Myocardial signal intensity decay after gadolinium injection: a fast and effective method for the diagnosis of cardiac amyloidosis

Late Gadolinium Enhancement (LGE) pattern of cardiac amyloidosis (CA) at cardiac magnetic resonance (CMR) examination is absent in approximately 30 % of patients. We tested whether the evaluation of myocardial gadolinium signal intensity (SI) decay (SID) has a higher diagnostic accuracy for CA. CMR was performed in 59 patients with systemic AL amyloidosis (36 males, 69 ± 10 years, mean ± SD), and 20 age/sex-matched healthy controls. LGE images were acquired every minute up to 8 min after gadolinium injection (time of inversion 250 ms). SI regions of interest were plotted in SI/time curves for endocardial (Endo) and epicardial layer of interventricular septum, cavity, and skeletal muscle as reference. SID (a negative exponential function described by the parameter T_SID) was expressed as number of heart beats (HB) from each ROI. The typical LGE pattern for CA was detected in 42 patients (Ty-LGE), while 17 showed either absent LGE or an atypical pattern (ATy-LGE). A definite CA diagnosis was confirmed in all Ty-LGE patients and in 10/17 ATy-LGE patients. At ROC analysis Endo-T_SID was the most accurate parameter to distinguish Ty-LGE and ATy-LGE patients from controls. A 269 HB threshold (mean + 2 SD Endo-T_SID measured in controls) identified 51/52 patients with definite CA diagnosis, with 98 % sensitivity, 93 % specificity, and 96 % diagnostic accuracy. A direct relation was found between the extracellular volume and Endo-T_SID in CA patients (r 0.72, 95 % CI 0.37–089, p < 0.001). the analysis of myocardial SID after gadolinium injection improves the accuracy of CMR for CA diagnosis.     

Putative hepatotoxic neoclerodane diterpenoids from Teucrium species

Fourteen neo-clerodane diterpenoids have been isolated from the acetone extract of the aerial parts of four species of Teucrium (T.alpestre, T. cuneifolium, T. divarication subsp. villosum, and T. flavum subsp. hellenicum) not previously studied chemically.     

Lung cancer incidence in young women vs. young men: A systematic analysis in 40 countries

Previous studies have reported converging lung cancer rates between sexes. We examine lung cancer incidence rates in young women vs. young men in 40 countries across five continents. Lung and bronchial cancer cases by 5-year age group (ages 30–64) and 5-year calendar period (1993–2012) were extracted from Cancer Incidence in Five Continents. Female-to-male incidence rate ratios (IRRs) and 95% confidence intervals (95%CIs) were calculated by age group and birth cohort. Among men, age-specific lung cancer incidence rates generally decreased in all countries, while in women the rates varied across countries with the trends in most countries stable or declining, albeit at a slower pace compared to those in men. As a result, the female-to-male IRRs increased among recent birth cohorts, with IRRs significantly greater than unity in Canada, Denmark, Germany, New Zealand, the Netherlands and the United States. For example, the IRRs in ages 45–49 year in the Netherlands increased from 0.7 (95% CI: 0.6–0.8) to 1.5 (95% CI: 1.4–1.7) in those born circa 1948 and 1963, respectively. Similar patterns, though nonsignificant, were found in 23 additional countries. These crossovers were largely driven by increasing adenocarcinoma incidence rates in women. For those countries with historical smoking data, smoking prevalence in women approached, but rarely exceeded, those of men. In conclusion, the emerging higher lung cancer incidence rates in young women compared to young men is widespread and not fully explained by sex differences in smoking patterns. Future studies are needed to identify reasons for the elevated incidence of lung cancer among young women.     

High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL

GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, c.IVS2-105A>G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available.     

Association between MDM2-SNP309 and age at colorectal cancer diagnosis according to p53 mutation status

A single-nucleotide polymorphism (SNP) in the promoter of the MDM2 gene, SNP309 (a T-->G change), was recently implicated in the early onset of cancer in individuals with Li-Fraumeni syndrome and of sporadic soft-tissue sarcoma. SNP309 induces an increase in the level of Mdm2 protein, which causes attenuation of the p53 pathway. To investigate the effect of this polymorphism in colorectal cancer pathogenesis, we genotyped 153 colorectal cancer patients who were randomly selected from among 330 consecutive patients stratified according to p53 mutation status and age at diagnosis, for alleles of MDM2-SNP309. Among the 77 patients with p53 wild-type tumors, the median age at colorectal cancer diagnosis was 71.5 years for patients with the T/T genotype and 61.0 years for patients with SNP309 (T/G or G/G genotype) (estimated difference between medians [Hodges-Lehmann method] = 8.0 years, 95% confidence interval = 1.0 to 16.0 years; P = .03 [two-sided Wilcoxon rank sum test]). Our data indicate that MDM2-SNP309 is a modifier of the age at colorectal cancer onset for patients whose tumors have a wild-type p53 gene.     

The no-reflow phenomenon is a post-mortem artifact

Summary Post-ischemic reperfusion impairment, (no-reflow phenomenon), was studied in rats subjected to 8–30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and³¹P-high energy phosphates (ATP/PCr) was observed.Brain intravascular perfusion defects were examined by injecting carbon blackintravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy andintraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats givenintraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in pale tissue areas suggestive of impaired perfusion (no-reflow). All rats given carbon blackintravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of pale tissue areas. In addition, post-ischemic cerebral reperfusion following 8–30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised.These findings indicate that the no-reflow phenomenon is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure.     

The role of ultrasound-guided aspiration biopsy of peripheral pulmonary nodules: our experience

BACKGROUND: Peripheral lung lesions are difficult to diagnose with conventional methods: ultrasound-guided aspiration biopsy is an interesting prospect having been reported to have good sensitivity and specificity. PATIENTS AND METHODS: From January 1991 to August 2001 we investigated, in 268 patients, the role of ultrasound-guided transthoracic fine needle aspiration for cytological diagnosis of peripheral lung lesions. Nodule sizes ranged from 1 to 10 cm. RESULTS: From 268 patients, we obtained 174 positive specimens for malignancy, of which 155 were positive for primary lung tumors and 19 for metastasis; 76 negative; 9 inadequate; and 9 aspecific. One patient developed pneumothorax after needle aspiration and one patient emophtoe. The nodule size did not affect complication rate and diagnostic outcome. CONCLUSION: This diagnostic procedure appears to be effective, safe and feasible, even in bedridden patients. The cost is low (70Euro), the examination is fast (5-6 minutes) and well-tolerated and, if the specimen is inadequate or non-specific, it is possible to repeat the examination. Ultrasound-guided aspiration biopsy can replace the TC-guided biopsy in patients with peripheral lung nodules.     

Foot and mouth disease virus. I. Stability of its ribonucleic acid.

A variable amount (30–90%) of fragmented molecules have been reported when the foot and mouth disease virus (FMDV) RNA is analyzed with different methods. In an attempt to find clues for this characteristic heterogeneity, FMDV-RNA was isolated from virions purified by two different methods. One of the methods, a variant of the usual purification procedure, rendered heterogeneous RNA molecules; with the other method, a shortened procedure, the results were strikingly different and the purified RNA proved to be homogeneous, even when submitted to different denaturation techniques and to digestion with proteases. The viral RNA was analyzed in sucrose gradients and by acrylamide-gel electrophoresis and the results obtained show that FMDV-RNA is a single-stranded molecule, having a molecular weight of 2.70 ± 0.05 × 10⁶. The origin and causes of the FMDV-RNA heterogeneity are discussed.     

Prognostic significance of race on biochemical control in patients with localized prostate cancer treated with permanent brachytherapy: multivariate and matched-pair analyses

PURPOSE: To compare PSA relapse-free survival (PSA-RFS) between African-American (AA) and white American (WA) males treated with permanent prostate brachytherapy (PPB) for clinically localized prostate cancer. METHODS AND MATERIALS: One thousand eighty-one consecutive patients, including 246 African-Americans, underwent PPB with 103Pd or 125I, alone or with external beam radiation therapy between September 1992 and September 1999. Computer-generated matching was performed to create two identical cohorts of WA and AA males, based on the use of neoadjuvant androgen ablation (NAAD), pretreatment PSA, and Gleason score. Presenting characteristics were used to define risk groups, as follows: Low risk had PSA 10 or Gleason score >or=7, and high risk had PSA >10 and Gleason score >or=7. PSA-RFS was calculated using the Kattan modification of the ASTRO definition, and the log-rank test was used to compare Kaplan-Meier PSA-RFS curves. Univariate and multivariate analyses were performed to determine predictors of PSA-RFS. RESULTS: Overall, univariate analysis revealed that AA males at presentation had lower disease stage (p = 0.01), had lower Gleason scores (p = 0.017), were younger (p = 0.001), and were more likely to receive NAAD (p = 0.001) than their WA counterparts. There were no differences in pretreatment PSA, isotope selection, use of external beam radiation therapy, median follow-up, or risk group classification between AA and WA males. Pretreatment PSA and Gleason score were significant predictors of PSA-RFS in multivariate analysis, and race was not significant. There was no significant difference between the 5-year PSA-RFS for AA males (84.0%) and the matched cohort of WA males (81.2%) (p = 0.384). Race was not a predictor of 5-year PSA-RFS among patients treated with or without NAAD and within low-, intermediate-, and high-risk groups. CONCLUSION: Race is not an independent predictor of 5-year PSA-RFS in patients with localized prostate cancer treated with PPB. This result is consistent with other studies that also show that race does not contribute to differences in outcome after definitive therapies for localized prostate cancer.