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Biomedical subjects

J Broderick

Publications and source records attributed to J Broderick.

At least 37 records · Page 2Linked to original sources

Reactive effects of diary self-assessment in chronic pain patients.

Several studies of experimental and acute clinical pain have indicated reactive effects of self-assessment on pain intensity and tolerance. A recent study of chronic pain patients (vonBaeyer 1994), however, failed to show these effects. The present investigation sought to determine whether reactive effects can be produced in chronic pain patients by an intensive self-assessment protocol. Using the methodology of ecological momentary assessment (EMA; Stone and Shiffman 1994), thirty-five chronic rheumatoid arthritis patients completed diaries of pain and mood seven times a day for 1 wk. Eighteen patients were included in the final sample because they responded to at least half of the number of hourly prompts for each of the 7 days. Using repeated measures analysis of the daily means, no significant effects of time were found for any measures. Reactive effects that result in an average change in pain levels over time, therefore, do not appear to be produced by intensive self-assessment in a naturalistic context. Results are discussed in terms of cognitive and behavioral theories of pain reactivity.

Adult↗

Thrombolytic therapy for cerebral infarction.

Until recently, no clinically effective therapy for acute ischemic stroke has been available. Recent advances in the use of thrombolytic therapy for ischemic stroke appear promising in clinical care. As the use of thrombolytic therapy in acute stroke progress, emergency physicians (EPs) will become increasingly involved in its implementation. The EP must be cognizant of both prior and ongoing investigations in acute ischemic stroke therapy. To that end, this article reviews research in the field of thrombolytic therapy for acute ischemic stroke.

Acute Disease↗

Prognostic value of the hyperdense middle cerebral artery sign and stroke scale score before ultraearly thrombolytic therapy.

PURPOSE: To determine the relationship between the hyperdense middle cerebral artery sign (HMCAS) and neurologic deficit, as evidenced by the National Institutes of Health (NIH) stroke scale score, and to determine the relationship of the HMCAS and the NIH stroke scale score to arteriographic findings after thrombolytic therapy. METHODS: Fifty-five patients with acute ischemic stroke were rated on the NIH stroke scale, were examined with CT, and were treated with intravenous alteplase within 90 minutes of symptom onset. Presence of the HMCAS was determined on the baseline CT scan by a neuroradiologist blinded to the patient's neurologic deficit. Patients with the HMCAS were compared with those without HMCAS with regard to baseline NIH stroke scale score, 2-hour NIH stroke scale score, findings at posttreatment arteriography, 3-month residual neurologic deficit, and 3-month ischemia volumes as evidenced on CT scans. RESULTS: Eighteen patients (33%) had the HMCAS. These patients had a median baseline NIH stroke scale score of 19.5 compared with a median score of 10 for the patients lacking the HMCAS sign. At 3 months, one (6%) of the HMCAS-positive patients was completely improved neurologically compared with 17 (47%) of the HMCAS-negative patients. Restricting analysis to those patients with a stroke scale score of 10 or greater (n = 37), 18 HMCAS-positive patients showed less early neurologic improvement, were less likely to be completely improved at 3 months, and had larger infarcts compared with the 19 HMCAS-negative patients. Compared with the HMCAS-positive and HMCAS-negative patients with a stroke scale score of 10 or greater, patients with a stroke scale score of less than 10 had fewer occlusive changes of the internal carotid and middle cerebral arteries on posttreatment arteriograms and had a better neurologic recovery at 3 months. CONCLUSION: The presence of the HMCAS on CT scans obtained within 90 minutes of stroke onset is associated with a major neurologic deficit, and in this study it predicted a poor clinical and radiologic outcome after intravenous thrombolytic therapy. However, a major neurologic deficit, defined as a stroke scale score of 10 or more, was better than a positive HMCAS as a predictor of poor neurologic outcome after thrombolytic therapy. Patients with a low stroke scale score (< 10) may benefit from ultraearly intravenous alteplase therapy.

Adult↗

3-D image analysis of intra-cerebral brain hemorrhage from digitized CT films.

A new 3-D technique for the segmentation and quantification of human spontaneous intra-cerebral brain hemorrhage (ICH) is presented in this paper. The algorithm for ICH primary region segmentation uses the spatially weighted K-means histogram-based clustering algorithm. The ICH edema region segmentation algorithm employs an iterative morphological processing of the ICH brain data. A volume rendering technique is used for the effective 3-D visualization of ICH segmented regions. A computer program is developed for use in the human spontaneous ICH study involving a large number of patients. Experimental measurements and visualization results are presented which were computed on real ICH patient brain data.

Algorithms↗

Frequency and accuracy of prehospital diagnosis of acute stroke.

BACKGROUND AND PURPOSE: This pilot study evaluated the frequency and accuracy of diagnosis of stroke made by prehospital care system dispatchers, emergency medical technicians (EMTs), and paramedics in one emergency medical services (EMS) system. In addition, the study determined patient prehospital triage and time intervals in the transport and examination of patients given a diagnosis of stroke by this EMS system. METHODS: We reviewed records of 4413 consecutive prehospital records of a two-tiered EMS system for patients with potential stroke. Hospital records were obtained for patients given a diagnosis of stroke or transient ischemic attack (TIA) by an EMS dispatcher, EMT, or paramedic. The EMS system studied serves a community of 13,000 within the greater Cincinnati area. RESULTS: Of 4413 EMS on-scene evaluations, the diagnosis of stroke or TIA was made by an EMT or paramedic for 96 patients (2%). Of the study population (n = 86), a final hospital discharge diagnosis of stroke or TIA was made for 62 patients (72%). EMS dispatchers correctly identified 52% and paramedics 72% of these 86 patients as having sustained a stroke or TIA. Twenty-two of the 86 patients required paramedic-level interventions, which included three intubations. Of the 24 patients whose symptoms were misdiagnosed as stroke or TIA by the paramedics, 16 (19%) had acute conditions for which effective therapies are available. Prehospital personnel arrived at the scene to examine potential stroke patients in a mean of 3 minutes after the emergency 911 call was received by the dispatcher. Patients transported by basic life support units (EMTs) arrived earlier at the hospital than did those transported by advanced life support units (paramedics) (40 +/- 1 versus 45 +/- 1 minutes, P = .004). However, patients transported by advanced life support units were seen by a physician sooner after arrival at the emergency department (10 +/- 2 versus 20 +/- 4 minutes, P = .02) and underwent computed tomography of the brain sooner (47 +/- 5 versus 69 +/- 10 minutes, P = .04). CONCLUSIONS: Prehospital evaluation of potential stroke patients can be accomplished promptly after the EMS system is activated. Urgent evaluation and transport of potential stroke patients is justified because paramedic-level interventions are frequently required and because almost 20% of patients with potential stroke have acute medical conditions for which effective specific therapies are available.

Aged↗

Coenzyme B12-dependent ribonucleotide reductase: evidence for the participation of five cysteine residues in ribonucleotide reduction.

Ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides and requires adenosylcobalamin (AdoCbl) as a cofactor. Recent cloning, sequencing, and expression of this protein [Booker, S., & Stubbe, J. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8352-8356] have now allowed its characterization by site-directed mutagenesis. The present study focuses on the role of five cysteines postulated to be required for catalysis. The choice of which of the ten cysteines of RTPR were to be mutated was based on extensive studies on the Escherichia coli ribonucleoside diphosphate reductase. Despite the differences between these two reductases in primary sequence, quaternary structure, and cofactor requirements, their mechanisms are strikingly similar. The mutagenesis studies reported herein further suggest that the complex role of the five cysteines is also very similar. A variety of single and double mutants of RTPR were prepared (C731S, C736S, C731 and 736S, C119S, C419S, C408S, and C305S), and their interaction with the normal substrate (CTP) was characterized under several sets of conditions. Mutants C731S, C736S, and C731 and 736S all catalyzed the formation of dCTP at rates similar to those of the wild-type (wt) enzyme in the presence of the artificial reductant DTT. In the presence of the in vivo reducing system (thioredoxin, thioredoxin reductase, and NADPH), however, each of these mutants catalyzed the formation of only 0.6-0.8 dCTPs per mole of enzyme. The inability of these mutants to catalyze multiple turnovers with respect to the in vivo reducing system suggests that their function might be to transfer reducing equivalents from thioredoxin into the active site disulfide of the reductase. Mutants C119S and C419S were targeted as being the active site cysteines, the ones which directly reduce the ribonucleotide substrate. As expected, neither of these mutants catalyzed the formation of dCTP. However, they did catalyze a time-dependent formation of cytosine, destruction of the cofactor, and the appearance of a chromophore associated with the protein--all phenotypes previously observed for the corresponding active site cysteines of the E. coli reductase. Mutant C408S was unable to catalyze dNTP production or cytosine release. Moreover, it was ineffective in catalyzing two additional reactions which are unique to this enzyme: the exchange of tritium from the 5' hydrogens of AdoCbl with H2O and the destruction of AdoCbl under anaerobic conditions to give 5'-deoxyadenosine and cob(II)alamin. These results are consistent with the role of this cysteine as the protein radical responsible for initiating catalysis.

Allosteric Regulation↗

Thrombolytic therapy for stroke.

The physiology of thrombi and the pharmacology of thrombolytic drugs are under active study and improved regimens for the dosing of thrombolytic agents have been developed. In the setting of myocardial infarction, recently reported differences among thrombolytic agents have been slight, including the frequency of thrombolysis-associated hemorrhagic stroke following tissue plasminogen activator or streptokinase. In the setting of ischemic stroke, recanalization rates following intravenous tissue plasminogen activator have been modest and at least partly dependent on clot size. Conclusions regarding clinical benefit will depend on the results of multicenter randomized trials that should available in 1995. Studies of locally administered intra-arterial thrombolytic therapy demonstrate high rates of clot lysis, but clinical benefits have yet to be established. The results of randomized trials will be important in clarifying any cause-effect relationships between thrombolytic therapy and symptomatic and asymptomatic intracranial hemorrhage. Thrombolytic therapy in the study of subarachnoid hemorrhage is under active investigation.

Animals↗

Baseline silent cerebral infarction in the Asymptomatic Carotid Atherosclerosis Study.

BACKGROUND AND PURPOSE: In a group of patients with high-grade asymptomatic carotid artery stenosis, we prospectively determined the prevalence and radiological characteristics of clinically asymptomatic brain infarction evident on computed tomography. Risk factors and extent of carotid disease were also determined. METHODS: Patients randomized into the Asymptomatic Carotid Atherosclerosis Study (ACAS) underwent a neurological history, a detailed stroke/transient ischemic attack questionnaire, and a detailed neurological examination. Computed tomography scans were examined by standardized criteria developed as part of a quality-control program supervised by a neuroradiologist. The presence, location, and size of all cerebral infarctions evident by computed tomography were determined. RESULTS: Among 1132 patients, 848 had no history of stroke or transient ischemic attack. One hundred twenty-six patients (15%) had a silent infarct; 95 (11%) had one, 24 (3%) had two, and 7 (1%) had three or more infarcts. The infarct size was small and deep for 117 patients (72%), less than one-half lobe for 45 (28%), and one-half to less than one lobe for 1 (0.5%). The silent infarcts were evenly distributed ipsilaterally and contralaterally to the study artery but were significantly more frequent in the right hemisphere (P < .05). Factors associated with silent infarction were abnormal gait (P < .001), abnormal deep tendon reflexes or plantar responses (P = .038), but not degree of carotid stenosis. Silent infarction was less frequent among this totally asymptomatic cohort (15%) compared with those with transient ischemic attacks (34/139, 25%; P < .001). CONCLUSIONS: Silent infarction in the setting of asymptomatic carotid stenosis is not uncommon, but silent infarctions are rarely sizable. The clinical significance of silent cerebral infarction in patients with asymptomatic carotid artery stenosis has yet to be established.

Adult↗

Management of intracerebral hemorrhage in a large metropolitan population.

The management of all patients with spontaneous, nonaneurysmal intracerebral hemorrhages that occurred in the 1.26 million population of Greater Cincinnati during 1988 was reviewed. Of the 188 patients with intracerebral hemorrhage, 26 had operative removal of their intracerebral hemorrhage, and 8 had removal of their intracerebral hemorrhage and an arteriovenous malformation. In 15 of the 34 patients, the operation was performed within 12 hours of onset. The operative removal of parenchymal hemorrhages was performed in 29% of cerebellar, 24% of lobar, 13% of deep, and 10% of pontine hemorrhages. Admission Glasgow Coma Scale scores were similar for operated and nonoperated patients (11 +/- 3 versus 11 +/- 3), but operated patients were significantly younger (58 +/- 17 versus 72 +/- 15 yr), were more likely to have a lobar hemorrhage (64 versus 43%) or a cerebellar hemorrhage (29 versus 7%), and had larger parenchymal hemorrhages (50 +/- 31 versus 37 +/- 38 ml). Operated patients had a borderline lower 30-day mortality (25%) than nonoperated patients (46%), but the overall morbidity and mortality for the two groups did not differ significantly. Patients undergoing an early operation were more critically ill preoperatively and had a greater 30-day mortality (45%) than did those patients undergoing a late operation (12%). Half of the 43% mortality for all hospitalized cases occurred during the first 2 days after onset, and two-thirds occurred during the first 4 days. Only 12% of all patients had a minor handicap or better at 30 days. Neurosurgeons in our community performed operative removal of parenchymal hemorrhage in nearly one fifth of all patients with intracerebral hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

Ribonucleotide reductases: radical enzymes with suicidal tendencies.

Ribonucleotide reductases isolated from E. coli and from L. leichmannii differ considerably in their primary and quaternary structures, as well as in their cofactor requirements. Despite these differences, studies with the wt enzymes and the normal substrate, and with the wt enzymes and a variety of mechanism-based inhibitors, demonstrate amazing mechanistic similarities between the two reductases. Recent studies with five cysteine mutants of both reductases reveal strikingly similar phenotypes, indicating that, despite the differences in the primary structures, the groups involved in catalysis in both enzymes appear to be similar.

Amino Acid Sequence↗

Lobar hemorrhage in the elderly. The undiminishing importance of hypertension.

BACKGROUND AND PURPOSE: We sought to determine whether hypertension is less common in primary lobar hemorrhage than intracerebral hemorrhage in other locations and whether the frequency of hypertension in lobar hemorrhage diminishes with advancing age. METHODS: We identified all cases of intracerebral hemorrhage in Greater Cincinnati during 1988 by review of hospital and autopsy records as well as computed tomographic and magnetic resonance scans. RESULTS: During 1988, 66 primary lobar hemorrhages occurred, constituting 46% of all intracerebral hemorrhages in those under 75 years of age and 34% in those age 75 and older. A history of hypertension was present in 67% of patients with lobar, 73% of those with deep, 73% of those with cerebellar, and 78% of those with pontine hemorrhages. Left ventricular hypertrophy was present in 21% of patients with lobar, 27% of those with deep, and 47% of those with pontine/cerebellar hemorrhages. The frequency of hypertension in patients with lobar hemorrhage did not decrease with advancing age. CONCLUSIONS: The proportion of all intracerebral hemorrhages that are lobar does not increase with advancing age. Hypertension is nearly as common in primary lobar hemorrhage as in deep, cerebellar, and pontine hemorrhages, and its importance as an associated condition for lobar hemorrhage does not diminish with advancing age.

Adult↗

Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group.

BACKGROUND AND PURPOSE: Early thrombolytic therapy with recombinant tissue-type plasminogen activator is a theoretically attractive approach to the treatment of acute focal cerebral ischemia. In preparation for a larger multicenter trial, three centers piloted a protocol for a randomized, double-blind, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator begun within 3 hours of the onset of symptoms of acute stroke to test its feasibility and to explore trends. METHODS: Eligible patients had pretreatment computed tomographic scanning, gave informed consent, and began treatment with either 0.85 mg/kg recombinant tissue-type plasminogen activator or placebo as soon as possible, but no later than 180 minutes after stroke onset. Patients were stratified by whether treatment was begun within 90 minutes or 91 to 180 minutes from onset. The primary end point was the proportion of patients in each group who improved by 4 or more points on the National Institutes of Health Stroke Scale at 24 hours, as determined by a separate blinded evaluator. RESULTS: Twenty-seven patients were randomized: 20 (10 recombinant tissue-type plasminogen activator, 10 placebo) within 90 minutes, and 7 (4 recombinant tissue-type plasminogen activator, 3 placebo) from 91 to 180 minutes. Median baseline Stroke Scale scores were 16 (minimum = 5, maximum = 26) for the recombinant tissue-type plasminogen activator-treated group and 11 (minimum = 3, maximum = 21) for the control subjects in the group treated within 90 minutes. Six patients treated with recombinant tissue-type plasminogen activator within 90 minutes improved by 4 or more points at 24 hours compared with 1 patient in the placebo group (P < .05, Fisher's Exact Test). Two patients in each group in the 91- to 180-minute arm improved. One fatal intracerebral hemorrhage occurred in the placebo group. CONCLUSIONS: A randomized, double-blind, placebo-controlled trial of recombinant tissue-type plasminogen activator very early in acute stroke is feasible. Preliminary observations suggest that recombinant tissue-type plasminogen activator treatment within 90 minutes may be associated with early neurological improvement. Larger studies are needed so that the potentially serious short-term risks of this treatment can be assessed in relation to meaningful long-term benefit.

Aged↗

Stroke in children within a major metropolitan area: the surprising importance of intracerebral hemorrhage.

Our objective was to determine the incidence rate of stroke and stroke subtypes in children. We reviewed the medical records, autopsy records, and brain imaging studies of all children with a possible stroke within the Greater Cincinnati metropolitan area population of nearly 1.3 million during 1988 and 1989. Traumatic brain hemorrhages and germinal matrix hemorrhages were excluded. Of the 295,577 children in Greater Cincinnati, medical records of 178 children were screened. Sixteen cases (13 whites and three blacks) less than age 15 years fit strictly defined criteria for first-ever stroke. The incidence rate for cerebral infarction was 1.2 cases per 100,000 (95% confidence interval, 0.3 to 2.0). The combined incidence rate for intracerebral hemorrhage and subarachnoid hemorrhage was 1.5 cases per 100,000 children (95% confidence interval, 0.4 to 2.3). The incidence rate of all stroke in white children was 2.6 cases per 100,000 (95% confidence interval, 1.2 to 4.1), compared to 3.1 per 100,000 in black children (95% confidence interval, 0 to 6.6). The combined 30-day mortality for intracerebral hemorrhage and subarachnoid hemorrhage was 22% (two of nine) compared to 14% (one of seven) for cerebral infarction. We conclude that in contrast to the picture in adults, hemorrhagic stroke among infants and children is at least as common as ischemic infarction.

Adolescent↗

Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes.

BACKGROUND AND PURPOSE: Thrombolytic agents hold theoretical promise as therapy for cerebral infarction. This study was designed to evaluate the safety of tissue plasminogen activator, to accomplish urgent patient treatment, and to estimate potential efficacy of tissue plasminogen activator. METHODS: Following neurological evaluation and computed tomography of the brain, patients with acute ischemic stroke were evaluated and treated with intravenous tissue plasminogen activator under an open-label, dose-escalation design within 90 minutes from symptom onset. End points examined included symptomatic and asymptomatic intracranial hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24 hours, and 3 months. RESULTS: Seventy-four patients were treated within 90 minutes of symptom onset over seven dose tiers of tissue plasminogen activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma with associated neurological deterioration occurred in three patients and was related to increasing doses of tissue plasminogen activator (p = 0.045). Intracranial hematoma did not occur in any of the 58 patients treated with less than or equal to 0.85 mg/kg. Major neurological improvement occurred in 22 patients (30%) at 2 hours from the initiation of tissue plasminogen activator and in a total of 34 patients (46%) at 24 hours, but major neurological improvement was not related to increasing doses of tissue plasminogen activator or to stroke type. CONCLUSIONS: Patients with acute stroke can be evaluated and treated within 90 minutes. Tissue plasminogen activator for acute ischemic infarction is not without risk, but the potential for clinical benefit justifies a randomized clinical trial. To date, differences in hemorrhagic risk or neurological benefit of tissue plasminogen activator for particular ischemic stroke types are not apparent.

Aged↗

Public perception of stroke warning signs and knowledge of potential risk factors.

CONTEXT: Decreasing the time from stroke onset to hospital arrival and improving control of stroke risk factors depend on public knowledge of stroke warning signs and risk factors. OBJECTIVE: To assess current public knowledge of stroke warning signs and risk factors. DESIGN: A population-based telephone interview survey using random digit dialing conducted in 1995. SETTING: The Greater Cincinnati, Ohio, metropolitan area, the population of which is similar to that of the United States overall in age, sex, percentage of blacks, and economic status. PARTICIPANTS: Respondents with age, race, and sex that matched the population of patients with acute stroke. MAIN OUTCOME MEASURES: Knowledge of risk factors for stroke and warning signs of stroke as defined by the National Institute of Neurological Disorders and Stroke. RESULTS: Telephone calls were made to 17634 households, which yielded 2642 demographically eligible individuals. Interviews were completed by 1880 respondents (response rate, 71.2%). A total of 1066 respondents (57%) correctly listed at least 1 of the 5 established stroke warning signs, and of all respondents, 1274 (68%) correctly listed at least 1 of the established stroke risk factors. Of the respondents, 469 (57%) of 818 respondents with a history of hypertension listed hypertension, 142 (35%) of 402 respondents who were current smokers listed smoking, and 32 (13%) of 255 respondents with diabetes listed diabetes as a risk factor for stroke. Compared with those younger than 75 years, respondents 75 years or older were less likely to correctly list at least 1 stroke warning sign (60% vs 47%, respectively; P<.001) and were less likely to list at least 1 stroke risk factor (72% vs 56%, respectively; P<.001). CONCLUSION: Considerable education is needed to increase the public's awareness of the warning signs and risk factors for stroke. Respondents with self-reported risk factors for stroke are largely unaware of their increased risk. The population at greatest risk for stroke, the very elderly, are the least knowledgeable about stroke warning signs and risk factors.

Adult↗