The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.     

Insulin resistance is associated with circulating fibrinogen levels in nondiabetic patients receiving peritoneal dialysis.

BACKGROUND: Insulin resistance (IR) and inflammation are associated with increased risk of cardiovascular disease in the general population. Continuous glucose absorption in peritoneal dialysis (PD) may induce hyperglycemia and hyperinsulinemia. METHODS: We evaluated IR in nondiabetic patients receiving PD, and analyzed the association between IR and systemic inflammation biomarkers by performing a cross-sectional study on ambulatory dialysis. A total of 25 nondiabetic patients receiving PD and 25 healthy individuals, matched for gender, age, and body mass index (BMI), were included. The PD group was composed of 11 men and 14 women, with a mean age of 47 +/- 14 years and mean BMI of 25.5 +/- 4.7 kg/m(2). The control group was composed of 10 men and 15 women, with a mean age of 45 +/- 12 years and BMI of 24.0 +/- 2.8 kg/m(2). RESULTS: IR was evaluated by the homeostasis model assessment method (HOMA-IR). Inflammation was assessed through high-sensitivity C-reactive protein (CRP) and fibrinogen. Body composition and truncal fat were evaluated by dual energy x-ray absorptiometry. HOMA-IR was significantly higher (P < .0001) in subjects receiving PD (4.9, range: 2.3-9.3 mmol/L x muU/mL) compared with healthy subjects (1.2, range: 0.4-4.8 mmol/L x muU/mL). As expected, compared with controls, patients receiving PD had significantly higher levels of insulin (26.5 +/- 7.5 muU/mL vs 6.3 +/- 3.4 muU/mL; P < .0001), CRP (6.3, range: 0.3-61.1 mg/L vs 2.4, range: 0.6-5.9 mg/L; P = .001), and fibrinogen (379 +/- 101 mg/dL vs 268 +/- 66 mg/dL; P < .0001). However, there were no significant differences in body and truncal fat mass between the groups. A significant correlation between HOMA-IR and fibrinogen (Rho = 0.48; P = .01) was observed. However, no correlation was found between HOMA-IR and CRP. Also, no significant correlations were found between HOMA-IR and body fat mass (Rho = 0.11), and between HOMA-IR and truncal fat mass (Rho = 0.19). CONCLUSIONS: Patients receiving PD demonstrate a state of IR that is associated with high circulating levels of fibrinogen. This suggests that hyperfibrinogenemia may be involved in the pathogenesis of IR in this setting.     

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.     

Phenotypic variability of a distinct deletion in McLeod syndrome

The X‐linked McLeod neuroacanthocytosis syndrome strongly resembles Huntington's disease and has been reported in various countries world‐wide. Herein, we report two Chilean brothers with predominant psychiatric features at disease onset including schizophrenia‐like psychosis and obsessive compulsive disorder. Molecular genetic analysis revealed a small deletion in the XK gene (938‐942delCTCTA), which has been already described in a North American patient of Anglo‐Saxon descent and a Japanese family, presenting with seizures, muscle atrophy or chorea yet absence of psychiatric features. These findings argue against a founder effect and indicate a profound phenotypic variability associated with the 938‐942delCTCTA deletion. Our report supports the inclusion of McLeod syndrome in the differential diagnosis of Huntington's disease as well as acute psychosis in male subjects. © 2007 Movement Disorder Society     

Genomic ancestry of a sample population from the state of São Paulo,Brazil

Allelic frequencies of eight autosomal short‐tandem repeat (STR) loci (TH01, TPOx, CSF1PO, vWA, FES/FPS, F13A1, F13B, and CD4) were determined in 400 individuals born in the State of São Paulo. No significant deviations from Hardy‐Weinberg equilibrium were found in any loci analyzed. The Unweighted Pair‐Group Method with Arithmetic Mean (UPGMA) tree constructed based on genetic distances revealed that the present population was grouped with Europeans, and separated from African and Amerindian populations. Estimates of admixture components based on the gene identity method revealed 79% European, 14% African, and 7% Amerindian contributions to this Brazilian population sample. Am. J. Hum. Biol. 18:702–705, 2006. © 2006 Wiley‐Liss, Inc.     

Computed tomography evaluation of temporomandibular joint alterations in patients with class II division 1 subdivision malocclusions: condyle-fossa relationship.

Thirty persons with Class II Division 1 subdivision malocclusions, ranging in age from 12 years 8 months to 42 years, underwent computed tomography of the temporomandibular joints. The images obtained from sagittal slices were used to assess the depth of the mandibular fossa, the angulation of the posterior wall of the articular tubercle, the condyle-fossa relationship, and the concentric position of the condyles associated with this malocclusion. Paired Student t tests were applied, and Pearson product moment correlations (r) were determined after measurements on both Class I and Class II sides were obtained. No statistically significant asymmetries were found in the depth of the mandibular fossa, the angulation of the posterior wall of the articular tubercle, or the condyle-fossa relationship. However, a statistically significant (P <.05) anterior positioning of the condyles was observed.     

Quantitative (82)Rb PET/CT: development and validation of myocardial perfusion database.

The use of myocardial perfusion (82)Rb PET/CT studies continues to increase but its accuracy using database quantification methods for the diagnosis of coronary artery disease (CAD) has not been established. METHODS: A sex-independent normal database and criteria for abnormality for rest-stress (82)Rb PET/CT myocardial perfusion imaging were developed and validated by evaluation of 281 patients (136 females: mean age +/- SD, 63.3 +/- 13.3 y; 145 males: mean age +/- SD, 63.9 +/- 12.8 y) who underwent a rest-adenosine stress (82)Rb PET/CT study. These patients were divided into 3 groups: (a) healthy group: 30 patients, with <5% likelihood of CAD (low likelihood [LLK]) based on sequential Bayesian analysis; these patients were used to generate the normal distribution; (b) pilot group: 174 patients; these patients were used to determine the optimal criteria for detecting and localizing the perfusion abnormality; and (c) validation group: 76 patients (23 with LLK of CAD and 53 who underwent coronary angiography; these patients were used for prospective validation. RESULTS: Of the 53 patients who underwent coronary angiography, 8 had <50% stenosis and 45 patients had at least one stenosis > or =50% in one major artery. Fifteen patients had single-vessel disease, 17 had double-vessel disease, and 13 had triple-vessel disease. The prospective validation shows a normalcy rate of 78% (18/23) for global CAD. The analyses by individual arteries show a normalcy rate of 96% (22/23) for the left anterior descending coronary artery, 96% for the left circumflex coronary artery (22/23), and 100% for the right coronary artery (23/23). The overall sensitivity for detection of CAD (> or =50% stenosis) was 93% (42/45). The overall specificity for detection of the absence of CAD (< or =50% stenosis) was 75% (6/8). Also, the positive predictive value for global CAD was 95% (42/44), the negative predictive value was 67% (6/9), and the accuracy was 91% (48/53). CONCLUSION: The quantitative (82)Rb PET/CT database created and validated in this study is highly accurate for the detection and localization of CAD. Physicians should consider using the quantitative output of these algorithms as decision support tools to aid with image interpretation.     

Seminested polymerase chain reaction (PCR) for detecting Helicobacter pylori DNA in carotid atheromas.

A polymerase chain reaction (PCR) method for the detection of the glmM gene, selected as Helicobacter pylori target sequence, was improved. While performing pathogenicity island cagA gene detection to discriminate pathogenic strains in atherosclerotic carotid samples, several cagA-positive but glmM-negative samples were found. Polymorphisms present in the region amplified in the nested PCR reaction could explain this result; primers were therefore designed to perform a seminested reaction; this modification optimized sensitivity while maintaining specificity. A real-time PCR for Helicobacter DNA detection was also setup. The combination of all 4 PCR reactions detected 83% of H. pylori DNA-positive samples in atherosclerotic carotid tissue, 64% of which were cagA gene positive.     

Pallidotomy in Parkinson's disease improves single-joint, repetitive, ballistic movements, but fails to modify multijoint, repetitive, gestural movements.

We studied 12 non-demented PD patients in on state before and 3 months after posteroventral pallidotomy (PVP), in order to evaluate the effects of surgery upon an unconstrained, multijoint skilled movement as well as a single joint, repetitive, ballistic movement. A Selspot II System was used for three-dimensional data acquisition, processing and reconstruction of limb trajectories. Specific wrist kinematic features of spatial accuracy (linearity and planarity), temporal attributes (acceleration and velocity), spatiotemporal relationships (velocity-curvature coupling), and joint kinematic variables (relationships between wrist and elbow velocities and relative arm angle amplitudes) for each cycle of movement were graphically and numerically analysed. QMC was applied to single joint, repetitive, ballistic movements. QMC significantly improved after PVP (P < 0.0006). However, wrist as well as joint kinematic variables of the gestural movements failed to change significantly after PVP. The lack of improvement of the kinematic abnormalities of the gestural movement in PD patients would indicate that they are unrelated to the basic motor deficit; most likely they are the result of a disruption of a complex of sensorimotor integration processes due to abnormal parieto-frontal basal ganglia interaction.     

Cyclic guanosine 3'3' monophosphate concentrations in pre-eclampsia: effects of hydralazine

Objective To elucidate the role of the L-arginine: nitric oxide pathway in pregnancy and pre-eclampsia.
Participants Pregnant women (nulliparous, age < 25 years). Normotensive pregnancy (   n = 22  ) was defined when blood pressure remained at levels of < 120/80 mmHg and there was no proteinuria. Women with pre-eclampsia (   n = 22  ) had blood pressure measurements of > 140/90 mmHg and proteinuria of > 300 mg/l. Nonpregnant normotensive women (   n = 22  ) were studied as controls.
Study Design Blood samples were taken for measurements of ionised calcium, atrial natriuretic factor, cyclic guanosine 3'5'monophophate (GMP), arginine and asymmetric dimethylarginine. Urine samples were collected for determination of cyclic GMP excretion. Cyclic GMP concentrations were also determined in 12 women with severe pre-eclampsia before and after treatment with hydralazine.
Results L-arginine, asymmetric dimethylarginine and atrial natriuretic factor were not different in any group. Cyclic GMP concentrations in plasma [0.94 (SD 0.23) nM] as well as in urine [50.1 (SD15.7)μM] were increased significantly (   P < 0.05  ) in normal pregnancy compared to nonpregnant controls [plasma mean 0.46 (SD 0.12) nM and urine mean 18.4 (SD 10.3) μM], but not in the pre-eclampsia group [plasma mean 0.48 (SD 0.10) nM and urine mean 24.1 (SD 14.5) μM]. Concentrations of cyclic GMP in plasma and urine increased significantly (   P < 0.05  ) in women treated with hydralazine.
Conclusions The differences in cyclic GMP concentrations may reflect differences in nitric oxide production. Hydralazine increases cyclic GMP concentrations in severely pre-eclamptic women. This action could explain the antihypertensive effect of hydralazine.