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Biomedical subjects

J W Harbison

Publications and source records attributed to J W Harbison.

At least 19 recordsLinked to original sources

Clinical considerations in selecting antiplatelet therapy in cerebrovascular disease.

Effective antiplatelet drugs--aspirin, ticlopidine, dipyridamole, and clopidogrel--are reviewed. Aspirin has remained the pharmacologic foundation of stroke prevention, primarily because of its low cost. It has been shown to provide a 22% relative risk reduction of stroke in high-risk patients. Its principal adverse effect is gastrotoxicity. Ticlopidine has been widely used in patients with a high risk of stroke who are sensitive to aspirin or in whom aspirin has failed. It has been associated with a median reduction in adenosine diphosphate-induced platelet aggregation of 70% in about 8-11 days. Ticlopidine has been shown to be superior to aspirin at three years in preventing stroke. The principal adverse effects are diarrhea and rash; there has been a 2.4% occurrence of neutropenia. In a trial comparing aspirin, dipyridamole, and a combination of the two, the risk of stroke was 18% lower with aspirin, 16% lower with dipyridamole, and 37% lower with combination therapy compared with placebo. The adverse-effect profile of dipyridamole has proven to be less problematic than that of aspirin or ticlopidine. In a trial comparing clopidogrel with aspirin, patients receiving clopidogrel had an annual 5.32% risk of ischemic stroke, myocardial infarction, or vascular death compared with 5.83% for patients receiving aspirin. Clopidogrel has been associated with a small occurrence of rash and diarrhea, and gastrointestinal intolerance and hemorrhage were less frequent with clopidogrel than with aspirin. Both aspirin and clopidogrel are associated with a low occurrence of neutropenia. Aspirin, ticlopidine, dipyridamole, and clopidogrel have earned a role in stroke prevention; the different adverse-effect profiles of the drugs will influence the choice of agent.

Aspirin↗

The risk of stroke in patients with first-ever retinal vs hemispheric transient ischemic attacks and high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial.

BACKGROUND: The prognosis of amaurosis fugax has been considered to be favorable compared with that of hemispheric transient ischemic attacks. However, this has remained uncertain for patients with significant carotid stenosis as the assessment of progression of the disease has been confounded when patients undergo carotid endarterectomy. In the North American Symptomatic Carotid Endarterectomy Trial, patients with high-grade (70% to 99%) carotid stenosis were randomized to receive either medical or surgical treatment, thus making an unconfounded analysis possible. METHOD: We identified 129 medically treated patients with high-grade carotid stenosis who had their first-ever transient ischemic attack as the entry event into the trial. Fifty-nine patients with retinal transient ischemic attacks (RTIAs) were compared with 70 patients with hemispheric transient ischemic attacks (HTIAs). RESULTS: Patients with HTIAs were older, with a higher prevalence of most risk factors for stroke. Average time of delay from the onset of transient ischemic attacks to medical treatment was longer for patients with RTIAs than for patients with HTIAs (48.5 vs 15.2 days). Kaplan-Meier estimates of the risk of ipsilateral stroke at 2 years were 16.6% +/- 5.6% for patients with RTIAs and 43.5% +/- 6.7% for patients with HTIAs (P = .002 for the difference in risk between RTIAs and HTIAs). From corresponding Cox's proportional hazards regression analyses, the risk of ipsilateral stroke ranged from 11.2% to 28.9% for patients with RTIAs and from 37.4% to 96.3% for patients with HTIAs across stenoses, spanning 75% to 95%. Overall, the relative risk of ipsilateral stroke (HTIAs compared with RTIAs) was 3.23 (95% confidence interval, 1.47 to 7.12), regardless of the degree of high-grade stenosis. CONCLUSION: To our knowledge, this study is the first report on the expected outcome for medically treated patients with high-grade (70% to 99%) carotid stenosis in whom the first-ever event was either an RTIA or HTIA. The presence of RTIAs carries a considerable risk of ipsilateral strokes, particularly at higher degrees of stenosis. However, in comparison with HTIAs, patients with RTIAs still have a better prognosis.

Aged↗

Ticlopidine versus aspirin for the prevention of recurrent stroke. Analysis of patients with minor stroke from the Ticlopidine Aspirin Stroke Study.

BACKGROUND AND PURPOSE: Ticlopidine has not been formally compared with aspirin in patients with a completed stroke. We therefore performed an analysis on a subgroup of patients from the Ticlopidine Aspirin Stroke Study (TASS) with a recent minor completed stroke as the qualifying ischemic event. METHODS: This was a multicenter, double-blind, randomized trial of patients with a recent history of cerebral ischemia. Eligible patients had a qualifying minor stroke within 3 months of study entry. All patients received either 650 mg aspirin twice daily or 250 mg ticlopidine twice daily for up to 5.8 years. The primary study end point was the first occurrence of nonfatal stroke or death from any cause. A secondary end point was the first occurrence of a fatal or nonfatal stroke. RESULTS: Minor stroke was the qualifying ischemic event in 927 patients (463 received ticlopidine and 464 received aspirin). The cumulative event rate at 1 year for nonfatal stroke or death was 6.3% for patients receiving ticlopidine and 10.8% for patients receiving aspirin, a 42% risk reduction in favor of ticlopidine. For fatal or nonfatal stroke, the cumulative event rate at 1 year was 4.8% for patients receiving ticlopidine and 7.5% for those receiving aspirin, a risk reduction of 36% for ticlopidine relative to aspirin. The overall risk reductions were 22.1% for nonfatal stroke or death and 19.9% for fatal or nonfatal stroke. Adverse reactions were reported in 58% of the ticlopidine patients and 51% of the aspirin patients. CONCLUSIONS: The results in this subgroup are consistent with the overall TASS results and show that ticlopidine is somewhat more effective than aspirin for reducing the risk of stroke in patients with a completed minor stroke.

Adult↗

The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke.

The Canadian American Ticlopidine Study (CATS) is a randomised, double-blind, placebo-controlled trial to assess the effect of ticlopidine (250 mg twice daily) in reducing the rate of subsequent occurrence of stroke, myocardial infarction, or vascular death in patients who have had a recent thromboembolic stroke. Twenty-five centres entered 1072 patients into the study between 1 week and 4 months after their qualifying stroke. The patients were treated and followed for up to 3 years (mean 24 months). In the efficacy analysis, the event rate per year for stroke, myocardial infarction or vascular death, considered together, was 15.3% in the placebo group and 10.8% in the ticlopidine group, representing a relative risk reduction with ticlopidine of 30.2% (95% confidence interval 7.5-48.3%; p = 0.006). Ticlopidine was beneficial for both men and women (relative risk reductions 28.1%, p = 0.037, and 34.2%, p = 0.045, respectively). Analysis by intention-to-treat gave a smaller estimate of risk reduction (23.3%, p = 0.020) for stroke, myocardial infarction, or vascular death. Adverse experiences associated with ticlopidine included neutropenia (severe in about 1% of cases) and skin rash and diarrhoea (severe in 2% of cases each); all were reversible. This study provides evidence of a beneficial effect of ticlopidine in both men and women with a recent thromboembolic stroke.

Aged↗

Perceptions of housestaff stress and dysfunction within the academic medical center.

Stress, emotional dysfunction, and work impairment are seen as accelerating phenomena in residency training, and have received increased attention in the medical literature. The authors review relevant literature in this area, and note continued deficiencies in programs for prevention and intervention. The present study focuses on the perceptions of key members of the academic hierarchy regarding housestaff stress and impairment. Chairmen, program directors, and chief residents in all specialties were asked to estimate the prevalence of several impairment syndromes, to describe any existing policies or programs to assist residents, and to express their opinions about developing such intervention strategies. The results are compared by respondent group, by resident postgraduate year, and by groupings of surgical and non-surgical programs. Suggestions for further research in this area are then offered.

Academic Medical Centers↗

The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Design, organization, and baseline results.

The Canadian American Ticlopidine Study is a randomized, placebo-controlled, double-blind, multicenter study to assess the efficacy and safety of ticlopidine hydrochloride in patients who have suffered a thromboembolic stroke no less than 1 week and no more than 4 months before entry into the study. The primary assessment of efficacy will be based on the cluster of outcome events recurrent stroke, myocardial infarction, or vascular death. Twenty-five clinical centers, 12 in Canada and 13 in the United States, entered a total of 1,072 patients during a 3-year recruitment period; these patients were randomly allocated to receive either 250 mg ticlopidine or identical-appearing placebo tablets twice daily for up to 3 years. Patient recruitment was completed in December 1986. Patients were followed for a maximum of 3 years or until the close of the study in December 1987; at that time an average follow-up of 25 months had been achieved. We summarize the protocol and organization of the study and document the methods of execution and analysis, with corresponding criteria, before disclosure of the treatment code to any of the study investigators. We also provide a clinical description of the patients at entry into the study.

Aged↗

Papilledema after acute head injury.

Low grade papilledema after acute, severe head injury was identified in 15 (3.5%) of 426 patients. Papilledema was recognized immediately after head injury in 1 patient, during the 1st week in 10 patients, and in the 2nd week or after in 4 patients. Initial computed tomographic scans showed evidence of brain injury in 11 of these patients. The intracranial pressure (ICP) was monitored continuously for 3 or more days in 9 patients; it was mildly elevated (20 to 40 mm Hg) in 7 patients and moderately elevated (40 to 60 mm Hg) in 2 patients. Intracranial hypertension was controllable in each patient. A sudden, severe, but transient increase in ICP best explained the immediate development of papilledema and survival of 1 patient. Sustained but mild to moderately elevated ICP accounted for papilledema appearing in the 1st week. Papilledema in the 2nd week or after occurred from impaired cerebrospinal fluid absorption and consequent communicating hydrocephalus or delayed focal or diffuse cerebral swelling. A lesser degree of head injury in patients with posttraumatic papilledema was suggested by a higher Glasgow coma score, milder and controllable elevations in ICP, and the absence of any fatality in this group. The favorable outcome was significant compared to the mortality of the more severely injured patients (chi square-4.327; P less than 0.04). Papilledema did not occur in 6 patients with sustained, severely elevated ICP (greater than 60 mm Hg) for 3 or more days. Each of these patients died. The severity of the trauma apparently accounts for the failure of papilledema to develop, possibly by arresting axoplasmic production and transport in retinal nerve fibers.

Acute Disease↗

Clinical significance of transient visual phenomena in the elderly.

To evaluate the significance of transient visual phenomena in the elderly patient, a retrospective study of 43 patients over 40 years of age (mean, 58) presenting between 1971 and 1982 was conducted. Historical, clinical and diagnostic features were collated and analyzed by computer. The study revealed that 31 patients were diagnosed as migraine and 12 as vertebrobasilar insufficiency based on features identified in this review. Follow-up was obtained in 90% of the patients with a mean follow-up of 2.4 years. In general, prognosis proved to be excellent, with two deaths of cardiac origin and an 81% incidence of remission or symptomatic improvement of the visual events. No retinal or cerebral strokes were observed and TIAs occurred in only 9% of the population. This study suggests that transient visual phenomena in the elderly are benign.

Adult↗

Neuro-ophthalmology of sphenoid sinus carcinoma.

Three cases of sphenoid sinus carcinoma observed personally and 39 identified in the English language publications are reviewed. Sphenoid carcinoma constitutes only 0.3 per cent of sinus cancer. Its symptoms and signs are nonspecific until the sinus wall is penetrated. Once breached, specific neuro-ophthalmological symptoms and signs ensue, resulting from involvement of anatomically contiguous structures. These are characterized most commonly by the sphenocavernous syndrome and less frequently by isolated sixth nerve palsies and visual loss. Identified best by plain radiography, polytomography and computerized tomography, diagnosis of sphenoid carcinoma requires direct biopsy. Treatment, principally with radiotherapy supplemented by chemotherapy, has been disappointing with most patients dead by three years. The authors believe that in rapidly evolving neuro-ophthalmological syndromes of basal origin, accompanied by intractable headache, sphenoid sinus cancer must be considered.

Blepharoptosis↗

Parainfectious optic neuritis. Report and review following varicella.

Severe loss of vision and bilateral optic disc edema occurred in a 10-year-old girl 38 days after the rash of varicella first appeared and subsequent encephalitis developed. Recovery of visual function was nearly complete, but optic atrophy persisted. Parainfectious optic neuritis following other viral infections, with the exception of herpes zoster, has a similar clinical profile: delayed onset, severe visual loss, optic disc edema, bilaterality, good recovery, and residual optic atrophy. Conduction delays in our patient's patterned visual evoked potentials implicated demyelination within the optic nerves. The often favorable recovery, frequency of delayed onset, and bilateral involvement of the optic nerves support an autoimmune process in the pathogenesis of parainfectious optic neuritis.

Chickenpox↗

Psychosis associated with clonazepam therapy for blepharospasm.

A 73-year-old woman with no previous psychiatric history received clonazepam maintenance therapy for essential blepharospasm. Visual, auditory, and tactile hallucinations as well as paranoid delusions were documented. Dose reduction resulted in complete disappearance of the hallucinations and reduction of paranoia to an acceptable level, with no exacerbation during the subsequent 12 months. To our knowledge, this is the first well documented report of psychosis induced by clonazepam. Psychosis was probably related to clonazepam-induced increased central nervous system serotonin and possible predisposition to organic brain syndrome by undocumented causes. Dose reduction is suggested as an alternative to discontinuing the drug when hallucinations or paranoia arise during clonazepam therapy, if no other satisfactory treatment is available and if adequate patient monitoring and protection exist.

Aged↗

Micromethod for detection of oligoclonal IgG in unconcentrated CSF by polyacrylamide gel electrophoresis.

A micromethod to detect oligoclonal IgG from 50 microL of unconcentrated CSF was developed by using polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE). Of 17 patients with multiple sclerosis, oligoclonal bands were demonstrated in 16 instances (94%) by micro-SDS-PAGE and in 13 (76%) by agarose gel electrophoresis. The corresponding figures among 30 patients with optic neuritis were 16 (54%) and five (17%), respectively, and among ten patients with other neurological disease the figures were two (20%) and none, respectively. Thus, micro-SDS-PAGE is more sensitive than agarose gel electrophoresis for detection of oligoclonal IgG. The small volume of unconcentrated CSF that is required enhances the usefulness of this test.

Adolescent↗

Further experience in the management of severe head injury.

A prospective and consecutive series of 225 patients with severe head injuries who were managed in a uniform way was analyzed to relate outcome to several clinical variables. Good recovery or moderate disability were achieved by 56% of the patients, 10% remained severely disabled or vegetative, and 34% died. Factors important in predicting a poor outcome included the presence of intracranial hematoma, increasing age, abnormal motor responses, impaired or absent eye movements or pupil light reflexes, early hypotension, hypoxemia or hypercarbia, and elevation of intracranial pressure over 20 mm Hg despite artificial ventilation. Most of these predictive factors were assessed on admission, but a subset of 158 patients was identified in whom coma was present on admission and was known to have persisted at least until the following day. Although the mortality in this subset (40%) was higher than in the total series, it was lower than in several comparable reported series of patients with severe head injury. Predictive correlations were equally strong in the entire series and in the subset of 158 patients with coma. A plea is made for inclusion in the definition of "severe head injury" of all patients who do not obey commands or utter recognizable words on admission to the hospital after early resuscitation.

Adolescent↗