Etiology of short stature in Northern India / Journal of the ASEAN Federation of Endocrine Societies

Objective@#Short stature can be caused by a great variety of congenital and acquired conditions, some of which present with additional symptoms and signs. Overall, the number of patients seeking medical attention for short stature may be considered as the tip of the iceberg. The objective of this study was to determine the pattern and etiological factors of short stature in children. @*Methodology@#A cross-sectional study was carried out in the Department of Endocrinology at a tertiary care health center in north India from August 2012 to June 2015. Four hundred and fifty one children (280 boys and 171 girls), ranging from 4 to 18 years presenting with short stature were studied. Anthropometric measurements were plotted on Indian standard growth charts. @*Results@#In this study, the male to female ratio was found to be 1.6:1, with mean chronological age of 11.6+3.2 years, and mean bone age of 7.8+2.8 years. The common etiologic factors in the order of frequency were constitutional delay in growth and puberty (41.2%), familial short stature (15.9%), type 1 diabetes mellitus (9.9%), and hypothyroidism (8.6%) while growth hormone deficiency (2.4%) was a relatively uncommon cause. The most common pathological cause for proportionate short stature was type 1 diabetes and for disproportionate short stature was hypothyroidism. Hypothyroidism caused the maximum retardation of bone age while the least bone age retardation was noticed in familial short stature. @*Conclusion@#Physiological/normal variants outnumbered the pathological causes of short stature. Endocrinological causes were found in almost one fourth of children with short stature; however, growth hormone deficiency was found in only 2.4% of the children.

Lentivirus mediated RNAi silence esophageal MDC1 Eca109 cell gene expression of the influence of nude mouse transplantation tumor radiosensitivity / 中华放射肿瘤学杂志

Objective To investigate the effects of inhibition of MDC1 protein expression on xenografted tumors in nude mice,and to observe the histopathological and cellular changes in nude mice.Methods Three pairs of effective and control short hairpin RNA targeting MDC1 mRNA were designed and cloned into the pSIH1-H1-copGFP vector.Real-time PCR and Western blot were used to determine the mRNA and protein expression of MDC1.After selection by copGFP reporter gene,cells were divided into negative transfection group (ECA109-N) and MDC1 transfection group (ECA109-M).The transfected cells were injected into nude mice.The mice were divided into ECA109 group,ECA109-N group,and ECA109-M group.Each group was divided into irradiation subgroup and non-irradiation subgroup.The changes in tumor size after irradiation were evaluated in each group.Western blot was used to measure the expression of CHK1,CHK2,and CHK2T68 in xenografted tumors.Flow cytometry was used to analyze the cell cycle distribution and apoptosis of tumor cells in nude mice.The variance analysis was used to compare the mean of multiple groups,and the SNK-q test was used in the two two groups.Results The pMDC1-shRNA plasmid was successfully constructed and used to transfect ECA109 cells.ECA109-M cells were obtained by stable transfection with the recombinant plasmid.All inoculated nude mice survived with visible xenografted tumors at the underside of the paw in about one week.There was no swelling and wound in inoculation sites.There was no significant difference in tumor size between different groups (P＞0.05).The tumor growth in the ECA109 group and the ECA109-N group significantly slowed down after irradiation with a dose of 15 Gy (P＜0.05).Compared with the other two groups,the ECA109-M group had a significant smaller tumor size,significantly slower relative tumor growth,and significantly higher growth inhibition (all P＜0.05).The q value of the ECA109-M group was 1.36.In the ECA109-M group,there were no significant changes in the protein expression of CHK1 and CHK2 after irradiation (P＞ 0.05);however,the phosphorylation of CHK2T68 protein was significantly reduced after irradiation (P＜0.05).There were no significant differences in cell cycle distribution or the proportion of apoptotic cells in tumor tissue between the three groups (P＞0.05).Conclusions Inhibition of MDC1 protein expression by RNA interference can effectively inhibit the growth of xenografted tumors after irradiation in the nude mice by increasing their radiosensitivity.

Identification of a Novel De Novo Mutation of the TAZ Gene in a Korean Patient with Barth Syndrome

Barth syndrome (BTHS) is a rare genetic disorder characterized by various types of cardiomyopathy, neutropenia, failure to thrive, skeletal myopathy, and 3-methylglutaconic aciduria. BTHS is caused by loss-of-function mutations in the tafazzin (TAZ) gene located on chromosome Xq28, leading to cardiolipin deficiency. We report a 13-month-old boy with BTHS who had a novel de novo mutation in the TAZ gene. To the best of our knowledge, this is the first reported case of a BTHS patient with a de novo mutation in Korea. This report will contribute towards expanding the knowledge on the mutation spectrum of the TAZ gene in BTHS.

Failure to thrive in babies and toddlers

Failure to thrive in a child is defined as 'lack of expected normal physical growth' or 'failure to gain weight'. Diagnosis requires repeated growth measurements over time using local, age-appropriate growth centile charts. Premature babies with appropriate growth velocity and children with 'catch-down' growth, constitutional growth delay or familial short stature show normal growth variants, and usually do not require further evaluation. In Singapore, the most common cause of failure to thrive in children is malnutrition secondary to psychosocial and caregiver factors. 'Picky eating' is common in the local setting and best managed with an authoritative feeding style from caregivers. Other causes are malabsorption and existing congenital or chronic medical conditions. Child neglect or abuse should always be ruled out. Iron deficiency is the most common complication. The family doctor plays a pivotal role in early detection, timely treatment, appropriate referrals and close monitoring of 'catch-up' growth in these children.

Enfermedad periodontal durante el embarazo y asociación con el retardo de crecimiento intrauterino / Periodontal disease during pregnancy and association with the intrauterine growth delay

Objetivo. Determinar la asociación entre la enfermedad periodontal y el retardo de crecimiento intrauterino (RCIU) en madres gestantes del tercer trimestre de gestación. Material y métodos. El estudio fue de casos y controles. La muestra estuvo constituida por 60 gestantes del tercer trimestre, dividida en dos grupos: 30 casos y 30 controles del Hospital Provincial Docente Belén, Lambayeque Perú en los meses de noviembre 2011 a febrero 2012. Con historias clínicas completas,diagnóstico definitivo de RCIU determinado por el ginecólogo del servicio y su confirmación a través de la biometría fetal. El examen clínico se evaluó mediante los índices de Lõe y Sillnes modificado (gingivitis), índice periodontal de Ramfjord (periodontitis) e índice de higiene oral simplificado (grado de higiene). Los resultados fueron manejados en porcentajes, utilizando la prueba U de Mann Whitney para determinar su significancia y la prueba de Odds Ratio. Resultados. Para gingivitis y periodontitis se halló que existe diferencia estadísticamente significativa entre las gestantes con y sin RCIU, gingivitis (p = 0,001)y en periodontitis (p = 0,000) y el nivel de riesgo fue de OR: 5,57 (IC 95% 1,7 a 18,5), OR: 16,3 (IC 95% 4,5 a 58,8) respectivamente. En presencia del grado de higiene oral se halló que existe diferencia significativa (p = 0,000) con un OR: 0,165 (IC 95% 0,052 a 0,522). Conclusiones. Existe asociación entre enfermedad periodontal y retardo de crecimiento intrauterino en madres gestantes del tercer trimestre.

Objective. To determine the association between periodontal disease and intrauterine growth delay (IGD) in pregnant women during the third trimester. Material and methods. It was a case control study. The sample consisted of 60 pregnant women during the third quarter, divided in two groups: 30 cases and 30 controls of the Docente Belén Hospital, Lambayeque Peru, during the months of November 2011 to February 2012. With complete medical histories, definitive diagnosis of IGD determined by the gynecologist of service and confirmed through fetal biometry. Clinical examination was assessed using the Lõe index andmodified Sillnes (gingivitis), periodontal index of Ramfjord (periodontitis) and simplified oral hygiene index (degree of hygiene). The results were presented as percentages, using the U test of Mann - Whitney to determine their significance and odds ratio test. Results. Gingivitis and periodontitis showed statistically significant difference between pregnant women with and without IGD, gingivitis (p = 0.001) and periodontitis (p = 0.000) and the level of risk was OR 5.57 (CI 95 % 1.7 to 18.5), OR: 16.3 (IC95% 4.5 to 58.8) respectively. In the presence of the degree of oral hygiene was found that significant difference (p = 0.000) with an OR: 0.165 (95% CI 0.052 to 0.522). Conclusions. There is association between periodontal disease and intrauterine growth delay in pregnant women during the 3rd quarter.

Dose response of CpG ODN1826 and its combination effect with X-ray irradiation on Lewis lung cancer in mice / 中华放射医学与防护杂志

Objective To explore the combination effect of unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) 1826 and X-rays on Lewis lung cancer in mouse and the dose response of CpG ODN.Methods The tumor-bearing mouse model was established by injecting Lewis lung cancer cells into the right infra-axillary dermis of mouse.Sixty-four C57BL /6 J mice were evenly randomized into eight groups with 8 mice each:control group,IR group,CpG OND1826 0.15 mg group,CpG OND1826 0.3 mg group,CpG OND1826 0.45 mg group,CpG OND1826 0.15 mg + IR group,CpG OND1826 0.30 mg+ IR group,and CpG OND1826 0.45 mg + IR group.On the 1st,2nd,and 9th days,CpG ODN was injected into mouse.After 3 hours of injection,the mice were start to irradiate with X-rays once a day on the 2nd-6th days,and the total dose was 12.50 Gy.Tumor growth and TGD were measured,and the apoptosis of tumor cells were examined with TUNEL.Results The Lewis lung cancer-bearing model was successfully established in all mice.Under the treatments of CpG OND1826 and irradiation,the tumor volumes were smaller than that of control group,and the tumor volumes of CpG OND1826 0.45 mg+IR group was the smallest.TUNEL results revealed that the apoptosis rate were (2.40 ± 0.51 )％ in control group,(5.62 ±0.50)％ in IR,(7.13±0.83)％ in CpG OND1826 0.15 mg,(11.63±1.06)％ in CpG OND1826 0.3 mg,(19.13 ±0.83)％ in CpG OND1826 0.45 rag,( 12.88±0.83)％ in CpG OND1826 0.15 mg+ IR,(20.57±2.37)％ in CpG OND1826 0.3 mg+ IR,and (28.17 ±3.31)％ in CpG OND1826 0.45 mg + IR group,and thus the apoptosis rate of every therapy group was higher than that in control ( t=11.15,7.91,17.82,39.48,24.73,16.61 and 17.05,P＜0.05).The apoptosis rates of CpG ODN1826 plus X-ray irradiation group were significantly higher than those in IR alone ( t =13.78,15.08 and 17.47,P＜0.05 ) or CpG ODN group (t=18.53,9.66and7.51,P＜0.05).Conclusions CpG ODN1826 can dramatically increase the efficiency of radiotherapy by inhibiting tumor growth and promoting lumor apoptosis.

Estudo das medidas pôndero-estaturais em crianças adenotonsilectomizadas / Study of weight and height development in children after adenotonsillectomy

A observação clínica diária do retardo de crescimento pôndero-estatural em crianças portadoras de hipertrofia obstrutiva das tonsilas faríngeas e palatinas é prática rotineira na otorrinolaringologia pediátrica e a correção cirúrgica dessa condição, em tempo hábil, através da adenotonsilectomia permite a retomada desse crescimento ("catch up growth"). OBJETIVO: Investigar o real ganho pôndero-estatural presente nessa população quando tratadas cirurgicamente. MATERIAL E MÉTODO: Através de um estudo clínico prospectivo, acompanhou-se durante 6 (seis) meses dois grupos de crianças portadoras de hipertrofia tonsilar faringopalatina, sendo o grupo 1 submetido à intervenção cirúrgica e o grupo 2, não. Todos os pacientes passaram pela aferição das medidas antropométricas (peso e altura), incluindo seus percentis para idade, no início e ao fim dos 6 (seis) meses. RESULTADOS: Enquanto o grupo 1 aumentou sua média final de altura em relação à média inicial em 6,66cm, o grupo controle aumentou sua média em 1,9cm (p=0,0004). Em relação ao peso, o grupo 1 aumentou em média 2150g, sendo que o grupo 2 apresentou aumento médio de 690g (p=0,0010). CONCLUSÃO: As crianças submetidas à adenotonsilectomia adquirem um maior potencial de crescimento pôndero-estatural em relação às crianças que não foram tratadas cirurgicamente.

The daily clinical observation of weight-height growth delays in children with obstructive hypertrophy of the pharyngeal and palatine tonsils is a workaday practice in pediatric otorhinolaryngology, and the surgical correction of this condition, when properly done in time, through adenotonsillectomy, can lead to a "catch up growth". AIM: To investigate the real weight-height gain present in this population when they are surgically treated. MATERIALS AND METHODS: Through a clinical prospective study, two groups of children carrying pharyngopalatine hypertrophy were followed up: group 1 was submitted to surgical intervention, and group 2 was not. All patients underwent standardization of anthropometrical measurements (weight and height), including their age-related percentiles, in the beginning and at the end of 06 (six) months. RESULTS: While group 1 increased its height average in relation to the initial average in 6.66cm, the control group increased its average in 1.9cm (p=0.0004). In relation to weight, group 1 increased 2150g in average, while group 2 presented an average increase of 690g (p=0.0010). CONCLUSIONS: The children that underwent adenotonsillectomy acquired a higher weight-height growth potential in relation to those children who were not operated.

Clinical Manifestation of Children with Failure to Thrive / 대한소아소화기영양학회지

PURPOSE: This study was to investigate the clinical manifestations of FTT in children. METHODS: From March 1997 to July 1999, clinical observations were made on patients with FTT who had visited to Samsung Medical Center. Detailed histories and through physical examinations were taken, and when suspected organic FTT, basic laboratory studies were done. RESULTS: Upon the review of medical records, we investigated the clinical manifestations of 74 children, aged 1 month and 13 year 1 month. The causes of FTT were composed of either physiologic (47.8%) or pathologic (52.2%) ones. Among the physiologic FTT, were there familial short stature (FSS, 14.5%), intrauterine growth retardation (IUGR, 14.5%), constitutional growth delay (CGD, 11.6%), idiosyncrasy and prematurity. Among pathologic causes, neurologic disorders (20%) are the most common causes of FTT, and then follow by GI (13.4%), allergic and infectious disorders in decreasing order. The data showed that average caloric intake in patients with FTT was 76.2% of recommended amount. FTT patients with CGD, IUGR, and idiosyncrasy had tendency to take small foods. The FTT children with prematurity, IUGR and pathologic FTT, were short and thin for their ages. However FTT children with CGD and FSS had tendency to be thin with relatively normal heights for their ages, in comparison with those of the children with prematurity, IUGR and pathologic FTT. CONCLUSION: The diagnosis of FTT was easily obtained with simple and through medical history, physical examination, and minimal laboratory tests. In this study, organic FTT was more prevalent than physiologic one. This results indicate that early intervention is mandatory, because children may develop significant long-term sequelae from nutritional deficiency.

Effect of Tumor Hypoxia on Efficacy of Tirapazamine Combined with Fractionated Irradiation in Mouse Tumor / 대한방사선종양학회지

PURPOSE: Tumor hypoxia can be overcome with hypoxic cytotoxin. In mouse tumor, tirapazamine's efficacy of the potentiating radiation effect was tested by the tumor oxygenation status combined with hyperfactionated radiotherapy. MATERIALS AND METHODS: The control and hypoxic mouse tumors were established by inoculation of RIF-1 tumor cells into the normal or previously irradiated back and thigh of C3H mice. When the tumors reached a proper size, both the control and hypoxic tumors were given hyperfractionated treatments (8 fractions/4 days) with saline (0.02 ml/g), tirapazamin (0.08 mM/0.02 ml/kg), irradiation (2.5 Gy), irradiation combined with tirapazamine given 30 minutes prior to each irradiation. The response was evaluated by the growth delay assay by measuring tumor size from day 0 (12 hrs prior to the first fractionation) to the day when the volume had 4-fold increase or cross sectional area had 2-fold increase. RESULTS: Overall growth pattern showed that tirapazamine potentiated radiation effect in back and thigh tumors grew in the normal and preirradiated tumor bed. With growth delay assay using reference point of initial tumor volume or cross sectional area, tirapazamine potentiated radiation effect 1.9 times for the control and 2.4 times for the hypoxic tumors in back, and 1.85 times for the control and 1.6 times for the hypoxic tumors. With reference of 4-fold increase of the initial volume or 2-fold increase of the cross sectional area, tirapazamine potentiated radiation effect 1.48 times for the control and 2.02 times for the hypxic tumors in back, and 1.85 times for the control and 1.6 times for the hypoxic tumors. CONCLUSION: Present result indicated that radiation response of hypoxic tumors was potentiated by tirapazamine in the back or thigh tumors grew in the control or preirradiated tumor bed, and potentiation of the hypoxic tumors was equal to or greater than that of the control tumors in the back or thigh.

Anti-tumor Effect of Combined Betacarotene with X-irradiation in the Mouse Fibrosarcoma : Cytotoxicity and Tumor Growth Delay / 대한방사선종양학회지

PURPOSE: To investigate whether combined beta-carotene with X-irradiation has more enhanced radition response than X-irradiation or not, we performed a experiment about in vitro cytotoxicity of beta-carotene and/or X-irradiation in the fibrosarcoma cells, tumor growth delay of combined beta-caroten with/or X-irradiation in the mouse fibrosarcoma. MATERIALS AND METHODS: 2% emulsion of beta-carotene was serially diluted and used. X-irradiation was given by 6 MeV linear accelerator. The cytotoxicity of beta-carotene in vitro was evaluated from clonogenic assay. To compare the cytotoxicity between combined beta-carotene with X-irradiation and X-irradiation group, 2 mg/ml of beta-carotene was contacted to fibrosarcoma (FSaII) cells for 1 hour before X-irradiation. For the tumor growth delay, single 20 Gy was given to FSaII tumor bearing C3H/N mice whic was classified as beta-crotene with X-irradiation group (n=6) and X-irradiation alone group (n=5). 0.2 ml of 20 mg/kg of beta-carotene were i.p. injected to mice 30 minute before X-irradiation in the beta-crotene with X-irradiation group. The tumor growth delay defined as the time which reach to 1,000 mm3 of tumor volume. RESULT: (1) Cytotoxicity in vitro; 1) survival fraction at beta-carotene concentration of 0.002, 0.02, 0.2 and 2 mg/ml were 0.69+/-0.07, 0.59+/-0.08, 0.08+/-0.008 and 0.02+/-0.006, respectively. 2) each survival fraction at 2, 4, 6 and 8 Gy in the 2 mg/ml of beta-carotene + X-irradiation group were 0.13+/-0.05, 0.03+/-0.005, 0.01+/-0.002 and 0.009+/-0.0008, respectively. But each survival fraction at same irradiation dose in the X- irradiation group were 0.66+/-0.05, 0.40+/-0.04, 0.11+/-0.01 and 0.03+/-0.006, respectively( p0.05). CONCLUSION: The contact of beta-caroten to FSaII cells showed mild cytotoxicity which was increased according to concentration. The cytotoxicity of combined beta-carotene with X-irradiation more increased than that of X-irradiation, additionaly. And there was significant difference of cytotoxicity between two groups. But there were no significant difference of the growth delay of fibrosarcoma between two groups.

Enhancing effect of CpG on sensitivity of Lewis lung cancer to X-ray radiation in mice / 中国肿瘤生物治疗杂志

Objective: To explore the role of cytosine-phosphate-guanine oligodeoxynucleotide(CpG ODN)in enhan- cing the radiosensitivity to X-ray in mouse with Lewis lung cancer.Methods: The tumor-bearing mouse model was in- duced by injevting Lewis lung cancer cells into the right infra-axillary dermis.Thirty-two C57BL/6J mice were evenly ran- domized into 4 groups.Group A: the control group;Group B: the X-Ray radiation group;Group C: the CpG group; Group D: the CpG plus X-Ray radiation group.Group B was treated with X-Ray radiation only(3 Gy/F,on day 1,3,5, 8,10,and 12;the total dose was 18 Gy);group C was administered with CpG ODN 0.05 mg on day 1,3,5,8,10, and 12;group D was administered with CpG ODN 6h before X-ray radiation.The tumor growth and tumor growth delay (TGD)were observed in all groups.Meanwhile,the pathological change of the tumor tissue was observed with H-E staining method and the apoptosis of tumor cells were examined with the method of TUNEL.Results: The Lewis hmg cancer-bearing model was successfolly established in mice.The tumor volumes of the treatment groups were smaller than that in lhe control group(P

Antitumor effect of Ganoderma lucidum: Cytotoxicity and Tumor Growth Delay(1) / 대한치료방사선과학회지

PURPOSE: To investigate the effect of aqueous extract of Ganoderma lucidum(G.I.) on the survival of tumor cells in vitro and on the growth of tumors in vivo. MATERIALS AND METHODS: Dried G.I. was made into powder, extracted with distilled water, filtered and diluted from a maximum concentration of 100 mg/ml in sequence. The cytotoxicity of G.O. in vitro was evaluated from its ability to reduce the clonogenicity of SCK tumor cells. For the tumor growth delay study, about 2' 105 of SCK tumor cells were subcutaneously inoculated in the legs of A/J mice. The first experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G/I. From the first day after tumor inoculation for 10 days. The second experimental group of mice were injected i.p. with 0.2ml of 250 mg/kg of G.I. either once a day for 10 days or twice a day for 5 days beginning from the 7th day after tumor inoculation. RESULTS: 1. Cytotoxicity in vitro; survival fraction, as judged from the curve, at G.I. concentration of 0.5,1,5,10,25,50 and 100 mg/ml were 1.0, 0.74+/-0.03, 0.18+/-0.03, 0.15+/-0.02, 0.006+/-0.002, 0.015 and 0.0015, respectively. 2. Tumor growth delay in vivo; a) the time required for the mean tumor volume to grow to 1,000mm3 was 11 days in the control group and 14 days in the experimental group. b) the time required for tumor volume to increase 4 times was 11 days in the control group while it was 10.5 and 12 days in the groups injected with G.I. once a day and twice a day from the 7th day after tumor inoculation respectively. CONCLUSION: Aqueous extracts of G.I. showed a marked cytotoxicity on the SCK mammary cells in vitro. Tumor growth delay was statistically significant when G.I. injection was started soon after tumor inoculation, but it was not significant when injection was started after the tumors were firmly established.