Risk factors for late-onset cytomegalovirus disease in donor seropositive/recipient seronegative kidney transplant recipients who receive antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) disease occurs frequently after cessation of antiviral prophylaxis in CMV-seronegative kidney transplant recipients from seropositive donors (D+R-), and the risk factors are incompletely defined. METHOD: We retrospectively assessed the incidence, clinical features, and risk factors for CMV disease in a cohort of D+R- kidney transplant recipients who received antiviral prophylaxis at a single US transplant center using descriptive statistics and Cox proportional hazards models. RESULTS: CMV disease developed in 29 of 113 (26%) D+R- patients at a median of 185 days (interquartile range 116-231 days) post transplant, including CMV syndrome (66%) and tissue invasive disease (34%). The incidence of CMV disease was higher in patients who underwent re-transplantation (57% vs. 24%) and this factor was independently associated with a higher risk of CMV disease in multivariable analysis (hazard ratio, 4.02; 95% confidence interval, 1.3-13; P = 0.016). Other demographic and transplant variables were not independently associated with a risk of late-onset CMV disease. CONCLUSIONS: Despite a comprehensive analysis of patient and transplant variables, only re-transplantation was identified as a risk factor for CMV disease in D+R- kidney transplant recipients who received antiviral prophylaxis, but had limited clinical predictive value. The development of novel laboratory markers to identify patients at greatest risk for CMV disease should be a priority for future studies.

Prophylactic amantadine dose and plasma concentration-effect relationships in healthy adults.

Amantadine dose, plasma concentration, prophylactic and adverse effect relationships for prevention of influenza A virus infection in healthy young adult subjects were investigated in a double-blind, placebo-controlled study. Seventy-four subjects with hemagglutination inhibition antibody titers less than or equal to 16 against an attenuated influenza A virus AF9/Montreal/3/72 (H3N2) were randomly allocated to groups taking 0 (placebo), 25, 100, or 150 mg amantadine syrup prophylactically twice a day for 31 doses. Eighteen other subjects were randomly allocated to control groups for investigation of drug toxicity (150 mg) or concurrent other virus infection (placebo). Steady-state trough plasma concentrations were 110 +/- 39, 302 +/- 80, and 572 +/- 207 ng/ml (X +/- SD) for the three amantadine doses and increased out of proportion to dose. Prophylaxis groups were challenged intranasally with virus after the fifth dose at steady state; control subjects received saline solution. No subject became ill. Input virus was recovered 48 or 72 hr after challenge from nose or throat swabs of nine of 21 subjects taking placebo, one of 18 subjects taking 100 mg amantadine, three of 18 subjects taking 25 mg amantadine, and six of 17 subjects taking 150 mg amantadine. There were no differences in seroconversion rates or adverse symptoms. Our data do not support a change in the recommended amantadine prophylactic dose for influenza A virus infection in healthy young adults. We defined trough steady-state plasma concentrations associated with the recommended amantadine dose of 100 mg twice a day that should be mimicked in devising dose schedules for populations with differing amantadine kinetics.

[Facing perinatal bereavement]. / Devant un deuil périnatal.

Pregnancy and childbirth are, for most women, wonderful and memorable experiences. Yet, without warning, they can have a heartbreaking outcome. Regardless of the stage of pregnancy at which a baby is lost, the family grieves the death. The authors of this article suggest how nurses can best support the couple, siblings, grandparents and significant others through their time of sorrow. The article highlights key points from the 1992 the Hôpital de Chicoutimi (Québec) reference guide entitled "Guide d'accompagnement des familles devant un deuil périnatal." The guide includes the types of grief and the six phases of grief resolution. It outlines specific nursing interventions and recommends various strategies for the nurse to help these families grieve their loss. Some strategies include the holding and cuddling of the baby by the parents, post-partum follow-up by nursing personnel and family therapy sessions. The authors suggest that nurses who are knowledgeable about the grief experiences of these parents will be better equipped to help other parents cope with similar grief. The increased knowledge will also assist nurses to sort out and deal with their own feelings on this subject. Nurses who are able to effectively care for these grieving families can often enhance their personal and professional self-esteem.

Live influenza vaccine: screening of attenuated virus strains by a 50% ciliary activity inhibition test in organ cultures of ferret trachea.

This study of three live attenuated inhibitor-resistant influenza vaccines showed that these preparations are usually antigenic and that they caused no significant reactions when characterized by an index of attenuation equal to or slightly better than 1.0 arbitrarily attributed to the 'reference' attenuated A/Hong Kong/68 strain of Beare and Bynoe. This index, measured in vitro on ferret tracheal rings, is expressed as the ratio of the time required for ciliary activity inhibition of 50% of the rings by the tested candidate vaccine strain and the 'reference' attenuated strain. Induction of heterologous antibodies was also observed. Oral administration of underattenuated perparations did not cause the severe reactions which were observed when the same vaccine was administered intranasally.

[Isolation of influenza viruses in different species of bird in Canada in 1978]. / Isolement de virus grippaux chez différentes espèces aviaires au Canada en 1978.

As part of the international program on the ecology of influenza virus in animals sponsored by W.H.O., 357 influenza A viruses isolated from 2 293 cloacal samples collected from ducks and other bird species in Eastern Canada during the 1978 season were characterized antigenically. Seven hemagglutinin (Hsw 1, H2, H3, Hav2, Hav4, Hav6, Hav7) and six neuraminidase subtypes (N1, N2, Neq2, Nav1, Nav5, Nav6) in 18 different combinations were found. A comparison with viruses isolated during previous seasons indicates that subtypes do change from year-to-year and from place-to-place. Isolation of few viruses from passerine birds requires additional studies to determine if these species are truly infected with influenza virus in nature. This large reservoir of influenza A viruses circulating at the same time in ducks may well be involved in the appearance of new viruses in other species, including humans.

Comparative sensitivity of counterimmunoelectrophoresis and double immunodiffusion tests for identification of influenza A viruses in birds isolates.

Fifty cloacal swab specimens which were found positive by haemagglutination after one or two passages in chicken embryonated eggs were examined for the presence of influenza A virus by counterimmunoelectrophoresis (CIE) and double immunodiffusion (DID) with anti-matrix and anti-nucleoprotein sera. CIE was as sensitive as DID with the anti-nucleoprotein serum and more sensitive with the anti-matrix serum when virus from allantoic fluid was concentrated with acid and disrupted with the detergent Sarcosyl. However, when the concentration step was by-passed and the virus was disrupted with Sarcosyl alone, CIE was substantially more sensitive. Forty-nine samples were positive for type A influenza with the anti-matrix serum and 37 with the anti-nucleoprotein serum. By DID, only 16 could be identified with the anti-matrix serum and none could be typed with the anti-nucleoprotein serum. Since CIE with anti-matrix serum is more sensitive than the DID tests, even with unconcentrated infected allantoic fluid, the CIE test is preferred for large-scale identification of influenze A virus in bird isolates.

Mouse response to influenza immunosomes.

Immunosome preparations consisting of surface glycoproteins, extracted from five influenza virus strains and anchored onto performed liposomes, were tested in mice. Serum antibody responses were essentially similar to those elicited by whole virus vaccines and higher than responses induced by subunit preparations. Antibody titres were assessed by haemagglutination-inhibition technique. Survival of mice immunized with 6 micrograms haemagglutinin of attenuated, inactivated, subunit or immunosome A/Aichi/2/68 vaccines and later challenged with variants of the same subtype was also assessed. All vaccine preparations induced similar percentage survival when mice were challenged with variants prevalent from 1968 to 1977. However, the attenuated vaccine induced a significant higher protection level against the 1979 variant.

Proprotein convertase PC1/3-related peptides are potent slow tight-binding inhibitors of murine PC1/3 and Hfurin.

The proprotein convertase PC1/3 belongs to the subtilisin/kexin-like endoprotease family and is synthesized as a preproenzyme. To investigate the function of its propeptide, murine proPC1/3 and preproPC1/3 were isolated from the inclusion bodies of recombinant preproPC1/3 baculovirus-infected insect cells, rendered soluble with 6 M guanidine HCl and 20 mM dithiothreitol, and purified by gel filtration and metal-binding affinity chromatography. Two NH2-terminal fragments containing the complete propeptide 1-84 region were obtained after CNBr cleavage, purified, and chemically characterized. Progress curve kinetic analysis with enzymatically active murine 71-kDa PC1/3 or 50-kDa human furin demonstrated that both fragments were potent slow tight-binding inhibitors of either enzyme with Ki in the low nanomolar range. Additional cleavages at Trp residues yielded fragment9-71, which no longer represents a potent inhibitor. Upon incubation at pH 5.5 in the presence of excess 71-kDa murine PC1/3, NH2-terminal fragment1-98 is cleaved at two sites, as revealed through Western blotting using NH2-terminal-directed PC1/3 antibodies. Finally, murine PC2 is inhibited by the proPC1/31-98 peptide, albeit at a much lesser extent with a micromolar Ki and in a strictly competitive manner. These results suggest that the proregion of PC1/3 is an important feature in regulating its activity.

Influenza viruses in birds: rapid identification by counterimmunoelectrophoresis.

Counterimmunoelectrophoresis with an antiserum raised in rabbits against the M protein of the avian N virus proved to be particularly useful for large-scale identification of influenza A virus isolates. Of a total of 231 hemagglutinating agents isolated from 1,656 rectal swabs collected from shore and open-country birds, 158 could be identified as influenza A viruses by counterimmunoelectrophoresis, and 75 were serologically related to Newcastle disease virus by hemagglutination inhibition with an antiserum to Newcastle disease virus. Two isolates contained a mixture of influenza A virus and Newcastle disease virus; although the Newcastle disease virus virus particles outnumbered the influenza A virus particles in a ratio of 1,000:1, as seen by electron microscopy, the latter could be readily detected by counterimmunoelectrophoresis. This type of assay appears to be of potential use for epidemiological surveillance of influenza virus isolated from humans and animals. It combines specificity, sensitivity, and simplicity.

Inhibition of ciliary activity in organ cultures of ferret trachea in reference to genetic and biological characters in influenza virus strains.

As reported previously, attenuated stable inhibitor-resistant influenza viruses can be screened by a 50% ciliary activity inhibition test in ferret tracheal organ cultures. This test was further applied to a 5 attenuated cold-adapted influenza strains and to 11 strains with known a percentage of RNA-RNA hybridization with the parental A/PR/8/34 (HON1) virus strain. Again, with one exception, attenuated strains could be clearly differentiated from virulent ones. It was concluded that virulence of influenza strains for man can be detected using this test regardless of the techniques used to prepare attenuated variants. A preliminary screening of attenuated candidates for live influenza vaccines can be achieved with confidence on ferret tracheal organ cultures.

Effect of anti-mouse macrophage serum on murine cytomegalovirus infection.

Rabbit anti-mouse macrophage serum (AMS) was used to study the role played by macrophages against murine cytomegalovirus infection. Treatment of mice with AMS enhanced morbidity and mortality following virus infection. These results are discussed in relation to the role of macrophages against virus infections.