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Biomedical subjects

I Hardy

Publications and source records attributed to I Hardy.

At least 19 recordsLinked to original sources
PubMed2005

Resistance mechanism development to the topoisomerase-I inhibitor Hoechst 33342 by Leishmania donovani.

The bisbenzimidazole compound Hoechst 33342 (Ho342) has been identified as a specific Topoisomerase-I (Topo-I) inhibitor in mammalian cells. More recently, we have reported the ability of Ho342 to target L. donovani Topo-I, leading to parasite growth inhibition in vitro by mechanisms involving DNA breakage and apoptosis-like phenomenon. As the Ho342 lead molecule (2,5'-Bi-1H-benzimidazole) can be used as a starting structure for derivative compounds more effective against Leishmania, defining the Ho342 resistance mechanism(s) in Leishmania represents an important strategic tool. In the present study, we selected resistant parasites to Ho342 (LdRHo.300). While we observed an increase of the Topo-I gene expression correlated by a higher Topo-I DNA relaxation activity, the Topo-I genes (LdTOP1A and LdTOP1B) sequencing did not reveal any mutation for the resistant parasites. Moreover, our results on Ho342 cellular accumulation suggested the presence of a potential energy-dependent Ho342 transporter in the wild-type parasite, and that an alteration of this transporter has occurred in LdRHo.300, leading to an altered drug accumulation. Collectively, Ho342 resistance characterization provided results supporting that the resistance developed by LdRHo.300 involves complex mechanisms, most likely dominated by an altered drug accumulation, providing new insight in the Ho342 resistance mechanisms.

Animals↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Successful control of epidemic diphtheria in the states of the Former Union of Soviet Socialist Republics: lessons learned.

Epidemic diphtheria reemerged in the Russian Federation in 1990 and spread to all Newly Independent States (NIS) and Baltic States by the end of 1994. Factors contributing to the epidemic included increased susceptibility of both children and adults, socioeconomic instability, population movement, deteriorating health infrastructure, initial shortages of vaccine, and delays in implementing control measures. In 1995, aggressive control strategies were implemented, and since then, all affected countries have reported decreases of diphtheria; however, continued efforts by national health authorities and international assistance are still needed. The legacy of this epidemic includes a reexamination of the global diphtheria control strategy, new laboratory techniques for diphtheria diagnosis and analysis, and a model for future public health emergencies in the successful collaboration of multiple international partners. The reemergence of diphtheria warns of an immediate threat of other epidemics in the NIS and Baltic States and a longer-term potential for the reemergence of vaccine-preventable diseases elsewhere. Continued investment in improved vaccines, control strategies, training, and laboratory techniques is needed.

Adult↗
PubMed2000

Assessment of vaccination coverage among adults 30-49 years of age following a mass diphtheria vaccination campaign: Ukraine, April 1995.

Ukraine has been experiencing epidemic diphtheria since 1991. In efforts to control this epidemic, a mass vaccination campaign was held in April 1995. Persons not vaccinated in the previous 3 years were considered eligible for vaccination with tetanus-diphtheria toxoids (Td). Two cluster sample surveys were conducted to determine vaccination coverage achieved. In the urban and rural survey areas, respectively, 628 and 618 persons 30-49 years of age were interviewed. Fifty-nine percent of urban and 58% of rural participants were eligible for vaccination. During the vaccination campaign, 58% (95% confidence interval [95% CI], 47.1-69.2) of eligible persons received Td in the urban area, compared with 92% (95% CI, 89.2-95.3) in the rural area. Apparent barriers to vaccination included misconceptions about the safety, efficacy, and need for booster doses of Td. Future vaccination campaigns should include targeted information and education messages. Mass vaccination campaigns can be successful in vaccinating large numbers of adults; however, in urban areas, additional efforts may be required to achieve levels of coverage adequate to confer herd immunity and interrupt the diphtheria epidemic.

Adult↗
PubMed1997

Perioperative use of the oesophageal Doppler probe (ODM II) on a patient scheduled for transmyocardial revascularization.

We describe the use of the continuous wave oesophageal Doppler monitor (ODM II) in the perioperative management of a patient with chronic obstructive coronary artery disease undergoing transmyocardial revascularization (TMR). The use of ODM II allowed both quantitative and qualitative assessment of cardiac function relatively noninvasively. It detected the successful transmyocardial penetration of a laser beam during operation by visual and auditory phenomena in addition to reflecting improvement in cardiac performance after operation.

Cardiac Output↗
PubMed1992

Varicella vaccine: the American experience.

Live attenuated varicella vaccine is safe and effective in preventing chickenpox. The best immune responses occur in healthy children. Leukemic children have a 50% incidence of mild-to-moderate adverse effects but have a high degree of protection once immune reactions to varicella-zoster virus (VZV) have developed. Adult vaccinees have a lower degree of protection (70%) than children. Vaccinees who develop breakthrough varicella usually have a modified infection. Another significant advantage of vaccination is that in leukemic children it leads to a lower incidence of zoster than after natural chickenpox. It is possible to differentiate between vaccine-type and wild-type VZV using a combination of polymerase chain reaction and restriction endonuclease digestion. A new assay for antibodies to VZV measured by latex agglutination reveals that 8-10 years after vaccination antibodies are detectable in greater than 90% of leukemic children who have not had breakthrough varicella.

Adult↗
PubMed1992

Restriction fragment length polymorphism of polymerase chain reaction products from vaccine and wild-type varicella-zoster virus isolates.

The nucleotide changes that result in two restriction endonuclease polymorphisms that differentiate wild-type varicella-zoster virus (VZV) from the vaccine strain were determined. Oligonucleotide primers that flank these sites were used to amplify the intervening sequences with the polymerase chain reaction to identify VZV DNA in clinical isolates. Restriction enzyme digestion of the amplification products distinguished vaccine and wild-type genomes from one another. This study confirms the feasibility of amplifying VZV sequences so that they may be detected in clinical specimens and provides a molecular epidemiological approach to strain identification of VZV in vesicular lesions.

Base Sequence↗
PubMed1991

The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group.

BACKGROUND: The Oka strain of live attenuated varicella vaccine is immunogenic and highly protective, but there has been concern about the risk of zoster after immunization. METHODS: We examined the incidence of zoster, risk factors for it, and measures of immune response in children with leukemia who received the vaccine and in appropriate controls. RESULTS: After a mean follow-up of 4.1 years, zoster was documented in 13 of the 548 vaccinated children with leukemia (2.4 percent). In a subgroup of 96 vaccinated children matched prospectively with 96 children with leukemia who had had natural varicella infections, there were 4 cases of zoster among the vaccinated children and 15 among the controls, for crude incidence rates of 0.80 and 2.46 cases per 100 person-years, respectively (P = 0.01). Of the total of 13 vaccinated children who had zoster, 11 had a skin rash due to varicella-zoster virus, either from the vaccine itself or from breakthrough varicella after household exposure in the period between immunization and the documentation of zoster. In the 268 children who had any type of rash caused by varicella-zoster virus after vaccination, as compared with those who did not have a rash, the relative risk of subsequent zoster was 5.75. For the 21 vaccinated children who received bone marrow transplants, as compared with those who did not, the relative risk of zoster was 7.5. Cell-mediated immunity as assessed by lymphocyte stimulation was lower in 4 children in whom zoster later developed than in 29 controls who had been vaccinated but who did not have zoster (mean stimulation index, 5.1 vs. 23.8; P = 0.0001). CONCLUSIONS: In children with leukemia who receive the live attenuated varicella vaccine, the subsequent incidence of zoster is lower than in children who have natural varicella infections.

Antibodies, Viral↗
PubMed1990

Management of donors for heart and heart-lung transplantation.

The quality of donor organs will determine the quality of life for the recipient and the importance of optimal management of the multi-organ donor is that the organs may benefit up to five, critically ill, patients. The basic principle is to maintain sufficient preload to minimise the need for inotropic support and it is recommended that all multiple organ donors should have central venous and arterial pressure monitoring in addition to adequate venous access. The importance of the choice of fluid for volume expansion and the management of the hormonal disturbances which follow brain death are considered.

Brain Death↗
PubMed1988

Simultaneous therapy with high-dose cisplatin and radiation for unresectable squamous cell cancer of the head and neck: a phase I-II study.

Studies using simultaneous radiation therapy and conventional doses of cisplatin have suggested improvement in local control and patient survival. This study was undertaken to determine toxicity and patient tolerance to concomitant high-dose cisplatin (40 mg/m2 per day X 5) and radiation (60 Gy in 6 wk +/- 10-Gy boost to residual tumor). Seventeen patients with advanced, inoperable squamous cell cancer primary tumor in the head and neck were treated (15 males and 2 females; median age, 57 yr). Cisplatin was started on day 1 of radiation therapy and repeated every 28 days for three cycles. Normal saline infusion (250 ml/hr) was started 12 hours prior to the first dose and continued 12 hours after the fifth dose. The daily dose of cisplatin was dissolved in 250 ml of 3% NaCl and given over 30 minutes. The cisplatin dose for subsequent cycles was reduced 10 mg/m2 per day only for a nadir granulocyte count less than 500/mm3 or fever greater than 101 degrees F during leukopenia. Of the 17 patients who started therapy, 15 have completed therapy; 1 patient died after one cycle, and 1 died after two cycles. Eleven patients received three cycles of cisplatin, and 10 patients required one dose reduction (6 at course 2 and 4 at course 3). Seven possible infections were successfully treated. Grade 2 neuropathy occurred in 3 patients, and renal toxicity greater than grade 1 occurred in 1 patient. Additional toxic effects were median WBC count nadir of 1.8 X 10(3)/mm3, platelet count nadir of 128 X 10(3)/mm3, hemoglobin nadir of 9.8 g/dl, and median weight loss of 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗