The calcitonin-calcium relation curve and calcitonin secretory parameters in renal patients with variable degrees of renal function

Increased calcitonin (CT) levels have been reported in chronicrenal failure, even before the uraemic phase and in the absenceof hypercalcaemia. Furthermore, a sigmoidal CT-calcium relationshipwas recently observed in rats and haemodialysed patients. We carried out the present investigation in order to assess:(a) whether the sigmoidal CT-calcium relationship is also evidentin renal patients with a variable degree of renal failure andin normal subjects; (b) whether the four secretory parametersalready described for the PTH-calcium relation curve might bedescribed for CT too; (c) whether any change in some, if any,of these secretory parameters could be found at a variable degreeof renal insufficiency. We studied 33 renal patients (RP), with a variable degree ofrenal failure (creatinine clearance ranging from 16 to 164ml/min),and 10 normal subjects (C). All RP and C were submitted to abasal evaluation including the assessment of (1) basal concentrationsof 1,25(OH)₂ vitamin D, 25(OH) vitamin D, mono-meric CT, intactPTH; (2) GFR by Cr⁵¹EDTA clearance. On the 2 subsequent days,a hypocalcaemic test (Na₂-EDTA about 37 mg/kg of body-weight/2h) and a hypercalcaemic test (Ca gluconate giving 8 mg/kg body-weight/2h of Ca element) were carried out for the assessment of bothCT and PTH secretory parameters. According to GFR values, theRP were divided into three groups: group RP1 (GFR > 70 ml/minper 1.73 m²; n = 10), group RP2 (GFR between 30 and 70 ml/minper 1.73 m²; n=15), group RP3 (GFR < 30 ml/min per 1.73 m²;n = 8). In most, but not all, RP and C a sigmoidal CT-calcium relationshipwas evident, opposite in direction to the PTH-calcium relationcurve. In these RP and C the four secretory parameters, characteristicfor the PTH-calcium secretion curve, were calculated for CTtoo. When pooled RP and C were considered, both minimal (9.0± 6.4 pg/ml) and maximal CT levels (71.8 ± 56.2pg/ml) significantly differed from basal levels (24.3±18 pg/ml; P<0.001). The CT set point (CT SP) and sensitivity(CT SENS) values were significantly higher and lower than thecorresponding PTH secretory parameters (CT SP 1.39 ±0.08 mmol/1, PTH SP 1.23 ± 0.05 mmol/1,P<0.001) (CTSENS 243 ± 67%/mmol, PTH SENS 598 ± 329%, P<0.001).However, the CT SP values were strictly correlated with PTHSP values (r = 0.78, P<0.001). When CT secretory parameterswere considered separately in the RP groups, increased levelsof basal (36.1±28.6pg/ml), minimal (17.9±10.4),and maximal (139.9 ± 39.7) CT levels were found in theRP3 group, when compared with both the other RP groups and C.No significant difference was found as regards the CT SP andCT SENS values between RP and CT. These results suggest that (1) CT secretion is homeo-staticallycontrolled by calcium changes in the same range of the PTH-calciumsystem; (2) a sigmoidal CT-calcium relationship is demonstrablein most (but not all) RP and C; in these subjects it is possibleto calculate the CT secretory parameters as for PTH; (3) theincrease in CT levels in the course of chronic renal failureis quite similar to the already known increase of PTH, and ischaracterized by the increase of basal, minimal and maximalCT values, suggesting that an increased secretion of CT by thethyroid C-cells (rather than CT retention due to a decreasein renal function), is responsible for these findings.     

Radiofrequency catheter ablation of an accessory pathway through an anomalous inferior vena cava with azygos continuation.

A 59-year-old man with Wolff-Parkinson-White syndrome and an infrahepatic interruption of his inferior vena cava with an azygos continuation underwent a successful ablation of a right anteroseptal accessory pathway with a femoral approach through the azygos vein and superior vena cava.     

Operative treatment of the post-traumatic boutonnière deformity. A modification of the direct anatomical repair technique

We report 20 cases of post-traumatic boutonnière deformity treated by a modification of the direct anatomical repair technique, particularly indicated in late cases which have complete passive motion. A swallow-tailed flap is excised from the fibrous tissue between the two ends of the central slip. The proximal one is then advanced up to the coaptation with the distal edge of the scarred capsular tissue at the insertion on the middle phalanx to which it is sutured in correct tension. Excellent results have been obtained in 72% of cases and good in 5.5%. The 16% of fair results are probably due to the fact that patients didn't use the splint post-operatively and didn't cooperative with physiotherapy.     

Increased expression of Ob-Rb and its relationship with the overexpression of TGF-beta1 and the stage of fibrosis in patients with nonalcoholic steatohepatitis.

AIMS: The main aim of this study was to examine the relationship of the leptin system in steatosis and nonalcoholic steatohepatitis (NASH). The study also analysed the pathogenic role of the leptin system in the development of hepatic fibrosis and its relation with the TGF-beta1 system. MATERIALS AND METHODS: The study included 90 subjects, 55 with NASH and 35 with simple steatosis. Gene expression of leptin, leptin receptor and TGF-beta mRNA was analysed by real-time PCR on liver tissue. Leptin serum levels were determined by RIA. Leptin receptor expression was also assessed by immunohistochemistry. RESULTS: Increased expression was found for leptin receptor mRNA (P=0.0016) and its protein (P<0.05) in patients with NASH, especially those with fibrosis. There was a marked increase in gene expression of TGF-beta1 in patients with NASH (P=0.0002). A strong correlation was demonstrated between leptin receptor gene expression and TGF-beta1 gene expression (P=0.023). No leptin expression was found in the liver tissue. All patients showed a marked hyperleptinemia, which was closely related to the anthropometric characteristics analysed and independent of development or not of NASH. CONCLUSIONS: The results of the study demonstrate for the first time increased leptin receptor expression in liver tissue and its relationship with overexpression of TGF-beta1 and the degree of hepatic fibrosis.     

Comparison of trends in ischaemic heart disease between North Karelia, Finland, and Kaunas, Lithuania, from 1971 to 1987

Objective—To compare the long-term trends in mortality and attack rate of ischaemic heart disease in North Karelia, Finland, and in Kaunas, Lithuania, from 1971 to 1987.

Design—Data on routine mortality statistics were obtained from the Central Statistical Office of Finland and from the Central City Archives of Kaunas. In addition, data from the community based myocardial infarction registers were used. The registers used similar diagnostic criteria and had operated in both areas during the entire study period.

Setting—The province of North Karelia in Finland and the city of Kaunas in Lithuania.

Subjects—The target populations were the people of North Karelia and Kaunas aged 35–64 years.

Main outcome measures—Mortality from ischaemic heart disease and the attack rate of acute myocardial infarction.

Results—In North Karelia mortality from ischaemic heart disease and the attack rate of acute myocardial infarction declined steeply both in men and women. This decline was accompanied by a decrease in total mortality. In Kaunas, both mortality and the attack rate increased in men but remained unchanged in women. In 1985 to 1987, age standardised total mortality per 100 000 inhabitants was similar in the two populations in men (1081 (95% confidence interval (CI) 1013 to 1149), in North Karelia; 1082 (95% CI 1032 to 1132), in Kaunas). The proportional mortality from ischaemic heart disease was considerably higher in North Karelia (40%) than in Kaunas (28%). In women, age standardised total mortality was lower in North Karelia (350 (95% CI 312–388)) than in Kaunas (440 (95% CI 413 to 467)). The proportional mortality from ischaemic heart disease in women was also higher in North Karelia (28%) than in Kaunas (13%).

Conclusions—Despite the remarkable decline in the occurrence of ischaemic heart disease, it still remains the most important cause of premature mortality in North Karelia. In Kaunas ischaemic heart disease mortality and attack rate increased in men. Experiences from successful cardiovascular disease prevention programmes in western countries, such as the North Karelia Project, should be exploited to prevent an increasing epidemic of ischaemic heart disease in eastern Europe.

     

Effect of subject expectancy on the THC intoxication and disposition from smoked hashish cigarettes.

Subject expectancy on cannabis effects was assessed in a balanced-placebo study in experienced consumers who smoked cigarettes containing hashish (200 mg hashish with 11.5% THC per 1 g tobacco cigarette) (n = 24) or placebo (n = 24). Although statistically significant differences were not found between subjects who received the drug with positive or negative expectancy, a tendency toward more marked subjective effects was shown in subjects who expected and received the drug. This trend was supported by the significant difference observed in the mean AUC0-25 of the heart rate between subjects who smoked hashish with positive or negative expectancies. In subjects who received hashish, the sum AUC0-205 of THC and COOH-THC of those who expected the drug was greater than in those who did not expect it (p less than 0.05). The ratio THC/COOH-THC AUC0-205 was lower in those with positive expectancy than in those with negative expectancy (p less than 0.02). An increased metabolism of THC was shown in subjects with positive expectancy. Positive expectancy induced powerful subjective effects in the absence of active THC. Expectancy appeared to influence smoking behavior, as seen in higher plasma levels of cannabinoids for the group who received the drug.     

Tumor suppressor protein p53 and anti-p53 autoantibodies in pediatric rheumatological diseases

The tumor suppressor protein p53 plays an important role in cell cycle regulation. One of the major features in rheumatic diseases is the abnormal proliferation of lymphocytes. p53 expression in peripheral blood mononuclear cells (by flowcytometry) and serum anti-p53 antibodies (by ELISA) were therefore measured in 18 children and adolescents with juvenile rheumatoid arthritis (JRA) and 17 with systemic lupus erythematosus (SLE) in comparison to 20 healthy controls, to determine their role. p53 expression in patients was insignificantly higher than that of controls (2.28 ± 2.71% vs. 1.08 ± 1.02%, respectively, p > 0.05) with 29.4% of the patients showing values above a cut-off level of 2.55% (95th percentile of controls). SLE patients with active disease had significantly higher p53 expression compared to controls and to patients with quiescent disease although no significant correlation with ESR or complement 3 was detected. Seropositivity to anti-p53 antibodies was observed in none of controls but in 22.8% of patients, all of whom, except one, had active disease. Seropositivity to anti-p53 antibodies was more prominent in lupus nephritis than in other presentations of SLE (p < 0.05). The mean p53 expression in seropositive patients was insignificantly higher than in seronegatives. p53 expression and seropositivity to anti-p53 were slightly higher in SLE than in JRA and were not significantly affected by the mode of therapy. Thus, the overexpression of p53 in some patients with active SLE and JRA might explain the abnormal proliferation of autoreactive lymphocytes that perpetuates the inflammatory response. The presence of anti-p53 antibodies might cause malfunctioning of p53 protein interfering with its regulatory functions.