Validation of metastasis-free survival as a surrogate endpoint for overall survival in localized prostate cancer in the era of docetaxel for castration-resistant prostate cancer.

BACKGROUND: Prior work from the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) consortium (ICECaP-1) demonstrated that metastasis-free survival (MFS) is a valid surrogate for overall survival (OS) in localized prostate cancer (PCa). This was based on data from patients treated predominantly before 2004, prior to docetaxel being available for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). We sought to validate surrogacy in a more contemporary era (ICECaP-2) with greater availability of docetaxel and other systemic therapies for mCRPC. PATIENTS AND METHODS: Eligible trials for ICECaP-2 were those providing individual patient data (IPD) after publication of ICECaP-1 and evaluating adjuvant/salvage therapy for localized PCa, and which collected MFS and OS data. MFS was defined as distant metastases or death from any cause, and OS was defined as death from any cause. Surrogacy was evaluated using a meta-analytic two-stage validation model, with an R2 ≥ 0.7 defined a priori as clinically relevant. RESULTS: A total of 15 164 IPD from 14 trials were included in ICECaP-2, with 70% of patients treated after 2004. The median follow-up was 8.3 years and the median postmetastasis survival was 3.1 years in ICECaP-2, compared with 1.9 years in ICECaP-1. For surrogacy condition 1, Kendall's tau was 0.92 for MFS with OS at the patient level, and R2 from weighted linear regression (WLR) of 8-year OS on 5-year MFS was 0.73 (95% confidence interval 0.53-0.82) at the trial level. For condition 2, R2 was 0.83 (95% confidence interval 0.64-0.89) from WLR of log[hazard ratio (HR)]-OS on log(HR)-MFS. The surrogate threshold effect on OS was an HR(MFS) of 0.81. CONCLUSIONS: MFS remained a valid surrogate for OS in a more contemporary era, where patients had greater access to docetaxel and other systemic therapies for mCRPC. This supports the use of MFS as the primary outcome measure for ongoing adjuvant trials in localized PCa.

Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015.

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.

Handrubbing with sprayed alcohol-based hand rub: an alternative method for effective hand hygiene.

BACKGROUND: Hand hygiene is crucial in infection prevention and control. It is unclear whether sprayed alcohol-based hand rub (ABHR) is non-inferior to the World Health Organization (WHO)-recommended method of handrubbing with poured ABHR. AIM: To test whether sprayed ABHR can be an alternative (non-inferior) method for effective hand hygiene with/without handrubbing. METHODS: A laboratory experiment was conducted with ABHR (isopropanol 60% v/v) according to European Norm 1500. Hand hygiene was performed by: (1) handrubbing with ABHR poured on to the palm of the hand; (2) handrubbing with sprayed ABHR; and (3) applying sprayed ABHR to hands without handrubbing. Hands were contaminated with Escherichia coli ATCC 10536, followed by hand hygiene and microbiological sampling. A generalized linear mixed model with a random intercept per subject was used to analyse the reduction in bacterial count following hand hygiene. FINDINGS: In total, 19 healthcare workers participated in the study. Handrubbing with sprayed ABHR was non-inferior [margin log10 0.6 colony-forming units (cfu)/mL] to the WHO-recommended method of handrubbing with poured ABHR; bacterial count reductions were log10 3.66 cfu/mL [95% confidence interval (CI) 1.68-5.64] and log10 3.46 cfu/mL (95% CI 1.27-5.65), respectively. Conversely, non-inferiority was not found for sprayed ABHR without handrubbing [bacterial count reduction log10 2.76 cfu/mL (95% CI 1.65-3.87)]. CONCLUSION: Handrubbing with sprayed ABHR was non-inferior to handrubbing with ABHR poured on to the palm of the hand to reduce bacterial counts on hands under experimental conditions. Handrubbing with sprayed ABHR may be an acceptable alternative hand hygiene method pending assessment in other settings and for other pathogens.

Antibacterial efficacy of handrubbing for 15 versus 30 seconds: EN 1500-based randomized experimental study with different loads of Staphylococcus aureus and Escherichia coli.

OBJECTIVES: Compliance with the World Health Organization 'how to handrub' action is suboptimal. Simplifying the hand-hygiene action may improve practice. However, it is crucial to preserve antibacterial efficacy. We tested the non-inferiority of 15 versus 30 seconds handrubbing for Staphylococcus aureus and Escherichia coli contamination at different loads, using hand-size customized alcohol-based handrub (ABHR) volumes. METHODS: In an EN1500-based study, 18 health-care workers (HCWs) with extensive experience in hand hygiene rubbed hands with a hand-size customized volume of isopropanol 60% v/v. They repeated the following sequence: hand contamination (E. coli or S. aureus; broth containing 108 or 106 CFU/mL); baseline fingertips sampling; handrubbing (15 or 30 seconds); re-sampling. The main outcome was log10 CFU corrected reduction factor (cRF) on HCWs' hands, applying a generalized linear mixed model with a random intercept for subject. RESULTS: The median cRF was 2.1 log10 (interquartile range 1.50-3.10). After fitting the model, cRF was significantly higher for S. aureus compared with E. coli but there was no significant effect for duration of handrubbing or contamination fluid concentration. Fifteen seconds of handrubbing was non-inferior to 30 (-0.06 log10, 95% CI -0.34 to 0.22; EN1500 0.60 log10 non-inferiority margin). This was confirmed in all pre-specified subgroups. CONCLUSION: Among experienced HCWs using a hand-size customized volume of ABHR, handrubbing for 15 seconds was non-inferior to 30 seconds in reducing bacterial load, irrespective of type of bacteria or contamination fluid concentration. This provides further support for a shorter, 15-seconds, hand-hygiene action.

Reexpression of the original tumor pattern by a human breast carcinoma cell line (MCF-7) in sponge culture.

A stable cell line (MCF-7), derived from a pleural effusion of a patient with metastatic breast carcinoma, was maintained in these laboratories for more than 3 years in conventional monolayer culture. To further characterize the tumor origin of the MCF-7 line, cells were grown on collagen-coated cellulos sponges. On the three-dimensional sponge matrix, the cells formed clusters, ductlike structures, and lumina similar to the patterns observed in the antecedent primary tumor and in the pleural metastasis. The similarity between the original tumor and the cells grown in sponge suggested that the MCF-7 cells did in fact retain the potential to express the histologic patterns of tumor, even in the absence of stroma support. This study confirmed the utility of sponge culture for the investigation of the retention of tumor characteristics by cultured cells of neoplastic origin.

Xenograft model of progressive human proliferative breast disease.

BACKGROUND: Progression of proliferative breast disease has been associated with increased risk for development of invasive carcinoma. Cell lines have been developed to facilitate the study of this process. Human cell line MCF10A originated from spontaneous immortalization of breast epithelial cells obtained from a patient with fibrocystic disease, and cell lines MCF10AneoN and MCF10AneoT were created by stable transfection of these cells with the neomycin-resistance gene and either the HRAS gene or the mutated T-24 HRAS gene, respectively. PURPOSE: Our goal was to develop an experimental model of progressive human proliferative breast disease. METHODS: MCF10A, MCF10AneoN, and MCF10AneoT cells were injected subcutaneously into the dorsal flank of male nude/beige (C57/BALB/c nu/nu bg/bg) mice (12 mice for each cell type). These mice were examined periodically for formation and persistence or growth of palpable nodules. One mouse per group was killed 1 week after cell injection; thereafter, mice were observed as long as possible. Cells were recovered from palpable lesions by enzymatic dissociation of the excised lesions. Cells re-established in tissue culture from a week-14 tumor (MCF10AneoT.TG1) were injected into 12 male nude/beige mice. Southern blot hybridization analysis of the HRAS gene locus and cytogenetic analyses were performed. RESULTS: Transplanted MCF10A and MCF10AneoN cells formed transient, small palpable nodules that regressed and disappeared during the 4th and 5th weeks. In 10 of the 12 mice, T-24 HRAS gene-transfected MCF10A cells (MCF10AneoT) formed small, flat nodules that persisted for at least 1 year. Three of these xenografts became carcinomas. One (removed 7 weeks after transplantation) was an undifferentiated carcinoma composed of polygonal cells with large, vesicular nuclei and numerous mitoses. The second (removed after 14 weeks) was an invasive squamous cell carcinoma. The third (removed after 56 weeks) was a moderately differentiated adenocarcinoma. Initially, xenografts of MCF10AneoT.TG1 cells showed intraductal proliferative changes; after 23 weeks, the lesions showed histologic features resembling those seen in atypical hyperplasia of the human breast, and later lesions showed characteristics of carcinoma in situ. The MCF10 lineage of cells of three MCF10AneoT.TG1 xenografts was confirmed by DNA fingerprinting and karyotype analysis. CONCLUSIONS: MCF10AneoT and MCF10AneoT.TG1 comprise a transplantable xenograft model that produces a broad spectrum of human proliferative breast disease. IMPLICATIONS: The reproducible establishment of representative stages in early breast cancer progression from the MCF10 model offers a new opportunity to analyze critical events of carcinogenesis and progression in breast cancer.

Phenotypic variance among cells isolated from spontaneous mouse mammary tumors in primary suspension culture.

A method is given for selecting epithelial cells directly from primary mammary tumors in Methocel suspension culture. The frequency of colony-forming units in primary tumors was approximately 10(-4). Colonies grew by cell division; formation and growth of colonies was cell density dependent. Five Methocel isolates were established in monolayer culture and characterized. Two were epithelial, evidenced by functional occluding junctions. The other three were not typed in vitro, although they formed carcinomas in vivo. All were subtetraploid by passage 10. There were variations in ability of the five Methocel isolates to reclone in suspension that appeared to be due to the evolution of anchorage-dependent variants during their growth in monolayer culture. These variants could be purified by limiting dilution plating on solid substrates. The five Methocel isolates and their derivative variants were used to determine correlations between transformation markers and tumorigenicity. Only three Methocel-derived sublines of nine tested, including two recloned in Methocel, were tumorigenic at all when inoculated in two sites of three syngeneic hosts, one athymic. The other six were nontumorigenic. The tumorigenic sublines were less tumorigenic than uncultured cells of parent tumors or parent tumor cells grown in primary monolayer culture. Thus, anchorage-independent growth is not a reliable marker for the tumorigenic mammary phenotype. No correlation was found between two other "contact-related" transformation markers, rapid growth rate and monolayer overgrowth, and tumorigenicity. The three transformation markers were expressed independently. Both tumorigenic and nontumorigenic sublines expressed mammary tumor virus antigens M.W. 28,000 protein and M.W. 52,000 glycoprotein, although only a minor fraction of cells contained the M.W. 52,000 glycoprotein. These data emphasize the heterogeneity of phenotypes in mammary tumors as well as differences between fibroblasts and mammary epithelium in models of neoplastic transformation.

Ultrastructural and immunocytochemical characterization of an immortalized human breast epithelial cell line, MCF-10.

The human breast epithelial cell line MCF-10 was derived from s.c. mastectomy tissue from a 36-year-old, parous, premenopausal woman with fibrocystic disease. It was initiated as a mortal cell line (MCF-10M), which senesces when transferred serially in 1.05 mM calcium. These cells spontaneously gave origin to two immortal sublines, MCF-10A, or attached cells, and MCF-10F, or floating cells, which have proliferated for more than 4 years in Dulbecco's modified essential medium and Ham's F-12 either with the customary calcium concentration of 1.05 mM (DMEM-H) or in medium containing 0.04 mM calcium or low calcium. Studies reported here indicate that MCF-10 is a mammary epithelial cell line. Electron microscopy showed that both MCF-10A and MCF-10F have characteristics of luminal ductal cells, but not of myoepithelial cells. When grown for more than 1200 days in Dulbecco's modified essential medium-Ham's F-12 and low calcium media, respectively, they maintained their epithelial characteristics, although the concentration of calcium exerted a powerful influence on cell morphology. Cells grown in Dulbecco's modified Eagle's medium-Ham's F12 medium are low cuboidal with numerous desmosomes and short microvilli, whereas those grown in low calcium medium have significantly reduced number of desmosomes, are more spherical, and have greater numbers of microvilli which are longer than those of cells grown in DMEM-H. The breast epithelial orgin of these cells was confirmed by immunocytochemical detection of epithelial sialomucins and keratins. The monoclonal antibodies MFA-breast and MC5 and the polyclonal antibody epithelial membrane antigen were used to detect the epithelial sialomucins. Keratins were characterized by using KA-4, K-14, AE1/AE3, and K-19 specific antibodies. It was concluded that MCF-10A and MCF-10F cells are breast epithelial cells and that they represent an important tool for studies of the basic processes of growth and carcinogenesis.

Nuclear matrix proteins in normal and breast cancer cells.

The progression from normal breast epithelium to a malignant phenotype may depend on changes in genetic events as well as failure of host mechanisms. Intermediate biomarkers are needed to more effectively identify malignant progression as well as to develop the potential for more specific treatments and prevention strategies. The nuclear matrix is the RNA-protein network which forms the skeleton of the nucleus and participates in DNA organization as well as multiple cellular functions. Nuclear matrix proteins have been demonstrated to be tissue and cell type specific as well as to reflect the state of cell differentiation and/or transformation. We prepared nuclear matrices from normal and cancer breast tissue from 10 patients with infiltrating ductal carcinoma of the breast as well as the MCF-10 mortal, immortal, and transfected breast cell lines. Nuclear matrices derived from normal human breast tissue and tumor tissue share common nuclear matrix proteins as well as demonstrate specific changes which appear to occur with the acquisition of the cancer phenotype. The MCF-10 cell lines demonstrate a phenotype that is intermediate between the normal and cancer tissue. These data suggest that the nuclear matrix may be an important biomarker in the pathogenesis of breast cancer.

Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10.

Two sublines of a breast epithelial cell culture, MCF-10, derived from human fibrocystic mammary tissue exhibit immortality after extended cultivation in low calcium concentrations (0.03-0.06 mM) and floating transfers in low calcium (MCF-10F), or by trypsin-Versene passages in the customary (normal) calcium levels, 1.05 mM (MCF-10A). Both sublines have been maintained as separate entities after 2.3 years (849 days) in vitro and at present have been in culture for longer than 4 years. MCF-10 has the characteristics of normal breast epithelium by the following criteria: (a) lack of tumorigenicity in nude mice; (b) three-dimensional growth in collagen; (c) growth in culture that is controlled by hormones and growth factors; (d) lack of anchorage-independent growth; and (e) dome formation in confluent cultures. Cytogenetic analysis prior to immortalization showed normal diploid cells; although later passages showed minimal rearrangement and near-diploidy, the immortal cells were not karyotypically normal. The emergence of an immortal culture in normal calcium media was not an inherent characteristic of the original tissue from which MCF-10 was derived since reactivated cryo-preserved cells from cultures grown for 0.3 and 1.2 years in low calcium were incapable of sustained growth in normal calcium.

Sequential imaging of indium-111-labeled monoclonal antibody in human mammary tumors hosted in nude mice.

Using a bifunctional chelating agent, indium-111 was attached to a monoclonal antibody 10- 3D2 , specific for a 126-kilodalton phosphoglycoprotein antigen associated with human mammary carcinoma, and was then used to localize and visualize human mammary tumors hosted in nude mice. Simultaneous tumor concentration of In-111-10- 3D2 was eight times greater than that of control I-125-MOPC-21. Uptake of F(ab')2 and Fab of 10- 3D2 was also compared. the scintigrams demonstrated that intact antibody provided the best images. Control In-111-labeled MOPC-21 and plasma did not show specific localization in the tumor. Uptake of In-111-labeled 10- 3D2 was also compared in two lines of human mammary tumors, BT-20 and HS- 578T . Imaging with 10- 3D2 was better for BT-20 than for HS- 578T . These studies demonstrated that (a) In-111-10- 3D2 can be utilized to image human mammary tumors hosted in nude mice; (b) intact antibody provided the best tumor images, although F(ab')2 had optimal target-to-background ratios for earlier imaging; and (c) different mammary tumor lines with possibly different concentrations of tumor-associated antigen showed different rates of uptake and apparent saturation with 10- 3D2 .

Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa.

Gram-negative sepsis is oftentimes complicated by activation of coagulation with disseminated intravascular coagulation and microthrombosis. This may contribute to the associated morbidity, multiple organ failure and death. Recent studies have established that the tissue factor-dependent pathway of blood coagulation has a significant participatory role in the initial endotoxin-induced activation of coagulation. Tissue factor (TF), expressed on the surface of activated monocytes and endothelial cells forms cell surface complexes with free circulating factors VII and VIIa. The latter complex proteolytically activates factors X and IX. Recent in vivo experiments have shown that a rapidly neutralizing TF monoclonal antibody prevents and arrests the endotoxin-induced activation of coagulation and similar studies have shown to reduce mortality in baboons. In this study we describe the preparation of a factor VII/VIIa neutralizing monoclonal Fab fragment and characterize its effect on in vivo activation of coagulation during experimental endotoxemia in chimpanzees. Four chimpanzees received a bolus intravenous injection of 4 ng/kg endotoxin in combination with Fab fragments of a factor VII/VIIa neutralizing murine monoclonal antibody (12D10) at a dose of either 50 micrograms/kg (n = 2) or 100 micrograms/kg (n = 2). Four control animals received a bolus injection of endotoxin alone. Administration of the 12D10 Fab fragments, immediately preceding the endotoxin bolus injection, effectively blocked the endotoxin-induced activation of coagulation. Plasma levels of products of in vivo activation, namely F1 + 2, TAT complexes and FpA remained at baseline values. The administration of 12D10 resulted in a rapid decline in factor VII/VIIa antigen levels which remained below 5 ng/ml for 180-240 min, followed by a rapid return to baseline levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen responsive proliferation of clonal human breast carcinoma cells in athymic mice.

A clone of MCF-7 (MCF-7ED), a cell in continuous in vitro cultivation derived from an estrogen-responsive human breast carcinoma, requires estrogen supplementation for progressive exponential (double time: 50--85 h) tumor growth in the mammary fat of athymic mice. The plasma concentration of estradiol which stimulated exponential growth of MCF-7ED corresponded to physiologic premenopausal levels in women. The tumors were carcinomas with murine and MCF-7ED cells intermixed. MCF-7ED cells could be repurified in subcultures of mixed tumors. Comparative studies of breast and non-breast cell lines showed concordance between the presence of estradiol receptor, sensitivity to the anti-estrogen tamoxifen for growth in vitro, and estradiol dependence for tumorigenic growth in athymic mice. Progesterone alone did not stimulate MCF-7ED growth, but acted synergistically with estrogen. Progesterone's action was to decrease tumor latent period, not to increase final tumor incidence or growth rate. Under estrogen-deficient conditions, condsitions approximating postmenopausal status in women, (10(-10) M in plasma), a dormant state was established between MCF-7ED cells and murine mammary stroma which could be maintained several months. The dormant state could be broken by introduction of estradiol, but not progesterone. This system should be useful for defining host and cancer cell determinants in estrogen-responsive breast cancer growth.

Solid wastes from nuclear power production.

Radioactivity in nuclear power effluents is negligible compared to that in retained wastes to be disposed of as solids. Two basic waste categories are those for which shallow disposal is accepted and those for which more extreme isolation is desired. The latter includes "high level" wastes and others contaminated with radionuclides with the unusual combined properties of long radioactive half-life and high specific radiotoxicity. The favored method for extreme isolation is emplacement in a deep stable geologic formation. Necessary technologies for waste treatment and disposal are considered available. The present program to implement these technologies is discussed, including the waste management significance of current policy on spent nuclear fuel reprocessing. Recent difficulties with shallow disposal of waste are summarized.

A natural glycoprotein inhibitor (NIF) of CD11b/CD18 reduces leukocyte adhesion in the liver after hemorrhagic shock.

This study was designed to assess the effect of neutrophil inhibitory factor (NIF), a novel specific inhibitor of CD11b/CD18 on hepatic leukocyte trafficking by intravital microscopy 5 h after hemorrhagic shock. Anesthetized rats were instrumented for invasive hemodynamical monitoring. Hemorrhagic shock was induced for 60 min by withdrawal of arterial blood (mean arterial blood pressure = 40 mmHg). Rats were adequately resuscitated for 5 h to achieve a mean arterial blood pressure > 100 mmHg and were randomly assigned to blinded treatment with NIF or placebo control protein administered as a single intravenous bolus (10 mg/kg) at the time of resuscitation. Intrahepatic leukocyte adhesion was evaluated by in vivo fluorescence microscopy. There were no significant differences observed in hemodynamic parameters between the shock groups throughout the study, however, NIF significantly reduced firm leukocyte adhesion in liver sinusoids. The results suggest that NIF may be beneficial in the attenuation of the pathological shock-induced leukocyte adhesion.

Monitoring rotavirus environmental contamination in a pediatric unit using polymerase chain reaction.

Rotavirus environmental contamination in a pediatric unit was investigated. Surfaces were swabbed, then viruses eluted, ultracentrifuged, and detected by polymerase chain reaction (PCR) amplification. Of 55 samples, 25 (46%) tested positive. Rotavirus RNA was more prevalent on surfaces in direct contact with children (thermometers and play mats) than on other environmental surfaces (washbasins, door handles, etc). PCR has proved useful for monitoring rotavirus environmental contamination.

Transforming and oncogenic potential of activated c-Ha-ras in three immortalized human breast epithelial cell lines.

The ability of activated c-Ha-ras (codon 12 valine) to transform human breast epithelial cells varied for three different immortalized normal human breast epithelial cell lines established from two different women. Although activated c-Ha-ras may transform and induce a preneoplastic phenotype in MCF10A cells, activated c-Ha-ras was not sufficient to transform MCF10-2A cells. Only two of three MCF10-2A clones which expressed mutant p21 protein acquired the ability to form colonies in soft agar. When xenografted into nude beige mice, two MCF10-2A clones formed squamous carcinomas and one formed no lesions at all. The ability to form tumors did not correlate with growth in soft agar. All three activated c-Ha-ras-transfected clones of MCF-12A formed colonies in soft agar but only two produced squamous carcinomas in nude beige mice. Unlike activated c-Ha-ras-transfected MCF10A cells, none of the activated c-Ha-ras-transfected MCF10-2A or MCF-12A clones formed ducts in xenografts. Rather, initial xenograft lesions consisted of nests of cells with squamous differentiation. These observations illustrate that additional events are involved in the transformation and progression of human breast epithelial cells with activated c-Ha-ras.

[Virus resistance in a hospital environment: overview of the virucide activity of disinfectants used in liquid form]. / Résistance des virus dans l'environnement hospitalier: le point sur l'activité virucide des désinfectants utilisés à l'état liquide.

Human pathogenic viruses can be detected in the hospital environment, on contaminated surfaces or medical instruments. Their transmission to patients or staff has already been reported. Lipophilic viruses (HIV, HBV, HCV,...) are susceptible to many liquid chemicals, but they can survive during short time on inadequately disinfected surfaces. Hydrophilic viruses, without envelope, are more resistant, but generally not associated with severe illnesses. Viruses survival in environment depends on many factors and is always improved with viral aggregation and low temperature, whereas organic matters and relative humidity effects are contrasted. The mechanism of virucide disinfectants is not yet well established, and their targets are not known with precision. Different disinfection procedures (disinfectant concentration, contact time, temperature, pH) can provide a similar virucidal activity on a given virus. The virucidal activity of a disinfectant is evaluated with a cell culture assay in Afnor guidelines. But, there are three major problems with this method, concerning need of high viruses titers, residual disinfectant cytotoxicity on cell culture, and non cultivable viruses. Non standardized tests are also described in papers, but their results can generally not be compared. Molecular biology improvements may lead to reproducible and sensitive tests. At present, no general disinfection procedure effective for most of the viruses, without risks for staff or materials, and with an acceptable economic cost can be recommended.