Interhemispheric and ipsilateral connections in Parkinson's disease: relation to mirror movements.

Mirror movements (MM) occur in early, asymmetric Parkinson's disease (PD). To examine the pathophysiology of MM in PD, we studied 13 PD patients with MM (PD-MM), 7 PD patients without MM (PD-NM), and 14 normal subjects. Cross-correlogram did not detect common synaptic input to motoneuron pools innervating homologous hand muscles in PD-MM patients. Transcranial magnetic stimulation studies showed no significant difference in ipsilateral motor-evoked potentials between PD-MM patients and normal subjects. The MM side of PD-MM patients showed a slower increase in ipsilateral silent period area with higher level of muscle contraction than the non-MM side and normal subjects. There was less interhemispheric inhibition (IHI) at long interstimulus intervals of 20 to 50 ms in PD-MM than PD-NM. IHI reduced short interval intracortical inhibition in normal subjects and PD-NM, but not in PD-MM. IHI significantly increased intracortical facilitation in PD-MM and PD-NM patients, but not in normal subjects. Our results suggest that MM in PD is due to activation of the contralateral motor cortex. PD-MM patients had reduced transcallosal inhibitory effects on cortical output neurons and on intracortical inhibitory circuits compared to PD-NM patients and controls. These deficits in transcallosal inhibition may contribute to MM in PD patients.     

Mechanisms of Tolerance Induced by Donor-Specific Transfusion and ICOS-B7h Blockade in a Model of CD4+ T-Cell-Mediated Allograft Rejection

The inducible co-stimulatory molecule (ICOS) has been shown to play a critical role in T-cell activation and differentiation, and the regulation of alloimmune responses in vivo. Using an MHC class II mismatched model of CD4(+) T-cell-mediated rejection, we found that treatment of mice with DST and ICOS-B7h blockade induced long-term skin allograft survival and donor-specific transplantation tolerance. ICOS blockade, either during antigen priming or during the effector phase, previously shown to alter the outcome of the immune response, had a similar effect on graft survival. DST and anti-B7h mAb reduced the frequency of IFN-gamma-producing allospecific cells but did not produce deviation to a T(H)2 phenotype. In an adoptive transfer model using ABM TCR transgenic mice directly reactive to I-A(bm12), DST and anti-B7h mAb reduced the number of allospecific CD4(+) T cells and increased CD4(+) T-cell apoptosis. These data demonstrate that DST and anti-B7h mAb induces transplantation tolerance to MHC class II mismatched skin grafts by a reduction of the alloreactive clone size that is, at least in part, dependent on apoptosis of host alloantigen-specific CD4(+) T cells.     

Is chronic nitrate therapy associated with a different clinical presentation of acute coronary syndrome?

BACKGROUND: Nitrate therapy can induce ischemic preconditioning with a consequent increase in tolerance to ischemia. In the context of acute coronary syndromes (ACS), nitrates may result in a different presentation. with greater protection. OBJECTIVES: To investigate in a population of patients with ACS whether previous chronic use of nitrates results in a different presentation of ACS. METHODS: We studied 287 patients (65 +/- 13 years, 66% male) admitted to our department in the first six months of 2005 with ACS (with and without ST-segment elevation). Of these, 8% were under nitrate therapy at the time of admission. In this group, 27% presented ACS without ST-segment elevation, while in the group without nitrates this value was 58% (p = 0.005). By univariate analysis, the use of nitrates was a predictor of the preferential occurrence of non-ST-segment elevation ACS (OR 0.27, 95% CI 0.10-0.71). After correction for the potential influence of variables (age, gender, previous revascularization and smoking) by multivariate logistic regression, nitrate therapy remained a borderline predictor of clinical presentation as non-ST-segment elevation ACS (OR 0.37, 95% CI 0.13-1.04, p = 0.059). CONCLUSIONS: Previous use of nitrates was associated with a tendency to present as non-ST-segment elevation ACS. This finding may be explained by the hypothesis that nitrates induce pharmacological preconditioning, reducing the transmural extent of myocardial infarction.     

Atypical absences and recurrent absence status in an adult with Angelman syndrome due to the UBE3A mutation.

Angelman syndrome is a neurogenetic disorder resulting in refractory epilepsy and profound psychomotor retardation in its most prevalent form, caused by deletion of maternal chromosome 15q11-13. We report the case of a 29-year-old, mentally retarded man with unusual electroencephalographic changes during periods of atypical absence status epilepticus, a previously unreported manifestation of the usually milder, drug-responsive epilepsy associated with Angelman syndrome due to the UBE3A mutation.[Published with video sequences].     

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.     

Silastic ring vertical gastric bypass: cohort study with 83% rate of 5-year follow-up

BackgroundSilastic ring vertical gastric bypass (SRVGB) with jejunal interposition is our standard operation for morbidly obese patients. We present the results of 5 years of follow-up in a cohort of patients who underwent SRVGB in 2001.MethodsThe records of all 160 consecutive patients who underwent SRVGB from January to December 2001 were reviewed. Of the 160 procedures, 143 were primary open cases, 14 were revisions from restrictive procedures, and 3 were laparoscopic cases. At 5 years, the body mass index and percentage of excess weight loss was available for 133 patients (83%) at office visits (n = 91, 68.4%), by telephone (n = 40, 30.1%), or by e-mail (n = 2, 1.5%).ResultsOf the 160 patients, 121 were women and 39 were men, with a mean age of 33.15 ± 10.0 years, percentage of ideal body weight of 195.7% ± 40.8%, and body mass index of 44.6 ± 9.3 kg/m². The mean hospital stay was 3 ± 1 days. One patient (.6%) died of a pulmonary embolus. Early complications included 3 cases (1.87%) of upper gastrointestinal bleeding and 4 gastric leaks (2.5%): 2 (1.36%) from primary cases and 2 (14.29%) from revisional cases. Late complications included 32 patients (20%) with incisional hernias, 20 (12.5%) with anemia, 14 (8.8%) with dumping, 4 (2.5%) with gastrojejunal stricture, 2 (1.25%) with intestinal obstruction, and 2 (1.25%) requiring silastic ring surgical removal. The 5-year follow-up data were available for 133 patients (83%). The mean body mass index in this group was 27 ± 5 kg/m², with a percentage of excess weight loss of 83% ± 18.3% at 5 years postoperatively.ConclusionThe results of our study have shown that SRVGB is an effective operation for promoting lasting weight loss, with acceptable mortality and complication rates.     

Effects of a toxin from the mucus of the caribbean sea anemone (Bunodosoma granulifera) on the ionic currents of single ventricular mammalian cardiomyocytes

The effects were studied of a toxin (Bainh) isolated from the secretion of the Caribbean sea anemone Bunodosoma granulifera on electrical and mechanical activities of rat ventricular muscle. The effects on the ionic currents of single rat and dog ventricular cardiomyocytes were studied using the whole-cell recording patch-clamp technique. In the concentration range from 1 to 10 mg/ml, Bainh increased the force of contraction and induced an increase in action potential duration of ventricular multicellular preparations. In single cardiomyocytes, at concentrations up to 10 mg/ml Bainh showed no significant effects on the sodium current. However, at 0.5–1 mg/ml it increased the L-type Ca current (I_CaL) by 25–50%. This increase in I_CaL was not voltage dependent and was reversible after washout. The transient outward current was not significantly affected by Bainh (1–10 mg/ml). In this concentration range, Bainh markedly (≈75%) increased the inward-going rectifier current, I_K1. This effect that was not voltage dependent and was fully reversible upon returning to control solution. It is suggested that these effects on ionic currents could explain the positive inotropic action of Bainh on cardiac multicellular preparations.     

Alcohol Intake and Withdrawal: Effects on Branched Chain Amino Acids and Alanine

The effects of chronic alcohol consumption on plasma branched chain amino acids and alanine concentrations were evaluated, and basal blood concentrations of these amino acids were determined after chronic ethanol intake and following a withdrawal period in 30 admitted alcoholics. After ethanol intake, alcoholics showed increased branched chain amino acid concentrations; the blood alanine concentrations were depressed after the withdrawal period. To evaluate the effect of ethanol on diurnal variations of these amino acids in the blood, a group of these patients underwent two isocaloric diets with and without wine. The diet with alcohol induced a sustained increase of branched chain amino acids persisting even after the postprandial phase with a decrease of alanine as compared to the diet without.