Effects of cognitive rehabilitation in Parkinson disease: a meta-analysis

Neurological Sciences - Cognitive symptoms are common in Parkinson’s disease (PD) and affect patients’ quality of life. Pharmacological interventions often do not improve such...     

Relation of myocardial histomorphometric features and left ventricular contractile reserve assessed by high-dose dobutamine stress echocardiography in patients with idiopathic dilated cardiomyopathy

BACKGROUND: This study was designed to determine the relationship between histomorphometric features and contractile reserve assessed by high-dose dobutamine stress echocardiography in patients with idiopathic dilated cardiomyopathy. METHODS: Twenty-four consecutive patients (21 men, aged 43.4+/-8.7 years) with idiopathic dilated cardiomyopathy underwent dobutamine stress echocardiography. Wall motion score index, ejection fraction, cardiac power output and end-systolic pressure/volume ratio were used as indices of left ventricular contractility. Left ventricular endomyocardial biopsy specimens (3-5 per patient) were routinely processed and stained with Masson trichrome, interstitial fibrosis and myocyte diameter were calculated quantitatively. RESULTS: Myocyte diameter and interstitial fibrosis showed strongest correlation with change in wall motion score index (r=-0.667, p<0.001, and r=-0.567, p=0.004, respectively), followed by change in ejection fraction (r=-0.603, p=0.002, and r=-0.467, p=0.021, respectively). Interstitial fibrosis showed no correlation with change of cardiac power output and end-systolic pressure/volume ratio, whereas myocyte diameter was associated with change of both indices (r=-0.565, p=0.004, and r=-0.455, p=0.025). CONCLUSIONS: Contractile reserve elicited by high-dose dobutamine is strongly related to the degree of histological disruption in patients with idiopathic dilated cardiomyopathy.     

Reduced Spontaneous Eye Blink Rates in Recreational Cocaine Users: Evidence for Dopaminergic Hypoactivity

Chronic use of cocaine is associated with a reduced density of dopaminergic D2 receptors in the striatum, with negative consequences for cognitive control processes. Increasing evidence suggests that cognitive control is also affected in recreational cocaine consumers. This study aimed at linking these observations to dopaminergic malfunction by studying the spontaneous eyeblink rate (EBR), a marker of striatal dopaminergic functioning, in adult recreational users and a cocaine-free sample that was matched on age, race, gender, and personality traits. Correlation analyses show that EBR is significantly reduced in recreational users compared to cocaine-free controls, suggesting that cocaine use induces hypoactivity in the subcortical dopamine system.     

Selective purging by human interleukin-2 activated lymphocytes of bone marrows contaminated with a lymphoma line or autologous leukaemic cells

The ability of recombinant interleukin 2 (rIL2) activated lymphocytes (LAK) to purge BM samples contaminated by tumour cells was evaluated. Human BM mononuclear cells were contaminated with 10% of the lymphoma line CA46 and then cultured in liquid medium containing 1000 U/ml of rIL2 and/or LAK autologous to the used BM. At the end of coculture the growth of residual tumour cells and of CFU-GM were evaluated by clonogenic assay. No tumour cell growth was observed in 5/5 independent experiments after 18 h of coculture with LAK. No significant inhibition of CFU-GM growth was also noted. Subsequently, the effect of LAK on BM obtained from four leukaemic patients and contaminated with 20-50% of their own AML and ALL cells was studied using MAb as a tool for identifying leukaemic cells. LAK eliminated 24-78% of contaminating cryopreserved uncultured autologous leukaemic cells. In five cases the BM was contaminated by a low (2%) amount of ALL cells. In these patients the monoclonal heavy chain rearrangement typical of ALL was no longer visible after coculture with LAK. Evidence for selective tumour cytotoxicity by LAK was confirmed by using autologous BM cells as hot and cold targets in a 51Cr release assay. Finally, successful haematologic reconstitution of lethally irradiated BALB/c mice was obtained using syngeneic BM cocultured with LAK. These results support the investigational use of rIL2 and LAK in the treatment of human leukaemia.     

Angioedema associated with angiotensin-converting enzyme inhibitor use: outcome after switching to a different treatment

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are associated with angioedema episodes that are potentially life-threatening. Few data are available on the outcome of patients reporting this adverse effect when they are switched to another drug. Scattered reports of angioedema associated with angiotensin II receptor blocker (ARB) use question the safety of using these drugs in patients with ACE inhibitor-related angioedema. We describe 64 consecutive patients with ACE inhibitor-related angioedema, the outcome after discontinuing this treatment, and the safety of using ARBs. METHODS: Retrospective analysis of 64 consecutive patients (January 1993 to June 2002) presenting with angioedema onset while receiving treatment with an ACE inhibitor. RESULTS: Patients were recommended to stop ACE inhibitor use, substituting it upon advice of the physician. Fifty-four patients were available for follow-up (median follow-up, 11 months; range, 1-80 months): 26 had switched to an ARB, 14 to a calcium antagonist, and 14 to other antihypertensive drugs. Angioedema disappeared or drastically reduced upon withdrawal of the ACE inhibitor in 46 patients (85%). For the remaining 8 patients, angioedema was due to a cause other than ACE inhibitor use in 2; angioedema persisted independent of the treatment and without apparent cause (idiopathic angioedema) in 4; angioedema persisted after switching to an ARB and disappeared upon its withdrawal in 2. CONCLUSIONS: Stopping ACE inhibitor use without further assessments is a successful measure in the large majority of patients developing angioedema while taking this drug. Only a small percentage of patients with ACE inhibitor-related angioedema continue with this symptom when switched to an ARB.     

A dose‐dense short‐term therapy for human immunodeficiency virus/acquired immunodeficiency syndrome patients with high‐risk Burkitt lymphoma or high‐grade B‐cell lymphoma: safety and efficacy results of the “CARMEN” phase II trial

A few prospective trials in HIV‐positive patients with Burkitt lymphoma (BL) or high‐grade B‐cell lymphoma (HGBL) have been reported. Investigated therapies have shown good efficacy but relevant safety problems, with high rates of interruptions, severe mucositis, septic complications, and fungal infections. Here, we report the results of a multicentre phase II trial addressing a new dose‐dense, short‐term therapy aimed at maintaining efficacy and improving tolerability. The experimental programme included a 36‐day polychemotherapy induction followed by high‐dose cytarabine‐based consolidation and response‐tailored BEAM (carmustine, etoposide, cyatarabine, and melphalan)‐ conditioned autologous stem cell transplantation (ASCT). This therapy would be considered active if ≥11 complete remissions (CR) after induction (primary endpoint) were recorded among 20 assessable patients. HIV‐positive adults (median age 42, range 26–58; 16 males) with untreated BL (n = 16), HGBL (n = 3) or double‐hit lymphoma (n = 1) were enrolled. All patients had high‐risk features, with meningeal and bone marrow infiltration in five and nine patients respectively. The experimental programme was safe and active in a multicentre setting, with only two episodes of grade 4 non‐haematological toxicity (hepatotoxicity and mucositis), and no cases of systemic fungal infections; two patients died of toxicity (bacterial infections). Response after induction (median duration: 47 days; interquartile range 41–54), was complete in 13 patients and partial in five [overall response rate = 90%; 95% confidence interval (CI) = 77–100]. All responders received consolidation, and five required autologous stem cell transplant. At a median follow‐up of 55 (41–89) months, 14 patients are relapse‐free and 15 are alive, with a five‐year progression‐free survival and an overall survival of 70% (95% CI = 60–80%) and 75% (95% CI = 66–84) respectively. No patient with cerebrospinal fluid (CSF)/meningeal lymphoma experienced central nervous system recurrence. With respect to previously reported regimens, this programme was delivered in a shorter period, and achieved the main goal of maintaining efficacy and improving tolerability.