Search PubMed⌕ Search

Biomedical subjects

L Kaiser

Publications and source records attributed to L Kaiser.

At least 19 recordsLinked to original sources
PubMed2001

Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir.

Volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) virus and treated with the neuraminidase (NA) inhibitor oseltamivir were monitored for the emergence of drug-resistant variants. Two (4%) of 54 resistant viruses were detected by NA inhibition assay among last-day isolates recovered from 54 drug recipients. They bore a substitution His274Tyr in the NA. Hemagglutinin (HA) variants detected in the placebo group differed from the egg-adapted inoculum virus by virtue of amino acid substitutions at residues 137, 225, or both. These variants had a higher affinity for Neu5Ac(alpha2-6)Gal-containing receptors, which are characteristic of human respiratory epithelium, than for Neu5Ac(alpha2-3)Gal-containing receptors, which are typical of chicken egg allantoic membrane. Although appearing to be more sensitive to oseltamivir in humans, the variants with increased affinity for Neu5Ac(alpha2-6)Gal receptors were less sensitive than the Neu5Ac(alpha2-3)Gal-binding variants in Madin-Darby canine kidney cells. Thus, HA affinity for receptors is an essential feature of influenza virus susceptibility to NA inhibitors, both in cell culture and in humans.

Acetamides↗
PubMed2001

Direct and indirect sublethal effects of Galanthus nivalis agglutinin (GNA) on the development of a potato-aphid parasitoid, Aphelinus abdominalis (Hymenoptera: Aphelinidae).

Snowdrop lectin (Galanthus nivalis agglutinin, GNA), has been shown to confer partial resistance to two potato aphids Myzus persicae and Aulacorthum solani, when incorporated in artificial diet and/or expressed in transgenic potato. First-tier laboratory-scale experiments were conducted to assess the potential effect of GNA on the aphid parasitoid Aphelinus abdominalis. GNA (0.1% w/v) was successfully delivered to Macrosiphum euphorbiae via artificial diet and induced a reduced growth rate and increased mortality compared to aphids fed a control diet. As aphid parasitoid larvae are endophagous, they may be exposed to GNA during their larval development and potential "chronic toxicity" on A. abdominalis was investigated. The amounts of GNA present in aphid and parasitoid tissues were estimated by western blotting. Results suggest that parasitoids excrete most of the GNA ingested. Sublethal effects of GNA on several parasitoid fitness parameters (parasitism success, parasitoid development and size, emergence success, progeny survival and sex ratio) were studied. No direct detrimental effect of GNA on A. abdominalis was observed. However, GNA had an indirect host-size-mediated effect on the sex ratio and the size of parasitoids developing in GNA-fed aphids. This work highlights the need to determine the exact "causes and effects" when assessing the ecological impact of transgenic plants on non-target beneficial insects. Such bioassays form the basis of a tiered risk assessment moving from laboratory studies assessing individuals towards field-scale experiments assessing populations.

Journal Article↗
PubMed2001

Clinical features of patients with acute respiratory illness and rhinovirus in their bronchoalveolar lavages.

BACKGROUND: Several reports in selected populations suggest that human rhinovirus (HRV) may be responsible for lower respiratory tract infections or pneumonia. We describe clinical features of all patients with rhinovirus cultured from their bronchoalveolar lavage (BAL) during a 10-yr period in a tertiary care center. METHODS: Results for viral culture of all lower respiratory specimens performed during a 10-year period at the University of Virginia Health Sciences Center were reviewed. A case was defined as any patient with a positive culture for HRV in a BAL specimen. A comprehensive review of the patients' medical records was performed. In one case, in situ hybridization (ISH) was performed in order to identify whether rhinoviral RNA was present in bronchial biopsy specimens. RESULTS: During the 10-year study period viruses were identified in 431 lower respiratory tract specimens, and were most frequently cytomegalovirus or herpes simplex virus. Twenty patients (ages, 2.5-86 year) had a bronchoalveolar specimen culture positive for HRV. All had an abnormal chest radiograph, 60% were admitted to the intensive care unit, and 25% expired during their hospitalization. In 18 patients (90%) various severe underlying conditions were identified including solid organ transplants in seven, malignancies in four and AIDS in two. An immunosuppressive disease or condition requiring immunosuppressive therapy was present in all cases. In addition to HRV, one or more potential pathogens were identified in respiratory specimens from 14 patients (70%). Histopathological abnormalities, ranging from fibropurulent debris in alveoli to diffuse alveolar damage, were present in 6 of 13 bronchial biopsies. In two cases without any other significant pathogens than HRV, acute inflammations with fibropurulent debris in alveoli were observed. One lung transplant patient showed intermittent recovery of HRV in her respiratory specimens during a 15-week time period, but ISH did not show HRV RNA in bronchial epithelial cells. CONCLUSION: Our observations suggest that HRV recovery from BALs or lower respiratory tract samples in highly immunocompromised patients is associated with severe lower respiratory tract illness. Whether HRV directly causes viral pneumonia or predispose to pulmonary injury and/or superinfection remains uncertain.

Academic Medical Centers↗
PubMed2001

The psychological effects of Hurricane Andrew on ethnic minority and Caucasian children and adolescents: a case study.

The impact of Hurricane Andrew on 212 African American, Caucasian, and Hispanic elementary and middle school children was examined at 6 months postdisaster. Using self-report instruments, this case study examined the predictive utility of several hypothesized mediators of children's reactions to disaster. Results showed higher levels of intrusive symptomatology for girls and for elementary school children as compared with their middle school counterparts. No differences were found with reference to race. The lack of findings concerning race is addressed, as well as implications for future studies.

Adolescent↗
PubMed2000

Impact of zanamivir on antibiotic use for respiratory events following acute influenza in adolescents and adults.

BACKGROUND: Influenza infections commonly lead to respiratory tract complications that result in antibiotic treatment. OBJECTIVES: To determine frequency of respiratory events leading to antibiotic use following influenza illness in adolescents and adults, and to assess whether treatment with topical zanamivir prevents these complications. METHODS: Meta-analysis of 7 randomized, double-blind, placebo-controlled trials; 3815 mainly healthy adolescents and adults (mean age, 34 years) with an influenzalike illness of less than 2 days' duration were randomly assigned to receive combined inhaled and intranasal zanamivir, inhaled zanamivir, or corresponding placebos. Twelve percent of enrolled subjects were high-risk patients. The main outcome was the incidence of respiratory events leading to antibiotic prescriptions in patients with proven influenza. RESULTS: Influenza infections were laboratory confirmed in 2499 (66%) of 3815 patients (influenza A in 88% and B in 12%). Placebo recipients developed a respiratory event leading to antibiotic use in 17% of cases, mainly for acute bronchitis or acute sinusitis. Among zanamivir-treated patients (n = 1494) the incidence of respiratory events leading to the use of antimicrobials was 11% (relative risk [RR] compared with placebo, 0.69; 95% confidence interval [CI], 0.57-0.84). Intranasal and inhaled zanamivir seemed to reduce the number of upper (RR, 0.59; 95% CI, 0.36-0.97) and lower respiratory tract events (RR, 0.64; 95% CI, 0.38-1.08). Inhaled zanamivir reduced the number of lower respiratory tract events (RR, 0.60; 95% CI, 0.42-0.85), but the reduction in the number of upper respiratory tract events was not statistically significant (RR, 0.90; 95% CI, 0.63-1.27). CONCLUSIONS: Respiratory complications or worsening of symptoms leading to antibiotic use occurred in about 17% of adolescents or adults with influenza infection. Early treatment of influenza illness with zanamivir reduced the number of these antibiotic prescriptions. Arch Intern Med. 2000;160:3234-3240.

Acute Disease↗
PubMed2000

Prevalence of heartworm infection in healthy cats in the lower peninsula of Michigan.

OBJECTIVE: To determine prevalence of heartworm infection among healthy, client-owned cats in the lower peninsula of Michigan. DESIGN: Cross-sectional prevalence study. ANIMALS: 1,348 healthy cats examined at private veterinary practices throughout the lower peninsula of Michigan. PROCEDURE: Sera were tested by use of an ELISA-based antigen test kit to determine infection and 2 commercially available antibody detection kits to determine exposure. A questionnaire was used to collect data to assess risk factors associated with infection. RESULTS: 25 cats had positive results for heartworm antigen, yielding an observed prevalence of 1.9%. Neither antibody test was reliable or provided reproducible results, and neither yielded positive results for more than 20% of the antigen-positive heartworm-infected cats. Multivariate regression indicated that cats from southeastern Michigan and cats > or = 2 years old had a higher risk of infection. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that most (80%) heartworm-infected cats in the lower peninsula of Michigan were from the southeastern part of the state, a pattern that closely paralleled the prevalence of heartworm infection in dogs. Therefore, knowledge of the regional prevalence of heartworm infection in dogs may be useful in assessing the risk of infection in cats. Results also suggested that currently available in-clinic heartworm antibody detection kits have limited utility in the diagnosis of heartworm infection in cats.

Animals↗
PubMed2000

[Parvovirus B19 infection in hydrops fetalis].

In a retrospective study from 210 foetal autopsies carried out in a period between 1992 and 1999 fifteen hydropic foetuses were found. The cause of the hydrops was shown to be Rh incompatibility in one case only. The cause of hydrops was not discernible in one case. In the others pathological examination clarified the cause and pathomechanism of non-immune hydrops. One isolated cystic hygroma, one monochorionic twin pregnancy with twin to twin transfusion, one case of sacrococcygeal teratoma and 4 cases of congenital heart diseases were reported. Postmortem interphase cytogenetic examination showed X0 monosomy in 2 cases. In further 4 foetuses pathognomic viral inclusions in the proerythroblasts raised the probability of parvovirus B19 infection what was confirmed by immunohistochemistry and electronmicroscopic examination. The occurrence of the parvovirus B19 associated cases of foetal hydrops was shown to be higher (4/15) in this series than in the literature. The accumulation of cases in 1998 is suggestive of an outbreak. The prenatal diagnostic implications and the attempts on further management are also discussed.

Adult↗
PubMed2000

Influenza virus neuraminidase inhibitors.

Neuraminidase promotes influenza virus release from infected cells and facilitates virus spread within the respiratory tract. Several potent and specific inhibitors of this enzyme have been developed, and two (zanamivir and oseltamivir) have been approved for human use. Unlike amantadine and rimantadine that target the M2 protein of influenza A viruses, these drugs inhibit replication of both influenza A and B viruses. Zanamivir is delivered by inhalation because of its low oral bioavailability whereas oseltamivir is administered by mouth. Early treatment with either drug reduces the severity and duration of influenza symptoms and associated complications. Both agents are effective for chemoprophylaxis. Because of a broader antiviral spectrum, better tolerance, and less potential for emergence of resistance than is seen with the M2 inhibitors, the neuraminidase inhibitors represent an important advance in the treatment of influenza.

Acetamides↗
PubMed2000

Time of initiation of antiretroviral therapy: impact on HIV-1 viraemia. The Swiss HIV Cohort Study.

OBJECTIVE: The current recommendation that patients infected with HIV-1 be treated early is based on little evidence. We examined whether the early initiation of antiretroviral treatment affects residual HIV-1 viraemia. METHODS: Viraemia was measured using an assay with a detection limit of 3 HIV-1 RNA copies/ml in drug-naive patients who started antiretroviral therapy at the time of primary HIV-1 infection (PHI) (n = 10), during chronic infection without immune suppression (CD4 cell counts > or = 500/mm3; median 577) (n = 10), or after immune suppression developed (CD4 cell counts < 500/mm3; median 113) (n = 21). RESULTS: In 249 samples collected 24 to 120 weeks after treatment initiation, the mean proportion of samples with HIV-1 RNA levels of less than 3 copies/ml was 75% for PHI patients compared with 32 and 8% for immunocompetent and immunosuppressed chronically infected patients, respectively. Fifty per cent of PHI patients, but none of the chronically infected patients, had persistently fewer than 3 HIV-1 RNA copies/mL. PHI patients had lower residual HIV-1 RNA levels than chronically infected patients, and immunocompetent patients had lower residual HIV-1 RNA levels than immunosuppressed patients (all pairwise, P< 0.001). The mean residual HIV-1 RNA level was independently associated with the initiation of therapy during PHI and baseline CD4 cell counts (P < 0.001 for both associations). CONCLUSION: Viraemia levels are associated with clinical progression and predict virological treatment failure. The initiation of antiretroviral therapy at the time of PHI and while CD4 cell counts are high results in lower residual viraemia. These results support early antiretroviral therapy in HIV-1-infected patients.

Anti-HIV Agents↗
PubMed2000

Correlation of prenatal clinical findings with those observed in fetal autopsies: pathological approach.

Our objective was to present a comprehensive description of the clinicopathological findings of 173 abortions, including 121 therapeutic and 52 spontaneous ones in the period between 1992 and 1998. In all of these fetuses pathological examination was carried out. It was complemented when indicated by immunohistochemistry, in situ hybridization, flow cytometry, and X-ray examination. In the 121 therapeutic abortions the distribution of malformations was: 45 central nervous system anomalies (37%), 12 genitourinary anomalies (10%), 25 gastrointestinal anomalies (21%), two respiratory system anomalies (1.65%), eight cardiac anomalies (6.6%) and 28 other anomalies (17.2%) as revealed by autopsy. From the clinically selected 52 spontaneous abortions, major malformations were seen in 15/52 cases. With the comparison of the pathological and clinical findings in 121 therapeutic abortions, the percentage of cases with correct clinical designation and no missed anomalies amounted for 49%. However in 51% additional or different lethal, severe, or major malformations were revealed or excluded by fetopathological examinations. In 4% the clinical observation and diagnosis were modified, but without implications for the therapeutic termination of pregnancy. The clinical indication could not be supported in another 3% of the cases.

Abortion, Spontaneous↗
PubMed2000

In vitro activity of pleconaril and AG7088 against selected serotypes and clinical isolates of human rhinoviruses.

BACKGROUND: We tested the in vitro activity of pleconaril and AG7088 against five numbered human rhinovirus (HRV) serotypes and 46 clinical HRV isolates of undefined serotype recovered from patients with common colds. Antiviral effect of pleconaril and AG7088 were assessed by cytophathic effect (CPE) inhibition assays in Ohio HeLaI cells using microscopic and spectrophotometric methods. Both compounds were tested at concentrations of 1.0, 0.1 and 0.01 microg/ml. For the numbered HRV serotypes, the median EC(50) value determined by the microscopic CPE inhibition was slightly better for AG7088 compared to pleconaril (P=0.02) but was similar by spectrophotometric assay (P=0.15). For clinical HRV isolates the median EC(50) value determined microscopically was 0.01 microg/ml range, <0.01-0.04 microg/ml) for AG7088 compared to 0.07 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). The median EC(50) value determined by spectrophotometric assay was 0.01 microg/ml (range, <0.01-0.04 microg/ml) for AG7088 compared to 0.04 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). By either the microscopic or spectrophotometric methods the median EC(50) value of AG7088 was <1.0 microg/ml for all isolates and was >10.0 microg/ml of pleconaril for approximately 9% of isolates. In vitro AG7088 appeared to be more potent and to have a broader antirhinoviral spectrum than pleconaril among clinical HRV isolates. The clinical relevance of these in vitro results needs to be determined in controlled clinical trials.

Antiviral Agents↗
PubMed2000

Short-term treatment with zanamivir to prevent influenza: results of a placebo-controlled study.

We explored the prophylactic activity of zanamivir after presumed exposure to influenza in the community. After close contacts with index cases of influenza-like illnesses, 575 subjects were randomized in 4 treatment groups: 144 received placebo, 141 received intranasal zanamivir, 144 received inhaled zanamivir, and 146 received inhaled plus intranasal zanamivir for 5 days. Of 25 subjects (4%) who developed symptomatic influenza during the 5 days of prophylaxis, 9 (36%) were in the placebo group, 8 (32%) were in the intranasal zanamivir group (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.30-2.72; P=.855), 3 (12%) were in the inhaled zanamivir group (OR, 0.27; 95% CI, 0.07-1.05; P=.058), and 5 (20%) were in the inhaled plus intranasal zanamivir group (OR, 0.52; 95% CI, 0.17-1.58; P=.247). Short-term treatment with intranasal zanamivir was ineffective. However, inhaled zanamivir treatment reduced the rate of influenza, which was 2%-3% among zanamivir recipients versus 6% among placebo recipients. Additional studies assessing a longer duration of postcontact prophylaxis are warranted.

Administration, Inhalation↗
PubMed2000

Developmental myosin heavy chains in the adult human diaphragm: coexpression patterns and effect of COPD.

In preliminary experiments we noted developmental (i.e., embryonic and neonatal) myosin heavy chains (MHCs) in the diaphragms of patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that this finding represented new fiber formation secondary to injury associated with the mechanical stress of COPD or previously undescribed MHCs in the human diaphragm. To distinguish between these possibilities, we analyzed diaphragmatic biopsies obtained from 9 patients with severe COPD (forced expiratory volume in 1 s = 21 +/- 2% predicted, residual volume = 283 +/- 22% predicted) and 10 age-matched controls. First, using immunocytochemistry with specific monoclonal antibodies, we noted that control diaphragms had greater proportions of fibers expressing embryonic (50 +/- 2 vs. 28 +/- 3%, P < 0.0001) and neonatal (52 +/- 2 vs. 32 +/- 3%, P < 0.001) MHCs than COPD diaphragms. Second, SDS-PAGE demonstrated that these developmental MHCs represented only a very small fraction of the diaphragmatic MHC content. Third, the RT-PCR demonstrated mRNA coding for embryonic and neonatal MHCs in COPD and control diaphragms. Last, COPD and control diaphragms exhibited normal histology on light microscopy. We conclude that the presence of developmental MHC isoforms does not indicate new fiber formation in diaphragms of patients with severe COPD. Although these results represent the first systematic description of embryonic and neonatal MHCs in normal adult human diaphragms, their function remains to be elucidated.

Adult↗
PubMed2000

[Symptoms and clinical and radiological signs predicting the bacterial origin of acute rhinosinusitis].

A minority of patients with common cold and upper respiratory tract infections have a bacterial infection and may benefit from antibiotic therapy. The present analysis set out to determine whether there were clinical symptoms or signs which could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis who are infected with pathogenic bacteria. Detailed clinical history and medical examination were obtained from 265 patients (mean age 35 years, 138 females and 127 males) presenting symptoms of upper respiratory tract infections but no fever above 38 degrees C. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae or M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Aggravating factors for severity of rhinosinusitis, such as severe nasal obstruction, inferior and/or middle turbinate hypertrophy, oedema of the middle meatus mucosa and septal defects, were not associated with the presence of bacteria. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms which were significantly associated in a multivariate model with the presence of bacteria included facial pain (p < 0.003), coloured nasal discharge (p < 0.003) and radiological maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening greater than 10 mm) (p < 0.002). This, the best predictive model, had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. We conclude that signs and symptoms of acute rhinosinusitis in patients with a mild to moderate clinical presentation are poor predictors of the presence of bacteria. In agreement with previous studies, culture of nasopharyngeal secretions may identify patients who would benefit from antibiotic treatment. Thus, antibiotic therapy should not be prescribed in the absence of bacteriological evidence.

Adolescent↗
PubMed1999

Transmission of antiretroviral-drug-resistant HIV-1 variants.

BACKGROUND: Resistance of HIV-1 to antiretroviral drugs is the main cause of antiretroviral-treatment failure. We assessed the transmission of drug-resistant variants among individuals with primary HIV-1 infection. METHODS: Population-based sequencing of the viral reverse-transcriptase and protease genes derived from plasma viral RNA was done in 82 consecutive individuals with documented primary HIV-1 infection from January, 1996, to July, 1998. Phenotypic resistance to protease inhibitors was assessed by recombinant virus assay in individuals with two or more mutations associated with resistance to protease inhibitors. FINDINGS: Zidovudine-resistance mutations were detected in seven (9%) of 82 individuals. Mutations associated with resistance to other reverse-transcriptase inhibitors (RTIs) were detected in two individuals. Primary-resistance mutations associated with protease inhibitors (V82A, L90M) were detected in three (4%) of 70 individuals; two of these had also RTI-resistance mutations. Decreased sensitivity to three or four protease inhibitors was seen in three individuals, one of whom was infected with HIV-1 variants that harboured 12 mutations associated with resistance to multiple RTI and protease inhibitors. INTERPRETATION: To introduce the best antiretroviral treatment, resistance testing should be done in recently HIV-1-infected individuals.

Adolescent↗
PubMed1999

Enteric infections and diarrhea in human immunodeficiency virus-infected persons: prospective community-based cohort study. Swiss HIV Cohort Study.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are at increased risk for diarrhea and enteric infections. We studied (1) the epidemiology of enteric pathogens associated with diarrhea, (2) the diagnostic yield of stool examination and endoscopic evaluation, (3) risks to develop diarrhea, and (4) the impact of diarrhea on patients' survival. METHODS: A total of 1933 participants in the Swiss HIV Cohort Study were prospectively followed up for a median of 25.5 months. A total of 560 diarrheal episodes were evaluated by standardized stool examination. Endoscopic evaluation was performed in 25% of patients with chronic diarrhea. RESULTS: The incidence of diarrhea was 14.2 per 100 person-years (95% confidence interval, 13.0-15.4). Among patients with CD4 cell counts below 0.05 x 10(9)/L, the probability to develop diarrhea within 1, 2, and 3 years was 48.5%, 74.3%, and 95.6%, respectively. The risk to develop diarrhea was increased among patients with severe immunodeficiency, homosexual men, and patients taking antiretroviral therapy. Pneumocystis carinii chemoprophylaxis did not reduce the risk of diarrhea. Diarrhea was an independent negative predictor of survival. Enteric pathogens were detected in 16.5% of 212 acute diarrheal episodes and in 46% of 348 chronic diarrheal episodes. The sensitivity of histological and stool examination was similar except for the diagnosis of intestinal cytomegalovirus infection and leishmaniasis, which required invasive evaluation. CONCLUSIONS: Intestinal infections were diagnosed in less than 50% of chronic diarrheal episodes. The prevalence of enteric pathogens tended to decrease during the observation period, possibly because of improved antiretroviral therapy. Endoscopic evaluation did not improve the diagnostic yield compared with stool examination except for the diagnosis of cytomegalovirus enteritis and leishmaniasis.

AIDS-Related Opportunistic Infections↗