Association of adiponectin, resistin and high sensitive CRP level with the metabolic syndrome in childhood and adolescence.

Early markers are required in pathophysiological process of obesity, MS and type 2 diabetes. We aimed to clarify the usefulness of serum adipokines (adiponectin, AD and resistin) and inflammatory markers to identify obese and overweight children with MS. Three hundred and seven of 2 491 subjects aged 11-19 with BMI> or =85 centile selected with a multistage, stratified sampling were included. Their height, weight and waist circumference were measured, all subjects underwent physical examination and standard OGTT. AD, resistin and hs-CRP were measured from baseline blood sample. The mean age of subjects was 14.2+/-1.8, 57.7% was girl (n=177) and 42.3% (n=130) boy. Of the 307 subjects 40 (13%) were classified as having MS. Serum AD levels were significantly lower in boys (p=0.02), and decreased while BMI increased, but this trend was not significant (p>0.05). Although median resistin values were higher in obese than others (20, 18.5, 17 ng/ml, respectively) it was not significant (p>0.05). In obese subjects, hs-CRP levels were significantly high (0.21 mg/L) (p=0.000). All three markers in obese and overweight children with and without MS were not significant (p>0.05). Girls with MS had lower adiponectin levels than those without MS. Waist circumference had the highest sensitivity and specificity for predicting MS in ROC analysis. The area under the curve (AUC) was 0.831 for WC standard error (SE) 0.033; 95% CI 0.767-0.896; p<0.0001. But the AUCs for the adiponectin, resistin, hs-CRP were not significant. In this study, we observed that adipokines or inflammatory markers have no predictive value in the diagnosis of MS. We concluded that the best marker for MS diagnosis is the measurement of waist circumference.

Withdrawal of inhaled steroids in children with non-cystic fibrosis bronchiectasis.

BACKGROUND: To study the effects of inhaled steroid withdrawal on bronchial hyperreactivity, sputum inflammatory markers and neutrophilic apoptosis in children with non-cystic fibrosis (non-CF) bronchiectasis. OBJECTIVES: To evaluate the role of inhaled steroids in the treatment of children with non-CF bronchiectasis with specific emphasis on the bronchial hyperreactivity and neutrophilic apoptosis. METHODS: Twenty-seven children with steady-state non-CF bronchiectasis were evaluated primarily with metacholine challenge tests and apoptotic neutrophil ratios in induced sputum and secondarily with symptom scores, pulmonary function tests and tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) levels and neutrophil ratios in induced sputum before and after 12-week withdrawal of inhaled steroids. RESULTS: There were 16 girls and 11 boys. Median (interquartile range) age was 11.4 (9.5-13.6) years, follow-up duration was 3.5 (2-6.5) years. Symptom scores (4 vs. 3; P = 0.27), oxygen saturation (95% vs. 97%; P = 0.06), pulmonary function tests (FEV1: 82% predicted vs. 83% predicted; P = 0.73), sputum neutrophil ratios (29.9% vs. 46.8%; P = 0.20), TNF-alpha (58 pg/mL vs. 44.5 pg/mL; P = 0.55) and IL-8 (2.7 ng/mL vs. 2.4 ng/mL; P = 0.82) levels in induced sputum were similar before and after 12-week withdrawal of inhaled steroids. However, the number of patients with bronchial hyperreactivity increased (37% vs. 63% of patients; P = 0.016) and neutrophilic apoptosis in induced sputum decreased (42.8% vs. 20.2%; P = 0.03) after withdrawal. CONCLUSION: In this study, 12 week-withdrawal of inhaled steroid treatment resulted in a significant increase in bronchial hyperreactivity and decrease in neutrophil apoptosis, but no change in sputum inflammatory markers in children with non-CF bronchiectasis was observed.

Effects of cholesteryl ester transfer protein TAQ1B polymorphism in renal transplant patients.

BACKGROUND: Dyslipidemia is an important complication in renal transplant patients. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester between high density lipoproteins and low density lipoproteins. The aim of this study was to investigate CETP Taq1B gene polymorphism and lipid abnormalities in renal transplant patients. METHODS: We studied 29 renal transplant patients and 29 healthy controls. CETP Taq1B polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism techniques. Serum lipid levels were measured enzymatically. Statistical analyses was performed by SPSS for Windows version 7.5. RESULTS: The frequencies of CETP Taq1B B1B1, B1B2, and B2B2 genotypes in patients were 44.8%, 34.5%, and 20.7%; and in control subjects, 37.9%, 37.9%, and 24.2%, respectively. The patients with B1B1 genotype displayed higher levels of total cholesterol (TC), triglycerides, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), and diastolic blood pressure (DBP). (P<.05). Also, patients showing a B1 allele had higher levels of TC, LDL-C, VLDL-C, and DBP compared to healthy controls (P<.05). CONCLUSION: We observed that CETP Taq1B B1 allele and B1B1 genotype have effects on the serum lipid profile among renal transplant patients.

Fibrinolytic activity and d-dimer levels in Behçet's syndrome.

OBJECTIVE: Thrombophlebitis occurs in a third of patients with Behçet's syndrome (BS). The thrombotic tendency in BS has been studied with inconclusive results perhaps due to the inadequate numbers of patients studied during the acute phase of the thrombosis as well as the lack of appropriate diseased controls. We have studied tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1), and d-dimer levels in BS patients with and without thrombosis both in the acute and chronic phases along with suitable diseased and healthy controls. METHODS: t-PA and PAI-1 were studied by ELISA and d-dimer by semiquantitative latex agglutination slide test in 30 BS patients without deep vein thrombosis (DVT), 10 BS with acute DVT (ADVT), 25 BS with chronic DVT, 27 with ankylosing spondylitis, 26 diffuse systemic sclerosis, 15 patients with ADVT due to other causes, 10 patients with sepsis, and 23 healthy controls. RESULTS: The t-PA levels in BS with ADVT were significantly lower than those in patients with ADVT due to other causes (7.4 +/- 6.2 vs. 13.4 +/- 6.3, P = 0.027) while PAI-1 levels did not show significant differences between the groups (P = 0.60). The numbers of patients with d-dimer levels of > or = 0.5 microg/ml in BS with ADVT were similar to those found in patients with ADVT due to other causes (9/10 vs. 14/14). CONCLUSION: The relatively low t-PA levels point to a defect in fibrinolysis in BS. d-dimer levels are increased in the acute phase of thrombosis in BS.

The effect of growth hormone treatment on biochemical indices in hypophosphatemic rickets.

BACKGROUND: Growth hormone (GH) in combination with conventional therapy in hypophosphatemic rickets (HR) has been shown to promote renal phosphate (P) conservation and to result in a better metabolic control. This study aimed at investigating the acute biochemical effects of GH in 7 patients (5 female, 2 male) with HR aged between 2.16 and 16 years. METHODS: Each patient received the following in a sequential design: oral P plus 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] therapy to determine the optimum doses for baseline requirement followed by GH-only therapy and GH +1,25-(OH)(2)D(3) therapy and GH + P +1,25-(OH)(2)D(3) therapy each for 2 weeks with 1 washout week off treatment in between. GH was given at a dose of 0.03 mg/kg/day s.c. on a daily basis. The dose of oral P used ranged between 500 and 2,000 mg/day, and the dose of 1,25-(OH)(2)D(3) ranged between 0.25 and 0.5 microg/day and was kept constant for each child throughout the study. RESULTS: Laboratory investigations repeated at the end of each treatment, and the first washout period showed that the serum P level was highest (2.9 ng/ml) during the GH + P + 1,25-(OH)(2)D(3) period with higher serum 1,25-(OH)(2)D(3) levels: 50.9 +/- (SD) 23.4 ng/l. Parathyroid hormone and alkaline phosphatase levels did not show a significant difference between the periods. The tubular P reabsorption rate showed an insignificant increase during GH therapy periods. CONCLUSION: Considering the fixed dose of P and calcitriol, it may be concluded that GH added to conventional treatment in HR resulted in a slight improvement in the biochemical parameters without any side effects at the short term.

Apo A-I binding to platelets detected by flow cytometry.

Lipoprotein-platelet interactions are very important in atherosclerosis and thrombosis. Several studies have been carried out on specific binding of various lipoproteins to platelets. But there is considerable disagreement about the details of these binding sites. Although low-density lipoprotein (LDL) receptors of several cells have been studied extensively, there is little datum about high-density lipoprotein (HDL) receptors. Apolipoprotein (apo) A-I may play a major role in the determination of the specificity of HDL receptors. In this study, binding of apo A-I to platelets was investigated by using a flow cytometric method. Citrated blood samples were obtained from five healthy and seven hypercholesterolemic subjects. Apo A-I antibody was incubated with the citrated whole blood before and after activation with ADP or thrombin receptor agonist peptide (TRAP). Then fluorescein isothiocyanate (FITC)-labeled secondary antibodies were added and analyzed on a Becton-Dickinson FACSort flow cytometer. In the hypercholesterolemic group, apo A-I binding to platelets was found to be significantly decreased after activation with TRAP (P<.05), but not after activation with ADP. In the control group, after platelet activation with ADP or TRAP, the apo A-I MFI values were not found to be significantly different from the values of resting platelets (P>.05). In this study, we demonstrated that apo A-I can bind to platelets, and this supports the hypothesis that apo A-I may play a major role in HDL binding to platelets.

Plasma adrenomedullin levels in asthmatic patients.

Adrenomedullin (ADM) is a newly discovered endogenous vasorelaxing peptide isolated from pheochromocytoma. Some experimental studies suggest that ADM plays a role in asthma. The purposes of the present study were to assess the plasma ADM levels in adults with mild to severe asthma and controls and to correlate those with the findings on lung function test results and other clinical indices. We recruited 16 mild, 10 moderate, and 11 severely asthmatic patients and 12 healthy controls. We measured the plasma concentrations of ADM in patients with asthma and in healthy subjects using RIA. We assessed FEV1, FEV1 predicted %, FEV1/FVC, symptom score, IgE, ECP, and morning and evening peak expiratory flow measurements. There was no significant difference between the asthmatic and the control group ADM levels, which were 26.3 +/- 24.2 pg/mL and 22.9 +/- 17.6 pg/mL, respectively. Furthermore, plasma ADM levels increased as the severity of the disease increased in asthmatic patients (20.7 +/- 14.4 pg/mL in mild, 25.2 +/- 24.3 pg/mL in moderate, and 35.5 +/- 33.6 pg/mL in severe asthmatics), although they did not result in any statistical significance. However, the plasma ADM levels correlated negatively with the FEV1 levels in the asthmatic group (p < 0.02, r = -0.37). Peripheral blood eosinophilia, IgE, and ECP levels did not correlate with plasma ADM levels. These results suggest that the measurement of ADM concentration in plasma will not be of diagnostic use in asthma, but may be a reflection of the severity of asthma.

Prolactin response to TRH in patients with panic disorder.

The effects of TRH administration (400 microg, i.v.) on the release of prolactin were examined in 15 patients who met DSM-III-R criteria for panic disorder and 15 normal control subjects. Four hundred micrograms TRH was given via IV route. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. The results demonstrate that prolactin responses to TRH did not differ between panic disorder patients and normal control subjects. When only women were evaluated, the findings indicate that women with PD tend to show excessive prolactin responses to TRH. The findings are discussed in view of findings from earlier reports.

[Gastritis localization and GERD incidence in patients with Cag A(+) and Cag A(-) Helicobacter pylori infection]. / Gastritislokalisation und gastroösophageale Refluxinzidenz bei der Helicobacter-pylori-Infektion mit Cag-A-positiven und Cag-A-negativen Stämmen.

The relationship between Helicobacter pylori (HP) and gastroesophageal reflux disease (GERD) is very complex and still not well understood. However, many issues, even those as basic as whether HP induces or protects against GERD, are still controversial. The gastritis location could play also a role in the induction of GERD. Some investigators suggested that infection by the Cag A strain of HP seems to have a positive association with reflux esophagitis. Therefore, the aim of this study was to investigate the relationship between GERD, gastritis location, HP infection and Cag A positivity.

Thyrotropin stimulating hormone response to thyrotropin releasing hormone in patients with panic disorder.

OBJECTIVE: The aim of this study is to assess thyrotropin stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in patients with panic disorder (PD). METHOD: The effects of TRH administration on the release of TSH were examined in 15 patients who met DSM-III-R criteria for PD and compared their test results with those of 15 normal control subjects. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. RESULTS: delta max TSH values were lower in the panic disorder patients than in the control subjects. Using the criterion of delta max TSH < or = 7 mlU/l, nine of the 15 panic disorder patients and four of the 15 control subjects had a blunted TSH response to TRH. CONCLUSIONS: These results confirm the findings from earlier reports that patients with PD show blunted TSH response to TRH which is similar to that seen in depressed patients.

A case of brachyolmia.

Brachyolmia refers to a form of skeletal dysplasia characterized by general platyspondyly without significant epiphyseal, metaphyseal or diaphyseal changes in long bones. Three, possibly four, types of brachyolmia have been defined: Type I-Hobaeck-Toledo type. Type II-Maroteaux and Type III. We report a patient with brachyolmia and present the clinical and radiological findings. A 15-year-old boy presented to our Outpatient Department because of his short stature. His height, weight, head circumference and arm span were 127 cm (< 3rd percentile), (3rd percentile) 39 kg, 55 cm (50th-75th percentile), and 142 cm respectively, and his upper segment/lower segment ratio was 0.91. His neck and trunk were short. He had severe kyphoscoliosis. Slit-lamp examination was normal. Radiologic features included platyspondyly in cervical, thoracic and lumbar vertebrae as well as kyphoscoliosis. Bilateral coxa valga and mild acetabular irregularities were noticed on pelvic radiographies. Levels of chondroitin and heparan sulphate as well as the glycosaminoglycan/creatinine ratio were elevated in the 24-hour urine specimen. The activities of N-acetylgalactosamine-6-sulphatase, beta-galactosidase and beta-hexosaminosidase were all normal in fibroblast culture. Although the x-ray findings of this patient are consistent with both Types I and III, recessive inheritance and glycosaminoglycan anomalies point to Type I brachyolmia.

Ocular involvement in two symptomatic congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (Gunther disease, CEP) is a rare autosomal recessive disorder of haeme biosynthesis. It is characterized by extreme photosensitivity and the excretion of large amounts of uroporphyrin I and coproporphyrin I in the urine and coproporphyrin I in the faeces. We have diagnosed two cases of congenital erythropoietic porphyria, who were first cousins once removed. They had recurrent skin bullae, scarring on the face and hands, hirsutism, discoloured fluorescent teeth, red urine, increased haemolysis and grossly increased excretion of porphyrin. Both children had blepharitis and their sclera gave pink fluorescence under long wave ultraviolet light, mainly in the interpalpebral fissures. All the features of our two patients, except the ocular lesions, conformed to cases of CEP reported in the literature. We have encountered no other reports on ocular lesions in CEP since first described by Chumbley in 1977.

Maternal, umbilical, uterine and amniotic prostaglandin E and F2 alpha levels in labour.

This paper confirms the important role played by prostaglandins in the induction of uterine contractions and the initiation of human labour, although the exact mechanism of action in labour remains unclear. Seventeen pregnant women at term were studied. Of these nine were in labour and the remainder underwent elective section. Prostaglandin E and F2 alpha levels were measured in maternal, umbilical and uterine plasma and amniotic fluid by radioimmunoassay. Levels of prostaglandin E were generally higher than prostaglandin F2 alpha but they were significantly lower in maternal and uterine plasma. Levels of prostaglandin F2 alpha were significantly higher in maternal plasma during labour. The highest levels of prostaglandin were found in amniotic fluid. Measurements indicate that the decreasing ratio of prostaglandin E/F2 alpha is more important in the initiation of labour than absolute levels of either prostaglandin.

Sebum production is increased in Behçet's syndrome and even more so in rheumatoid arthritis.

Sebum production is under hormonal control. We had shown that male sex is associated with more severe disease in Behçet's syndrome and the acneiform skin lesion of this disorder is not different from ordinary acne, an androgen-dependent lesion. Sebum excretion rate was higher in patients with Behçet's syndrome than in healthy controls, children and patients with ankylosing spondylitis. On the other hand, patients with rheumatoid arthritis had high levels of sebum excretion rate comparable to those found in patients with acne vulgaris. These suggest the presence of a sebotrophic hormone and/or other hormonal effects in Behçet's syndrome and rheumatoid arthritis.

Von Willebrand factor in Behçet's syndrome.

Plasma von Willebrand factor F VIII related antigen levels were elevated in 13 patients with Behçet's syndrome and vascular disease compared to 17 with Behçet's syndrome without vascular involvement and 23 healthy controls. As expected 12 diseased controls, 9 of whom had systemic sclerosis, had still higher levels of F VIII related antigen.

Subcellular distribution, properties and interrelationship of oestrogen receptors in endometrium and other target tissues.

More than half of the extranuclear receptor content of resting cells is associated with cytoplasmic structures. Subfractionation of microsomes reveals a preponderance of "basic" (low electrophoretic mobility) receptor in rough endoplasmic reticulum. Surfynol-dithiothreitol extracts of smooth membranes are rich in "acidic" (high electrophoretic mobility) receptor. Trypsin increases the yields up to seven-fold, and this increase is correlated (r = 0.993) with the acidic receptor content and 5'-nucleotidase activity of these microsomal preparations. Acidic microsomal "cytosolic" and nuclear receptor can be degraded to the "basic" variety of streptomyces hyaluronidase. All forms give rise to a tryptic fragment with unchanged affinity for oestradiol and dimerization ability. Basic receptor isolated after enzymatic conversion of acidic receptor is microheterogenous on isoelectric focusing, but gives rise to only one precipitation arc versus the IgG fraction of a polyclonal antiserum. The precipitation arc can be recharged with labelled oestradiol and autoradiographed. Non-immune IgG's from (unspecific) soluble complexes with oestrogen receptors, but not with their tryptic fragments. The polyclonal antioestrogen receptor IgG fraction precipitates the oestradiol-tagged tryptic receptor fragment from all subcellular sources of all homologous (porcine) and heterologous (human, ovine, bovine, goat, rabbit, guinea pig, rat) target tissues tested. Organ specificity can therefore be excluded and a high degree of phylogenetic conservation of the oestrogen receptor's protein moiety is implied. The presence, in the immune IgG fraction, of steroid releasing antibodies, which apparently distort the binding site, should spur the search for monoclonal antibodies with similar properties.

2. Mechanism of steroid action. Immunoreactivity of the core of estrogen receptors found in different subcellular compartments of target cells from a variety of mammalian species.

A goat antiserum was raised by immunization with the endoglycosidase fission product of porcine estrogen receptor. Its IgG fraction was employed for ascertaining the interrelationship of receptor forms extracted from three subcellular compartments of target cells and for comparing receptors from various species. Unspecific alignments of (non-immune) IgGs giving rise to soluble complexes were avoided by removal of the receptor entity responsible with carrier-attached trypsin. Coincubation of the estradiol-tagged tryptic receptor cores and immune IgG resulted in the formation of labelled precipitates and in the release of estradiol from its binding site, in every instance tested. A minimum of three common antigenic determinants must therefore exist not only on all porcine receptor forms, but also on human, ovine, bovine, rabbit, guinea-pig and rat estrogen receptors, pointing to a high degree of phylogenetic conservation.

Validation of the common-core hypothesis of estrogen receptors with precipitating and steroid-releasing antibodies.

The immunoglobulin G fraction of a goat antiserum raised against a presumed endoglycosidase-fission product of estradiol receptor from porcine uteri contains some antibodies which precipitate the estradiol/receptor complex and others which release the steroid from the protein. Subcellular receptor forms and receptors from different porcine target organs react in the same fashion as do human, ovine, bovine, guinea pig, rabbit and rat estradiol receptors.