Changes in bone remodeling rate influence the degree of mineralization of bone which is a determinant of bone strength: therapeutic implications.
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Adult↗
Biomedical subjects
G Boivin
Publications and source records attributed to G Boivin.
Mechanisms of action and therapeutic potential of strontium in bone.
The processes of bone resorption and formation are tightly governed by a variety of systemic and local regulatory agents. In addition, minerals and trace elements affect bone formation and resorption through direct or indirect effects on bone cells or bone mineral. Some trace elements closely chemically related to calcium, such as strontium (Sr), have pharmacological effects on bone when present at levels higher than those required for normal cell physiology. Indeed, strontium was found to exert several effects on bone cells. In addition to its antiresorptive activity, strontium was found to have anabolic activity in bone, and this may have significant beneficial effects on bone balance in normal and osteopenic animals. Accordingly, strontium has been thought to have potential interest in the treatment of osteoporosis. This review summarizes the mechanisms of action of strontium on bone cells, the evidence for its beneficial effects on bone mass in vivo, and its potential therapeutic effects in osteopenic disorders.
Animals↗
Molecular evolution of influenza A/H3N2 viruses in the province of Québec (Canada) during the 1997-2000 period.
In this study, we compared antigenic (hemagglutination inhibition (HI) assay) and molecular (sequencing of the hemagglutinin (HA1) gene) characterization of influenza isolates collected in the Province of Québec (Canada) during the last three flu seasons (1997-2000). Twenty-three isolates were tested by a standard HI assay and 37 by sequencing of the HA1 gene for their homology to the A/H3N2 vaccine strains A/Wuhan/359/95 (1997-1998) and A/Sydney/5/97 (1998-1999 and 1999-2000). By HI, two isolates were antigenically similar to A/Wuhan/359/95 (both from 1997 to 1998), 16 were similar to A/Sydney/5/97 (1997-2000) and no conclusions could be inferred for the other five isolates due to identical HI titers for the two vaccine strains (n=4) or insufficient viral titer (n=1). Sequence analysis revealed that four isolates from 1997 to 1998 were related to A/Wuhan/359/95 whereas the others (n=4) from 1997 to 1998, as well as all isolates from 1998 to 1999 (n=18) and 1999 to 2000 (n=11) were closer to A/Sydney/5/97. The mean number of amino acid differences for the 33 A/Sydney/5/97-like isolates compared with the homologous vaccine strain was 6.3 (1.9%), 9.2 (2.8%) and 13.6 (4.1%) for those collected in 1997-1998, 1998-1999, and 1999-2000, respectively. Phylogenetic analysis confirmed that a progressive drift occurred among our A/H3N2 influenza isolates over the last three flu seasons. Furthermore, it revealed that isolates collected during the last two flu seasons were in fact more related to A/Panama/2007/99 (2000-2001 vaccine strain) than to A/Sydney/5/97. Our studies suggest that molecular analysis of the HA1 gene should complement the HI assay for a more accurate analysis of influenza A virus drift.
Antigens, Viral↗
Incorporation and distribution of strontium in bone.
The distribution and incorporation of strontium into bone has been examined in rats, monkeys, and humans after oral administration of strontium (either strontium chloride or strontium ranelate). After repeated administration for a sufficient period of time (at least 4 weeks in rats), strontium incorporation into bone reaches a plateau level. This plateau appears to be lower in females than in males due to a difference in the absorption process. Steady-state plasma strontium levels are reached more rapidly than in bones, and within 10 days in the rat. The strontium levels in bone vary according to the anatomical site. However, strontium levels at different skeletal sites are strongly correlated, and the strontium content of the lumbar vertebra may be estimated from iliac crest bone biopsies in monkeys. The strontium levels in bone also vary according to the bone structure and higher amounts of strontium are found in cancellous bone than in cortical bone. Furthermore, at the crystal level, higher concentrations of strontium are observed in newly formed bone than in old bone. After withdrawal of treatment, the bone strontium content rapidly decreases in monkeys. The relatively high clearance rate of strontium from bone can be explained by the mechanisms of its incorporation. Strontium is mainly incorporated by exchange onto the crystal surface. In new bone, only a few strontium atoms may be incorporated into the crystal by ionic substitution of calcium. After treatment withdrawal, strontium exchanged onto the crystal is rapidly eliminated, which leads to a rapid decrease in total bone strontium levels. In summary, incorporation of strontium into bone, mainly by exchange onto the crystal surface, is dependent on the duration of treatment, dose, gender, and skeletal site. Nevertheless, bone strontium content is highly correlated with plasma strontium levels and, in bone, between the different skeletal sites.
Administration, Oral↗
Lack of emergence of cytomegalovirus UL97 mutations conferring ganciclovir (GCV) resistance following preemptive GCV therapy in allogeneic stem cell transplant recipients.
Fifty allogeneic stem cell transplant recipients were enrolled in a prospective cytomegalovirus pp65 antigenemia-guided preemptive therapy trial. Among these, 10 of 34 patients who received ganciclovir exhibited sustained and/or recurrent antigenemia despite treatment. Thirteen leukocyte preparations from these 10 subjects were screened for the presence of the most frequent cytomegalovirus UL97 mutations conferring ganciclovir resistance. None of these mutations were detected after mean and median ganciclovir exposures of 31.6 and 28.0 days, respectively.
Antigens, Viral↗
Evaluation of a rapid optical immunoassay for influenza viruses (FLU OIA test) in comparison with cell culture and reverse transcription-PCR.
The FLU OIA test was evaluated with 146 throat swab specimens from subjects with a flu-like illness in six Canadian clinics during the 1999-2000 flu season. The rate of positivity of the FLU OIA test (41.5%) was significantly lower than that of cell culture (55.2%) or reverse transcription-PCR (55.9%) during a season in which only influenza A virus was detected.
Adolescent↗
Highly reliable heterologous system for evaluating resistance of clinical herpes simplex virus isolates to nucleoside analogues.
Clinical resistance of herpes simplex virus (HSV) types 1 and 2 to acyclovir (ACV) is usually caused by the presence of point mutations within the coding region of the viral thymidine kinase (TK) gene. The distinction between viral TK mutations involved in ACV resistance or part of viral polymorphism can be difficult to evaluate with current methodologies based on transfection and homologous recombination. We have developed and validated a new heterologous system based on the expression of the viral TK gene by the protozoan parasite Leishmania, normally devoid of TK activity. The viral TK genes from 5 ACV-susceptible and 13 ACV-resistant clinical HSV isolates and from the reference strains MS2 (type 2) and KOS (type 1) were transfected as part of an episomal expression vector in Leishmania. The susceptibility of TK-recombinant parasites to ganciclovir (GCV), a closely related nucleoside analogue, was evaluated by a simple measurement of the absorbance of Leishmania cultures grown in the presence of the drug. Expression of the TK gene from ACV-susceptible clinical isolates resulted in Leishmania susceptibility to GCV, whereas expression of a TK gene with frameshift mutations or nucleotide substitutions from ACV-resistant isolates gave rise to parasites with high levels of GCV resistance. The expression of the HSV TK gene in Leishmania provides an easy, reliable, and sensitive assay for evaluating HSV susceptibility to nucleoside analogues and for assessing the role of specific viral TK mutations.
Acyclovir↗
Case study: rapid emergence of a cytomegalovirus UL97 mutant in a heart-transplant recipient on pre-emptive ganciclovir therapy.
A cytomegalovirus (CMV) strain containing a mutation in the UL97 gene (Leu595Ser), which is known to confer ganciclovir resistance, emerged rapidly in a heart-transplant recipient after 54 days of antigenaemia-guided ganciclovir therapy. The emergence of this viral mutant, while the patient was receiving oral ganciclovir 1000 mg three times daily, was associated with increasing CMV pp65 antigenaemia levels despite the re-instatement of intravenous ganciclovir 5 mg/kg twice daily. The antiviral regimen was then switched to intravenous foscarnet 90 mg/kg, administered either twice daily, once daily or every other day, which resulted in a rapid decrease of CMV antigenaemia levels and prevented the development of CMV-associated disease. Frequent monitoring of the CMV viral load and/or mutational studies are warranted in highly immunocompromised transplant recipients to prevent the development of CMV disease caused by ganciclovir-resistant strains.
Antiviral Agents↗
Predicting influenza infections during epidemics with use of a clinical case definition.
Combined pharyngeal and nasal swab specimens were collected from 100 subjects who presented with a flu-like illness (fever >37.8 degrees C plus 2 of 4 symptoms: cough, myalgia, sore throat, and headache) of <72 hours' duration at 3 different clinics in the province of Quebec, Canada, during the 1998-1999 flu season. The rate of laboratory-confirmed influenza infection was 72% according to cell culture findings and 79% according to the results of multiplex reverse-transcription polymerase chain reaction (RT-PCR) analysis (85%, influenza AH3; 15%, influenza B). All subjects for whom these results were discordant (negative culture and positive PCR) presented with a temperature > or =38.2 degrees C as well as 3 or 4 of the symptoms in the clinical case definition. Stepwise logistic regression showed that cough (odds ratio [OR], 6.7; 95% confidence interval [CI], 1.4-34.1; P=.02) and fever (OR, 3.1; 95% CI, 1.4-8.0; P=.01) were the only factors significantly associated with a positive PCR test for influenza. The positive predictive value, negative predictive value, sensitivity, and the specificity of a case definition including fever (temperature of >38 degrees C) and cough for the diagnosis of influenza infection during this flu season were 86.8%, 39.3%, 77.6%, and 55.0%, respectively.
Adult↗
Evaluation of the human herpesvirus 8 DNA load in blood and Kaposi's sarcoma skin lesions from AIDS patients on highly active antiretroviral therapy.
OBJECTIVES: To evaluate the human herpesvirus 8 (HHV-8) DNA load in peripheral blood mononuclear cells (PBMC) and Kaposi's sarcoma (KS) skin lesions of subjects with AIDS and to correlate these measures with the tumour load. DESIGN: Assessment of the HHV-8 DNA load was performed every 3 months in PBMC and every 6 months in KS skin lesions from seven subjects with AIDS who were receiving highly active antiretroviral therapy (HAART). METHODS: The HHV-8 DNA load was determined by a quantitative-competitive PCR using 0.2 microg of DNA from PBMC or KS skin biopsies. Staging of KS was performed by evaluating the number and type of cutaneous KS lesions. RESULTS: The three subjects with the most extensive and active (nodular) KS had the highest amounts of HHV-8 DNA in KS skin lesions and the lowest CD4 T cell counts (< 200 x 10(6)/l). In contrast, the four other subjects with regressing KS while on HAART had a low viral load in their KS lesions. All but one subject who also had multicentric Castleman's disease had low amounts of HHV-8 DNA in PBMC. CONCLUSION: There is a strong relationship between the tumour burden and the HHV-8 viral load in KS skin lesions of subjects with AIDS, reinforcing the causal link between this herpesvirus and AIDS-related KS.
AIDS-Related Opportunistic Infections↗
Human herpesvirus 8 infection of the genital tract of HIV-seropositive and HIV-seronegative women at risk of sexually transmitted diseases. Canadian Women's HIV Study Group.
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AIDS-Related Opportunistic Infections↗
Rapid antiviral effect of inhaled zanamivir in the treatment of naturally occurring influenza in otherwise healthy adults.
The antiviral and clinical effects of inhaled zanamivir (10 mg twice daily for 5 days, started within the first or second day of a flulike illness) were evaluated in a randomized, placebo-controlled trial during the 1997-1998 influenza season in Canada. Pharyngeal secretions were collected with swabs every 12 h during 6 days, and symptoms were self-evaluated twice daily during 14 days. After only 12 h of treatment (1 dose), median virus titers decreased by 1.0 log10 TCID50/mL in the zanamivir group (n=17), compared with a 0. 42-log10 increase in the placebo group (n=10; P=.08). This was associated with a 4.5-day (47.4%) reduction in the median time to alleviation of all significant flu symptoms in the zanamivir recipients (P=.03 after adjusting for the initial virus titer and the time between onset of symptoms and treatment). Resistance to zanamivir was not detected in virus isolates by either phenotypic or genotypic assays.
Administration, Inhalation↗
Clearance of cytomegalovirus viremia after initiation of highly active antiretroviral therapy.
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Adult↗
Quantitative analysis of cytomegalovirus (CMV) viremia using the pp65 antigenemia assay and the COBAS AMPLICOR CMV MONITOR PCR test after blood and marrow allogeneic transplantation.
The performance of a commercially available qualitative PCR test for plasma (AMPLICOR CMV Test; Roche Diagnostics) and a quantitative PCR test for plasma and leukocytes (COBAS AMPLICOR CMV MONITOR Test; Roche Diagnostics) was evaluated with samples from 50 blood or marrow allogeneic transplant recipients who received short courses of sequential ganciclovir therapy (2 weeks intravenously followed by 2 weeks orally) based on a positive cytomegalovirus (CMV) pp65 antigenemia (AG) assay. The number of persons with a positive CMV test was significantly higher for leukocyte-based assays (AG, 67.5%; PCR, 62.5%) compared to both quantitative and qualitative PCR tests of plasma (42.5 and 35%, respectively). One person developed CMV disease during the study despite a negative AG assay; in this particular case, all PCR assays were found to be positive 10 days before his death. There was a trend for earlier positivity after transplantation and more rapid negativity after initiation of ganciclovir for the tests performed on leukocytes. The mean number of CMV copies as assessed by PCR was significantly higher in leukocytes than in plasma (P = 0.02). Overall, excellent agreement (kappa coefficient, >0.75) was found only between the two PCR assays (qualitative and quantitative) based on plasma. These results suggest that either the pp65 AG assay or the COBAS AMPLICOR CMV MONITOR Test using leukocytes could be used to safely monitor CMV viremia in related allogeneic blood or marrow transplant recipients. Such a strategy will result in preemptive treatment for about two-thirds of the persons with a relatively low rate (<33%) of secondary viremic episodes following short courses of ganciclovir therapy.
Bone Marrow Transplantation↗
Geographical origin of an introduced pest species, Delia radicum (Diptera: anthomyiidae), determined by RAPD analysis and egg micromorphology.
The origin of introduction of the cabbage root fly, Delia radicum Linnaeus to the north-eastern coast of North America in the 19th century has been assumed to be from Europe. From that point of introduction, D. radicum gradually spread westward to occupy available ecological niches. DNA fingerprinting and egg micromorphology were used to determine the most likely geographical origin of the North American populations of this species. Forty-five informative RAPD loci obtained from ten primers and three criteria for egg micromorphology were studied. These characters indicated a common origin for the North American populations and a high similarity between populations from North America and north-western Europe. The results suggest a single entrance point of D. radicum into North America, probably via the north-eastern coast (New York area) from north-western Europe. The implications of this study in assisting selection of natural enemies of this important agricultural pest are discussed.
Animals↗
Recent advances in management of genital herpes.
OBJECTIVE: To provide an update on new diagnostic tests and antiviral strategies for managing genital herpes. QUALITY OF EVIDENCE: Treatment guidelines are based on randomized clinical trials and recommendations from the Expert Working Group on Canadian Guidelines for Sexually Transmitted Diseases. Recommendations concerning other aspects of managing genital herpes (e.g., indications for using type-specific serologic tests) are mainly based on expert opinion. MAIN MESSAGE: Genital herpes is one of the most common sexually transmitted diseases, affecting about 20% of sexually active people; up to 80% of cases are undiagnosed. Because of frequent atypical presentation and the emotional burden associated with genital herpes, clinical diagnosis should be confirmed by viral culture. Type-specific serologic assays are now available, but their use is often restricted to special situations and requires adequate counseling. New antivirals (valacyclovir and famciclovir) with improved pharmacokinetic profiles have now been approved for episodic treatment of recurrences and suppressive therapy. CONCLUSION: Wise use of new diagnostic assays for herpes simplex coupled with more convenient treatment regimens should provide better management of patients with genital herpes.
2-Aminopurine↗
Expression of the late cytomegalovirus (CMV) pp150 transcript in leukocytes of AIDS patients is associated with a high viral DNA load in leukocytes and presence of CMV DNA in plasma.
The expression of a late cytomegalovirus (CMV) transcript (pp150) was sought in peripheral blood leukocytes (PBL) of subjects with AIDS and correlated with the amounts of CMV DNA in PBL and plasma, by means of quantitative polymerase chain reaction (PCR). The detection of the late CMV transcript was associated with a high number of CMV DNA copies in PBL (P=.0015) and with a positive CMV PCR assay in plasma (P<.001). Expression of CMV pp150 mRNA was best predicted by viral DNA thresholds corresponding to 7058 and 30 copies in PBL and plasma, respectively. The detection of CMV pp150 mRNA was associated with the presence of CMV disease in a univariate analysis but not in a multivariate analysis after controlling for the viral DNA load in PBL. Thus, active viral replication as determined by a high CMV DNA load in PBL is reflected by expression of the late CMV transcript in the same cells and by the presence of CMV DNA in plasma.
AIDS-Related Opportunistic Infections↗