Erzsébet Toldy

[Effects of rectal indomethacin in the prevention of post-ERCP acute pancreatitis].

UNLABELLED Recently non-steroidal anti-inflammatory drugs have seemed to reduce the frequency of post-ERCP pancreatitis in some prospective controlled trials, but the results have to be confirmed by further studies. AIM To evaluate the efficacy of rectally administered indomethacin for the reduction of incidence of post-ERCP pancreatitis. METHOD A prospective randomized placebo-controlled study was conducted in 228 patients who underwent ERCP. Patients were randomized to receive a suppository containing 100 mg indomethacin or an inert placebo 10 mins before ERCP. Patients were evaluated clinically and biochemically by using serum amylase levels measured 24 h after the procedure. RESULTS Pancreatitis and hyperamylasemia occurred more frequently in the placebo group, but the difference was not significant. In respect to the rate of pancreatitis, this tendency could particularly be observed in females, in patients older than 60 years and in patients with BMI lower than 25; however, it completely failed in cases with pancreatic duct filling or in those with pancreatic EST. CONCLUSIONS Rectal indomethacin given before ERCP did not prove to be statistically effective in the reduction of the incidence of post-procedure pancreatitis. Further, controlled multicenter studies are required to assess safely the potential efficacy of indomethacin in the prevention of pancreatitis following ERCP.

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

AIM To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. METHODS A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. RESULTS Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. CONCLUSION 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis.

Macroprolactinemia: the consequences of a laboratory pitfall.

The objective of this study was to assess the prevalence of macroprolactin, a macromolecule with reduced bioactivity, in hyperprolactinemic patients. Prolactin was measured before and after precipitation of macroprolactin by polyethylene glycol in 306 patients. Only patients with prolactin values >700 mIU/L (n = 270) entered the study. In 23% of the patients, macroprolactinemia was found. In women, the occurrence of macroprolactinemia increased with advancing age (< 30 yr: 16%; 30-45 yr: 28%; > 45 yr: 42%; p < 0.05). A priori clinical signs of hyperprolactinemia (morphological abnormalities in pituitary imaging, galactorrhea infertility) occurred significantly less frequently in macroprolactinemia than in true hyperprolactinemia. In eight females macroprolactinemia and true hyperprolactinemia appeared simultaneously. To avoid diagnostic and therapeutic pitfalls, the screening for macroprolactinemia of all patients with prolactin levels of > 700 mIU/ L is recommended.

Influence of sampling and storage conditions on plasma renin activity and plasma renin concentration

BACKGROUND Because no systematic study on the comparison of the stability of plasma renin activity (PRA) and renin concentration (REN) under different preanalytical conditions has been reported, we examined the impact of several sampling and storage conditions. METHODS Blood samples were collected into prechilled tubes and into tubes at room temperature and processed within 30 min or kept at room temperature or at 0-5 degrees C for 2 h. The stability of PRA and REN after storage at - 20 degrees C was also analysed. PRA and REN were determined with radioimmunoassay (DiaSorin) and chemiluminescent immunometric method (LIAISON, DiaSorin), respectively. RESULTS When blood samples were kept at room temperature for 2 h, the PRA and REN decreased significantly (p < 0.001), but both remained unchanged if samples were placed at 0-5 degrees C for the same time period. The REN was significantly higher in samples collected in prechilled tubes and refrigerated within 30 min at 0-5 degrees C compared to samples processed at room temperature (p < 0.05). During storage at -20 degrees C for 7 weeks the PRA decreased by 31.9 +/- 4.7%, while the change in REN remained below 5%. CONCLUSION Different sampling and storage conditions differentially influence the PRA and REN, which makes it necessary to apply well-defined preanalytical procedures for PRA and REN measurements.

Genomic binding sites and biological effects of the vitamin D: VDR complex in multiple sclerosis

Environmental factors greatly contribute to the development of complex trait disorders. With the rapid developments in the fields of biotechnology and informatics, the investigations of molecular interactions between host and environmental factors became very detailed and comprehensive. The effects of ultraviolet irradiation, vitamin D synthesis, and receptor binding, and then the involvements of the ligand–receptor complexes in the regulation of cell function received much attention in the last few years and paralleled the accumulation of information concerning genetic determinants of disease susceptibility, transcriptional regulation, cell cycle, mitochondrial biochemistry, and many other elements of cell biology. The importance of vitamin D in contributing to immune regulation, autoimmunity, and susceptibility to multiple sclerosis (MS) is now also recognized, and there are ongoing treatment trials with vitamin D to define whether it is capable of modifying susceptibility to or the course of the disease. This survey aims to capture that part of vitamin D research that helps to better understand the interactions of this molecule and its receptor with the human genome, and the downstream effects of these interactions relevant to immune homeostasis and MS. This relatively narrow scope reveals a very complex molecular network underlying inflammatory demyelination and allows us to hope that a better understanding of the roles of vitamin D and other environmental factors will once make the risk of MS modifiable or, to some degrees, the disease preventable.

Use of mesenchymal stem cells from adult bone marrow for injured tissue repair

Mesenchymal stem cells are known as being multipotent and exhibit the potential for differentiation into different cells/tissue lineages, including cartilage, bone, adipose tissue, tendon, and ligament. These pluripotent mesenchymal progenitor cells are denoted as stromal or mesenchymal stem cells. Bone marrow contains two main cell types: hematopoietic cells and stromal cells. The stem cells for non hematopoietic tissues are referred as mesenchymal cells because of their ability to differentiate as mesenchymal or stromal cells. Mesenchymal cells are easily obtainable from bone marrow by means of minimally invasive approach and can be expanded in culture and permitted to differentiate into the desired lineage. The differentiation can be reached by the application of bioactive signaling molecules, specific growth factors. The transforming growth factor beta (TGF-beta) superfamily member proteins such as the bone morphogenetic proteins (BMP-s) are the most important factors of chondrogenic and osteogenic differentiation of mesenchymal stem cells. From the series of recently identified factors, BMP 2,4 and 7 may play an important role in chondrogenic and osteogenic differentiation proteins. Little is known, however, about the signaling pathway involved in tenogenesis of mesenchymal stem cells, but there are some encouraging data about fibroblastic differentiation. The success of growth factor therapy needs a delivery system with biomaterials. Mesenchymal stem cells have become promising vehicles for gene therapy, cell therapy and tissue engineering. In present review, authors deal with the experimental investigations and with the clinical application of the adult bone marrow derived mesenchymal stem cells with bioactive molecules, growth factors.

Comparative analytical evaluation of thyroid hormone levels in pregnancy and in women taking oral contraceptives: a study from an iodine deficient area

Increase of serum thyroxine binding globulin (TBG) resulting from estrogen action may lead to problems in thyroid diagnostics. The aim of the present study was to define the most diagnostically reliable thyroid parameters in women exposed to differentially elevated estrogens. Sera of three groups of healthy women were analyzed: women taking no medicine (controls), those taking oral contraceptives and pregnant women (in weeks 16 or 32 of gestation). All women involved in the study lived in a moderately iodine-deficient geographical area. Thyroid stimulating hormone (TSH), TBG, total thyroxine (T4), total triiodothyronine (T3) and free T3 were determined and free T4 indices (total T4 × T3 uptake; total T4/thyroxine binding capacity (TBC); total T4/TBG) were calculated. Free T4 was measured simultaneously with a one-step T4-analog enzyme-linked immunosorbent assay (ELISA), a labeled T4 antibody radioimmunoassay (RIA), and a two-step microparticle enzyme immunoassay (MEIA). Estrogen-dependent differences were found in all investigated parameters; however, they remained in the reference interval for TSH, total T4 × T3 uptake, total T4/TBC, free T3 and free T4 MEIA. It was concluded that simultaneous estimations of free T4 and free T3 should follow a primary TSH measurement. The necessity of a distinct reference range has emerged for free thyroid hormones in midterm and late pregnancy as well as in the use of oral contraceptives, especially in iodine-deficient areas.

Association of lean and fat body mass, bone biomarkers and gonadal steroids with bone mass during pre- and midpuberty.

Background/Aims: The association of bone mass with body composition, bone turnover markers and gonadal steroids was examined in Hungarian children during pre- and midpuberty. Methods: Two hundred and thirty-seven 7- to 16-year-old subjects (56% girls) were investigated. Bone mineral density (BMD), fat mass and total and appendicular lean mass were estimated with dual-energy X-ray absorptiometry (Lunar Prodigy). The fat mass index and appendicular lean mass index (LMI) were calculated. Serum bone markers, parathyroid hormone, estradiol and testosterone were analyzed. Associations between variables were evaluated by multiple regression analysis. Results: During prepuberty, bone biomarkers, gonadal steroids and appendicular LMI were associated with bone mass in both genders (p < 0.05). During midpuberty, girls’ bone turnover markers were negatively associated with bone mass (p < 0.001). In prepuberty, appendicular LMI and β-crosslaps were predictors of bone mass in both genders. During midpuberty, appendicular LMI and gonadal steroids positively contributed to bone mass in both genders, while osteocalcin exerted a negative influence on total and L1–L4 spine BMD in girls and on L1–L4 BMD in boys (all p < 0.001). Conclusions: Predictors for bone development varied according to Tanner stage and gender. The most significant determinants of bone mass were appendicular LMI and estradiol.

Serum thyroglobulin antibody levels within or near to the reference range may interfere with thyroglobulin measurement.

High concentration of thyroglobulin antibodies (TgAb) is a major limiting factor of thyroglobulin measurements in patients with differentiated thyroid cancer. We investigated whether thyroglobulin antibody added to serum samples could interfere with the thyroglobulin assay. Thyroglobulin levels in serum samples with different concentrations of thyroglobulin were measured by electrochemiluminescence immunoassay before and after the addition of increasing concentrations of thyroglobulin antibody using the secondary calibrator solution of the thyroglobulin assay kit containing sheep thyroglobulin antibody to reach thyroglobulin antibody levels within or near to the reference range. Thyroglobulin and thyroglobulin antibody concentrations were also measured in 134 serum samples from 27 patients after thyroid ablation. There was a strong negative association (slope = −1.179) between thyroglobulin antibody and thyroglobulin concentrations in samples with added thyroglobulin antibody (beta = −0.86; P < 0.001). Changes in thyroglobulin concentrations were described mathematically as loss of thyroglobulin% = −0.2408 × Ln(thyroglobulin antibody IU/ml) + 0.1944. Thyroglobulin concentrations were significantly lower than those calculated from experiments with added thyroglobulin antibody in 26/134 samples from patients after thyroid ablation. We conclude that if the same TgAb interference exists in the presence of naturally occurring human TgAb, our observation may prove to be useful during follow-up of patients with differentiated thyroid cancer. However, further studies are needed to explore the clinical relevance of thyroglobulin antibody levels within or near to the reference range in monitoring these patients.

Maternal hyperandrogenism beginning from early pregnancy and progressing until delivery does not produce virilization of a female newborn

A 33-year-old primagravida with a history of polycystic ovary syndrome was referred because of symptoms of moderate hyperandrogenism. Serum hormone levels, measured regularly from the 7th week of pregnancy until delivery, showed very high increases of testosterone, androstenedione and estradiol. Ultrasound showed no evidence of adrenal or ovarian masses. She delivered a female newborn with normal female external genitalia. Umbilical cord hormone levels were normal, except for a modest increase of serum testosterone. After delivery the androgen levels of the mother returned to normal and the symptoms of hyperandrogenism were also slightly improved.