reviewed renal biopsies using the Oxford classification criteria. In this sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities were uncommon. Serum creatinine increases >50% and >100% were observed in five (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD. After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum creatinine values less than a 50% increase, respectively. Using Cox proportional hazards regression, the presence of segmental glomerulosclerosis was the only factor that significantly associated with a >50% increase in serum creatinine. Clinical remission occurred in 53 (37.5%) patients after a median of 48 months. Proteinuria>0.5 and >1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients, respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41 (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59 (41.8%) patients were treated with renin-angiotensin blockers because of hypertension or increasing proteinuria. In summary, the long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent.

Cricopharyngeal myotomy in the treatment of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant myopathic disease which provokes oropharyngeal dysphagia, palpabral ptosis and proximal limb weakness. It is the abnormal expression of the GCG triplet in the PABPN1 gene on chromosome 14 that causes this disease. The study of the oropharyngeal dysphagia that these patients suffer from should include upper gastrointestinal endoscopy, barium video-radiology and oesophageal manometry. Genetic study confirms the diagnosis. We report 6 patients (3 of whom were siblings) referred to our department with a confirmed diagnosis of OPMD, who underwent cricopharyngeal myotomy to achieve normal swallowing.

Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.

TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis.

BACKGROUND: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. METHODS: TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. RESULTS: Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. CONCLUSIONS: We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.

Spatial relationships between nitrogen status and pitch canker disease in slash pine planted adjacent to a poultry operation.

Pitch canker disease (Fusarium circinatum Nirenberg & O'Donnell) causes serious shoot dieback, reduced growth and mortality in pines found in the southern and western USA, and has been linked to nutrient imbalances. Poultry houses with forced-air ventilation systems produce nitrogen (N) emissions. This study analyzed spatial correlations between pitch canker disease and foliar, forest floor, soil, and throughfall N in a slash pine (Pinus elliottii var. elliottii Engelm.) plantation adjacent to a poultry operation in north Florida, USA. Tissue and throughfall N concentrations were highest near the poultry houses and remained elevated for 400 m. Disease incidence ranged from 57-71% near the poultry houses and was spatially correlated with N levels. Similarly, stem mortality ranged from 41-53% in the most heavily impacted area, and declined to 0-9% at distances greater than 400 m. These results suggest that nutritional processes exacerbate changes in disease susceptibility and expression in slash pine.

PCR assays for the early detection of BKV infection in 125 Spanish kidney transplant patients.

BK virus (BKV) reactivation arises from immunocompromised conditions and can produce a tubulointerstitial nephropathy (BKVN) in kidney transplant recipients (KTR). Approximately 5% of KTR develop BKVN, and about 45% of these lose their graft. Therefore, using molecular tools to test for BKV may be helpful in early detection. A series of 125 Spanish KTR, originating from a single transplant center, were studied in relation to BKV infection in the first post-transplant year. First, we carried out a urinary cytological study, looking for decoy cells as a possible marker of virus replication. Secondly, in all positive cytological samples and in some negative cytological samples (selected at random), we performed qualitative polymerase chain reaction (PCR) assays in serum and urine amplifying two different genome regions (LT and VP1). A transcription control region (TCR)-BK polymorphism sequence analysis was also performed in those BK PCR positive cases. Twenty-three of 125 (18.4%) KTR presented decoy cells in at least one urinary cytological sample. Molecular studies revealed that 10 of 125 (8%) KTR were BK PCR-serum positive cases (seven LT+/VP1- and three LT+/VP1+); and 13 of 40 (32.5%) KTR were BK PCR-urine positive cases (five LT+/VP1- and eight LT+/VP1+). When we compared PCR-urine and cytological results in 40 KTR, only 15% (six cases) revealed simultaneous positivity in both studies. In the context of clinical graft dysfunction, three patients demonstrated BK DNA presence in the renal biopsy. Finally, sequence analysis of the TCR was performed in 13 BK-PCR positive cases determining the AS, JL, WW, and WW-like viral variants. TCR sequence analysis, allows us to demonstrate the possible implication of the donor in BK infection studying four BK-PCR positive patients paired by donor.

Renal transplantation in children with posterior urethral valves.

The objective of this study was to analyze whether renal transplantation (RT) in children with posterior urethral valves (PUV) constitutes a special group with respect to groups with different etiologies of end-stage renal disease (ESRD). Between 1979 and 2004, 22 RT were performed in 19 children with PUV. The median age at RT was 10 years (range: 1.3-17). Immunosuppression was provided by triple therapy and polyclonal/monoclonal antibodies. This group was compared with the two control groups: (1) glomerulopathy (n=62) and (2) pyelonephritis/dysplasia (n=42) without lower urinary tract disease, transplanted in the same period. Ten graft losses occurred in 22 transplants: thrombosis (2), acute rejection (3), chronic graft nephropathy (2), and death of patients (3) with a functioning graft in the 1st postoperative month. We did not find significant differences versus the control group in renal function or probability of graft or patient survival at 1, 5, and 10 years. We observed a greater risk of urological complication in patients with PUV. RT with PUV constitutes a special group due to the compulsory young age and the need for careful and complex medicosurgical management; nevertheless, the results achieved were similar to those obtained in our general RT population.

LT, VP1 and TCR-BKV sequence analysis in a patient with post-transplant BKV nephropathy associated with EBV-related PTLD.

A 10-year-old boy kidney transplant recipient (KTR) developed an abdominal post-transplant lymphoproliferative syndrome (PTLD) followed by BK virus nephropathy (BKVN). BK virus (BKV) and Epstein-Barr virus (EBV) were studied in renal and PTLD tissue by polymerase chain reaction (PCR) assay. Afterwards, the patient was monitored in relation to BKV in urine and serum; transcription control region (TCR)-BK polymorphism sequence analysis was also performed. In the PCR assay, both early large T antigen (LT) and late (VP1) transcriptional BKV coding regions were found in renal tissue, whereas EBV and only LT-BK were detected in PTLD abdominal tissue. On the other hand, TCR sequence analysis revealed the AS genomic BK variant.