Genetic and molecular findings of 38 Iranian patients with chronic granulomatous disease caused by p47-phox defect.

One of the components of NADPH oxidase is p47-phox, encoded by NCF1 gene. This study aims to find new genetic changes and clinical features in 38 Iranian patients with autosomal recessive chronic granulomatous disease (AR-CGD) caused by NCF1 gene defect. Patients who had abnormal NBT and DHR-1,2,3 assay with loss of p47-phox in Western blotting were included in this study. After recording demographic and clinical data, PCR amplification was performed followed by direct sequencing for all exons and exon-intron boundaries. The most common form of CGD in Iran was AR-CGD due to consanguinity marriages. Among patients with AR-CGD, NCF1 deficiency was found to be more common than other forms. Cutaneous involvements (53%), pulmonary infections (50%) and lymphadenopathy (29%) were more prevalent than other clinical manifestations of CGD. Mutation analysis of NCF1 gene identified five different mutations. Homozygous delta GT deletion (c.75_76delGT) was the most frequent mutation and was detected in more than 63% of families. Six families had a nonsense mutation in exon 7 (c.579G > A). Two novel mutations were found in exon 4 in two families, including a missense mutation (c.328C > T) and a nine-nucleotide deletion (c.331_339delTGTCCCCAC). Genetic detection of these mutations may result in early diagnosis and prevention of possible complications of the disease. This could be useful for timely decision-making for haematopoietic stem cell transplantation and for carrier detection as well as prenatal diagnosis of next children in the affected families. Our findings might help to predict outcomes, raise awareness and help effective treatment in these patients.

Fatal type 7 adenovirus associated with human bocavirus infection in a healthy child.

Adenovirus is a common cause of acute upper respiratory tract infection and rarely causes respiratory failure or septic shock in immunocompetent patients. Severe disease is confined to immunocompromised patients. Human bocavirus (HBoV) is known as the fourth most common virus in respiratory samples from healthy subjects. In patients with respiratory complaints, it can be found alone or, more often, in combination with other viruses known to cause respiratory complaints. A well-documented fatal case of HBoV and adenovirus pneumonia with myocarditis in an immunocompetent child is described.

Inheritance pattern and clinical aspects of 93 Iranian patients with chronic granulomatous disease.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran. METHODS: Clinical and functional investigations were conducted in 93 Iranian CGD patients from 75 families. RESULTS: Most of the patients were AR-CGD (87.1%). This was related to consanguineous marriages (p = 0.001). The age of onset of symptoms and diagnosis were lower in XL-CGD compared with AR-CGD (p < 0.0001 for both). Among AR-CGD patients, p47phox defect was the predominant subtype (55.5%). The most common clinical features in patients were lymphadenopathy (65.6%) and pulmonary involvement (57%). XL-CGD patients were affected more frequently with severe infectious manifestations. CONCLUSIONS: Although XL-CGD is the most common type of the disease worldwide, only 12 patients (12.9%) were XL-CGD in our study. The relatively high frequency of AR-CGD is probable due to widely common consanguineous marriages in Iran.

Monitoring of serum vancomycin concentrations in pediatric patients with normal renal function.

Vancomycin is a a glycopeptide antibiotic with bacetiocidal effects on gram positive bacteria by interfering with cell wall synthesis. The necessity for monitoring of serum vancomycin concentrations (SVCs) has been recently noticed at many institutions because of concerns for its nephrotoxicity. We aimed to describe the SVCs monitoring in pediatric patients, in an effort to determine subtherapeutic or toxic levels. The medical records were reviewed for all patients older than 60 days of age admitted to the general or subspecialty services who received intravenous vancomycin at Children's Medical Hospital in Tehran, Iran between July 2003 and December 2005. Because pharmacokinetic parameters for children with cancer may be different, this group was evaluated separately. During the study, 167 infants and children without cancer and 42 patients with cancer; aged between 3 months to 17.5 years were treated with vancomycin for various infections. In children without cancer, peak SVCs were in an adequate therapeutic range for 93% of patients (8-55 microg/ml). For children with cancer, peak SVCs was lower than 10 microg/ml (10%), and trough values were lower than 5 microg/ml (21%). In conclusion, according to the results of this research, due to different pharmacokinetics of vancomycin in cancerous patients, the monitoring of vancomycin plasma concentrations is necessary for the best therapeutic antibacterial activities with a fewer occurrence of serious adverse effects.

A randomized trial of ceftriaxone versus trimethoprim-sulfamethoxazole to prevent ventriculoperitoneal shunt infection.

BACKGROUND AND PURPOSE: Shunt infection represents a particularly morbid condition, which can also result in mortality. In order to decrease the high morbidity and mortality rates, prevention is an essential step. The purpose of this study was to compare the prophylactic use of ceftriaxone and trimethoprim-sulfamethoxazole (SXT) for the prevention of ventriculoperitoneal (VP) shunt infection. METHODS: In this prospective, single-institution, randomized clinical trial, 107 children with hydrocephalus and an indication for shunting were randomly assigned to prophylaxis with ceftriaxone (n = 50) or SXT (55), each administered as a single dose during anesthesia and two divided doses postoperatively. Patients were followed up for at least one year. RESULTS: The mean age of patients was 15 months, and 85% were aged 6 months or younger. During the first postoperative year, meningitis occurred in 13.5% of patients receiving ceftriaxone and 14.5% of the SXT group, with no statistically significant difference between the groups. Younger age, presence of cerebrospinal fluid leakage and aqueductal stenosis as a cause of hydrocephalus showed significant correlation with meningitis occurrence on univariate analysis. However, only the latter 2 factors were associated with meningitis on multivariate analysis. The risk of shunt infection did not correlate with the gender of the patient, time of VP shunt surgery, or duration of hospitalization for shunting. CONCLUSION: Ceftriaxone and SXT showed similar efficacy in preventing shunt infection. Cerebrospinal fluid leakage before or after VP shunt placement and aqueductal stenosis were independent risk factors for meningitis after VP shunt.

Adverse reactions to antibiotics in hospitalized Iranian children.

BACKGROUND AND PURPOSE: The aim of this study was to determine the frequency of adverse reactions to antibiotics by organ system in hospitalized children in the infectious ward of a pediatric diseases referral center in Iran. METHODS: All patients treated with antibiotics were evaluated daily for the presence of ADRs during a 5-month period. For each suspected ADR, a specialized questionnaire was completed in order to obtain the information necessary for analysis of ADRs. RESULTS: Among 300 patients, 65 ADRs were seen in 36 patients (12%) during their hospitalization. Pneumonia was the most common reason for administering antibiotics; ceftriaxone and rifampin were the most frequently implicated antibiotics in ADRs. There was a significant relationship between the number of drugs used and the rate of ADRs (p=0.0001). The most commonly affected organ systems were skin and appendages, and the gastrointestinal system. Maculopapular rashes were the most frequent skin ADRs. CONCLUSIONS: As antibiotics are the most frequently used drugs in children, and also because of significant relationship between the number of drugs used and ADRs, limited use and careful selection of type and dose of antibiotics as well as close clinical observation are very important in minimizing ADRs.

Osteomyelitis as a late complication of Bacille Calmette-Guérin vaccination.

Bacille Calmette-Guérin (BCG) osteomyelitis is a very rare complication of BCG vaccination. We report a 14-month-old boy who received BCG vaccination at birth. He developed pain and swelling in his left calf at 11 months of age. BCG osteomyelitis was diagnosed in right femur and left tibia. He had no evidence of immunodeficiency. After antituberculous therapy and surgical treatment, the bone lesions disappeared and he was discharged from hospital without any sequela during 11 months of follow-up.

Spinal epidural abscess in a neonate.

A case of purulent spinal epidural abscess in a 20-day-old girl is presented. The patient had symptoms of fever, localized back pain and swelling over the interscapular area. The diagnosis was made by magnetic resonance imaging. Purulent material grew Staphylococcus aureus from the lesion. Because of severe cord compression surgical laminotomy and drainage were performed, and antibiotics were administered. One year later she was doing well without neurologic sequelae.