Fibromuscular dysplasia: noninvasive evaluation of unusual case of renal and mesenteric involvement

Fibromuscular dysplasia is the most common cause of renovascular hypertension in young patients. It primarily involves the renal and carotid arteries, and it is less common in the coronary, iliac, and visceral arteries. Digital subtraction angiography is still the best investigation to determine the location, extent, and complications of renal artery involvement. However, currently, other imaging modalities such as ultrasonography, computed tomography, and magnetic resonance imaging can reveal these findings noninvasively. We present the case of a 43-year-old woman who presented with high blood pressure and headache. Imaging revealed fibromuscular dysplasia of the renal arteries and the superior mesentery artery.     

Is Liver Resection Justified in Advanced Hepatocellular Carcinoma? Results of an Observational Study in 464 Patients

Background and Objective  The role of liver resection in advanced hepatocellular carcinoma (multinodular or with macroscopic vascular involvement) is still controversial. The aim of this study is to evaluate the role of surgical resection compared to other therapeutic modalities in patients with advanced hepatocellular carcinoma (HCC). Methods  Four hundred sixty four patients with HCC observed from 1991 to 2007 were included in the study. All the patients were evaluated for the treatment of HCC in relation to the severity of liver impairment and tumor stage. All the patients included in the study had no evidence of distant metastases. Results  Median follow up time for surviving patients was 25 months (range 1–155). Two-hundred and eighty-three patients were in Child–Pugh class A, 161 in class B, and 20 in class C. Two-hundred and seventy-one patients had single HCC, 121 patients had two or three HCCs, and 72 more than three HCCs. One-hundred and thirty-six patients (29.3%) were submitted to liver resection (LR), 232 (50.0%) to local ablative therapies (LAT) (ethanol injection, radiofrequency ablation, chemoembolization), eight (1.7%) to liver transplantation (LT), and 88 (19%) to supportive therapy (ST). Median survival time for all patients was 36 months (95% CI 24–36). Median survival time was 57 months for LR, 30 months for LAT, and 8 months for ST, with a 5-year survival of 47%, 20%, and 2.5%, respectively (p = 0.001). Actuarial 5-year survival for patients submitted to LT was 75%. Overall survival was significantly shorter in patients with multiple HCCs compared to single HCC, with median survival times of 39, 16, and 11 months for patients with a single HCC, with two to three HCCs, and with more than three HCCs, respectively (p = 0.01). Survival for patients with single HCC was significantly longer in patients submitted to LR compared to LAT and ST with median survival times of 57, 37, and 14 months, respectively (p = 0.02). Also, in patients with multinodular HCCs (2–3 HCCs) LR showed the best results with a median survival time of 58 months compared to 22 and 8 months for LAT and ST (p = 0.01). In patients with more than three HCCs, LR did not show different results compared to LAT and ST. Seventy-three patients had evidence of macroscopic vascular involvement; median survival in this subgroup of patients was significantly shorter compared to patients without vascular involvement, 10 and 36 months, respectively. Survival for patients with macroscopic vascular involvement submitted to LR or LAT was significant longer compared to ST, with mean survivals of 27, 30, and 12 months, respectively (p = 0.01). Conclusions  The present study shows that the surgery can achieve good results in patients with single HCC and good liver function. Also, patients with multinodular HCCs (two to three nodules) could benefit from LR where survival is longer than after LAT or ST. In patients with more than three HCCs, LR have similar results of LAT. Macroscopic vascular invasion is a major prognostic factor, and the LR is justified in selected patients, where it can allow good long-term results compared to ST. This study was presented as Quick Shot oral presentation of the Surgical Society Alimentary Tract at Digestive Disease Week, May 20, 2008, San Diego Convention Center, San Diego, CA, USA and as oral presentation at 23rd Annual SSAT Residents & Fellows Research Conference, May 17, 2008, Omni San Diego, San Diego, CA.     

Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV‐ERBα gene,a critical component of the circadian clock system

Objective: The aim of our study was to investigate the association between REV‐ERBα gene (NR1D1) single nucleotide polymorphisms (SNPs) and bipolar disorder (BP) in a case‐control sample of Sardinian ancestry and evaluate its effect on age at onset (AAO) of BP. Methods: We genotyped SNPs rs12941497 (SNP1) and rs939347 (SNP2), located, respectively, in the first intron and in the 5′UTR region of the gene, in a sample comprised of 300 bipolar patients and 300 healthy controls of Sardinian ancestry. We also studied AAO by means of admixture analysis, obtaining a cutoff point of age 22 and then carrying out association analysis between the two AAO groups. Results: In the case‐control comparison, single marker analysis showed no association for any of the SNPs tested. Haplotype analysis showed a nominally significant association for two haplotypes of SNPs 1‐2. Comparing the early‐ and later‐onset groups, nominal association was found for SNP1. Haplotype analysis showed that one haplotype was nominally associated with the later‐onset group. Conclusions: Our results, indicating a nominal association of the REV‐ERBα gene with BP, suggest a possible role of REV‐ERBα in the pathogenesis of BP. Further investigation of larger independent samples and different populations is warranted.     

Prediction of recurrent venous thromboembolism by measuring ProC Global

In patients with venous thromboembolism (VTE) a laboratory assay that globally measures the overall thrombophilic tendency is not available. We hypothesized that determination of ProC((R)) Global, a plasma assay which tests the global function of the protein C pathway, could be used to stratify patients according to their risk of recurrent VTE. We prospectively followed 774 patients with first spontaneousVTE for a mean time of 52 months. ProC Global normalized ratio (NR) was measured in plasma by use of a commercially available assay based on activated partial thromboplastin time. Ninety-eight of the 774 patients had recurrentVTE. Patients with ProC Global NR > or = 0.75 had a relative risk of recurrence of 0.59 (95% CI 0.40-0.87) as compared with those with lower ratio. After four years, cumulative probability of recurrence was 8.6% in patients with ProC Global NR > or = 0.75 and 17.4% in patients with a lower ratio (p = 0.006). Patients with a high ProC Global NR have a low risk of recurrent VTE. ProC Global NR can be used to stratify patients with a first unprovoked VTE according to their risk of recurrence.     

Brain regional α-[<Superscript>11</Superscript>C]methyl-<Emphasis Type="SmallCaps">L</Emphasis>-tryptophan trapping,used as an index of 5-HT synthesis,in healthy adults: absence of an age effect

Purpose Previous functional neuroimaging studies suggest that selective aspects of the brain serotonin (5-HT) system change during the aging process. Here, we assessed the effects of aging on the brain regional α-[¹¹C]methyl-L-tryptophan (α-[¹¹C]MTrp) trapping rate constant (K*; μl·g⁻¹·min⁻¹), which, with certain assumptions, could be taken as a proxy of 5-HT synthesis. Methods Thirty-six healthy right-handed subjects had positron emission tomography (PET) scans following injection with α-[¹¹C]MTrp [18 males aged 46.6 ± 22.2 years (range 20–80 years) and 18 females aged 33.0 ± 15.5 years (range 20–80 years)]. The trapping rate constant, K*, was calculated with the graphical method for irreversible ligands using the sinus-venous input function. A priori selected volumes of interest (VOIs) were defined using an automatic algorithm. Results VOI analysis showed no correlation between age and brain regional K* values. As reported by others, significant age-related reductions of gray matter were observed in the thalamus and frontal and cingulate cortices; even with partial volume correction there was still no significant relationship between K* and age. Further exploratory SPM voxelwise correlation between age and α-[¹¹C]MTrp trapping, using p = 0.05 (uncorrected), as well as voxel-based morphometry, was in agreement with the VOI analysis. Conclusion The dissociation between age-related changes in brain anatomy and this index of serotonin synthesis suggests independent mechanisms underlying the normal aging process.     

The pacemaker current: from basics to the clinics

Activation of the pacemaker ("funny," I_f) current during diastole is the main process underlying generation of the diastolic depolarization and spontaneous activity of cardiac pacemaker cells. I_f modulation by autonomic transmitters is responsible for the chronotropic regulation of heart rate. Given its role in pacemaking, I_f has been a major target of investigation aimed to exploit its rate-controlling function in a clinical perspective. In this short review, we describe some of the most recent clinically relevant applications of the concept of I_f-based pacemaking.