Epidemiological profile of spinal cord injuries at a tertiary rehabilitation center in Kuwait.

STUDY DESIGN: Retrospective, descriptive study. OBJECTIVE: To describe the epidemiological profile of patients with spinal cord injury (SCI) in Kuwait. SETTING: Physical Medicine and Rehabilitation Hospital, Kuwait. METHODS: Review of medical records of 241 adult patients with SCI admitted during the period 2010-2015. The data collected included gender, age, etiology, neurological and vertebral level of injury and American Spinal Injury Association impairment scale (AIS). RESULTS: There were 155 (64.3%) traumatic SCI (TSCI) and 86 (35.7%) non-traumatic SCI (NTSCI) patients. In TSCI, the male to female ratio was 4.3:1, and in NTSCI it was 1.5:1. Road traffic accident was the most common cause of TSCI (52.9%), followed by fall from height (32.9%). Acute disc prolapse was the most common cause of NTSCI (29.1%), followed by degenerative disc disease (26.7%) and tumors (17.4%). Paraplegia (41.3%) was more common in TSCI, the level of injury being thoracic in 61% of cases. Cauda equina syndrome was the most common presentation in NTSCI (40.7%). CONCLUSION: Road traffic accident was found to be the main cause of TSCI in Kuwait, whereas acute and degenerative disc lesions were the leading causes in NTSCI. Prevention strategies should be directed toward these causes to reduce the incidence of SCI in Kuwait.

Cell transplantation and clinical reality: Kuwait experience in persons with spinal cord injury.

STUDY DESIGN: Retrospective observational. OBJECTIVES: To compare objective (neurological examination) and subjective (patients perception) recovery in patients with spinal cord injury (SCI) who chose to undergo cell transplantation therapies (CTT) outside of clinical trials abroad. SETTING: Physical Medicine and Rehabilitation Hospital, Kuwait. METHODS: Nine patients with SCI who had undergone CTT outside Kuwait were identified and their neurological pre-transplantation evaluation according the International Standards for Neurological Classification of SCI (ISNCSCI) was collected from hospital records. Post transplantation ISNCSCI examination was conducted during follow-up visits and scores were completed between pre and post CTT. In addition to the ISNCSCI evaluation, change in disability status, and patient's perception of improvement after stem cell transplantation were examined. RESULTS: Overall, 8 males and 1 female with chronic SCI underwent CTT (42 ± 38.2 months post SCI) in various centers (China, Egypt, Germany, India, and Iran). On follow-up post CTT assessment (89.2 ± 36 months post SCI), 55.5% of individuals reported perceived improvement as follows: increased deep tissue sensation below the injury (100%) or increase in bladder sensation (11.1%). Objective examination after CTT revealed that none of the examined individuals demonstrated improvement in their motor scores or neurological level of SCI. CONCLUSION: We were not able to objectively document clinically useful improvements in sensorimotor, autonomic, or functional status in individuals after CTT.

Synthesis and biological evaluation of naphthalene-1,4-dione derivatives as potent antimycobacterial agents.

The recent increase in the incidence of tuberculosis with the emergence of multi-drug resistant (MDR) cases has lead to the search for new drugs that are effective against MDR strains of Mycobacterium tuberculosis (M. tb) and can augment the potential of existing drugs against tuberculosis. In the present study a series of naphthalene-1,4-dione derivatives were synthesized and evaluated for their in vitro antimycobacterial activity against M. tb H37Rv strain. Preliminary results indicated that most of the compounds demonstrated significant antimycobacterial activities. The most effective compounds of the series 7, 8 and 10 have MIC values of 3.13 microg/mL and growth inhibition of 99%. Compound 7 has an IC50 value of 0.49 microg/mL. Compounds 1, 3 and 18 with MIC values of 3.13 microg/mL also showed 96-98% growth inhibition. The objective of our study is to generate new leads through different mode of action and to optimize their structure to display the potent efficacy.

Breast-feeding initiation and determinants of exclusive breast-feeding - a questionnaire survey in an urban population of western Nepal.

OBJECTIVE: To assess rates of initiation of breast-feeding and exclusive breast-feeding within 2 months after delivery and to determine the factors influencing exclusive breast-feeding. DESIGN: A health worker-administered questionnaire survey was carried out during the time period 1 August-30 September 2005. SETTING: Immunisation clinics of Pokhara, a submetropolitan city in western Nepal. SUBJECTS: Three hundred and eighty-five mothers who had delivered a child within the previous 2 months. RESULTS: The rates of initiation within 1 h and within 24 h of delivery were 72.7 and 84.4%, respectively. Within 2 months after delivery, exclusive breast-feeding was practised by 82.3% of the mothers. Breast milk/colostrum was given as the first feed to 332 (86.2%) babies but 17.2% of them were either given expressed breast milk or were put to the breast of another lactating mother. Pre-lacteal feeds were given to 14% of the babies. The common pre-lacteal feeds given were formula feeds (6.2%), sugar water (5.9%) and cow's milk (2.8%). Complementary feeds were introduced by 12.7% of the mothers. By logistic regression analysis, friends' feeding practices, type of delivery and baby's first feed were the factors influencing exclusive breast-feeding practice of the mothers. CONCLUSIONS: Despite the higher rates of initiation and exclusive breast-feeding, practices such as pre-lacteal feeds and premature introduction of complementary feeds are of great concern in this urban population. There is a need for promotion of good breast-feeding practices among expectant mothers and also the community, especially the families, taking into account the local traditions and customs.

Pattern of cardiac diseases in children in Pokhara, Nepal.

OBJECTIVE: The objective of the study was to point out the relative public health problems of cardiac diseases in childhood. MATERIAL AND METHODS: A study of the cardiac diseases in children attending the Paediatric OPD of Manipal Teaching Hospital, Pokhara, Nepal was done over a period of 2 years. The idea was to see the pattern of diseases, as being a developing country, these diseases would be a large public health problem. 107 cases had been studied and it was found that 52% were congenital heart diseases and 25% were rheumatic heart diseases. Other cases included dilated cardiomyopathy, Pericardial diseases and a few cases of hypertension. All the cases were investigated by ECG, X-ray and echocardiographic studies. These cases are under follow up and some have undergone surgical treatment. RESULTS: In this study in a short period of 2 years we had 107 cases of heart diseases of which 51% were CHD, 25% RHD and others were pericardial disease, DCM, hypertension and some had no demonstrable lesions. All the cases of RHD are being followed by regular Penicillin prophylaxis. Among them one has had mitral valve replacement done and 2 had mitral valvotomy. Of the CHD cases 5 cases have had VSD operated upon, one PDA also had surgery and one case of Fallot's is shortly going to undergo corrective surgery. CONCLUSION: Heart disease in neonates could be benign or very significant and a high level of suspicion and knowledge of physiology will differentiate between the two. Early recognition of CHD will help to treat the child and if possible get corrective surgery done. Similarly a history of rheumatic fever is important and all children need to be followed up till at least 18 years of age.

Meckel-Gruber syndrome.

Meckel- Gruber syndrome is a rare lethal, autosomal disorder. It has been linked to chromosome 17. It consists of a triad of occipital meningoencephalocoele, large polycystic kidneys and post-axial polydactyly. Death is mainly due to pulmonary hypoplasia. We report this rare case which presented with many associated defects.

Rh iso-immunisation with syndrome of hepatocellular damage. An unusual presentation with review of literature.

Rh iso-immunisation is prevalent in many underdeveloped countries. Severe haemolytic anaemia with or without hydrops fetalis, dangerous level of haemolytic unconjugated bilirubin and imminent bilirubin encephalopathy are the hallmarks of haemolytic disease of the newborn. The investigative protocols and efficient management of this entity are adequately described in literature. An unusual manifestation of this disease with severe hepatocellular damage and conjugated hyperbilirubinemia was noticed in a neonate. The literature has been reviewed and the specific symptom complex has been attributed to 'syndrome of hepatocellular damage', which is a rare accompaniment of haemolytic disease of the newborn. Attempts have been made to describe the syndrome in detail, with latest reference regarding complete workup and management. Few useful tips for prevention of the disease in a community background have been suggested.

Effect of mutating the regulatory phosphoserine and conserved threonine on the activity of the expressed catalytic domain of Acanthamoeba myosin I heavy chain kinase.

Phosphorylation of Ser-627 is both necessary and sufficient for full activity of the expressed 35-kDa catalytic domain of myosin I heavy chain kinase (MIHCK). Ser-627 lies in the variable loop between highly conserved residues DFG and APE at a position at which a phosphorylated Ser/Thr also occurs in many other Ser/Thr protein kinases. The variable loop of MIHCK contains two other hydroxyamino acids: Thr-631, which is conserved in almost all Ser/Thr kinases, and Thr-632, which is not conserved. We determined the effects on the kinase activity of the expressed catalytic domain of mutating Ser-627, Thr-631, and Thr-632 individually to Ala, Asp, and Glu. The S627A mutant was substantially less active than wild type (wt), with a lower kcat and higher Km for both peptide substrate and ATP, but was more active than unphosphorylated wt. The S627D and S627E mutants were also less active than phosphorylated wt, i.e., acidic amino acids cannot substitute for phospho-Ser-627. The activity of the T631A mutant was as low as that of the S627A mutant, whereas the T632A mutant was as active as phosphorylated wt, indicating that highly conserved Thr-631, although not phosphorylated, is essential for catalytic activity. Asp and Glu substitutions for Thr-631 and Thr-632 were inhibitory to various degrees. Molecular modeling indicated that Thr-631 can hydrogen bond with conserved residue Asp-591 in the catalytic loop and that similar interactions are possible for other kinases whose activities also are regulated by phosphorylation in the variable loop. Thus, this conserved Thr residue may be essential for the activities of other Ser/Thr protein kinases as well as for the activity of MIHCK.

Aberrant O-glycosylation in the collagenous domain of pro alpha2(I) procollagen subunits synthesized by chemically transformed hamster fibroblasts.

Chemically transformed Syrian hamster embryo fibroblasts (NQT-SHE) do not synthesize the pro alpha1(I) subunit of type I collagen, but they secrete two forms of the pro alpha2(I) subunit (N33 and N50) with abnormal post-translational modifications localized in the alpha2CB3,5 cyanogen bromide peptide of the collagenous domain (B. Peterkofsky and W. Prather (1992) J. Biol. Chem. 267 5388-5395). Isoelectric focusing and treatment of the modified chains with glycosidases and biotinylated Jacalin lectin identified the modifications as Gal beta1,3-GalNAc-O-Ser/Thr with or without a terminal sialic acid in an alpha2,6 linkage. Unhydroxylated N33 alpha-chains also reacted with Jacalin, confirming that the abnormal modification was O-glycosylation and not hyperhydroxylation of proline or lysine. Cells were treated with benzyl GalNAc, a competitive inhibitor of galactosyl transferase that prevents addition of Gal to GalNAc-O-Ser/Thr and thus blocks elongation of O-glycosyl chains. Treated cells secreted pro alpha2(I) chains containing GalNAc-O-Ser/Thr but no galactose or sialic acid, which suggested that Gal addition takes place before sialylation. Treatment of NQT-SHE cells with monensin and brefeldin A inhibited secretion and led to intracellular accumulation of pro alpha2(I) chains that contained only GalNAc. Therefore, it appears that GalNAc addition to pro alpha2(I) chains in NQT-SHE cells occurs in the cis-Golgi, while sialic acid and galactose are added in the trans-Golgi network. The pro alpha2(I) chains produced by NQT-SHE cells most likely are modified because they are in the denatured state, and thus potential O-glycosylation sites become available that would not be exposed in normal triple helical procollagen.

Purification of bovine lysosomal alpha-mannosidase, characterization of its gene and determination of two mutations that cause alpha-mannosidosis.

Bovine kidney lysosomal alpha-mannosidase was purified to homogeneity and the gene was cloned. The gene was organized in 24 exons that spanned 16 kb and its corresponding cDNA contained an open reading frame of 2997 bp beginning from a putative ATG start codon. The deduced amino acid sequence contained a signal peptide of 50 amino acids adjacent to a protein sequence of 949 amino acids that was cleaved into five peptides in the mature enzyme; starting with the peptide derived from the N-terminal part of this precursor, their molecular masses were 35/38 (peptide a), 11/13 (peptide b), 22 (peptide c), 38 (peptide d) and 13/15 kDa (peptide e). Variation in the degree of N-glycosylation accounts for molecular mass heterogeneities of peptides a, b and e. Peptides a, b and c were disulphide-linked. A T961-->C transition, resulting in Phe321-->Leu substitution, was identified in the cDNA of alpha-mannosidosis-affected Angus cattle. In affected Galloway cattle, a G662-->A transition that causes Arg221-->His substitution was identified. Phe321 and Arg221 are conserved among the alpha-mannosidase class-2 family, indicating that the substitutions resulted from disease-causing mutations in these breeds.

alpha-Mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings.

a-Mannosidosis (MIM 248500) is an autosomal recessive lysosomal storage disorder resulting from deficient activity of lysosomal alpha-mannosidase (LAMAN) (EC 3.2.1.24). The disease is characterized by massive intracellular accumulation of mannose-rich oligosaccharides with resulting mental retardation, hearing loss, immune deficiency and skeletal changes. We report here the purification and characterization of human placenta LAMAN. The enzyme is synthesized as a single-chain precursor which is processed into three glycopeptides of 70, 42 and 15 kDa. The 70 kDa peptide is further partially proteolysed into three more peptides that are joined by disulfide bridges. The laman cDNA sequence was assembled from overlapping fragments obtained by PCR on human fibroblast and human lung cDNA. The deduced amino acid sequence contains a putative signal peptide of 48 amino acids followed by a polypeptide sequence of 962 amino acids. Northern blot analyses revealed a single transcript of approximately 3.5 kb present in all tissues examined but at varying levels. Two affected siblings of Palestinian origin were homozygous for a mutation that causes a His-->Leu replacement at a position which is conserved among class 2 alpha-mannosidases from several species.

New experimental model for the evaluation of adaptogenic products.

A new animal model for evaluating improvement in physical work performance and endurance in an adverse environment is described. In this model, rats in restraint were exposed to 5 degrees C at 480 mmHg atmospheric pressure. Results were compared to an animal forced to swim in water at 23 degrees C. In both the models, colonic temperature (Tr) of the rats was continually monitored during exposure to adverse environment and during recovery at 32 degrees C and normal atmospheric pressure. The time and pattern for Tr fall to 23 degrees C and its recovery to 37 degrees C were used as measures of endurance. The cold-hypoxia-restraint model was found to provide more precise results compared with the cold-swimming model. Panax ginseng root and Ginkgo biloba leaf extracts were compared for their positive endurance-promoting properties using both models.