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Biomedical subjects

David Ross

Publications and source records attributed to David Ross.

69 records · Page 4Linked to original sources

Liberalization of donor criteria in lung transplantation.

Donor shortage remains a major obstacle to widespread application of lung transplantation. In region 5, including California, Nevada, New Mexico, Utah, and Arizona, the United Network of Organ Sharing (UNOS) database median waiting time for lung transplant candidates in 2000-2001 exceeded 17 months. The purpose of this study was to determine the impact of liberalization of donor criteria on median waiting time and short-term outcome of lung transplantation. From September 1999 to October 2002, 42 patients underwent lung transplantation from nonstandard donors. The donors were classified as nonstandard due to (1) infiltrate on chest radiograph (n = 33), (2) PaO2 < 300 on FiO2 1.0 and PEEP 5 (n = 3), (3) PaO2 < 100 on FiO2 0.4 and PEEP 5 (n = 3), (4) purulent sputum on bronchoscopy (n = 22), and (5) smoking history greater than 50 pack-years (n = 1). Perioperative characteristics and short-term outcome of this group was analyzed. The median waiting time for this cohort was 114 days (range, 10-1267), as compared with the national UNOS database median waiting time of 24 months between 1996 and 2001. The incidence of ischemia reperfusion injury was 2.3 per cent. None of the recipients developed pneumonia. The median ventilator support time was 2 days (range, 1-95). The median ICU stay and hospital stay were 4 days (range, 2-103) and 14 days (range, 5-194), respectively. The 3-month survival was 97.6 per cent. Selective liberalization of donor lung criteria can decrease the waiting time and is associated with favorable short-term outcome. Utilization of nonstandard lungs can expand the donor pool.

Cohort Studies↗

Syphilis in pregnancy in Tanzania. II. The effectiveness of antenatal syphilis screening and single-dose benzathine penicillin treatment for the prevention of adverse pregnancy outcomes.

Treatment for maternal syphilis with single-dose benzathine penicillin (2.4 million units intramuscularly) is being implemented in many parts of sub-Saharan Africa. To examine the effectiveness of this regimen, a prospective cohort of 1688 pregnant women was recruited in Tanzania. Birth outcomes were compared among women treated for high-titer (n=133; rapid plasma reagin [RPR] titer > or = 1:8 and Treponema pallidum hemagglutination assay [TPHA]/fluorescent treponemal antibody [FTA] positive) and low-titer (n=249; RPR titer <1:8 and TPHA/FTA positive) active syphilis and 950 uninfected women. Stillbirth or low-birth-weight live births were observed in 2.3% and 6.3%, respectively, of women treated for high-titer active syphilis and in 2.5% and 9.2%, respectively, of seronegative women. There was no increased risk for adverse pregnancy outcome for women treated for high-titer active syphilis (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.4-1.4) or low-titer active syphilis (OR, 0.95; 95% CI, 0.6-1.5), compared with seronegative women. Single-dose treatment is effective in preventing adverse pregnancy outcomes attributable to maternal syphilis.

Adolescent↗

Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy.

To measure the impact of maternal syphilis on pregnancy outcome in the Mwanza Region of Tanzania, 380 previously unscreened pregnant women were recruited into a retrospective cohort at delivery and tested for syphilis. Stillbirth was observed in 18 (25%) of 73 women with high-titer active syphilis (i.e., women with a rapid plasma reagin titer > or = 1 :8 and a positive Treponema pallidum hemagglutination assay or indirect fluorescent treponemal antibody test result), compared with 3 (1%) of 233 uninfected women (risk ratio [RR], 18.1; P<.001). Women with high-titer active syphilis were also at the greatest risk of having low-birth-weight or preterm live births (RR, 3.0 and 6.1, respectively), compared with women with other serological stages of syphilis. Among unscreened women, 51% of stillbirths, 24% of preterm live births, and 17% of all adverse pregnancy outcomes were attributable to maternal syphilis. Syphilis continues to be a major cause of pregnancy loss and adverse pregnancy outcome among women who do not receive antenatal syphilis screening and treatment.

Adult↗

Microfluidic temperature gradient focusing.

A new technique is described for the concentration and separation of ionic species in solution within microchannels or capillaries. Concentration is achieved by balancing the electrophoretic velocity of an analyte against the bulk flow of solution in the presence of a temperature gradient. With an appropriate buffer, the temperature gradient can generate a corresponding gradient in the electrophoretic velocity, so that the electrophoretic and bulk velocities sum to zero at a unique point, and the analyte will be focused at that point. The technique is demonstrated for a variety of analytes, including fluorescent dyes, amino acids, DNA, proteins, and particles, and is shown to be capable of greater than 10,000-fold concentration of a dilute analyte.

Journal Article↗

Incidence of HIV infection in stable sexual partnerships: a retrospective cohort study of 1802 couples in Mwanza Region, Tanzania.

OBJECTIVE: To describe the dynamics of HIV transmission in stable sexual partnerships in rural Tanzania. DESIGN: Retrospective cohort study nested within community-randomized trial to investigate the impact of a sexually transmitted disease treatment program. METHODS: A cohort of 1802 couples was followed up for 2 years, with the HIV status of each couple assessed at baseline and follow-up. RESULTS: At baseline, 96.7% of couples were concordant-negative, 0.9% were concordant-positive, 1.2% were discordant with the male partner being HIV-positive, and 1.2% were discordant with the female partner being HIV-positive. Individuals living with an HIV-positive partner were more likely to be HIV-positive at baseline (women: odds ratio [OR] = 75.7, 95% confidence interval [CI]: 33.4-172; men: OR = 62.4, CI: 28.5-137). Seroincidence rates in discordant couples were 10 per 100 person-years (py) and 5 per 100 py for women and men, respectively (rate ratio [RR] = 2.0, CI: 0.28-22.1). In concordant-negative couples, seroincidence rates were 0.17 per 100 py in women and 0.45 per 100 py in men (RR = 0.38, CI: 0.12-1.04). Individuals living in discordant couples were at a greatly increased risk of infection compared with individuals in concordant-negative couples (RR = 57.9, CI: 12.0-244 for women; RR = 11.0, CI: 1.2-47.5 for men). CONCLUSION: Men were more likely than women to introduce HIV infection in concordant-negative partnerships. In discordant couples, incidence in HIV-negative women was twice as high as in men. HIV-negative individuals in discordant partnerships are at high risk of infection, and preventive interventions targeted at such individuals are urgently needed.

Adult↗

Comparison of HIV prevalences in community-based and antenatal clinic surveys in rural Mwanza, Tanzania.

OBJECTIVES: First, to compare the prevalence of HIV infection among women in the general population and antenatal clinic (ANC) attenders in rural Mwanza, Tanzania, and second, to validate a method for adjusting HIV prevalence in ANC attenders to estimate the prevalence in the general female population aged 15-44 years. METHODS: A cross-sectional population survey was conducted in 12 rural communities of Mwanza Region between 1991 and 1992. From the same communities sequential ANC attenders were recruited on two occasions between 1991 and 1993. Consenting subjects were interviewed, examined, treated and a serum sample was tested for HIV. The HIV prevalence in women in the general population was compared with unadjusted and adjusted prevalences in ANC attenders. Parity-adjusted prevalences were obtained by applying correction factors to the observed prevalences in parous and nulliparous ANC attenders. RESULTS: A total of 5675 women aged 15-44 years from the general population and 2265 ANC attenders had complete socio-demographic and laboratory data. Unadjusted HIV prevalence was significantly lower in ANC attenders (3.6%) than women from the general population (4.7%, P = 0.025), but after adjustment there was no significant difference between the two groups (4.6 versus 4.7%, P = 0.95). CONCLUSION: In this rural population, the HIV prevalence in ANC attenders underestimated the prevalence among women in the general population, but this difference was eliminated by applying parity-based correction factors. Information on parity should be routinely collected in ANC-based HIV sentinel surveillance.

Adolescent↗

Subcellular localization of NAD(P)H:quinone oxidoreductase 1 in human cancer cells.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is implicated in both chemoprevention and bioactivation of DNA-damaging antitumor agents. NQO1 is mainly cytosolic, but distribution in other cellular compartments, particularly in tumor cells, is poorly defined. Nuclear NQO1 in HT29 human colon carcinoma and H661 human non-small cell lung cancer cells was observed using both confocal microscopy and immunoelectron microscopy. NQO1 was not detected in mitochondria, golgi, or endoplasmic reticulum. In addition, purified intact nuclei from HT29 cells contained immunoreactive NQO1, which was catalytically active as determined by conventional activity assay. In summary, we have confirmed the presence of nuclear NQO1, which has implications for chemoprotection and bioactivation of DNA-damaging antitumor agents.

Antineoplastic Agents↗

Herpes simplex virus type 2 infection increases HIV incidence: a prospective study in rural Tanzania.

OBJECTIVES: To quantify the association between prevalent or incident Herpes simplex virus type-2 (HSV2) infection and the incidence of HIV seroconversion among adults in the general population in rural Tanzania. STUDY POPULATION: Adults aged 15-54 years sampled randomly from 12 rural communities in Mwanza Region, Tanzania and recruited to a randomized trial of improved treatment of sexually transmitted diseases. STUDY DESIGN: Unmatched case-control study nested within trial cohort. METHODS: Participants included 127 cases who seroconverted to HIV during the 2-year follow-up period and 636 randomly selected controls who remained HIV negative. Subjects were tested for HSV2 serology at baseline and follow-up, and associations between HIV and HSV2 were analysed with adjustment for socio-demographic and behavioural factors. RESULTS: After adjusting for confounding factors, a strong association between HSV2 infection and HIV seroconversion was observed in men (test for trend: P < 0.001), with adjusted odds ratios (OR) of 6.12 [95% confidence interval (CI), 2.52-14.9] in those HSV2 positive at baseline, and 16.8 (95% CI, 6.06-46.3) in those acquiring HSV2 infection during follow-up. A weaker association was observed in women (tests for trend: P = 0.14), with adjusted OR of 1.32 (95% CI, 0.62-2.78) and 2.36 (95% CI, 0.81-6.84), respectively. Population attributable fractions of incident HIV infection due to HSV2 were estimated as 74% in men and 22% in women. CONCLUSIONS: The results suggest that HSV2 plays an important role in the transmission of HIV infection in this population. There is an urgent need to identify effective HSV2 control measures in order to reduce HIV incidence in Africa.

Adolescent↗

Interaction of the molecular chaperone Hsp70 with human NAD(P)H:quinone oxidoreductase 1.

NAD(P)H:quinone oxidoreductase 1 (EC; DT-Diaphorase, NQO1) is predominantly a cytosolic flavoenzyme that catalyzes a two-electron reduction. Using human tumor cell lines devoid of NQO1 enzymatic activity, we have previously identified a single nucleotide polymorphism (NQO1*2 allele) in the human NQO1 gene. This mutation has been characterized as a genetic polymorphism (NQO1*2), which leads to greatly diminished levels of protein due to rapid degradation of the NQO1*2 protein by the ubiquitin proteasomal pathway (UPP). In an attempt to decipher the mechanism responsible for the differential stability of wild-type NQO1*1 and mutant NQO1*2 proteins, we have investigated the interactions of these proteins with molecular chaperones of the Hsp family. Using co-immunoprecipitation studies (co-IPs), no association was observed between Hsp90 and either wild-type NQO1*1 or mutant NQO1*2 proteins. Hsp70, however, was found to associate with NQO1*1 protein in cells when co-IPs were performed with an anti-NQO1 antibody followed by immunoblotting with an anti-Hsp70 antibody or vice versa. Hsp40 could also be detected in the immunoprecipitated protein complex. Experiments were also performed using either the NQO1*1 or NQO1*2 coding regions in an in vitro transcription/translation system employing rabbit reticulocyte lysates (RRLs). Consistent with the cellular data, co-IP experiments in RRLs demonstrated an association of Hsp70 with wild-type NQO1*1 protein but not with NQO1*2 protein. To further elucidate the role of the association of Hsp70 with the NQO1*1 protein, site-directed mutagenesis was used to modify a proposed Hsp70 binding site near the N terminus of the NQO1 protein. We generated a plasmid containing an NQO1*1 coding region with a mutated Hsp70 binding site (isoleucine to aspartic acid at position 8, NQO1*1/I8D). In contrast to the NQO1*1 protein translated in RRLs, the NQO1*1/I8D protein did not associate with Hsp70, as demonstrated by co-IP, was catalytically inactive, and was degraded by the UPP. These data suggest that the association of Hsp70 with NQO1*1 may play an important role in the stability and functionality of the NQO1 protein.

Alleles↗

Rapid microfluidic mixing.

A preformed T-microchannel imprinted in polycarbonate was postmodified with a pulsed UV excimer laser (KrF, 248 nm) to create a series of slanted wells at the junction. The presence of the wells leads to a high degree of lateral transport within the channel and rapid mixing of two confluent streams undergoing electroosmotic flow. Several mixer designs were fabricated and investigated. All designs were relatively successful at low flow rates (0.06 cm/s, > or = 75% mixing), but had varying degrees of success at high flow rates (0.81 cm/s, 45-80% mixing). For example, one design operating at high flow rates was able to split an incoming fluorescent stream into two streams of varying concentrations depending on the number of slanted wells present. The final mixer design was able to overcome stream splitting at high flow rates, and it was shown that the two incoming streams were 80% mixed within 443 microm of the T-junction for a flow rate of 0.81 cm/s. Without the presence of the mixer and at the same high flow rate, a channel length of 2.3 cm would be required to achieve the same extent of mixing when relying upon molecular diffusion entirely, while 6.9 cm would be required for 99% mixing.

Equipment Design↗

Rapidly progressive idiopathic dilation of the right atrium in infancy associated with dynamic obstruction of the airways.

We present a young infant with rapidly progressive idiopathic dilation of the right atrium, complicated by symptomatic and dynamic obstruction of the airways secondary to proximal obstruction which was reversed subsequent to surgical reduction of the right atrium. We discuss the surgical implications of the distorted cardiac anatomy, along with post-operative complications, which included refractory arrhythmias.

Airway Obstruction↗

Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice.

The effects of high-fat feeding on the development of obesity were evaluated in intercellular adhesion molecule-1 (ICAM-1) knockout and C57BL/6J (B6) male mice fed a high-fat diet for < or =50 days. Serum and tissues were collected at baseline and after 1, 11, and 50 days on the diet. After 11 days on the diet, ICAM-1-deficient, but not B6, mice developed fatty livers and showed a significant increase in inguinal fat pad weight. At day 50, ICAM-1-deficient mice weighed less, and their adiposity index and circulating leptin levels were significantly lower than those of B6 controls. To better understand the early differential response to the diet, liver gene expression was analyzed at three time points by use of Affymetrix GeneChips. In both strains, a similar pattern of gene expression was detected in response to the high-fat diet. However, sterol regulatory element-binding protein-1, apolipoprotein A4, and adipsin mRNAs were significantly induced in ICAM-1-deficient livers, suggesting that these genes and their associated pathways may be involved in the acute diet response observed in the knockout mice.

Animals↗

Tracking retinal motion with a scanning laser ophthalmoscope.

The vast majority of people with low vision retain some functional vision to perform everyday tasks. To study the effectiveness and efficiency of the visual tasks performed by people with low vision, knowing the movement patterns of their preferred retinal locus (PRL) used for fixation, saccade, and pursuit is critical. The scanning laser ophthalmoscope (SLO) has been used to acquire retinal images while a subject is performing a visual tracking exercise. SLO data has traditionally been analyzed with the use of manual techniques that are both time-consuming and prone to errors due to operator fatigue. To improve the speed and accuracy of the analysis of retinal motion from SLO image sequences, we developed an automated image processing technique and tested it using MATLAB(TM) (The MathWorks, Natick, MA) software. The new software technique was experimentally tested on both normal- and low-vision subjects and compared with the results obtained using manual techniques. The findings indicate that the new technique works very well for most subjects, fairing poorly only in subjects where the quality of the SLO images was substandard.

Adult↗