Haplotypes and gene expression implicate the MAPT region for Parkinson disease: the GenePD Study.

Background: Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum.

Use of the TIMI frame count in the assessment of coronary artery blood flow and microvascular function over the past 15 years.

Since its introduction, the TIMI frame count method has contributed to the understanding of the pathophysiology of coronary artery disease. In this article, the evolution of the TFC method and its applicability in the assessment of various therapeutic modalities are described.

Current and emerging treatments for cervical dystonia.

Cervical dystonia (CD), also known as spasmodic torticollis, is the most common of the focal dystonias. Muscle hypertrophy is present in nearly all patients, and neck pain is associated with CD in about 80% of patients. Remissions can occur in about 20% of patients, though most last under a year.

Cardiac function during steep Trendelenburg position and CO2 pneumoperitoneum for robotic-assisted prostatectomy: a trans-oesophageal Doppler probe study.

Background: Haemodynamic changes associated with pneumoperitoneum and steep Trendelenburg position were investigated in non-obese, ASA I-II males, using general anaesthesia (sevoflurane in air/O2, 40%) undergoing robotic-assisted laparoscopic prostatectomy.

Methods: A trans-oesophageal echo-Doppler probe (Arrow International) measured cardiovascular changes in heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance (SVR), stroke volume (SV) and aortic diameter (AoD) in 35 of 37 males. Assessments were conducted after induction of general anaesthesia in: the supine position; at 45 degrees Trendelenburg; Trendelenburg + pnuemoperitoneum (intra-abdominal 15 mmHg); and at the end of surgery in the supine position.

Overview of Parkinson's disease.

This overview of Parkinson's disease is designed to serve as a background to the discussion elsewhere in this supplement on the pharmacotherapy used in its management. Parkinson's disease is a common progressive neurodegenerative condition associated with significant disability and negative impact on quality of life. Although the cause of Parkinson's disease is unknown, the pathologic manifestation involves the loss or dysfunction of dopaminergic neurons in the substantia nigra pars compacta.

Oncologic emergencies: the anesthesiologist's perspective.

Cancer is the second leading cause of death in the United States. During the course of treatment, a cancer patient may present emergently to the hospital because of either the cancer itself or a manifestation of cancer therapy. Rarely, patients with cancer can present to the operating room with several emergent conditions that require the services of an anesthesiologist.

Interference of a four-hole aperture for on-chip quantitative two-dimensional differential phase imaging.

We present a novel on-chip method for quantitative two-dimensional differential phase imaging. This technique uses four circular holes (600 nm diameter, 1.2 mum spacing) arranged in a 'plus' pattern that are fabricated in a layer of metal above a complementary metal-oxide semiconductor (CMOS) imaging sensor.

Results from a 2-year centralized tolcapone liver enzyme monitoring program.

Objectives: Tolcapone, administered with levodopa/carbidopa to patients with Parkinson disease, is an effective and generally well-tolerated adjunctive therapy. However, 4 early cases of hepatotoxicity causing 3 deaths in patients not properly monitored gave rise to more rigorous liver function test monitoring guidelines and a liver function test monitoring program in which blood samples from tolcapone-treated patients were tested and results were collected in a central database. We analyzed these results to determine the percentages of patients with at least 1 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation above the upper limit of normal (ULN) and at least 1 elevation greater than 2 times the ULN.

Good statistical practice in pharmacology. Problem 1.

Background And Purpose: This paper is intended to assist pharmacologists in making the most of statistical analysis and in avoiding common errors that can lead to false conclusions.

Approach: A scenario is presented where a pathway inhibitor increased blood pressure responses to an agonist by about one third. The fictional experimenter concludes that the inhibitor enhanced the responses to the agonist, but has not applied any statistical analysis.

Good statistical practice in pharmacology. Problem 2.

Background And Purpose: This paper is intended to assist pharmacologists to make the most of statistical analysis and in avoid common errors.

Approach: A scenario is presented where an experimenter performed an experiment to test the effects of two drugs on cultured cells. Analysis of the results, expressed as percentage of control, by a one-way ANOVA yielded P=0.

Impact of iodinated contrast injections on percent diameter coronary arterial stenosis and implications for trials of intracoronary pharmacotherapies in patients with ST-elevation myocardial infarction.

Administration of fibrinolytic, antiplatelet, and antithrombotic agents by the intracoronary route may disaggregate clot, but the potential role of the mechanical force of the injection itself in decreasing clot burden has not been studied. Patients with ST-segment elevation myocardial infarction who were pretreated in the emergency room (ER) with unfractionated heparin and aspirin in the TITAN-TIMI 34 study were randomized to treatment with eptifibatide in the ER (n = 131) versus after diagnostic catheterization (n = 150). Quantitative coronary angiography was used to assess change in diameter stenosis from time of first contrast injection to injection before percutaneous coronary intervention (PCI) immediately preceding wire placement down the culprit artery in a matching view.

Complete ascertainment of Parkinson disease in the Swedish Twin Registry.

This report describes the ascertainment of Parkinson disease (PD) in all individuals aged 50 years or older (49,814 individuals) from the Swedish Twin Registry. In phase one of the study, all twins were screened for PD using telephone interviews, with a response rate of 72.7%.

Safety and efficacy of newly formulated selegiline orally disintegrating tablets as an adjunct to levodopa in the management of 'off' episodes in patients with Parkinson's disease.

Objective: Patients receiving levodopa for Parkinson's disease experience motor fluctuations and immobility ('off' episodes) between doses. This study assessed adjunctive Zelapar (selegiline orally disintegrating tablet (ODT)) for managing off episodes and for long-term safety.

Methods: This open-label extension evaluated long-term safety, efficacy, and tolerability of adjunctive selegiline ODT 2.

Diagnostic and prognostic value of ambulatory ECG (Holter) monitoring in patients with coronary heart disease: a review.

Silent ischemia, the most common expression of atherosclerotic heart disease, affects approximately 30-50% of patients during their activities of daily living. The present review provides a comprehensive and practical summary of current knowledge on perioperative myocardial ischemia through MEDLINE searches up to June 2005, using keywords including "silent ischemia," "transient ischemia," and "Holter monitoring." Holter monitoring (i.

Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age: the GenePD Study.

Background: Polymorphisms in the glutathione S-transferase pi gene (GSTP1), encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson disease (PD) with exposure to pesticides. Using the GenePD Study sample of familial PD cases, we explored whether GSTP1 polymorphisms were associated with the age at onset of PD symptoms and whether that relation was modified by exposure to herbicides.

Methods: Seven single-nucleotide polymorphisms (SNPs) were genotyped and tested for association with PD onset age in men in three strata: no exposure to herbicides, residential exposure to herbicides, and occupational exposure to herbicides.

Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study.

Background: The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD).

Objective: To evaluate the influence of heterozygosity for parkin mutation on onset age in a sample of families with at least 2 PD-affected members.

Design: Clinical and genetic study.

Principles: when there should be no difference--how to fail to reject the null hypothesis.

It is common to perform experiments in which a 'success' is claimed when the null hypothesis is discarded. However, there is a category of experiment that has become important in which a success is when the null hypothesis is not rejected. Failing to discard the null hypothesis is different from proving it to be valid, a distinction that is particularly important in experiments in which any inadequacy of experimental design or implementation enhances the likelihood of a success.

The effect of propofol on acid-base balance and ionic composition of venous and arterial blood in goats.

The aim of the present study was to determine the effect of propofol on acid-base balance and ionic composition of arterial and venous blood in clinically healthy goats. The experiment was performed on ten adult goats. Propofol was administered intravenously at bolus dose of 6 mg/kg bw.

BDNF genetic variants are associated with onset age of familial Parkinson disease: GenePD Study.

Brain-derived neurotrophic factor (BDNF) stimulates neuronal growth and protects nigral dopamine neurons in animal models of Parkinson disease (PD). Therefore, BDNF is a candidate gene for PD. The authors investigated five single-nucleotide polymorphisms in 597 cases of familial PD.

Management of pain and nausea in outpatient surgery.

The cost associated with surgical procedures has been dramatically decreased by the ability to perform these procedures on an outpatient basis. Pain and nausea, two common symptoms after anesthesia and surgical procedures, are among the greatest concerns for patients and their family members. As a result of the distress and sequelae associated with these symptoms, clinicians have attempted to determine the optimal intraoperative and postoperative symptom management for patients.

Selegiline orally disintegrating tablets for the treatment of Parkinson's disease.

Selegiline orally disintegrating tablet is a potent, selective and irreversible inhibitor of monoamine oxidase type B. It is delivered in an innovative formulation that largely bypasses the gut and first-pass hepatic metabolism by allowing transbuccal absorption. Selegiline orally disintegrating tablet dissolves in the mouth within seconds and is rapidly absorbed directly into the systemic circulation, increasing parent drug bioavailability and lowering plasma metabolites compared with conventional oral formulations.

Effects of interchanging hyperopic defocus and form deprivation stimuli in normal and optic nerve-sectioned chicks.

To test the hypothesis that the same mechanisms mediate form deprivation and lens-induced myopia, the ocular growth responses of chicks alternately exposed to lenses and diffusers at regular intervals (3h) were compared to those of chicks exposed to either negative lenses or diffusers alone. In total, there were four experiments: (1) -15 D lenses and/or diffusers on normal birds, (2) -15 D lenses and/or diffusers on optic nerve-sectioned (ONS) birds, (3) -5/-10/-15 D lenses (sequentially applied) and/or diffusers on normal birds and (4) -5/-10/-15 D lenses and/or diffusers on ONS birds. All treatments were monocular.

Laparoscopic cryptorchidectomy in dogs --report of 15 cases.

The study aimed at determining the usability of laparoscopic cryptorchidectomy in treating cases of simple cryptorchidism and neoplastic testes in dogs. The presence of one or both testes inside the peritoneal cavity was confirmed in this study by an ultrasonographic examination employing the use of a 6.5 MHz convex head.

Laparoscopic removal of gastric foreign bodies in dogs--comparison of manual suturing and stapling viscerosynthesis.

This study was an attempt to evaluate the application of various laparoscopic techniques of removing foreign bodies from the stomach in dogs in comparison to conventional laparotomy. The research was conducted on two groups of 10 dogs each with clinically confirmed foreign bodies in the stomach. In case of all patients, a laparoscopic instrument, EndoBag, was used for the removal of the foreign body from the stomach and the abdominal cavity.