PubMed Health⌕ Search

Biomedical subjects

J Marler

Publications and source records attributed to J Marler.

16 recordsLinked to original sources
PubMed2001

Advances in the genetics of cerebrovascular disease and stroke.

MEDLINE searches identified epidemiologic, experimental, and clinical studies on the genetics of cerebrovascular disease and stroke, including the following topics: genetic epidemiology of stroke; genetics of systemic disorders that cause ischemic stroke, including coagulation disorders, connective tissue disorders, vasculopathies, metabolic disorders, and disorders of unknown etiology; and genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries in stroke genetics involve the genetic basis of monogenic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and sickle cell disease. Reproducing similar advances in other forms of cerebrovascular disease and stroke will be more difficult because their inheritance is complex, multigenic, and heterogeneous. However, the future is promising with the application of molecular genetic approaches such as linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses as well as the transmission/disequilibrium test--a statistical method for detection of linkage between a marker and a disease-susceptibility locus.

Cerebral Hemorrhage↗
PubMed2000

Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States: findings of the national conference on cardiovascular disease prevention.

A workshop was held September 27 through 29, 1999, to address issues relating to national trends in mortality and morbidity from cardiovascular diseases; the apparent slowing of declines in mortality from cardiovascular diseases; levels and trends in risk factors for cardiovascular diseases; disparities in cardiovascular diseases by race/ethnicity, socioeconomic status, and geography; trends in cardiovascular disease preventive and treatment services; and strategies for efforts to reduce cardiovascular diseases overall and to reduce disparities among subpopulations. The conference concluded that coronary heart disease mortality is still declining in the United States as a whole, although perhaps at a slower rate than in the 1980s; that stroke mortality rates have declined little, if at all, since 1990; and that there are striking differences in cardiovascular death rates by race/ethnicity, socioeconomic status, and geography. Trends in risk factors are consistent with a slowing of the decline in mortality; there has been little recent progress in risk factors such as smoking, physical inactivity, and hypertension control. There are increasing levels of obesity and type 2 diabetes, with major differences among subpopulations. There is considerable activity in population-wide prevention, primary prevention for higher risk people, and secondary prevention, but wide disparities exist among groups on the basis of socioeconomic status and geography, pointing to major gaps in efforts to use available, proven approaches to control cardiovascular diseases. Recommendations for strategies to attain the year 2010 health objectives were made.

Cardiovascular Diseases↗
PubMed2000

Osteochondral reconstruction of a non-weight-bearing joint using a high-density porous polyethylene implant.

Currently, there is no reliable reconstructive modality allowing anatomic resurfacing of traumatic digital osteochondral articular defects. The purpose of the present study is to demonstrate the utility of Medpor, a high-density porous polyethylene (HDPP) scaffold biomaterial that can (1) be readily contoured to fit any joint defect, (2) permit stable internal fixation, and (3) permit osteocyte and chondrocyte ingrowth and subsequent articular cartilage resurfacing necessary to restore joint congruity. HDPP has gained wide acceptance for use in craniofacial and skeletal reconstruction and augmentation. An avian non-weight-bearing joint model was designed to study the role of the HDPP implant in small joint reconstruction. An osteochondral defect was created with a 5-mm circular punch in the humeral articular surface of both glenohumeral joints of 32 adult White Leghorn chickens. In each animal, one defect was press-fitted with a correspondingly sized HDPP implant (HDPP implant group); the contralateral defect was filled with the original osteochondral plug (isograft group) or left unrepaired (control group). At 2 weeks, and 1, 3, and 6 months,joints from each group were harvested and evaluated. Over the 6-month study period, joints in the control group demonstrated healing with dense collagenous scar tissue leaving residual defects at the articular surfaces and significant degenerative disease of the glenohumeral joints radiographically. Joints in the isograft group demonstrated near-complete resorption with some preservation of the cartilaginous cap but overall depression of the articular surface and significant degenerative joint disease. Joints in the HDPP implant group demonstrated stable fixation by highly mineralized bony trabecular ingrowth, preservation of the articular contour of the humeral head, and no evidence of significant degenerative joint disease. These findings indicate a potential role for this high-density porous polyethylene implant in the reconstruction of small joint articular and osseous defects.

Animals↗
PubMed1999

Skeletal muscle tissue engineering using isolated myoblasts on synthetic biodegradable polymers: preliminary studies.

Skeletal muscle is responsible for the control of voluntary movement and the maintenance of structural contours of the body. Muscle loss or deficiency is encountered in various pathological states, and attempts to correct them have been employed with limited success. The aim of the present study was to tissue engineer three-dimensional vascularized skeletal muscle using isolated myoblasts attached to synthetic biodegradable polymer for tissue replacement in the enhancement of muscle regeneration. Myoblasts derived from neonatal rats (3-5-day-old), Fisher CDF-F344, were seeded onto polyglycolic acid meshes and implanted into the omentum of syngeneic adult Fisher CDF-F344 rats. Rats were sacrificed on day 30 and day 45 after the transplantation, and the cell-polymer constructs were harvested for morphological analysis. Histological analysis of the constructs were performed by hematoxylin and eosin, and immunohistochemical staining was positive for alpha sarcomeric actin and desmin skeletal muscle marker. Viable myoblasts organized between strands of degrading polymer mesh formed the new tissue, and vascularization of the entire construct was observed. Organization of neomuscle strands surrounded by vascularized tissue composed of degrading polymer and fusing myoblasts demonstrated the ability of myoblast constructs to survive, reorganize and regenerate tissue-like structures. Since myoblast transplantation to date has been limited to the cellular level of replacement, myoblast-polyglycolic acid constructs may be useful in defining the application of tissue engineering for future skeletal muscle transplantations.

Actins↗
PubMed1999

Underlying structure of the National Institutes of Health Stroke Scale: results of a factor analysis. NINDS tPA Stroke Trial Investigators.

BACKGROUND AND PURPOSE: No stroke scale has been validated as an outcome measure using data from a clinical trial demonstrating a positive therapeutic effect. Therefore, we proposed to use data from the National Institute of Neurological Disorders and Stroke (NINDS) tPA Stroke Trial to determine whether the National Institutes of Health Stroke Scale (NIHSS) was valid in patients treated with tissue plasminogen activator (tPA) and to explore the underlying clinimetric structure of the NIHSS. METHODS: We performed an exploratory factor analysis of NIHSS data from Part 1 (n=291) of the NINDS tPA Stroke Trial to derive a hypothesized underlying factor structure. We then performed a confirmatory factor analysis of this structure using NIHSS data from Part 2 of the same trial (n=333). We then tested whether this final factor structure could be found in tPA- and placebo-treated patients serially over time after stroke treatment. Using 3-month outcome data, we tested for an association between the NIHSS and other measures of stroke outcome. RESULTS: The exploratory analysis suggested that there were 2 factors underlying the NIHSS, representing left and right brain function, confirming the content validity of the scale. An alternative structure composed of 4 factors could be derived, with a better goodness of fit: the first 2 factors could represent left brain cortical and motor function, respectively, and the second 2 factors could represent right brain cortical and motor function, respectively. The same factor structures were then found in tPA and placebo patient groups studied serially over time, confirming the exploratory analysis. All 3-month clinical outcomes were associated with each other at subsequent time points, confirming predictive validity. CONCLUSIONS: This is the first study of the validity of a stroke scale in patients treated with effective stroke therapy. The NIHSS appeared to be valid in patients with acute stroke and for finding treatment-related differences. The scale was valid when used serially over time after stroke, up to 3 months, and showed good agreement with other measures of outcome.

Brain↗
PubMed1998

Transplantation of cells in matrices for tissue regeneration.

Tissue engineering is a field that has truly emerged in the last decade. It has brought together diverse technologies, e.g. cell culture, polymer chemistry and transplantation. The creation of matrices to guide tissue regeneration allows manipulation at several levels, i.e. the cells employed, the choice of polymer and the design of construct assembly methods. We present experience using such constructs to guide regeneration of diverse tissues, e.g. liver, intestine, urologic tissue, skin, cartilage, bone and cardiovascular structures. Emerging concepts in using cell/polymer constructs include the need for appropriate modeling of the micromechanical environments of different tissues, as well as the necessity of finding new strategies to achieve vascularization of tissues for transplant. Finally, the concept of applying tissue-engineered structures to non-native sites is discussed.

Journal Article↗
PubMed1998

Comparison of RapID yeast plus system with API 20C system for identification of common, new, and emerging yeast pathogens.

The ability to identify yeast isolates by the new enzymatic RapID Yeast Plus System was compared to the ability to identify yeast isolates by the API 20C system. A total of 447 yeast isolates representing Blastoschizomyces capitatus, 17 Candida spp., 5 Cryptococcus spp., Geotrichum spp., 2 Hanseniaspora spp., Hansenula anomala, Hansenula wingei, 3 Rhodotorula spp., Saccharomyces cerevisiae, Sporobolomyces salmonicolor, Trichosporon beigelii, and 2 Prototheca spp. were evaluated. Also, five quality control strains (Candida spp. and Cryptococcus laurentii) with well-documented reactivities by the RapID Yeast Plus System were used. Each isolate was evaluated by both methods with a 48-h culture grown at 30 degrees C on Sabouraud dextrose agar (Emmons modification) by following the recommendations of the manufacturers. The RapID Yeast Plus System enzymatic reactions were read after 4 h of incubation, and the API 20C carbohydrate assimilation identification profiles were obtained after 72 h of incubation. There was good (95.7%) agreement between the identifications obtained by the two methods with the eight common Candida spp. and with Cryptococcus neoformans. The agreement was lower when the emerging Candida spp. and other yeast-like pathogens were tested (79.1 and 75.2%, respectively). These preliminary data suggest the potential utility of the RapID Yeast Plus System for use in the clinical laboratory for the rapid identification of common yeast pathogens as well as certain new and emerging species.

Yeasts↗
PubMed1997

TPA in acute stroke.

Explore the source record for details and available documents.

Cerebrovascular Disorders↗
PubMed1996

Use of a global test for multiple outcomes in stroke trials with application to the National Institute of Neurological Disorders and Stroke t-PA Stroke Trial.

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) held a workshop on statistical approaches to analysis of acute stroke trials that have multiple pre-specified outcomes. An objective was to plan for statistical analysis of the NINDS t-PA Stroke Trial, a randomized, double-blind, placebo-controlled trial of recombinant tissue plasminogen activator (rt-PA) for patients with acute ischemic stroke. Treatment success was defined as a "consistent and persuasive difference" in the proportion of patients achieving favorable outcomes on the Barthel Index, Modified Rankin Scale, Glasgow Outcome Scale, and National Institutes of Health Stroke Scale. The Data and Safety Monitoring Committee for the trial recommended this outcome because the committee did not believe that a positive result for a single outcome would provide sufficient evidence of efficacy. SUMMARY OF COMMENT: Workshop participants accepted the global test as a viable approach to testing the primary trial hypothesis. Clinician participants advocated categorizing outcomes as favorable/unfavorable, outcomes more clinically meaningful than continuous outcomes for evaluating a drug with potentially serious side effects. They agreed that a global test was appropriate for ischemic stroke when no single outcome is accepted. Hypothetical, special-case examples illustrate that highly correlated outcomes diminish the power of the global test. NINDS t-PA Stroke Trial data demonstrate the clinical interpretability of the global test. CONCLUSIONS: Workshop participants concluded that a global statistic should be used to test the trial's primary hypothesis accompanied by secondary tests of individual outcomes. Workshop participants recommended familiarizing the clinical/scientific community with the global approach.

Acute Disease↗
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

Blood pressure during the first minutes of focal cerebral ischemia.

STUDY OBJECTIVE: To determine whether blood pressure declines spontaneously during the first minutes and hours of focal cerebral ischemia. DESIGN: Multiple blood pressure measurements as part of an urgent stroke therapy trial (treatment within 90 minutes of stroke onset). SETTING: Thirteen hospitals in three metropolitan communities. PARTICIPANTS: Sixty-nine patients (mean age, 65 +/- 9 years) with acute ischemic stroke who were participants in a phase I urgent stroke therapy trial of recombinant tissue plasminogen activator. MAIN OUTCOME MEASURE: Blood pressures recorded at the scene of stroke by life-squad personnel, in the emergency department, and in the ICU. RESULTS: The mean time from stroke onset to the time of first blood pressure measurement was 19 +/- 13 minutes. Twenty-four of the 69 patients in the urgent stroke therapy trial had an initial systolic blood pressure of at least 160 mm Hg. Of these, 23 had a significant decline in systolic and diastolic blood pressure during the first 90 minutes after the onset of stroke (mean change in systolic pressure, -29 +/- 22 mm Hg, P < .001; mean change in diastolic pressure, -10 +/- 14 mm Hg, P < .01). No patients received antihypertensive therapy during the time in which the decline in blood pressure was noted. CONCLUSION: Mildly or moderately elevated blood pressure frequently declines spontaneously during the first minutes and hours of focal cerebral ischemia and generally does not require urgent pharmacologic treatment.

Acute Disease↗
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↗
PubMed1990

Pilot study of nicardipine for acute ischemic stroke.

The author performed a pilot study of nicardipine (NC), a Ca(+)+ channel blocker, to study its dosing, toxicity, and possible efficacy for hemispheric cerebral infarction within 12 hours (mean 6.9 hr) of onset to determine the advisability of proceeding with a multi-centered controlled trial. NC was administered IV (3 to 7 mg/hr) X 72 hours by titrating dose to mean arterial blood pressure (MABP not less than 10% of baseline), then orally X 30 days. Forty-three patients have been entered; mean age 63 (range 34-89), 25 male and 18 female. Only 3 had CT evidence of infarct on entry. Results have shown improvement in a 100-point (pt) graded exam (40 pts at entry, 68 pts at 3 months). Of 20 patients completing 3 months' evaluation, 17 improved and none worsened. Sixteen out of 20 were at home and 8 had minimal or no impairment. Mean Barthel's index was 72. Mean maximal serum NC level was 75 ng/mL. MABP decreased from 103 (entry) to 83 (72 hours). A larger controlled study is warranted to determine the efficacy of NC for acute cerebral infarct.

Acute Disease↗
PubMed1989

Use of high dose naloxone in acute stroke: possible side-effects.

The effects of high dose naloxone in humans have not been studied extensively. We treated 36 patients who had acute ischemic cerebral infarction with high doses of naloxone to evaluate potential efficacy and toxicity. All patients were treated with a 160-mg/m2 (4-mg/kg) loading dose followed by 80 mg/m2.h (2 mg/kg.h) x 24 h. There were no statistically significant changes in group mean arterial pressure, respiratory rate, or heart rate in response to the loading dose or infusion, although clinically significant changes did occur in four patients. Twenty-three patients had adverse reactions possibly related to naloxone, the most common of which were nausea (n = 20), bradycardia and/or hypotension (n = 3), myoclonus (n = 1), and hypertension (n = 1). Seven patients had naloxone discontinued for possible adverse reactions. All adverse reactions abated with discontinuation of naloxone and/or pharmacologic therapy when indicated. No deaths were attributable to naloxone treatment. High dose naloxone appears to be well tolerated in the majority of elderly patients with acute cerebral infarction.

Adult↗
PubMed1983

P1 deficiency in shiverer myelin is expressed by Schwann cells in shiverer dystrophic normal mouse chimaera nerves.

The myelin basic protein (P1) deficiency in shiverer myelin is expressed in shiverer reversible normal mouse chimaera nerves. Chimaera examined with immunocytochemical techniques have revealed populations of both densely labeled and unreacting myelinated Schwann cells. Single axons can innervate both Schwann cell types, demonstrating that the expression of P1 in Schwann cell myelin is unrelated to the shiverer or normal genotype of the neuron. The coexistence of both Schwann cell types in single nerves indicates that multiple progenitor Schwann cells are allocated to developing nerves and the mosaic patterns expressed further suggest that such cells tend to proliferate relatively small coherent clones of Schwann cells.

Animals↗