Homocysteine Metabolism and Hematological Parameters in Early Stage of Phenytoin Treated Epileptic Children.

BACKGROUND: Long-term antiepileptic drug (AED) therapy has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. Earlier published studies showed conflicting results about the levels of hematological parameters, serum homocysteine, folate, and vitamin B12, in epileptics treated with phenytoin monotherapy. Therefore, we evaluated homocysteine metabolism and hematological parameters in early stage of phenytoin treated epileptic children. METHODS: A total of 64 newly diagnosed epileptic children with mean age 10.09 ± 2.56 years were enrolled at the start of study. However, after 3 months follow up, the final total sample size was only 50 epileptic children. Fourteen children dropped out of study due to poor follow up. Serum homocysteine levels were measured by enzyme immunoassay method. Serum folate and vitamin B12 levels were estimated by Competitive Chemiluminescent Enzyme Immunoassay method. Hematological parameters were analysed by an automated hematology analyzer (Cell counter), Sysmex XT-1800i, using commercially available reagents. RESULTS: In our study the anthropometric and hematological parameters did not show any significant difference after phenytoin monotherapy as compared to before therapy in epileptic children. The serum homocysteine level in epileptic children was found to be significantly increased after phenytoin (PHT) monotherapy as compared to before therapy. Moreover, a highly significant decrease was observed in the serum folate and vitamin B12 levels after phenytoin monotherapy as compared to before therapy in epileptic children. CONCLUSIONS: Phenytoin monotherapy may cause a significant increase in the levels of serum homocysteine and a significant decrease in the serum folate and vitamin B12 levels in children with epilepsy, and the significant changes in above mentioned parameters occur early in the course of treatment. This could be responsible for a higher prevalence of cardiovascular incidents in epileptic children taking phenytoin monotherapy. Therefore, it may be useful to do early screening and treatment of increased serum homocysteine levels in epileptic children under phenytoin monotherapy to prevent atherosclerosis and its complications. Hematological parameters should also be strictly monitored regularly in individuals administered with PHT monotherapy. If there are persistent alterations, the administration of the drugs should be discontinued.

Serum Homocysteine, Folate, and Vitamin B12 Levels in Carbamazepine Treated Epileptic Children.

BACKGROUND: Antiepileptic drugs (AEDs) have been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. Therefore, we evaluated whether differences exist in homocysteine, folate, and vitamin B12 levels in children receiving carbamazepine (CBZ) monotherapy. METHODS: A total of 58 newly diagnosed epileptic children with ages ranging from 2 to 15 years were enrolled at the start of study. However, after 3 months follow up, the final total sample size was only 50 epileptic children. Eight children dropped out of the study due to poor follow up. Serum homocysteine levels were measured by enzyme immunoassay method. Serum folate and vitamin B12 levels were estimated by Competitive Chemiluminescent Enzyme Immunoassay method. RESULTS: The serum homocysteine level in epileptic children was found to be significantly increased after carbamazepine (CBZ) monotherapy as compared to before therapy. Moreover, a highly significant decrease was observed in the serum folate and vitamin B12 levels, after carbamazepine monotherapy as compared to before therapy in epileptic children. CONCLUSIONS: Carbamazepine monotherapy may cause a significant increase in the levels of homocysteine and a significant decrease in the levels of serum folate and vitamin B12 in children with epilepsy, significant changes in above mentioned parameters occurring early in the course of treatment. The atherogenic effect of increased serum homocysteine level is well established, and patients under carbamazepine monotherapy should be monitored for possible atherogenic effects. Therefore, it may be useful to measure serum homocysteine, folate, and vitamin B12 concentrations routinely in children with epilepsy taking carbamazepine monotherapy and be treated when their levels are found to be disturbed.

Evaluate the Effect of Valproate Monotherapy on the Serum Homocysteine, Folate and Vitamin B12 Levels in Epileptic Children.

BACKGROUND: The data regarding Valproate and its influence on serum folate and homocysteine levels are conflicting. The aim of this study was to evaluate whether differences exist in homocysteine, folate, and vitamin B12 levels in children receiving Valproate. METHODS: A total of 55 newly diagnosed epileptic children with ages ranging from 2 to 15 years were enrolled at the start of study but after 3 months follow up, the total sample size finally was only 50 epileptic children. 5 children dropped out of study due to poor follow up. 50 age and gender matched healthy control subjects were also studied on enrollment at the start of study. Serum homocysteine levels were analyzed by enzyme immunoassay method using the kits provided by Axis-Shield Diagnostics Ltd (Dundee DD2 1XA, United Kingdom). Serum folate and serum vitamin B12 were estimated by Competitive Chemiluminescent Enzyme Immunoassay method. RESULTS: The serum homocysteine level in epileptic children was found to be significantly increased after Valproate monotherapy as compared to before therapy. Moreover, a highly significant decrease was observed in the levels of serum folate in epileptic children after Valproate monotherapy as compared to before therapy. But a non significant difference was observed in serum vitamin B12 levels in epileptic children before and after Valproate monotherapy. CONCLUSIONS: Thus, we conclude that there is a significant increase in the levels of homocysteine and a significant decrease in the concentration of serum folate while vitamin B12 decreases non-significantly after Valproate monotherapy. The atherogenic effect of increased serum homocysteine level is well established; the patients under Valproate monotherapy should be monitored for possible atherogenic effects. Considering the above observation and results of children undergoing Valproate monotherapy, these children should be screened for levels of serum homocysteine, folate, and vitamin B12 and treated when their levels are found to be disturbed.

Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

JUSTIFICATION: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders. PROCESS: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors. OBJECTIVES: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor. STATEMENT: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.

Asthma control test and peak expiratory flow rate: independent pediatric asthma management tools.

BACKGROUND: Management of asthma reflects the complexity of the pathogenesis. According to current National Heart Lung Blood Institute (NHLBI) guidelines, asthma control can be assessed using the validated asthma control test, measures of airway function, and overall assessment of risk and quality of life. We hypothesized that the asthma control test and measures of airway function are independent tools in asthma management. We also studied whether the presence of nasal symptoms is correlated to these measures. METHODS: Serial visits (n = 45) to a pediatric respiratory clinic in an underserved area of San Diego County with a predominantly Hispanic population were reviewed. Patients were included if they were able to perform airway function tests and had more than one provider visit. Patients with other major diseases were excluded. We determined whether uncontrolled asthmatics, defined as an Asthma Control test (ACT) score of 19 or less, had lower % predicted peak expiratory flow Measurements as a group compared to those with higher scores. In addition, the individual ACT and airway function results were analyzed. Patients with and without nasal symptoms at the time of presentation were sub-analyzed to determine differences in ACT and peak flow measurements. RESULTS: Based on n = 45 physician visits, the mean ACT score was 21 +/- 3.3 (range 12-25) and the mean peak expiratory flow rate (PEFR) was 87.4% +/- 11 (range 65-109%). Patients with ACT scores < or = to 19 or lower (< or = 90%) PEFRs were determined not to have more nasal symptoms. The measures of ACT and peak expiratory flow were independent and not correlated. CONCLUSIONS: Our study indicates that ACT and PEFR are distinct parameters used to manage patients in a pediatric outreach asthma clinic.

Cloning and characterization of a new intestinal inflammation-associated colonic epithelial Ste20-related protein kinase isoform.

Intestinal epithelial cells respond to inflammatory extracellular stimuli by activating mitogen activated protein kinase (MAPK) signaling, which mediates numerous pathophysiological effects, including intestinal inflammation. Here, we show that a novel isoform of SPS1-related proline alanine-rich kinase (SPAK/STE20) is involved in this inflammatory signaling cascade. We cloned and characterized a SPAK isoform from inflamed colon tissue, and found that this SPAK isoform lacked the characteristic PAPA box and alphaF loop found in SPAK. Based on genomic sequence analysis the lack of PAPA box and alphaF loop in colonic SPAK isoform was the result of specific splicing that affect exon 1 and exon 7 of the SPAK gene. The SPAK isoform was found in inflamed and non-inflamed colon tissues as well as Caco2-BBE cells, but not in other tissues, such as liver, spleen, brain, prostate and kidney. In vitro analyses demonstrated that the SPAK isoform possessed serine/threonine kinase activity, which could be abolished by a substitution of isoleucine for the lysine at position 34 in the ATP-binding site of the catalytic domain. Treatment of Caco2-BBE cells with the pro-inflammatory cytokine, interferon gamma, induced expression of the SPAK isoform. Over-expression of the SPAK isoform in Caco2-BBE cells led to nuclear translocation of an N-terminal fragment of the SPAK isoform, as well as activation of p38 MAP kinase signaling cascades and increased intestinal barrier permeability. These findings collectively suggest that pro-inflammatory cytokine signaling may induce expression of this novel SPAK isoform in intestinal epithelia, triggering the signaling cascades that govern intestinal inflammation.

Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediated by reciprocal secretion of adenosine and IL-6.

Adenosine is formed in the intestinal lumen during active inflammation from neutrophil-derived 5' AMP. Using intestinal epithelial cell line T84, we studied the effect of adenosine on the secretion of IL-6, a proinflammatory cytokine involved in neutrophil degranulation and lymphocyte differentiation. Stimulation of T84 monolayers with either apical or basolateral adenosine induces A2b receptor-mediated increase in IL-6 secretion, which is polarized to the apical (luminal) compartment. In addition, Salmonella typhimurium, TNF-alpha, and forskolin, known inducers of IL-6 secretion in intestinal epithelial cells, also stimulate IL-6 secretion into the apical compartment. We show that IL6 promoter induction by adenosine occurs through cAMP-mediated activation of nuclear cAMP-responsive element-binding protein (CREB). We also show that IL-6 released in the luminal (apical) compartment achieves a sufficient concentration to activate neutrophils (from which the adenosine signal originates), since such IL-6 is found to induce an intracellular [Ca(++)] flux in neutrophils. We conclude that adenosine released in the intestinal lumen during active inflammation may induce IL-6 secretion, which is mediated by cAMP/CREB activation and occurs in an apically polarized fashion. This would allow sequential activation of neutrophil degranulation in the lumen -- a flow of events that would, in an epithelium-dependent fashion, enhance microbicidal activity of neutrophils as they arrive in the intestinal lumen.

Goniometric Assessment of Muscle Tone of Preterm Infants and Impact of Gestational Age on Its Maturation in Indian Setting.

CONTEXT: The normative data on muscle tone of preterm infants by goniometric assessment in Indian setting are scarce. AIM: The aim of this study it to provide a normative objective data of muscle tone of preterm infants by gestation using goniometer. SETTINGS AND DESIGN: This was a prospective, observational study including preterm infants admitted in a tertiary care hospital from North India. SUBJECTS AND METHODS: The objective dimension of muscle tone assessment of 204 healthy preterm infants was done; 61 infants completed follow-up till 40 weeks' postconceptional age (PCA) and were compared to term infants. STATISTICAL ANALYSIS USED: SPSS (version 16.0) was used. The intergroup comparison was done through ANOVA, and the localization of differences between the groups was determined through multiple comparisons by post hoc test. RESULTS: Mean gestational age was 34.3 ± 1.7 weeks. Angles were as follows: adductor = 100.1 ± 8.7, popliteal = 118.9 ± 8.6, dorsiflexion = 39.0 ± 9.0, heel to ear = 121.90 ± 7.90, wrist flexion = 46.0 ± 10.2, and arm recoil = 122.2° ± 16.6°. The evolution of muscle tone as indicated by heel-to-ear angle shows progressive maturation from 32 weeks' gestation while adductor angle, popliteal angle, and arm recoil mature predominantly after 36 weeks' gestation. Comparison of preterm infants to term at 40 weeks' PCA demonstrated significantly less tone in all except posture and heel to ear. CONCLUSIONS: Goniometric assessment provides a objective normative data of muscle tone for preterm infants. Maturation of heel to ear and posture evolves from 32 weeks onwards and are the earliest neurologic marker to mature in preterm infants independent of the gestational age at birth.

Joint Involvement in Children with Celiac Disease.

OBJECTIVE: To determine early joint involvement as detected by ultrasonography in children with newly diagnosed celiac disease, and in children with celiac disease on gluten-free diet for more than 6 months. METHODS: Cross-sectional comparative study evaluating joint abnormalities by ultrasonography. RESULTS: Ultrasonography showed abnormalities in 19 out of 60 (31.7%) children with newly diagnosed celiac disease as compared to 2 (3.3%) out of 60 in those on a gluten-free diet for more than 6 months. CONCLUSION: Subclinical synovitis as detected by ultrasound is a frequent finding in newly diagnosed children with celiac disease.

Glial cell line-derived neurotrophic factor-mediated enteric neuronal survival involves glycogen synthase kinase-3beta phosphorylation and coupling with 14-3-3.

Glial cell line-derived neurotrophic factor (GDNF) promotes the growth and survival of enteric neurons, but the mechanisms involved are poorly understood. GDNF is known to promote the survival of enteric neurons through activation of the PI3-Kinase/Akt signaling pathway. We investigated the role of glycogen synthase kinase-3beta (GSK-3beta) in enteric neuronal survival, and the ability of GDNF to regulate the activity of GSK-3beta using primary rat embryonic enteric neurons. GDNF, through activation of the PI3-kinase pathway enhanced the phosphorylation of GSK-3beta at its N-terminal serine-9 residue, and promoted the association of GSK-3beta with 14-3-3. Transfection of a constitutively active S9A-GSK-3beta mutant prevented the survival effects of GDNF, whereas a dominant negative GSK-3beta construct prevented GDNF withdrawal-induced cell death. Increased GSK-3beta activity was associated with an increase in tau phosphorylation. Thus, GDNF promotes enteric neuronal survival by modulating GSK-3beta and its downstream target tau. Inhibitors of GSK-3beta activity may have therapeutic potential in improving enteric neuronal survival.

Interleukin-12 enhances clinical experimental autoimmune myasthenia gravis in susceptible but not resistant mice.

Experimental autoimmune myasthenia gravis (EAMG) is induced by antibodies against the nicotinic acetylcholine receptor (AChR). Studies indicate a role for interferon-gamma (IFN-gamma) in EAMG. We examined the effect of IL-12, a major inducer of IFN-gamma production, on EAMG in C57BL/6 mice. Five doses of IL-12 accelerated and enhanced clinical disease in AChR-immunized mice. Control B6 mice, IFN-gamma gene-knockout mice, and EAMG-resistant bm12 mice showed no enhancement of disease. Shifting to a Th1-type antibody isotype distribution was insufficient to cause disease. Other factors, such as direct effects of Th1 cytokines on muscle tissue, may be involved in EAMG susceptibility.

Oprelvekin. Genetics Institute.

Genetics Institute has developed and launched oprelvekin (rhIL-11; Neumega), a recombinant form of human IL-11. In November 1997, the FDA cleared oprelvekin for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in susceptible patients with non-myeloid malignancies 12703021. The product was launched at the end of 1997 [312556]. By December 1999, phase III trials for Crohn's disease (CD) were underway [363007]. Genetics Institute had commenced a 150-patient phase II trial for mild-to-moderate CD and mucositis and the company planned to file regulatory procedures for the indication of CD in 1999 [271210]. An oral formulation for this indication has been developed. Oprelvekin is also undergoing phase I clinical trials for colitis [396157], phase II clinical trials for rheumatoid arthritis [413835] and clinical trials for psoriasis [299644]. In March 1997, Wyeth-Ayerst became the licensee for Europe, Africa, Latin America and Asia (with the exception of Japan). Genetics Institute holds marketing rights for North America [239273]. In Japan, oprelvekin is being developed by Genetics Institute and Yamanouchi; phase III trials have commenced [295049] and were ongoing in May 2001 [411763]. In April 1996, analysts at Yamaichi estimated launch in 2001 and maximum annual sales of over yen 10 billion [215896]. In January 1998, Morgan Stanley Dean Witter predicted Yamanouchi's share of sales to be yen 1 billion in 2001, rising to yen 2 billion in 2002 [315458]. Sales of oprelvekin were US $34 million for Genetics institute in fiscal 2000 while, in July 2001, Credit Suisse First Boston estimated that this figure will be US $30 million and US $34 million in 2001 and 2002, respectively [416883].

Alicaforsen. Isis Pharmaceuticals.

Alicaforsen (ISIS-2302) is an RNase H-dependent antisense inhibitor of the intercellular adhesion molecule ICAM-1 under development by Isis Pharmaceuticals, for the potential treatment of a variety of inflammatory disorders [175741]. As of April 1997 it was in phase III trials for Crohn's disease (CD); however, the trial failed and, in December 1999, the company suspended development for this indication [352801]. In October 2000, the company re-initiated development in CD [384820] and new phase III trials had begin by May 2001 [409704]. In August 2000, phase II studies of alicaforsen in an enema formulation for ulcerative colitis and a topical formulation for psoriasis were ongoing [378715]. Development of the compound for the potential treatment of rheumatoid arthritis (RA) was discontinued in 1999 [347579]. By the end of 1998, alicaforsen was in phase II trials for kidney transplant rejection. At this time, these trials were expected to finish in mid-1999 [343460]. However, they were ongoing in September 1999, although no further development has been reported for this indication since that time [338672]. In February 1995, Isis Pharmaceuticals and Boehringer Ingelheim (BI) signed a collaborative agreement on cell adhesion inhibitors, including alicaforsen [174111]. By early 1999, Isis and BI were to decide on the next developmental step for alicaforsen following further analyses of its performance against CD [292915], [315439]. Their joint development agreement was terminated in 1999; Isis regained rights to the product and by September 1999 was in talks to license alicaforsen to another partner for CD [338672]. In June 2000, Cytogenix entered into a sponsored research agreement with Baylor College of Medicine at the Texas Medical Center Houston for the use of its ssDNA expression system for the development of antisense strategies directed against intercellular adhesion molecules for the purpose of reducing lung inflammation and injury in disease states and conditions [369677]. US-05514788, and other patents, cover antisense cell adhesion molecule inhibitors [212289], [234792].

Peak expiratory flow rate of carpet weaving children.

OBJECTIVE: To assess the adverse influence of carpet weaving on lung functions and the nurtritional status of children employed in such factories. DESIGN: Comparison of the peak expiratory flow rate (PEFR) of the study group with controls of similar socio-economic status and correlate it with anthropometric values. SETTING: Field study. SUBJECTS: One hundred and ten boys, 6-15 years of age engaged in 23 carpet weaving factories of Jaipur city. OUTCOME MEASURES: Linear regression analysis using age, height and weight as independent variables and PEFR as the dependent variable. RESULTS: PEFR of carpet weaving children were significantly lower (p < 0.05) than controls for all except 6-7 years group. The height, weight and chest circumference of these children were also lower (p < 0.05). PEFR did not show significant difference when children were grouped according to their height. CONCLUSIONS: Children working in carpet weaving factories are shorter and lighter compared to normal school going children. As a consequence of the growth retardation, their PEFR values were also lower as compared to normal children.

Health status of carpet weaving children.

A cross-sectional study was undertaken to determine the health status of children engaged in carpet weaving factories of Jaipur City. Two hundred and ninety school going boys of similar socio-economic status served as controls. A higher prevalence of signs of nutritional deficiencies was observed in carpet weaving children. Analysis of the presenting complaints and the illness suffered in the past six months also revealed a significantly higher morbidity in these children. A statistically significant difference was also observed in anthropometric measurements of the two groups.

PIP: In India, 110 boys, 6-13 years old, working in 23 carpet-weaving factories within a 2 km perimeter of the walls around Jaipur in Rajasthan were compared with 290 age- and neighborhood-matched male students (controls) to determine the health and nutritional status of the child laborers. The cases had worked nonstop for most days of the month for the past 6 months. They had been employed, on average, for 3.4 years (range, 0.5-6.5). They worked 10-14 hours/day and were allowed at least one short tea break. Common working conditions included overcrowding (20/23 factories), improper ventilation, and poor lighting (particularly in basement factories). The boys either squatted or crouched for long hours. Good personal hygiene was more common among the students than the weavers (94.8% vs. 76.4%). In all age groups except the 6-7 year and 7-8 year groups, the students had greater weight and height than the weavers (p 0.05) (e.g., 13-14 years, height = 146.9 vs. 139.9 cm; weight = 32.5 vs. 28.9 kg). They even had a bigger chest circumference (p 0.05) (e.g., 13-14 years, 62.3 vs. 58.8 cm). The weavers were more likely than the students to suffer from headaches (34.2% vs. 15.9%; p 0.001), backache (18.2% vs. 5.9%; p 0.001), lower limb pains (15.5% vs. 5.2%; p 0.001), and acute respiratory infections (26.4% vs. 15.2%; p 0.005). They were also more likely to have signs of nutritional deficiency (conjunctival pallor; angular stomatitis; Bitot's spots; lusterless hair; Koilonychia nails; and spongy gums). The controls were more likely to be immunized than the cases. These findings reveal that carpet weaving takes a heavy toll on the health status of the child laborers. They need frequent medical care.

Colonic motor dysfunction in human diabetes is associated with enteric neuronal loss and increased oxidative stress.

BACKGROUND: Gastrointestinal dysfunction is very common in diabetic patients. We assessed the changes in the colonic enteric nervous system using colectomy specimens and intestinal biopsies from diabetic subjects and age-matched controls. METHODS: In control and diabetic colons, we determined the total ganglion area (hematoxylin-eosin staining), changes in neuronal markers-protein gene product 9.5, peripherin, neuronal nitric oxide synthase (nNOS), neuropeptide Y (NPY), choline acetyl transferase (ChAT) and vasoactive intestinal peptide (by immunostaining), apoptosis (cleaved caspase-3 staining) and reduced glutathione levels. Superoxide dismutase mRNA was determined in enteric ganglia isolated by laser capture micro dissection. Isometric muscle recording was used to assess contraction and relaxation responses of colonic circular muscle strips. Apoptosis in enteric neurons under hyperglycemia in vitro was determined by cleaved caspase-3 Western blotting and protective effects of lipoic acid were evaluated. KEY RESULTS: Diabetic subjects had higher incidence of lower gastrointestinal symptoms like constipation and diarrhea at baseline prior to surgery. Diabetic ganglia displayed significant decrease in ganglion size due to enhanced apoptosis and loss of peripherin, nNOS, NPY, and ChAT neurons. Reduced glutathione levels in the diabetic colon (HbA1C > 7%) were significantly less than the control, indicating increased oxidative stress. Colonic circular muscle strips from diabetic subjects showed impaired contraction and relaxation responses compared with the healthy controls. Hyperglycemia-induced cleaved caspase-3 in enteric neurons was reversed by lipoic acid. CONCLUSIONS & INFERENCES: Our data demonstrate loss of enteric neurons in the colon due to increased oxidative stress and apoptosis which may cause the motility disturbances seen in human diabetes. Antioxidants may be of therapeutic value for preventing motility disorders in diabetes.

Hutchinson-Gilford progeria syndrome.

Progeria is a rare genetic disorder characterized by premature aging, involving the skin, bones, heart, and blood vessels. We report a 4-year-old boy who presented with clinical manifestations of progeria. He had characteristic facies, prominent eyes, scalp and leg veins, senile look, loss of scalp hair, eyebrows and eyelashes, stunted growth, and sclerodermatous changes. The present case is reported due to its rarity.