Lumbar Puncture Ordering and Results in the Pediatric Population: A Promising Data Source for Surveillance Systems

Background: The Centers for Disease Control and Prevention is incorporating laboratory data into real-time surveillance systems. When normal patterns of laboratory test orders and results are modeled, aberrations can be detected. Because many test orders are available electronically well before results, atypical patterns of test ordering may signal outbreaks.
Objectives: The authors sought to characterize baseline patterns in the ordering and early results of lumbar punctures, motivated by the possibility of using these data for real-time surveillance for early detection of meningitis or encephalitis outbreaks.
Methods: Retrospective cohorts of pediatric emergency department patients at a single hospital (1993–2003) and from the National Hospital and Ambulatory Medical Care Survey (1992–2000) were used for analysis.
Results: Test ordering exhibits seasonal patterns, with monthly peaks in January and August (p < 0.0001). For the hospital cohort, the rate of cerebrospinal fluid pleocytosis exhibits seasonal patterns (p < 0.0001), with a peak from August to October. This is strongly associated with the rate and pattern of clinical neurologic disease (p < 0.0001). A long-term secular decline in daily test ordering is evident, dropping from 5.3 to 2.9 in the hospital sample, and from 371.8 to 185.3 in the national sample (p < 0.001). The long-term rate of pleocytosis has declined (p < 0.0001), though the yield of testing for pleocytosis has improved (p = 0.0104).
Conclusions: Laboratory test patterns correspond with those of clinical disease and are a promising source of surveillance data. Using such data for real-time monitoring requires specific adjustments for patient age, periodicities, and secular trends.     

GJB2 mutations: passage through Iran

Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and chromosome 13 g.1777179_2085947del (the deletion more commonly known as del (GJB6-D13S1830) that includes a portion of GJB6 and is hereafter called Delta(GJB6-D13S1830)) to the autosomal recessive non-syndromic deafness (ARNSD) genetic load in Iran. Probands from 664 different nuclear families were investigated. GJB2-related deafness was found in 111 families (16.7%). The carrier frequency of the 35delG mutation showed a geographic variation that is supported by studies in neighboring countries. Delta(GJB6-D13S1830) was not found. Our prevalence data for GJB2-related deafness reveal a geographic pattern that mirrors the south-to-north European gradient and supports a founder effect in southeastern Europe.     

Development of an immune function assay by measuring intracellular adenosine triphosphate (iATP) levels in mitogen-stimulated CD4+ T lymphocytes

We developed an immune function assay for monitoring CD4+ T cells activity based on changes in intracellular adenosine triphosphate (iATP) levels after phytohemagglutinin (PHA) stimulation. Blood samples were obtained from 40 healthy subjects and 30 RTRs and incubated with 5 µg/mL of PHA for 15–18 hr at 37°C and 5% CO₂. Afterward, the CD4+ T cells were separated by antibody-coated magnetic beads and lysed. Then, iATP content in unstimulated and stimulated conditions was measured by luciferin-luciferase reaction using a log-log standard curve. The iATP levels showed significant increase in CD4+ T cells in both healthy persons (mean: 550 ± 142 ng/mL vs. 109 ± 54 ng/mL) and RTRs (mean: 394 ± 160 ng/mL vs. 52 ± 37 ng/mL) after PHA stimulation (P < 0.001). However, the iATP production in RTRs was significantly lower than that in healthy individuals; both prior to and after stimulation with PHA (P < 0.001). No gender-specific difference in iATP production was observed between women and men subjects. This rapid and low-cost assay reflects the degree of immune cell function through assessment of CD4+ T cells activation. Thus, it can be used for evaluation of immune system status in immunodeficient individuals as well as in immunosuppressed transplant recipients who needs drug adjustment.     

Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options

Background

Adenosine kinase deficiency is a recently described defect affecting methionine metabolism with a severe clinical phenotype comprising mainly neurological and hepatic impairment and dysmorphism.

Methods

Clinical data of 11 additional patients from eight families with adenosine kinase deficiency were gathered through a retrospective questionnaire. Two liver biopsies of one patient were systematically evaluated.

Results

The main clinical symptoms are mild to severe liver dysfunction with neonatal onset, muscular hypotonia, global developmental retardation and dysmorphism (especially frontal bossing). Hepatic involvement is not a constant finding. Most patients have epilepsy and recurrent hypoglycemia due to hyperinsulinism. Major biochemical findings are intermittent hypermethioninemia, increased S-adenosylmethionine and S-adenosylhomocysteine in plasma and increased adenosine in urine. S-adenosylmethionine and S-adenosylhomocysteine are the most reliable biochemical markers. The major histological finding was pronounced microvesicular hepatic steatosis. Therapeutic trials with a methionine restricted diet indicate a potential beneficial effect on biochemical and clinical parameters in four patients and hyperinsulinism was responsive to diazoxide in two patients.

Conclusion

Adenosine kinase deficiency is a severe inborn error at the cross-road of methionine and adenosine metabolism that mainly causes dysmorphism, brain and liver symptoms, but also recurrent hypoglycemia. The clinical phenotype varies from an exclusively neurological to a multi-organ manifestation. Methionine-restricted diet should be considered as a therapeutic option.

     

Should patients with complex febrile seizure be admitted for further management?

Background and aims

Children with first complex febrile seizure (CFS) are often admitted for observation. The goals of this study were 1) to assess the risk of seizure recurrence during admission, 2) to determine whether early EEG affects acute management.

Positive guaiac and bloody stool are poor predictors of intussusception

Background

Currant jelly stool is a late manifestation of intussusception and is rarely seen in clinical practice. Other forms of GI bleeding have not been thoroughly studied and little is known about their respective diagnostic values.

Hb Dhonburi (Neapolis) [beta126(H4)Val-->Gly] identified in a family from northern Iran

Thalassemias are the most common hereditary diseases in Iran, resulting from synthesis defects in one or more hemoglobin (Hb) subunits. The majority of patients suffer from beta-thalassemia (thal), but cases with microcytic hypochromic anemia and normal electrophoretic patterns are suspected to have alpha- or silent beta-thal. A family from the northern part of Iran, an area highly prevalent for thalassemias, was referred to us for prenatal diagnosis. The hematological data of the father indicated a pattern of beta-thal minor. Reverse hybridization analysis for the most common beta-globin mutations identified IVS-II-1 (G-->A) in the heterozygous state. The maternal laboratory data indicated a case more compatible with alpha-thal. Iron deficient anemia was ruled out, and common alpha-thal point mutations and deletions were investigated. As no mutation was detected, chain synthesis was performed and showed an alpha/beta chain ratio of 2.1, that was in the range of beta-thal minor. DNA sequencing of the entire beta-globin gene identified a heterozygous GTG-->GGG (Val-->Gly) mutation at codon 126, also known as Hb Dhonburi (Neapolis). Prenatal diagnosis of the fetal DNA showed the absence of the IVS-II-1 and codon 126 anomalies. This result demonstrates the importance of screening of individuals with mild microcytic hypochromic anemia for both alpha- and silent beta-thal mutations.     

Provider and Systems Factors in Diabetes Quality of Care

A gap exists in knowledge and the observed frequency with which patients with diabetes actually receive treatment for optimal cardiovascular risk reduction. Many interventions to improve quality of care have been targeted at the health systems level and provider organizations. Changes in several domains of care and investment in quality by organizational leaders are needed to make long-lasting improvements. In the studies reviewed, the most effective strategies often have multiple components, whereas the use of one single strategy, such as reminders only or an educational intervention, is less effective. More studies are needed to examine the effect of several care management strategies simultaneously, such as use of clinical information systems, provider financial incentives, and organizational model on processes of care and outcomes.     

The Effectiveness of Self-care Program on the Life Quality of Patients with Multiple Sclerosis in 2015

This study aimed to investigate the effectiveness of self-care plan on the life quality of patients with Multiple sclerosis (MS). The samples in this study included all the patients with MS under medical coverage of Iranian Association of supporting patients with MS in Tehran in 2015 who were studied as Convenience sampling and based on the inclusion and exclusion criteria. In this study, Dr. Madani's self-care program as an intervention and The World Health Organization Quality of Life (WHOQOL)-BREF for assessment of consequences were used. Spss software using Wilcoxon and ANOVA tests were used to analyze the data. Values are significant at P value less than 0.05. Before the intervention, the quality of life was 59.91 ± 13.39 and after the intervention, it was 69.37 ± 11.73 and there was a significant difference between them (P value < 0.001). Also, there was a significant difference between the items of life quality-including the physical, psychological and social relationships and living environment items-before and after the interventions. Self-care program has an effect on the quality of life and physical, psychological and social relationships and living environment items.     

CTG expansion & haplotype analysis in DM1 gene in healthy Iranian population

Myotonic dystrophy type 1 (DM1) is due to an unstable expansion of CTG repeat in the DMPK gene (19q13.3). The CTG repeat is highly polymorphic (5 to 37) in healthy individuals. According to the hypothesis that expanded (CTG)n alleles originated from larger normal alleles, there may exist a correlation between the prevalence of DM1 and the frequency of large size normal alleles. Strong linkage disequilibrium between different length alleles and the three biallelic markers, Alu, Hinf1 and Taq1, has been reported. OBJECTIVE: To determine the distribution of normal alleles, the frequency of larger normal alleles and analysis of the three biallelic markers, in healthy Iranian controls. MATERIAL AND METHODS: Polymerase chain reaction (PCR) was conducted on two hundred unrelated healthy individuals from different ethnic groups living in Iran to determine the size of the alleles. Markers were analyzed by PCR/RFLP on 174 chromosomes from other control healthy individuals. RESULTS: Our data reveals that 23.7% of alleles had 5 CTG repeats and 7.2% of alleles had > 18 CTG repeats. The analysis of haplotypes revealed that 75% of CTG5 and 80% of CTG > 18 had the (+++) haplotype. CONCLUSION: The frequency of alleles with CTG > 18 in Iran is similar to that of Western Europe and Japan.