Pretransplantation diagnosis and staging of hepatocellular carcinoma in patients with cirrhosis: value of dual-phase helical CT

OBJECTIVE: The objective of our study was to prospectively evaluate the results of helical CT in the detection of hepatocellular carcinoma (HCC) in patients with cirrhosis undergoing orthotopic liver transplantation. SUBJECTS AND METHODS. Eighty-five patients with cirrhosis were studied preoperatively with biphasic helical CT. Arterial, portal, and equilibrium phase images were obtained after injection of 170 mL of contrast material at 5 mL/sec. The prospective CT interpretation was compared with pathologic results on a lesion-by-lesion basis. RESULTS: Pathologic examination found 85 cases of HCC in 51 patients. Helical CT enabled a correct diagnosis of HCC in 67 of 85 lesions for a sensitivity of 78.8%. HCC nodules were hypervascular in the arterial phase and hypovascular in the equilibrium phase in 63.5% (54/85) of patients. The false-negative rate was 21% (n = 18), and the positive predictive value was 88%. We had nine false-positive findings (11.8%) related to hemangiomas, transient hepatic attenuation differences, and regenerative nodules. Helical CT detected 61% (23/38) of lesions smaller than 2 cm and 93.6% (44/47) of lesions 2 cm or larger. CONCLUSION: Helical CT is a useful preoperative imaging technique in cirrhotic patients who are candidates for orthotopic liver transplantation, although it is relatively insensitive for detection of small lesions (< 2 cm).     

Treatment and capitation integration

The scarce integration and coordination of treatment is considered to be a very important problem in our health system. Can capitation, which means something like "charging a fee on each citizen based on his/her treatment necessities" resolve this problem? Can capitation favor clinical and treatment integration?     

Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation

Summary.Background: Evidence from in vitro studies suggests that antioxidant olive oil phenolic compounds can prevent LDL oxidation. However, in vivo evidence in support of this hypothesis is sparse.Aim of the study: to establish the antioxidant effect of olive oils with differences in their phenolic compounds content in humansMethods: A controlled, double blind, cross-over, randomized, clinical trial using three similar olive oils with increasing phenolic concentration (from 0 to 150 mg/Kg) was conducted in 30 healthy volunteers. Olive oils were administered over three periods of 3 weeks preceded by two-week washout periods.Results: Urinary tyrosol and hydroxytyrosol increased (p < 0.020), in vivo plasma oxidized LDL decreased (p = 0.006), and ex vivo resistance of LDL to oxidation increased (p = 0.012) with the phenolic content of the olive oil administered. After virgin olive oil administration, an increase (p = 0.029) was observed in HDL cholesterol levels.Conclusions: Sustained consumption of virgin olive oil with the high phenolic content was more effective in protecting LDL from oxidation and in rising HDL cholesterol levels than that of other type of olive oils. Dose-dependent changes in oxidative stress markers, and phenolic compounds in urine, were observed with the phenolic content of the olive oil administered. Our results support the hypothesis that virgin olive oil consumption could provide benefits in the prevention of oxidative processes.* Participants of the SOLOS-Investigation are listed in the Appendix.     

Relationship of socioeconomic status with cardiovascular risk factors and lifestyle in a Mediterranean population

BACKGROUND: Socioeconomic status greatly affects cardiovascular risk factors and lifestyle. Aim of the study To analyse the relationship between socioeconomic status and both cardiovascular risk factors and behavioural variables. AIM OF THE STUDY: To analyse the relationship between socioeconomic status and both cardiovascular risk factors and behavioural variables. METHODS: The present random sample of 838 men and 910 women of the 25 to 74 year old general population of Gerona according to the 1991 census, included cardiovascular risk factor measurements (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glycaemia, systolic blood pressure, diastolic blood pressure, body mass index, waist to hip ratio, and waist circumferences) and evaluation of dietary habits, alcohol consumption, smoking, and leisure-time physical activity with corresponding questionnaires. RESULTS: In this study, we used lifestyle factors (leisure-time physical activity, tobacco consumption, and alcohol drinking habits) in addition to dietary habits to determine whether changes in these factors correlate with the socioeconomic status, classified as degree of educational level, in a representative Spanish Mediterranean population. Multiple linear regression analysis adjusted for several confounders revealed a direct association of LDL-cholesterol (p = 0.03) and body mass index (p = 0.02) with low levels of educational status in men and women, respectively. A higher educational status was directly (p = 0.04) related to the smoking status in women. The two composite dietary scores, indicating overall dietary quality and cardiovascular protecting properties, were not associated with low socioeconomic status in our population. CONCLUSION: Dietary habits, alcohol drinking, and leisure-time physical activity seems not to be affected by educational status in either gender. This finding might partially explain the relationship between cardiovascular risk factors and socioeconomic status in our population. The importance of cultural values in the rural area of the Spanish province seems to be the stronger factor compared with education.     

Olive oils high in phenolic compounds modulate oxidative/antioxidative status in men

The aim of the present study was to evaluate whether olive oils high in phenolic compounds influence the oxidative/antioxidative status in humans. Healthy men (n = 12) participated in a double-blind, randomized, crossover study in which 3 olive oils with low (LPC), moderate (MPC), and high (HPC) phenolic content were given as raw doses (25 mL/d) for 4 consecutive days preceded by 10-d washout periods. Volunteers followed a strict very low-antioxidant diet the 3 d before and during the intervention periods. Short-term consumption of olive oils decreased plasma oxidized LDL (oxLDL), 8-oxo-dG in mitochondrial DNA and urine, malondialdehyde in urine (P < 0.05 for linear trend), and increased HDL cholesterol and glutathione peroxidase activity (P < 0.05 for linear trend), in a dose-dependent manner with the phenolic content of the olive oil administered. At d 4, oxLDL after MPC and HPC, and 8-oxo-dG after HPC administration (25 mL, respectively), were reduced when the men were in the postprandial state (P < 0.05). Phenolic compounds in plasma increased dose dependently during this stage with the phenolic content of the olive oils at 1, 2, 4, and 6 h, respectively (P < 0.01). Their concentrations increased in plasma and urine samples in a dose-dependent manner after short-term consumption of the olive oils (P < 0.01). In conclusion, the olive oil phenolic content modulated the oxidative/antioxidative status of healthy men who consumed a very low-antioxidant diet.     

A differential gene expression profile reveals overexpression of RUNX1/AML1 in invasive endometrioid carcinoma

Endometrial carcinoma is the most common gynecological malignant disease in industrialized countries. Two clinicopathological types of endometrial carcinoma have been described, based on estrogen relation and grade: endometrioid carcinoma (EEC) and non-EEC (NEEC). Some of the molecular events that occur during the development of endometrial carcinoma have been characterized, showing a dualistic genetic model for EEC and NEEC. However, the molecular bases for endometrial tumorigenesis are not clearly elucidated. In the present work, we attempted to identify new genes that could trigger cell transformation in EEC. We analyzed the differential gene expression profile between tumoral and nontumoral endometrial specimens with cDNA array hybridization. Among the 53 genes for which expression was found to be altered in EEC, the acute myeloid leukemia proto-oncogene, RUNX1/AML1, was one of the most highly up-regulated. The gene expression levels of RUNX1/AML1 were quantified by real-time quantitative PCR, and protein levels were characterized by tissue array immunohistochemistry. Real-time quantitative PCR validated RUNX1/AML1 up-regulation in EEC and demonstrated a specific and significantly stronger up-regulation in those tumor stages associated with myometrial invasion. Furthermore, tissue array immunohistochemistry showed that RUNX1/AML1 up-regulation correlates to the process of tumorigenesis, from normal atrophic endometrium to simple and complex hyperplasia and then, on to carcinoma. These results demonstrate for the first time the up-regulation of RUNX1/AML1 in EEC correlating with the initial steps of myometrial infiltration.     

Phase II study of temozolomide and cisplatin as primary treatment prior to radiotherapy in newly diagnosed glioblastoma multiforme patients with measurable disease. A study of the Spanish Medical Neuro-Oncology Group (GENOM)

This phase II study evaluates the activity of temozolomide and cisplatin administered before radiation therapy in newly diagnosed glioblastoma multiforme patients, in terms of response, time to progression and survival.Patients and methods: Forty patients with measurable disease after surgery, a Karnofsky status> 60, and Barthel Index> 10 were included. They were treated with three cycles of temozolomide 200 mg/m²/day for 5 days and cisplatin 100 mg/m² on day 1. Conventional focal radiation therapy to 60 Gy was administered after response evaluation.Results: Three patients were not evaluable for central reviewed response but all 40 were evaluable for toxicity, time to progression and survival. Objective responses by Macdonald criteria on an intent to treat basis were 45% including complete response in three patients (7.5%), and partial response in 15 patients (37.5%). Responses were seen in biopsy-only patients (33.4%) as well as in partial surgery patients (52%). Median survival for all patients was 12.5 months. Biopsy-only patients had a median survival of 12.8 months. Grade 3 to 4 neutropenia was the most important toxicity, and occurred in 37.5% of patients. A delay in 18.2% and a dose reduction in 9.6% of cycles were necessary due to myelosuppression on day 28. Two patients had neutropenic fever resulting in one treatment-related death. Eighty-two percent of patients received radiotherapy.Conclusion: This regimen has significant activity, as it induces objective responses even in biopsy-only patients, appearing to improve their median survival. A better combination schedule is needed to improve the toxicity profile.     

p21(WAF1/Cip1) is not involved in kainic acid-induced apoptosis in murine cerebellar granule cells

Kainic acid (KA) treatment induced neuronal death and apoptosis in murine cerebellar granule cells (CGNs) cultures from both wild-type and knockout p21(-/-) mice. There was not statistically significant difference in the percentage of neuronal apoptosis among strains. KA-induced neurotoxicity was prevented in the presence of NBQX (20 microM) and GYKI 52446 (20 microM), but not by z-VAD-fmk, suggesting that caspases are not involved in the apoptotic process. Data suggest that p21(WAF/Cip) was unable to modulate KA-induced apoptosis in murine CGNs.     

White matter alterations associated with chromosomal disorders

White matter alterations in chromosomal disorders have been reported mainly in 18q-syndrome. Our aim was to evaluate white matter alterations in patients with chromosomal abnormalities detected through conventional cytogenetic techniques. Forty-four patients with chromosomal abnormalities, excluding trisomy 21, were diagnosed in our hospital between May 1999 and December 2002 (24 males, 20 females; mean age 6 years 4 months [SD 3 years 2 months], range 0 to 18 years). Of the 44 patients, 14 had brain magnetic resonance imaging (12 males, 2 females; mean age 4 years 2 months [SD 4 years 4 months]; five with sex chromosomal disorders [SCD] and nine with autosomal chromosomal disorders [ACD]). Of these 14 patients, eight (four with SCD and four with ACD) had abnormal white matter findings of similar patterns. These patients had pseudonodular, subcortical, and periventricular white matter high signal intensity images in T2, and fluid-attenuated inversion recovery sequences that were isolated or confluent. The images did not correlate with the neurological clinical state. Given that eight of the 14 patients showed these lesions, their prevalence in different chromosomal abnormalities appears to be high, even though they have not been well reported in the literature. To our knowledge, these alterations have never been described in SCD. We concluded that unknown factors related to the myelination processes may be localized in different chromosomes.