Paroxetine versus amitriptyline in patients with recurrent major depression: A double-blind trial

INTRODUCTION: Long-term exposure to antidepressants is required to prevent relapses and recurrences in patients with recurrent major depression. Furthermore, a good pharmacological compliance is the key to successful long-term treatment. Since the early phases of a treatment influence long-term compliance and compliance is adversely affected by poorly tolerated treatments, efficacy and tolerability of paroxetine and amitryptiline over 12 weeks were compared as an introduction to the issue of long-term compliance to these two agents. METHOD: A 12-week, randomized, double-blind, doubledummy, parallel-group trial which involved 129 patients with recurrent major depression. RESULTS: Both paroxetine and amitriptyline were effective in controlling the symptoms of depression, as shown by the reduction in HAMD total score and CGI severity-of-illness score at endpoint compared to baseline. There was no statistically or clinically significant difference between the two treatments in terms of efficacy. However, marked numerical differences were noted in tolerability: the percentage of patients who reported treatment-emergent adverse experiences was greater in the amitriptyline group (40.0% vs 28.1%). This difference was mainly due to anticholinergic adverse events, which were six times more frequent with amitriptyline than with paroxetine. CONCLUSION: When compared with amitriptyline, paroxetine should allow patients with recurrent major depression to receive an equally effective treatment with a relatively lower incidence of adverse experiences.     

Family History of Suicide and Personality

The objective of this study was to analyze the impact of family history of suicidal behaviour on psychopathlogical features of inmates. A sample of 1,179 prisoners had a psychiatric interview including the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA). Prisoners completed the Barratt Impulsivity Scale (BIS), Buss-Durkee Hostility Inventory (BDHI), and Eysenck Personality Questionnaire (EPQ). Prisoners with a family history of suicide were compared with prisoners without a family history of suicide on clinical and personality variables. Seventy of the 1,179 prisoners (5.9%) had a family history of suicide. Significantly more FHS positive prisoners had attempted suicide compared with FHS negative prisoners (36% vs. 12%, P < 0.0001). Significantly more FHS positive prisoners had a previous history of convictions, a history of juvenile convictions, and had exhibited aggressive behavior in jail. FHS positive prisoners had significantly higher aggression scores on the BGLHA, higher hostility scores on the BDHI, higher impulsivity scores on the BIS, and higher neuroticism scores on the EPQ. A family history of suicide may be a useful clinical indicator that a prisoner is at increased risk for suicidal behaviour and may have problems with impulsive-aggression.     

Production of polyacrylamide gradient gel for lipoprotein electrophoretic separation

BACKGROUND: Small LDL are associated with risk of coronary heart disease. Gradient gel electrophoresis for LDL separation is not a simple method and high-quality non-denaturing gradient gels are lacking. METHODS: In this paper, we describe a method for the preparation of a polyacrylamide gel system that consists of an upper linear gradient gel (1.8-10%) and a lower homogeneous gel (16%) for the determination of LDL size. RESULTS: The linear gradient is highly reproducible. Intra-inter gel coefficients of variation for LDL particle size are lower than 0.6%. CONCLUSION: Effective LDL size measurement from pre-stained serum samples is possible in a stable gel.     

Long-term oral sodium bicarbonate supplementation does not improve serum albumin levels in hemodialysis patients

Metabolic acidosis, a frequent event in hemodialysis patients, has been implicated as a potential cause of protein-energy malnutrition. Unfortunately, correction of metabolic acidosis by means of high bicarbonate concentration in the dialysate does not seem to lead to significant changes in nutritional parameters. The project was a single-arm, open-label, 12-month pilot study at a university-based tertiary care center aimed at evaluating whether correction of metabolic acidosis through long-term oral sodium bicarbonate supplementation improves serum albumin levels and other nutritional parameters in patients undergoing maintenance hemodialysis. Twenty highly acidotic hemodialysis patients patients were invited to consume an oral supplementation of sodium bicarbonate (1 g, thrice daily), for 12 months. Patients were followed at baseline and every month, until month 12. At each follow-up visit, dry body weight, BMI, blood pressure, presence of edema, venous bicarbonate, and serum albumin were measured. Total lymphocyte count, fasting total cholesterol and C-reactive protein were assessed every 2 months. At baseline and at 12 months, the subjective global assessment of nutritional status and the protein equivalent of nitrogen appearance normalized to actual body weight were determined. Plasma bicarbonate level rose from 18.1 +/- 2.7 to 22.1 +/- 4.5 mmol/l after 10 months (p = 0.001). Mean serum albumin levels were 3.8 +/- 0.2 mg/dl at baseline and 3.9 +/- 0.2 at the end of the study. Repeated measure ANOVA showed that there was no significant effect of bicarbonate treatment on serum albumin levels (p = 0.29), dry weight (p = 0.1), serum total cholesterol (p = 0.97), total lymphocyte count (p = 0.69), or C-reactive protein (p = 0.85). Mean subjective global assessment score was 4.53 +/- 0.37 at baseline and 4.58 +/- 0.54 at 12 months (p = 0.1). Mean nPNA (g/kg/day) was 0.86 +/- 0.05 at baseline and 0.85 +/- 0.08 at month 12. The present study demonstrates that long-term oral sodium bicarbonate at the dose of 1 gram thrice daily has no significant effect on nutritional status of HD patients.     

Pathological gambling in Parkinson's disease: Subthalamic oscillations during economics decisions

Pathological gambling develops in up to 8% of patients with Parkinson's disease. Although the pathophysiology of gambling remains unclear, several findings argue for a dysfunction in the basal ganglia circuits. To clarify the role of the subthalamic nucleus in pathological gambling, we studied its activity during economics decisions. We analyzed local field potentials recorded from deep brain stimulation electrodes in the subthalamic nucleus while parkinsonian patients with (n = 8) and without (n = 9) pathological gambling engaged in an economics decision‐making task comprising conflictual trials (involving possible risk‐taking) and non conflictual trials. In all parkinsonian patients, subthalamic low frequencies (2–12 Hz) increased during economics decisions. Whereas, in patients without gambling, low‐frequency oscillations exhibited a similar pattern during conflictual and non conflictual stimuli, in those with gambling, low‐frequency activity increased significantly more during conflictual than during non conflictual stimuli. The specific low‐frequency oscillatory pattern recorded in patients with Parkinson's disease who gamble could reflect a subthalamic dysfunction that makes their decisional threshold highly sensitive to risky options. When parkinsonian patients process stimuli related to an economics task, low‐frequency subthalamic activity increases. This task‐related change suggests that the cognitive‐affective system that drives economics decisional processes includes the subthalamic nucleus. The specific subthalamic neuronal activity during conflictual decisions in patients with pathological gambling supports the idea that the subthalamic nucleus is involved in behavioral strategies and in the pathophysiology of gambling. © 2013 International Parkinson and Movement Disorder Society     

Pulse wave analysis to assess systemic blood flow during mechanical biventricular support

Measurement of systemic blood flow is of crucial importance in patients on mechanical circulatory support (MCS). We reported the case of a 65-year-old female patient in severe cardiogenic shock undergoing left (Jarvik 2000 axial flow pump) and right (Levitronix-Centrimag centrifugal pump) ventricular assist device implant. Evaluation of blood flow was obtained by ultrasonic flowmetry, continuous thermodilution technique, and pressure recording analytical method (PRAM). This pulse contour system allows beat-by-beat systemic blood flow assessment from the analysis of radial artery pressure waveform. At a Jarvik pump speed < or = 10000 rotations per minutes (rpm), thermodilution and PRAM showed similar blood flow values. At a Jarvik pump speed > or = 11000 rpm, the aortic valve did not open and PRAM did not provide blood flow values due to nonpulsatile blood flow. The present paper describes the first experience with PRAM in a single patient on MCS. Further studies are required to assess the validity of PRAM as an additional monitoring system in the setting of ventricular assist device support.     

Targeted therapy with bevacizumab and erlotinib tailored to the molecular profile of patients with recurrent glioblastoma. Preliminary experience

Background

Advances in comprehension of molecular biology of glioblastoma (GBM) have led to the development of targeted therapies. The aim of the present study was to evaluate the efficacy and safety of a targeted therapeutic approach in which administration of bevacizumab and erlotinib was tailored on the molecular profile of recurrent GBM.

Methods

We prospectively enrolled ten adult patients suffering from recurrent GBM who had undergone surgical resection and standard chemo-radiotherapy. Tumor tissue was assessed for the expression of EGFRvIII and MGMT promoter methylation by RT-PCR, and for PTEN and VEGF expression by immunohistochemistry. Normal PTEN status was required for inclusion. Patients with VEGF overexpressing tumors (10/10) were treated with bevacizumab (10 mg/kg iv every 2 weeks in 6-week?cycles); patients whose tumor expressed EGFRvIII (4/10) added erlotinib (150 mg/day orally; 300 mg/day if on enzyme-inducing antiepileptic drugs). Therapy was continued until disease progression or unacceptable toxicity. Primary endpoints of the study were response rate (RR), 6-month progression-free survival (PFS-6), and safety profile.

Results

The RR and PFS-6 were 100 % (4/4) and 50 % (3/6) in patients treated with bevacizumab+erlotinib (n?=?4) and bevacizumab (n?=?6), respectively. In the whole cohort (n?=?10), RR and PFS-6 were both 70 % (7/10); median PFS and overall survival (OS) were 8.0 (3.0–31.0) and 9.5 (5.0–31.0) months, respectively. No grade 3/4 adverse events were observed; three patients treated with bevacizumab+erlotinib displayed grade 1/2 rash not requiring dose reduction; one patient treated with bevacizumab developed intratumoral hemorrhage requiring treatment discontinuation.

Conclusion

To our knowledge, this is the first study on recurrent GBM in which administration of bevacizumab and erlotinib was tailored on the molecular profile of the patient’s tumor. Although we treated a limited number of patients, we obtained significantly higher RR and PFS-6 than those reported in a previous trial lacking molecular tumor analysis.     

A double-blind, randomized, multicenter, Italian study of frovatriptan versus almotriptan for the acute treatment of migraine

The objective of this study was to evaluate patients’ satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1–3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting <3 months. At study end patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain free and pain relief episodes at 2 and 4 h, and recurrent and sustained pain free episodes within 48 h. Of the 133 patients (86%, intention-to-treat population) 114 of them expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (3.1 ± 1.3) and almotriptan (3.4 ± 1.3). The rates of pain free (30% frovatriptan vs. 32% almotriptan) and pain relief (54% vs. 56%) episodes at 2 h did not significantly differ between treatments. This was the case also at 4 h (pain free: 56% vs. 59%; pain relief: 75% vs. 72%). Recurrent episodes were significantly (P < 0.05) less frequent under frovatriptan (30% vs. 44%), also for the attacks treated within 30 min. No significant differences were observed in sustained pain free episodes (21% vs. 18%). The tolerability profile was similar between the two drugs. In conclusion, our study suggests that frovatriptan has a similar efficacy of almotriptan in the short-term, while some advantages are observed during long-term treatment.     

Immortalization of Human Neural Stem Cells with the c-Myc Mutant T58A

Human neural stem cells (hNSC) represent an essential source of renewable brain cells for both experimental studies and cell replacement therapies. Their relatively slow rate of proliferation and physiological senescence in culture make their use cumbersome under some experimental and pre-clinical settings. The immortalization of hNSC with the v-myc gene (v-IhNSC) has been shown to generate stem cells endowed with enhanced proliferative capacity, which greatly facilitates the study of hNSCs, both in vitro and in vivo. Despite the excellent safety properties displayed by v-IhNSCs – which do not transform in vitro and are not tumorigenic in vivo – the v-myc gene contains several mutations and recombination elements, whose role(s) and effects remains to be elucidated, yielding unresolved safety concerns. To address this issue, we used a c-myc T58A retroviral vector to establish an immortal cell line (T-IhNSC) from the same hNSCs used to generate the original v-IhNSCs and compared their characteristics with the latter, with hNSC and with hNSC immortalized using c-myc wt (c-IhNSC). T-IhNSCs displayed an enhanced self-renewal ability, with their proliferative capacity and clonogenic potential being remarkably comparable to those of v-IhNSC and higher than wild type hNSCs and c-IhNSCs. Upon growth factors removal, T-IhNSC promptly gave rise to well-differentiated neurons, astrocytes and most importantly, to a heretofore undocumented high percentage of human oligodendrocytes (up to 23%). Persistent growth-factor dependence, steady functional properties, lack of ability to generate colonies in soft-agar colony-forming assay and to establish tumors upon orthotopic transplantation, point to the fact that immortalization by c-myc T58A does not bring about tumorigenicity in hNSCs. Hence, this work describes a novel and continuous cell line of immortalized human multipotent neural stem cells, in which the immortalizing agent is represented by a single gene which, in turn, carries a single and well characterized mutation. From a different perspective, these data report on a safe approach to increase human neural stem cells propagation in culture, without altering their basic properties. These T-IhNSC line provides a versatile model for the elucidation of the mechanisms involved in human neural stem cells expansion and for development of high throughput assays for both basic and translational research on human neural cell development. The improved proclivity of T-IhNSC to generate human oligodendrocytes propose T-IhNSC as a feasible candidate for the design of experimental and, perhaps, therapeutic approaches in demyelinating diseases.