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Biomedical subjects

J Grotta

Publications and source records attributed to J Grotta.

35 records · Page 2Linked to original sources
PubMed1995

Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial.

BACKGROUND AND PURPOSE: CGS 19755 is a competitive N-methyl-D-aspartate (NMDA) receptor antagonist that limits neuronal damage in animal stroke models. The objectives of this multicenter (7 centers), randomized, double-blind, placebo-controlled, ascending-dose phase IIa study were to evaluate the safety and tolerability of CGS 19755 and obtain pharmacokinetic and preliminary data on its efficacious dose range in patients treated within 12 hours of hemispheric ischemic stroke. METHODS: At each dose level, 6 patients were randomized to one or two intravenous bolus doses of CGS 19755, and 2 patients were randomized to placebo. An unblinded safety and monitoring committee-evaluated results at each dose before ascending to the next level. All patients at the first level (1 mg/kg) received two doses separated by 12 hours. The first 2 patients at 2 mg/kg received two doses, but adverse experiences occurred in both; subsequent patient groups received single doses of 2.0, 1.75, or 1.5 mg/kg. RESULTS: Adverse experiences (agitation, hallucinations, confusion, paranoia, and delirium) occurred in all 6 patients treated with 2 mg/kg, and in 3 of 5 at 1.75 mg/kg. Similar but milder adverse experiences were noted in 4 of 7 patients at 1.5 mg/kg and 1 of 6 patients at 1.0 mg/kg. Adverse experiences began between 20 minutes and 22 hours (mean, 8 hours) after treatment and lasted 2 to 60 hours (mean, 24 hours). Mortality was 1 of 8 in patients receiving placebo and 3 of 24 in treated patients. In treated survivors, median and mean percent improvement in National Institutes of Health Stroke Scale scores from baseline to terminal visit (mean, 86 days) was comparable at all doses, and 95% of treated patients had Barthel Index scores of > or = 70 at the terminal visit. CONCLUSIONS: We conclude that a single intravenous dose of 1.5 mg/kg CGS 19755 is safe and tolerable in patients with acute ischemic stroke. An efficacy trial is indicated.

Acute Disease↗
PubMed1995

Subjective experiences of 24 patients dramatically recovering from stroke.

BACKGROUND: There are no reports describing patients' perception of having a stroke and then dramatically recovering. SUMMARY OF REPORT: We interviewed 24 patients randomized at our center to intravenous tissue plasminogen activator or placebo in an ongoing multicenter blinded prospective study. These patients demonstrated at least 50% improvement or an absolute improvement of 5 points on the National Institutes of Health Stroke Scale during the first 24 hours after treatment, with 7 patients returning completely to normal. Twelve of 24 of the strokes involved the right middle cerebral artery, 2 of 24 the right posterior cerebral artery, 8 of 24 the left middle cerebral artery, and 2 of 24 the basilar artery territory. CT scans at 24 hours or 1 week showed infarction in 19 of 24. Most patients (19 of 24) could clearly recall the exact circumstances involving the onset of their stroke, but only 12 of 24 were aware of the magnitude of their neurological deficit (7 of 14 right hemisphere and 4 of 8 left hemisphere patients). Only 6 of 24 were aware of their improvement when it occurred (3 of 14 right hemisphere and 2 of 8 left hemisphere patients). Five of 24 remembered positive phenomena such as warmth or tingling during their recovery, and only 2 patients demonstrated euphoria. Most patients seemed peculiarly unaware or blasé about their deficit and improvement. CONCLUSIONS: Most patients with acute stroke are not aware of the severity of their problem, and recovering patients do not remember important events during the next 24 hours. This occurs with either right or left hemisphere lesions and may have a significant impact on early stroke recognition.

Awareness↗
PubMed1995

Elective intubation for neurologic deterioration after stroke.

OBJECTIVE: To provide data to guide physicians and family when deciding whether a patient should be electively intubated after ischemic stroke. DESIGN: Chart review and patient interview. Clinical course, neurologic outcome, and financial and psychosocial effect of the decision to intubate were determined. SETTING: Neurology/Neurosurgery critical care unit. PATIENTS: Of our last 250 acute carotid territory ischemic stroke cases, we found 20 patients (8%) who were electively intubated, after CT and neurologic assessment, for neurologic deterioration. INTERVENTIONS: All patients received standard medical therapy. RESULTS: Intubation occurred 3 hours to 7 days (mean, 41 hours) after the onset of symptoms; six of 20 patients required intubation within the first 6 hours. Once clinical deterioration began, 10 of 20 patients required intubation within 1 hour. Six of 20 patients were discharged alive; two subsequently died, one is mostly dependent, two became mostly independent (one of these had a hemicraniectomy and is still improving, and the other died of an intercurrent illness 4 years after her stroke), and one is totally independent. The four "good" outcome survivors were distinguished by higher Glasgow Coma Scale scores (9.2 versus 5.9), and extubation was usually possible within 72 hours. For nonsurvivors, mean hospitalization after intubation was 6.4 days. In survivors, the monthly uninsured cost was $0 to $2,000, and caregivers experienced moderate stress. The same decision would be repeated by 76% of caregivers; 53% of caregivers would want intubation for themselves. CONCLUSIONS: Satisfactory outcome is possible in the 8% of ischemic stroke patients requiring elective intubation. Possible predictors of good outcome include less severe depression of consciousness at the time of intubation, extubation within 3 days, and hemicraniectomy. In retrospect, most families would repeat the decision to intubate. Further study in more patients of the cost/benefit of cerebral resuscitation after stroke is greatly needed.

Adult↗
PubMed1994

Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group.

BACKGROUND AND PURPOSE: Despite the frequent use of clinical rating scales in multicenter therapeutic stroke trials, no generally acceptable method exists to train and certify investigators to use the instrument consistently. We desired to train investigators to use the National Institutes of Health Stroke Scale in a study of acute stroke therapy so that all examiners rated patients comparably. METHODS: We devised a two-camera videotape method that optimizes the visual presentation of examination findings. We then measured the effectiveness of the training by asking each investigator to evaluate a set of 11 patients, also on videotape. We tabulated the evaluations, devised a scoring system, and calculated measures of interobserver agreement among the participants in this study. RESULTS: We trained and certified 162 investigators. We found moderate to excellent agreement on most Stroke Scale items (unweighted kappa > 0.60). Two items, facial paresis and ataxia, exhibited poor agreement (unweighted kappa < 0.40) and should be revised in future editions of the scale. Performance improved with video training compared with previous studies. Inclusion of the motor rating of the unaffected limbs in the total score did not affect reliability. CONCLUSIONS: Video training and certification is a practical and effective method to standardize the use of examination scales. Two cameras must be used during the taping of patients to accurately present the clinical findings. This method is easily adapted to any study in which a large number of investigators will be enrolling patients at multiple clinical centers.

Cerebrovascular Disorders↗
PubMed1993

New uses for calcium channel blockers. Therapeutic implications.

Calcium antagonists block calcium entry into cells, resulting in relaxation of smooth muscle and limitation of the cytotoxic effects of ischaemia in various organ systems. They are most frequently used for clinical conditions requiring vasodilatation, i.e. hypertension and Raynaud's phenomenon, and this also suggests that the most common adverse effect of these drugs for noncardiovascular indications is an unwanted decline in blood pressure. Other uses include treatment of supraventricular arrhythmias and angina. There is some evidence that these drugs retard the development of atherosclerosis. Calcium channel blockers also improve renal reperfusion and may reduce renal insufficiency due to various nephrotoxins, and are particularly useful in renal transplantation for protection against cyclosporin toxicity and post-transplant acute tubular necrosis. These drugs are also useful in pregnancy-induced hypertension and unwanted uterine contraction. Affective disorders and malignancies may be other conditions which benefit from calcium antagonist therapy. Calcium antagonists, in particular nimodipine which is most selective for the cerebral vasculature, have been approved for treating vasospasm after subarachnoid haemorrhage. They are probably also effective for treatment of migraine. Calcium channel blockers may be effective for treating acute cerebral infarction, but results of clinical trials to date have been equivocal, largely because it has been difficult to recruit patients within the short interval after the onset of stroke when these drugs would be most effective, and because of the unwanted hypotensive effect of high doses.

Animals↗
PubMed1991

Early treatment of ischemic stroke with a calcium antagonist.

We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified.

Blood Pressure↗
PubMed1991

Recognition and management of poststroke depression in the elderly.

Depression occurs in 30-50% of stroke survivors and is an important determinant of functional outcome in these patients. Depression after stroke has a biological basis and can be successfully treated. Tricyclic drugs are the first line of treatment therapy but their side effects need to be considered and patients undergoing this treatment need to be carefully monitored.

Aged↗
PubMed1989

Sjögren's syndrome and other rheumatic disorders presenting to a neurology service.

A prospective study of 100 consecutive admissions to a university neurology inpatient service was done to assess the prevalence and spectrum of autoimmune rheumatic disorders, most specifically Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and lupus anticoagulant (LA)-associated disorders. All patients underwent a physical exam (PE), a rheumatic disease questionnaire, and serologic testing (ANA, RF, and LA). The 100 patients consisted of 36 men and 64 women, aged 17 to 98 (mean 60) years and included 47 white, 45 black and eight other. Definite rheumatic diseases were found in 11%. These included three with previously undiagnosed SS and neurologic symptoms of seizures and dementia, psychiatric disease, and embolic cerebrovascular accident (CVA). Also present were three CVA patients with LA; one migraine patient with known SLE and LA; and one each with CNS Whipples disease, Behcet's disease, isolated CNS angiitis, and B27+ spondyloarthritis. With respect to SS questions and PE findings, three groups of patients were identified: --Questionnaire; +PE 14 patients, aged 33-81 (mean 73) years; 13 F, 1 M who were not further evaluated although significant seroreactivity was present in three (RF 2, LA 1). --Questionnaire; -PE 16 patients, aged 32-98 (mean 56) years; 13 F, 3 M. Four patients had further evaluation, diagnostic for SS in three of them (3/3 abnormal lip biopsies, 2/3 KCS, 2/3 anti-Ro). Another four had unexplained seroreactivity (ANA 2, RF 1, LA 1). --Questionnaire; +PE 12 patients, aged 24-77 (mean 54) years; 10 F, 2 M, not further evaluated although four had seroreactivity in the setting of idiopathic neurologic disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Whole blood viscosity parameters and cerebral blood flow.

This report describes the statistical relationship of several whole blood viscosity parameters and cerebral blood flow (CBF) in 53 consecutive patients and normal controls. Significant correlations were present between CBF and serum fibrinogen (P = .05), hematocrit (P less than .05), and a relationship involving both fibrinogen and hematocrit (P less than .01). We conclude that heightened whole blood viscosity does correlate with decreased cerebral blood flow in the ranges measured in our patients, that both fibrinogen and hematocrit must be taken into consideration in viscosity determinations, and that changes in viscosity may have an important effect on CBF in regions of low flow.

Adult↗
PubMedDate not supplied

Fibrinogen, blood viscosity, and cerebral ischemia.

This study examines the effect of fibrinogen and consequent blood viscosity reduction on cerebral blood flow and cellular injury following severe cerebral ischemia for 30 minutes in 78 Wistar rats. In half of these rats 10 to 15 cc's of blood was removed and replaced with a mixture of 5% albumin and autologous red blood cells maintaining a constant hematocrit but resulting in a 30% decrease in fibrinogen and corresponding reduction in viscosity. Fibrinogen reduction in a slight increase in baseline CBF and the elimination of post-ischemic hyperemia at 24 hours. Both study and control animals showed a similar decrease in CBF at 30 minutes and 2 hours. There was no significant difference in the severity of ischemic cellular change between the fibrinogen reduction group and controls, although there was a significant inverse relationship between the amount of viscosity change and severity of cellular injury within the treatment group. Fibrinogen reduction alone cannot significantly ameliorate ischemic injury in this model. Viscosity reduction therapy should include reduction of hematocrit and alteration of red cell deformability.

Animals↗
PubMedDate not supplied

The effect of nicardipine on neuronal function following ischemia.

In cerebral ischemia, it has been proposed that calcium influx into neurons results in irreversible cellular injury during reperfusion. We administered nicardipine, a dihydropyridine calcium entry blocker, by continuous subcutaneous infusion to twenty five rats beginning before (PR) or following (PO) ischemia, and compared somatosensory evoked potentials (SEPs) to twenty eight ischemic control animals. Comparable ischemic cellular changes were seen in the hippocampi of all animals. SEP amplitude was higher in both the PR (p less than .005) and PO (p less than .0005) groups compared to controls. This effect was found in all three components (P1, N1, P2) of the evoked response. Plasma nicardipine levels of 6-10 ng/ml were associated with mild hypotension. We conclude that nicardipine improved neuronal function as measured by SEPs when administered before or after ischemia, most likely by interrupting the cytotoxic events occurring in cortical neurons during reperfusion.

Animals↗