Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

Purpose Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution.Methods Six patients (aged 62–81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second ¹²³I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration.Results After amitriptyline administration, there was a decrease in regional MIBG uptake in 10±4 segments per patient [62/120 segments (52%): 37 segments with a 5–10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions.Conclusion A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging.     

Brain tumor classification by proton MR spectroscopy: comparison of diagnostic accuracy at short and long TE

BACKGROUND AND PURPOSE: Different TE can be used for obtaining MR spectra of brain tumors. The purpose of this study was to determine the influence of the TE used in brain tumor classification by comparing the performance of spectra obtained at two different TE (30 ms and 136 ms). METHODS: One hundred fifty-one studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas, 16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were retrospectively selected from a series of 378 consecutive examinations of brain masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of interest were normalized to water. Tumors were classified into four groups (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma-metastases) by means of linear discriminant analysis. The performance of linear discriminant analysis at each TE was assessed by using the leave-one-out method. RESULTS: Tumor classification was slightly better at short TE (123 [81%] of 151 cases correctly classified) than at long TE (118 [78%] of 151 cases correctly classified). Meningioma was the only group that showed higher sensitivity and specificity at long TE. Improved results were obtained when both TE were considered simultaneously: the suggested diagnosis was correct in 105 (94%) of 112 cases when both TE agreed, whereas the correct diagnosis was suggested by at least one TE in 136 (90%) of 151 cases. CONCLUSION: Short TE provides slightly better tumor classification, and results improve when both TE are considered simultaneously. Meningioma was the only tumor group in which long TE performed better than short TE.     

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.