Prevalence and Risk Factors of Hypovitaminosis-D in Children with Cognitive and Movement Disorders.

OBJECTIVES: To document the prevalence of hypovitaminosis-D in children with intellectual and movement disorders and to identify the risk factors in vitamin D deficient children. METHODS: This is a cross-sectional study on 90 children with neurodevelopmental disabilities. The prevalence of hypovitaminosis-D and the risk factors such as sun exposure, age-appropriate mobility, diet, skin color and anti-epileptic medications were examined in children with cognitive disorders and movement disorders. RESULTS: The mean serum vitamin D level in children with cognitive disability (n = 46) was found to be 26.7 ± 16.3 ng/L and in the children with movement disability (n = 44) it was 27.9 ± 10.5 ng/L. Though the risk factors were found in greater numbers in children in the deficient group (vitamin D < 30 ng/L), the difference between the two groups was not significant. Of the 90 children, 86 (95.5%) had at least one sign of vitamin D deficiency. Lowest levels of vitamin D were seen in autistic spectrum disorder and learning disabilities in the Cognitive Disability group and hemiplegia in the Movement Disability group. CONCLUSIONS: The prevalence of vitamin D deficiency in children with neurodevelopmental disabilities was 72.2%, with 76.1% in the cognitive disability group and 68.2% in the movement disability group. The risk factors were more common in vitamin D deficient children.

Six-month clinical outcome of cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients previously maintained on sandimmun neoral.

The trial objective was to investigate the feasibility and safety of conversion to a generic microemulsion cyclosporine in stable renal transplant patients premaintained on Neoral. We enrolled 75 patients from seven centers in five Middle Eastern countries monitored them for 6 months after conversion to Sigmasporin Microral. Readings at 0, 0.5, 1, 2, 3, 4.5, and 6 months included cyclosporine blood level, serum creatinine, liver enzymes, lipid profile, blood sugar, blood pressure and adverse events. Patients included 54 men and 21 women of mean age 38.9 +/- 10.7 years at 30.3 +/- 29.3 months post-transplantation maintained on Sigmasporin Microral dose of 2.8 +/- 1.0 mg/kg per day; they were observed to be stable throughout the study period as reflected by the therapeutic blood C0 level of 181.6 +/- 102.1 and C2 of 759.2 +/- 384.4. Their absorption profile as represented by C2/C0 was 4.9 +/- 2.8, and C2/cyclosporine dose of 282.3 +/- 128.8. An average serum creatinine level of 116.1 +/- 29.5 micromol/L denoted stable graft function and their liver enzymes did not change during the study. No new-onset cases of hypertension, diabetes mellitus, or hyperlipidemia were reported among the patients. Graft function was stable for all patients, except for two incidences of mild acute rejection and two of mild cyclosporine nephrotoxicity; graft and patient survival rates were both 100%. Results of this 6-month study showed that Sigmasporin Microral was effective to maintain stable renal function in kidney transplant patients converted from Neoral with similar safety and tolerability profiles as those reported in the literature.

Therapeutic equivalence and mg:mg switch ability of a generic cyclosporine microemulsion formulation (Sigmasporin Microral) in stable renal transplant patients maintained on Sandimmun Neoral.

We tested a hypothesized pharmacokinetic difference between the reference (Sandimmun Neoral) and test (Sigmasporin Microral) products to prove therapeutic equivalence in an open, multiple fixed dose, one-way crossover, multicenter, and multinational study over a period of 29 days. Forty two stable renal transplant recipients maintained on Sandimmun Neoral were enrolled. Whole blood was collected at day 14 of the study at 0, 0.5, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after reference dosing and the same schedule was repeated at day 29 after switching on an mg:mg basis to the test product at day 15 of the study. Analysis of variance was performed for the pharmacokinetic parameters (area under the curve [AUC]0-12, maximum concentration [Cmax]) of cyclosporine using log-transformed values. Tolerability was assessed by vital signs, adverse events, and laboratory investigations. The 90% confidence interval (CI) test for the Ln-transformed, pharmacokinetic parameters was all within the US Food and Drug Administration acceptable range of 80% to 125%, as Ln area under the steady-state curve (AUCss) was within the range of 92.56 to 103.55 and Ln Cmax was within the range of 85.73 to 103.58; the same also applied for AUC0-4, which may be considered the area of greatest inter- and intra-patient variability. Furthermore, in line with the newly adopted recommendations of the Expert Advisory Committee on Bioavailability and Bioequivalence of Health Canada, the 90% CI for AUCss was within the narrow range of 90% to 112%. No significant difference in tolerability was recorded between the two products. Sigmasporin Microral (Julphar) was found to be bioequivalent and clinically interchangeable on an mg:mg basis with Sandimmun Neoral (Novartis).

Plasma N terminal pro-brain natriuretic peptide levels and its determinants in a multi-ethnic population.

This study documents the determinants and plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) among hypertensive and normotensive subjects in a multi-ethnic population in the United Arab Emirates (UAE). We obtained demographic, anthropometric and clinical data, together with fasting NT-proBNP and biochemical indices from 128 hypertensive patients and 138 normotensive subjects matched for age, gender and ethnicity. Plasma NT-proBNP levels were significantly (P<0.001), and several-fold higher among hypertensives (median 5.92, inter quartile range (IQR): 1.79-18.48 pmol/l) than normotensives (median 1.78, IQR: 0.59-4.32 pmol/l) in the total study population, and the same was true for the ethnic groups separately. Similarly, plasma levels of glucose, blood urea nitrogen (BUN) and creatinine, but not insulin, were significantly (P<0.05) higher among hypertensives than normotensives. For all subjects combined, log NT-proBNP correlated positively and significantly with age (P<0.01), log glucose (P<0.05), systolic blood pressure (SBP, P<0.001), log BUN (P<0.001) and log creatinine (P<0.001). Multivariate regression analysis showed that NT-proBNP levels were independently and positively correlated with SBP, age, gender, log BUN, Emirati and South East Asian ethnic groups and inversely associated with current exercise. In conclusion, we found circulating levels of NT-proBNP to be significantly increased in hypertensive versus normotensive subjects in the UAE and independently related to SBP, age, gender, indices of renal function and possibly exercise. Our results further suggest a possible modulating effect of ethnicity on NT-proBNP levels.

The clinical profile of children in India with pigmentary anomalies along the lines of Blaschko and central nervous system manifestations.

The aim of this study was to describe the clinical profile of children with congenital pigmentary anomalies along Blaschko lines and the associated manifestations in the central nervous system. Twenty-six children aged 12 years or less (14 boys and 12 girls), with hypopigmentation and hyperpigmentation along Blaschko lines and central nervous system manifestations were included during the period June 2001 to December 2003. Detailed physical, cutaneous, and systemic examinations were carried out. Relevant investigations included histopathology, karyotyping, electroencephalogram, computerized tomography scans, and magnetic resonance imaging of the brain whenever possible. Twenty children had hyperpigmentation along the lines of Blaschko, four had hypopigmentation, and two had a combination of the two. Eight children had diffuse involvement. Of these, two each had hypomelanosis of Ito, incontinentia pigmenti and linear and whorled nevoid hypermelanosis. The remaining 20 patients could not be categorized as any of the described entities. The majority (92.3%) of patients manifested skin and central nervous system disorders before the age of 2 years. Hyperpigmentation along Blaschko lines was significantly higher in patients with central nervous system manifestations (p = 0.01). Developmental delay was the most frequent central nervous system presentation. Multiple systems were affected, including the eyes. Histology was useful to distinguish incontinentia pigmenti from other types of nevoid hyperpigmentation.

Camptodactyly in Sotos syndrome.

We describe a girl with Sotos syndrome presenting at two and a half years age with developmental delay. She has camptodactyly which has not previously been reported in Sotos syndrome but is a common finding in Weaver syndrome. Both these conditions have been reported to have NSD1 gene mutations. This report is consistent with the conditions being allelic.

Aqueous shunts for glaucoma.

BACKGROUND: Aqueous shunts are employed for intraocular pressure (IOP) control in primary and secondary glaucomas that fail medical, laser, and other surgical therapies. OBJECTIVES: This review compares aqueous shunts for IOP control and safety. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, PubMed, EMBASE, NRR all in January 2006, LILACS to February 2004 and reference lists of included trials. SELECTION CRITERIA: We included all randomized and quasi-randomized trials in which one arm of the study involved shunts. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for included studies and a third adjudicated discrepancies. We contacted investigators for missing information. We used fixed-effect models and summarized continuous outcomes using mean differences. MAIN RESULTS: We included fifteen trials with a total of 1153 participants with mixed diagnoses. Five studies reported details sufficient to verify the method of randomization but only two had adequate allocation concealment. Data collection and follow-up times were variable.Meta-analysis of two trials comparing Ahmed implant with trabeculectomy found trabeculectomy resulted in lower mean IOPs 11 to 13 months later (mean difference 3.81 mm Hg, 95% CI 1.94 to 5.69 mm Hg). Meta-analysis of two trials comparing double-plate Molteno implant with the Schocket shunt was not done due to substantial heterogeneity. One study comparing ridged with standard double-plate Molteno implants found no clinically significant differences in outcome. Two trials investigating the effectiveness of adjunctive mitomycin (MMC) with the Molteno and Ahmed implants found no evidence of benefit with MMC. Two trials that investigated surgical technique variations with the Ahmed found no benefit with partial tube ligation or excision of Tenon's capsule. One study concluded there were outcome advantages with a double versus a single-plate Molteno implant and one trial comparing the 350 mm(2) and 500 mm(2) Baerveldt shunts found no clinically significant advantage of the larger device but neither of these trials included all patients randomized. One study suggested improved clinical outcome when MMC was employed with a newly described shunt including ultrasound supporting the conclusion. One small study did not demonstrate an outcome advantage to systemic steroid use postoperatively with single-plate Molteno shunts. One study comparing endocyclophotocoagulation (ECP) with Ahmed implant in complicated glaucomas found no evidence of better IOP control with Ahmed implant over ECP. AUTHORS' CONCLUSIONS: Relatively few randomized trials have been published on aqueous shunts and methodology and data quality among them is poor. To date there is no evidence of superiority of one shunt over another.

Bedtime diazepam enhances well-being in children with spastic cerebral palsy.

In work with children with cerebral palsy at Ashirvad, Child Development and Research Centre, Chennai, India, the authors were confronted with fretful children who resisted any attempt to mobilize their limbs due to hypertonia and muscle spasm. It was found that administering a bedtime dose of diazepam to reduce hypertonia and muscle spasm alongside passive stretching exercises significantly improved the behaviour of the child. There was significant improvement in the well-being of the child during the activities of daily living and this reduced the family's burden of caring for the child. In this double blind, placebo-controlled, randomized clinical trial, each child received a bedtime dose of diazepam or placebo. The bedtime diazepam relaxed the muscles and this made the passive stretching easy and the movements sustained the muscle relaxation during the day. There were fewer unwarranted crying spells during the day and less wakefulness during the night. The adverse effect of day time sedation was not observed with the use of a single dose of diazepam at bedtime.

The efficacy of diazepam in enhancing motor function in children with spastic cerebral palsy.

Muscle spasm and hypertonia limit mobility in children with spastic cerebral palsy. This double-blind, placebo-controlled, randomized controlled clinical trial studies the clinical efficacy of a low dose of diazepam in enhancing movement in children with spastic cerebral palsy. One hundred and eighty children fulfilled the criteria and were randomly allocated to receive one of two doses of diazepam or placebo at bedtime; 173 completed the study. There was a significant reduction of hypertonia, improvement in the range of passive movement, and an increase in spontaneous movement in the children who received diazepam. There was no report of daytime drowsiness. In developing countries, where cost factors often determine choice of drug, diazepam is a cheap and effective way of relieving spasm and stiffness, optimizing physical therapy and facilitating movement in children with spasticity.

Use of antihypertensive agents in the management of patients with acute ischemic stroke.

BACKGROUND: To protect the ischemic penumbra, guidelines have recommended against treating all but the severest elevations in blood pressure during acute ischemic stroke. OBJECTIVE: To determine how often antihypertensive agents were used in routine clinical practice and whether this use was consistent with guideline recommendations. METHODS: The records of patients discharged with ischemic stroke in 2000 at Baystate Medical Center in Springfield, MA, were reviewed. Adherence was evaluated by examining the use of antihypertensive agents in the context of daily blood pressure recordings during the first 4 days of hospitalization. Therapy was considered appropriate in the setting of severe hypertension (systolic blood pressure of >220 mm Hg or mean arterial blood pressure of >130 mm Hg) and potentially harmful in the setting of relative (systolic blood pressure of <120 mm Hg or mean arterial blood pressure of <85 mm Hg) or absolute (systolic blood pressure of <90 mm Hg or mean arterial blood pressure of <60 mm Hg) hypotension. RESULTS: One hundred (65%) of the 154 ischemic stroke patients were treated with antihypertensive agents. Forty-two percent of those who had received therapy prior to admission had their regimen intensified, and 36% of previously untreated patients had therapy initiated. Sixteen (11%) patients had hypertension severe enough to warrant treatment upon arrival, and 34 (22%) had at least one episode of severe hypertension during the first 4 hospital days. Sixty-five (65%) patients developed relative hypotension on a day when antihypertensive agents were administered, and five (5%) developed absolute hypotension. CONCLUSIONS: Most patients with acute ischemic stroke are treated with antihypertensive agents despite the absence of severe hypertension. Although low blood pressure is common among treated patients, frank hypotension is unusual.

Perioperative management of liver transplantation patients.

Perioperative care involves many disciplines, each of which contributes in important ways. Changes in liver-transplantation care during the last 40 years can be attributed to the accumulation of improvements, discoveries, and technologic improvements across different disciplines. Here we review some of the articles that were published during the last year that relate to these advances.

A child returns to her mother....

There are various expressions of attachment and separation processes in children under 5 years of age. One particular experience in the life of a mother and her daughter is illustrated here. The woman, having lost her young husband following a brief illness, had concealed her grief and pain in an attempt to be brave and to face the future. She decided to send her 5-year-old daughter to a residential school. This was her way of adjusting to her distress and providing the best for her daughter. That was the beginning of the separation-anxiety process which left stress reactions in the mother and the child. The story of the mother and child is one of gradual recovery from their grief and loss. This story takes us into the dynamics of the attachment-separation process in children, to which we need to pay special attention as part of our commitment to child development.