Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome

OBJECTIVE: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV-seropositive individuals. The aim of the study was to compare the main features of HCC in HIV-seropositive individuals with those in to HIV-negative patients. PATIENTS AND METHODS: All HIV-infected subjects with a diagnosis of HCC included in three cancer registry databases were enrolled in the study as cases. HCC cases that occurred in the province of Brescia, North Italy, in the period 1995-1998 and all cases reported at the Italian Liver Cancer Project were enrolled as controls. All data were collected using a standardized case report form. The main clinical and epidemiological characteristics of patients with HCC and their survival were compared between HIV-positive and uninfected subjects. RESULTS: Forty-one HIV-infected subjects with HCC were identified. Multivariate analysis adjusted for age and sex identified an association between HIV infection and HCV infection [odds ratio (OR), 11; P = 0.005], and infiltrating tumours and/or extranodal metastasis at presentation (OR = 11.8; P < 0.001). HIV infection was independently associated with shorter survival (hazard ratio, 1.63; P = 0.015). CONCLUSIONS: HCC in HIV-infected patients is mainly associated with underlying chronic hepatitis C and has a more aggressive clinical course. Thus, preventative strategies (including the treatment of hepatitis C) should be implemented in the management of HIV/HCV-coinfected patients.     

Patterns of antimicrobial use and antimicrobial resistance among healthy children in Bolivia

Summary
objective   To determine the incidence of antimicrobial-resistant, nonpathogenic Escherichia coli among healthy children aged 6–72 months in Camiri town and a rural village, Javillo, in south-eastern Bolivia.
method   A community-based survey: stool samples were obtained from 296 healthy children selected by modified cluster sampling in Camiri and all 25 eligible children in Javillo. E. coli isolates were tested for antimicrobial susceptibility according to the standard disc diffusion method. By a questionnaire survey of 12 pharmacies and by using simulated patients, we investigated the antimicrobial availability and the usage patterns in Camiri town.
results   In Camiri, over 90%, and in Javillo over 70% of children carried E. coli resistant to ampicillin, trimethoprim-sulphamethoxazole (TMP/SMX) or tetracycline. Overall, 63% of children carried E. coli with multiple resistance to ampicillin, TMP/SMX, tetracycline and chloramphenicol. In the simulated patients study, antimicrobials were dispensed inappropriately for 92% of adults and 40% of children with watery diarrhoea, and were under-prescribed for males with urethral discharge (67%) or females with fever and dysuria (58%). The dose and/or duration of antimicrobials dispensed was almost always too low.
conclusion  Our study showed a disturbingly high prevalence of carriage of nonpathogenic E. coli resistant to antimicrobials. The prevalence of resistance to ampicillin and TMP/SMX was higher than that previously reported in developing countries. The existence of a large reservoir of resistance genes in healthy individuals in developing countries represents a threat to the success of antimicrobial therapy throughout the world. Programmes to improve rational and effective drug use in developing countries are urgently needed.     

The use of a telematic connection for the follow-up of hypertensive patients improves the cardiovascular prognosis

BACKGROUND: Inadequate blood pressure (BP) control could be due to incorrect management of hypertensives caused by the lack of interaction between general practitioners (GP) and hypertension specialists. OBJECTIVES: To test the effectiveness on BP and total cardiovascular risk (TCVR) control of an internet-based digital network connecting specialists and GPs. METHODS: We created a network among the Hypertension Clinic, Federico II University (Naples, Italy), 23 hospital-based hypertension clinics and 60 GPs from the area (CampaniaSalute Network, CS). Randomized GPs enrolled in CS could update online records of patients (n = 1979). As a control, we included 2045 patients referred to the specialist clinics by GPs from outside the network. All patients completed a 2-year follow-up. RESULTS: CS provided a larger reduction in BP [systolic/diastolic BP (SBP/DBP): 7.3 +/- 0.4/5.4 +/- 0.3 versus 4.1 +/- 0.4/3.1 +/- 0.26 mmHg, CS versus control; P < 0.001 for both] and percentage of patients with BP < 140/90 mmHg (CS versus control: baseline, 33 versus 34%, NS; end of follow-up, 51 versus 47%, chi = 13.371; P < 0.001). A European Society of Hypertension-European Society of Cardiology (ESH/ESC) TCVR score was calculated [from 1 (average) to 5 (very high TCVR)]. The CS group showed a reduction in the mean TCVR score (CS: from 3.5 +/- 0.02 to 3.2 +/- 0, P < 0.01, ANOVA; control group: 3.5 +/- 0.03 to 3.4 +/- 0.03, NS) and, accordingly, fatal and non-fatal major cardiovascular events (MACE) were less frequent (2.9 versus 4.3%; chi = 5.047, P < 0.02). CS predicts fewer MACE in multiple binary regression analysis (beta:-7.27, P < 0.008) reducing the risk for MACE compared to control [odds ratio (OR): 0.838; 95% confidence interval (CI): 0.73-0.96]. CONCLUSION: Our results support the idea that telemedicine can achieve better control of BP and TCVR.     

Role of kinin B2 receptor signaling in the recruitment of circulating progenitor cells with neovascularization potential

Reduced migratory function of circulating angiogenic progenitor cells (CPCs) has been associated with impaired neovascularization in patients with cardiovascular disease (CVD). Previous findings underline the role of the kallikrein-kinin system in angiogenesis. We now demonstrate the involvement of the kinin B2 receptor (B(2)R) in the recruitment of CPCs to sites of ischemia and in their proangiogenic action. In healthy subjects, B(2)R was abundantly present on CD133(+) and CD34(+) CPCs as well as cultured endothelial progenitor cells (EPCs) derived from blood mononuclear cells (MNCs), whereas kinin B1 receptor expression was barely detectable. In transwell migration assays, bradykinin (BK) exerts a potent chemoattractant activity on CD133(+) and CD34(+) CPCs and EPCs via a B(2)R/phosphoinositide 3-kinase/eNOS-mediated mechanism. Migration toward BK was able to attract an MNC subpopulation enriched in CPCs with in vitro proangiogenic activity, as assessed by Matrigel assay. CPCs from cardiovascular disease patients showed low B(2)R levels and decreased migratory capacity toward BK. When injected systemically into wild-type mice with unilateral limb ischemia, bone marrow MNCs from syngenic B(2)R-deficient mice resulted in reduced homing of sca-1(+) and cKit(+)flk1(+) progenitors to ischemic muscles, impaired reparative neovascularization, and delayed perfusion recovery as compared with wild-type MNCs. Similarly, blockade of the B(2)R by systemic administration of icatibant prevented the beneficial effect of bone marrow MNC transplantation. BK-induced migration represents a novel mechanism mediating homing of circulating angiogenic progenitors. Reduction of BK sensitivity in progenitor cells from cardiovascular disease patients might contribute to impaired neovascularization after ischemic complications.     

Patients with a history of stable or unstable coronary heart disease have different acute phase responses to an inflammatory stimulus

Increased levels of acute phase proteins (APP) in serum are associated with vulnerability of atherosclerotic plaques and acute manifestations of coronary heart disease (CHD). APP have been viewed as indexes of active vascular inflammation or as mediators of atherothrombosis. In the present study we tested the hypothesis that individuals who develop stable or unstable forms of CHD might have different innate responses to an inflammatory stimulus. We compared changes in plasma C-reactive protein (CRP) and serum amyloid A (SAA) concentrations 48 h after a standardized inflammatory stimulus (adjuvanted influenza vaccination) in patients with quiescent CHD that had been manifested at onset as inducible myocardial ischemia (Group 1, n=26) or as acute coronary syndromes (ACS) (Group 2, n=34). Selected patients were free from inflammatory or other conditions that might affect the immune response. CRP concentration increased significantly after vaccination in both groups (Group 1: 0.47 [0.21-0.86] to 0.56 [0.32-1.17]mg/L, p=0.005; Group 2: 0.64 [0.21-1.09] to 0.75 [0.33-1.48]mg/L, p=0.003), without significant differences between groups in absolute or percentage changes. By contrast, SAA did not change after vaccination in Group 1 (14.4 [8.9-19.5] to 14.8 [10.3-18.8]mg/L, p=0.88) but increased significantly in Group 2 (16.9 [10.0-21.5] to 19.2 [11.3-29.1]mg/L, p=0.002), with significant differences between the groups in absolute and percentage terms (p=0.015 and 0.019, respectively). Changes in CRP and SAA, both absolute and percentage, were significantly correlated in Group 2 (r=0.60 and 0.66, both p<0.001). The responsiveness of plasma SAA to an inflammatory stimulus in Group 2 alone suggests a pro-inflammatory status in patients prone to acute coronary syndrome but not in those with inducible myocardial ischemia.     

毒性结节性甲状腺肿的外科治疗(附66例报告)

目的总结毒性结节性甲状腺肿的治疗体会。方法对1990～2006年收治的66例毒性结节性甲状腺肿行手术治疗的临床资料进行回顾性分析。结果66例中42例采用硫脲类药物加碘剂进行术前准备,10例采用心得安加碘剂准备,14例单用碘剂准备。除1例病人因甲状腺癌外都采用甲状腺次全切除术,术后无甲状腺危象,无永久性喉返神经损伤及甲状旁腺功能减低等并发症。结论手术治疗毒性甲状腺肿是安全有效的,须行合理的术前准备及选择适当的手术方式。     

不同免疫原免疫小鼠后抗细粒棘球绦虫感染的免疫功能观察

目的 观察经猪囊尾蚴和细粒棘球绦虫抗原免疫的昆明小鼠后,感染细粒棘球绦虫后的免疫功能。方法将4种细粒棘球蚴和猪囊尾蚴体抗原及分泌抗原分别免疫4组小鼠,观察其诱发的抗体水平、对囊肿抑制率及其免疫细胞功能。结果 E.gPS组抑制率(77.1％)显著高于其它3组(P<0.05),其湿重(374±12.3mg)与对照组(163.0±53.7mg)相比差异具有非常显著性(q=5.9671,P<0.01);与另外3组比较差异也均有显著性(q=4.2061、4.3796、4.8670,P<0.05)。巨噬细胞吞噬指数(IM):E.gPS组显著高于对照组、C.cSW组及E.gCF组(q=9.9592、8.3332、8.6719,P均<0.01)。胸腺指数(IT):E.gPS组、E.gCF组显著低于对照组(q=5.2242、5.6189,P均<0.01)和C.cSW组(q=4.0466、4.4391,P均<0.05)。脾脏指数(IS):E.gPS组显著高于C.cSW组(q=4.8251,P<0.01)、E.gCF组和对照组(q=4.4078、3.3374,P均<0.05)。结论 经E.gPS抗原免疫的昆明小鼠明显增强了抗细粒棘球绦虫感染的免疫功能。     

Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels

Ghrelin, the recently identified endogenous ligand of the GH secretagogue receptor, is a gut-brain peptide with endocrine, orexigenic, and gastrointestinal effects. In rodents it increases circulating gastrin and insulin levels, whereas in man it appears to decrease insulin secretion despite a rise in blood glucose levels. The aim of the present study was to evaluate the effects of ghrelin administration on total circulating somatostatin (SS), pancreatic polypeptide (PP), and gastrin levels compared with those elicited on insulin, glucose, and GH. Eight healthy volunteers of normal weight (four women and four men) were injected with 3.3 microg/kg ghrelin or saline after an overnight fast on 2 different days. Blood was taken every 15 min for 1 h and then every 30 min for 2 h. As expected, ghrelin injection elicited a prompt GH and glucose increase with a peak at 30 min and an insulin decrease with a nadir at 60 min. Gastrin concentrations were not modified, whereas significant rises were observed in both SS (in a biphasic pattern with peaks at 15 and 120 min) and PP (which increased promptly with a peak at 15 min). A significant negative correlation was found between SS (first peak) and insulin changes (r = -0.86; P < 0.01). In conclusion, this study clearly demonstrates that ghrelin stimulates SS and PP release in man. Although the underlying mechanisms and biological significance of these pharmacological effects remain to be elucidated, a causal relationship between the SS increase and the insulin changes may be hypothesized. Finally, these findings strongly support ghrelin's postulated role in linking the endocrine control of energy balance and growth with the regulation of gastrointestinal functions.