Thrombolysis of cerebral clot embolism in rat: effect of treatment delay.

Rats submitted to focal cerebral ischemia by middle cerebral artery clot embolism were treated with recombinant tissue plasminogen activator (rt-PA) at increasing delays (1.5, 3 and 4.5 h) after the onset of ischemia.

Quantitative T*(2) and T'(2) maps during reversible focal cerebral ischemia in rats: separation of blood oxygenation from nonsusceptibility-based contributions.

Quantitative imaging contrast is evaluated which allows the selective measurement of the blood oxygenation state during cerebral ischemia within a multiparametric imaging study on rats. In a first step, the ambiguities arising in T*(2)-weighted images due to T*(2) heterogeneity are eliminated by calculating T*(2) maps. Then, 1/T'(2) maps are calculated according to 1/T'(2) = 1/T*(2) - 1/T(2) to eliminate nonsusceptibility-induced changes of 1/T*(2) after the induction of stroke.

Rapid monitoring of diffusion, DC potential, and blood oxygenation changes during global ischemia. Effects of hypoglycemia, hyperglycemia, and TTX.

Background And Purpose: The increasing interest in diffusion-weighted MRI (MRI) for diagnosis and monitoring of acute stroke in humans calls for a sound understanding of the underlying mechanisms of this image contrast in acute cerebral ischemia. The present study aimed to show that a rapid decrease in brain-water apparent diffusion coefficient (ADC) occurs coincident with anoxic depolarization and that this change is delayed by hyperglycemia and sodium channel blockade but accelerated by hypoglycemia.

Methods: Rats were divided into groups: normoglycemic, hypoglycemic, and hyperglycemic, and those given local tetrodotoxin (TTX) application.

Gradient echo time dependence and quantitative parameter maps for somatosensory activation in rats at 7 T.

The dependence of functional magnetic resonance imaging (MRI) contrast on the gradient echo time TE in T2*-weighted blood oxygenation level-dependent (BOLD) fast low-angle shot (FLASH) imaging has been studied at 7 T for electrical forepaw stimulation in alpha-chloralose anesthetized rats. The observed variation of both the activation signal intensity and spatial pattern with echo time TE, resulting from the regional heterogeneity of T2*, was assessed by the calculation of quantitative T2* and quantitative STE = 0 maps, the latter representing the back-extrapolated signal intensity for TE = 0. The subsequently determined T2* and STE = 0 activation maps allowed a pixelwise separation of true BOLD from inflow contributions to forepaw stimulation-induced signal change in the somatosensory cortex of rat brain.

Intensive speech treatment for patients with Parkinson's disease: short-and long-term comparison of two techniques.

The purpose of this study was to evaluate the long-term (12 months) effects of two forms of speech treatment on the speech and voice deficits that occur in Parkinson's disease. Thirty-five patients with idiopathic Parkinson's disease were assigned to one of two speech treatment groups: voice and respiration (The Lee Silverman Voice Treatment [LSVT]) or placebo (respiration) treatment. Vocal intensity data from before, immediately after, and at 6 and 12 months after speech treatment revealed statistically significant differences between the treatment groups.

The natural history of Parkinson's disease in the pre-levodopa and post-levodopa eras.

Since Parkinson's disease was first described by James Parkinson in 1817, the natural history has been confounded by various treatment modalities: the replenishment of deficient dopamine, the addition of the dopamine agonists, and the more recent addition of drugs whose putative action may slow the natural history of the disease. Nevertheless it remains a disease that is slowly and inexorably progressive over several decades. The quality of life during this progression can be improved, and the duration of life before inanition produces life-threatening complications can be extended.

Bilateral fetal grafts for Parkinson's disease: 22 months' results.

Five patients with severe Parkinson's disease underwent bilateral multiple graft implants of nondissociated fetal mesodiencephalic tissues. Graft implantation was performed in China following CT-guided stereotactic placement of a novel delivery system. Follow-up has demonstrated substantially reduced levodopa requirements and clinical improvements of motor, postural functions and reduction of freezing and on-off phenomenon.

An examination of male-female differences in progression and mortality of Parkinson's disease.

We conducted disability and mortality studies to determine if the male preponderance usually found in Parkinson's disease (PD) was reflected in different courses of the diseases in the 2 sexes. We analyzed longitudinal disability score in 47 men and 23 women with PD followed for 6 years at UCLA. We found no significant differences between the sexes in mean disability scores in any of the 6 years.

Effect of age at onset on progression and mortality in Parkinson's disease.

We examined longitudinal disability scores in 54 patients with Parkinson's disease followed for 6 years at UCLA. We sorted data into 3 groups based on age at onset of symptoms: group A, onset under 50 years; group B, 50 to 59 years; group C, 60 years or older. There were no significant differences between groups initially.

Multi-center study of Parkinson mortality with early versus later dopa treatment.

Four geographically diverse centers provided data on mortality in 359 patients with Parkinson's disease, the majority of whom began dopa treatment during the early experimental trials of 1968 to 1970. Patients were classified into three groups based on the duration of symptoms prior to starting dopa treatment: Group 1, 1 to 3 years; Group 2, 4 to 6 years; Group 3, 7 to 9 years. After 15 years of treatment and 3,689 person-years of observation, Group 1 had an observed-to-expected mortality ratio of 1.

Parkinson's disease: progression and mortality.

Patients with Parkinson's disease were compared during two 15-year periods before and after the introduction of levodopa. With levodopa treatment: The duration of illness at each stage of severity was 3 to 5 years longer; at every duration of illness, death and disability were reduced 1.5- to 3-fold, except in patients whose treatment had been delayed; abnormal involuntary movements that interfered with function occurred in 24% of patients; severe fluctuations that required rescheduling of activities occurred in 29% of patients; severe AIMs and fluctuations were rare during the first 3 years of treatment, but remained constant thereafter, without progressive increase; prevalence of severe fluctuations was related only to age of onset of disease: If under 50, severe fluctuations developed in 66%, if age 50 to 59 at onset, they developed in 30%, if over age 60, in only 6%; average age at death was 6 years older; and observed/expected mortality was 1.

Result of chronic levodopa therapy and its modification by bromocriptine in Parkinson's disease.

15 years' experience with Parkinson's disease treated with levodopa was compared to the 15 years before the advent of levodopa. Progression to severe disability and death was prolonged, at each stage of severity, by 3 to 5 years. At each duration of illness, the percentage of patients with severe disability was reduced significantly.

Low dosages of bromocriptine added to levodopa in Parkinson's disease.

Thirty-six patients with Parkinson's disease, on levodopa, were admitted to a double-blind, parallel, 40-week study of adjunct bromocriptine in dosages increased by 2.5 mg every 4 weeks. A 37% improvement of the mean neurologic deficit score was obtained at the maximal daily dosage of 20 mg.

The discovery, fermentation, isolation, and structure of antibiotic A33853 and its tetraacetyl derivative.

The structure of antibiotic A33853, isolated from the culture broth of Streptomyces sp., NRRL 12068, is reported. The structure was deduced from an X-ray crystallographic study of its tetraacetyl derivative.

Bromocriptine and its use in Parkinsonism.

Bromocriptine is a potent dopamine agonist which directly stimulates dopamine receptors. In the corpus striatum, this action results in alleviation of many of the signs and symptoms of parkinsonism. The effectiveness of bromocriptine may persist for at least one to two years; results of more prolonged treatment are not available.

Chronic levodopa and renal function.

Renal function studies were performed in seventeen patients, under metabolic ward conditions, before the initiation of therapy with levodopa. These studies were repeated during the first two to three weeks of treatment and, again, after one to two years of chronic therapy. There were no significant differences between the results of pre- and post-therapy studies, except that the blood urea nitrogen was slightly, but significantly, elevated in the nine patients who had been on the drug for one to two years.

Increased dosage of carbidopa in patients with Parkinson's disease receiving low doses of levodopa. A pilot study.

Twenty-one patients with Parkinson's disease were studied because their low maintenance dosages of carbidopa-levodopa in the customary ratio of 1:10 provided less than the daily 75 mg of carbidopa believed necessary to achieve full inhibition of extracerebral dopa decarboxylation. The dosage of carbidopa was increased 2.5 times to between 75 and 150 mg daily, while the mean dosage of levodopa essentially was unchanged.

Neuropsychological impairment with schizophrenia vs. acute and chronic cerebral lesions.

Performed detailed neuropsychological evaluations with 25 recently hospitalized schizophrenics in whom systematic neurologic workups had failed to reveal CNS disease. Efforts were made to minimize possible effects of drug-induced extrapyramidal symptoms on test performance. Although the schizophrenics showed some neuropsychological impairment relative to 25 normals, their deficits were not as severe as those of patients known to have either acute or chronic brain disorders (N = 25).

Hypothalamic atrophy.

A patient, who has been followed for thirteen years, developed the first symptoms of progressive hypothalamic atrophy at the age of 39. The diagnosis was confirmed by pneumoencephalography five years after onset. Hypothalamic dysfunction was manifested clinically by loss of libido, impotence, obesity, polydypsia, somnolence, and rage attacks.

Dopamine excretion and vulnerability to drug-induced Parkinsonism. Schizophrenic patients.

Before and during a standardized course of trifluoperazine therapy, 18 schizophrenic patients underwent repeated examinations for extrapyramidal motor signs, clinical psychopathology, and urinary excretion of free and conjugated forms of dopamine and its metabolites. Patients excreting more free dopamine and metabolites, or showing less complete conjugation, before drug treatment, were much less likely than others to develop parkinsonian akinesia and rigidity during drug treatment. Neither catatonic rigidity nor akinesia before treatment was predictive of a parkinsonian response to trifluoperazine, but pretreatment tremor may have been.

A32390A, a new biologically active metabolite. I. Discovery and fermentation studies.

A32390A is an isonitrile-containing derivative of diacyl D-mannitol. The compound is produced in fermentation as the major component of a metabolic complex known as A32390. A32390A inhibits dopamine-beta-hydroxylase reduces heart and adrenal norepinephrine levels, lowers blood pressure in hypertensive rats, and possesses antibiotic activity vs.