Quantitative OCT analysis of idiopathic perifoveal telangiectasia

PURPOSE: To identify and quantitate specific changes in optical coherence tomography (OCT) images of patients with type 2 idiopathic perifoveal telangiectasia (IPT). METHODS: In a prospectively designed, observational, case-control study, 28 eyes of 14 consecutive patients with IPT were examined with OCT and compared with eyes of 14 unaffected control subjects. Light reflectivity profiles of raw scan data of OCT images were quantitatively analyzed for differences in distance between different retinal reflectivity layers and their respective reflectivities. Maculae were examined in four separate regions: (1) central fovea, (2) nasal perifovea, (3) temporal perifovea, and (4) outside the fovea. RESULTS: Retinal thinning, shortening of the photoreceptor outer segments and loss of reflectivity of the photoreceptor ellipsoid region were found in the central foveal region as well as the nasal and temporal perifoveal regions in eyes with IPT. In addition, increased reflectivity of the outer nuclear layer was found in a sharply demarcated area of the inferotemporal perifoveal region in all affected eyes. Retinal tissue located more than 2000 mum away from the foveola was indistinguishable from that in normal eyes. CONCLUSIONS: Quantitative OCT analysis shows unique and specific changes in the photoreceptors of the central macula in IPT which can be detected from first clinical presentation. These changes may be of use as an additional diagnostic tool. Correlation of the findings in the outer nuclear layer with histologic studies may help identify the nature of the reflectivity increase and define more clearly the type of damage sustained by the photoreceptors in this condition.

Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis

AIMS: Juvenile idiopathic arthritis (JIA) is often associated with severe chronic anterior uveitis (CAU), and immunosuppressive therapy may be required. In this study, the value of cyclosporine A (CsA) as monotherapy or as combination therapy for treating uveitis was studied in a large cohort of JIA children. METHODS: Multicentre retrospective study including 82 JIA children (girls n=60) suffering from unilateral or bilateral (n=55) CAU. The indication for CsA was active uveitis, although patients were on topical or systemic corticosteroids, MTX, or other immunosuppressive drugs. RESULTS: Inactivity of uveitis during the entire treatment period (mean 3.9 years) was obtained with CsA monotherapy in 6 of 25 (24%) patients, but more often when CsA was combined with the immunosuppressives (35/72 patients; 48.6%, P=0.037), or MTX (18/37 patients, 48.6%, P=0.065), which had already been given. With CsA (mean dosage 2.9 mg/kg), systemic immunosuppressive drugs and steroids could be reduced by >or=50% (n=19) or topical steroids reduced to

Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging

OBJECTIVES: To study the validity of both rheumatological and orthodontic examinations and ultrasound (US) as screening methods for early diagnosis of TMJ arthritis against the gold standard MRI. METHODS: Thirty consecutive juvenile idiopathic arthritis (JIA) patients were included in this pilot study. Rheumatological and orthodontic examinations as well as US were performed within 1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast enhancement of synovium or bone were considered signs of active arthritis on MRI. RESULTS: A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ involvement on MRI. This was associated with condylar deformity in 9/19 (47%) patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients, respectively, as having no signs of inflammation. The best predictor for active arthritis on MRI was a reduced maximum mouth opening. CONCLUSION: None of the methods tested was able to reliably predict the presence or absence of MRI-proven inflammation in the TMJ in our cohort of JIA patients. US was the least useful of all methods tested to exclude active TMJ arthritis.

What a patient with refractory idiopathic detrusor overactivity should know about botulinum neurotoxin type a injection

PURPOSE: We documented the effects of intradetrusor injections of botulinum neurotoxin type A (Botox(R)) for refractory idiopathic detrusor overactivity so that prospective patients maybe properly informed about possible improvement in quality of life, the duration of interinjection intervals and the risk of clean intermittent self-catheterization. MATERIALS AND METHODS: A total of 81 consecutive patients with refractory idiopathic detrusor overactivity treated with intradetrusor injections of 200 U botulinum neurotoxin type A at 20 sites per injection course were evaluated in this prospective, nonrandomized, open label cohort study. The primary outcome was changes in quality of life, as assessed by the short form of the Urogenital Distress Inventory and the Incontinence Impact Questionnaire before and after treatment. Secondary outcomes were the interinjection interval and the need for clean intermittent self-catheterization. RESULTS: After intradetrusor botulinum neurotoxin type A injections there was significant improvement in quality of life, which was sustained after repeat injections. Mean Urogenital Distress Inventory and Incontinence Impact Questionnaire scores decreased from 56 to 26 and 59 to 21 after injection 1 in 81 patients, from 52 to 30 and 51 to 24 after injection 2 in 24, from 40 to 19 and 43 to 17 after injection 3 in 13, from 44 to 17 and 61 to 15 after injection 4 in 6 and from 51 to 17 and 63 to 14 after injection 5 in 4, respectively. The median interinjection interval was 15, 12, 14 and 13 months between injections 1 and 2, 2 and 3, 3 and 4, and 4 and 5, respectively. Considering a post-void residual urine of greater than 100 ml with lower urinary tract symptoms as the indication for clean intermittent self-catheterization, the overall clean intermittent self-catheterization rate after treatment was 43%. CONCLUSIONS: Intradetrusor botulinum neurotoxin type A injections for refractory idiopathic detrusor overactivity significantly improved quality of life. This effect was sustained after repeat injection. More than 2 of 5 patients with refractory idiopathic detrusor overactivity required clean intermittent self-catheterization after botulinum neurotoxin type A injections and all prospective patients should be informed about this.

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Low bone mass in idiopathic renal stone formers: magnitude and significance

To assess bone mineral density (BMD) in idiopathic calcium nephrolithiasis, dual-energy x-ray absorptiometry was performed at lumbar spine, upper femur (femoral neck, Ward's triangle, and total area), distal tibial diaphysis, and distal tibial epiphysis in 110 male idiopathic calcium stone formers (ICSF); 49 with and 61 without hypercalciuria on free-choice diet). Results were compared with those obtained in 234 healthy male controls, using (1) noncorrected BMD, (2) BMD corrected for age, height, and BMI, and (3) a skeletal score based on a tercile distribution of BMD values at following four sites: lumbar spine, Ward's triangle, tibial diaphysis, and tibial epiphysis. After correction, BMD--and therefore also skeletal score--tended to be lower in the stone formers than in controls at five of the six measurement sites, that is, lumbar spine, upper femur, Ward's triangle, tibial diaphysis, and tibial epiphysis, limit of significance being reached for the last two sites without difference between hypercalciuric (HCSF) and normocalciuric stone formers (NCSF). Estimated current daily calcium intake was significantly lower in patients (616 +/- 499 mg/24 h, mean +/- SEM) than in controls (773 +/- 532, p = 0.02). Of 17 patients who in the past had received a low-calcium diet for at least 1 year, 10 had a low skeletal score (4-6) whereas only 1 had a high score (10-12; p = 0.037). Of the 12 stone formers in the study with skeletal score 4 (i.e., the lowest), 8 had experienced in the past one or more fractures of any kind versus only 19 of the remaining 77 patients with skeletal score 5-12 (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Phenotypes and echocardiographic characteristics of a European population of domestic shorthair cats with idiopathic hypertrophic cardiomyopathy

111 Domestic Shorthair cats with idiopathic hypertrophic cardiomyopathy were reviewed retrospectively. Two-dimensional echocardiography was used to classify cases in 6 established phenotypes. Hypertrophy was diffuse in 61 % of cats and involved major portions of the ventricular septum and the left ventricular free wall (phenotype D). In the remaining cats, distribution of hypertrophy was more segmental and was identified on the papillary muscles exclusively (phenotype A, 6 %), on the anterior and basal portion of the ventricular septum (phenotype B, 12 %), on the entire septum (phenotype C, 14 %), or on the left ventricular free wall (phenotype E, 7 %). Echocardiographic characteristics and clinical findings were determined for each phenotype to study the correlation between distribution of hypertrophy and clinical implications. 31 cats demonstrated systolic anterior motion of the mitral valve, 75 % of them belonged to phenotype C of hypertrophy. Left ventricular-outflow turbulences were identified more frequently with patterns of hypertrophy involving the ventricular septum (65.5 %), while prevalence of mitral regurgitation was higher when hypertrophy included the papillary muscles (phenotypes A and E, 85 % and 87 %, respectively). Left atrial dilatation occurred more frequently when hypertrophy was diffuse or confined to the left ventricular free wall (61 % of cats with phenotype D or E) rather than to the ventricular septum (31 % of cats with phenotype B or C).

Loss-of-function mutation of the SCN3B-encoded sodium channel {beta}3 subunit associated with a case of idiopathic ventricular fibrillation.

AIMS Loss-of-function mutations in the SCN5A-encoded sodium channel SCN5A or Nav1.5 have been identified in idiopathic ventricular fibrillation (IVF) in the absence of Brugada syndrome phenotype. Nav1.5 is regulated by four sodium channel auxiliary beta subunits. Here, we report a case with IVF and a novel mutation in the SCN3B-encoded sodium channel beta subunit Navbeta3 that causes a loss of function of Nav1.5 channels in vitro. METHODS AND RESULTS Comprehensive open reading frame mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, GPD1L, four sodium channel beta subunit genes (SCN1-4B), and targeted scan of RYR2 was performed. A novel missense mutation, Navbeta3-V54G, was identified in a 20-year-old male following witnessed collapse and defibrillation from VF. The ECG exhibited epsilon waves, and imaging studies demonstrated a structurally normal heart. The mutated residue was highly conserved across species, localized to the Navbeta3 extracellular domain, and absent in 800 reference alleles. We found that HEK-293 cells had endogenous Navbeta3, but COS cells did not. Co-expression of Nav1.5 with Navbeta3-V54G (with or without co-expression of the Navbeta1 subunit) in both HEK-293 cells and COS cells revealed a significant decrease in peak sodium current and a positive shift of inactivation compared with WT. Co-immunoprecipitation experiments showed association of Navbeta3 with Nav1.5, and immunocytochemistry demonstrated a dramatic decrease in trafficking to the plasma membrane when co-expressed with mutant Navbeta3-V54G. CONCLUSION This study provides molecular and cellular evidence implicating mutations in Navbeta3 as a cause of IVF.

Radiofrequency catheter ablation of idiopathic ventricular tachycardia originating in the main stem of the pulmonary artery.

We report the case of a patient in whom successful radiofrequency catheter ablation of an idiopathic ventricular tachycardia (VT) originating in the main stem of the pulmonary artery was performed. After successful ablation of the index arrhythmia, which was an idiopathic right ventricular outflow tract VT, a second VT with a different QRS morphology was reproducibly induced. Mapping of the second VT revealed the presence of myocardium approximately 2 cm above the pulmonary valve. Application of radiofrequency energy at this site resulted in termination and noninducibility of this VT. After 6-month follow-up, the patient remained free from VT recurrences.

Electrocardiographic pattern as a guide for management and radiofrequency ablation of idiopathic ventricular tachycardia.

BACKGROUND Idiopathic ventricular tachycardia (VT) often originates from the right ventricular outflow tract (RVOT), but foci deep to the endocardium, in the epicardium, or in the left ventricle are not uncommon. Although these extra-RVOT foci can be targeted with ablation, risks involved are higher and success rates lower. Simple electrocardiographic (ECG) criteria allowing (1) discrimination of RVOT foci from extra-RVOT foci and (2) assessment of the chance of success of a right heart ablation procedure are desirable. METHODS Twenty-five consecutive patients referred for radiofrequency (RF) ablation of idiopathic VT or severely symptomatic idiopathic ventricular premature contractions were included. Localization of VT origin and success rates of VT ablation in the RVOT were analyzed according to the ECG pattern. RESULTS The analysis of the R wave in V2 was the strongest single predictor of whether the VT had an RVOT or an extra-RVOT origin. An R wave amplitude < or =30% of the QRS amplitude designated the VT focus in the RVOT with positive and negative predictive values of 95 and 100%, respectively. Analysis of R wave duration in V2 had similar predictive values, whereas the R/S transition zone in precordial leads had slightly lower predictive values. Seventeen of 20 arrhythmias (85%) with an R wave amplitude < or =30% of the QRS amplitude in V2 could be successfully abolished by an exclusively right heart procedure. CONCLUSIONS The analysis of ECG pattern makes it possible to guide the management of patients with idiopathic VT in predicting the arrhythmias that can be safely targeted with RF ablation from the RVOT with high success rates.

Idiopathic ventricular outflow tract arrhythmias from the great cardiac vein: Challenges and risks of catheter ablation

INTRODUCTION Catheter ablation for idiopathic ventricular arrhythmia is well established but epicardial origin, proximity to coronary arteries, and limited accessibility may complicate ablation from the venous system in particular from the great cardiac vein (GCV). METHODS Between April 2009 and October 2010 14 patients (56 ± 15 years; 9 male) out of a total group of 117 patients with idiopathic outflow tract tachycardias were included undergoing ablation for idiopathic VT or premature ventricular contractions (PVC) originating from GCV. All patients in whom the PVC arose from the GCV were subject to the study. In these patients angiography of the left coronary system was performed with the ablation catheter at the site of earliest activation. RESULTS Successful ablation was performed in 6/14 (43%) and long-term success was achieved in 5/14 (36%) patients. In 4/14 patients (28.6%) ablation was not performed. In another 4 patients (26.7%), ablation did not abolish the PVC/VT. In the majority, the anatomical proximity to the left coronary system prohibited effective RF application. In 3 patients RF application resulted in a coronary spasm with complete regression as revealed in repeat coronary angiography. CONCLUSION A relevant proportion idiopathic VT/PVC can safely be ablated from the GCV without significant permanent coronary artery stenosis after RF application. Our data furthermore demonstrate that damage to the coronary artery system is likely to be transient.

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING Academic and private hospitals. PARTICIPANTS Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION The study was terminated early. CONCLUSION Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE Gilead Sciences.

Heterozygous GHR gene mutation in a child with idiopathic short stature.

Abstract Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subjects.