Oral Contraceptives Moderately Effect Bone Resorption Markers and Serum-Soluble Interleukin-6 Receptor Concentrations

This study investigated the effect of ethinylestradiol(EE2)-containing oral contraceptives on mineral and bone metabolism and on serum soluble-interleukin-6-receptor (sIL-6R) during the menstrual cycle. Twelve women, aged 24.3 +/- 2.9 years, were examined. Blood and 24-hour and fasting urine samples were obtained during one menstrual cycle between cycle day 3-5 (t(1)), cycle day 10-12 (t(2)), cycle day 24-26 (t(3)), and again on day 3-5 of the next cycle (t(4)). EE2 intake was 0 mg at t(1), 30 mg at t(2), 30 mg at t(3) and 0 mg at t(4). Fasting renal phosphorus and calcium excretions were slightly reduced at t(2) and t(3) compared with t(1) and t(4) (P < 0.05-0.001). Moreover, renal excretion of the bone resorption marker C-Teleopeptide was at t(3) reduced by 26% compared with t(1)(P < 0.01) and by 13% compared with t(4)(P > 0.05). Fasting sIL-6R levels were 16.5% lower at t(2) and 12% lower at t(3) than at t(4) (P < 0.01 and P < 0.05). sIL-6R was correlated with total deoxypyridinoline excretion (r = +0.35; P < 0.05) and with fasting renal excretions of calcium (r = +0.36; P < 0.05) and phosphorus (r = +0.29; P < 0.05). In summary, our data suggest that in young women, cyclic monthly oral contraceptive intake is associated with small, but significant variations in bone resorption processes and in serum sIL-6R levels. Results are a further indication that monthly fluctuations of bone resorption in young women are mediated by sex hormones and that osteoclastic activity is stimulated by cytokines in vivo.     

Association of factor V Leiden mutation with delayed graft function, acute rejection episodes and long-term graft dysfunction in kidney transplant recipients

We analysed whether the factor V Leiden mutation--the most common hereditary predisposing factor for venous thrombosis--is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87: 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 +/- 2.06 dialysis in GA patients; 4.2 +/- 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of l/creatinine per year was significantly lower in patients with the GA genotype (GA patients: -0.0204 +/- 0.008 dl/mg per year; GG patients: 0.0104 +/- 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 +/- 16.6 mg/24 h per year; GG patients: 4.9 +/- 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.     

Ciglitazone inhibits plasmin-induced proinflammatory monocyte activation via modulation of p38 MAP kinase activity

Plasmin triggers chemotaxis and NF-kappa B- and AP-1-mediated proinflammatory gene expression in human peripheral monocytes (PM). Compared with macrophages and dendritic cells, PM express mainly the peroxisome proliferator-activated receptor (PPAR) gamma and traces of PPAR alpha as detected by semiquantitative RT-PCR and immunoblotting. The PPAR gamma agonist ciglitazone, but not the PPAR alpha agonist clofibric acid, concentration-dependently inhibited the plasmin-, but not the FMLP-induced PM chemotaxis. Similarly, release of interleukin (IL)-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha from plasmin-stimulated PM was concentration-dependently inhibited by ciglitazone, but not by clofibric acid, while the LPS-induced TNF-alpha release remained unaffected by any of both PPAR agonists. Ciglitazone activates PPAR gamma as shown by a novel surface plasmon resonance analysis and inhibits the plasmin-induced activation of NF-kappa B and AP-1. It also inhibits p38 MAPK phosphorylation essential for the plasmin-induced PM chemotaxis and gene activation. Thus, activation of PPAR gamma by ciglitazone may allow controLling of the plasmin-mediated recruitment and activation of PM at sites of inflammation.     

Long-term refractive and visual outcome after penetrating keratoplasty only versus the triple procedure in Fuchs' dystrophy

Background Long-term refractive and visual outcome after penetrating keratoplasty (PK) only and the triple procedure in eyes with Fuchs' endothelial dystrophy were assessed and compared.Design Retrospective, non-randomized, cross-sectional, clinical, single-centre study.Methods Ninety-two eyes of 87 patients were divided into two groups. Group 1 consisted of 28 eyes (mean age 62±13 years) that had undergone PK only and group 2 consisted of 64 eyes (mean age 69±10 years) that had undergone the triple procedure. Inclusion criteria were: (1) Fuchs' dystrophy, (2) central nonmechanical trephination, (3) double-running suturing technique and (4) availability of ‘two-sutures-out’ findings.In all eyes, a central trephination was performed (donor trephination from the epithelial side) using the 193-nm excimer laser along metal masks with eight ‘orientation teeth/notches’. A double-running 10–0 nylon suture was applied in all eyes. Subjective refractometry (trial glasses), standard keratometry (Zeiss) and corneal topography analysis (TMS-1, Tomey) were performed in all eyes with ‘two-sutures-in’, ‘one-suture-out’, and ‘two-sutures-out’. Main outcome measures included refractive cylinder, keratometric and topographic net astigmatism, keratometric and topographic central power, best-corrected visual acuity (BCVA), spherical equivalent (SE) of manifest refraction, surface regularity index (SRI), surface asymmetry index (SAI), and regularity of keratometry mires.Results The results were compared between the two groups (i.e. group 1 vs group 2) at various stages (i.e. ‘two-sutures-in’, ‘one-suture-out’, ‘two-sutures-out’). Refractive cylinder in dioptres [D] was 2.5/2.0/2.5 vs 2.0/1.5/3.0, keratometric astigmatism [D] was 3.5/2.6/3.0 vs 3.5/3.1/3.5 and topographic astigmatism [D] was 3.9/4.1/4.9 vs 4.2/5.0/5.1. Keratometric central power [D] was 41.7/42.4/43.8 vs 41.5/41.9/43.3 and topographic central power [D] was 42.3/43.6/43.7 vs 42.6/41.8/44.3. BCVA was 0.5/0.6/0.6 vs 0.5/0.5/0.5. SE [D] was 0.0 /0.0/–0.5 vs –0.5/–0.5/–1.1. SRI was 1.5/1.1/1.0 vs 1.4/1.4/1.2 and SAI was 1.0/0.8/1.0 vs 1.3/1.2/1.0. The proportion of ‘regular’ and ‘mildly irregular’ keratometry mires was 44% / 69% / 68% vs 29% / 46% / 66%. The differences between the two groups did not reach statistical significance at any of the stages.Conclusions Refractive and visual outcome after the triple procedure did not differ significantly from that after PK only. Therefore, we recommend the triple procedure in elderly patients with Fuchs’ dystrophy and cataract to avoid delayed visual rehabilitation and a second surgical procedure.     

Neuroblastom

Monatsschrift Kinderheilkunde -     

Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group

The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children.     

Standards for total body fat and fat-free mass in infants

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altman's method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.