Assessing Prognostic Significance of Preoperative Alpha-Fetoprotein in Hepatitis B-Associated Hepatocellular Carcinoma: Normal is not the New Normal

Background

Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear.

Methods

Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan–Meier analysis and multivariable Cox proportional hazards regression models.

Results

Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4–4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30–1.98), disease-free survival (HR = 1.26; 95 % CI 1.10–1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07–1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1–5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7–327,560.0 ng/mL) and Ishak stage 6 cirrhosis.

Conclusions

Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC.     

老年高血压患者血压昼夜节律对左室肥厚的影响

【摘要】 目的 研究老年高血压患者的血压昼夜节律变化对左室肥厚的影响。方法 选取我院126例高血压患者,根据心脏彩超提示左室肥厚情况分为肥厚组（n=52例）和非肥厚组（n=74例）。比较两组动态血压指标及血压变异性,进行多因素分析探讨血压变异性对左室肥厚的影响。 结果 高血压肥厚组24h平均收缩压（24hSBP）、白天平均收缩压（dSBP）、夜间平均收缩压（nSBP）、24h收缩压标准差（24hSSD）、24h舒张压标准差（24hDSD）、白天收缩压标准差（dSSD）、夜间收缩压标准差（nSSD）均高于非肥厚组,差异有统计学意义（P＜005）。Logistic回归分析显示,24h SBP 与dSSD、nSSD为左室肥厚的独立危险因素（P＜005）。结论 老年高血压患者的24h SBP 与dSSD、nSSD是影响左室肥厚的独立危险因素,平稳控制血压对防止左室肥厚的发生有一定影响。     

超低频振动对人体影响的研究

为研究超低频振动对人的视力、操作能力、胃电图、人体平衡稳定性和主观感觉的影响。实验采用０．２５、０．５、０．６３、０．８和１．０Ｈｚ五个振动频率，并参考之轴振动（头－足向）运动病频率范围，将实验结果按三个频段进行了分析。被试者取半仰卧位。结果表明，视力、操作能力、平衡稳定性不但与频率有关，而且随振动加速度的增加而降低。除视力外，它们随频率变化的规律符合所分频段含义，胃电图主频率改变和主观感觉级测试进一步说明了这一点。０．２５Ｈｚ不仅处在Ｚ轴全身振动的运动病敏感频段，而且也是Ｘ轴全身振动的敏感频率。因此，载人航天飞行中，不仅应避开０．２５Ｈｚ的Ｚ轴全身振动，而且也应避开０．２５Ｈｚ的ｘ轴全身振动。     

Abnormal clonogenic potential of T cells from multiple myeloma patients

Peripheral blood lymphocytes (PBLs) from multiple myeloma patients are defective in both proportion and absolute numbers of OKT4+ cells and have a normal proportion but reduced absolute number of OKT8+ cells. To assess the functional capabilities of the T cells in myeloma patients, we cloned the T cells in PBLs using limiting dilution conditions in which 100% of OKT4+ and OKT8+ T cells in normal PBLs are able to form a clone. In contrast, the OKT8+ cells from PBLs of five of seven multiple myeloma patients were severely compromised in their clonogenic potential; only 7% to 25% of OKT8+ T cells appeared to give rise to a clone. Clonogenic potential of the OKT4+ cells in patients was more nearly normal. Analysis of two multiple myeloma patients with abnormally low numbers of T cells in PBLs revealed the existence of abnormalities in the progenitors of T cell clones. In both patients, two to three times as many T cell clones were observed as would have been expected based on the number of PBLs cultured at limiting dilution, indicating that OKT4-8- cells in PBLs are capable of giving rise to OKT4+ and, at lower frequency, to OKT8+ clonal progeny in vitro. We conclude that purely quantitative assessment of T cell subsets should be interpreted with caution, since proportionately normal numbers of OKT8+ cells in patient PBLs are seriously compromised in their ability to give rise to clonal progeny in vitro, and since there appears to be a OKT4-8- population of T cells in PBLs that are committed to become OKT4+ or OKT8+ T cells, but are unable to do so in vivo.     

Measurement of Protein Synthetic Activity by Determination of Peptidyl[3H]puromycin Formation in Liver Slices after Ethanol Administration

We investigated the utility of [3H]puromycin as an alternate and adjunct precursor to amino acids for measuring protein synthetic activity in rat liver slices. Slices were incubated in the presence of either [3H]puromycin or radiolabeled valine to compare the incorporation of these isotopic precursors into nascent hepatocellular proteins. Compared to liver slices from controls, comparable decreases in the incorporation of both [3H]puromycin and labeled valine were observed in experiments using slices from fasted rats and in slices preincubated with 25 mM ethanol. Radiolabeling of nascent polypeptides with either [3H]puromycin or labeled valine in liver slices from rats fed a liquid diet containing ethanol was also decreased compared to slices from pair-fed control and chow-fed animals. Our results demonstrated the validity of using [3H]puromycin to detect changes in protein synthetic activity under these conditions. The potential advantage of using [3H]puromycin for in vivo studies is discussed.     

Effects of Ethanol on Reproduction and Arterial Hypertension in Spontaneously Hypertensive and Normotensive Rats: a Preliminary Communication

Ethanol consumption and spontaneous (essential) hypertension are important fetal and maternal risk factors. Alone, they contribute to embryopathy (fetal alcohol syndrome) or maternal organ pathology and fetal loss in hypertensive pregnancies. Combined, the effects of ethanol consumption on the progress of a hypertensive pregnancy have not been adequately investigated. In the present study, groups of O-A strain genetic hypertensive (SHR: groups 1 and 2) and Wistar-Kyoto normotensive (WKY: groups 3 and 4) pregnant rats were given 20 ml/kg of distilled water by gavage to serve as controls [groups 1 (SHR) and 3 (WKY)] or 3.2 g/kg of ethanol [groups 2 (SHR) and 4 (WKY)] from days 6 to 15 of gestation. During acclimation, hypertension developed in SHR rats (WKY pressures were 105 to 114 mm Hg; SHR pressures were 137 to 148 mm Hg). From day 6 to 15 of gestation, ethanol-consuming rats (groups 2 and 4) had higher arterial pressures than controls (groups 1 and 3). Pregnant SHR rats given ethanol did not experience a prebirthing hypotension. On gestation day 20, most offspring (84%, group 2; 86%, group 4) of alcoholic dams were dead or malformed. Intrauterine growth retardation occurred in group 4. Hydrocephalus, microphthalmia, and mild hydronephrosis and hydroureter were common in live offspring of group 2 dams. Hydronephrosis and hydroureter were increased in group 4 pups. Variant cranial ossification was noted in group 2 and 4 pups. These preliminary data suggest an altered hypertensive response during pregnancy in alcohol-consuming rats and confirm the embryopathic effects of relatively high levels of ethanol consumed during the critical period of organogenesis in two additional strains of rats.     

Histopathologic staining of low temperature cutaneous burns: Comparing biomarkers of epithelial and vascular injury reveals utility of HMGB1 and hematoxylin phloxine saffron

Histopathology remains the gold standard for evaluation of burn depth, progression, and healing, but burn literature offers little guidance on the best stains for analysis of these complex and evolving injuries. A battery of histochemical and immunohistochemical stains was compared on adjacent sections to determine the best stains for histopathologic study and imaging of burns. Using a validated porcine model of vertical burn progression, full‐thickness cutaneous biopsies were stained using hematoxylin and eosin, Hematoxylin phloxine saffron (HPS), Masson Trichrome, Elastin Von Gieson, Movatt's Pentachrome, vimentin, CD31, KI‐67, caspase 3a, and high mobility group box 1. Depth of collagen degeneration, cellular necrosis, apoptosis, and vascular occlusion; and reparative processes of cellular hyperplasia, reepithelialization, and new collagen deposition were measured by ocular microscopy. High mobility group box 1 was superior for necrosis between 1 and 24 hours postburn. Vimentin underestimated necrosis until 48 hours postburn. For overall assessment, hematoxylin and eosin and HPS were comparable, except for analysis of thermally injured collagen, vessel occlusion, erythrocyte extravasation, and polariscopic study of collagen deposition, where HPS was superior. HPS stain offers specific advantages in histopathologic burn analysis. Inexpensive and rapid to produce, HPS allows users to analyze eosinophilic components more precisely than standard hematoxylin and eosin.