Tres versiones del "Ogtt Squeezer", un programa para evaluar de un vistazo la información metabólica de la curva de tolerancia a la glucosa / Three versions of the "Ogtt Squeezer", a program to evaluate ataglance the metabolic information of the oral glucose tolerance test

El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.

Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.

The Value of Cardiotocography for Evaluation of Fetal Condition and Outcome in Women Presenting with Less Fetal Movement

Objective: In this study our main goal is to determine the valueof cardiotocography for evaluation of fetal condition andoutcome in women presenting with less fetal movement.Method: This cross-sectional study was done at Department ofObstetrics and Gynaecology, Bangabandhu Sheikh MujibMedical University (BSMMU), Dhaka between June 2015 -December 2016. Where women >34 weeks’ gestation withsingleton pregnancies presenting during the study period withmaternal perception of less fetal movement (LFM) in the outpatient Department of Obstetrics and Gynecology in BSMMU.Results: During the study, the mean age was found25.61±5.65 years varied from 19 to 38 years in normal CTGand 24.82±3.81 years varied from 19 to 38 years in abnormalCTG. Majority patients were primiparous in both groups (56.0%vs. 52.0%). More than half (52.0%) of the patients in normalCTG and a half (50.0%) in abnormal CTG patients were camefrom lower middle-income group family. Emergency caesareansection was 12.0% and 42.0% in normal and abnormal CTGrespectively. Emergency caesarean section was significantlyhigher in abnormal CTG. At 1-minute APGAR score £7 wasfound 94.0% babies in normal CTG and 78.0% in abnormalCTG. Needed resuscitation was 4.0% in normal CTG and22.0% in abnormal CTG. Admission to NICU 10.0% babies innormal CTG and 36.0% in abnormal CTG.Conclusions: Decelerations, tachycardia and non-reactive(absent of accelerations) were the more common types ofabnormal CTG. Emergency caesarean section, low APGARscore, needed resuscitation, admission to NICU and prolongedhospital stay were higher in abnormal CTG. CTG can becontinued as a good screening test of fetal surveillance but it isnot the sole criteria to influence the management of high-riskpregnancies.

Admission test cardiotocography in labour as a predictor of foetal outcome in high risk pregnancies

Background: Continuous fetal heart monitoring in all pregnant women in labour has gained prominence in obstetric practice in the recent years. The aim of this study was to emphasize on the role of admission cardiotocography (CTG) in labour as a predictor of foetal outcome in high risk pregnancies.Methods: This was a prospective observational study done on 340 high risk patients admitted in labour with a period of gestation of ≥37 weeks. An admission CTG which consists of a 20-minute recording of FHR and uterine contractions was taken and the foetal outcome was correlated with it. The non-parametric Chi-square test was used for statistical calculations and a p valve of <0.05 was considered to designate statistical significance.Results: The admission CTG was reactive in 69.4% of all patients, equivocal in 22.2% and pathological in 8.4% of the 340 recruited patients. A total of 37.5% of the patients were post-dated followed by 20.6% of pregnancy incuded hypertensive patients. The neonatal outcomes in terms of fetal distress, meconium stained liquor, NICU admission were considerably higher in pathological test. The specificity of the test was 53.3%, and the negative predictive was    86.49%.Conclusions: Admission CTG is a simple, useful screening test and serves as a non-invasive tool in forecasting the adverse foetal outcomes in high risk pregnancies.

Genotype-phenotype correlations in pediatric patients with myotonic dystrophy type 1 / 소아과

PURPOSE: Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. METHODS: We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats ( < 1,000 vs. ≥1,000). RESULTS: We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. CONCLUSION: Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.

Cortical Thickness and White Matter Integrity are Associated with CTG Expansion Size in Myotonic Dystrophy Type I

PURPOSE: Myotonic dystrophy type 1 (DM1) is characterized by progressive muscular weakness with symptoms caused by involvement of the brain. The aim of this study was to delineate global changes in cortical thickness and white matter integrity in patients with DM1, compared to age-matched healthy controls, and in brain areas highly correlated with CTG repeat size. MATERIALS AND METHODS: Cortical thickness and white matter integrity were compared in nine adult DM1 patients and age matched healthy controls using T1-weighted and diffusion tensor imaging. The patients' intelligence quotient (IQ) and CTG repeat size were measured in each individual. RESULTS: Cortical thickness was significantly reduced in the frontal, temporal, and occipital cortices, while tract-based spatial statistics showed decreased diffusion metrics in widespread areas, including the bilateral orbitofrontal, anterior frontal, insular, external capsule, and occipital cortices in DM1 patients, compared to controls. Additionally, thickness was negatively correlated with the number of CTG repeats in those areas. White matter integrity was negatively correlated with CTG repeats in the left entorhinal, anterior corona radiata, orbitofrontal, and lateral occipital areas. No statistically significant correlation was found between IQ scores and the size of CTG repeats. CONCLUSION: Our results suggest that DM1 is associated with wide distributions of network changes in both gray and white matter. Some of areas related to cognition showed significant correlations with CTG repeats.

Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians.

Background & objectives: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to β-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India. Methods: A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2. Results: The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups. Interpretation & conclusions: Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.

To compare intrapartum cardiotocographic (CTG) recording with conventional intermittent auscultation during labor.

Standard evaluation of fetal well-being during labor includes the periodic assessment of the fetal heart rate (FHR), its pattern and response to intrapartum stimuli and events. Effective methods of evaluation and meaningful interpretation of FHR data range from non-invasive techniques like Intermittent Auscultation, continuous electronic fetal heart rate (FHR) monitoring to invasive techniques of fetal blood gas analysis and fetal ECG.

Evaluation of Perinatal Outcome by Antenatal CTG and Umbilical Artery Doppler in Pre-eclamptic Mothers.

This was a well-controlled hospital-based longitudinal prospective randomized study with a sole focus on pre-eclampsia cases, where cardiotocography (CTG) and colored Doppler were the two special investigative tools applied to examine the perinatal outcome. The study concluded with a note that antenatal CTG is a useful objective test to know the intrauterine fetal status but it cannot forecast the fetal behavior during labor, neither does it provide a guide to optimize the timing of induction of labor (IOL) or termination by cesarean section. Color Doppler indices done after 34 weeks definitely give a qualitative assessment of fetoplacental perfusion but it cannot predict the said perfusion during labor - when there occurs a degree of compromise with the uterus contracting repetitively. Ultrasonography (USG) for fetal biometry and liquor volume is a good test to determine small for gestational age or intrauterine growth restriction (IUGR) as the case may be taking cognizance of other factors e.g., preeclampsia, fetal congenital anomaly, etc. Every mother with pre-eclampsia needs to be evaluated both clinically, biochemically and ultrasonologically. Understanding the limitation of antenatal CTG and color Doppler indices, these should be applied in a few selected cases e.g., increased fetal movement, IUGR, which is reassuring to both the patient and the doctor who can wait till a reasonable degree of fetal maturity occurs before one goes for IOL or a cesarean section. Patients with a suspicious CTG should undergo continuous CTG during labor - otherwise there is always a tendency to go for an early lower-segment cesarean section (LSCS). For a pre-eclamptic mother with a pathological CTG the decision is an elective LSCS; whereas, cases with pathological CTG but normal Doppler indices the judgment is too difficult. The answer then would lie on factors like whether the pre-eclampsia is controlled and whether the biochemical and hematological parameters are within normal limits. Of course thanks to the presence of a special newborn care unit (SNCU) nearby.

The Correlation Analysis between Short Term Variation and Basal Heart Rate and Short Time Monitoring Analysis / 中国医学物理学杂志

Objective: Fetal monitoring is extremely important in perinatal care. Analysis of cardiotocogragh(CTG) can suppose if the fetus is lack of oxygen, distressed, acidosis, etc. in order to take measures timely. Methods: We have designed Meticare analysis software package to analyze 867 pieces of CTG data, and researched the relationship between short term variation (STV) and basal heart rate(BHR) by statistics, and short time monitoring analysis based on STV. Results: The amplitude of fetal heart rate curve variation(long term variation) tended to decrease when BHR increasing, with the negative correlation and regression equation STV = 9.866-0.02×BHR. Positive correlation exists between 5 and 10 mimute-STV, with the regression equation STV_(10min)=2.861-0.596×STV_(5min).Conclusion: STV calculated by 5 minutes CTG data can forecast the one by 10 minutes data as a reference demanded by Dawes & Redman criterion. If fetal doppler contains STV analysis function, out-patient fetal heart auscultation will be more significant. After 30 weeks pregnancy, with the STV decreasing, fetal distress, asphyxia, low birth weight, and even mortality increasing. BHR increasing should cause attention that STV might decrease, when monitoring with no analysis functional devices or fetal dopplars.

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans / 대한진단검사의학회지

BACKGROUND: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant muscular dystrophy caused by expansion of cytosine-thymine-guanine (CTG) trinucleotide repeats in the myotonic dystrophy protein kinase (DMPK) gene. The clinical features of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations. The aim of this study was to characterize the molecular and clinical spectra of DM1 in Koreans. METHODS: The CTG repeats of 283 Korean individuals were tested by PCR fragment analysis and Southern blot. The following characteristics were assessed retrospectively: spectrum of CTG expansions, clinical findings, genotype-phenotype correlation, anticipation, and genetic instability. RESULTS: One-hundred twenty-four patients were confirmed as DM1 by molecular tests, and the CTG expansions ranged from 50 to 2,770 repeats (median 480 repeats). The most frequent clinical features were myotonia, muscular weakness, and family history. Patients with muscular weakness or dysfunction of the central nervous system harbored larger CTG expansions than those without each symptom (P<0.05). The age of onset was inversely correlated with the size of the CTG expansion (gamma=-0.422, P<0.001). The instability of CTG expansion representing as the maximum difference between sibships was observed from 50 to 700 repeats in nine families. Clinical anticipation and the increase in CTG repeat were significantly higher in maternally transmitted alleles (P=0.002). CONCLUSIONS: Molecular genetic tests are not only essential for diagnosis, but also helpful for suggesting the spectrum and relationship between genotype and phenotype in Korean DM1 patients.

A Case of Congenital Myotonic Dystrophy Diagnosed by Molecular Genetics

Congenital myotonic dystrophy is a progressive degenerative disease of the neuromuscular system, usually inherited in an autosomal dominant fashion. Affected infant presents with varying degrees of respiratory failure, often necessitating immediate and prolonged ventilatory assistance. An expression of a CTG (cystosine-thymine-guanine) repeat in the 3'-unsaturated region of a protein kinase gene contributes to the development of myotonic dystrophy. We experienced a case of congenital myotonic dystrophy in a male neonate with respiratory difficulty, hypotonia and difficulty in sucking and swallowing. His mother had mild manifestations of adult type myotonic dystrophy. PCR analysis revealed that CTG repeats in the myotonic dystrophy gene of the neonate and the mother were about 800 and 100 respectively.

A Case of Familial Spinocerebellar Ataxia Type 8

Spinocerebellar ataxia type 8 (SCA8), originally described in a family characterized by pure cerebellar ataxia, is caused by the expansion of combined CTA/CTG repeats on chromosome 13q21. We experienced a 26-year-old man who presented with a 10-years history of slowly progressive gait ataxia, dysarthria and blepharospasm. We performed genetic studies for SCA1, 2, 3, 6, 7 and 8, and detected CTA/CTG repeat expansion in the SCA8 gene. We now report the first Korean familial case of SCA8 confirmed by genetic study.

CAG Repeats of KCNN3 Gene in the Patients with Schizophrenia / 신경정신의학

OBJECTS:We investigated a possible association between the polymorphic trinucleotide repeat(TNR) expansion in neuronal potassium channel gene KCNN3 and schizophrenia. METHODS: CAG/CTG repeat distribution in KCNN3, CTG18.1 and ERDA1 was examined and the copy number of ligation product in repeat expansion detection(RED) was measured in Korean patients with schizophrenia(n=245) and ethnically matched healthy controls(n=116). RESULTS: Longer alleles in the KCNN3 gene were over-represented in patients. The frequency of alleles with CAG repeats longer than 19 copy in the KCNN3 gene was higher in the patients with schizophrenia as compared to controls(73.3% vs. 65.1%;p=0.029, Fisher's exact test). And this difference was more prominent in schizophrenic patients with familial background(p=0.03, Fisher's exact test). We found no difference in the frequency of longer alleles between negative and positive subtypes of schizophrenia. Ligation product size in RED and alleles with CAG repeat number in the CTG18.1 gene was not increased in the patients. The copy number of ligation product in RED was highly correlated with CAG/CTG copies of ERDA1 in the patient group(r=0.45, p<0.001) as well as in the control group(r=0.44, p<0.001). However, CAG repeat length in the KCNN3 gene was not correlated with ERDA1 score. CONCLUSIONS: Our results support the hypothesis that the longer allele of KCNN3 may be considered as a candidate gene for schizophrenia, especially in the case with familial background. And the RED assay results was affected by the CAG copy number of ERDA1.

Clinical Significance of CTG Repeat Expansion in Korean Myotonic Dystrophy Patients

BACKGROUND: Myotonic dystrophy is the most common type of muscular dystrophy affecting adults, associated with the expansion of triplet repeat DNA sequences. A hallmark of the inherited disease with trinucleotide repeat DNA expansion is the clinical and genetic anticipation. The copy numbers of the CTG repeat are known to be related to the severity and the onset age of clinical symptoms. METHODS: The copy numbers of the CTG repeats were determined using PCR amplification and Southern blotting. The clinical manisfestations of 34 patients from 14 families who had the CTG repeat expansion were evaluated based on the muscular disability rating scale and the electrophysiological study. RESULTS: There was a significant positive correlation between the clinical scores and the size of the amplification of trinucleotide repeat, and a negative correlation with the age of onset. In 9 patients with copy numbers of CTG repeats between 61 and 100, 8 cases were asymptomatic and myotonic discharges were not seen in 71% of patients. Larger expanded bands, earlier onset, and worse symptoms were evident with each successive generation. CONCLUSIONS: Molecular genetic analysis with CTG repeat expansion might be useful in the detection and the genetic counseling of myotonic dystrophy patients.

The CTG Repeat Polymorphisms of Myotonic Dystrophy (DM) Gene in Korean Population

Myotonic dystrophy(DM) is caused by the expansion of CTG trinucleotide repeat near the 3' end of the gene encoding for a member of protein kinase gene family (DMPK). The normal range of the CTG repeat was determined in 178 nomal individuals (141 unrelated individuals and 37 of 9 families) by polymerase chain reaction (PCR), polyacrylamide gel electrophoresis and silver staining method. And the expansion of the CTG repeats in a DM family was analyzed with Southern analysis. In normal population, the range of CTG repeat is between 5 and 34 and 19 different alleles were obserbed in that range, and (CTG)11-14 alleles were predominant. 4 members of an affected family showed the 0.5 - 2.0 kb size expansion of CTG repeats. In this study we could predict the incidence of DM in Korea as 1 in 20,000 and we could establish the diagnostic procedure for myotonic dystrophy.

Comparative analysis on CTG repeat numbers with BAEP,SEP and VEP in myotonic dystrophy / 临床神经病学杂志

Objective To study the relationship between the changes of cytosine,thymine,guanine(CTG)repeat numbers and brain stem BAEP,SEP and VEP in patients with myotonic dystrophy(DM) and their family members.Methods The repeat numbers of CTG,BAEP, SEP and VEP of DM gene were determined by PCR amplification and DNA hybridization in 5 patients with DM and 16 members from 3 families.Results The repeat numbers of CTG in 10 normal persons were 30,BAEP,SEP and VEP were normal.The repeat numbers of CTG in 5 patients with DM were over 85,two cases of them were over 1605,they were significantly higher than the normal persons.4 cases in 16 family members were normal,CTG repeat numbers of 12 cases were over normal genes,CTG repeat numbers were related to clinical symptom, BAEP,SEP and VEP.Conclusion The gene diagnosis of DM was found to be consistent with its clinical symptom,the changes of BAEP,SEP and VEP.