26 research outputs found

    Use of ACTH and prednisolone in infantile spasms: Experience from a developing country

    Get PDF
    SummaryBackground: Adrenocorticotrophic hormone (ACTH) and prednisone are both used to treat infantile spasms (IS) in West syndrome. In many countries, ACTH is expensive and difficult to obtain whereas, prednisone or prednisolone are cheap, given orally and easily available.Aims: The purpose of this retrospective data analysis was to compare the efficacy and cost of ACTH and prednisolone in the treatment of IS from the perspective of a developing country.Methods: Patients admitted with West syndrome in Children's Hospital, Islamabad, between January 1995 and December 2001 were included in the analysis. The diagnosis was made after eliciting a history of characteristic seizures and detecting hypsarrhythmia on the EEG. Parents were offered the use of either ACTH administered by intramuscular injection or prednisolone given orally. ACTH was expensive and difficult to obtain whereas prednisolone was cheap and easily available.Results: One hundred and five children were included in the study. Sixty-three were boys and their age ranged from 2 months to 3 years with a mean of 11 months. Thirty-three children received ACTH injections; 27 showed improvement and 11 remained spasms free after discontinuation of injections. Seventy-two patients were given oral prednisolone, 51 responded and 17 remained spasms free after oral steroids were stopped. Overall outcome was similar in both groups. The cost of ACTH injection was more than 100 times the cost of oral prednisolone.Conclusion: No significant difference was seen in the final outcome in both treatment groups. Since prednisolone is inexpensive, easily available and given orally, it is the preferred mode of therapy

    N-Acetonylsaccharin

    Get PDF
    In the title compound [systematic name: 2-(2-oxoprop­yl)-1,2-benzothia­zol-3(2H)-one 1,1-dioxide], C10H9NO4S, the benzo­thia­zole unit is essentially planar [maximum deviation = 0.0490 (9) Å for the S atom] and the oxopropyl group is inclined at an angle 75.61 (8)° with respect to its mean plane. In the crystal, mol­ecules are held together by weak inter­molecular C—H⋯O non-classical hydrogen bonds, resulting in centrosymmetric dimeric units, forming 14-membered ring systems which may be described as R 2 2(14) ring motifs. Moreover, mol­ecules lying about inversion centers show π–π inter­actions, with centroid–centroid separations between the benzene rings of 3.676 (2) Å

    The Genome Atlas Resource

    Get PDF

    Pak. J. of Neurol. Surg. - Vol. 14, No. 1, Jan. – Jun., 2010 -35- ORIGINAL ARTICLE Clinical Features, Etiological Factors, Neurological Imaging and Outcome in Children with Ischemic Stroke

    Get PDF
    Objective was to study etiological factors, clinical features, neuroradiological findings, Outcome in infants and children who present with ischemic stroke.Study design: It was a descriptive study.Setting: It was a hospital based study which was conducted in the Children Hospital, Pakistan Institute of Medical Sciences from 1st August 2002 to 30th December 2003.Method: In this study children were included who presented with weakness, altered sensorium, seizures, or any focal deficit. CT brain was done in all these children. Those having evidence of infarct were studied for clinical features, etiological factors and out come. Those having neurological infection, trauma, brain tumor, and abscess were excluded from the study. For data analysis, SPSS 8 software was used.Results: Total of studied thirty patients were enrolled in the study. Age range was from two month to twelve years. Male to female ratio was 3.3 to 1. Sixteen (53%) were 6-12 years of age while 12 (40%) were 2-5 years age and only 2 (6.6%) were below one year of age. Etiological factors were identified in 12 (40%) of the patients, out of which cardiac pathology was found in most of the patients i.e. is 10 (33.3%).There were 2 (6.6%) patients having deficiency of protein C and S .No predisposing factor was identified in 18 (60%) patients. Clinical presentation was studied and was found 29 (96.6%) patients presented with hemiperesis. Facial weakness was present in 15 (56%) of children. Seizures were present in 16 (53.3%) of patients, while 11 (13%) were uncon-scious. Thirteen (43%) were febrile on presentation. Seven (23%) were having swallowing problem, 4 (13.3%) were having headache and only 3 (10%) got visual problem. Middle cerebral artery infarct was commonest seen in that is 19 (63.3%) cases. Lanticulo striate artery infarct was found in 5 (16.3%). Anterior cerebral artery infarct was 4 (13.3%) and only 2 (6.6%) were having Posterior cerebral artery infarct. Complications were also studied in these patients. Seizures were present in 18 (60%) of patients. Nine (30%) developed mild to severe chest infection, while 10 (33.3%) later on develop urinary tract infection. Weight loss was observed in 11 (36.6%) patients. Outcome was studied with the help of Glasgow coma outcome scale. Ten (33.3%) patients showed good outcome, moderate disability was present in 14 (46.6%) of patients, and severe disability was present in 4 (13.3%) of patients, 2 (6.6%) patients died.Conclusion: It was concluded that ischemic stroke is not rare in Pakistani children. Cardiac disease is the most important and preventable predisposing factor for ischemic stroke. Every effort should be made to diagnose and treat the congenital cardiac disease as early as possible. Middle cerebral artery infarct was the most common infarct. Computed tomography of brain was found to be very useful and sensitive investigation for diagnosis of ischemic infarct. If available neuroimaging studies should be performed in suspected stroke children. Mortality is low while morbidity was quite high among the survivors. Since this was a hospital based study and may not represent general pediatric age group, therefore large scale population based studies should be planned for the future

    2-(2-Oxo-2-phenyl­ethyl)-1,2-benziso­thia­zol-3(2H)-one 1,1-dioxide

    Get PDF
    In the title compound, C15H11NO4S, the benzothia­zole unit is essentially planar [maximum deviation = 0.0644 (14) Å for the N atom] and forms a dihedral angle 54.43 (6)° with the phenyl ring. In the crystal structure, weak bifurcated C—H⋯O hydrogen bonds involving the carbonyl O atoms as acceptors result in R 2 2(7) ring motifs

    Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

    Get PDF
    The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

    Characterization of greater middle eastern genetic variation for enhanced disease gene discovery

    Get PDF
    The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia1-3, has resulted in an elevated burden of recessive disease4. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized ‘genetic purging’. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics

    Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

    Get PDF
    The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Using exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with myristic acid alkyne (YnMyr) chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), aged 1-50 years, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%) and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%) and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each) as well as hypertrophy of the clava (24%) were common neuroimaging findings. Acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localization and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-myristoylation was similarly affected in acbd6-deficient zebrafish and X. tropicalis models, including Fus, Marcks and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders

    Effectiveness of Massage Therapy for Treatment of Infantile Colic

    No full text
    Background: To compare modes of administration of massage therapy for management of infantile colic. Methods: This prospective study included exclusively breast fed infants less than 4 months of age and diagnosed as cases of infantile colic. Patients were randomly assigned to receive a standard massage either during colic episode (group A) or as daily care (group B) or no intervention at all (group C). Change in mean duration of crying (minutes/day) was primary outcome while weight gain and number of patients showing 50% reduction in crying time were secondary out comes. Results: A significant reduction of crying time was observed only in group A compared to other two groups (p<0.005) on day 7, 14 and 21 of therapy. Majority of patients (90.3%) in group A showed 50% reduction in basal crying time. Patients in group A showed better weight gain compared to group B and group C but this was not significant (p value= 0.385). Conclusion: Massage therapy is better than no intervention for colic

    Hematological Scoring System for Early Diagnosis of Neonatal Sepsis

    No full text
    Background: To determine the accuracy of a simple and cost effective haematological scoring system (HSS) in the early diagnosis of neonatal sepsis using blood culture as a gold standard.Methods: In this prospective cross sectional study newborns (n=170) with history of prolonged rupture of membranes, maternal intrapartum fever > 1010 F or clinical signs of sepsis namely; neonatal fever ≥ 1010 F, poor feeding and lethargy or depressed neonatal reflexes were included in the study. All the newborn babies with history of delayed cry, meconium aspiration, congenital anomaly, history of antibiotics administration prior to admission to the baby or mother, intrapartum and neonatal death in sibling with similar presentation (rule out inborn error of metabolism) were excluded. Patient was scored according to haematological scoring system (HSS), incorporating increase or decrease in leucocytes count, absolute neutrophil count and platelet count. CRP estimation and blood culture were also performed. Score of more than 3 was considered as positive .Results: The mean age of participants was 12.4 ± 7.3 days, of which 54.1% were male. Most neonates(52.4%) were in the age group up to 10 days and 61% were preterm. The HSS was found to have a sensitivity of 90%, specificity of 74.5%, Positive Predictive Value was 65.9% and Negative Predictive Value was 93.2%Conclusion: HSS is a simple cost effective tool to detect neonatal sepsis with high sensitivity and an acceptable specificity
    corecore