Therapeutic efficacy of tirilazad in experimental multiple cerebral emboli: a randomized, controlled trial

OBJECTIVE: A significant proportion of patients who undergo cardiac surgery or carotid endarterectomy appear to develop subtle cognitive deficits, with the occurrence of multiple cerebral microemboli documented by Doppler ultrasound during these procedures. We used an experimental multiple cerebral embolism model to test whether treatment with tirilazad (U74006F), a putative inhibitor of lipid peroxidation, would improve functional outcome after multiple brain emboli. DESIGN: Randomized, controlled trial. SETTING: Animal care facility procedure room. SUBJECTS: A total of 44 New Zealand White rabbits weighing 2 to 3.0 kg. INTERVENTIONS: Variable quantities of 125I-labeled 50-microns microspheres were injected via a carotid catheter to produce multifocal brain ischemia. Rabbits randomly received either: tirilazad (3 mg/kg i.v.) 5 mins before embolization (pretreatment), or 30 mins after embolization (posttreatment) followed by 1.5 mg/kg every 5 hrs x 3 doses. A third group received vehicle only (control) 5 mins before, followed by three doses every 5 hrs. MEASUREMENTS AND MAIN RESULTS: The animals were rated by a blinded observer at 18 hrs after ischemia and scored as either grossly abnormal/dead or normal. The animals were killed and the amount of microspheres in the brain that were required to produce abnormal function at 18 hrs was calculated for each group. To determine if tirilazad also modified leukocyte function during ischemia, neutrophil adhesion to laminin was determined at baseline and 18 hrs after ischemia using a myeloperoxidase assay. In this study, pretreatment, but not posttreatment with tirilazad produced a significant reduction in neurologic deficits. Tirilazad also attenuated postischemic increases in neutrophil adhesion. CONCLUSIONS: Tirilazad pretreatment reduces neurologic deficits from multiple cerebral emboli. This significant protective effect suggests that pretreatment with tirilazad may play a role in clinical situations where the risk of cerebral emboli is high, with changes in leukocyte adherence as a potential mechanism.     

Increased mortality after successful treatment for Hodgkin's disease

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.     

Predominance and characteristics of Burkitt lymphoma among children with non-Hodgkin lymphoma in northeastern Brazil

The purpose of this paper was to define the histologic distribution, clinical features, and treatment response of childhood non-Hodgkin lymphoma (NHL) in northeastern Brazil. We reviewed medical records and histopathologic studies of 98 children treated for NHL from 1980 to 1987 at a major pediatric cancer center in Recife, Brazil. Treatment outcome was evaluated in relation to tumor burden (stage and serum LDH) and type of therapy (LSA2L2 vs other multiagent chemotherapy). There was a striking predominance of the small noncleaved cell (Burkitt) subtype, which occurred in 92 of the 98 children and adolescents diagnosed with NHL. Subsequent analyses focused on these patients. The majority (n = 84) had advanced (stage III/IV) disease at diagnosis. The abdomen was the most common site of disease (84 cases); jaw involvement was rare (three cases). Five-year event-free survival (excluding treatment refusals) was significantly better for patients with limited vs advanced stage disease (75 +/- 14% vs 42 +/- 6%; P < 0.04). Elevated serum LDH (>500 U/l) was associated with a poorer outcome (P = 0.008). The type of chemotherapy did not affect EFS (P = 0.95). Only 39% of patients are long-term survivors, reflecting the high rate of septic deaths (25% of patients) and parental refusal/abandonment of therapy (10%). Epstein-Barr virus (EBV) was detected in tumor cells from eight of the 11 cases studied. In clinical presentation, these cases resemble sporadic Burkitt lymphoma, yet in their apparent responsiveness to LSA2L2 therapy and association with EBV, they do not. Childhood NHL in northeastern Brazil is predominantly of the Burkitt subtype, and is associated with clinical features that appear to distinguish it from the endemic and sporadic forms of this tumor. These cases may represent a third or intermediate subtype of Burkitt lymphoma.     

A quantitative framework for analyzing epicardial activation patterns during ventricular fibrillation

We have developed a method for quantifying the complexity of activation patterns observed during ventricular fibrillation (VF) that is based on our previously reported methodology for decomposing epicardial mapping data into a set of isolated wavefronts. One-half second datasets are acquired from a 21 x 24 array of unipolar electrodes (1 mm spacing), and the wavefronts are isolated. A correlation technique is used to compute the similarity between all possible pairs of the isolated wavefronts. From these data, the wavefronts are sorted into clusters, each of which represents a recurring wavefront morphology. We define multiplicity (M) as the number of clusters needed to account for 90% of the total activations in the VF episode. M measures the complexity of the rhythm. In repetitive patterns (e.g., sinus rhythm), M = 1, indicating that the same morphology repeatedly activates the mapped region. Typically, in VF, M > 1, with larger numbers representing more complex, disorganized patterns. As an example, we computed M at 5, 10, 15, and 20 sec after electrical induction of VF in six pigs. M decreased significantly (p < 0.001), suggesting increasing organization during this period.     

No-load versus load loss

The theory of transformer losses expressed as no-load loss and load loss is briefly reviewed in this article. Mathematical expressions for per-unit loss as a function of load are developed based on rated and actual load. Present value equations are used to express the cost of losses as a function of transformer characteristics, electricity cost, and discount rate. Three methods are presented for expressing the cost of losses in forms that can be used to evaluate bids.     

External fixation for pelvic ring disruptions

The application of external fixation for acute treatment of unstable pelvic fractures can be a lifesaving procedure; however, it must be coordinated with other efforts of the trauma team. The patient with a pelvic fracture must be adequately resuscitated and carefully evaluated. This evaluation includes a careful physical examination and radiographic studies, which include plain films and computerized tomography. A proper evaluation enables classification of the pelvic injury and appropriate selection of patients that require acute pelvic external fixation. In this article, both open and percutaneous techniques for pin placement and fixator frame configurations are discussed.     

Chronic orbital hematic cysts: a case for craniofacial correction

Chronic hematic cysts are rare conditions that usually present to the ophthalmic surgeons with displacement of the globe. There is usually no, or minimal, bone involvement. Two patients with unusual presentations of chronic orbital hematic cysts are reported. These cysts resulted in significant expansion and erosion of the bony orbits. The presentation, operative findings, and reconstruction are reported and discussed.     

Comparison of single-dose oral grepafloxacin with cefixime for treatment of uncomplicated gonorrhea in men. The STD Study Group

In a randomized open study, 351 male patients with uncomplicated gonorrhea were given single oral doses of grepafloxacin (400 mg) or cefixime (400 mg). In the 299 microbiologically evaluable patients, urethral infections were cured in 99% (147 of 149) of those receiving grepafloxacin and 97% (145 of 150) of those given cefixime. Eradication rates for both regimens were 100% in the 16% (47 of 299) of participants who were infected with penicillin-resistant Neisseria gonorrhoeae and 97% in the 21% (62 of 299) of participants infected with tetracycline-resistant strains. Grepafloxacin is a well-tolerated alternative to cefixime for treatment of uncomplicated gonorrhea in males.