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Biomedical subjects

S Holte

Publications and source records attributed to S Holte.

17 recordsLinked to original sources

Kinetics of hepatitis B viral load during 48 weeks of treatment with 600 mg vs 100 mg of lamivudine daily.

Oral therapy for chronic hepatitis B remains suboptimal. Mathematical modelling of viral decay kinetics to rapidly assess potential antiviral regimens has proved valuable for human immunodeficiency virus and cytomegalovirus. We defined the kinetics of viral replication in 10 chronic hepatitis B patients randomized to lamivudine 100 mg vs 600 mg for 48 weeks. Viral decay kinetics conformed to a biphasic pattern in nine of 10 subjects. Persons receiving 600 mg daily of lamivudine exhibited a 1.6-fold faster decay rate in the infected cell compartment (0.028/day vs 0.017/day, P = 0.06) and a greater overall change in serum viral load when compared with those receiving 100 mg (4.06 vs 1.52 log(10) copies/mL, P = 0.08). More potent therapy appeared to result in more rapid decrease in the infected cell population. Studies using mathematical modelling of viral decay may be a useful method to evaluate single or combination therapy for HBV infection in vivo.

Adult↗

Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment.

HIV-1-infected patients treated early with combination antiretrovirals respond favorably, but not all maintain viral suppression and improved HIV-specific Th function. To understand if genetic factors contribute to this variation, we prospectively evaluated over 18 months 21 early-treated patients stratified by alleles of class II haplotypes. All seven subjects with the DRB1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus suppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher mean lymphoproliferation and IFN-gamma secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were identified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 haplotype, have an important impact on virologic and immunologic responses. The advantage of the haplotype may relate to selection of key HIV-1 Th1 epitopes in highly conserved regions with avid binding to class II molecules. Eliciting responses to the promiscuous epitope region may be beneficial in vaccine strategies.

Acquired Immunodeficiency Syndrome↗

Readiness for HIV vaccine trials: changes in willingness and knowledge among high-risk populations in the HIV network for prevention trials. The HIVNET Vaccine Preparedness Study Protocol Team.

Longitudinal data were analyzed to determine changes in willingness to participate in HIV vaccine efficacy trials and knowledge of vaccine trial concepts among populations at high risk of HIV-1 infection. Gay men (MSM), male and female injection drug users, and non-injecting women at heterosexual risk were recruited (n = 4892). Follow-up visits occurred every 6 months up to 18 months. Willingness was significantly lower at follow-up visits compared with at baseline. Knowledge levels increased for all study populations. Problematic concepts were possible effects of the vaccine on the immune system and lack of knowledge about efficacy of a vaccine before the start of a trial. For concepts concerning safety, blinding, and guarantees of future participation in trials, MSM men had significant increases in knowledge, but little to no change occurred for the other populations. An increase in knowledge was associated with becoming not willing, particularly among MSM with low knowledge levels. At least half of high-risk participants were consistently willing to participate in future vaccine efficacy trials and with basic vaccine education, knowledge levels increased. Continued educational efforts at the community and individual level are needed to address certain vaccine trial concepts and to increase knowledge levels in all potential study populations.

AIDS Vaccines↗

Randomized controlled trial of audio computer-assisted self-interviewing: utility and acceptability in longitudinal studies. HIVNET Vaccine Preparedness Study Protocol Team.

Recent studies have reported on the utility of audio computer-assisted self-interviewing (ACASI) in surveys of human immunodeficiency virus (HIV) risk behaviors that involve a single assessment. This paper reports the results of a test of ACASI within a longitudinal study of HIV risk behavior and infection. Study participants (gay men (n = 1,974) and injection drug users (n = 903)) were randomly assigned to either ACASI or interviewer-administered assessment at their second follow-up visit 12 months after baseline. Significantly more of the sexually active gay men assessed via ACASI reported having sexual partners who were HIV antibody positive (odds ratio = 1.36, 95% confidence interval: 1.08, 1.72), and a higher proportion reported unprotected receptive anal intercourse. Among injection drug users (IDUs), our hypothesis was partially supported. Significantly more IDUs assessed via ACASI reported using a needle after another person without cleaning it (odds ratio = 2.40, 95% confidence interval: 1.34, 4.30). ACASI-assessed IDUs reported similar rates of needle sharing and needle exchange use but a lower frequency of injection. Participants reported few problems using ACASI, and it was well accepted among members of both risk groups. Sixty percent of the participants felt that the ACASI elicited more honest responses than did interviewer-administered questionnaires. Together, these data are consistent with prior research findings and suggest that ACASI can enhance the quality of behavioral assessment and provide an acceptable method for collecting self-reports of HIV risk behavior in longitudinal studies and clinical trials of prevention interventions.

Adolescent↗

Feasibility of chemoprophylaxis studies in high risk HIV-seronegative populations.

Administration of antiretroviral medications-recommended to prevent HIV infection after occupational exposure-has not been evaluated for safety or efficacy following nonoccupational exposure. HIV-seronegative persons at increased risk for HIV exposure completed a self-administered questionnaire assessing their willingness to join studies of this approach. Of 4,572 respondents, 60% were willing to join a study of a "morning-after" pill; dosing three times a day and mild side effects reduced willingness to 30%. Men who have sex with men (MSM) who reported unprotected anal intercourse in the prior 6 months were significantly more likely to be willing to join a morning-after study than MSM who did not (p = 0.006). MSM favored a preventive HIV vaccine over oral chemoprophylaxis; other populations preferred oral chemoprophylaxis. Interest in studies declined as the hypothetical regimen became more demanding. Studies must emphasize the unknown efficacy of this approach, given increased interest among MSM at greater risk of exposure.

AIDS Vaccines↗

Use of reality "female condoms" for anal sex by US men who have sex with men. HIVNET Vaccine Preparedness Study Protocol Team.

OBJECTIVES: This study assessed use of Reality "female condoms" for anal sex by HIV-seronegative men who have sex with men and are at high risk for HIV infection. METHODS: Self-administered questionnaires were completed by 2277 participants in a 6-city prospective cohort study. RESULTS: Of the 1084 (48%) men who had heard of using the female condom for anal sex, 145 (13%) reported using it in the prior 6 months. Users were at greater risk than nonusers: 47 receptive and 35 insertive users reported problems, including bleeding by the receptive partner (4). CONCLUSIONS: Redesign of the female condom could increase acceptability and use by men who have sex with men and could address possible safety concerns.

Adult↗

A population-based family study (II): Segregation analysis.

We used segregation analysis to investigate the genetic etiology of the disease in Problem 2A. Under the assumption of a dominant major gene, our analysis suggests a major gene with relative risk of 58 and an allele frequency of 0.013. Under an additive gene assumption, it appears that there may be two genes with relative risks of 39 and 17 and allele frequencies of 0.015 and 0.075, respectively.

Case-Control Studies↗

Seroprevalence of human papillomavirus types 6 and 16 capsid antibodies in homosexual men.

Human papillomavirus (HPV) has been implicated in the pathogenesis of anal carcinoma, which is increased in homosexual men. Little is known about the serologic response to HPV in normal or immunosuppressed men; therefore, HIV-infected and -uninfected homosexual men were screened for HPV-6 and -16 capsid antibodies. HIV-infected men had increased HPV DNA detection but did not significantly differ in the prevalence of serum HPV antibodies. HPV-6 DNA detection and the presence of anal warts were significantly correlated with serum antibody overall and in the HIV-infected subgroup. HPV-16 DNA detection was not significantly correlated with serum antibody overall or in either subgroup; however, HIV-infected men with high-grade anal squamous intraepithelial lesions were significantly more likely to have HPV-16 antibodies. HIV-infected men are able to generate an antibody response to HPV, and a lack of serum HPV antibodies cannot explain the increased HPV-associated disease seen in HIV-infected men.

AIDS-Related Opportunistic Infections↗

Risk of contralateral breast cancer among women with carcinoma in situ of the breast.

BACKGROUND: Information is limited on the risk of contralateral breast cancer after a diagnosis of breast carcinoma in situ (BCIS). METHODS: In western Washington, between 1974 and 1993, 1929 women with a first primary ductal carcinoma in situ (DCIS) and 282 women with a first primary lobular carcinoma in situ (LCIS) were followed for contralateral breast cancer. Rates of contralateral invasive breast cancer and BCIS were compared with population rates of first primary breast cancer using Poisson regression to adjust for age and calendar year. RESULTS: The rate of contralateral invasive disease after BCIS was approximately twice the population rate for women with DCIS and three times the population rate for women with LCIS; relative rates decreased somewhat with increasing time since diagnosis of LCIS, but were fairly stable after DCIS. The relative rate of contralateral DCIS after BCIS was substantially higher than for contralateral invasive disease, but dropped dramatically after the first year after the initial BCIS, especially among women with LCIS. Contralateral BCIS usually was of the same histologic type as the initial BCIS; histologic concordance of BCIS was 71% for women with an initial LCIS and 78% for women with DCIS. CONCLUSIONS: Data suggest that the rate of contralateral invasive breast cancer is elevated for at least 5 years after a diagnosis of BCIS compared with the rate of first primary breast cancer in the population, and that the rate is only slightly higher for women with LCIS than for women with DCIS. The markedly elevated rate of contralateral DCIS may result in large part from increased medical surveillance of women diagnosed with BCIS, especially during the first year after the initial diagnosis.

Adult↗

Effects of different designs and extension of a food frequency questionnaire on response rate, completeness of data and food frequency responses.

The authors studied how the introduction of several modifications to a basic food frequency questionnaire can influence the results of dietary surveys. Modifications covered eight combinations based on three levels: increasing versus decreasing order of frequency categories; questionnaires without versus with questions about portion sizes, and questionnaires without versus with extra non-dietary questions. The sample included 6783 women between the ages of 40 and 70 years who took part in mammography screening. The women were randomly assigned to one of the eight study groups. All of the women in each group received one of the eight differently modified questionnaires. The forms extended in length by extra non-dietary questions and portion size categories resulted in a 20% higher total non-response compared to the shorter basic form. Partial non-response was significantly lower for all four questionnaire types that included portion sizes. When portion sizes were included in the questionnaire, the reported mean frequency of consumption was significantly reduced for fat (-10 times per month), milk (-6), bread (-5), vegetables (-2) and fish (-0.4). The decreasing order of responses to the frequency categories was associated with a statistically significant increase in the frequency responses for bread (2.6 times per month), vegetables (2) and fish (0.6). These data provide evidence that the design and extension of food frequency questionnaires influence the results of dietary studies.

Adult↗

Comparison between theophylline and an adenosine non-blocking xanthine in acute asthma.

Enprofylline, a drug without adenosine antagonism and theophylline, a potent adenosine antagonist, were compared, double-blind, randomized, in acute asthma (n = 33). The drugs were given intravenously as loading over 10 min followed by maintenance infusion for 24 h. Mean final plasma levels were very high with enprofylline (14 mg.l), and larger than calculated with theophylline (16 mg.l). Seven patients had maximum levels of enprofylline ranging between 16 and 42 mg.l. Extreme plasma levels of enprofylline were not associated with any theophylline-like central nervous system excitatory effects related to seizure-inducing ability. Some irregularities in the heart rhythm did not raise clinical problems and no significant difference between enprofylline and theophylline was recorded. At 1 h patients on enprofylline (mean plasma level: 5.7 mg.l) and theophylline (12.2 mg.l) had improved their peak expiratory flow rates by 31% and 15% (p less than 0.05), respectively. The improvement in lung function after 24 hours did not differ between treatments suggesting that the high levels of enprofylline were supramaximal for its anti-asthma effects in this situation. In conclusion, with enprofylline it is demonstrated that an adenosine non-blocking xanthine derivative may lack CNS-excitatory effects, but be more potent than theophylline in the treatment of acute asthma.

Acute Disease↗

A preliminary evaluation of the Scanditronix PC2048-15B brain scanner.

The PC2048-15B is the brain version of the new generation of Scanditronix positron camera systems. It is based on a detection unit with 16 scintillating crystals mounted on 2 dual photomultiplier tubes. A system description is given and preliminary test results including spatial resolution, sensitivity to true and random coincidences, scatter correction, and count rate linearity are presented.

Brain↗

Scatter fraction: measurement and correction.

The concept of scatter in Positron Emission Tomography is reviewed regarding origin and influence on data. Different ways to measure and correct for scatter are discussed.

Scattering, Radiation↗

A preliminary evaluation of a dual crystal positron camera.

The whole-body positron camera PC2048-7WB, manufactured by Scanditronix AB, is based on a detection unit with two scintillating crystals on each photomultiplier tube. The design ideas are specified and a system description is given. Preliminary test results including spatial resolution, time resolution, scatter correction, homogeneity, sensitivity, and count rate linearity are presented.

Evaluation Studies as Topic↗

Performance characteristics of an eight-ring whole body PET scanner.

The technical characteristics of the multislice whole-body positron emission tomographic scanner (model PC4096-15WB Scanditronix) and its performance parameters are described. Spatial resolution at the center of the field of view was found to be 4.9 mm in-plane and 4.6 mm (cross slices) and 6.0 mm (direct slices) in the axial direction. The sensitivity for true and scattered coincidences is approximately 5,000 cps for direct slices and 7,100 cps for cross slices. At an activity concentration of 37 kBq/ml the system deadtime was approximately 5%. By measuring a uniform phantom with a cold cylindrical insert (5.0 cm diameter), the scatter fraction was found to be approximately 5%. The mean global uniformity over all 15 slices was 6.5%, whereas the local uniformity was found to be 4.3%. No systematic nonuniformities were observed. Finally, various methods for attenuation correction (transmission scan, contour finding, ellipse) were utilized to test their effects on the resulting reconstructed images.

Adult↗

A computerized brain atlas: construction, anatomical content, and some applications.

An adjustable computerized atlas of the human brain has been developed, which can be adapted to fit individual anatomy. It is primarily intended for positron emission tomography (PET) but may also be used for single photon emission CT, transmission CT, magnetic resonance imaging, and neuroimaging-based procedures, such as stereotactic surgery and radiotherapy. The atlas is based on anatomical information obtained from brains fixed in situ soon after death. All structures have been drawn in on digitized photos of slices from one cryosectioned brain. The definition and classification of the anatomical structures and divisions are in agreement with the standard textbooks of anatomy, and the nomenclature is that of the Nomina Anatomica of 1965. The boundaries of the cortical cytoarchitectonic areas (Brodmann areas) have been determined using information from several sources, since three-dimensional literature data on their distribution are incomplete, scarce, and partly contradictory. However, no analysis of the cytoarchitectonics of the atlas brain itself has been undertaken. At present the data base contains three-dimensional representations of the brain surface, the ventricular system, the cortical gyri and sulci, as well as the Brodmann cytoarchitectonic areas. The major basal ganglia, the brain stem nuclei, the lobuli of the vermis, and the cerebellar hemispheres are also included. The computerized atlas can be used to improve the quantification and evaluation of PET data in several ways. For instance, it can serve as a guide in selecting regions of interest. It may also facilitate comparisons of data from different individuals or groups of individuals, by applying the inverse atlas transformation to PET data volume, thus relating the PET information to the anatomy of the reference atlas rather than to the patient's anatomy. Reformatted PET data from individuals can thus be averaged, and averages from different categories or different functional states of patients can be compared.

Anatomy, Artistic↗