Serotonin Transporter and Tryptophan Hydroxylase Gene Variations Mediate Working Memory Deficits of Cocaine Users

Cocaine users consistently develop working memory (WM) impairments but the mediating molecular mechanisms are unknown so far. Recent evidence suggests that the serotonin (5-HT) system is altered by chronic cocaine use, while also being involved in WM processing. Thus, we investigated the effects of genetic variations impacting 5-HT activity and of peripheral 5-HT transporter (5-HTT) mRNA expression on WM performance in cocaine users and stimulant naive controls. Two hundred twenty participants (126 cocaine users, 94 controls) were assessed with visuospatial, spatial, and verbal WM tasks, genotyped for the length polymorphism in the promoter region of the 5-HTT (5-HTTLPR), the variable number of tandem repeats in the second intron of the 5-HTT (VNTR In2), two single-nucleotide polymorphisms (rs4570625 and rs1386497) in the tryptophan hydroxylase-2 (TPH2) gene and quantified for peripheral 5-HTT mRNA expression in whole-blood samples. Several significant gene × environment interactions between 5-HT genotypes and cocaine use on WM emerged: in cocaine users, the long/long (5-HTTLPR), 9+10/9+10 (VNTR In2) and C/C (TPH2 rs1386497) genotypes were risk alleles for WM impairments, whereas in healthy controls these polymorphisms were associated with improved WM performance. Analogously, high 5-HTT mRNA levels were associated with worse executive WM performance in cocaine users but with increased performance in controls. These gene × environment interactions suggest that the 5-HT system has an important role in the development of cognitive deficits in chronic cocaine users. Hence, pharmacological compounds targeting 5-HT neurotransmission might be promising for the treatment of cognitive deficits in cocaine dependence.     

Incidence and characteristics of transient St-segment elevation during transseptal puncture

Journal of Interventional Cardiac Electrophysiology - Delineate retrospectively and prospectively the incidence and characteristics of transient ST-segment elevation during transseptal puncture....     

Outcomes in a Community-Based Intensive Cardiac Rehabilitation Program: Comparison with Hospital-Based and Academic Programs

Background

The purpose of this study was to test the hypothesis that a community-based intensive cardiac rehabilitation program could produce positive changes in risk factor profile and outcomes in an at-risk population.

Gradual Onset of Dysphagia: A Study of Patients with Oculopharyngeal Muscular Dystrophy

This study describes five patients with slowly developing dysphagia secondary to oculopharyngeal muscular dystrophy (OPMD), a progressive neurological disorder characterized by gradual onset of dysphagia, ptosis, and facial and trunk limb weakness. OPMD is a genetic disorder that affects formerly healthy adults who typically begin to experience symptoms in the fourth or fifth decade of life. Despite the debilitating nature of the disease, it is common for affected individuals to live to old age. Because of the gradual progression of dysphagia, as well as the deterioration of articulation, resonance, and breath support, patients with OPMD may come to the attention of physicians, nurses, and speech pathologists before a diagnosis is made. We hope to heighten awareness of how these subjects developed strategies to cope with their swallowing problems without medical intevention until the disease was producing marked symptoms. Patients with suspected dysphagia should be questioned about overt problems with eating and swallowing, but also about their adaptations and compensatory strategies. A Clinical Interview Questionnaire is included that may yield additional information about hidden dysphagia.     

Consecutive regression of concurrent laryngeal and gastric MALT lymphoma after anti-Helicobacter pylori therapy

The most common primary lymphoma of the gastrointestinal tract is B-cell lymphoma arising from mucosa-associated lymphoid tissue known as MALT lymphoma. Although the majority of these lesions affect the stomach and are associated with Helicobacter pylori organisms, sites other than the gastrointestinal tract may be affected. This case report describes a patient with concomitant laryngeal MALT lymphoma and Helicobacter pylori-related gastric MALT lymphoma derived from the same clone as confirmed by PCR. Treatment of Helicobacter pylori infection in this patient using antibiotics led to regression of both lesions. This patient remains in remission at 46-month follow-up. This is the first case report on the regression of a laryngeal MALT lymphoma after Helicobacter pylori eradication. We suggest that all patients presenting with extragastric MALT lymphoma should undergo upper gastrointestinal endoscopy with gastric biopsies for the determination of Helicobacter pylori status and presence of concomitant gastric MALT lymphoma, followed by a course of anti-Helicobacter pylori antibiotic therapy. Nonresponders may subsequently be considered for surgery and/or chemo/radiation therapy.     

Trandolapril and endothelin antagonist LU-135252 in the treatment of the fructose-induced hypertensive,hyperinsulinemic, hypertriglyceridemic rat

BACKGROUND: In view of the demonstrated interaction between endothelin and the renin-angiotensin system, the antihypertensive effect of combined therapy with an endothelin antagonist LU-135252 and the angiotensin converting enzyme inhibitor trandolapril, was studied in fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic male Sprague-Dawley rats. METHODS: Forty animals were fed a fructose-enriched diet (Tekled, Harlan) for 5 weeks, as follows: group A, fructose only; group B, trandolapril 0.1 mg/kg/day added during the last 2 weeks; group C, LU-135252 100 mg/kg/day added during the last 2 weeks; group D, both trandolapril and LU-135252 added the last 2 weeks. Systolic blood pressure (BP) was measured weekly in conscious rats by the indirect tail-cuff method. Blood samples from a retro-orbital sinus puncture were taken at the beginning of the experiment and after 3 and 5 weeks and examined for insulin and triglyceride concentrations. RESULTS: Systolic BP decreased in group B (trandolapril) from 148.8 +/- 9.8 at 3 weeks to 138.3 +/- 8.7 mm Hg after 5 weeks; in group C (endothelin antagonist) from 155.1 +/- 5.5 to 142.5 +/- 10.6 mm Hg; and in group D (combination) from 154.6 +/- 10.9 to 121.2 +/- 8.9 mm Hg. Triglyceride levels decreased only in the combined trandolapril/endothelin antagonist group from 167.6 +/- 55.3 in the third week to 134.9 +/- 53.7 mg/dL after 5 weeks. Insulin levels decreased only on combination therapy from 7.4 +/- 3.6 to 5.3 +/- 3.8 ng/mL during the same period. The BP decrease was additive compared with the respective individual substances. CONCLUSIONS: The trandolapril/endothelin antagonist combination appears to offer a rational antihypertensive combination that is superior to that of either drug alone. This finding applies to the specific rat model studied in which BP, insulin, and triglycerides were increased by fructose diet.     

Amifostine does not prevent activation of TGFbeta1 but induces smad 7 activation in megakaryocytes irradiated in vivo

Experiments were undertaken to assess the role of amifostine in the activation of latent TGFbeta1 and in the smad proteins cascade (smad 2/3, smad4, smad7), focusing on megakaryocytes, in the bone marrow irradiated in vivo. Non-irradiated megakaryocytes were negative for active TGFbeta1. Immunopositivity to active TGFbeta1 was detected in megakaryocytes 10 days after irradiation in amifostine- treated and untreated marrows. Smad 2/3 and smad 4 were strongly positive in the nucleus of megakaryocytes 10 days after irradiation. At the same time, a predominant hypocellular bone marrow with foci of hematopoiesis was observed with few megakaryocytes. An increase in the number of reticulin fibers was also seen. In amifostine-treated marrows, smad 2/3 and smad4 were not detected in the nucleus but were positive in the cytoplasm of megakaryocytes 10 days after irradiation. Coincidentally, bone marrows were cellular with megakaryocytes. Smad7 immunoexpression was detected in the cytoplasm of megakaryocytes in the non-irradiated, amifostine-treated and in the irradiated, amifostine-treated marrows. Data indicate that amifostine does not prevent latent TGFbeta1 activation in irradiated megakaryocytes. While TGFbeta1 signal transduction occurs in megakaryocytes in untreated bone marrows, it is inhibited in megakaryocytes in amifostine-treated marrows due to the induction of smad 7 activation. This is the first report showing smad 7 activation by amifostine. Our results also suggest a role for TGFbeta1 as an inhibitor of megakaryocytes in vivo.     

Effect of focused cardiopulmonary ultrasonography on clinical outcome of septic shock: a randomized study

ObjectiveTo investigate the effect of focused ultrasonography on clinical outcomes of septic shock.MethodsPatients with septic shock were randomized into an integrated cardiopulmonary ultrasonography (ICUS) group and conventional (CON) group. Within 1 hour of admission, the ICUS group underwent ICUS examination for hemodynamic decision-making, while the CON group received standard treatment. The primary endpoint was 28-day mortality after admission. The secondary endpoints were cumulative fluid administration in the first 6, 24, and 72 hours; use of vasoactive drugs; lactate clearance; duration of ventilation; and ICU stay.ResultsNinety-four qualified patients were enrolled (ICUS group, 49; CON group, 45). ICUS showed no significant effect on 28-day mortality. Within the initial 6 hours, the ICUS group tended to have a higher fluid balance and fluid intake than the CON group. The duration of vasopressor support was shorter in the ICUS group. There were no differences in the cumulative fluid infusion within 24 or 72 hours, lactate clearance, ICU stay, or duration of ventilation.ConclusionsThe initially focused ICUS did not affect the clinical outcomes of septic shock, but it tended to be associated with a higher fluid balance within the initial 6 hours and shorter duration of vasopressor support.