Fetal neural grafts for Huntington's disease: a prospective view.

Intrastriatal transplantation of striatal neuroblasts from human fetuses is a promising approach for treatment of Huntington's disease, on the basis of many experimental animal studies and, most recently, pilot clinical trials. Technically, several issues remain to be resolved (e.g., the precise site of dissection of the fetal tissue; the number and location of the fetal striatal implants; or the use of immunosuppressive therapy), and await larger-scale trials and purposely designed protocols. Further clinical data must also be obtained, and preliminary promising results must be replicated in a patient group large enough to provide conclusive results. It is important to establish (1) the amount of clinical benefit provided to the patient by the grafted cells; (2) the anticipated duration of clinical benefits; and (3) the secondary rate of decline after the benefit of the graft has been overbalanced. Evaluation of these parameters will require very long-term follow-up of the patients involved, over several years after grafting, before the technique can eventually be proposed widely to patients.     

Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with beta-blocker or diltiazem.

Ranolazine (RS 43285) is a new piperazine derivative with anti-ischemic properties attributed to a modulation of myocardial metabolism. Its antianginal action was assessed in 104 patients recruited in a double-blind, crossover, randomized study comparing placebo with a single dose of ranolazine (10, 60, 120, and 240 mg). All patients had chronic stable angina pectoris and remained symptomatic (at least 0.1 mV ST-segment depression and angina during prestudy exercise testing) despite treatment with a beta-blocker or with diltiazem. No significant effects of ranolazine on exercise duration or time to angina were observed after the dose of 10, 60, and 120 mg. After the 240 mg dose, however, significant improvement in exercise duration (+13.1% in the combined group, two-tailed p = 0.002; +14.3% in the beta-blocker group, p = 0.009; +11.9% in the diltiazem group, p = 0.06), in time to angina (+56.8 s, p = 0.008), and in time to 1 mm ST-segment depression was observed. The cumulative proportion of patients who improved their time to angina by at least 30 s above placebo were 25, 42, 50, and 72% with the doses of 10, 60, 120, and 240 mg, respectively. Sixty-seven percent of the patients with ranolazine plasma levels above 500 ng/ml improved their time to angina against 40% at plasma levels below 500 ng/ml and summed ST-segment depression during exercise and recovery was also significantly reduced at these plasma concentrations. Both heart rate and arterial pressure at rest and at peak exercise were unchanged after ranolazine, 240 mg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-Related Hemodynamic and Electrocardiographic Effects of the Calcium Promoter BAY y 5959 in the Presence or Absence of Congestive Heart Failure

Objectives. The aim of this study was to assess the cardiovascular effects of BAY y 5959, a calcium promoter modulating myocardial calcium channels, in the presence or absence of congestive heart failure.

Background. There is still a clinical need for short-term administration of intravenous positive inotropes. BAY y 5959 was developed as a new approach to increase myocardial performance by selectively enhancing calcium influx in the myocytes.

Methods. Forty-one patients (21 without and 20 with congestive heart failure) were studied in an open label, dose-ranging study. Hemodynamic variables (including left ventricular [LV] angiography) and plasma samples were obtained at baseline and after 20 min of intravenous infusion of BAY y 5959 at doses ranging from 0.25 to 4.5 μg/kg body weight per min.

Results. In both study groups, BAY y 5959 produced dose-dependent increases in the indexes of inotropic state, without affecting isovolumetric relaxation rate. The magnitude of the response was comparable in patients with or without heart failure (average 38% increase in maximal first derivative of LV pressure [dP/dt max] at plasma levels of 100 μg/liter). BAY y 5959 also induced mild but statistically significant bradycardia and significantly decreased end-systolic volume while producing a leftward shift of the pressure-volume loop. Mean aortic pressure was unaffected at doses up to 3.0 μg/kg per min, and cardiac index improved in patients with heart failure at doses of 2.0 μg/kg per min (+23%, p < 0.05). However, at a dose of 4.5 μg/kg per min, mean aortic pressure and LV systolic wall stress increased, suggesting systemic vasoconstriction. The QT interval was also prolonged significantly at most doses.

Conclusions. BAY y 5959 exhibits positive inotropic effects in patients with and without heart failure. The optimal response— combining bradycardia, reduced preload and improved cardiac output—appeared to be achieved at a dose of 2.0 μg/kg per min. The impact of QT prolongation with regard to potential antiarrhythmic or proarrhythmic effects is unclear at this time.     

Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin,FGF2, and SERCA2a into Ischemic Heart

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Objectively characterizing Huntington’s disease using a novel upper limb dexterity test

Journal of Neurology - The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent...     

The Application of Rules in Morphology,Syntax and Number Processing: A Case of Selective Deficit of Procedural or Executive Mechanisms?

Declarative memory is a long-term store for facts, concepts and words. Procedural memory subserves the learning and control of sensorimotor and cognitive skills, including the mental grammar. In this study, we report a single-case study of a mild aphasic patient who showed procedural deficits in the presence of preserved declarative memory abilities. We administered several experiments to explore rule application in morphology, syntax and number processing. Results partly support the differentiation between declarative and procedural memory. Moreover, the patient's performance varied according to the domain in which rules were to be applied, which underlines the need for more fine-grained distinctions in cognition between procedural rules.     

Initial Experience of Single-Port Surgery Assisted by Percutaneous Instruments for Gastric Bypass: a Combination of Safety and Minimally Invasive Surgery

Background

We present here the first reported cases of patients undergoing gastric bypass with a hybrid technique that involves a new concept of percutaneous instruments and provides the advantages of minimally invasive single-port surgery while maintaining the triangulation, safety, and timing of operative procedures.

Methods

This was a prospective pilot study of eight patients selected for gastric bypass between December 2011 and January 2012 and treated by a technique that combined single SSL port and percutaneous surgical set PPS. We performed hand-sewn gastrojejunostomy in all cases. We analyzed preliminary results at 1 month and focused on the feasibility of the technique, duration of surgery, perioperative complications, and cosmetic results. The Ethics Committee of our institution approved this study and we obtained the informed consent of each patient.

Results

We completed the procedure successfully in all patients. No conversions to laparotomy or classic laparoscopy were required. The average time of surgery was 112 min (85–155). Length of hospital stay was 4 days (3–5). One patient was re-admitted on the seventh postoperative day for gastrointestinal bleeding from the gastrojejunostomy suture and treated by endoscopic clipping. Residual scars were less than 2 cm for the single midline port and 2 mm for the percutaneous instruments.

Conclusions

This new technique combines the advantages of single-port surgery with the safety of conventional laparoscopy by using percutaneous instruments and leaves minimal scarring. It is likely that the use of percutaneous instrumentation will become widespread in all areas of laparoscopic surgery.     

Neurohormones in patients with ischemic left ventricular dysfunction

Measurements of plasma neurohormones in patients with left ventricular dysfunction are generally performed for research purpose rather than for diagnostic purpose or to guide therapy. These studies have shown that in patients with left ventricular dysfunction, several neurohormonal systems were activated, even in the absence of symptoms of congestive heart failure. This suggested that the cardiovascular system was not in a steady state and pointed out potential culprits for the progression of the disease. It has also been shown that the levels of several of these markers, particularly plasma norepinephrine, had an important prognostic value. Another value of neurohormonal studies obviously is the design of new therapeutic approaches aimed at improving symptoms and prognosis. In this respect, important therapeutic successes have been obtained with agents that interfere with the actions of some of these neurohormonal systems, such as with the use of the angiotensin-converting enzyme (ACE) inhibitors, particularly captopril and enalapril, and to a lesser extent, with beta-blockers. It can therefore be expected that, in the future, most patients with severe ischemic dysfunction will be treated with an ACE inhibitor. Nonetheless, neurohormonal control is not complete with these drugs; powerful vasoconstrictor forces, such as endothelin-1, remain activated, and an escape of angiotensin II from the control of ACE inhibition may exist. Thus, morbidity (e.g., progression towards congestive heart failure and angina pectoris) and mortality remain high despite treatment with ACE inhibitors. In the search for further improvements, the new generation of long-acting dihydropyridines is worth considering. Their afterload reducing action, coupled with powerful coronary vasodilation, might hypothetically delay the progression of ischemic LV dysfunction. In addition, the improved pharmacokinetic profile of these drugs avoiding wide peak and trough variations in plasma levels may avoid triggering some neurohormonal reflexes.     

Production and consumption of methane in freshwater lake ecosystems

The atmospheric concentration of methane (CH₄), a major greenhouse gas, is mainly controlled by the activities of methane-producing (methanogens) and methane-consuming (methanotrophs) microorganisms. Freshwater lakes are identified as one of the main CH₄ sources, as it was estimated that they contribute to 6-16% of natural CH₄ emissions. It is therefore critical to better understanding the biogeochemical cycling of CH₄ in these ecosystems. In this paper, the effects of environmental factors on methanogenic and methanotrophic rates are reviewed and an inventory of the methanogens and methanotrophs at the genus/species level in freshwater lakes is given. We focus on the anaerobic oxidation of methane, which is a still poorly known process but increasingly reported in freshwater lakes.