The 5-HT1A and 5-HT2A/2C receptor antagonists WAY-100635 and ritanserin do not attenuate D-fenfluramine-induced fos expression in the brain

In a prospective randomised study we investigated end-tidal carbon dioxide levels during standard versus active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) assuming that the end-tital carbon dioxide reflects cardiac output during resuscitation. In each group 60 patients with out-of-hospital cardiac arrest were treated either with the standard or the ACD method. End-tidal CO2 (p(et)CO2, mmHg) was assessed with a side-stream capnometer following intubation and then every 2 min up to 10 min or restoration of spontaneous circulation (ROSC). There was no difference in p(et)CO2 between both patient groups. However, CO2 was significantly higher in patients who were admitted to hospital as compared to patients declared dead at the scene. All of the admitted patients had a p(et)CO2 of at least 15 mmHg no later than 2 min following intubation, none of the dead patients ever exceeded 15.5 mmHg. From these data we conclude that capnometry adds valuable information to the estimation of a patient's prognosis in the field (threshold, 15 mmHg), but we could not detect any difference in p(et)CO2 between ACD and standard CPR.     

The Coventry Award. Modular tibial insert micromotion. A concern with contemporary knee implants

This study investigates micromotion between modular tibial components, one of the causes of wear on the undersurface of polyethylene inserts. The authors measured motion at the interface of nine contemporary total knee implant designs by mechanically testing the implants in a servohydraulic testing machine. Anteroposterior and mediolateral motion between the tibial insert and baseplate were measured with an extensometer placed across the interface. These tests revealed that in all implants analyzed, sufficient motion occurred to create fretting at the modular interface. Although the testing configuration in this study was not a stimulation of in situ loading patterns, the authors observed hundreds of microns of motion even under a 100 N load and variability between implants of the same design, showing that there is room for improvement among locking mechanisms in modular total knee implants.     

An examination of gender and racial differences among Missouri insanity acquittees

This study examines gender and racial differences among Missouri insanity acquittees, which included 42 African American females, 279 African American males, 63 Caucasian females, and 458 Caucasian males. Significant differences across the four groups were not found in age, current marital status, a diagnosis of borderline intellectual functioning/mental retardation, committing crimes of assault and burglary, and whether insanity acquittees ever received conditional releases to reside in the community. Some variations across the four gender/race categories were related to race (diagnoses of schizophrenia, mood disorders, and other Axis I diagnoses), but variations were more frequently related to gender (whether ever married; diagnoses of substance abuse, sexual disorders, antisocial personality disorder, borderline personality disorder, and any personality disorder; committing crimes of murder, sexual offenses, and serious offenses; and current residential status). African American males were identified as being an at-risk population. They were the most likely to have a schizophrenia diagnosis, a substance abuse diagnosis, an antisocial personality disorder diagnosis, and to be hospitalized on the survey date. Implications for treatment and future research are explored.     

The use of inhaled nitric oxide in a wide variety of clinical problems

Inhaled nitric oxide (NO) clearly decreased pulmonary vascular resistance in pediatric patients with pulmonary hypertension, regardless of the underlying origin of the pulmonary hypertension. In persistent pulmonary hypertension of the neonate (PPHN) and CHD, the use of inhaled NO appears to improve the outcome of these patients. In acute respiratory distress syndrome (ARDS) and surfactant deficiency the role of inhaled NO therapy remains unclear. The use of inhaled NO is safe in a carefully monitored setting with a delivery system designed to minimize the generation of NO2.     

Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.     

From noxiustoxin to Shiva-3, a peptide toxic to the sporogonic development of Plasmodium berghei

This communication reviews shortly the main structural and functional characteristics of Noxiustoxin, a 39 amino acid residue peptide, maintained closely packed by three-disulfide bridges and its effects on excitable membranes. Shiva-3, a cecropin like-peptide composed of 38 amino acid residues is also briefly reviewed. Its design and synthesis was made possible by the expertise gained through the work previously performed with Noxiustoxin. One of the most prominent functional characteristics of Shiva-3 is the toxic effect upon the sporogonic development of Plasmodium berghei (responsible for a murine version of malaria). A synthetic Shiva-3 gene was constructed by recursive polymerase-chain reaction (PCR) methodology and expressed using the vector pGEX2T as a hybrid protein between the glutathione-S-transferase at the N-terminal and Shiva-3 in the C-terminal part of the hybrid. The recombinant protein kills bacteria and Plasmodium berghei. The future aim of this work is to produce a transgenic mosquito that carries the message for synthesis and excretion of Shiva-3 and similar peptides, in the midgut of mosquitoes, in an attempt to control the spreading of human malaria.     

Stereotactic radiosurgery for tentorial meningiomas

Radical microsurgical resection is the procedure of choice for tentorial meningiomas. Despite advances in microsurgery, tentorial meningiomas continue to challenge surgeons and patients. To evaluate the response of tentorial meningiomas, we evaluated 41 patients who had Gamma knife stereotactic radiosurgery during a 9 year period. Patient age varied from 32 to 79 years. Headache, trigeminal neuralgia, or facial paraesthesia were the most common presenting symptoms. Sensory deficits in the distribution of the trigeminal nerve were the most common finding. Eighteen patients (44%) had undergone between 1 and 5 (mean, 1.9) resections prior to radiosurgery; 23 had tumors diagnosed by neuroimaging. The average tumor diameter in this series was 20 mm. The maximum tumor dose varied from 24 to 40 Gy (mean, 30.5 Gy), and the tumor margin dose varied from 12 to 20 Gy (mean, 15.3 Gy). During the average follow-up interval of 3 years (range, 1-8 years), 19 patients had clinical improvement, 20 remained stable, and 2 patients deteriorated. Follow-up imaging showed a reduction in tumor size in 18 patients, no further tumor growth in 22, and an increase in tumor size in one (overall tumor control rate of 98%). Stereotactic radiosurgery using the Gamma Knife was a safe and effective primary or adjuvant treatment for patients with tentorial meningiomas.