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Biomedical subjects

R B Lipton

Publications and source records attributed to R B Lipton.

At least 253 records · Page 14Linked to original sources

Giant cell arteritis causes recurrent posterior circulation transient ischemic attacks which respond to corticosteroid.

A 67-year-old man presented with recurrent clinically diverse posterior circulation transient ischemic attacks which continued despite full anticoagulation. Giant cell arteritis was suspected because of a markedly elevated erythrocyte sedimentation rate and confirmed by temporal artery biopsy. Treatment with corticosteroids resulted in a prompt and enduring resolution of clinical symptoms. Giant cell arteritis may represent a treatable cause of posterior circulation transient ischemic attacks, uniquely responsive to corticosteroids.

Aged↗

Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma.

Taxol, a plant product, has significant activity against certain rodent and human xenograft tumors. It promotes microtubule assembly in vitro, in contrast to vinca alkaloids, which inhibit assembly. In this phase I study, taxol was administered as a 24-hour continuous intravenous (IV) infusion in 65 courses to 26 patients. A premedication regimen of dexamethasone, cimetidine, and diphenhydramine was used to prevent the acute hypersensitivity reactions observed in previous studies of taxol. Only one episode of mild stridor occurred in this study. Peripheral neuropathy was the dose-limiting toxicity and was observed in 40% of patients treated at a dose of 250 mg/m2. Significant neutropenia of brief duration was also common. Pharmacokinetic studies by a high-performance liquid chromatography (HPLC) method demonstrated that drug plasma concentrations increased during the 24-hour infusion and then declined rapidly. Peak plasma concentrations correlated with dose, and less than 5% of taxol was excreted in the urine. Most of the drug was bound to serum components. Partial responses of more than 3 months' duration were observed in four of 12 melanoma patients treated. The recommended phase II dose of taxol on this schedule is 250 mg/m2. Priority should be given to the study of taxol in melanoma.

Alkaloids↗

Back pain in the cancer patient: an algorithm for evaluation and management.

Epidural spinal cord compression is common in patients with metastatic cancer. Back pain is usually the first symptom and may be present for months before neurologic abnormalities occur. A favorable outcome depends on early diagnosis and treatment. For the management of this problem, we propose an algorithm that begins with the treatment of patients who need emergency care and proceeds with an orderly approach to the evaluation of less urgent cases. The central elements include the criteria for myelography and the rational use of corticosteroids, radiation therapy, and surgery.

Algorithms↗

Progressive multifocal leukoencephalopathy: clinical and radiographic features.

Between April 1982 and March 1984 7 pathologically confirmed cases of progressive multifocal leukoencephalopathy (PML) were diagnosed at our institution. Only 1 case had been seen in the preceding twenty years. Four patients had acquired immunodeficiency syndrome (AIDS). The others had chronic lymphocytic leukemia, Hodgkin's lymphoma, and systemic lupus erythematosus. All patients presented with progressive neurological deficits. In most, the initial computed tomographic (CT) scan was disproportionately less abnormal than the clinical findings. In 5 patients the first CT scan revealed hypodensities of the cerebral white matter which lacked mass effect and did not enhance with contrast agent. The lesions were observed to enlarge progressively on CT scans but often lagged behind the rate of clinical evolution. Although 3 patients were treated with cytosine arabinoside, none improved. PML had similar clinical, radiographic, and pathological features in the AIDS and non-AIDs patients. Of 79 AIDS patients cared for at our institution between December 1979 and December 1983, 3.8% had PML. PML should be suspected in AIDS patients in the presence of the characteristic CT features, especially when CT-clinical dissociation occurs.

Acquired Immunodeficiency Syndrome↗

Gradual loss and recovery of vision in temporal arteritis.

Visual loss in temporal arteritis is usually sudden and irreversible. In this article, we describe a patient who complained of slowly progressive visual loss in one eye, eventually followed by loss of vision in the other eye and ophthalmoparesis. A biopsy specimen confirmed the diagnosis of temporal arteritis. Steroid therapy resulted in almost total recovery of vision. The gradual loss and recovery of vision is attributed to reversible ischemia of the optic nerve. This case broadens the spectrum of temporal arteritis to include complaints of progressive visual loss over several months.

Aged↗

Eye movement dysfunctions in psychiatric patients: a review.

Impairments of smooth pursuit eye movements occur in a high proportion of schizophrenic patients and in a lower but significant percentage of patients with affective psychoses, as well as patients with structural and metabolic disorders of the central nervous system. These findings have been confirmed using a wide range of tracking tasks, recording techniques, and scoring procedures, and therefore cannot be attributed to measurement artifact. The eye movement disruption in schizophrenics does not seem to result from drug treatment or simple inattention. Eye tracking pattern appears to be under genetic control and some impairments may reflect a predisposition to functional psychosis. The smooth pursuit eye movement impairment has been attributed to a central nervous system dysfunction that manifests itself in a disorder of nonvoluntary attention. The study of other oculomotor functions, such as the oculocephalic reflex, optokinetic and vestibular nystagmus, and saccadic eye movements, suggests that the locus of the central nervous system disruption is above the brainstem.

Adult↗

Saccadic eye movements in psychotic patients.

Schizophrenic and manic-depressive patients executed saccades to target displacements of 2 to 24 degrees. The latencies, velocities, and accuracy of their saccadic eye movements were normal, although patients' saccadic latencies increased more than controls' for stimulus displacements greater than 10 degrees. In contrast to their normal saccadic latencies, patients had significantly slower than normal mean finger-press latencies. The results have implications for the significance of motoric and attentional deficits in the major psychoses.

Adolescent↗

Pursuit eye movements in psychopathology: effects of target characteristics.

Tests of smooth pursuit eye movements using two types of targets, at three different frequencies, with two types of superimposed cognitive tasks were performed by 16 manic-depressive patients, 16 schizophrenic patients, and 14 normal subjects. The results showed that patients track more poorly than normals at all frequencies with either a real pendulum or an electronically driven target. Tracking efficiency of all subjects is improved by both superimposed cognitive tasks. Differences between patients and nonpatients exist under all experimental conditions.

Adult↗

Horizontal and vertical pursuit eye movements, the oculocephalic reflex, and the functional psychoses.

Sixteen schizophrenic patients, 16 manic-depressive patients, and 14 nonpatient control subjects were tested for horizontal and vertical smooth pursuit eye movements (SPEM) and the oculocephalic reflex. All patients with impaired horizontal pursuit also displayed disrupted vertical pursuit, suggesting that a common mechanism underlies these abnormalities. The oculocephalic reflex was intact in 96% of the subjects whether or not pursuit was disrupted, suggesting that the locus of the eye movement disorder in psychosis may be cortical. For horizontal pursuit, there were significant differences between schizophrenics and nonpatient controls, and between manic depressives and nonpatient controls, but not between schizophrenics and manic depressives, suggesting that the SPEM disruption occurs with significant prevalence in major functional psychoses and not only in schizophrenia.

Bipolar Disorder↗

Smooth pursuit eye movements, schizophrenia, and distraction.

This study tested whether smooth pursuit eye-movement dysfunctions, prevalent in a large population of schizophrenic patients, are distinguishable from impaired pursuit induced in normals by a distracting task. Results showed clear qualitative and quantitative distinctions between records of 23 distracted normals and those of 15 schizophrenics.

Attention↗

Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study.

BACKGROUND: Although most persons with migraine treat their headaches with over-the-counter medication, systematic data on the safety and efficacy of widely used treatment, including acetaminophen, are sparse. METHODS: This is a randomized, double-blind, placebo-controlled study comparing oral acetaminophen, 1000 mg (two 500-mg Extra Strength Tylenol tablets), with identical placebo in the treatment of a single acute migraine attack. Eligible subjects met International Headache Society diagnostic criteria for migraine with or without aura. Patients who usually required bed rest with their headaches or who vomited more than 20% of the time were excluded. MAIN OUTCOME MEASURES: The percentage of subjects who, at 2 hours after dosing, experienced a change in baseline pain intensity from severe or moderate pain to mild or no pain (headache response); and pain intensity difference from baseline at the 2-hour postmedication assessment. RESULTS: The headache response rate 2 hours after dosing was 57.8% in the acetaminophen group and 38.7% in the placebo group (P =.002). Pain-free rates at 2 hours were 22.4% in the acetaminophen group and 11.3% in the placebo group (P =.01). The mean pain intensity difference from baseline 2 hours after dosing was 1.08 in the acetaminophen group and 0.73 in the placebo group (P<.001). At 2 hours, other migraine headache characteristics, such as functional disability (P =.002), photophobia (P =.02), and phonophobia (P =.08), were significantly improved after treatment with acetaminophen vs placebo. CONCLUSIONS: Acetaminophen was highly effective for treating pain, functional disability, photophobia, and phonophobia in a population-based sample of persons with migraine, excluding the most disabled persons with migraine. The drug also had an excellent safety profile and was well tolerated. Arch Intern Med. 2000;160:3486-3492.

Acetaminophen↗

Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) Study: A randomized trial.

CONTEXT: Various guidelines recommend different strategies for selecting and sequencing acute treatments for migraine. In step care, treatment is escalated after first-line medications fail. In stratified care, initial treatment is based on measurement of the severity of illness or other factors. These strategies for migraine have not been rigorously evaluated. OBJECTIVE: To compare the clinical benefits of 3 strategies: stratified care, step care within attacks, and step care across attacks, among patients with migraine. DESIGN AND SETTING: Randomized, controlled, parallel-group clinical trial conducted by the Disability in Strategies Study group from December 1997 to March 1999 in 88 clinical centers in 13 countries. PATIENTS: A total of 835 adult migraine patients with a Migraine Disability Assessment Scale (MIDAS) grade of II, III, or IV were analyzed as the efficacy population; the safety analysis included 930 patients. INTERVENTIONS: Patients were randomly assigned to receive (1) stratified care (n = 279), in which patients with MIDAS grade II treated up to 6 attacks with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg, and patients with MIDAS grade III and IV treated up to 6 attacks with zolmitriptan, 2.5 mg; (2) step care across attacks (n = 271), in which initial treatment was with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg. Patients not responding in at least 2 of the first 3 attacks switched to zolmitriptan, 2.5 mg, to treat the remaining 3 attacks; and (3) step care within attacks (n = 285), in which initial treatment for all attacks was with aspirin, 800 to 1000 mg, plus metoclopramide, 20 mg. Patients not responding to treatment after 2 hours in each attack escalated treatment to zolmitriptan, 2.5 mg. MAIN OUTCOME MEASURES: Headache response, achieved if pain intensity was reduced from severe or moderate at baseline to mild or no pain at 2 hours; and disability time per treated attack at 4 hours for all 6 attacks, compared among the 3 groups. RESULTS: Headache response at 2 hours was significantly greater across 6 attacks in the stratified care treatment group (52.7%) than in either the step care across attacks group (40.6%; P<.001) or the step care within attacks group (36.4%; P<.001). Disability time (6 attacks) was significantly lower in the stratified care group (mean area under the curve [AUC], 185.0 mm. h) than in the step care across attacks group (mean AUC, 209.4 mm. h; P<.001) or the step care within attacks group (mean AUC, 199.7 mm. h; P<.001). The incidence of adverse events was higher in the stratified care group (321 events) vs both step care groups (159 events in across-attack group; 217 in within-attack group), although most events were of mild-to-moderate intensity. CONCLUSION: Our results indicate that as a treatment strategy, stratified care provides significantly better clinical outcomes than step care strategies within or across attacks as measured by headache response and disability time. JAMA. 2000;284:2599-2605.

Adult↗

A change point model for estimating the onset of cognitive decline in preclinical Alzheimer's disease.

Dementia is characterized by accelerated cognitive decline before and after diagnosis as compared to normal ageing. Determining the time at which that rate of decline begins to accelerate in persons who will develop dementia is important both in describing the natural history of the disease process and in identifying the optimal time window for which treatments might be useful. We model that time at which the rate of decline begins to accelerate in persons who develop dementia relative to those who do not by using a change point in a mixed linear model. A profile likelihood method is proposed to draw inferences about the change point. The method is applied to data from the Bronx Ageing Study, a cohort study of 488 initially non-demented community-dwelling elderly individuals who have been examined at approximately 12-month intervals over 15 years. Cognitive function was measured using the Buschke Selective Reminding test, a memory test with high reliability and known discriminative validity for detecting dementia. We found that the rate of cognitive decline as measured by this test in this cohort increases on average 5.1 years before the diagnosis of dementia.

Aged↗

Migraine: clinical features and diagnosis.

Migraine is a syndrome characterized by recurrent headaches with or without aura. Triggers include foods, hormonal changes, and stressors. Migraine must be differentiated from other unilateral headache disorders and from headaches due to other neurologic and systemic diseases.

Diagnosis, Differential↗

Memory and mental status correlates of modified Braak staging.

We assessed the relationships of performance on memory and mental status tests and neuropathologic stage of Alzheimer's disease as defined by Braak and Braak in 29 patients from a prospective clinicopathologic series. We predicted that memory changes would occur at an earlier Braak stage than mental status changes. Staging was accomplished by matching the topographic distribution of neurofibrillary lesions detected with tau immunocytochemistry to the best fitting diagram published by Braak and Braak. Higher Braak stages were associated with decrements in performance on both memory and mental status tests. As predicted, memory performance declined from stages II to III and mental status did not decline until stages III to IV. The association between memory and Braak stage was unchanged after adjusting for neocortical senile plaques, whereas adjustments for Braak stage eliminated the association between cognitive functioning and amyloid burden. We conclude that Braak staging provides a useful summary of Alzheimer's disease neuropathology, which is associated with both memory and mental status performance.

Aged↗