BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.     

Heart rate analysis in 24 patients treated with 150 mg amitriptyline per day

Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a standardized heart rate analysis (HRA) before therapy and after 14 days. The battery of cardiovascular reflex tests included the determination of the coefficient of variation (CV) while resting and during deep respiration, a spectral analysis of heart rate, the heart rate response to standing, and the Valsalva manoeuvre. The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex. On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests (P<0.0001), probably due to the anticholinergic side effects of amitriptyline. Heart rate increased form 78.1 to 93.6 bpm on average (P<0.0001). Abnormal CV at rest was registered in 96% of the patients; during deep respiration 29% showed abnormal CV results. An abnormal spectral analysis was found in 100% of the cases (low frequency peak: 42%, mid-frequency peak: 100%, high frequency peak: 79%). The heart rate response to standing was abnormal in 75% and the Valsalva test in 33% of the cases. Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy. As yet, the consequences of these changes for the patients have not been sufficiently elucidated.     

Human Y-79 retinoblastoma cells express functional corticotropin-releasing hormone receptors

In human Y-79 retinoblastoma cells corticotropin-releasing hormone (CRH) produces a marked and rapid increase of adenylate cyclase activity. The concentration of the peptide producing half-maximal stimulation is 60 nM. The effect of CRH is significantly antagonized by the specific CRH receptor antagonist alpha-helical CHR 9-41 and is mimicked by sauvagine and urotensin I, two peptides displaying sequence homology with CRH. These results demonstrate the presence of functional CRH receptors in human Y-79 retinoblastoma cells and suggest that this cell line may be a suitable model in which to study the action of CRH on human retinal cell function.     

Quantitative assessment of technetium-99m methoxyisobutylisonitrile planar perfusion heart studies: application. of multivariate analysis to patient classification

A quantified evaluation of planar cardiac perfusion scintigrams (the objective of the study), obtained using technetium-99m methoxyisobutylisonitrile (MIBI) was performed on the basis of an analysis of circumferential profile curves, representing the perfusion as seen in three typical projections. The analysis involved the curves obtained both at rest and after stress, and was based on a comparison of their shape (trend) with the normal trend (normative evaluation). The latter was obtained by means of an original method of iterative fitting of individual curves into the database. The base consisted of curves recorded in 53 patients (separately in males and females) with normal perfusion of the left ventricle (group I, the reference group). A group of 90 patients suspected of having coronary artery disease (group II) was subdivided into two subgroups on the basis of coronary arteriography: (a) those with and (b) those without critical stenosis of at least one artery. Profile curves characterising the LV perfusion were obtained at rest and after stress. Defects of perfusion were quantified by comparison of individual curves with the normal trends. By means of multivariate analysis it was demonstrated that vectors of mean values characterising the scintigraphically assessed defects of LV perfusion in the two subgroups of group II differed very significantly (P<10^–5). Applying methods of discriminant analysis, a classification of patients from group II was performed into those with probable defects of perfusion and those free of such defects. The sensitivity, specificity and accuracy of diagnosis of coronary ischaemia, based on quantified planar^99mTc-MIBI scintigraphy, reached 86%, 87% and 87%, respectively.     

Cementoblastoma related to a primary tooth: a case report

Cementoblastomas are benign lesions of the odontogenic ectomesenchyme that rarely occur related to the primary dentition, especially on the left side of the mandible. This study describes a case of a true cementoblastoma related to the left second primary mandibular molar in a 7-year-old child (the largest one seen in the left side of the mandible). Additionally, the radiographic and histologic findings of the lesion are described in details.     

Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

Nephrology and renal replacement therapy in Romania--transition still continues (Cinderella story revisited).

INTRODUCTION. This report describes the current status of nephrology and renal replacement therapy (RRT) in Romania, a country with previously limited facilities, highlighting national changes in the European context. METHODS: Trends in RRT development were analysed in 2003, on a national basis, using the same questionnaires as in previous surveys (1991, 1995). Survival data and prognostic risk factors were calculated retrospectively from a large representative sample of 2284 patients starting RRT between January 1, 1995 and December 31, 2001 (44% of the total RRT population investigated). RESULTS: In 2003, RRT incidence [128 per million population (p.m.p.)] and prevalence (250 p.m.p.) were six and five times higher, respectively, than in 1995. The annual rate of increase in the stock of RRT patients (11%) was supported mainly by an exponential development of the continuous ambulatory peritoneal dialysis (CAPD) population (+600%), while the haemodialysis (HD) growth rate was stable (+33%) and renal transplantation made a marginal contribution. Renal care infrastructure followed the same trend: nephrology departments (+100%) and nephrologists (+205%). The characteristics of RRT incident patients changed accordingly to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). The estimated overall survival of RRT patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4-91.8] and 62.2% at 5 years (CI 59.4-65.0). Patients' survival was negatively influenced (Cox regression analysis) by age >65 years (P < 0.001), lack of pre-dialysis monitoring by a nephrologist [P = 0.01, hazards ratio (HR) = 0.8], severe anaemia, lack of erythropoetin treatment (P < 0.001, HR = 0.6), and co-morbidity, e.g. cardiovascular diseases (P < 0.001, HR = 1.8) and diabetes mellitus (P < 0.001, HR = 2.2). CONCLUSIONS: Although the rate of increase in RRT patient stock in 1996-2003 in Romania was the highest in Europe, the prevalence remained below the European mean. As CAPD had the greatest expansion, followed by HD, an effective transplantation programme must be set up to overcome the imbalance. The quality of RRT appears to be good and survival was similar to that in other registries. Further evolution implies strategies of prevention, based on national surveys, supported by the Romanian Renal Registry.     

Sex features at menarche in relation to gonadotropin, estradiol and sex hormone-binding globulin concentrations in girls with constitutional delay of puberty. Preliminary report.

OBJECTIVE: Constitutional delay of puberty (CDP) is the absence of secondary sexual features in otherwise healthy girls past the 13th year of life. The aim of the present work was to follow the development of estrogen-dependent sexual features, determine the concentrations of gonadotropins, estradiol and sex hormone-binding globulin (SHBG) in girls with CDP at menarche and compare the findings with normal controls. METHODS: We enrolled 11 girls with CDP and 40 controls. Primary, secondary and tertiary sexual features were studied at menarche +/- 3 months. The size of the ovaries and uterus was measured using transabdominal ultrasound. Maturation of breasts and pubic hair was staged according to Tanner. Concentrations of gonadotropins (follicle-stimulating hormone (FSH), luteinizing hormone) and estradiol were measured with immunoenzymatic methods. For measurement of SHBG, a radioimmunoassay was applied. RESULTS: Menarche in CDP girls usually appeared with Stage IV or V of breast development and Stage IV of pubic hair development according to Tanner. CDP girls demonstrated a significantly smaller volume of the uterine body at menarche compared with controls (p = 0.0004). Significantly lower levels of FSH (p = 0.0363) and estradiol (p = 0.0332), as well as a tendency towards lower levels of SHBG, were revealed in CDP girls at menarche. CONCLUSION: In CDP girls, menarche is accompanied by more mature tertiary sexual features, apparently resulting from longer exposure of estrogen-dependent tissues to the action of bioactive endogenous estrogens. The smaller volume of the uterine body in CDP girls at menarche may be attributed to decreased concentrations of FSH and estradiol, as well as to the possibility of decreased insulin-like growth factor-1 and increased neuropeptide Y levels.