Novel measures of inflammation and insulin resistance are related to obesity and fitness in a diverse sample of 11-14 year olds: The HEALTHY Study.

BACKGROUND: GlycA is a novel serum marker of systemic inflammation. There is no information on GlycA in pediatric populations, how it differs by gender or its association with body mass index (BMI) or fitness. Lipoprotein insulin resistance index (LP-IR) is a serum measure of insulin resistance, which is related to changes in BMI group in adolescents, but its relationship with fitness is unknown. The current study examined the independent associations between fitness and BMI with GlycA and LP-IR among US adolescents. METHODS: Participants were 1664 US adolescents from the HEALTHY study with complete 6th and 8th grade BMI, fitness and blood data. GlycA and LP-IR were measured by nuclear magnetic resonance spectroscopy. Three BMI groups and three fitness groups were created. Linear mixed models examined associations between GlycA, LP-IR, fitness and BMI. RESULTS: LP-IR decreased between 6th and 8th grade. GlycA increased among girls but decreased among boys. At 8th grade, median GlycA values were 27 (7.6%) µmol l(-1) higher (381 versus 354) for girls than boys. Median GlycA 6th grade values were 9% higher in obese girls than healthy weight girls. Overall, there was strong evidence (P<0.001) that GlycA was higher in higher BMI groups. Fitness was negatively associated with GlycA (r=-0.37 and -0.35) and LP-IR (r=-0.34 and -0.18) at the 6th and 8th grade assessments. As BMI category increased and fitness category decreased, GlycA and LP-IR levels increased. Lowest GlycA was found in the low BMI/high fitness group. CONCLUSIONS: GlycA was associated with BMI and fitness among in US adolescents. These findings suggest that there are independent effects for BMI and fitness group with both GlycA and LP-IR. Future studies should validate the role of GlycA and LP-IR to evaluate the effects of interventions to modify obesity and fitness to improve systemic inflammation and insulin resistance.

Placental vascular endothelial growth factor expression in pregnancies complicated by type 1 diabetes.

UNLABELLED: Type 1 diabetes mellitus (T1DM) is still associated with increased risk of severe maternal and foetal complications but their pathomechanism remains unclear. OBJECTIVES: we investigated the possible role of placental vascular endothelial growth factor (VEGF) and VEGF single nucleotide polymorphisms (SNP) in foetal development in T1DM pregnancies. Sixty seven pregnant women with T1DM and singleton pregnancy were enrolled into the study. Results demonstrated higher expression of placental VEGF in women who delivered neonates with birth weight (NBW)>4000g. No such correlation was found in the overall T1DM group and in women who delivered appropriate for gestational age (AGA) and small for gestational age (SGA) newborns. We also demonstrated a significant correlation between 3(rd) trimester mean blood glucose, HbA1C and placental VEGF. No such correlation was found for the 1(st) and 2(nd) trimesters. Top placental VEGF expression and placental mass were found in women who delivered large for gestational age (LGA) newborns. We also found a statistically significant difference in homozygous and heterozygous frequency variants of VEGF SNPs in study groups. We conclude that the increased placental VEGF together with impaired metabolic control may have a role in stimulating foetal overgrowth in T1DM pregnancy.

Recruitment and retention strategies and methods in the HEALTHY study.

HEALTHY was a 3-year middle school-based primary prevention trial to reduce modifiable risk factors for type 2 diabetes in youth. The study was conducted at seven centers across the country. This paper describes the recruitment and retention activities employed in the study. Schools and students were the focus of recruitment and retention. Each center was responsible for the recruitment of six schools; eligibility was based on ability to enroll a sufficient number of predominately minority and lower socioeconomic status students. Study staff met with district superintendents and school principals to verify the eligibility of schools, and to ascertain how appropriate the school would be for conducting the trial. Sixth grade students were recruited employing a variety of techniques; students and their parents did not know whether their school was randomized to the intervention or control arm. This cohort was followed through sixth, seventh and eighth grades. In the eighth grade, an additional sample of students who were not originally enrolled in the study was recruited in a similar manner to participate in data collection to allow for cross-sectional and dose-response secondary analyses. Parents signed informed consent forms and children signed informed assent forms, as per the needs of the local Institutional Review Board. Parents received a letter describing the results of the health screening for their children after data collection in sixth and eighth grades. Retention of schools and students was critical for the success of the study and was encouraged through the use of financial incentives and other strategies. To a large extent, student withdrawal due to out-migration (transfer and geographical relocation) was beyond the ability of the study to control. A multi-level approach that proactively addressed school and parent concerns was crucial for the success of recruitment and retention in the HEALTHY study.

Social marketing-based communications to integrate and support the HEALTHY study intervention.

The HEALTHY study was a randomized, controlled, multicenter, middle school-based, multifaceted intervention designed to reduce risk factors for the development of type 2 diabetes. The study randomized 42 middle schools to intervention or control, and followed students from the sixth to the eighth grades. Participants were a racially, ethnically and geographically diverse cohort from across the United States. Here, we describe the conceptual underpinnings and design of the social marketing-based communications component of the HEALTHY study intervention that combined changes in the school nutrition and physical education (PE) environment with behavior change initiatives. The communications intervention component coordinated multiple elements to deliver campaigns that served to integrate and support all aspects of the HEALTHY intervention. The campaigns unfolded across five semesters of middle school, each targeting a specific theme related to the HEALTHY objectives. Communications campaigns comprised (1) core elements such as branding, posters, banners and visual and verbal messaging, (2) student events supporting the nutrition, PE and behavior intervention components through the application of social marketing and communications strategies, including the incorporation of student-generated media and (3) distribution of premiums and theme enhancers to extend the visibility of the study beyond the intervention environment. Formative research conducted with students, parents and school administrators was used to refine the communications strategy. Student peer communicators selected from the student body were involved to influence the normative student environment. Marketing and creative design experts developed a brand, logo, activities and materials. In the latter half of the study, student-generated messages and media were used to reflect local interests and culture and enhance peer influence. The HEALTHY intervention delivery and impact were strengthened by the communications strategies. The HEALTHY experience provides practical considerations for systematically incorporating a social marketing-based communications approach within future school-based health behavior interventions.

Leptin gene, leptin gene polymorphisms and body weight in pregnant women with diabetes mellitus type I.

UNLABELLED: There have been several genetic causes of obesity discussed by past authors, among others leptin, that have provided information regarding signaling pathways in energy expenditure in humans. Genetic variants of the leptin gene and its receptor may influence body weight. AIM: To investigate the role of the leptin gene's polymorphism promotion region (2548 G/A) and the leptin gene receptor polymorphism (668 A/G) and its associations with body weight in pregnant women with type 1 diabetes (PGDM-1). METHODS: 78 PGDM-1 were qualified to the study group (SG) which was divided into normal and over-weight individuals according to BMI criteria. The control group (CG) consisted of first trimester healthy pregnant women with normal body weight. Genetic variants of the leptin gene and its receptor were analyzed using PCR-RFLP assays. Within the SG, the following metabolic parameters were estimated: MBG, HbA1C, insulin dose, LDL, HDL, T-CHOL, creatinine, creatinine clearance and blood pressure. RESULTS: There was a trend found among the majority of homozygous A and G variants in LEP -2548 G/A and LEPR 668 A/G in over-weight and obese individuals in comparison to normal-weight subjects (CG). There were no specific differences found in selected first trimester metabolic parameters in relation to patients' genotypes.

The significance of C3435T point mutation of the MDR1 gene in endometrial cancer.

The P-glycoprotein (P-gp) plays an important role in carcinogen distribution and is connected with cell differentiation and apoptotic processes leading to carcinogenesis. Interindividual differences in P-gp activity could modulate susceptibility to cancer development. The MDR1 gene, coding for P-gp, is highly polymorphic and some mutations modulate P-gp activity. Recently, association between the MDR1 C3435T polymorphism and the cancer susceptibility was shown. We have hypothesized that MDR1 polymorphism could influence endometrial cancer susceptibility. We have matched 198 women with endometrial cancer and 198 controls. An additional group of 488 healthy volunteers was investigated. The MDR1 C3435T polymorphism was tested by LightCycler assay. The distribution of MDR1 3435 genotypes was significantly different between cases and controls (P = 0.006). Genotypes containing at least one 3435T allele were statistically significant more frequent in the endometrial cancer group (86.8% vs 75.2%, OR 2.18, P = 0.004). Our observation suggests that MDR1 C3435T polymorphism is correlated with endometrial cancer susceptibility.

Studies on leptin and leptin receptor gene expression in myometrium and uterine myomas of gnRH analogue-treated women.

AIM: To test if treatment with GnRH analogue, which leads to a significant reduction in myoma volume, changes expression of leptin genes and gene coding leptin receptor isoforms in uterine myomas and in the surrounding unaltered myometrium. METHODS: Using RT-PCR, expression of leptin genes and leptin receptor genes was studied in myomas and in the surrounding myometrium in women with uterine myomas, untreated or treated with GnRH analogue. In the randomly selected cases presence of leptin protein and of leptin receptor proteins was examined also by Western blotting. RESULTS: Expression of leptin genes was demonstrated both in myomas and in the surrounding myometrium, and a similar pattern of expression was found for leptin receptor isoforms. The results of RT-PCR were confirmed by Western blotting, which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues. Treatment with GnRH analogue had no effect on the expression pattern of studied genes. CONCLUSION: The results of the present study on the administration of GnRH analogue to females with myomas suggest that no direct or immediate inter-relationship exists between expression of leptin genes in uterine myomas on one hand and estrogen, progesterone and leptin levels in the blood on the other. Expression seems to be of a more durable nature but factors that induce such expression remain unknown.

Further studies on leptin and leptin receptor expression in myometrium and uterine myomas.

AIM: Examination of the potential role of leptin in the development of uterine myomas. Expression of the leptin gene and leptin receptor gene was tested in the myometrium of healthy women, and in myomas and the surrounding myometrium of women with benign tumors. METHODS: Using RT-PCR, expression of the leptin gene and leptin receptor gene were studied in myomas and in the surrounding myometrium in 30 women with uterine myomas at various phases of the menstrual cycle, and in the myometrium of ten women in a control group. Presence of leptin gene proteins and leptin receptor gene proteins in the women was also examined by Western blotting. RESULTS: Using RT-PCR, expression of the leptin gene was demonstrated both in myomas and in the surrounding myometrium. In contrast, expression of the gene could not be detected in the myometrium of healthy women. The results were confirmed by Western blotting, which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues. CONCLUSION: Demonstration of the expression of leptin genes and leptin proteins in uterine myomas and in the surrounding myometrium, and their absence in the myometrium of healthy women suggests the involvement of leptin in the development of uterine myomas.

Uncommon case of a foreign body ingestion with consecutive small-bowel obstruction in a child.

A 12-year-old boy with Lennox syndrome presented with an acute abdomen and a history of progressive abdominal pain and vomiting over 3 weeks. The uncommon finding in this case was a foreign body detected in a lower loop of the jejunum causing radiological and clinical signs of jejunitis/ileitis. The foreign body had to be removed surgically and turned out to be a hard (originally soft) plastic part of a towel rack.

The role of leptin in breast cancer.

Leptin, the protein hormone produced mainly by adipocytes, placenta and mammary epithelium plays a significant role in, e.g., control of metabolism, reproductive processes, immune processes, angiogenesis, haemopoiesis and oxidation of lipids. Since some authors link leptin to mechanisms of mammary cancer development, the clinical data has been screened to allow evaluation of the hypothesis.

Evaluation of soluble intracellular adhesion molecule-1 (sICAM-1) in benign and malignant ovarian masses.

PURPOSE: To evaluate serum ICAM-1 levels preoperatively in patients with ovarian masses. METHODS: Estimation by ELISA assay in 101 women with pelvic tumours and 16 healthy controls was performed. Correlations of sICAM-1 levels with CA-125, Tumour Volume Index, morphological score and pathological findings were studied. RESULTS: Fifty-one ovarian tumours were malignant, five were borderline and 45 benign. Mean levels of sICAM-1 were respectively, 311.1 +/- 182.9 ng/ml, 172.6 +/- 40.1 ng/ml, 241.8 +/- 74.1 ng/ml and 195.6 +/- 68.7 ng/ml for controls. The area under ROC curve for sICAM-1 was 0.72 (95% CI 0.58-0.82), the cut-off 250 ng/ml, corresponding to 81.3% sensitivity and 52.9% specificity. Serum ICAM-1 correlated with morphological score (r = 0.51, p < 0.001), but not with FIGO stage, tumour grade, Tumour Volume Index and CA-125. CONCLUSION: sICAM-1 concentrations are higher in patients with malignant tumours, but poorly correlate with clinical status. The clinical use alone in ovarian malignancy detection and tumour differentiation seems to have limited application. Combinations of CA-125 and sICAM-1 could improve the test characteristics.

[Polymorphism of gene angiotensin converting enzyme in pregnancy induced hypertension]. / Polimorfizm genu kodujacego konwertaze angiotensyny i w nadcisnieniu indukowanym ciaza.

In the recent years genetic background of pregnancy induced hypertension (PIH) are intensively investigated. Genetically determined differences in activity of renin-angiotensin system (RAS) are of importance to hypertension susceptibility. The insertion/deletion (I/D) polymorphism of angiotensin I converting enzyme (ACE) was suggested to play an important role in the aetiology of idiopathic hypertension. We have tested if this polymorphism could be associated with PIH. ACE polymorphism was investigated in 87 pregnant women with PIH and in 110 healthy pregnant women (control group). Investigation was performed by polymerase chain reaction (PCR). We have amplified genomic DNA excteracted by phenol-chloroform method from blood leucocytes. We have detected overrepresentation of the I allele in the PIH group (47.2% and 41.4% in PIH and controls, respectively). ACE genotype frequency in control group was in agreement with expected values, according to Hardy-Weinberg law, but in the PIH group the obtained values were different from expected. This observation confirmed the possible role of I allele in aetiology of PIH, and we believe that continuation of this investigation is necessary.

[Analysis of interleukin-6 serum concentration in trophoblastic tumors prognosis]. / Wartosc kliniczna analizy stezen interleukiny-6 u kobiet chorych na rozrosty i nowotwory trofoblastu.

OBJECTIVES: Our purpose was to estimate the prognosis based on Il-6 concentration in cases of trophoblastic tumors. MATERIALS AND METHODS: The study population was 65 women suffering from hydatiform mola or choriocarcinoma. We divided them into two groups: 30 patients who required only operative management and 35 patients who required operative procedures and additional chemotherapy. The observation period was 6 months. Blood samples were collected every 4 weeks. Concentration of Il-6 was measured in ELISA assay. RESULTS: The serum Il-6 concentration was significantly higher in cases of trophoblastic diseases than in the group of healthy women and higher in patients who required chemotherapy after operation (451.0 +/- 88.5 pg/ml), than in patients treated only surgically (257.1 +/- 77.1 pg/ml). CONCLUSIONS: Patients with hydatiform mola and choriocarcinoma reveal higher concentration of Il-6 than healthy women. It is associated with disease prognosis and allows to determine at the time of establishing a diagnosis, whether a patient can be treated only surgically or requires an additional chemotherapy.

[Chorion carcinoma: failure of treatment]. / Rak kosmówki--niepowodzenie leczenia.

Between 1986-1998 in University Oncology Gynecology Department in Poznan, Poland were treated 23 women with choriocarcinoma. Despite of intensive chemotherapy 3 women were dead. In the report we present the history of this choriocarcinomas making effect to answer why our therapy was ineffective.

[Gestational trophoblastic disease: the epidemiological analysis of 342 cases]. / Rozrosty i nowotwory trofoblastu--analiza epidemiologiczna 342 chorych.

Between 1987-1996 dates were collected to assess frequency and risk factors for gestational trophoblastic disease in a case-control study of 342 women with trophoblastic tumors and 342 pregnant women admitted for deliveries or spontaneous abortion to University Hospitals in Poznan, Poland. Were analyzed the age of women obstetric history, place of live and repeat appearance of hydatidiform mole. The risk of trophoblastic disease increased with increase in maternal age and above third pregnancy. The risk independent of living in town or in the country. The second and more incident of hydatidiform mole was associated with greater risk of malignant sequele. The study of the pregnancy of gestational trophoblastic disease was led in Great Poland in the support on the date from all pathologic centres in this region and public demographic office. The frequently of hydatidiform mole was between 1987-1996 2.32 per 100,000 women, and 0.76 for 1000 live birth (1 HM for 1315 live birth). The frequently of choriocarcinoma was 0.08 per 100,000 women (and 0.38 per 10,000 live birth (1 CHA per 26,315 live birth).

[Gestational hypertension (GH) and a1166c polymorphism of angiotensin II type 1 receptor]. / Nadcisnienie ciazowe (GH) a polimorfizm A1166C receptora typu 1 angiotensyny II (AT1).

INTRODUCTION: Recent studies have suggested an association between genetic background of renin-angiotensin system (RAS) and the pathogenesis of pregnancy induced hypertension (PIH). However, the role of the gene coding for angiotensin II receptor (AT1) polymorphism in PIH is not fully understood, thus the aim of the present study was to determine the frequency of A1166C mutation in women with gestational hypertension (GH) and to establish the role of this polymorphism on the susceptibility to the PIH development. PATIENTS & METHODS: We have analysed 88 women with PIH and 113 healthy pregnant women as a controls. Genomic DNA was extracted from leucocytes using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). RESULTS: We have detected overrepresentation of mutated homozygous genotypes in the PIH group (11.4% in the PIH versus 2.7% in the controls). Homozygous wild-type genotypes were underrepresented in the PIH group (48.9% in PIH and 56.6% in controls). The frequency of heterozygotes was similar in both groups. Statistically significant overrepresentation of allele with mutation in the PIH group (31.3% in the women with PIH, and 23.0% in the controls) (O.R. = 1.5, p = 0.04) was observed. CONCLUSION: We suggest that presence of A1166C mutation is a risk factor for the development of PIH.

[Glycoforms of alpha-1-acid glycoprotein in trophoblastic tumors prognosis]. / Znaczenie rokownicze glikoform alpha 1-kwasnej glikoproteiny w rozrostach i nowotworach trofoblastu.

OBJECTIVES: Our purpose was to define the pattern of AGP glycolysation and concentration in cases of trophoblastic tumors. MATERIALS AND METHODS: The study population was 65 women suffering from hydatiform mola or choriocarcinoma. We divided them into two groups: 30 patients who required only operative management and 35 patients who required operative procedures and additional chemiotherapy. The observation period was 6 months. Blood samples were collected every 4 weeks. Concentration of AGP was measured in radial immunodyfusion. Glycolysation pattern was defined in Concanavalin A crossed affinoimmunoelectroforetic analysis. RESULTS: The serum AGP concentration was significantly higher in patients treated only surgically (1026.1 +/- 241.0 mg/l) than in patients who required chemotherapy after operation (740.3 +/- 103.0 mg/l). AGP microheterogeneity was represented by 2 to 4 glycoforms. CONCLUSIONS: Patients with hydatiform molar and choriocarcinoma reveal characteristic changes in concentration and microheterogeneity of AGP, which are associated with disease prognosis. They allow to determine at the time of establishing a diagnosis, whether a patient can be treated only surgically or with additional chemotherapy.

Quantification of human polyomavirus JC in brain tissue and cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy by competitive PCR.

Activation of human polyomavirus JC (JCV) infection is the cause of the central nervous system (CNS) disease progressive multifocal leukoencephalopathy (PML). Previous studies with uncontrolled quantification systems suggested that the virus load in the CNS correlates with the state of disease and might reflect therapeutic effects. Therefore the aim of this study was the development of a competitive system with standard PCR techniques that allowed rapid detection of JCV subtypes, simultaneous differentiation of the two human polyomaviruses JCV and BKV and absolute quantification of the virus burden in initial diagnosis and progressive disease states. Subtype- and species-specificity of the PCR was achieved with the development of a degenerative PCR primer pair that detected JCV DNA in a range regularly found in PML samples, but did not amplify BKV DNA. The accuracy of the system was evaluated by quantification of known amounts of cloned JCV DNA with a competitive JCV-specific template that exhibited a comparable amplification rate to that of the native product. The calibration study demonstrated a linear correlation over a wide range of DNA concentrations on the background of buffer or JCV-negative diagnostic samples. The reliability of the system for PML diagnosis was analysed by calibration and determination of the virus burden in tissue and cerebrospinal fluid (CSF) of 11 PML patients confirming the accuracy in both types of samples under diagnostic conditions. Comparison of the JCV DNA concentration in tissue and CSF by a tightly controlled quantification technique revealed for the first time differences in a range of about four orders of magnitude and a variable virus load in CSF samples taken at comparable states of disease. This pointed to an individual course of virus shedding and demonstrates that a controlled competitive PCR system of high accuracy is essential for reliable quantification of virus DNA either in initial diagnosis, in progressive disease or for the evaluation of therapeutic effects.

[Cesarean section for the second twin during the course of delivering twins]. / Ciecie cesarskie na drugim plodzie w przebiegu porodu ciazy blizniaczej.

We have analysed 6 cases of twin pregnancies with vertex presentation of the first foetus. In this cases after delivery of the first twin by vaginal route caesarean, section was made. Caesarean section of the second twin was made because of: transversal presentation with fetal distress syndrom (four cases), umbilical cord drop (one case), and premature placenta ablation (one case). We have determined acid base balance and Apgar score. We have noted worse results for the second twin, independently too of the time between deliveries both twins. Caesarean section of the second twin is the rarely clinical situation, but in motivated situation is accepted and reasonable solution.

[Triplet gestation--analysis of pregnancy course, delivery and neonatal outcome, based on personal material]. / Ciaza trojacza--analiza przebiegu ciazy, porodu, stanu noworodków, na podstawie materialu wlasnego.

UNLABELLED: Triplet gestation appears in 0.1-0.3% of all pregnancies and it is high risk pregnancy for mother and foetus. It appears more frequently in Afroamerican women, rarely in Japan women. In multifetal pregnancy early prenatal diagnosis and management are very important. AIM: Analysing course of pregnancy, way of delivery, condition of newborns, influence of environmental factors, and concomitant diseases in triplets gestation. MATERIAL: 30 women treated between 1989-1998, in Division of Perinatology, University of Medical Sciences in Poznan, Poland. RESULTS: 21 pregnancies were ended by caesarean section, 9 by vaginal delivery. Apgar score for II and III foetus decreases significantly. pH value of umbilical artery was without significant differences. CONCLUSIONS: Almost all triplets have ended preterm. Route of delivery of triplets have to be considered individually. Environment factors could play an important role in multifetal pregnancy.