Assessment of heavy metals by ICP-OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

Arsenic (As) and cadmium (Cd) have recently emerged as major health concerns owing to their strong association with diabetes mellitus (DM). We aimed to investigate the heavy metals exposure towards incidence of DM at various enzymatic and hormonal levels. Additionally, association of As and Cd with Zinc (Zn, essential metal) was also evaluated. Spot urine samples were collected to assess As, Cd and Zn through ICP-OES. Serum was analyzed by assay method for fasting blood glucose, liver and renal function biomarkers. ELISA was performed to investigate the impact of heavy metals on HbA1c, α-amylase, DPP-IV, IGF-1, leptin, GSH, MDA, SOD, HDL, FFA, TG and interleukin (IL)-6. Association of heavy metals with DM was measured by odds ratio (OR) and level of significance was assessed by Chi-squared test. Unpaired student's t-test was used to compare DM-associated risk factors in heavy metals-exposed and unexposed participants. As and Cd were detectable in 75.4% and 83% participants with mean concentration of 75.5 ppb and 54.5 ppb, respectively. For As exposure, OR in the third quartile was maximum ie 1.34 (95% CI, 0.80 to 2.23), however the result was not statistically significant (P > .05). For Cd exposure, OR in the fourth quartile was considerably high, 1.62 (95% CI, 1.00 to 2.61), with a significant probability value (P < .05). Urinary Cd was negatively associated with Zn. As and Cd exposure increases the incidence of DM in the general population. Impaired hormonal and enzymatic levels in diabetic and non-diabetic exposed participants reflect the multiple organ damage by heavy metal exposure.     

Unusual Case of West Nile Virus Flaccid Paralysis in a 10-Year-Old Child

West Nile virus infection is asymptomatic in most cases. West Nile virus neuroinvasive disease includes encephalitis, meningitis, and/or acute flaccid paralysis. In children, acute flaccid paralysis as the solo presentation of West Nile virus disease is rare. It develops abruptly and progresses rapidly early in the disease course. We report on a 10-year-old child who presented with a slowly progressive left leg flaccid paralysis over 4 weeks. He tested positive for West Nile virus in both blood and cerebrospinal fluid. Spinal MRI showed enhancement of the ventral nerve roots. This was also supported by electrophysiological studies. One week after the plateauing of his left leg paralysis, he was readmitted to the hospital with left hand weakness. Complete recovery of his recurrent weakness was observed after prompt 5-day course of intravenous immunoglobulin G therapy. However, no improvement was noticed in the left foot drop. To our knowledge, this is the first case report of West Nile virus disease in children presented with a slowly progressive flaccid paralysis, and a recurrent weakness recovered after intravenous immunoglobulin G administration.     

Does the introduction of new technology change population demographics? Minimally invasive technologies and endometrial polyps

OBJECTIVE: To determine if the characteristics of women with endometrial polyps changed as minimally invasive modalities for diagnosis and surgical treatment were integrated to our clinical practice. MATERIALS AND METHODS: The pathologic reports of all women diagnosed with endometrial polyps in 1990 (220 patients) and 1996 (386 patients) were reviewed. The respective medical records were reviewed for anthropomorphic factors, bleeding pattern, diagnosis, and modality of surgical removal. Comparisons of dichotomous data and analysis of nominal variables with two or more categories were carried out with the chi(2) test. RESULTS: Differences in patient characteristics or pattern of bleeding were minimal. In both groups, endometrial polyps were more frequent in women with abnormal bleeding, reaching almost 80%. Diagnostic and therapeutic modalities were significantly different in 1990 vs. 1996. Diagnosis by ultrasound increased fivefold (3.6 vs. 16.8%) and operative hysteroscopy increased threefold (6.4 vs. 19.7). The frequency of incidental diagnosis of endometrial polyps at the time of hysterectomy decreased significantly. The most frequent modality of surgery done in 1990 was dilatation and curettage (44.6%), followed in frequency by endometrial biopsy and abdominal hysterectomy. In contrast, the most frequent modality in 1996 was hysteroscopic resection (36.8%), followed by dilatation and curettage (12.8%). CONCLUSIONS: The introduction of minimally invasive methods of diagnosis and treatment of endometrial polyps has not changed the overall patient population with this lesion.     

Mutations in betaB3-crystallin associated with autosomal recessive cataract in two Pakistani families

PURPOSE: To identify the disease locus for autosomal recessive congenital cataracts in consanguineous Pakistani families. METHODS: Two Pakistani families were ascertained, patients were examined, blood samples were collected, and DNA was isolated. A genome-wide scan was performed using >382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. Two-point lod scores were calculated, haplotypes were formed by inspection, and candidate genes were sequenced. Real-time quantitative PCR techniques were used to determine the mRNA levels, and molecular modeling was performed to gain a better understanding of the significance of the disease-causing mutation. RESULTS: In the genome-wide scan, maximum lod scores of 2.67 and 2.77 for family 60004 and 2.02 and 2.04 for family 60006 were obtained for markers D22S539 and D22S315, respectively. The linked region, 22.7 cM (10 Mb) flanked by markers D22S420 and D22S1163, contains the beta-crystallin gene cluster including the genes CRYBA4, CRYBB1, CRYBB2, and CRYBB3. Sequencing of these genes showed a G-->C transition in exon 6 of CRYBB3 resulting in a p.G165R change in the betaB3-crystallin protein that cosegregates with the disease in both families. Real-time PCR analysis suggested that betaB3-crystallin mRNA levels approximate those of other betagamma-crystallins. Molecular modeling predicted changes in electrostatic potential that would be expected to reduce the stability of the fourth Greek-key motif, and hence the entire protein, dramatically. CONCLUSIONS: For the first time, a mutation in CRYBB3 is reported in two consanguineous Pakistani families with autosomal recessive congenital cataracts.     

Social use of language in children with reactive attachment disorder and autism spectrum disorders

Children with a diagnosis of reactive attachment disorder (RAD) appear to show difficulties in social understanding. We aimed to compare the pragmatic language functioning of children with (RAD) and autism spectrum disorder (ASD). Assessments were made in three groups of children aged 5–8 years, with verbal IQ estimates in the normal range: 35 with a RAD diagnosis, 52 with an ASD diagnosis and 39 with typical development. The Children’s Communication Checklist (CCC) was used to compare their pragmatic language skills, and ADI-R algorithms were used to compare autistic symptomatology, according to parent report. According to the CCC, the RAD group demonstrated significant problems in their use of context, rapport and social relationships with a degree of severity equivalent to children in the ASD comparison group. More than 60% of the group with RAD met ADI-R clinical criteria on the Use of Language and Other Social Communication Skills subscale, 46% on the Reciprocal Social Interaction subscale, and 20% had significant repetitive and stereotyped behaviours. Children with RAD appear to be at least as impaired as children with ASD in certain domains of social relatedness, particularly in their pragmatic language skills.     

Autosomal recessive retinitis pigmentosa is associated with mutations in RP1 in three consanguineous Pakistani families

PURPOSE: To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa in three consanguineous Pakistani families. METHODS: Blood samples were collected and DNA was extracted. A genome-wide scan was performed by using 382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members, and lod scores were calculated. RESULTS: A genome-wide scan of 25 families gave an hlod = 4.53 with D8S260. Retinitis pigmentosa in all three families mapped to a 14.21-cM (21.19-Mb) region on chromosome 8 at q11, flanked by D8S532 and D8S260. This region harbors RP1, which is known to cause autosomal dominant retinitis pigmentosa. Sequencing of the coding exons of RP1 showed mutations in all three families: two single-base deletions, c.4703delA and c.5400delA, resulting in a frame shift, and a 4-bp insertion, c.1606insTGAA, all causing premature termination of the protein. All affected individuals in these families are homozygous for the mutations. Parents and siblings heterozygous for the mutant allele did not show any signs or symptoms of RP. CONCLUSIONS: These results provide strong evidence that mutations in RP1 can result in recessive as well as dominant retinitis pigmentosa. The findings suggest that truncation of RP1 before the BIF motif or within the terminal portion results in a simple loss of RP1 function, producing a recessive inheritance pattern. In contrast, disruption of RP1 within or immediately after the BIF domain may result in a protein with a deleterious effect and hence a dominant inheritance pattern.