Transfer of clonidine and dexmedetomidine across the isolated perfused human placenta

Background: The placental transfer of the a₂ receptor agonist clonidine, earlier used as an adjuvant in obstetric epidural analgesia, was compared with the transfer of the newer and more %-selective agonist dexmedetomidine.
Methods: Term placentas were obtained immediately after delivery with maternal consent and a 2-hour recycling perfusion of a single placental cotyledon was performed. Disappearance from the maternal circulation, accumulation in placental tissue and appearance in the fetal circulation of clonidine or dexmedetomidine with the reference compound antipyrine were followed in 4 experiments for both drugs.
Results: At 2 hours the percent dexmedetomidine found in the fetal circulation was 12.5 (SD 5.1)%, while 48.1 (SD 20.3)% was found in the perfused placental cotyledon. A higher mean clonidine than dexmedetomidine concentration was achieved in the fetal circulation (1.90 vs. 0.56 nmol/l, P <0.05). At 2 hours the percent clonidine found in the fetal circulation was 22.1 (SD 2.4)% ( P <0.05), while 11.3 (SD 3.3)% ( P <0.05) was re tained in the perfused placental cotyledon. The transfer indexes, describing maternal-to-fetal transfer of dexmedetomidine and clonidine normalized with the transfer of antipyrine, were 0.88 (SD 0.07) and 1.04 (SD 0.08) respectively ( P <0.05).
Conclusions: Dexmedetomidine disappeared faster than clonidine from the maternal circulation, while even less dexmedetomidine was transported into the fetal circulation. This was due to its greater placental tissue retention, the basis for which probably is the higher lipophilicity of dexmedetomidine.     

A case repot of Merkel cell carcinoma on chronic lymphocytic leukemia: differential diagnosis of coexisting lymphadenopathy and indications for early aggressive treatment

Background  

Chronic lymphocytic leukemia (CLL) is a monoclonal disorder, characterized by a progressive proliferation of functionally incompetent B lymphocytes. There is increased evidence of association between CLL and skin cancers, including the uncommon Merkel cell carcinoma (MCC).     

Serum cholesterol and high density lipoprotein cholesterol distributions in patients with acute myocardial infarction and in the general population of Kuopio Province,Eastern Finland

Abstract. As part of the FINMONICA project, serum total cholesterol (TC) and high density lipoprotein cholesterol (HDLC) concentrations were determined in 1216 AMI patients (937 men. 279 women) aged 35–64 years in the province of Kuopio in eastern Finland during the 5-year period 1983–87. The distributions were compared with the corresponding distributions in a representative sample of the general population of the same area (1026 men, 1021 women). The mean serum TC levels did not differ between the AMI patients and the normal population. Only the prevalence of a very high serum TC level (> 8.0 mmol l^?1) among women was significantly higher in the AMI group than in the population sample. On the other hand, in both sexes the age-adjusted mean HDLC was significantly lower in the AMI group than in the population sample. Our findings emphasize the importance of HDLC measurement as a part of the assessment of the lipid risk factor profile in patients with AMI.     

Diagnostic features of acute myocardial infarction – changes over time from 1983 to 1990: results from the FINMONICA AMI register study

Abstract. Objectives . To examine, whether the acute myocardial infarctions (AMIs) are becoming smaller. Design . Analysis of electrocardiogram (ECG) and enzyme findings of community-based AMI registers in three geographical areas of Finland during the 8-year period 1983–90. Setting . In the FINMONICA AMI Register, all suspected coronary events in persons aged 25–64 years have been registered since 1983 according to the protocol of the WHO MONICA project in the provinces of North Karelia and Kuopio in eastern Finland and Turku/Loimaa area in south-western Finland. Subjects . Each consecutive case of suspected AMI originating from the monitored populations. During the study period, 11487 definite or possible AMIs were registered. Main outcome measures . Trends in ECG findings classified as definite or probable, and trends in enzyme findings classified as abnormal or equivocal. Results . Of the registered AMIs, 8439 (73.5%) reached the hospital alive and survived ≥ 24 h from the beginning of the symptoms. They were included in the analyses of this report and divided further, to first ever AMIs (n = 5392) and to recurrent AMIs (3047). During the study period, the proportion of ECG findings classified as definite on the basis of the serial Minnesota coding declined in men 3.1% year^?1 (P < 0.0001) on average for first AMIs and 1.9% year^?1 (P = 0.004) for recurrent AMIs. In women, the corresponding declines were 1.9% year^?1 (P = 0.007) and 1.6% year^?1 (P = 0.02), respectively. Also, the proportion of enzymes classified as abnormal declined amongst men 2.2% year (P < 0.0001) for first AMIs and 2.8% year^?1 (P < 0.0001) for recurrent AMIs. In women, the corresponding declines for abnormal enzymes was 1.3% year^?1 (P = 0.13) and 3.0% year^?1 (P = 0.02). These findings were consistent in all three areas with different registration teams and different laboratories. The proportion of definite ECG findings amongst patients hospitalized for AMI declined almost by half and the proportion of abnormal enzyme findings declined almost by one-third during the study period. Conclusions . Our findings are compatible with the clinical observation that the hospitalized AMIs are becoming smaller. The timing and magnitude of the changes suggest that they are mainly caused by decreased risk-factor levels in the population. Improved treatment of coronary heart disease and changed hospital admission policy are likely to be contributing factors.     

Thyroid autoimmunity is associated with higher urinary iodine concentrations in an iodine-deficient area of Northwestern Greece.

Northwestern Greece was identified in the 1960s for its high prevalence of endemic goiter and iodine deficiency. Although iodized salt has been commercially available since then, a recent epidemiological survey of 3916 schoolchildren found that low-grade goiter is still prevalent in endemic proportions (21%). The aim of this study was to further assess the cause of goiter and the severity of iodine deficiency in children from this endemic area of Greece. Of the 800 children with clinically detectable goiter, 97 children (60 girls and 37 boys, 8-15 years) were recruited for determination of urinary iodine excretion, as well as assessment of thyroid volume and function and detection of antithyroid antibodies. The median urinary iodine concentration was 8.4 microg/dL, indicative of a mild iodine deficiency. Thyroid function was normal in all but 11 children who had subclinical hypothyroidism. Sixteen children (16.5%), including all those with subclinical hypothyroidism, were positive for antithyroid antibodies. Their median urinary iodine concentration (20.6 microg/dL) was higher compared to children who were negative for antibodies (7.4 microg/dL; p<0.001). The mean thyroid volume by ultrasonography (12.2+/-4.1 mL) was above the upper limit of normal for this age group. Thyroid volume was inversely related to the urinary iodine content in the children with negative antithyroid antibodies. Iodine deficiency is still prevalent in northwestern Greece although of mild severity and constitutes the primary cause of goiter among schoolchildren. However, it appears that autoimmune thyroiditis is emerging as a frequent cause of goiter in those children with sufficient iodine intake.     

Study of growth hormone secretion and action in growth-retarded children with juvenile chronic arthritis (JCA).

The stimulated and spontaneous growth hormone (GH) secretion and the response to GH action were assessed in growth-retarded children with juvenile chronic arthritis (JCA), in order to determine the underlying mechanisms of growth retardation in such children. Six children (4 boys and 2 girls aged 10.7-13.8 years) with active JCA of systemic onset were included in the study which involved: (1) anthropometric measurements; (2) assessment of GH responses to insulin-induced hypoglycaemia and clonidine stimulation; (3) assessment of the nocturnal pulsatile GH secretion by measuring GH in blood samples obtained every 20 min from 20.00 to 08.00 h; and (4) the IGF-I generation test. As a control, the latter test was also performed in eight aged-matched children with physiological delay in puberty. Biosynthetic hGH (0.1 IU/kg BW) was administered s. c. for 4 days and blood samples were taken at baseline and the morning after the last GH injection for measurement of IGF-I and IGFBP-3.All six children with JCA were prepubertal and their growth velocity was <3 cm/year. The GH responses to both stimulation tests were normal (peak GH >20 mU/l). Analysis of the pulsatile GH secretion during the night revealed three-to-four GH pulses of normal amplitude (>20 mU/l). IGF-I (26.7+/-4.6 nmol/l, mean+/-SD) and IGFBP-3 (2.1+/-0.2 mg/l) levels were lower in the patients compared with the controls (43.0+/-3.7 nmol/l and 2.8+/-0.2 mg/l, respectively, P<0.01). Following stimulation with exogenous hGH, there was a significant increase in IGF-I and IGFBP-3 levels in the control group (85 and 73%, respectively), but only a small increase in the patients (31 and 14%).It appears that stimulated and spontaneous GH secretion is normal in children with active systemic JCA, but the response to endogenous and exogenous GH with regard to IGF-I and IGFBP-3 production is impaired, indicating a degree of GH insensitivity in such children.     

Long‐Term Clinical Outcomes of the One‐Stent Technique versus the Two‐Stent Technique for Non‐Left Main True Coronary Bifurcation Disease in the Era of Drug‐Eluting Stents

Background

Few studies have compared the long‐term major adverse cardiac events (MACEs) between the one‐stent technique (stenting only the main branch) and the two‐stent technique (stenting of both the main and side branches) for the treatment of true coronary bifurcation lesions in the drug‐eluting stent era. Therefore, we investigated this issue using the large nationwide coronary bifurcation registry.

Methods

The 1,147 patients with non‐left main coronary true bifurcation lesions underwent percutaneous coronary intervention in the Korea Coronary Bifurcation Stent (COBIS) registry. All patients were stratified based on the stent placement technique: one stent (n = 898) versus two stents (n = 249). MACE, including death, nonfatal myocardial infarction (MI), and repeat vessel and lesion revascularization (TVR and TLR), were evaluated.

Results

The median follow‐up duration was 20 months. The MACEs did not differ between the 2 groups. Findings from the one‐stent group were similar to those of the two‐stent group in composite of death, MI, or TVR, based on analysis by crude, multivariate Cox hazard regression model, inverse‐probability‐of‐treatment weighting (hazard ratio [HR] 0.911, 95% confidence interval (CI) 0.614–1.351; HR 0.685 95% CI 0.381–1.232; HR 1.235, 95% CI 0.331–4.605, respectively). In further analysis with propensity score matching, the overall findings were consistent.

Conclusions

The findings of the present study indicate that the one‐stent technique was not inferior to the two‐stent technique for the treatment of non‐left main true coronary bifurcation lesions in terms of long‐term MACEs. (J Interven Cardiol 2013;26:245–253)