Standards, Options, and Recommendations for the management of patients with malignant mesothelioma of the pleura. Fédération Nationale des Centres de Lutte Contre le Cancer

The "Standards, Options and Recommandations" (SOR), started in 1993, are a collaborative project between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcomes for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary experts group, with feedback from specialists in cancer care delivery. The objectives are to develop a clinical practice guideline with definitions of Standards. Options and Recommendations for the clinical care of malignant pleural mesothelioma. Data have been identified by literature search using Medline (1966-June 1997) and personal references lists. The main criteria considered were incidence, risk factors, pronostic factors and efficacy of cancer treatment. Once the guideline was defined, the document was submitted to 40 independent reviewers for peer review, and to the medical committees of the 20 French Cancer Centres for review and agreement. The results are: 1) systematic assessment of (professional) exposure to asbestos is based on a standardized interrogatory, completed by specific consultation for professional disease; 2) diagnostic and clinical staging is based on multiple biopsies under thoracoscopy and thoracic scanner; 3) there is no indication for extemporaneous examination, immunocytochemistry should use cytokeratine, EMA, vimentine, ACE, Leu-M1; 4) clinical care: the recommended staging classification is the IMIG (International Mesothelioma Interest Group) classification; 5) validated, independent pronostic factors are stage of disease patient's functional status and histologic type (i.e. epithelial lesions are of better prognosis); 6) treatment is based on symptomatic and palliative treatment options. Anticancer treatments (surgery, chemotherapy, immunotherapy, radiotherapy) did not show significant improvement of survival. The inclusion of patients in clinical trials is recommended.     

Discarded needles do not increase soon after the opening of a needle exchange program

This study examines the effect of a Needle Exchange Program (NEP) on the quantity and geographic distribution of discarded needles on the streets of Baltimore, Maryland, and presents methods to survey discarded needles in the community. A random sample of 32 city blocks located within high-drug-use census tracts, stratified by east and west sides of the city and by proximity to the NEP, was selected for survey. Three teams surveyed the number of needles and the number of drug vials and unbroken glass bottles ("trash") to control for practice effects. Surveillance was conducted prior to initiation of the NEP in August 1994 and 1 and 2 months thereafter. Over the three study periods, the absolute count of discarded needles was 106, 130, and 128, respectively; the number of vials and bottles was 3,048, 3,825, and 3,796, respectively. The initial nonstatistically significant increase in needles (mean change = 0.38, 95% confidence interval (CI) -0.18 to 0.93) was offset by accounting for background trash. Regression models fitted with the generalized estimating equation method, which accounted for within-block correlation over time, showed no significant increase in the number of needles after adjustment for trash during the first 2 months of the NEP's operation. These data suggest that the initiation of NEPs does not result in an increase in the number of discarded needles on the street.     

Massive air embolus to the left ventricle: diagnosis and monitoring by serial echocardiography

Air embolization is an unusual but potentially dangerous complication in left heart catheterization. Microbubbles can be detected with two-dimensional echocardiography, which is often used for this purpose during open heart and bypass surgeries. Permanent neurologic sequelae and hemodynamic collapse can result from embolization of air bubbles to the cerebral and coronary circulations, respectively. Hyperbaric oxygen is the treatment of choice for cerebral air embolization. We present a 39-year-old man who had air embolization during left ventriculography in the form of a large pocket of "pooled" air. The patient was treated with conservative therapy successfully. Two-dimensional transthoracic echocardiography was used to document the presence of the air and follow its dissolution.     

Is there a "non-MAO" macromolecular target for L-deprenyl?: Studies on MAOB mutant mice

Several irreversible inhibitors of monoamine oxidase B, can promote survival of damaged neurons in several animal models of cerebral injury. Today it is evident that this effect is not a consequence of monoamine inhibition. Instead it has been proposed that L-deprenyl may act via an unrelated non-monoamine oxidase type- of binding site. In the present study we have investigated if brain tissue from MAOB knockout mice contain such "non-MAO" binding sites for radiolabelled deprenyl. Interestingly, no binding of L-deprenyl was observed indicating that the mother compound does not act directly via a macromolecular target. This is enticing since several alternative mechanisms of action have been proposed in the literature.     

Why adding rice hull ash can benefit beer clarification

Filter aids continue to play an important role in the beer brewing process. The majority of commercial products are either diatomite- or perlite based. However, rice hull ash, a by-product from the incineration of rice hulls, has been shown to be an effective filter aid in the filtration of raw sugar liquors. A research team from the Cuban Research Institute of Sugar Cane Derivatives (ICIDCA) has gone on to investigate its ability to clarify beer. The findings of their study are presented below.     

Molecular typing of Neisseria gonorrhoeae causing repeated infections: evolution of porin during passage within a community

Thirty-three Neisseria gonorrhoeae isolates from 15 persons infected multiple times with the same serovar were compared using por gene sequencing, opa-typing, and arbitrarily primed-polymerase chain reaction. All three molecular techniques were more discriminatory than serotyping and identified differences between some isolates belonging to the same serovar. Although there were differences among Por sequences within some serovars, 10 of 15 subjects became reinfected with gonococci expressing identical Por proteins. Sequence analysis of por genes revealed evidence of horizontal genetic exchange and point mutations in potential surface-exposed regions during passage in the community.     

Organized cell swimming motions in Bacillus subtilis colonies: patterns of short-lived whirls and jets

The swimming motions of cells within Bacillus subtilis colonies, as well as the associated fluid flows, were analyzed from video films produced during colony growth and expansion on wet agar surfaces. Individual cells in very wet dense populations moved at rates between 76 and 116 microm/s. Swimming cells were organized into patterns of whirls, each approximately 1,000 microm2, and jets of about 95 by 12 microm. Whirls and jets were short-lived, lasting only about 0.25 s. Patterns within given areas constantly repeated with a periodicity of approximately 1 s. Whirls of a given direction became disorganized and then re-formed, usually into whirls moving in the opposite direction. Pattern elements were also organized with respect to one another in the colony. Neighboring whirls usually turned in opposite directions. This correlation decreased as a function of distance between whirls. Fluid flows associated with whirls and jets were measured by observing the movement of marker latex spheres added to colonies. The average velocity of markers traveling in whirls was 19 microm/s, whereas those traveling in jets moved at 27 microm/s. The paths followed by markers were aligned with the direction of cell motion, suggesting that cells create flows moving with them into whirls and along jets. When colonies became dry, swimming motions ceased except in regions close to the periphery and in isolated islands where cells traveled in slow whirls at about 4 microm/s. The addition of water resulted in immediate though transient rapid swimming (> 80 microm/s) in characteristic whirl and jet patterns. The rate of swimming decreased to 13 microm/s within 2 min, however, as the water diffused into the agar. Organized swimming patterns were nevertheless preserved throughout this period. These findings show that cell swimming in colonies is highly organized.     

Severe leukopenia and dysregulated erythropoiesis in SCID mice persistently infected with the parvovirus minute virus of mice

Parvovirus minute virus of mice strain i (MVMi) infects committed granulocyte-macrophage CFU and erythroid burst-forming unit (CFU-GM and BFU-E, respectively) and pluripotent (CFU-S) mouse hematopoietic progenitors in vitro. To study the effects of MVMi infection on mouse hemopoiesis in the absence of a specific immune response, adult SCID mice were inoculated by the natural intranasal route of infection and monitored for hematopoietic and viral multiplication parameters. Infected animals developed a very severe viral-dose-dependent leukopenia by 30 days postinfection (d.p.i.) that led to death within 100 days, even though the number of circulating platelets and erythrocytes remained unaltered throughout the disease. In the bone marrow of every lethally inoculated mouse, a deep suppression of CFU-GM and BFU-E clonogenic progenitors occurring during the 20- to 35-d.p.i. interval corresponded with the maximal MVMi production, as determined by the accumulation of virus DNA replicative intermediates and the yield of infectious virus. Viral productive infection was limited to a small subset of primitive cells expressing the major replicative viral antigen (NS-1 protein), the numbers of which declined with the disease. However, the infection induced a sharp and lasting unbalance of the marrow hemopoiesis, denoted by a marked depletion of granulomacrophagic cells (GR-1(+) and MAC-1(+)) concomitant with a twofold absolute increase in erythroid cells (TER-119(+)). A stimulated definitive erythropoiesis in the infected mice was further evidenced by a 12-fold increase per femur of recognizable proerythroblasts, a quantitative apoptosis confined to uninfected TER-119(+) cells, as well as by a 4-fold elevation in the number of circulating reticulocytes. Therefore, MVMi targets and suppresses primitive hemopoietic progenitors leading to a very severe leukopenia, but compensatory mechanisms are mounted specifically by the erythroid lineage that maintain an effective erythropoiesis. The results show that infection of SCID mice with the parvovirus MVMi causes a novel dysregulation of murine hemopoiesis in vivo.     

The effects of helix breaking mutations in the diphtheria toxin transmembrane domain helix layers of the fusion toxin DAB389IL-2

The fusion protein toxin DAB389IL-2 is composed of the catalytic and transmembrane domains of diphtheria toxin genetically linked to human interleukin 2 (IL-2). This fusion toxin is selectively toxic for eukaryotic cells which express the high-affinity form of the IL-2 receptor and the mechanism of intoxication parallels that of native diphtheria toxin. We used site-directed mutagenesis to introduce Pro residues into each of the three helical layers of the transmembrane domain. Although each of the mutations results in the complete loss of cytotoxic activity, individual mutants were found to vary with respect to channel formation in planar lipid bilayers, binding affinity and melting temperature. We propose that each of the three helix layers plays a critical role in the productive delivery of the catalytic domain to the cell cytosol.      

Increased number of cardiomyocytes in cross-sections from tachycardia-induced cardiomyopathic hearts

Based on positive identification of DNA replication and mitotic division in cardiomyocytes isolated from failing hearts, it has been proposed that adult ventricular cardiomyocytes can gain the capacity to proliferate with progression of heart failure. However, due to the lack of a reliable method to distinctly image individual cardiac cells within the myocardial syntitium, such a concept still remains largely controversial. In the present study, we used laser confocal microscopy, to image cross-sections of intact myocardium stained with fluorescein-conjugated wheat germ agglutinin and propidium iodide. This approach allowed to clearly separate the profile of individual myocytes within cardiac tissue sections. We found that in the left ventricles of dogs, subjected to tachycardia-induced cardiomyopathy, the number of cells was significantly increased in both longitudinal and transversal sections. Treatment with the angiotensin-converting enzyme inhibitor, enalapril, reversed these changes to values similar to those found in controls. Therefore, this study provides evidence, at the in situ level, for cellular hyperplasia in heart failure. This supports the more general notion that adult cardiomyocytes may not be terminally differentiated, and that an increase in cell number could contribute to the increase in left ventricular mass observed with progression of disease.