Multidrug resistant 1 (MDR1) C3435T and G2677T gene polymorphism: impact on the risk of acute rejection in pediatric kidney transplant recipients.

BACKGROUND: Tacrolimus is the backbone drug in kidney transplantation. Single nucleotide polymorphism of Multidrug resistant 1 gene can affect tacrolimus metabolism consequently it can affect tacrolimus trough level and incidence of acute rejection. The aim of this study is to investigate the impact of Multidrug resistant 1 gene, C3435T and G2677T Single nucleotide polymorphisms on tacrolimus pharmacokinetics and on the risk of acute rejection in pediatric kidney transplant recipients. METHODS: Typing of Multidrug resistant 1 gene, C3435T and G2677T gene polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 83 pediatric kidney transplant recipients and 80 matched healthy controls. RESULTS: In Multidrug resistant 1 gene (C3435T), CC, CT genotypes and C allele were significantly associated with risk of acute rejection when compared to none acute rejection group (P = 0.008, 0.001 and 0.01 respectively). The required tacrolimus doses to achieve trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after kidney transplantation. While, in Multidrug resistant 1 gene (G2677T), GT, TT genotypes and T allele were associated with acute rejection when compared to none acute rejection (P = 0.023, 0.033 and 0.028 respectively). The required tacrolimus doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after kidney transplantation. CONCLUSION: The C allele, CC and CT genotypes of Multidrug resistant 1 gene (C3435T) and the T allele, GT and TT genotypes of Multidrug resistant 1 gene (G2677T) gene polymorphism may be risk factors for acute rejection and this can be attributed to their effect on tacrolimus pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better outcome.

Evaluation of gastro-oesophageal reflux disease in wheezy infants using 24-h oesophageal combined impedance and pH monitoring.

BACKGROUND AND STUDY AIMS: Gastro-oesophageal reflux disease (GERD) is incriminated as a cause of non-asthmatic infantile wheeze. To date, no diagnostic test is considered standard for GERD-related airway reflux diagnosis. Oesophageal combined multiple channel intraluminal impedance and pH (MII-pH) monitoring is proposed to be a sensitive tool for evaluation of all GERD including infantile wheeze. We aimed to determine the GERD prevalence amongst wheezy infants in the first year of life using combined MII-pH versus pH monitoring alone and evaluate the sensitivity and specificity of objective MII-pH monitoring parameters in GERD-associated infantile wheeze diagnosis compared to those of lipid-laden macrophage index (LLMI). PATIENTS AND METHODS: Thirty-eight wheezy infants below 1year of age were evaluated for GERD using oesophageal combined MII-pH monitoring and LLMI. RESULTS: Totally, 60.5% of cases had abnormal MII-pH; only 7.9% of them had abnormal pH monitoring. LLMI was significantly higher in wheezy infants with abnormal MII-pH than infants with normal MII-pH monitoring (112±88 versus 70±48; P=0.036). The current definitions of abnormal MII-pH study, reflux index≥10% and distal reflux episodes≥100, had low sensitivity (23%) but high specificity (100% and 96%, respectively) in GERD-related aspiration diagnosis defined by LLMI≥100. Using ROC curves, bolus contact time≥2.4% and proximal reflux episodes≥46 had 61% and 54% sensitivity and 64% and 76% specificity, respectively, in GERD-related aspiration diagnosis. CONCLUSION: Combined MII-pH is superior to pH monitoring in reflux-associated infantile wheeze diagnosis. Objective data including proximal reflux episodes and bolus contact time should be combined with the current parameters used in reflux-associated infantile wheeze diagnosis.

Clinical Utility of Bronchoalveolar Lavage Pepsin in Diagnosis of Gastroesophageal Reflux among Wheezy Infants.

Background. There is no gold standard test for diagnosis of gastroesophageal reflux disease (GERD) associated infantile wheezing. Objectives. To evaluate the value of bronchoalveolar lavage (BAL) pepsin assay in diagnosis of GERD in wheezy infants. Methods. Fifty-two wheezy infants were evaluated for GERD using esophageal combined impedance-pH (MII-pH) monitoring, esophagogastroduodenoscopy with esophageal biopsies, and BAL pepsin. Tracheobronchial aspirates from 10 healthy infants planned for surgery without history of respiratory problems were examined for pepsin. Results. Wheezy infants with silent reflux and wheezy infants with typical GERD symptoms but normal MII-pH had significantly higher BAL pepsin compared to healthy control (45.3 ± 8.6 and 42.8 ± 8 versus 29 ± 2.6, P < 0.0001 and P = 0.011, resp.). BAL pepsin had sensitivity (61.7%, 72 %, and 70%) and specificity (55.5%, 52.9%, and 53%) to diagnose GERD associated infantile wheeze compared to abnormal MII-pH, reflux esophagitis, and lipid laden macrophage index, respectively. Conclusion. A stepwise approach for assessment of GERD in wheezy infants is advised. In those with silent reflux, a trial of antireflux therapy is warranted with no need for further pepsin assay. But when combined MII-pH is negative despite the presence of typical GERD symptoms, pepsin assay will be needed to rule out GERD related aspiration.

Unilateral Emphysema in Infancy, a Rare Presentation of Aberrant Bronchial Artery: Case Report and Review of Literature.

Aberrant bronchial arteries are rarely seen and may originate from various vascular structures. Hemoptysis is the most common clinical presentation of cases with anomalous bronchial artery. We report a case of a 1-month-old infant presented with respiratory distress and left lung emphysema. Radiologic investigations and bronchoscopy revealed that the cause is an aberrant left bronchial artery compressing the left main bronchus. Surgical division of the aberrant vessel was performed with gradual improvement of the emphysema and respiratory distress. Unilateral emphysema due to vascular compression was previously reported. However, to the best of our knowledge, this is the first reported case of aberrant bronchial artery presenting with external compression of a main bronchus and unilateral emphysema. Also, this is the youngest reported case with an aberrant bronchial artery.

Endobronchial inflammatory pseudotumor: a rare cause of a pneumothorax in children.

Inflammatory pseudotumors of the lung are a group of non-neoplastic tumors, which are mainly of parenchymal origin and rarely endobronchial. We report a case of a 9-year-old girl who presented with left-sided tension pneumothorax and subcutaneous emphysema. After emergency management, chest computed tomography revealed an ill-defined left lung mass. Rigid bronchoscopy revealed a mass occluding the left main bronchus at the origin of the left upper lobe bronchus. Initially, the mass was thought to be a foreign body granuloma. Few weeks later, the child presented with recurrence of the same clinical, radiologic, and bronchoscopic outcomes. Histologic examination after the repeat bronchoscopic excision revealed the lesion to be consistent with inflammatory pseudotumor. Left upper lobectomy was performed with a complete resolution of symptoms and no recurrence was observed during the 2 years of follow-up. To the best of our knowledge, this is the first reported case of inflammatory pseudotumor presenting with tension pneumothorax.