Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance.

AIMS: To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. METHODS: Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. RESULTS: Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. CONCLUSION: Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Application of the dual-tagging gene trap method combined with a novel automatic selection system to identify genes involved in germ cell development in Drosophila melanogaster.

The passage of highly specialized germ cells to future generations is essential for the maintenance of species. To date, conventional genetic screens identified relatively few genes that are involved in germ cell development. We aimed to identify germ line specific genes on the X chromosome of Drosophila melanogaster by the application of a new method: the dual-tagging gene-trap system (GT). A modified version of the gene-trap element was used in our experiments and the resulting insertional mutants were screened for grandchild-less phenotype with the help of the attached-X system and a sensitized genetic background developed in our laboratory. Among the 800 insertions mapped to the X chromosome 33 new mutations were identified that exhibited grandchild-less phenotype, 6 gave visible phenotype and 12 were conditional lethal. The cloning of a selected group of the 33 lines showing grandchild-less phenotype confirmed that we have identified new candidates for genes involved in germ cell development. One of them named pebbled (peb) is discussed in details in this paper. Finally, we also describe a novel automatic selection system developed in our laboratory which enables the extension of the GT mutagenesis to the autosomes.

Immunologic and molecular biologic characterization of pleural involvement in a case of T-chronic lymphocytic leukemia.

Pleural involvement is a rare complication of chronic lymphocytic leukemia (CLL). We report a CLL case of T-cell origin (documented by cell surface marker as well as DNA rearrangement studies) where the lymphoid cells of the pleural fluid were found to belong to the same monoclonal population of T cells as those of the peripheral blood.

P-glycoprotein is overexpressed and functional in severely heat-shocked hepatoma cells.

BACKGROUND: Hyperthermia is used in the treatment of some human malignancies. Thermotolerance may interfere with the efficacy of hyperthermic treatment, and thermotolerant cells may also display an enhanced resistance to some anticancer drugs. We have earlier isolated stable heat-resistant rat hepatoma variants and examined whether heat resistance influenced the drug sensitivity of the cells. MATERIALS AND METHODS: Heat-resistant variants were isolated by ten repeated cycles of heat exposure at 45 degrees C for 80 min. Highly multidrug-resistant variants were isolated by stepwise selection with colchicine. RESULTS: The heat-resistant variants became moderately multidrug resistant. This resistance was further increased by stepwise selection with colchicine (highly multidrug resistant variants). The levels of P-glycoprotein were elevated both in moderately and highly drug resistant variants. Decreased retention of antitumor drugs was observed in the multidrug resistant variants, verapamil increased doxorubicin retention significantly. Estradiol was almost without effect, while tamoxifen increased the drug uptake. Amplification of the MDR gene occurred in a part of the highly multidrug resistant variants. CONCLUSIONS: Acquired stable heat resistance of cancer cells can prevent the efficacy not only of hyperthermic treatment, but also the success of chemotherapy.

Bone mineral content and density in asymptomatic children with coeliac disease on a gluten-free diet.

OBJECTIVES: Osteoporosis is a complication of coeliac disease. A gluten-free diet improves but does not normalize bone mineral density in adult patients. Only limited data are available regarding the influence of the disease and diet on bone mineralization in children. The aim of this study was to evaluate the radial bone mineral content and density in children and adolescents who are asymptomatic on a gluten-free diet. SUBJECTS AND METHODS: The bone mineral content (BMC) and density (BMD) values of the non-dominant radius midshaft in 91 children (53 girls, 38 boys, mean age 11.7 years, mean duration of disease 8.7 years) were determined by single-photon absorptiometry. At the diagnosis and at least three years after commencement of a gluten-free diet, serum calcium, phosphorus, albumin concentrations and alkaline phosphatase activities were measured in all patients, and intact parathormone concentrations in 16 patients. RESULTS: The mean BMC Z-score value in the female adolescent group only was significantly lower than normal (mean Z-score -1.04, P < 0.01). In contrast, the mean BMD Z-score was significantly higher compared to a healthy population both in girls (mean Z-score +1.36, P < 0.001) and in boys (mean Z-score +0.53, P < 0.02), as well as in the total patient group (mean Z-score +1.01, P < 0.001). The radial diameter was significantly smaller than normal in both pre-pubertal and adolescent groups. Serum laboratory parameters of asymptomatic patients were in the normal range. The parathormone mean value was significantly lower after at least three years of gluten-free diet than at diagnosis (mean +/- SD 3.77 +/- 1.07 versus 7.89 +/- 2.54 pmol/l, P < 0.01), but significantly higher compared to controls (2.89 +/- 0.90 pmol/l, P < 0.05). CONCLUSIONS: These data indicate that treated, asymptomatic coeliac children and adolescents have normal or even higher radius mineral density values than controls, but the bone size remains reduced. Although there is no direct evidence of calcium malabsorption in this cohort of coeliac patients, the slightly higher parathormone levels, together with some other factors, particularly delayed puberty, may result in reduced bone size.

[Effect of somatostatin on metabolic changes following ERCP ]. / Die Wirkung von Somatostatin auf Stoffwechselveränderungen nach ERCP.

An investigation was carried out on the ameliorating effect of cyclic somatostatin on the biochemical changes and impairment of glucose tolerance which follow endoscopic retrograde pancreatography. Serum amylase and plasma insulin and glucagon levels were significantly lower in a group of 20 patients receiving somatostatin prior to pancreatic radiography than in 35 control patients without such pretreatment. (Maximum increases in control and somatostatin-pretreated patients, respectively were: amylase: 4695 +/- 290; 1037 +/- 155 U/l p less than 0.001; insulin: 504 +/- 89; 179 +/- 43 pmol/l p less than 0.001; glucagon: 394 +/- 44; 62 +/- 13 pmol/l p less than 0.05.) Impairment of glucose tolerance was also considerably less in the patients given prophylactic somatostatin. These results indicate that postpancreatographic metabolic abnormalities can be ameliorated, or possibly even prevented altogether, by prior administration of somatostatin.

[Serum and salivary testosterone levels in erectile dysfunction]. / A szérum és nyál tesztoszteron szintje erectilis dysfunctióban.

In this study 66 male patients with erectile dysfunction were investigated. The authors measured the testosterone levels in serum and in saliva, which latter represent with good accuracy the serum levels of free testosterone. The mean serum total testosterone level was 17.6 nmol/L (confidence intervals: 15.5 and 20.2 nmol/L, normal range: 10-50 nmol/L). The mean salivary free testosterone level was 218.5 pmol/L (confidence intervals: 198.3 and 239.9 pmol/L, normal range: 200-1000 pmol/L). Low salivary (free) testosterone levels were found in 36.4% of patients, while only in 10.6% of patients had low serum testosterone levels (p = 0.01, by binomial test). Although there is a relationship between serum and salivary testosterone levels (r = 0.41, p < 0.001), the patients with low salivary (free) testosterone levels have in major part a normal serum total testosterone level. These data indicate that a considerable proportion of patients with erectile dysfunction have androgen deficiency. The serum total testosterone level is not a sensitive indicator to detection of hypogonadism. The androgen substitution therapy has a beneficial effect on erectile dysfunction in a significant part of patients. The measurement of free testosterone level in saliva may have an important role both in the diagnosis of diseases characterized by androgen deficiency and hyperandrogenic status.

[Possibilities of non-hormonal drug treatment of osteoporosis]. / Az osteoporosis nem hormonpótló gyógyszeres kezelési lehetöségei.

In many countries osteoporosis is the most common metabolic bone diseases. A great deal is known about the pathophysiology and the treatment of the disease. There is a lot of treatment possibilities and many new treatments are being tested. Therapeutic agents for osteoporosis are correspondingly classified as substances primarily inhibiting bone turnover (most of them are inhibitors of bone resorption as well) and agents that appear capable of restoring bone mass previously lost (stimulators of bone formation). From a didactic point of view the distinction of these to groups is generally accepted, but pharmacologically there is a considerable overlap between two. In this review the authors evaluate non-hormonal drugs, which are being used widely in the treatment of osteoporosis. The key points of the evaluation are the mechanism of action, the effects on bone mass, bone strength and fracture.

[Low birth weight, adrenal and sex hormones and their correlation with carbohydrate metabolism and cardiovascular physiology, investigated in young adulthood] . / Kis születési súlyú fiatal felnóttek mellékvesehormonjainak vizsgálata és ezek összefüggése a szénhidrát-anyagcsere és a cardiovascularis rendszer egyes paramétereivel.

It is known that the prevalence of cardiovascular diseases, hypertension, noninsulin dependent diabetes mellitus and dyslipidemia in the late adulthood are in connection with intrauterine retardation, characterized by low birth weight. One possible explanation of this phenomenon is the abnormality of hypothalamus-hypophysis-adrenal cortex axis due to the accelerated growth. The authors investigated the steroid levels of young adults; whom birth weight were under 2500 g, and examined the relationship between hormone levels and some parameters of glucose metabolism and cardiovascular system. 75 subjects (43 female and 32 male patients, mean age: 19.6 and 19.8 years, respectively; range 18-22 ys) with low birth weight and without any sign of chronic disease, and 30 healthy, age-matched controls with normal birth weight were investigated. The basal serum cortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), androstenedione (AD), 17-hydroxyprogesterone (17OHP), estradiol (OE), sex-hormone binding globulin (SHBG), FSH, LH and insulin levels were determined. Moreover, oral glucose tolerance test with 75 g glucose (OGTT), impedance cardiography as well as ambulatory blood pressure monitoring were done by all subjects. In both sexes in subjects with low birth weight the mean serum cortisol level was significantly higher, than in the normal controls. In female patients the serum DHEA, DHEAS, AD, and 17OHP levels were significantly higher than in the controls. Moreover, among these females a relationship was found between the elevations of adrenal and gonadal steroids and hyperinsulinemia, characterized by increased insulin response during OGTT. In male subjects a significant correlation was found between serum cortisol levels and systolic blood pressure and heart rate. In females there was a positive relationship between serum DHEA and heart rate. Summarized, the basic abnormality in patients with low birth weight seems to be a relative hypercortisolism, and in females because of hyperinsulinemia exists a mild hyperandrogenism as well. The hypercortisolism may cause cardiovascular abnormalities in males directly, while in females indirectly through the hyperinsulinemia and hyperandrogenism. These subtle abnormalities can be detected when no clinical signs present themselves, in young adulthood, giving the opportunity of taking preventive actions.

[Zinc excretion in osteoporotic women]. / Cinkürítés osteoporosisos nökben.

Urinary zinc excretion was detected in 24 normal and 25 age matched osteoporotic women. The osteoporotic group was classified in two groups on the basis of bone mineral density (BMD) measurements. Urinary zinc excretion was 327 micrograms/g creat. in healthy subjects and 488 micrograms/g creat. in the "common porotic group". In the "trabecular porotic group" (decreased BMC with DEXA at the lumbar spine alone or together with the femoral neck, but with normal radius BMD) it was 455 micrograms/g creatinine while in the "cortical porotic group" (decreased BMD with SPA at the radius midshaft and/or all the sites measured) the zinc excretion was even higher, 588 micrograms/g creat. The difference between the normal and porotic groups was statistically significant, while within the porotic groups it was not, however the tendency was remarkable. A close significant correlation exists between BMC of radius and urinary zinc excretion. In the osteoporotic group the urinary calcium excretion was significantly higher, than in normal group (220.2 vs 145.2 mg/g creat, p < 0.01). The correlation between the urinary zinc and calcium excretion was not significantly statistically. Elevated urinary zinc excretion is characteristic in both types of involutional osteoporosis in women and therefore seems to be a potential new simple marker of bone resorption.

[Atrial natriuretic peptide in dumping syndrome]. / Pitvari nátriuretikus peptid dumping szindrómában.

The significance of atrial natriuretic factor (ANF) was investigated in the maintenance of the fluid volume in hypovolemia associated with dumping syndrome following gastric resection. The study was performed on 10 patients with Billroth II procedure. Ten age and sex matched patients--without previous gastric surgery served as controls. Each patient underwent oral glucose challenge. The patients following gastric resection underwent an other glucose challenge with intravenous infusion for the maintenance of the fluid volume. All patients with gastric resection showed subjective symptoms of the early dumping syndrome with significant (p less than 0.001) increases in heart rate and in hematocrit, while plasma ANF level decreased significantly (p less than 0.01). Significant negative correlation was found between the changes in hematocrit and the changes in plasma ANF level (r = -0.89; p less than 0.001). Neither the subjective symptoms characteristic for early dumping syndrome, nor changes in the laboratory parameters were noted in the patients during the challenge with infusion. The results show that the hypovolemia in dumping syndrome is associated with significant decreased ANF activity, and in the regulation of ANF release besides the well known stimulating effect of hypervolemia, there exists an inhibition of secretion in volume depleted states.

[Treatment of postmenopausal osteoporosis with low doses of calcitonin and a calcitonin-anabolic combination]. / Postmenopausás osteoporosis kezelése kis adag kalcitoninnal és kalcitonin-anabolikum kombinációval: 3 éves kezelési tapasztalat.

Menopausal osteoporotic women (age: 49-69, mean: 59.5 years) with crush fractures of the spine were treated with low doses of calcitonin (Miacalcic, 350 U/month), or with calcitonin + anabolic steroid (Retabolil, 50 mg/month). Efficacy of the therapy was controlled by single foton absorptiometry of midshaft and distal radius, by X-ray morphometry and by registering new crush fractures of the spine. Calcitonin monotherapy stopped further bone loss for two years, but at the end of the third year both absorptiometric values, as well as the radiomorphometrical index of the lumbar spine decreased significantly. In patients on calcitonin+anabolic steroid the decrease was just significant and only at radius midshaft, while at the other measured sites it was not. Two new crush fractures per 1396 patient-months occurred. Intermittent administration of low-dose calcitonin, especially together with an anabolic steroid seems to be a safe and effective therapy in established osteoporosis.

[Mean value of bone mineral content in Hungary measured by dual-photon absorptiometry]. / A csontok ásványianyag-tartalmának magyarországi átlagértékei kettös energiájú rntgenfoton absorptiometriával mért adatok alapján.

Bone mineral content and density of the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry in normal volunteers (89 women, 77 men) in different age groups. Peak values in both sexes occurred in the 3rd decade and are about 25% higher in men than those in women. In women the bone loss begins around 40 years at lumbar spine and also at the femoral neck. The rate of bone loss in the 6th decade--according to the menopause--significantly accelerates. The diminution in the 8th decade is higher again. In men the decrease of the lumbar spine density is also significant in connection with the ageing process, but the rate of the bone loss is slower, than in women. The femoral neck density and mineral content values begin to decrease at the 4th decade. The decrease of bone mineral content and density of femoral neck are equivalent in both sexes but some difference exists in the velocity. The data were compared with West-european values. The values of the femoral neck are lower, while those of the lumbar spine in the 5th decade in the female are higher in the Hungarian population. The reason of this difference may be the consequence of the obesity of the Hungarian female population.

[The effect of somatostatin in dumping syndrome]. / A somatostatin hatása dumping-szindrómában.

The effect of cyclic somatostatin on early and late dumping syndrome was studied in 12 patients with gastric resection. Each patient underwent two glucose challenges with 75 grams of glucose administered orally. In the control study isotonic sodium chloride was given, while in the other study cyclic somatostatin in a dose of 250 micrograms bolus injection followed by infusion of 80 ng/kg/min for a period of 270 minutes. In the control study all patients showed subjective symptoms of the early dumping syndrome with significant increases in pulse rate, hematocrit, and vasoactive intestinal polypeptide. Ten patients showed asymptomatic hypoglycemia, as a sign of the late dumping syndrome associated with a significant increases of insulin, gastric inhibitory peptide and glucagon levels. During the administration of somatostatin these changes failed to develop. These results indicate that somatostatin alleviates the symptoms of early and late postprandial dumping syndrome.

[Testosterone-dihydrotestosterone ratio in the differential diagnosis of pancreatic disease]. / A testosteron-dihydrotestosteron hányados a pancreas betegségek elkülönítö diagnosztikájában.

Serum testosterone (T), dihydrotestosterone (DT) and androstendione (AD) concentration were determined in male patients with pancreatic cancer (n = 14), chronic pancreatitis (n = 26), other malignancies of the gastrointestinal tract (n = 19) and in control subjects (n = 16). The T level was decreased in patients with pancreatic cancer relative to other groups of patients but the difference was not statistically significant. The T/DT ratio was significantly lower in pancreatic cancer (2.5 +/- 1.0) compared to chronic pancreatitis (9.6 +/- 2.3, p 0.01). The specificity of the ratio is 84%, while the sensitivity was found to be 92%. The discriminative value was found to be 4. The T/DT ratio seems to be a valuable marker in the differentiation of pancreatic cancer from chronic pancreatitis.

[Mineral content in bones of children with symptomless celiac disease and gluten-free diet]. / Glutenmentes diétán tünetmentes coeliakiás gyermekek csont ásványianyag-tartalmának vizsgálata.

Osteoporosis is a complication of adult celiac disease. The gluten-free diet improves but does not normalize bone mineral density. Only few and conflicting data are known about the influence of the disease and diet on bone mineralization in children. The aim of this study was to evaluate the radial bone mineral content (BMC) and density (BMD) in children and adolescents who are asymptomatic on gluten-free diet. The BMD and BMC values of non-dominant radius midshaft in ninety-one children (53 girls and 38 boys, mean age: 11.7 years, mean duration of disease: 8.7 years) were determined by single photon absorptiometry. At the diagnosis and at least three years after gluten-free diet, serum calcium, phosphorous and albumin concentrations and alkaline phosphatase activities were determined in all, and additionally intact parathormone concentrations in 16 patients. The mean BMC Z-score value in the entire study population did not differ from the value of normal age-matched population (mean Z-score: -0.27), but in female adolescent group was significantly lower than the normal value (mean Z-score: -1.04, p < 0.01). In contrast, the mean BMC Z-score value was significantly higher than in normal value in girls (mean Z-score: +1.36, p < 0.001), in boys (mean Z-score: +0.53, p < 0.02) as well as in the total patients group (mean Z-score: +1.01, p < 0.001). The diameter of radius midshaft was significantly smaller in all age group than the normal mean value. Serum laboratory parameters of asymptomatic patients were in the normal range. The serum parathormone value in treated patients was significantly lower than in untreated celiac children (mean +/- SD: 3.77 +/- 1.07 versus 7.89 +/- 2.54, p < 0.01), but significantly higher compared to controls (2.89 +/- 0.9, p < 0.05). The data indicate that the gluten-free diet alone is not able to normalize bone mineralization in children. The significant increase of serum parathormone level in treated asymptomatic patients may be explained by the lower calcium content of gluten-free diet. The authors suppose that low calcium supply in children similarly to adult patients can lead to increased parathormone secretion, which can cause the retardation of bone growth even in treated patients with celiac disease.

[Spinal and appendicular osteoporosis in streak gonad syndrome. Photon absorptiometric and roentgen-morphometric studies]. / Axiális és appendikuláris osteoporosis csíkgonád szindrómában foton abszorpciometriás és röntgenmorfometriás vizsgálatok.

Patterns of bone loss in the axial and the appendicular skeleton were studied in 48 women with streak gonad syndrome (age: between 14-38 years, mean: 25.5 years). Bone mineral content was measured in vivo at the lumbar spine and right femoral neck by dual photon absorptiometry and at the midradius and distal radius by single photon absorptiometry. The bone mineral status of 20 patients was evaluated by radiomorphometrical indices of the metacarpals, femorals and lumbar spine, too. Mean bone mineral content and radiomorphometrical indices were significantly lower in patients with streak gonad syndrome than in age-matched normal subjects at all three scanning sites. The patients lost cortical and trabecular bone mineral content at the same rate, suggesting that bone loss in streak gonad syndrome is a generalized phenomenon. In spite of serious bone loss osteoporotic fractures were not observed in the patients, in contrast to patients with pathological post-menopausal osteoporosis having equal degree of bone deficiency. The authors did not find any relationship between the occurrence of osteoporosis and the karyotype of the patients. It is suggested that the osteoporosis in streak gonad syndrome--at least after puberty--is a consequence of gonadal hormone deficiency.

Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis.

BACKGROUND: The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis. METHODS: One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D(3) were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures. RESULTS: One hundred and thirty patients were included in the final analysis. Patients with fractures (n = 21) had lower 25(OH) vitamin D(3) levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D(3) concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy. CONCLUSION: Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.

Bone mineral density and parathyroid function in patients on maintenance hemodialysis.

BACKGROUND: The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details. METHODS: In a cross-sectional design, data from 270 patients (age 55 ± 15 years, 60% men, all Caucasian) on maintenance hemodialysis were analyzed. All patients underwent dual energy X-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and distal radius (DR). In addition to routine laboratory tests, blood samples were collected for iPTH, serum markers of bone metabolism (alkaline phosphatase, type I collagen crosslinked-C-telopeptide) and 25OH vitamin D. RESULTS: Based on Z-scores, bone mineral density was moderately reduced only at the femoral neck in the total cohort. The average Z-score of the "low PTH" group (iPTH < 100 pg/ml) was not different from the Z-score of patients with iPTH in the "target range" (100-300 pg/ml) at any measurement site. While iPTH was negatively correlated with BMD at all measurement sites in patients with iPTH > 100 pg/ml (rho = -0.255, -0.278 and -0.251 for LS, FN and DR, respectively, P < 0.001 for all), BMD was independent of iPTH in patients with iPTH < 100 pg/ml. Furthermore, iPTH was not associated with serum markers of bone metabolism, but these markers were negatively correlated with BMD in the "low PTH" group. CONCLUSIONS: Low PTH levels are not associated with low BMD in patients with end-stage kidney disease. Furthermore, bone metabolism seems to be independent of iPTH in patients with relative hypoparathyroidism likely reflecting skeletal resistance to PTH.

Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn's disease.

BACKGROUND: Adalimumab is a fully human monoclonal antibody targeting tumour necrosis factor with proven efficacy in the treatment of Crohn's disease (CD). AIM: To investigate the predictors of medium-term clinical efficacy and mucosal healing during adalimumab therapy, in patients with CD, in specialised centres approved for biological therapy in Hungary. METHODS: Data capture of the 201 CD patients was standardised and prospective (male/female: 112/89, median age: 33.0 years, duration: 8 years). Previous infliximab therapy had been administered in 48% of patients, concomitant steroids in 41%, azathioprine in 69% and combined therapy in 27% of patients. RESULTS: Overall clinical response and remission rates at 24 weeks were 78% and 52%, respectively; at 52 weeks were 69% and 44%, respectively. Endoscopic improvement and healing were achieved in 43% and 24% of patients. In a logistic regression model, clinical efficacy and CRP at week 12, need for combined immunosuppression at induction, shorter disease duration and smoking were identified as independent predictors for 12-month clinical outcome, whereas CRP at week 12, clinical remission at week 24, inflammatory parameters and nonsmoking were associated to endoscopic improvement/healing. Intensification to weekly dosing was needed in 16% of patients. Parallel azathioprine therapy and clinical remission at week 12 were inversely associated with dose escalation. CONCLUSIONS: Clinical efficacy and normalised CRP at week 12 (early deep clinical remission) are associated with medium-term clinical efficacy and mucosal healing during adalimumab therapy, whereas need for combined immunosuppression at induction and smoking status are predictors for non-response. Parallel azathioprine therapy may decrease the probability for dose escalation.