Prognostic impact of renal impairment and sodium imbalance in patients undergoing transjugular intrahepatic portosystemic shunting for the prevention of variceal rebleeding

BACKGROUND/AIM: Kidney function and portal pressure have prognostic relevance in nonshunted patients with cirrhosis. Since insertion of a transjugular intrahepatic portosystemic shunt (TIPS) reduces portal pressure and may improve the renal function, the aim of the present study was to investigate the prognostic role of renal impairment and portal hemodynamics in patients with compensated cirrhosis electively shunted due to recurrent variceal hemorrhages. METHODS: Data of 101 consecutive and prospectively followed patients with compensated cirrhosis (bilirubin <5 mg/dl) undergoing elective TIPS due to recurrent variceal bleeding (45 died, and 8 were transplanted during the follow-up period) were evaluated in a multivariate Cox model. RESULTS: Creatinine and sodium were identified as the only independent predictors of survival in this model. The 90th percentile of creatinine (>1.7 mg/dl) defined a subgroup with a similar poor prognosis as the 90th percentile of the model for end-stage liver disease (MELD) score. Neither baseline nor post-TIPS portal pressure correlated with the long-term outcome. CONCLUSIONS: In compensated patients undergoing TIPS due to variceal bleeding, renal impairment indicates a poor prognosis. Portal hemodynamic parameters are not predictive of survival in TIPS patients.     

Blood lead level is associated with elevated blood pressure in blacks

Chronic lead exposure has been associated with elevated blood pressure in epidemiological studies. It is not known whether the previously observed relation between blood lead and hypertension persists after significant reductions have been made in environmental lead contamination. We examined the relation between blood lead levels and blood pressure in a representative sample of 14 952 whites and blacks aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey. Blood lead was measured by atomic absorption spectrophotometry and blood pressure by standard sphygmomanometry. Mean blood lead levels were significantly higher for black men and women (5.4 and 3.4 microg/dL, respectively) compared with white men and women (4.4 and 3.0 microg/dL, respectively). After multivariate adjustment for important covariables, each standard deviation higher blood lead (3.3 microg/dL) was associated with a 0.82 (95% confidence interval [CI], 0.19 to 1.44) mm Hg and a 1.55 (95% CI, 0.47 to 2.64) mm Hg higher systolic blood pressure among black men and women, respectively. In contrast, blood lead level was not associated with blood pressure among white men or women. The multivariate-adjusted odds ratio (95% CI) of hypertension associated with a 1-SD higher level of blood lead was 1.08 (95% CI, 0.99 to 1.19) for black men and 1.39 (95% CI, 1.21 to 1.61) for black women. These findings suggest that increased levels of blood lead remain an important environmental risk factor for elevated blood pressure in blacks.     

Influence of patient personality in the treatment of rheumatoid arthritis

Individualized treatment of rheumatoid arthritis (RA) based on genetic/serologic factors is increasingly accepted. Moreover, patients are more actively involved in the management of their disease. However, personality has received little attention with respect to perception of the need and adherence to treatment. Our objective was to evaluate whether patient personality was associated with the acceptance or rejection of more aggressive early treatment. We performed a cross-sectional study in two hospitals with early arthritis clinics where sociodemographic, clinical, and therapeutic variables are systematically recorded. Patients completed Eysenck Personality Questionnaire, Multidimensional Health Locus of Control, Pain-Related Self-Statement Scale and Pain-Related Control Scale. Aggressive treatment was considered if patients received more than two DMARDs or biological agents during the first year of follow-up. Multivariate logistic regression analysis was performed to determine predictors of aggressive treatment. One hundred seventy-six RA patients were included (80 % women, disease begin median age 55 years). Treatment was considered aggressive in 57.9 % of the sample. Scores were high in extraversion in 50.8 % of patients, neuroticism in 29.5 % and psychoticism in 14.7 %. Neuroticism was the only factor associated with aggressive treatment, which was less probable (p = 0.04, OR = 0.40). Neuroticism also decreased the possibility of receiving a combination of biologics and DMARDs (p = 0.04, OR = 0.28). Patients with high scores on neuroticism are more worried, obsessive and hypochondriac, leading them to reject more aggressive therapy. It is important to educate about their disease so that they will accept more aggressive approaches in clear cases of poor outcome.     

Coronary endothelial vasomotor function and vascular remodeling in heart transplant recipients randomized for tacrolimus or cyclosporine immunosuppression.

OBJECTIVES: This study aimed to compare changes in coronary endothelial function, systemic endothelin-1 (ET-1) levels, and vascular remodeling in heart transplant recipients randomized to cyclosporin A (CyA) or tacrolimus (Tac) immunosuppression. BACKGROUND: Functional endothelial abnormalities and intimal thickening are sensitive measures of early cardiac allograft vasculopathy (CAV). METHODS: The randomized, prospective study was performed in two groups of 22 patients, maintained on Tac or CyA and mycophenolate mofetil immunosuppression, 1 and 12 months after heart transplantation. We investigated epicardial luminal diameter, coronary blood flow velocity, and ET-1 plasma levels at 1 and 12 months after transplantation. Structural coronary alterations were determined using intravascular ultrasound. RESULTS: Epicardial vasomotor function at baseline and during follow-up was comparable between the groups. Deterioration of microvascular endothelial function during follow-up was significantly enhanced in the CyA versus Tac group (p < 0.05). Circulating ET-1 concentration increased in the CyA group but significantly decreased over time in the Tac group (CyA +17% vs. Tac -25%; p < 0.05). The time-dependent increase in mean intimal area was significantly enhanced in the CyA versus Tac group, whereas the vessel area significantly increased during follow-up in the Tac compared with the CyA group. CONCLUSIONS: Epicardial endothelial function is comparable between CyA- and Tac-treated patients. Microvascular endothelial function deteriorates more in CyA-treated patients, a finding that correlates with enhanced ET-1 concentration and an increased intimal area during follow-up. The mean vessel area in the Tac group increased over time, indicating positive vascular remodeling. Tac is superior to CyA with respect to microvascular endothelial function, intimal thickening, and vascular remodeling.     

The alternate iron transport pathway: mobilferrin and integrin in reticulocytes

Iron transport in reticulocytes is known to occur via the well-described transferrin-receptor–endosome pathway. An alternative pathway for iron transport independent of transferrin has been postulated in reticulocytes and other cells. Transport of iron into reticulocytes from ferric citrate solutions was shown to be saturable and independent of transferrin. During transport of iron from ferric citrate, both cell surface integrins, and a soluble protein, mobilferrin, were labelled. This demonstrated that the reticulocyte transferrin independent pathway for iron transport involved integrins and mobilferrin similar to intestinal absorptive cells. This pathway would be expected to transport iron into cells under conditions of iron overload and was capable of providing iron for haemoglobin synthesis. Mobilferrin was also radiolabelled when radioiron labelled transferrin was incubated with reticulocytes and this occurred with a different time course than was observed following reticulocyte exposure to radiolabelled ferric citrate. This suggested that mobilferrin may serve as an intermediary in both pathways.     

Do changes in visceral sensory function determine the development of dyspepsia during treatment with aspirin?

BACKGROUND & AIMS: We hypothesized that the development of dyspeptic symptoms during treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) would be linked to alterations in gastric mechanosensory function and gastric emptying. METHODS: In the first study, gastric mechanosensory thresholds (barostat technique) and gastric emptying ((13)C-octanoic breath test) were measured and endoscopy was performed at entry and after 5 days of treatment with aspirin (500 mg 3 times daily) in 8 patients with functional dyspepsia (initially without symptoms) and 8 healthy controls. In a second, double-blind, placebo-controlled, cross-over study, 6 new patients with functional dyspepsia and 6 controls were started with either placebo or aspirin for 5 days. Sensory thresholds were tested after the fifth day of aspirin or placebo treatment. Abdominal symptoms were assessed daily. RESULTS: In the first study, 6 of 8 patients and 3 of 8 controls, and in the second trial 6 of 6 patients and 1 of 6 healthy subjects, developed dyspepsia on aspirin (P < 0.005 patients vs. healthy subjects). No symptoms occurred during placebo treatment. Lanza scores were not associated with symptoms. After aspirin, sensory thresholds increased in both studies in subjects without development of symptoms (by 25.9% +/- 7.9%, and 31.0% +/- 4.1%, respectively, all P < 0.05), whereas there was no significant increase in subjects who developed symptoms (-11.2% +/- 5.3% and -3.4% +/- 13.4%, all P > 0.4). Neither thresholds nor symptoms were linked with the severity of mucosal damage, baseline gastric emptying (t1/2), or changes of gastric emptying (all P > 0.4). CONCLUSIONS: Failure to increase sensory thresholds during treatment with aspirin is associated with the development of dyspepsia.     

Vitamin D deficiency among HIV type 1-infected individuals in the Netherlands: effects of antiretroviral therapy

Vitamin D regulates bone metabolism but has also immunoregulatory properties. In HIV-infected patients bone disorders are increasingly observed. Furthermore, low 1,25(OH)(2)D(3) levels have been associated with low CD4(+) counts, immunological hyperactivity, and AIDS progression rates. Few studies have examined the vitamin D status in HIV-infected patients. This study will specifically focus on the effects of antiretroviral agents on vitamin D status. Furthermore, the effect of vitamin D status on CD4 cell recovery after initiation of HAART will be evaluated. Among 252 included patients the prevalence of vitamin D deficiency (<35 nmol/liter from April to September and <25 nmol/liter from October to March) was 29%. Female sex, younger age, dark skin, and NNRTI treatment were significant risk factors in univariate analysis, although in multivariate analyses skin pigmentation remained the only independent risk factor. Median 25(OH)D(3) levels were significantly lower in white NNRTI-treated patients [54.5(27.9-73.8) nmol/liter] compared to white PI-treated patients [77.3 (46.6-100.0) nmol/liter, p = 0.007], while among nonwhites no difference was observed. Both PI- and NNRTI-treated patients had significantly higher blood PTH levels than patients without treatment. Moreover, NNRTI treatment puts patients at risk of elevated PTH levels (>6.5 pmol/liter). Linear regression analysis showed that vitamin D status did not affect CD4 cell recovery after initiation of HAART. In conclusion, 29% of the HIV-1-infected patients had vitamin D deficiency, with skin color as an independent risk factor. NNRTI treatment may add more risk for vitamin D deficiency. Both PI- and NNRTI-treated patients showed higher PTH levels and might therefore be at risk of bone problems. Evaluation of 25(OH)D(3) and PTH levels, especially in NNRTI-treated and dark skinned HIV-1-infected patients, is necessary to detect and treat vitamin D deficiency early.     

Correlation between immunohistochemical expression of proliferating cell nuclear antigen and flow cytometry parameters in colorectal neoplasia

PURPOSE: Proliferating cell nuclear antigen immunohistochemical expression and flow cytometry techniques were used in this study to estimate the proliferation tendency and biologic aggressiveness in benign and malignant epithelial tumors of the colon and rectum. METHODS: Thirty-five adenomas and 60 adenocarcinomas were studied immunohistochemically concerning proliferating cell nuclear antigen positivity in tumor cell nuclei. In addition, flow cytometry techniques were used to estimate the DNA content and percentage of tumor cells in the S-phase. RESULTS: The mean proliferating cell nuclear antigen score for adenomas was 38 percent compared with a mean score of 50.4 percent for adenocarcinomas that were studied (P <0.05). In dysplastic areas of malignantly transformed adenomas (n=5), the highest proliferating cell nuclear antigen score (80 percent) was focally observed. Taking flow cytometry parameters into account, we found out that proliferating cell nuclear antigen can be used as an indirect indicator of the number of cells in the S-phase (SPF) but not as an independent prognostic factor. Statistical significance was found between Type III (aneuploid carcinomas) and increased proliferating cell nuclear antigen expression (proliferating cell nuclear antigen score ? 60 percent). Furthermore, aneuploidy was especially found on cancer located on the left colon (44 percent vs. 14 percent of right colon neoplasms). Considering DNA ploidy of the above neoplasms, the aneuploid adenocarcinomas had a tendency for poorer prognosis especially if they were related to Dukes Stage C female patients. CONCLUSIONS: The comparative assessment of the above parameters might be of considerable importance in the study of the proliferation activity of any form of colorectal neoplasia.     

Multimodal Functional Neuroimaging by Simultaneous BOLD fMRI and Fiber-Optic Calcium Recordings and Optogenetic Control

Recent developments of optogenetic tools and fluorescence-based calcium recording techniques enable the manipulation and monitoring of neural circuits on a cellular level. Non-invasive imaging of brain networks, however, requires the application of methods such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), which is commonly used for functional neuroimaging. While BOLD fMRI provides brain-wide non-invasive reading of the hemodynamic response, it is only an indirect measure of neural activity. Direct observation of neural responses requires electrophysiological or optical methods. The latter can be combined with optogenetic control of neuronal circuits and are MRI compatible. Yet, simultaneous optical recordings are still limited to fiber-optic-based approaches. Here, we review the integration of optical recordings and optogenetic manipulation into fMRI experiments. As a practical example, we describe how BOLD fMRI in a 9.4-T small animal MR scanner can be combined with in vivo fiber-optic calcium recordings and optogenetic control in a multimodal setup. We present simultaneous BOLD fMRI and calcium recordings under optogenetic control in rat. We outline details about MR coil configuration, choice, and usage of opsins and chemically and genetically encoded calcium sensors, fiber implantation, appropriate light power for stimulation, and calcium signal detection, to provide a glimpse into challenges and opportunities of this multimodal molecular neuroimaging approach.