Rasagiline-associated motor improvement in PD occurs without worsening of cognitive and behavioral symptoms.

BACKGROUND: Cognitive and behavioral adverse events (AEs) such as hallucinations, confusion, depression, somnolence and other sleep disorders commonly limit effective management of motor symptoms in PD. Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a novel, second-generation, selective, irreversible monoamine oxidase type B inhibitor, demonstrated in monotherapy and adjunctive trials to be effective for PD with excellent tolerability. METHODS: The occurrence of cognitive and behavioral AEs and the change from baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) part I mental subscores were reviewed in two multicenter, randomized, placebo-controlled, 26-week trials of rasagiline for early and moderate-to-advanced patients with PD. The UPDRS is a multi-item rating scale specific to PD; part I rates the patient's intellectual impairment, thought disorders, depression and motivation/initiative. RESULTS: The TEMPO study evaluated rasagiline monotherapy in early PD patients (n=404). The PRESTO study evaluated rasagiline as adjunctive therapy in moderate-to-advanced PD patients with motor complications who were receiving optimized levodopa/carbidopa (n=472). In the analysis of adverse event reporting for both studies, no cognitive and behavioral AE in either the rasagiline 1 mg or placebo groups exceeded 10% of the study population and the frequency differences between rasagiline 1 mg and placebo never exceeded 3%. There was no adverse effect on the UPDRS mental subscore relative to placebo in either of the two studies. CONCLUSION: Rasagiline 1 mg once daily improves PD symptoms and motor fluctuations in early and moderate-to-advanced PD patients without causing significant cognitive and behavioral AE or adverse changes in mentation, behavior and mood.

Environmental public health surveillance: possible estuary-associated syndrome.

Public health surveillance involves the collection, analysis, and dissemination of data for use in public health practice. A surveillance system includes the capacity to collect and analyze data as well as the ability to disseminate the data to public health agencies that can undertake effective prevention and control activities. An emerging issue in environmental public health surveillance involves human exposure to the toxins produced by microorganisms present in oceans and estuaries. One of these organisms is Pfiesteria piscicida Steidinger & Burkholder, a dinoflagellate found in estuaries along the Atlantic and gulf coasts of the United States. There have been reports of both human illness associated with occupational exposures to concentrated laboratory cultures of P. piscicida and massive fill kills associated with the presence of the organism in rivers and estuaries. These reports, and anecdotal reports from people who worked on rivers where the organism has been found, generated concern that environmental exposures to P. piscicida, similar organisms, or perhaps a toxin or toxins produced by the organism(s), could cause adverse human health effects. To begin to evaluate the public health burden associated with P. piscicida, investigators from the National Center for Environmental Health at Centers for Disease Control and Prevention and health agencies from states along the Atlantic coast collaborated to develop a passive surveillance system for collecting, classifying, and tracking public inquiries about the organism. Specifically, the group developed exposure and symptom criteria and developed data collection and reporting capabilities to capture the human health parameters collectively referred to as possible estuary-associated syndrome (PEAS). The surveillance system was implemented in six states (Delaware, Florida, Maryland, North Carolina, South Carolina, Virginia) beginning in June 1998. From 1 June 1998 through 30 June 2001, the six state health agencies participating in the PEAS surveillance system received 3,859 calls: 3,768 callers requested information and 91 callers reported symptoms. Five individuals have been identified as meeting PEAS criteria.

Myoclonus and its disorders.

This article defines myoclonus, describes the numerous causes of myoclonus, and summarizes various classification schemes. The electrodiagnostic characteristics and pathophysiology of this movement disorder are described. Treatment of the various forms of myoclonus is also discussed.

The 1996 New York blizzard: impact on noninjury emergency visits.

The purpose of this study was to investigate the impact of the January 1996 New York blizzard on emergency visits to 12 Suffolk County hospitals for 10 noninjury health conditions. Emergency charts from the blizzard week (January 7-11) and a nonblizzard week (January 21-25) were reviewed and information was abstracted from the records meeting the criteria. Blizzard conditions were associated with increased visits for myocardial infarction/angina, primarily shoveling-related, and with decreased visits for asthma. Diagnoses for the other noninjury conditions did not differ significantly between time periods. The decrease in asthma visits possibly resulted from asthmatics avoiding exposure to blizzard conditions. An unexpected finding was that most patients with shoveling-related myocardial infarction/angina did not report pre-existing heart disease. Also of interest was that one quarter of myocardial infarction/angina visits by women were reportedly shoveling-related. This suggests that health warnings may be less effective at decreasing shoveling-induced myocardial infarction if they are directed primarily at men and at people with heart disease.

Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families.

OBJECTIVE: To determine the incidence of spinocerebellar ataxia (SCA) types 1, 2, 3, 6, and 7 and Friedreich's ataxia (FA) among a large panel of ataxia families. BACKGROUND: The ataxias are a clinically and genetically heterogeneous group of neurodegenerative diseases that variably affect the cerebellum, brainstem, and spinocerebellar tracts. Trinucleotide repeat expansions have been shown to be the mutational mechanism for five dominantly inherited SCAs as well as FA. METHODS: We collected DNA samples and clinical data from patients representing 361 families with adult-onset ataxia of unknown etiology. Patients with a clinical diagnosis of FA were specifically excluded from our collection. RESULTS: Among the 178 dominant kindreds, we found SCA1 expansion at a frequency of 5.6%, SCA2 expansion at a frequency of 15.2%, SCA3 expansion at a frequency of 20.8%, SCA6 expansion at a frequency of 15.2%, and SCA7 expansion at a frequency of 4.5%. FA alleles were found in 11.4% of apparently recessive and 5.2% of apparently sporadic patients. Among these patients the repeat sizes for one or both FA alleles were relatively small, with sizes for the smaller allele ranging from 90 to 600 GAA repeats. The clinical presentation for these patients is atypical for FA, with one or more of the following characteristics: adult onset of disease, retained tendon reflexes, normal plantar response, and intact or partially intact sensory perceptions. CONCLUSIONS: Pathogenic trinucleotide repeat expansions were found among 61% of the dominant kindreds. Among patients with apparently recessive or negative family histories of ataxia, 6.8% and 4.4% tested positive for a CAG expansion at one of the dominant loci, and 11.4 and 5.2% of patients with apparently recessive or sporadic forms of ataxia had FA expansions. Because of the significant implications that a dominant versus recessive inheritance pattern has for future generations, it is important to screen patients who do not have a clearly dominant inheritance pattern for expansions at both the FA and the dominant ataxia loci.

Single-voxel proton MR spectroscopy of nonneoplastic brain lesions suggestive of a neoplasm.

BACKGROUND AND PURPOSE: MR spectroscopy is used to characterize biochemical components of normal and abnormal brain tissue. We sought to evaluate common histologic findings in a diverse group of nonneoplastic diseases in patients with in vivo MR spectroscopic profiles suggestive of a CNS neoplasm. METHODS: During a 2-year period, 241 patients with suspected neoplastic CNS lesions detected on MR images were studied with MR spectroscopy. Of these, five patients with a nonneoplastic diagnosis were identified retrospectively; a sixth patient without tissue diagnosis was added. MR spectroscopic findings consistent with a neoplasm included elevated choline and decreased N-acetylaspartate and creatine, with or without detectable mobile lipid and lactate peaks. RESULTS: The histologic specimens in all five patients for whom tissue diagnoses were available showed significant WBC infiltrates, with both interstitial and perivascular accumulations of lymphocytes, macrophages, histiocytes, and (in one case) plasma cells. Reactive astrogliosis was also prominent in most tissue samples. This cellular immune response was an integral component of the underlying disorder in these patients, including fulminant demyelination in two patients, human herpesvirus 6 encephalitis in one patient, organizing hematoma from a small arteriovenous malformation in one patient, and inflammatory pseudotumor in one patient. Although no histologic data were available in the sixth patient, neoplasm was considered unlikely on the basis of ongoing clinical and neuroradiologic improvement without specific therapy. CONCLUSION: Nonneoplastic disease processes in the CNS may elicit a reactive proliferation of cellular elements of the immune system and of glial tissue that is associated with MR spectroscopic profiles indistinguishable from CNS neoplasms with current in vivo MR spectroscopic techniques. Such false-positive findings substantiate the need for histologic examination of tissue as the standard of reference for the diagnosis of intracranial mass lesions.

Fulminant progression of demyelinating disease after valproate-induced encephalopathy.

We report the clinical, radiologic, and pathologic features of a patient who had fulminant demyelinating disease and who experienced acute progression of his disease after an episode of valproate-induced hyperammonemic encephalopathy. The role hyperammonemia played in the progression of the demyelination is uncertain. This case raises concern of a possible risk with the use of valproic acid in the subset of patients with fulminant demyelinating disease.

Peritoneal solvent drag reflection coefficients are within the physiological range.

Previous estimates of the peritoneal solvent drag reflection coefficient (sigma) are widely disparate; some are outside the range expected for a semipermeable membrane (i.e., between 0 and 1). We have evaluated a novel method for determining sigma in a rabbit model of peritoneal dialysis. Test solute was infused intravenously, and sequential 2-hour isotonic and hypertonic exchanges (40 ml/kg) were performed in random order. Test solute was also added to the instilled hypertonic dialysis solution to inhibit transperitoneal solute diffusion during this exchange. Eight experiments were performed with creatinine as test solute and glucose as osmotic solute, and six experiments were performed with glucose as test solute and mannitol as osmotic solute. When using isotonic dialysis solution, the dialysate/plasma concentration ratio (D/P) for both test solutes increased throughout the exchange (p < 0.001). When using hypertonic dialysis solution, D/P creatinine was initially near 1 and decreased during the 1st hour of the exchange (p < 0.05); D/P glucose (as test solute) was initially 0.82 +/- (SEM) 0.07 and did not change during the exchange. The peritoneal diffusive permeability-area product (PA) was determined by fitting a mathematical model to the time dependence of the dialysate test solute concentration during the isotonic exchange using PA as an adjustable parameter, and sigma was determined in like manner during the hypertonic exchange using sigma as an adjustable parameter (and assuming a PA value equal to that during the isotonic exchange). The creatinine PA (1.37 +/- 0.28 ml/min) was higher than that for glucose (0.62 +/- 0.07 ml/min) as expected based on their solution diffusion coefficients. Creatinine and glucose sigma values were 0.38 +/- 0.06 and 0.43 +/- 0.05, respectively. We conclude that peritoneal sigma values for creatinine and glucose are within the physiological range.

Age and smoking-adjusted lung cancer incidence in a Utah county with a steel mill.

In a recent study of urban air pollution, a Utah county with a steel mill was compared with a county without a steel mill. The result was that 38% of respiratory cancer deaths could be attributed to the air pollution emanating from the mill. Rates for smoking in this previous study were not adjusted, but assumed rats were similar in both counties. We used smoking information obtained from an ongoing radon and lung cancer case-control study to adjust for smoking, and no difference was found in incidence rates of respiratory cancer in the county with the steel mill, compared with the other urban counties and the rural counties among male and female nonsmokers and male smokers. There was a slight excess of lung cancer among female smokers in the county with the steel mill when compared with the other urban counties (rate ratio [RR] = 1.3, 95% confidence interval [95% CI] = 1.0-1.6), but there was no effect in nonsmoking women. We conclude that the findings of the previous study can be explained by differences in smoking rates between the county with the steel mill and the other counties.

Convection does not govern plasma to dialysate transport of protein.

The dependence of protein clearance on molecular size during peritoneal dialysis can be explained by assuming that either convection or diffusion is the major mechanism governing plasma to dialysate transport of protein. If convection is the predominant transport mechanism, then plasma-to-dialysate transport rates for protein should not decrease when the protein concentration in the instilled dialysis solution is increased. In the present study, plasma-to-dialysate transport rates for fluorescein-labeled protein tracers, alpha-lactalbumin and immunoglobulin G (IgG), were determined during a six hour isotonic exchange (25 ml/kg) in New Zealand White rabbits. The protein tracers were continuously infused into the bloodstream to keep plasma concentrations relatively constant, and transperitoneal transport rates were determined either with or without tracer protein added to the instilled dialysis solution. Plasma-to-dialysate transport rates were greater for alpha-lactalbumin than for IgG as expected based on the molecular size of these proteins. Transport rates for both alpha-lactalbumin and IgG decreased when tracer protein was added to the instilled dialysis solution. The present observations do not support convection as the major mechanism governing plasma to dialysate transport of protein during peritoneal dialysis.

Macromolecule adsorption to hemodialysis membranes depends on molecular size.

Adsorption to hemodialysis membranes was studied by determining the binding kinetics of model macromolecules, polydisperse DEAE dextran (molecular radii 10-70 A), to an acrylonitrile-methallyl sulfonate copolymer membrane. Hemodialyzers were studied in a postdilution hemofiltration circuit where both blood path output and ultrafiltrate streams were returned to the reservoir. Changes in the reservoir concentration of and sieving coefficients for DEAE dextran were monitored over 24 h. Decreases (or increases) in reservoir concentration were assumed to result from adsorption to (or desorption from) the membrane. Small macromolecules adsorbed rapidly to the membrane but later desorbed. This rapid adsorption resulted in low initial sieving coefficients. Large macromolecules adsorbed slowly over the entire 24-hour study period. Additional experiments suggested that desorption of small macromolecules was due to displacement by large macromolecules. Adsorption and desorption of macromolecules to hemodialysis membranes are dynamic processes and depend on molecular size.