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Biomedical subjects

L Caplan

Publications and source records attributed to L Caplan.

At least 19 recordsLinked to original sources

Antiplatelets, ACE inhibitors, and statins combination reduces stroke severity and tissue at risk.

BACKGROUND: Antiplatelets (APL), angiotensin-converting enzyme (ACE) inhibitors (ACEI), and statins (STAT) are commonly used for stroke prevention. The authors examined whether combination therapy with these agents has additive protective effects in reducing ischemic stroke severity. METHODS: The authors retrospectively analyzed data from 210 consecutive patients presenting within 24 hours of stroke onset. Baseline NIH Stroke Scale (NIHSS) score and diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and PWI-DWI mismatch lesion volumes as clinical and radiologic measures of stroke severity were measured among patients who were not taking APL, ACEI, or STAT before stroke onset vs those who were taking APL alone or in combination with either ACEI, STAT, or both. RESULTS: Sixty-nine patients were not on APL, ACEI, or STAT at stroke onset; 47 were on APL alone, 43 on dual (14 APL + STAT, 29 APL + ACEI), and 20 on triple combination therapy. Patients on triple therapy had lower NIHSS score (p = 0.001) and smaller mean PWI-DWI mismatch lesion volumes (p = 0.03) than those on two agents, APL alone, or no prestroke therapy. Higher percentages of patients on triple therapy had shorter length of hospitalization and better functional status upon discharge. Age, risk factor profile, blood pressure, glucose levels, onset to evaluation time, stroke subtypes, and DWI lesion volumes were comparable among all groups. CONCLUSIONS: Prestroke use of available drugs for stroke prevention, in combination, may result in additive reduction in stroke severity, as measured by NIH Stroke Scale, and the volume of ischemic tissue at risk, as assessed by perfusion-weighted imaging-diffusion-weighted imaging mismatch. These findings require further validation in larger-scale, randomized, prospective studies.

Aged↗

Impaired washout--embolism and ischemic stroke: further examples and proof of concept.

We previously posited that impaired washout of emboli was an important mechanism of brain infarction in patients with cerebral hypoperfusion. Hyperviscosity and hypoperfusion enhance thrombus formation promoting embolization of fresh thrombi. Hypoperfusion also reduces dissolution of emboli due to reduced flow velocity leading to classic hemodynamic patterns of stroke. To prove this concept further, we identified patients with severe hemodynamic compromise of either arterial or venous origin, or both, and natural or iatrogenic mechanisms of embolism. Three conditions were investigated in a stroke MRI protocol: 5 patients who had conventional cerebral angiography for the diagnosis of moyamoya disease, 1 patient with atrial fibrillation and thrombosis of the left transverse dural sinus and 1 patient with a patent foramen ovale with atrial septum aneurysm presenting with thrombosis of cortical cerebral veins. In all patients, subcortical arterial embolization within an atypical borderzone of hypoperfusion was observed.

Adult↗

An examination of daily activities and their scripts across the adult lifespan.

In two normative studies, we examined daily scripted activities from the perspective that scripts are frequency-based knowledge structures. In Study 1 individuals recorded their daily activities for 7 consecutive days. Fifteen activities that were reported with low, moderate, and high frequency were selected for Study 2, in which individuals generated a script for each activity. The 18 most frequently generated events from each script are reported, along with their centrality and distinctiveness rankings and the number of individuals reporting each event. Overall, the mean number of events generated increased with increasing script frequency, suggesting that script representations are subject to frequency effects. Also, we found a high level of consistency across the three age groups in the events generated in each script and in their corresponding rankings of centrality and distinctiveness. Finally, we found no evidence of age or gender bias in the frequency or recency of engaging in each of the scripted activities.

Activities of Daily Living↗

Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease.

BACKGROUND: Fabry's disease, lysosomal alpha-galactosidase A deficiency, results from the progressive accumulation of globotriaosylceramide and related glycosphingolipids. Affected patients have microvascular disease of the kidneys, heart, and brain. METHODS: We evaluated the safety and effectiveness of recombinant alpha-galactosidase A in a multicenter, randomized, placebo-controlled, double-blind study of 58 patients who were treated every 2 weeks for 20 weeks. Thereafter, all patients received recombinant alpha-galactosidase A in an open-label extension study. The primary efficacy end point was the percentage of patients in whom renal microvascular endothelial deposits of globotriaosylceramide were cleared (reduced to normal or near-normal levels). We also evaluated the histologic clearance of microvascular endothelial deposits of globotriaosylceramide in the endomyocardium and skin, as well as changes in the level of pain and the quality of life. RESULTS: In the double-blind study, 20 of the 29 patients in the recombinant alpha-galactosidase A group (69 percent) had no microvascular endothelial deposits of globotriaosylceramide after 20 weeks, as compared with none of the 29 patients in the placebo group (P<0.001). Patients in the recombinant alpha-galactosidase A group also had decreased microvascular endothelial deposits of globotriaosylceramide in the skin (P<0.001) and heart (P<0.001). Plasma levels of globotriaosylceramide were directly correlated with clearance of the microvascular deposits. After six months of open-label therapy, all patients in the former placebo group and 98 percent of patients in the former recombinant alpha-galactosidase A group who had biopsies had clearance of microvascular endothelial deposits of globotriaosylceramide. The incidence of most treatment-related adverse events was similar in the two groups, with the exception of mild-to-moderate infusion reactions (i.e., rigors and fever), which were more common in the recombinant alpha-galactosidase A group. IgG seroconversion occurred in 88 percent of patients who received recombinant alpha-galactosidase A. CONCLUSIONS: Recombinant alpha-galactosidase A replacement therapy cleared microvascular endothelial deposits of globotriaosylceramide from the kidneys, heart, and skin in patients with Fabry's disease, reversing the pathogenesis of the chief clinical manifestations of this disease.

Adolescent↗

Relationship between magnetic resonance arterial patency and perfusion-diffusion mismatch in acute ischemic stroke and its potential clinical use.

BACKGROUND: In patients with acute ischemic stroke the magnetic resonance (MR) perfusion-diffusion mismatch pattern (perfusion lesion at least 20% larger than the lesion on diffusion-weighted imaging) may indicate ischemically threatened but viable tissue. To our knowledge, the relationship of this MR pattern to serial changes in MR angiography (MRA) has not been reported. OBJECTIVES: To investigate the relationship between MRA changes and patterns of diffusion-weighted imaging and perfusion abnormalities and to determine if the information obtained could be used in clinical management. METHODS: The MR studies of 35 patients who had undergone sequential multimodality MR imaging studies within the first 4 days of stroke were reviewed. All lesions were in the internal carotid artery territory distribution. Magnetic resonance angiographies were read by 2 observers blinded to the clinical data. RESULTS: During the first 24 hours a perfusion-diffusion mismatch was present in 22 (92%) of the 24 patients with an MRA arterial occlusive lesion. (At this time 5 [46%] of the 11 patients with a normal MRA [P =.006] also had a mismatch.) Two to 4 days after stroke, of these 22 patients resolution of the mismatch occurred in 8 (87%) of 9 patients with recanalization on MRA compared with 5 (39%) of 13 patients without arterial recanalization (P =.03). Resolution of mismatch occurred in 3 (60%) of 5 patients with a normal MRA and a mismatch at the first time point. CONCLUSIONS: Concordance between MRA and the MR perfusion-diffusion mismatch pattern provides supportive evidence for an arterial vascular basis for this MR signature in acute stroke. Discordance between MRA lesions and mismatch may result from arterial branch occlusions undetected by MRA or from an alternate mechanism for the mismatch. The MR imaging patterns identified extend our understanding of the pathophysiology of stroke and may contribute to the improvement of stroke management in the future.

Acute Disease↗

Local critical power is an index of local endurance.

The hypothesis that critical power (CP) is significantly lower than the maximal aerobic power of the knee extensors has been tested in nine endurance-trained subjects, seven gymnasts and seven weight lifters. CP was calculated as being equal to the slope of the linear relationship between exhaustion time and work performed at exhaustion on a knee-extension ergometer. CP was compared with the power output at the end of a progressive knee-extension exercise (P(peak)) and the power outputs corresponding to exhaustion times equal to 4 (P(4 min)), 6 (P(6 min)), 8 (P(8 min)) and 10 min (P(10 min)), calculated according to the linear relationship between work and exhaustion time. The hypothesis that CP corresponds to a steady state in metabolic and physiological parameters was tested in the gymnasts and the weight lifters by comparing CP with the fatigue thresholds of the integrated electromyogram (iEMG(FT)), lactate level (La(FT)), oxygen uptake (VO(2FT)) and heart rate (HR(FT)). The results of the present study demonstrate that the value of CP of a local exercise cannot be considered as the equivalent of the maximal aerobic power for general exercises. The values of P(4 min), P(6 min), P(8 min), P(10 min) and P(peak) were significantly higher than CP, and corresponded to 138, 126, 119, 115 and 151% CP, respectively. The results of the present study indicate that CP can be considered as an index of muscular endurance. Indeed, La(FT), iEMG (FT), VO(2FT) and HR(FT) were not significantly different from CP. All of these fatigue thresholds were significantly correlated with CP (r > 0.92). Moreover, the highest coefficient of correlation (r=0.71; P < 0.01) between the percentage of maximal aerobic power in cycling that corresponds to a blood lactate concentration of 4 mmol x l(-1) (OBLA%) and the different local aerobic indices was observed with CP.

Adult↗

Surgical reconstruction of the extracranial vertebral artery: management and outcome.

PURPOSE: The purpose of this study was to identify the risk and outcome of reconstruction of the extracranial vertebral artery (ECVA). METHOD: The study was conducted as a retrospective review of 369 consecutive ECVA reconstructions. RESULTS: The clinical presentations consisted of hemispheric symptoms alone in 4% of the cases, hemispheric and vertebrobasilar symptoms in 30%, and vertebrobasilar symptoms alone in 60%. The cause of the lesion was atherosclerosis (n = 300), extrinsic compression (n = 42), dissection (n = 7), radiation arteritis (n = 5), intimal hyperplasia (n = 3), fibromuscular dysplasia (n = 2), previous surgical ligation (n = 3), aneurysm (n = 2), and other (n = 5). All the patients underwent preoperative arteriography. There were 252 proximal ECVA reconstructions (218 transpositions, 42 bypass grafting procedures, and two other) and 117 distal ECVA reconstructions (85 bypass grafting procedures, 25 transpositions, and seven other). In 83 patients, the ECVA operation was performed concomitant with a carotid or supraaortic trunk reconstruction. This series was analyzed in two separate sets: before 1991 (n = 215), when changes in indications and management were occurring; and after 1991 (n = 154), when we acquired a dedicated anesthesia team and digital arteriography in the operating room and established uniform protocols for the management of ECVA disease. The stroke, death, and stroke/death rates for the period before 1991 were, respectively, 4. 1%, 3.2% and 5.1%. The stroke, death, and stroke/death rates for the period after 1991 were, respectively, 1.9%, 0.6% and 1.9%. The patency rate at 5 years was 80%. The survival rate at 5 years was 70%. Most of the deaths during the follow-up period were caused by cardiac disease. Among the survivors, the protection rate from stroke was 97%. CONCLUSION: The changes in operative selection and management have improved the results of ECVA reconstruction. The data reported for ECVA reconstruction in patients who underwent operation since 1991 reflect the outcome of ECVA reconstruction today. In our experience, a reconstruction of the ECVA is less risky than a carotid reconstruction.

Angiography↗

Factors that may discourage annual mammography among low-income women with access to free mammograms: a study using multi-ethnic, multiracial focus groups.

Age-eligible women enrolled in the National Breast and Cervical Cancer Early Detection Program can obtain free or low-cost mammograms annually, but many do not routinely complete rescreening. This study investigated the rescreening behavior of low-income women by conducting 8 focus groups in Texas with enrollees who had access to free mammograms. Concerns mentioned in the focus groups included fear of radiation, anxiety that the test might not find a cancer that was there, and worries that cancer might be detected. In all groups, some women mentioned the embarrassment, discomfort, or pain they experienced during a prior mammogram, although no one indicated they would refuse to have another mammogram because of these concerns. Findings highlight the useful insights that can be obtained from focus groups and underscore the need for more research on aspects of the experience of mammography that may affect rescreening.

Adult↗

Thrombolysis in acute ischemic stroke: controlled trials and clinical experience.

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) is approved in the United States for treatment of acute ischemic stroke. Approval was granted after a large, randomized, placebo-controlled study by the National Institute of Neurological Disorders and Stroke (NINDS) showed a significant improvement in 3-month outcomes with rtPA despite a significant risk for symptomatic hemorrhage. Two other trials, the first and second European Cooperative Acute Stroke Study (ECASS I and II), have shown comparable results, but neither was statistically positive for the predefined primary end point. An analysis of the risk/benefit profile of rtPA therapy based on the results of these three trials indicates that the treatment is effective and, when administered within 3 hours of symptom onset at a dose of 0.9 mg/kg, the benefits by far outweigh the risks for eligible patients. Even with the 6-hour time window of the two ECASS trials, a combined analysis of the three studies shows the number of disabled or dead patients to be significantly reduced. Preliminary data collected on the use of rtPA outside of clinical trials in the United States and Europe suggest that, when rtPA is used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United States, rtPA is underutilized. The most substantial treatment barrier is the narrow time window, which may be expanded if long-term experience shows that this is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicians may help to overcome this difficulty.

Acute Disease↗

Self-reported infectious mononucleosis and 6 cancers: a population-based, case-control study.

A study was undertaken to estimate the magnitude of association between self-reported infectious mononucleosis (IM) and 6 types of cancer, including Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal cancer, nasal cancer, primary liver cancer, and sarcoma. Cases were male, aged 15-39 y in 1968, who lived in 8 cancer registry areas. Controls were men selected by random-digit telephone dialing. Cases included 1511 persons with non-Hodgkin's lymphoma, 343 with Hodgkin's disease, 386 with sarcoma and 168, 113 and 70 with primary liver, nasopharyngeal and nasal cancers, respectively. There were 1910 controls. For the 6 cancers combined, the overall odds ratio for IM occurring < 5 and > or = 5 y of the reference date were 5.40 [95% (Confidence Interval (CI) = 1.61, 18.09] and 1.08 (0.84, 1.40), respectively. Analogous values were 4.59 (1.25, 16.85) and 1.07 (0.78, 1.48) for non-Hodgkin's lymphoma and 7.49 (1.52, 36.92) and 1.35 (0.87, 2.09) for Hodgkin's disease. There was the suggestion of a protective association with IM occurring > or = 5 y before cancer onset for the 4 non-lymphomatous cancers. Strongly positive associations between self-reported IM and 6 types of cancer were observed for IM occurring < 5 y before the onset of cancer. There was a suggestion, which is noted with extreme caution, that IM earlier in life might have had a protective association with the 4 non-lymphomatous cancers.

Adolescent↗

Breast cancer risk and alcohol consumption: results from a large case-control study.

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.

Adult↗