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Biomedical subjects

M J Wright

Publications and source records attributed to M J Wright.

At least 19 recordsLinked to original sources
PubMed2000

The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes.

Activation of protein kinase C (PKC) and more recently mitogen-activated protein kinases (MAPKs) have been associated with the cardioprotective effect of ischemic preconditioning. We examined the interplay between these kinases in a characterized model of ischemic preconditioning in cultured rat neonatal ventricular cardiocytes where ectopic expression of active PKC-delta results in protection. Two members of the MAPK family, p38 and p42/44, were activated transiently during preconditioning by brief simulated ischemia/reoxygenation. Overexpression of active PKC-delta, rather than augmenting, completely abolished this activation. We therefore determined whether a similar process occurred during lethal prolonged simulated ischemia. In contrast to ischemia, brief, lethal-simulated ischemia activated only p38 (2.8+/-0.45 vs. basal, P<0.01), which was attenuated by expression of active PKC-delta or by preconditioning (0.48+/-0.1 vs. ischemia, P<0.01). To determine whether reduced p38 activation was the cause or an effect of protection, we used SB203580, a p38 inhibitor. SB203580 reduced ischemic injury (CK release 38.0+/-3.1%, LDH release 77.3+/-4.0%, and MTT bioreduction 127.1+/-4.8% of control, n=20, P<0.05). To determine whether p38 activation was isoform selective, myocytes were infected with adenoviruses encoding wild-type p38alpha or p38beta. Transfected p38alpha and beta show differential activation (P<0.001) during sustained simulated ischemia, with p38alpha remaining activated (1.48+/-0.36 vs. basal) but p38beta deactivated (0.36+/-0.1 vs. basal, P<0.01). Prior preconditioning prevented the activation of p38alpha (0.65+/-0.11 vs. ischemia, P<0.05). Moreover, cells expressing a dominant negative p38alpha, which prevented ischemic p38 activation, were resistant to lethal simulated ischemia (CK release 82.9+/-3.9% and MTT bioreduction 130.2+/-6.5% of control, n=8, P<0.05). Thus, inhibition of p38alpha activation during ischemia reduces injury and may contribute to preconditioning-induced cardioprotection in this model.

Animals↗
PubMed2000

Use of an unmanned police car to reduce traffic speed.

OBJECTIVE: Motor vehicle collisions are the most common mechanism of traumatic death. Speeding is often implicated as a causal factor in motor vehicle crashes. One potential intervention, to prevent speeding, is the placement of a roadside unmanned police car. This study sought to answer the following questions: is speeding reduced by this intervention, does this intervention lose effectiveness over time, and when the car is removed, do motorists resume speeding? METHODS: A radarless speed detector was placed on a roadway that had a history of speed-related collisions. Baseline speeds were recorded for 12 days. Thereafter, an unmanned police cruiser was parked near the road, and speeds were recorded for 10 days. The police car was removed, and data collection continued 1 more week. The difference between the proportion of motorists exceeding 45-mph in the baseline period and the decoy intervention period was tested by using a chi2 test. RESULTS: During the baseline surveillance, 72.0% of vehicles (186,578 of 259,074 motorists) had speeds greater than 45 mph. After placement of the unmanned police car, 41.0% of motorists (92,272 of 225,026 motorists) exceeded 45 mph (p < .0001). Over the 10-day study period, when the decoy police car was in place, the percentage of motorists exceeding 45 mph gradually increased from 27.2% to 47.4%. Upon removal of the police car, speeding returned approximately to baseline, with 67.5% of motorists (120,640 of 178,752 motorists) exceeding 45-mph. CONCLUSION: Parking an unmanned police car beside a road was associated with a large reduction in speeding over a 10-day period. Removal of the unmanned police car resulted in a return to preintervention speeding.

Accidents, Traffic↗
PubMed2000

Accuracy of administrative data in trauma: splenic injuries as an example.

BACKGROUND: Accurate data are needed to evaluate clinical outcomes, therapeutic modalities, and quality of care in trauma. Administrative data, usually used for billing, have been used to evaluate performance and assess therapy in other medical specialties. This study was performed to determine whether administrative databases are accurate in the recording of information about trauma patients with splenic injuries. METHODS: Patients who had blunt splenic injuries were identified using a state trauma registry. The medical records of those patients were reviewed. The data collected by chart review were compared with data in the statewide administrative database of patients who had splenic injuries at the same four Level I and II trauma centers in the same 5-year period. Age, sex, admission date, and hospital were matched to assure comparison of the identical cohort. chi2 analysis was used to compare dichotomous data and Student's t test continuous data. RESULTS: The administrative database identified 641 and the trauma registry identified 529 patients with a diagnosis of splenic injury. A total of 401 patients were found in both databases. Of these, 120 (22.7%) patients were not recorded in the administrative database. Injury Severity Score was underreported by the administrative database (25.74 +/- 14.7 vs. 19.52 +/- 11, p < 0.0001). The administrative database underreported orthopedic, chest, and head injuries (317 vs. 215, 325 vs. 228, and 234 vs. 155, respectively; all p < 0.0001). Use of abdominal computed tomographic scan and diagnostic peritoneal lavage were also underreported (260 vs. 56 and 104 vs.17, both p < 0.0001). The number of operations on the spleen and number of orthopedic procedures were underreported (259 vs. 225, p < 0.014 and 147 vs. 94, p < 0.0001). Complications were markedly underreported by the administrative database (200 vs. 47, p < 0.0001) CONCLUSION: This study shows that administrative data lack accuracy in the recording of associated injuries, injury severity, diagnostics, procedures, and outcomes data in patients with splenic injuries. Whether these data should be used to evaluate treatment modalities or quality of care in trauma is questionable.

Adult↗
PubMed2000

Perioperative intracranial hemorrhage in achondroplasia: a case report.

We report a case of a 35-year-old man with achondroplasia who previously had thoracolumbar decompressive laminectomies, who developed recurrence of spinal stenosis at the thoracolumbar junction. The patient underwent standard repeat thoracolumbar decompression, removal of a disc, and spinal fusion with instrumentation in the prone position. Postoperatively the patient was confused. Computed tomography (CT) revealed hemorrhages in both cerebellar hemispheres with surrounding edema and mild mass effect. These were interpreted as venous hemorrhages. Conservative therapy was successful. This is the first case report of perioperative venous intracranial hemorrhage in the context of spinal surgery for achondroplasia. Distinctive anatomic characteristics of achondroplasia, combined with several potentially modifiable aspects of his management, may have predisposed the patient to this complication.

Achondroplasia↗
PubMed2000

Blunt pancreatic trauma: a difficult injury.

The diagnosis and initial management of hemodynamically stable blunt pancreatic trauma should include a high index of suspicion when a patient has sustained a severe force vector in the anterior-posterior direction of the abdominal cavity. Patients who are hemodynamically stable should have physical examination, computed tomography (CT) of the abdomen, and serial determinations of serum amylase levels. If CT shows any suggestion of injury to the pancreas, such as fluid between the splenic vein and the posterior border of the pancreas, follow-up endoscopic retrograde pancreatography (ERP) should be done. In patients with a significant retroperitoneal hematoma, ERP should be followed by noncontrast CT for the evaluation of extravasation of contrast material. If ERP shows ductal disruption or follow-up CT shows extravasation of contrast, operative management is indicated. The astute physician should always remember that the most difficult aspect of pancreatic injury is timely diagnosis.

Adult↗
PubMed2000

A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study.

PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.

Humans↗
PubMed2000

Current management of pelvic fractures.

Blunt pelvic injuries are becoming more common in this era of high-speed, high-energy collisions. At least 5% of blunt injuries result in pelvic fracture. With mortality rates approaching 55% for severe crush injuries of the pelvis, early stabilization and control of bleeding, as well as assessment for other injuries, requires a focused, multidisciplinary approach. We discuss early management and stabilization of severe pelvic fractures.

Accidents, Traffic↗
PubMed1999

Limitation of ankle range of motion in survivors of acute lymphoblastic leukemia: a cross-sectional study.

BACKGROUND: The purpose of this study was to evaluate and determine the factors related to active and passive dorsiflexion range of motion (DF-ROM) in survivors of acute lymphoblastic leukemia (ALL), which is the most obvious impairment of musculoskeletal function in such children. PROCEDURE: The subjects included 54 survivors of ALL treated on Dana-Farber Cancer Institute protocols and 54 comparable healthy children. Bilateral active and passive DF-ROM were measured with the knee extended. RESULTS: The survivors of ALL had significantly less active and passive DF-ROM (6.4 vs. 16.8, 10.5 vs. 18.8 degrees, respectively, P < 0.001) than the comparison children. Weight for age at the time of assessment and change in height during treatment showed significant negative correlations with DF-ROM. Length of time-off treatment was not associated with DF-ROM. CONCLUSIONS: Multiple regression analyses identified the variables of age at diagnosis and gender as significant predictors of both DF-ROM measures following treatment. Children diagnosed at a younger age and females were at greater risk for restricted DF-ROM. Close monitoring and preventative therapy programs for this complication are warranted for children, especially young girls receiving treatment for ALL.

Adolescent↗
PubMed1999

Visual discrimination of direction changes based upon two types of angular motion.

We address the question of how the visual system analyses changes in direction. Using plaid stimuli, we define type O direction changes which entail a change in the orientations of the plaid components, and type V direction changes in which the orientations of the components remain constant, relative to the observer but their relative speeds change. Lower thresholds for discriminating type O and type V direction changes were compared. Type O thresholds for clockwise/anticlockwise direction change were very low (0.2-0.5 degree), were resistant to directional noise, and showed a low-pass relationship with drift velocity. Type V thresholds on the other hand were higher (1-5 degrees), and exhibited a bandpass relationship with drift velocity. Type O direction changes gave low thresholds at short inter-stimulus intervals (ISI) (< 160 ms) and higher thresholds (successive orientation discrimination) at long ISI (240 ms-12.8 s). Type V thresholds, on the other hand, exhibited no short-range process and performance at short ISI, was no better than for successive direction discrimination at long ISI. A two-stage rotary motion model is sufficient to explain the discrimination of type O direction changes and results rule out a model based on velocity discrimination. For type V direction changes, a two-stage mechanism is insufficient and results are consistent with a minimum of three computational stages.

Humans↗
PubMed1999

Low thrombogenicity of polyethylene glycol-grafted cellulose membranes does not influence heparin requirements in hemodialysis.

Heparin is the most commonly used anticoagulant for hemodialysis despite potentially serious side effects. Polyethylene glycol-grafted cellulose (PGC) membranes produce less activation of the coagulation cascade than cuprophane membranes. Anecdotally, we found some patients required a surprisingly low level of anticoagulation using these membranes. We compared the anticoagulant requirement of the PGC membrane with that of the cuprophane membrane in this randomized, prospective, crossover study. Sixty-three patients were randomized to treatment using either membrane, and heparin administration was progressively reduced to the lowest dose that prevented visible clotting in excess of that normally encountered. Patients underwent dialysis at this dose for 1 month, after which the heparin requirement and Kt/Vurea (1.162 x ln [urea pre/urea post]) were assessed. This process was then repeated for each patient using the other membrane, and the results were compared. Heparin administration during dialysis was reduced from a mean loading dose of 29.0 +/- 9.4 to 1.5 +/- 3.2 IU/kg for both membranes and a mean maintenance infusion of 14.0 +/- 6.7 to 0.77 +/- 1.6 IU/kg/h for both membranes (both P < 0.0001 v full anticoagulation; no difference between membranes). The Kt/Vurea was not significantly altered. Forty-six patients with PGC and 45 patients with cuprophane membranes underwent dialysis successfully without heparin during dialysis, and the other patients were using considerably reduced doses. Aspirin and warfarin had no effect on the heparin requirement. These results do not support the theory that PGC membranes have a lower anticoagulant requirement than cuprophane membranes; however, they suggest that dialysis can be performed successfully with much smaller anticoagulant doses than are currently in common use.

Anticoagulants↗
PubMed1998

Long-term gross motor performance following treatment for acute lymphoblastic leukemia.

BACKGROUND: The primary purpose of this descriptive study was to determine the long-term effects of cancer treatment in childhood on musculoskeletal function and gross motor skills. PROCEDURE: Musculoskeletal and gross motor function were assessed in a cohort of 36 survivors of acute lymphoblastic leukemia (ALL) seen in a pediatric tertiary care referral centre, compared to 36 age and gender matched comparison subjects. Basic gross motor skills were assessed using dimensions D: standing, and E: walking, running, and jumping of the Gross Motor Function Measure (GMFM). Strength, balance, and running speed and agility were assessed using the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP). Hand grip strength and ankle dorsiflexion range of motion were also measured. Findings in the children with ALL were compared by dependent (paired) t-tests to those in age and gender matched children. RESULTS: The GMFM scores for standing were 98.7% and for walking, running, and jumping were 99% of normal. The mean standard scores for the BOTMP were significantly lower than those of the comparison group: strength 11.5 vs. 19.4, balance 9.4 vs. 15.5, and running speed and agility 9.9 vs. 16.6. The ALL subjects had less hand grip strength 156.3 vs. 190.2, and less ankle dorsiflexion 7.5 vs. 16.1 degrees than the comparison group. The survivors of childhood leukemia were able to perform most basic gross motor functions. However, musculoskeletal impairment was evident and levels of motor proficiency were significantly poorer than those of age and gender matched children. CONCLUSIONS: Programs to promote physical activity and limit disability may improve gross motor function and increase overall quality-of-life in survivors of leukemia in childhood.

Adolescent↗