Cystic Fibrosis in Korean Children: A Case Report Identified by a Quantitative Pilocarpine Iontophoresis Sweat Test and Genetic Analysis

Cystic fibrosis (CF) is inherited as an autosomal recessive trait, and the mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene contributes to the CF syndrome. Although CF is common in Caucasians, it is known to be rare in Asians. Recently, we experienced two cases of CF in Korean children. The patients were girls with chronic productive cough since early infancy. Chest computed tomography showed the diffuse bronchiectasis in both lungs, and their diagnosis was confirmed by the repeated analysis of a quantitative pilocarpine iontophoresis test (QPIT). The sweat chloride concentrations of the first patient were 108.1 mM/L and 96.7 mM/L. The genetic analysis revealed that she was the compound heterozygote of Q1291X and IVS8 T5-M470V. In the second case, the sweat chloride concentrations were 95.0 mM/L and 77.5 mM/L. Although we performed a comprehensive search for the coding regions and exon-intron splicing junctions of CFTR gene, no obvious disease-related mutations were detected in the second case. To our knowledge, this is the first report of CF in Korean children identified by a QPIT and genetic analysis. The possibility of CF should be suspected in those patients with chronic respiratory symptoms even in Korea

Correlation of three immunohistochemically detected markers of neuroendocrine differentiation with clinical predictors of disease progression in prostate cancer

<p>Abstract</p> <p>Background</p> <p>The importance of immuno-histological detection of neuroendocrine differentiation in prostatic adenocarcinoma with respect to disease at presentation and Gleason grade is gaining acceptance. There is limited literature on the relative significance of three commonly used markers of NE differentiation i.e. Chromogranin A (CgA), Neuron specific enolase (NSE) and Synaptophysin (Syn). In the current work we have assessed the correlation of immuno-histological detection of neuroendocrine differentiation in prostatic adenocarcinoma with respect to disease at presentation and Gleason grade and to determine the relative value of various markers.</p> <p>Materials and methods</p> <p>Consecutive samples of malignant prostatic specimens (Transurethral resection of prostate or radical retropubic prostatectomy) from 84 patients between January 1991 and December 1998 were evaluated by immunohistochemical staining (PAP technique) using selected neuroendocrine tumor markers i.e. Chromogranin A (CgA), Neuron specific enolase (NSE), and Synaptophysin (Syn). According to the stage at diagnosis, patients were divided into three groups. Group (i) included patients who had organ confined disease, group (ii) included patients with locally invasive disease, and group (iii) with distant metastasis. NE expression was correlated with Gleason sum and clinical stage at presentation and analyzed using Chi-Square test and one way ANNOVA.</p> <p>Results</p> <p>The mean age of the patients was 70 ± 9.2 years. Group I had 14 patients, group II had 31 patients and group III had 39 patients. CgA was detected in 33 cases, Syn in 8 cases, and NSE in 44 cases. Expression of CgA was seen in 7% of group I, 37% in group II and 35% of group III patients (p 0.059). CgA (p 0.024) and NSE (p 0.006) had a significantly higher expression with worsening Gleason grade.</p> <p>Conclusion</p> <p>CgA has a better correlation with disease at presentation than other markers used. Both NSE and CgA had increasing expression with worsening histological grade this correlation has a potential for use as a prognostic indicator. Limitations in the current work included small number and retrospective nature of work. The findings of this work needs validation in a larger cohort.</p

Predictors of insufficient sweat production during confirmatory testing for cystic fibrosis

Michigan's Newborn Screening (NBS) Program began statewide screening for cystic fibrosis (CF) in October 2007. Confirmatory sweat testing is performed in infants having initial immunoreactive trypsinogen concentrations ≥99.8th percentile or ≥96th percentile and at least one CF mutation identified by DNA analysis. Some infants fail to produce a sufficient quantity of sweat (QNS—quantity not sufficient) to test for CF, meaning disease confirmation is delayed and sweat testing is later repeated. In this study, we evaluate predictors of QNS results. Information from the linked birth certificates and NBS diagnostic confirmation data were used. The study population was resident infants born in Michigan in 2008 who underwent a sweat test. Bivariate analyses revealed that preterm birth, low birth weight, CF care center, and race were significantly associated with QNS sweat testing results. Adjusted analyses indicated that preterm infants were 2.4 times more likely to have QNS results (95% CI 0.9, 6.4). When age at time of test, accounting for gestational age (gestational age at delivery plus postdelivery age of life = corrected age), was used in the multivariable model, infants <39 weeks were 7.4 times more likely to have QNS results (95% CI 2.5, 21.8). Waiting to sweat test until an infant is aged 39 weeks or more (corrected age) would likely reduce the rate of QNS results, thereby reducing the burden of repeat sweat testing on families and healthcare providers. Further research is necessary to understand the impact of potential delays in diagnosis/treatment relative to postponing sweat testing. Pediatr Pulmonol. 2011; 46:23–30. © 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78485/1/21318_ftp.pd