Subthalamic deep brain stimulation for the treatment of Parkinson disease

Background and purposeThe role of subthalamic nucleus deep brain stimulation (STN DBS) in the treatment of Parkinson disease (PD) is well established. The authors present a group of patients diagnosed with PD who were treated with STN DBS.Material and methodsBetween 2008 and 2009, 32 female and 34 male patients with PD were treated with STN DBS. Mean age at implantation was 57 ± 12 years. PD lasted from 6 to 21 years (mean 10 years). Patients were qualified for the surgery according to the CAPSIT-PD criteria. The STN was identified with direct and indirect methods. Macrostimulation and microrecording for STN identification were used in all cases. A unilateral STN DBS system was implanted in two cases and bilateral implantation was performed among rest of the group. Outcome was assessed six months after implantation.ResultsThe mean reduction of UPDRS III score among 51 patients who underwent follow-up was 45% (5-89%). Reduction of levodopa consumption varied from 15 to 100%. Infection forced the authors to remove the DBS system in one case four months after implantation. Skin erosion above the internal pulse generator was noted in four cases.ConclusionsCardinal symptoms of Parkinson's disease can be safely and effectively treated with STN DBS in selected group of patients.     

Clinical characteristics of 304 kindreds evaluated for familial dilated cardiomyopathy

BackgroundFamilial dilated cardiomyopathy (FDC) is dilated cardiomyopathy of unknown cause occurring in 2 or more closely related family members.Methods and ResultsMembers of 304 families suspected to have FDC were evaluated by family history (FH) and medical record review and were categorized as affected with idiopathic dilated cardiomyopathy (IDC), unaffected, unknown, or no data. Pedigrees were categorized with confirmed FDC, probable FDC, possible FDC or IDC based on strength of evidence. Of the 304 pedigrees, 125 were categorized as confirmed FDC, 48 were probable FDC, 72 were possible FDC, and 59 had sporadic, nonfamilial IDC. Numbers of living first- and second-degree family members, and median number of relatives available for FH was greatest with confirmed FDC, and diminished for probable and possible FDC, and IDC categories. LV dimensions increased and LV function worsened in index patients along the spectrum from confirmed FDC, probable FDC, possible FDC and IDC, and a greater proportion of IDC patients underwent heart transplant. However, the age of onset, duration of disease, the time to death or heart transplant, and most other findings were similar among the 4 categories.ConclusionClinical characteristics of IDC and FDC are similar, precluding an FDC diagnosis from clinical features only.     

Tobacco smoke exposure induces nicotine dependence in rats

Rationale

Tobacco smoke contains nicotine and many other compounds that act in concert on the brain reward system. Therefore, animal models are needed that allow the investigation of chronic exposure to the full spectrum of tobacco smoke constituents.

Objectives

The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats.

Methods

The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Somatic signs were recorded from a checklist of nicotine abstinence signs. Nicotine self-administration sessions were conducted to investigate if tobacco smoke exposure affects the motivation to self-administer nicotine. Nicotinic receptor autoradiography was used to investigate if exposure to tobacco smoke affects central α7 nicotinic acetylcholine receptor (nAChR) and non-α7 nAChR levels (primarily α4β2 nAChRs).

Results

The nAChR antagonist mecamylamine dose-dependently elevated the brain reward thresholds of the rats exposed to tobacco smoke and did not affect the brain reward thresholds of the untreated control rats. Furthermore, mecamylamine induced more somatic withdrawal signs in the smoke-exposed rats than in the control rats. Nicotine self-administration was decreased 1 day after the last tobacco smoke exposure sessions and was returned to control levels 5 days later. Tobacco smoke exposure increased the α7 nAChR density in the CA2/3 area and the stratum oriens and increased the non-α7 nAChR density in the dentate gyrus.

Conclusion

Tobacco smoke exposure leads to nicotine dependence as indicated by precipitated affective and somatic withdrawal signs and induces an upregulation of nAChRs in the hippocampus.     

Collagen composite biomaterials resist contraction while allowing development of adipocytic soft tissue in vitro

Soft tissue defects resulting from tumor resection or trauma require surgery to restore the body's contours. Because autologous tissues or synthetic implant reconstructions can be less than ideal, engineered tissues produced in vitro are being developed as alternatives. Collagen gels have been proposed for this application because they are biocompatible and can be shaped to fill a specific defect. In the present study, constructs of collagen gels with embedded short collagen fibers (which are more permeable than plain collagen gels and which maintain size and shape in culture) were seeded with preadipocytes and cultured in vitro. The addition of increasing volume fractions of embedded fibers limited cell-mediated contraction of the constructs. Including epithelial cell-seeded collagen gel layers resulted in more contraction, but still less than that observed in constructs without fibers. Constructs with embedded collagen fibers contained significantly more cells at all time points examined when compared to constructs without embedded fibers. Mature adipocytes were observed throughout constructs after 21 days in culture; spectroscopic analyses indicated lipid inclusion in constructs seeded with preadipocytes, which differed from analyses of natural porcine adipose tissue. These results support the promise of collagen composites as a biomaterial for use in producing soft tissues in vitro.     

Combining pharmacological mobilization with intramyocardial delivery of bone marrow cells over-expressing VEGF is more effective for cardiac repair

We postulated that combining cell based hVEGF165 gene delivery with cytokine-induced mobilization of bone marrow cells (BMC) may give better prognosis in an infarcted heart. Forty-eight myoabalated female C57BL/6J mice (20-25 g) received 1 x 10(6) BMC from transgenic GFP+ male mice. One month later, acute myocardial infarction (MI) model was developed by coronary artery ligation. Animals were grouped (N = 12) to receive intramyocardial injections of 10 microl DMEM without cells (group 1; group 2) or with 1x10(5) mesenchymal stem cells (MSC) over-expressing hVEGF165 (group 3; group 4). The animals received either cytokine therapy (group 2 and 4) or saline solution (group 1 and 3) for 7 days after MI. Hemodynamic data were obtained 4 weeks after MI using Millar's P-V system and cardiac tissue was harvested for immunohistological studies. We observed regeneration and extensive survival of BMC in and around the infarcted myocardium in groups 3 and 4. Blood vessel density was markedly enhanced in group 4 as compared with groups 1 and 2 in peri-infarct area. Fibrotic area was significantly reduced with improved LV-contractile function in group 2 and 4. LV-systolic and diastolic functions were well-preserved in group 4 as indicated by +dP/dt, -dP/dt and Tau (glantz). We therefore conclude that transplantation of MSC overexpressing VEGF combined with cytokine induced BMC mobilization is superior to either of the monotherapy approach for angiomyogenesis and LV-function recovery.     

Comparative responsiveness of Short-Form 12 and Minnesota Living With Heart Failure Questionnaire in patients with heart failure

BACKGROUND: The Short-Form 12 (SF-12) and Living With Heart Failure Questionnaire (LHFQ) are commonly used to measure quality of life (QOL) in heart failure outcomes research. Their comparative responsiveness, however, has not been documented. METHODS AND RESULTS: A prospective cohort study was conducted among patients attending a university-based heart failure clinic between April 1997 and September 1998. All patients received comprehensive heart failure care management. QOL of patients was assessed by the SF-12 and LHFQ at baseline and 3 months. Of 87 patients completing follow-up, the mean change score was 10.1 for the LHFQ and 5.8 for the SF-12 (both Ps < .001). The change scores of the instruments were correlated (r = 0.61; P < .001). The SF-12 had a greater ability than the LHFQ to statistically detect change in physical health but was less sensitive to changes in mental health. The LHFQ performed better than the SF-12 in the ability to distinguish the differences in perceived global health transition. CONCLUSION: The LHFQ is more responsive than the SF-12 to changes in QOL. The SF-12 should not be used alone to measure the changes in QOL of patients with heart failure.     

Management of hypertension in liver transplant patients

Hypertension is a common co-morbidity and a frequent complication in liver transplant patients. The aim of this paper is to concisely review available clinical data and propose a hypertension treatment algorithm in liver transplant patients. Calcium channel blockers are mainstay of the treatment due to their potent vasodilatory effects. Dihydropyridine calcium channel blockers are preferable due to their least interaction with cytochrome P450 enzyme system and, therefore, minimal risk of potential disruption of immunosuppressive drug levels. Beta-blockers may be considered first line drugs in patients with resting tachycardia and in those with high cardiac outputs. Data support the use of beta-blockers for patients intolerant or unresponsive to calcium channel blockers. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have little value when used early after liver transplant but may have a more pronounced role during the later periods. Diuretics may be of value in combination with other drugs, especially to counteract the potassium-retaining effects of calcineurin inhibitors. Treatment of post liver transplantation hypertension in patients with co-morbid conditions such as coronary artery disease, diabetes mellitus, congestive heart failure, and renal disease will likely require combination therapy.