Review and critical analysis of available in vitro dissolution tests.

The procedures recommended in Publications 30 and 66 by ICRP for calculating radiation doses from inhaled or ingested radionuclides include classification of material on the basis of different parameters, among which transportability plays a major role, The allocation of transportable Classes or absorption Types should, whenever possible, be based on animal or human data. However, when such in vivo data are unavailable, it becomes appropriate to consider the use of other approaches, among which in vitro dissolution techniques are reasonable alternatives. This paper reviews and critically analyzes in vitro dissolution techniques that have been described historically and recommends methods shown to be useful in estimating the in vivo solubility of radioactive particles.

Intracellular behaviour of uranium(VI) on renal epithelial cell in culture (LLC-PK1): influence of uranium speciation.

The main objective of this work was to assess the potentiality of in vitro models to study and understand the uranium-induced cytotoxicity on renal cells. Cytotoxicity and morphological studies were performed in a tubular proximal original established cell line (LLC-PK1 cell line). Dose-dependent cytotoxicity response was obtained with the uranium bicarbonate complex. In vitro experiments revealed a toxicity of uranium-bicarbonate complexes after a 24-h exposition and for concentrations ranging from 7 x 10(-4) M to 10(-3) M. In contrast, a lack of cytotoxicity of uranium(VI) citrate complexes studied using the same experimental conditions was noticed. Furthermore, electron transmission microscopy and X-ray microanalysis studies, after exposition of LLC-PK1 cells to the uranium-bicarbonate system ([U] = 8 x 10(-4) M) revealed that uranium entered into the cells and it was precipitated within the cytoplasmic compartment as uranyl phosphate needles. Similar morphological studies conducted with citrate complexes did not show any intake of uranium by LLC-PK1 cells. Experiments conducted in phosphate free culture medium showed that uranium was incorporated as a soluble material and that the association of the metal with phosphate ions occurred in the cytoplasmic compartment of LLC-PK1 cells.

Effect of aging on the amide group of bone matrix, measured by FTIR spectrophotometry, in adult subjects deceased as a result of violent death.

In order to determine the effects of age on bone quality, human bone tissue taken from adult subjects deceased from violent death was analyzed by means of fast Fourier transform infrared spectrophotometry (FTIR) in the Diffuse Reflectance mode (DR). This technique allows the characterization of both the mineral and organic parts of bone in a nondestructive manner. Only the organic part is discussed in this report. A quantitative change in the entire organic part of bone tissue is observed with the aging of subjects. The effects of these changes on bone strength were not measured.

Risk of Hepatitis A Infection among Young Travelers to Developing Countries: The Need for Vaccination.

In France, as in most industrialized countries, the seroprevalence of hepatitis A virus (HAV) infection decreases due to improvements in hygiene and sanitation, but is still frequent in developing countries.1 In a cohort of military recruits followed up in France, this rate fell from 50% in 1978 to 16% in 1994.2 It is likely, therefore, that young travelers from industrialized countries would not have prior immunity and would be more susceptible to HAV infection when visiting endemic areas.3 However, a safe and effective vaccine for hepatitis A has been available since 1992.4 To highlight the need for this vaccination in young people traveling to such countries, we report a cluster of cases of hepatitis A in a troop of French scouts after they visited a West African village.

Nifedipine and blood glucose in normal human volunteers.

The effect of nifedipine, a calcium antagonist on fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion was studied in healthy nondiabetic volunteers. Nifedipine 10mg twice daily for four weeks did not affect fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion.

Incidence and prognosis of cytomegalovirus infections following allogenic bone marrow transplantation.

The incidence and the outcome of cytomegalovirus (CMV) infections were evaluated in 83 adult recipients of allogenic bone marrow transplantation. Virological and serological surveillance was performed weekly for 3 months posttransplant, and then every other week or every month until 1 year. CMV infection occurred in 45 patients, with a cumulative risk of 62% at 1 year and 66% at 2 years. In multivariate analysis, two factors significantly influenced the incidence of CMV infection: patients with pretransplant positive anti-CMV titres had a risk of infection of 72% at 1 year versus 33% for patients with negative titres. Patients with acute myeloid leukemia were also infected more frequently (85% at 1 year) than patients with acute lymphoblastic leukemia (56%), chronic granulocytic leukemia (45%), or aplastic anemia (47%). In both univariate and multivariate analysis, CMV infection was not associated with a worse prognosis. However, 5 (out of 10) cases of lethal interstitial pneumonitis were associated with CMV, and two patients died of possible CMV encephalitis. All these patients had been suffering from severe acute or chronic graft versus host disease.

Prevalence of CMV ELISA antibody: titer and neutralizing activity in intramuscular immune globulin of placental origin.

The treatment of human CMV infection in transplant recipients by intravenous or intramuscular administration with high doses of hyperimmune or normal Ig showed inconsistent results. In fact, all hyperimmune Ig preparations were produced from high anti-CMV Ab titer plasma selected either by ELISA, complement fixation, or indirect hemagglutination test. These tests may not investigate the neutralizing activity of antibodies (Ab). We, therefore compared the ELISA titers with the neutralizing Ab titers in various normal Ig preparations from plasma or placenta and for intramuscular or intravenous use. Hyperimmune plasmatic Igs were also included. All the preparations were tested at a 5% dilution. We report the following data: (1) There is a poor correlation between ELISA and neutralization test. (2) The Igs of placental origin have significantly higher ELISA anti-CMV Ab titers than plasmatic normal Igs. They show the same neutralizing activity. (3) When compared with the normal intravenous Ig, normal intramuscular Igs show significantly higher titers with both techniques (P less than .0001). (4) Normal intramuscular Igs from placenta offer similar ELISA Ab titers and similar or higher neutralizing activity than hyperimmune Igs purified from plasma. It would be worth using Igs with high neutralizing activity in CMV prophylaxis in order to correlate in vitro tests and in vivo protection. In this respect, normal intramuscular Igs from placenta might be challenged in a clinical trial.

[Risk of transmission of cytomegalovirus infection from mother to newborn infant]. / Risque de transmission de l'infection à cytomégalovirus de la mère au nouveau-né.

A systematic prospective study of the incidence of cytomegalovirus (CMV) infection during pregnancy and contamination of the neonate was set up in a Maternity Hospital in Lyons. Over 7,000 pregnancies have been followed up since 1982 with serological and virological investigations. CMV infection was found in 5 p. 100 of patients. A urine collection was obtained at birth in 641 of the neonates. CMV was isolated in 16 cases and the transmission of the infection was studied with respect to the immune status of the mother. When CMV infection was demonstrated in the mother by serology and excretion of the virus, 45.5 p. 100 of babies were contaminated (10/22). In cases of reinfection, the incidence of neonatal contamination was 3.1 p. 100 (3/98). Ten of the 11 primary infections diagnosed were associated with viral excretion and the infection was transmitted to the child in 50 p. 100 of cases (5/10). The high incidence of transmission of CMV infection after a primary maternal infection supports data previously published by Stagno and Kumar in the U.S.A. and Ahlfors in Sweden.

[Immunological diagnosis of cytomegalovirus infections. Application to blood transfusion centers]. / Diagnostic immunologique des infections à cytomégalovirus. Application aux centres de transfusion sanguine.

The Blood Transfusion Centers (B.T.C.) are mainly concerned with the selection of CMV infection free blood donors, the screening of the anti CMV antibody high titre plasma donors and the evaluation of specific anti CMV Immunoglobulin preparations. Various serological methods could be used but they are of different value depending the purposes of the B.T.C. The neutralization test (Nt), with the addition of complement is specific and detects the protecting AB against the glycoproteins of the viral envelope. The complement fixation test (CF) using extracts of CMV infected cells as antigen largely varies in its sensitivity according to the quality of the antigen. In any case, the CF test is not sensitive enough to detect a latent CMV infection in a certain percentage of the non immunosuppressed adults, but could be used for the selection of anti CMV antibody high titres carriers. Three sensitive methods: passive haemagglutination, indirect immunofluorescence and indirect ELISA tests, might be used for the detection of latent CMV infections. They detect various AB against various internal and external components of the CMV. They are submitted to various sources of errors. The sensitivity of the indirect IF test is mainly restricted by the quality of the antigen preparation, its specificity by the presence of anti cells antibodies in the sera, the Fc receptors in the antigens and the specificity of the conjugates. The indirect ELISA which is submitted to the same causes of errors is a highly sensitive test, easy to perform, reagents are available, and automatic processors have been developed. When compared with the previous techniques, the ELISA test is suitable for the screening of CMV free donors, when it is performed with an highly sensitive antigen. It could be also used for the screening of high antibody titre carriers: its correlation with the CF test is quite good (r = 0,82). When comparatively applied to the titration of Immunoglobulins preparations, made from plasmas or placentas, for either IM or IV administration, the Elisa test gives AB titres different from those obtained with Nt and indirect IF. The calibration of a standard Immunoglobulin reagent is urgently needed and double blind clinical assays of the protective effect of various preparations of specific anti CMV Immunoglobulins have to be promptly designed.

[Clinical use of immunoglobulin titers of anti-cytomegalovirus antibodies]. / Utilisation clinique des immunoglobulines titrées en anticorps anti-CMV.

The frequency and severity of CMV infections in kidney, bone marrow, heart transplant recipients, in polytransfused patients, in immunodeficiencies and in newborns with congenital or peri-natal infection prompted clinical trials of immunoglobulins (Ig) with anti-CMV activity. Among the various methods for titrating Ig of plasmatic or placental origin, polyvalent or hyperimmune, ELISA would be the most sensitive assay and the neutralizing reaction might be the better reflection of a protective effect. In kidney transplantation, two non-randomized clinical trials have suggested a curative effect in association to other treatments, especially when given early. In bone marrow transplantation, three randomized studies have shown a prophylactic effect on incidence of symptomatic infections, interstitial pneumonias due to CMV, but only in seronegative patients not treated with leucocyte transfusions. No effect was observed on the time of infection, the survival of patients, the incidence of surinfections or graft versus host disease. The prophylactic effect of anti-CMV Ig in kidney and heart transplantation as well as in newborns has still to be documented in randomized trials. The possible clinical benefit for the patients and the mode of preparation of effective anti-CMV antibodies need further investigations.

[Necrotizing enterocolitis and cytomegalovirus infection (author's transl)]. / Entérocolite nécrosante et infection à cytomégalovirus.

During an 18-month period, 11 cases of necrotizing enterocolitis (NEC) were diagnosed in infants treated in Neonate Department. This represents 1% of total admissions. Six cases occurred during hospitalization. Clinically, the disease took three different forms: surgical form, medical form responding well to exclusive parenteral feeding and isolated haemorrhagic form, which deserves discussion. Seven of these infants had cytomegalovirus (CMV) infection. NEC accounted for 22% of clinical symptoms in CMV infection. These data suggest that the cytomegalovirus may act as aggravating factor in NEC.

[Comparative value of temperature marker and neutralization test for subtyping of herpes simplex viruses (author's transl)]. / Valeur comparée du marquage thermique et de la neutralisation pour le typage des virus de l'herpès simplex.

Two methods for the differentiation of herpes simplex virus (HSV)--rct and neutralization by specific antisera--have been applied to 8 prototype strains and 105 strains isolated from various clinical cases. The evaluation of the II/I index allows to choose the most specific rabbit antisera. The rct 40 degrees 3 C marker test gives comparable results for HSV grown in RK13 and human fibroblasts as well; it is in agreement with the immunological test in 48% of the cases. The delta tc values used to express the immunological typing allow to differentiate 76% of the strains (types 1 and 2). The others (24%) are equally neutralized by both specific antisera; they represent "intermediate" strains. The infection of man and animal by HSV (type 1, 2 or "intermediate") also produces heterospecific antibodies in variable amount. From clinical and immunological data rises the hypothesis that "intermediate" strains derive from HSV1 strains by antigenic variation during a persistent infection.