Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can)

Objective

To investigate metabolic factors and their possible impact on risk of thyroid cancer.

Methods

A prospective cohort study was conducted based on seven population-based cohorts in Norway, Austria, and Sweden, in the Metabolic syndrome and Cancer project (Me-Can). Altogether 578,700 men and women with a mean age of 44.0 years at baseline were followed for on average 12.0 years. Relative risk of incident thyroid cancer was assessed by levels of BMI, blood pressure, and blood levels of glucose, cholesterol, triglycerides, and by a combined metabolic syndrome (MetS) score. Risk estimates were investigated for quintiles, and a z score distribution of exposures was analyzed using Cox proportional hazards regression.

Results

During follow-up, 255 women and 133 men were diagnosed with thyroid cancer. In women, there was an inverse association between glucose and thyroid cancer risk, with adjusted RR: 95% CI was 0.61 (0.41?C0.90), p trend = 0.02 in the fifth versus the first quintile, and a positive association between BMI and thyroid cancer risk with a significant trend over quintiles. There was no association between the other metabolic factors, single or combined (Met-S), and thyroid cancer.

Conclusion

In women, BMI was positively, while blood glucose levels were inversely, associated with thyroid cancer.     

子宫颈腺癌石蜡包埋组织中人类乳头状瘤病毒型别分布及其与患者年龄的关系

 【摘要】　目的　探讨子宫颈腺癌中人类乳头状瘤病毒（HPV）的分布情况及HPV感染与患者年龄的关系。方法　采用描述流行病学研究设计,纳入32例来自一项多中心临床研究的经病理确诊的子宫颈腺癌患者的标本。采用三明治技术进行石蜡包埋组织的切片,SPF10-PCR技术进行DNA扩增,使用反向杂交线型探针检测技术（LiPA）进行HPV分型;对所有切片进行病理阅片和诊断,分析确诊为子宫颈腺癌标本的HPV分布情况,并行统计学分析。结果　32例腺癌患者中,HPV阳性率为53.1 %（17／32）。HPV-18为最主要HPV型别,占HPV阳性患者的47.4 %（8／17）,其次为HPV-16,占HPV阳性患者的26.3 %（5／17）。检测到的其他型别为HPV-39、HPV-45和HPV-66;多重感染者1例（HPV-18和HPV-66）。HPV-16与HPV-18相比,其阳性的腺癌患者平均年龄分别为48.6和40.6岁,差异有统计学意义（P＝0.048）。采用<50岁以及≥50岁作为年龄分组,HPV任意型别阳性率在两个年龄组中的差异无统计学意义（P＝0.074）。HPV-18在两个年龄组的腺癌患者和HPV阳性腺癌患者中的分布均差异有统计学意义（P＝0.003、P＝0.029）。HPV-16在两个年龄组腺癌患者中和在HPV阳性的腺癌患者中的分布差异无统计学意义（P＝1、P＝0.6）。HPV-16和（或）HPV-18感染在两个年龄组HPV阳性腺癌患者中的阳性率差异无统计学意义（P＝0.052）,但在全部腺癌患者两个年龄组中阳性率差异有统计学意义（P＝0.005）。结论　HPV-18和HPV-16是子宫颈腺癌中最主要分布的两种HPV型别。HPV阳性尤其HPV-18阳性在年轻的腺癌患者中更为常见。HPV-16阳性较HPV-18阳性在年龄较大的妇女中更为常见。     

Impact of moderate renal insufficiency on restenosis and adverse clinical events after sirolimus-eluting and bare metal stent implantation (from the SIRIUS trials)

Whether drug-eluting stents are effective and safe in patients with moderate renal insufficiency (RI) is unknown. We performed a pooled analysis of data from 3 blinded randomized trials of sirolimus-eluting stents (SESs) versus bare metal stents (BMSs; SIRIUS, C-SIRIUS, E-SIRIUS) that included 1,510 patients. Clinical and angiographic outcomes were stratified by the presence of RI defined by creatinine clearance calculated by the Cockcroft-Gault formula (normal ≥ 90, mild 60 to 89, moderate < 60 ml/min). Patients with baseline creatinine > 3.0 mg/dl were excluded from these trials. Baseline mild RI was present in 517 patients (34.7%, mean creatinine clearance 75.7 ml/min) and moderate RI in 228 patients (15.3%, mean creatinine clearance 47.2 ml/min). Treatment with SESs resulted in lower rates of 8-month angiographic restenosis rates in patients with RI (mild RI 6.7% vs 42.6%, p < 0.001; moderate RI 9.7% vs 39.7%, p < 0.001) and without baseline RI (7.7% vs 37.2%, p < 0.001). One-year target vessel revascularization rates were similarly decreased with SESs in patients with (mild RI 4.7% vs 24.2%, p < 0.001; moderate RI 5.5% vs 26.9%, p < 0.001) and without (8.1% vs 22.4%, p < 0.001) RI, and this benefit was maintained at 5 years. Compared to patients with normal or mild RI, patients with moderate RI had higher rates of overall mortality and cardiac death at 1 year and 5 years (death 2.6% vs 0.6%, p <0.01, and 17.5% vs 6.3%, p < 0.01, at 1 year and 5 years, respectively; cardiac death 1.3% vs 0.2%, p = 0.05, and 6.6% vs 3.4%, p = 0.04, at 1 year and 5 years, respectively). However, there was no differential effect of SESs versus BMSs on any safety end point. In conclusion, patients with moderate RI have a nearly threefold increase in 5-year mortality after percutaneous coronary intervention compared to patients without RI. The effectiveness of SESs in decreasing restenosis compared to BMSs in patients with moderate RI was preserved and rates of death and myocardial infarction were not adversely affected.     

Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects

Molecular ultrasound is capable of elucidating the expression of angiogenic markers in vivo. However, the capability of the method for volumetric "multitarget quantification" and for the assessment of antiangiogenic therapy response has rather been investigated. Therefore, we generated cyanoacrylate microbubbles linked to vascular endothelial growth factor receptor 2 (VEGFR2) and alphavbeta3 integrin binding ligands and quantified their accumulation in squamous cell carcinoma xenografts (HaCaT-ras-A-5RT3) in mice with the quantitative volumetric ultrasound scanning technique, sensitive particle acoustic quantification. Specificity of VEGFR2 and alphavbeta3 integrin binding microbubbles was shown, and changes in marker expression during matrix metalloproteinase inhibitor treatment were investigated. In tumors, accumulation of targeted microbubbles was significantly higher compared with nonspecific ones and could be inhibited competitively by addition of the free ligand in excess. Also, multimarker imaging could successfully be done during the same imaging session. Molecular ultrasound further indicated a significant increase of VEGFR2 and alphavbeta3 integrin expression during tumor growth and a considerable decrease in both marker densities after matrix metalloproteinase inhibitor treatment. Histologic data suggested that the increasing VEGFR2 and alphavbeta3 integrin concentrations in tumors during growth are related to an up-regulation of its expression by the endothelial cells, whereas its decrease under therapy is more related to the decreasing relative vessel density. In conclusion, targeted ultrasound appears feasible for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive assessment of therapy effects in vivo.     

Histiotypic electrophysiological responses of cultured neuronal networks to ethanol

Embryonic murine neuronal networks cultured on substrate-integrated microelectrode arrays were used to quantify acute electrophysiological effects of ethanol by using extracellular, multichannel recording of action potentials. Spontaneously active frontal cortex cultures showed repeatable, concentration-dependent sensitivities to ethanol, with initial inhibition at 20 mM and a spike rate 50% effective concentration (EC₅₀) of 48.8±5.4 mM. Ethanol concentrations of greater than 100 mM led to cessation of activity. The ethanol inhibitions up to the maximum tested 160 mM were reversible. Although ethanol did not change the shape of action potentials, unit-specific spike pattern effects were found. At 40 mM, ethanol decreased neuronal firing in 71%, increased firing in 20%, and generated no effect in 9% of all units observed (14 cultures, 200 discriminated units). The effects of combined application of ethanol and fluoxetine were additive. Excellent agreement with findings obtained from experimental studies with animals validates the use of these in vitro systems for alcohol research.     

Acute Changes in Oxyhemoglobin Affinity EFFECTS ON OXYGEN TRANSPORT AND UTILIZATION

It has been postulated that 2,3-diphosphoglycerate (DPG)-mediated changes in oxyhemoglobin affinity play an important role in oxygen delivery; however, the effect of an acute increase in affinity without changing red cell mass has not been systematically evaluated. This study was designed to measure changes in oxygen transport and oxygen consumption produced by an acute increase in oxyhemoglobin affinity caused by an autologous exchange transfusion using DPG-depleted stored blood.From each of 10 5-kg rhesus monkeys, 100 ml of blood was taken on the 1st and 3rd wk of the study and each stored in 25 ml of acid-citrate-dextrose storage solution. On the 5th wk, each animal underwent an exchange transfusion with 200 ml of its stored blood. Hemodynamic data were obtained before and 30 min after transfusion. The oxyhemoglobin dissociation curve shifted to the left (P(50) changed from 33.9 to 27.2 mm Hg), as mean red cell DPG decreased from 28.6 to 12.7 mumol/g of hemoglobin. No significant change was noted in pH, P(CO2), base deficit, arterial or venous percent saturation of hemoglobin, cardiac output, or oxygen consumption. However, a fall in mixed venous P(O2) from 35.3 to 27.9 mm Hg occurred.Thus, an acute shift of the oxyhemoglobin curve to the left was accompanied by a significant decrease in the mixed venous P(O2) without evidence of acidosis, decreased oxygen consumption, or a compensatory increase in cardiac output.     

Endothelial lipase provides an alternative pathway for FFA uptake in lipoprotein lipase-deficient mouse adipose tissue

Lipoprotein lipase (LPL) is thought to be the only enzyme responsible for the catabolism of triglycerides (TGs) associated with TG-rich lipoproteins in adipose tissue (AT). However, LPL deficiency in humans and induced mutant mice is not associated with decreased fat mass. We investigated whether endothelial lipase (EL), a recently discovered phospholipase, might represent an alternative mechanism for the uptake of phospholipid-derived fatty acids in murine lipoprotein-deficient AT. When LPL was expressed in AT and isolated murine adipocytes, EL mRNA was not detectable. In contrast, mouse AT and isolated adipocytes that lacked LPL expressed large amounts of EL mRNA. The cellular phospholipase activity in LPL-deficient fat pads was increased 4-fold compared with control fat pads and could be inhibited to control levels by a specific EL antibody. Fatty acids produced by EL activity were absorbed by adipocytes and incorporated into the TG moiety of AT. Our results suggest that EL activity in AT and other peripheral tissues might contribute to the tissue uptake of free fatty acids, which could have important implications for the metabolism of plasma lipoproteins.     

Increased plasma levels of NT-proANP and NT-proBNP as markers of cardiac dysfunction in septic patients

The family of natriuretic peptides comprises several structurally related 22-53-amino acid peptides, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are vasoactive peptides with vasodilator and diuretic properties and play an important role in cardiovascular homeostasis. The salutary cardiovascular effects of natriuretic peptides suggest that ANP and BNP may have a pathophysiological significance in the cardiac dysfunction of septic patients. We determined plasma levels of the stable N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) as well as troponin I (TNI) as a marker of myocardial cell injury by ELISA methods in 19 septic patients and 19 healthy controls at day one of severe sepsis. Left ventricular ejection fraction (LVEF) was determined on day 1 of severe sepsis by echocardiography. Significantly higher concentrations of NT-proANP were measured in non-survivors (mean = 13415 pmol/l +/- SEM = 4295) and survivors (mean = 7386 pmol/l +/- SEM = 1807) as compared to controls (mean = 1404 pmol/l +/- SEM = 181; p<0.001). Levels of NT-proBNP were also significantly higher in non-survivors (mean = 3439 pmol/l +/- SEM = 1246; p<0.05) and survivors (mean = 1009 pmol/l +/- SEM = 263; p<0.001) as compared to controls (mean = 200 pmol/l +/- SEM = 24) and correlated well with an increase in TNI-levels (r = 0.71; p<0.001). NT-proANP and NT-proBNP may serve as useful laboratory markers to indicate myocardial dysfunction and may help to differentiate between survivors and non-survivors of severe sepsis.     

Differences in T cell subsets between men and women with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder, occurring predominantly in women. We studied by flow cytofluorimetry the T cell subsets in men and women with ITP and compared them with healthy sex-matched volunteers. In healthy controls, women were found to have higher proportions of T helper/inducer (Th/i) and lower T suppressor/cytotoxic (Ts/c) lymphocytes and consequently higher Th/i:Ts/c ratios than men. Accordingly, in clinical surveys, patients and controls should be matched for sex for proper comparisons. In patients with ITP in its active phase, an imbalance in T cell subsets was found in both sexes. The perturbation was more severe in women who had a marked decrease in number and proportion of Th/i lymphocytes and an increase in the proportion of Ts/c lymphocytes, whereas in men only, the proportion of Th/i lymphocytes was decreased. When patients with active disease were compared to those with ITP in remission, the decrease in Th/i subsets still persisted in both sexes but the Ts/c subset in women had returned to normal proportions. Therefore, the immune imbalance in ITP is more marked in women than men; imbalances in both Th/i and Ts/c are present in women while Ts/c appears not to be involved in men.