Visual feedback has differential effects on reaching movements in Parkinson's and Alzheimer's disease

We examine the role of visual feedback in the programming and execution of reaching movement in patients with Parkinson's disease without cognitive impairment and patients with Alzheimer's disease without extrapyramidal signs. Controls were normally aging subjects. All subjects moved a cursor to targets on a digitizing tablet without seeing their limb. Starting and target positions were always visible on a screen while, during movement, cursor position was either visible or blanked. They were instructed to make uncorrected movements, as fast and as accurate as possible without minimizing reaction time. In absence of visual feedback, movement accuracy in patients with AD was severely impaired. Hand paths of parkinsonian patients were as accurate as normal subjects' with similar temporal velocity profiles and movement speed. With cursor feedback, accuracy was the same in the three groups, although movement speed and transport phase in patients with Alzheimer's disease were significantly reduced compared to the other groups. Also, movements of parkinsonian patients showed shorter transport phase and lower mean velocity than controls'. The different characteristics of the motor performance suggests that in the two diseases visual information is used differently for both motor programming and execution: patients with Alzheimer's disease, while scarcely using feed forward commands, relied on continuous on-line external cues. The correlation of motor performance with cognitive impairment argues against the hypothesis of basal ganglia involvement in AD. The motor abnormalities we found may represent early subclinical manifestation of apraxic disturbance. Parkinsonian patients showed higher reliance on feedback commands only with cursor feedback: this could be explained by their difficulty in engaging effectively automatic routines when distractors are present.     

Tolerance to ischemia and hypoxia is reduced in aged human myocardium

BACKGROUND: Recovery of cardiac function after cardiac surgery and other interventional cardiac procedures in elderly patients is inferior to that in younger patients, suggesting that the aged myocardium is more sensitive to ischemia and other stresses. Although convincing data from animal studies of senescence now exist, there is a dearth of controlled in vitro studies that examine the specific response of aged human myocardium to the stress of hypoxia or ischemia. OBJECTIVE: We sought to determine the effect of age on the capacity of human atrial trabeculae to recover contractile function after in vitro hypoxic or ischemic stress. METHODS: Atrial pectinate trabeculae were dissected from the tip of 58 right atrial appendages harvested during an operation in patients aged between 34 and 89 years and electrically stimulated at 1 Hz in oxygenated Ringer's solution at 37 degrees C. Tissues experienced 30 minutes of either hypoxia (N(2) and perfusate) or simulated ischemia (humidified N(2) without perfusate) and were returned to normoxia for recovery of function for 30 minutes. Developed force and other contractile variables were determined during each period. RESULTS: Under normoxic conditions, no significant age difference was observed for any contractile function variable. However, after hypoxia, the old (70-89 years) and intermediate age groups (60-69 years) showed reduced recovery of developed force (48.5% +/- 22.2% [n = 11] and 44.9% +/- 19% [n = 12], respectively) compared with that found (66.4% +/- 19.7% [n = 15]) in the younger (34-59 years) group (mean +/- SD, P =.02). Similarly, after simulated ischemia, the groups of 70- to 89-year-old and 60- to 69-year-old subjects showed reduced recovery of developed force (35.7% +/- 17% [n = 5] and 51.1% +/- 11.8% [n = 9], respectively) compared with that found (68.2% +/- 10.4% [n = 6]) in the group of 34- to 59-year-old subjects (P =.01). Multivariable analysis, comparing 20 factors of surgical patient characteristics and recovery of developed force, found that only age (P =.01) and hypertension (P =.01) were predictors of reduced recovery of developed force after either hypoxia or simulated ischemia. CONCLUSIONS: In aged human atrial myocardium, the capacity to recover contractile function after in vitro hypoxia or simulated ischemia is reduced compared with the younger myocardium of mature adults. These findings suggest that enhanced myocardial protective strategies may be indicated for elderly patients undergoing cardiac surgery.     

Evaluation of recombinant tissue-type plasminogen activator in adhesion prevention and neoangiogenesis in a rat experimental adhesion model

This study was designed to test the effect of recombinant tissue-type plasminogen activator (rt-PA) in reducing adhesion formation and to observe its influence on peritoneal neoangiogenesis. In 20 Wistar rats, a 4-cm midline incision was made, and a square piece of Silastic, 0.5×0.5 cm and 0.2 mm thick, was fixed on the right side of the peritoneum with two separate angular stitches of nylon 9/O. The rats were randomized into two groups of 10 animals each. In the first group we injected 0.2 mg of rt-PA intraperitoneally three times a day. The second group of 10 rats was used as a control group. Each rat was reoperated on day 12. Intraperitoneal injection of rt-PA seemed not to affect adhesion formation, as a 100% adhesion rate was reported in the treated group compared with 90% of the control group. The results showed that rt-PA acts on the neoangiogenesis involved in postsurgical adhesion formation by reducing the size and length of the vessels. This action seems to slow down peritoneal healing with a negative effect on postsurgical adhesion prevention.     

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

'Low dose' 99mTc-Sestamibi for radioguided surgery of primary hyperparathyroidism.

AIM: In this study, we evaluated the efficacy of low dose (99m)Tc-Sestamibi administration for radioguided parathyroid surgery in patients with primary hyperparathyroidism (PHPT). METHODS: Three hundred consecutive PHPT patients were studied between September, 1999 and July, 2003. Pre-operative work-up included (99m)Tc-pertechnetate/(99m)Tc-Sestamibi subtraction scintigraphy and high resolution ultrasonography (US). 37MBq of (99m)Tc-Sestamibi was injected i.v. in the operating suite approximately 10 min prior to the beginning of the surgical procedure for intraoperative radiolocalization; quick parathyroid hormone (QPTH) assays were performed. RESULTS: Two hundred and seven of the 211 patients selected for minimally-invasive radioguided parathyroidectomy (MIRP) were successfully treated for a solitary parathyroid adenoma (PA) through a 2-2.5 cm skin incision (mean operative time 35 min, mean hospital stay 1.2 days). In the 89 patients selected for traditional bilateral neck exploration (BNE), radioguided surgery was not as successful in the identification of the PA, especially in patients with (99m)Tc-Sestamibi-avid thyroid nodules. Nevertheless, the combination of probe and QPTH measurement was very helpful in patients with multigland disease. CONCLUSIONS: Low-dose (99m)Tc-Sestamibi administered few minutes before surgery is sufficient for MIRP in patients with high likelihood of a solitary PA and without concomitant (99m)Tc-Sestamibi-avid thyroid nodules. The combination of radioguided surgery and QPTH measurements is very useful in the early identification of unanticipated multigland disease.     

Effector gammadelta T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma.

The aim of this study was to investigate the in vitro immunomodulatory effects of zoledronic acid (Zol) on peripheral blood Vgamma9/Vdelta2 (gammadelta) T cells of normal donors and multiple myeloma (MM) patients. gammadelta T cells were stimulated with Zol and low doses of interleukin-2 (IL-2), and then analyzed for proliferation, cytokine production, and generation of effector activity against myeloma cell lines and primary myeloma cells. Proliferation of gammadelta T cells was observed in 100% of normal donors and 50% of MM patients. gammadelta T cells produced IFN-gamma, surface mobilized the CD107a and CD107b antigens, and exerted direct cell-to-cell antimyeloma activity irrespective of the ability to proliferate to Zol and IL-2. The memory phenotype was predominant in the MM gammadelta T cells that proliferated in response to Zol (responders), whereas effector cells were predominant in those that did not (nonresponders). Zol induced antimyeloma activity through the monocyte-dependent activation of gammadelta T cells and by enhancing the immunosensitivity of myeloma cells to gammadelta T cells. Mevastatin, a specific inhibitor of hydroxy-methylglutaryl-CoA reductase, completely abrogated this antimyeloma activity.     

Gastrointestinal haemorrhage due to erosion of the duodenal wall by a biliary stent

Complications from improperly placed biliary stents are not uncommon. Free loose wires from the ends of an uncovered stent can irritate and damage adjacent mucosal surfaces. Effective management can be achieved via percutaneous placement of a second stent to alter the orientation of the original stent.     

Nicotine-induced smooth muscle cell proliferation is mediated through bFGF and TGF-beta 1

BACKGROUND: Cigarette smoking influences and enhances the development of atherosclerosis. We investigated if nicotine, an important constituent of cigarette smoking, has a stimulatory effect on bovine smooth muscle cell proliferation in vitro through the mediation of bFGF and TGF-beta 1. METHODS: Bovine aortic smooth muscle cells (SMC) were stimulated with (-)-nicotine at various concentrations ranging from 6 x 10(-4) mol/L to 6 x 10(-8) mol/L. SMC viability and count were assessed. The presence of bFGF and TGF-beta 1 in serum-free conditioned media was determined by the inhibition antibody-binding assay, and the mitogenic activity of (-)-nicotine on SMC was analyzed by the 3H-thymidine uptake. Polymerase chain reaction was used to study the expression of bFGF and TGF-beta 1. RESULTS: The bFGF release after (-)-nicotine stimulation was greater than in the controls, whereas TGF-beta 1 release was lower. The greatest mitogenic activity was found at a (-)-nicotine concentration of 6 x 10(-6) mol/L. The addition of monoclonal antibody anti-bFGF decreased the 3H-thymidine uptake of SMC exposed to (-)-nicotine, whereas the addition of monoclonal antibody anti-TGF-beta 1 increased the 3H-thymidine uptake of stimulated SMC. bFGF mRNA expression was significantly higher in SMC exposed to (-)-nicotine than in the controls, but TGF-beta 1 mRNA expression was significantly lower in SMC exposed to 6 x 10(-6) mol/L (-)-nicotine than in SMC treated with the other concentrations of (-)-nicotine and in controls. CONCLUSIONS: Nicotine is a potent regulator of bFGF and TGF-beta 1 production and release by aortic SMC, and it seems to play an important role in the development and progression of atherosclerosis and neointimal fibrous hyperplasia.     

Extended (D2) lymphadenectomy in gastric cancer: a five year experience

The extent of lymph node dissection in stomach adenocarcinoma is currently under debate. Japanese data strongly support the therapeutic value of extended lymphadenectomy (D2 node dissection), whereas in Western countries several prospective trials have recently been completed with contrasting results. During the period May 1993 to May 1998, 164 patients with gastric cancer were observed: 136 patients, treated with a radical surgical procedure including lymph node dissection according to the guidelines of the Japanese Research Society for Gastric Cancer, were eligible for our analysis. Clinical, histopathological, and surgical factors were examined for their influence on long-term survival. Our results on morbidity and mortality rates are similar to Japanese series: we suggest that the experience and training of the surgeon and his personal attitude towards extensive lymph node dissection may, therefore, be a major factor influencing the morbidity associated with the procedure. The relatively high estimated 3-year survival rate (52%) suggests support for extended lymphadenectomy (D2 dissection) in gastric cancer as standard treatment.