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Biomedical subjects

L Anderson

Publications and source records attributed to L Anderson.

At least 145 records · Page 8Linked to original sources

Seroprevalence of HIV and risk behaviors among young homosexual and bisexual men. The San Francisco/Berkeley Young Men's Survey.

OBJECTIVE: To estimate the prevalence of human immunodeficiency virus (HIV) infection and risk behaviors among young homosexual and bisexual men sampled from public venues in San Francisco and Berkeley, Calif. DESIGN: A survey of 425 young homosexual and bisexual men sampled from 26 locations during 1992 and 1993. Participants were interviewed and blood specimens were drawn and tested for HIV, level of CD4+ T lymphocytes, and markers of hepatitis B and syphilis. SETTING: Public venues in San Francisco and Berkeley, including street corners and sidewalks, dance clubs, bars, and parks. POPULATION STUDIED: Homosexual and bisexual men aged 17 to 22 years. MAIN OUTCOME MEASURES: Prevalence of HIV infection and risk behaviors. RESULTS: The HIV seroprevalence was 9.4% (95% confidence interval, 6.8% to 12.6%). The prevalence of markers for hepatitis B was 19.8% (95% confidence interval, 16.1% to 23.9%), and that for syphilis was 1.0% (95% confidence interval, 0.3% to 2.4%). The HIV seroprevalence was significantly higher among African Americans (21.2%) than among other racial/ethnic groups (P = .002). Approximately one third (32.7%) of the participants reported unprotected anal intercourse, and 11.8% reported injecting drug use in the previous 6 months. At the time of interview, 70.0% of the HIV-infected men did not know that they were HIV seropositive, and only 22.5% were receiving medical care for HIV infection. CONCLUSIONS: The prevalence of HIV infection is high among this young population of homosexual and bisexual men, particularly among young African-American men. The high rates of HIV-related risk behaviors suggest a considerable risk for HIV transmission in this population. Prevention programs and health services need to be tailored to address the needs of a new generation of homosexual and bisexual men.

Adolescent↗

Quantifying the effect of dose inhomogeneity in brachytherapy: application to permanent prostatic implant with 125I seeds.

PURPOSE: To quantitate the influence of dose inhomogeneity on brachytherapy efficacy. METHODS AND MATERIALS: A computed tomography-based system of planning, implementation and evaluation was used to generate tumor-specific dose-volume histograms of eight permanent 125I implants of prostate cancers. The radiobiological effect was then assessed, voxel by voxel, in terms of the biologically effective dose and the associated cell inactivation. The overall cell survival of the entire target volume was then computed. To evaluate the influence of inhomogeneity, the dose-volume histogram was modified in an iterative fashion, with the corresponding surviving fraction calculated after each step. Specifically, the volume in the highest dose bin was combined with that in the next bin to give a new frequency distribution from which cell survival was generated. Tumor control probability (TCP) was also used as an endpoint, using the same iterative procedure. RESULTS: Doses 20-30% higher than D99 (the dose that covered 99% of the target volume) contributed to additional cell inactivation, but still higher doses did not further increase cell kill. With homogeneous irradiation at D99 as a reference, we defined the inhomogeneity enhancement factor as the ratio of the biologic effective dose of the actual implant to that of the reference dose distribution. The calculated enhancement factors were inversely dependent on tumor potential doubling time (Tp), about 1.2-1.3 for a Tp of 30 days, and between 1.3 and 1.7 if Tp = 10 days, with higher values for implants with low D99. Dose inhomogeneity enhanced TCP. For implants with high control probabilities does significantly higher (> 20%) than the D99 value did not further enhance the tumor control probabilities. In contrast, for implants with relatively low tumor control and D99 values, the control probability continued to increase with doses significantly higher than D99, up to a dose of 2 x D99. The underlying reasons were the incorporation of patient "population averaging" in the calculation and the saturation of tumor control dose response at about 120 Gy. CONCLUSION: Dose heterogeneity in implants increased tumor cell kill and local control probability, although doses > 20% higher than the prescription dose is wasted. The increase the beneficial effect of dose inhomogeneity may be greatest when most needed.

Brachytherapy↗

Three-dimensional reconstructions of the primary palate region in normal human embryos.

Our knowledge of the precise spatial relationships of human primary palate morphogenesis remains poorly defined. This is due to intrinsic difficulties that exist in the study of the subject matter and a lack of adequate methodologies. We present a novel new method to allow precise three-dimensional (3-D) visualization of developing embryonic structures in previously sectioned embryos. In our study we focus on human primary palate development. Five normal human embryos from the Carnegie collection were used. 3-D reconstructions appear similar to scanning electron micrographs (SEM); however, unlike in SEM studies, the original specimen has been previously sectioned histologically. 3-D reconstruction from serial sections involved 1) histological preparation of specimen, 2) projection onto digitizing board, 3) digitization, 4) automated reassembly, and 5) relay to interactive optical disc recorder. Detailed observations of each reconstruction were then made. Data generated in this manner may also be used in the near future for quantitative morphometrics. Thus, 3-D reconstruction techniques presented in this paper generated precise spatial information on the development of the human primary palate.

Cleft Lip↗

Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study.

OBJECTIVE: To evaluate the efficacy and tolerability of oral methotrexate (MTX) in rheumatoid arthritis (RA) in a long-term prospective trial. METHODS: One hundred twenty-three patients with RA who completed a 9-month multicenter randomized trial comparing MTX and auranofin enrolled in this 5-year prospective study of MTX. RESULTS: Significant (P = 0.0001) improvement compared with baseline was noted in all clinical disease variables, functional status, and the Westergren erythrocyte sedimentation rate (ESR). "Marked improvement" occurred in 87 (71%) and 85 (69%) of the patients, respectively, in the joint pain/tenderness index and the joint swelling index at the last evaluable visit. Forty-four patients (36%) withdrew during the study. Eight (7%) withdrew due to lack of efficacy, and 8 (7%) due to adverse experiences, including 1 patient with cirrhosis. At 5 years, 64% of patients were still taking MTX and completed the study. CONCLUSION: This large prospective study of long-term MTX treatment demonstrates sustained clinical response and improvement in the Westergren ESR and functional assessment scores, with an acceptable toxicity profile.

Adult↗

Evidence against DNA polymerase beta as a candidate gene for Werner syndrome.

Werner syndrome (WS) is a rare autosomal recessive disorder of humans characterized by the premature onset and accelerated rate of development of several major age-related disorders. An aberration in DNA replication or repair is suggested by the evidence of genome instability. Since the structural gene for DNA polymerase beta maps within the region of the WS mutation on the short arm of chromosome 8 and is involved in both DNA repair and DNA replication, we evaluated its candidacy as the WS gene. Several independent lines of evidence did not support that hypothesis: (1) activity gels showed normal enzyme activity and electrophoretic mobility; (2) nucleotide sequence analysis of the entire coding region failed to reveal mutations (although indicated mistakes in the published sequence); (3) single-strand conformation polymorphism (SSCP) and heteroduplex analyses failed to reveal evidence of mutations in the promoter region; (4) a newly discerned polymorphism failed to reveal evidence of homozygosity by descent in a consanguineous patient; and 5) fluorescence in situ hybridization (FISH) analysis placed the DNA polymerase beta gene centromeric to D8S135 at 8p11.2 and thus beyond the region of peak LOD scores for WS.

Cell Line↗

Clinical stage 1 non-Hodgkin's lymphoma: long-term follow-up of patients treated by the British National Lymphoma Investigation with radiotherapy alone as initial therapy.

A retrospective analysis was performed of 451 adult patients with clinical stage 1/1E non-Hodgkin's lymphoma treated initially with radiotherapy alone. Histopathologically 208 patients had low-grade disease and 243 patients high-grade disease. The complete remission (CR) rate was higher in patients with low-grade disease (98%) than in those with high-grade disease (84%) (P < 0.0001). The relapse rate was similar in both histological categories, and relapse usually occurred within 5 years. The resulting overall actuarial percentage of patients achieving CR and remaining disease free (at 10 years) was 47% in patients with low-grade disease and 45% for those with high-grade disease. Salvage therapy was frequently successful in younger patients, and the overall cause-specific survival at 10 years was 71% for low-grade disease and 67% for high-grade disease. In those patients under 60 years of age at diagnosis, the overall cause-specific survival at 10 years was 84% and 80% for those with low-grade and high-grade disease respectively. These long-term results in young patients with clinical stage 1 disease are encouraging, and it will be difficult to demonstrate improved survival with initial chemotherapy either with or without radiotherapy, until new prognostic factors are found to identify poor-risk patients.

Adult↗

Hybrid LOPP/EVA is not better than LOPP alternating with EVAP: a prematurely terminated British National Lymphoma Investigation randomized trial.

In a British National Lymphoma Investigation (BNLI) trial, patients with advanced Hodgkin's disease (stages IB, IIB, III, and IV) were randomized between initial treatment with a LOPP alternating with EVAP regimen and a LOPP/EVA hybrid regimen. The two regimens contained identical drug dosages and varied only in their scheduling. The complete remission (CR) rate in the hybrid regimen was significantly less than that in the alternating regimen, and the trial was terminated after approximately 18 months since there appeared to be no chance of the hybrid regimen ever proving superior to the alternating regimen. A total of 160 patients were entered into the trial before recruitment was terminated, 86 being randomized to the alternating regimen and 83 to the hybrid regimen. The CR rates for the alternating and hybrid arms were 65% and 40%, respectively (p < 0.002). The CR relapse-free survivals at 2 years in these two arms were 85% and 79%, respectively (p = 0.7); the overall disease-free survivals at 2 years were 57% and 32%; and the overall survivals at 2 years were 88% and 78% (p = 0.5). This trial emphasizes the impact of drug scheduling, which should be taken into account in the design of future hybrid regimens.

Adolescent↗

Late mortality in young BNLI patients cured of Hodgkin's disease.

A retrospective analysis was made of 1057 young patients (aged 15-29) with Hodgkin's disease (HD) who were entered into British National Lymphoma Investigation (BNLI) trials and studies between 1970 and 1992, and who had attained complete remission and remained disease-free thereafter from either their first-line (n = 774) or second-line (n = 283) treatment. Overall survivals at 20 years for those remaining disease-free from first-line and second-line treatment were 93% and 84%, respectively, compared to a survival of approximately 98.5% in the general population. In young patients cured by modern first-line therapeutic techniques, long-term survival should in future be only a little below that expected in the general population, and the emphasis of future trials should be directed towards the improvement of the efficacy of first-line treatment.

Adolescent↗

Measurement of the attenuation coefficient for Livermore Thoracic Phantom lungs fabricated using contemporary materials.

The University of Cincinnati has reproduced the original formulation for the Livermore Thoracic Phantom lungs using contemporary materials and has adopted the linear attenuation coefficient as the primary quality assurance parameter for evaluating the performance capabilities of these new lung phantoms. The Livermore Thoracic Phantom was originally fabricated in 1978 to intercalibrate detector systems used to measure plutonium and other low-energy, photon emitting radionuclides deposited in the respiratory tract. The linear attenuation coefficient is a critical performance indicator for these phantom lungs since the presence of any material with a high effective atomic number (where Z > or = 20) will make a significant change in the photoelectric cross section, the predominant mode of interaction for plutonium x rays. A set of test lungs was fabricated with KCl to introduce a known quantity of 40K in the phantom and to determine, by measurement and calculations, what change would be made to the attenuation coefficient at photon energies below 100 keV as a result of the modified formulation. The KCl increased the linear attenuation coefficient below 60 keV by more than a factor of two, which would produce a substantial systematic error in any subsequent calibration measurements performed with these modified phantom lungs. These results support use of the attenuation coefficient as an important performance indicator for the Livermore Thoracic Phantom lungs and also suggest that KCl not be added to the lung tissue substitute formulation as a means to incorporate 40K in the phantom for low energy calibrations.

Humans↗

Calcium waves and dynamics visualized by confocal microscopy in Xenopus oocytes expressing cloned TRH receptors.

Laser scanning confocal microscopy was used to analyse changes in free cytosolic calcium ([Ca2+]i) in Xenopus laevis oocytes expressing the cloned rat TRH receptor in response to TRH. In oocytes expressing TRH receptors, TRH invariably evoked a dose-dependent, biphasic calcium response. This response consisted of an initial transient planar wave of calcium propagating just below the surface of the membrane followed by a slower, secondary calcium phase. The TRH antagonist, chlordiazepoxide, markedly inhibited this calcium wave. The origins of calcium involved in this biphasic response were investigated using a variety of intra- and extra-cellular calcium antagonists. The intracellular calcium antagonists thapsigargin and TMB-8 reduced the initial and to a lesser extent the secondary phase of the planar calcium wave. In contrast, EGTA and the calcium channel blocker nifedipine produced a profound inhibition of the secondary phase while the initial phase was only slightly reduced. These results indicate that the release of intracellular calcium is predominantly responsible for the initial phase of the calcium wave while the influx of extracellular calcium is mainly involved in the secondary phase. Qualitative changes in the patterns of calcium release induced by TRH were observed following pretreatment with intracellular calcium antagonists. Following pretreatment with these compounds, TRH induced spiral or regenerative calcium waves. Addition of EGTA to the extracellular medium did not alter these responses confirming the importance of intracellular calcium in the generation of these spiral calcium waves. This study demonstrates the nature and multiplicity of regulating mechanisms of [Ca2+]i following activation of TRH receptors expressed in Xenopus oocytes.

Animals↗

Prevalence of periodontal pathogens with varying metabolic control of diabetes mellitus.

The purpose of this study was to determine the prevalence of 5 periodontal pathogens in individuals with diabetes mellitus. Subjects (n = 107) 20-70 years of age with type 1 (n = 60) or 2 (n = 47) diabetes mellitus were studied for the occurrence of the periodontal pathogens A. actinomycetemcomitans, F. nucleatum, E. corrodens, P. gingivalis and P. intermedia. Subgingival plaque was sampled in each subject from a single site exhibiting the greatest inflammation. The evaluation of selected periodontal bacterial pathogens was based on an immunoassay utilizing bacterial specific monoclonal antibodies. 35% of the sites harbored P. gingivalis, 28% F. nucleatum and 21% E. corrodens. A. actinomycetemcomitans and P. intermedia were found in less than 10% of the sites. Subjects for whom the probing depth at the sampled site was > or = 4 mm were more often found to have detectable pathogens than those with a probing depth < or = 3 mm. Diabetic factors such as duration, type and metabolic control of the disease had no statistically significant effect on the prevalence of these bacteria.

Adult↗

The Cell-Sweep. A new cervical cytology sampling device.

The Cell-Sweep, a new cervical cytology sampling device, was prospectively evaluated. From September 1, 1992, to October 31, 1992, 548 cervical cytology smears were prepared using the Cell-Sweep. They were compared to 524 cervical smears performed between January 1, 1993, and February 28, 1993, using the Cytobrush and Ayre spatula. One smear in the Cell-Sweep group and nine in the Cytobrush/Ayre spatula group were unsatisfactory for evaluation secondary to drying artifact (P < .01). Seven (1.2%) of the Cell-Sweep smears and 13 (2.4%) of the Cytobrush/Ayre spatula smears were inadequate due to obscuring of the epithelial cells by blood (P = .11). Of the smears obtained with the Cell-Sweep, 66 (12%) contained no endocervical component versus 42 (8%) of the smears obtained with the Cytobrush/Ayre spatula (P = .03). In the Cell-Sweep group there were 130 (23.7%) abnormal smears versus 110 (20.9%) in the Cytobrush/Ayre spatula group (P = .3). However, high grade squamous intraepithelial lesions (SILs) were identified in 10 (1.8%) smears obtained with the Cell-Sweep and in 2 (0.4%) obtained with the Cytobrush/Ayre spatula (P = .02). The Cell-Sweep produced a small proportion of unsatisfactory smears due to drying artifact or blood. Even though the proportion of smears lacking endocervical cells was statistically greater with the Cell-Sweep than with the Cytobrush/Ayre spatula, there was no difference in the rate of detection of atypical squamous cells and low grade SIL. The Cell-Sweep appears to detect an increased number of high grade SILs. This device deserves further study with histopathologic correlation.

Adolescent↗