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Robert J O'Connell

Publications and source records attributed to Robert J O'Connell.

10 recordsLinked to original sources
PubMed2007

Regulation of the gating of BKCa channel by lipid bilayer thickness.

Transmembrane segments of ion channels tend to match the hydrophobic thickness of lipid bilayers to minimize mismatch energy and to maintain their proper organization and function. To probe how ion channels respond to mismatch with lipid bilayers of different thicknesses, we examined the single channel activities of BK(Ca) (hSlo alpha-subunit) channels in planar bilayers of binary mixtures of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) with phosphatidylcholines (PCs) of varying chain lengths, including PC 14:1, PC 18:1, PC 22:1, PC 24:1, and with porcine brain sphingomyelin. Bilayer thickness and structure was measured with small angle x-ray diffraction and atomic force microscopy. The open probability (P(o)) of the BK(Ca) channel was finely tuned by bilayer thickness, first decreasing with increases in bilayer thickness from PC 14:1 to PC 22:1 and then increasing from PC 22:1 to PC 24:1 and to porcine brain sphingomyelin. Single channel kinetic analyses revealed that the mean open time of the channel increased monotonically with bilayer thickness and, therefore, could not account for the biphasic changes in P(o). The mean closed time increased with bilayer thickness from PC 14:1 up to PC 22:1 and then decreased with further increases in bilayer thickness to PC 24:1 and sphingomyelin, correlating with changes in P(o). This is consistent with the proposition that bilayer thickness affects channel activity mainly through altering the stability of the closed state. We suggest a simple mechanical model that combines forces of lateral stress within the lipid bilayer with local hydrophobic mismatch between lipids and the protein to account for the biphasic modulation of BK(Ca) gating.

Calcium↗
PubMed2006

Effectiveness of highly-active antiretroviral therapy by race/ethnicity.

OBJECTIVE: To determine the effectiveness of HAART by race/ethnicity. DESIGN: Prospective multicenter cohort study. METHODS: We studied 991 African-Americans and 911 European-Americans enrolled in the United States Military's Tri-Service AIDS Clinical Consortium Natural History Study who had dates of HIV seroconversion known within 5 years and followed between 1990 and 2002. We determined the rate of disease progression to AIDS and death for subjects in this cohort. Multivariable models evaluated race, pre-HAART (1990-1995) and HAART (1996-2002) eras, age, gender and military service. RESULTS: In the pre-HAART era, African-Americans had a statistically nonsignificant trend towards better outcomes: the relative hazards (RH) of AIDS and death for African-Americans compared to European-Americans were 0.85 [95% confidence interval (CI), 0.68-1.05] and 0.77 (95% CI, 0.55-1.08), respectively. In the HAART era, outcomes were similar by race: 1.17 (95% CI, 0.86-1.61) for AIDS and 1.11 (95% CI, 0.81-1.53) for death with overlapping Kaplan-Meier curves. Relative to the pre-HAART era, the adjusted RH of AIDS in the HAART era was 0.41 (95% CI, 0.31-0.54) and 0.30 (95% CI, 0.22-0.40) for African-American and European-American participants, respectively. Analogous RH for death were 0.55 (95% CI, 0.38-0.80) and 0.38 (95% CI, 0.27-0.54). The precipitous declines in AIDS and death in the HAART era were not statistically different by race. CONCLUSIONS: : In a large multi-racial cohort with equal access to health care, HIV treatment outcomes by race/ethnicity were similar.

AIDS-Related Opportunistic Infections↗
PubMed2006

Sensitivity of the Multispot HIV-1/HIV-2 rapid test using samples from human immunodeficiency virus type 1-positive individuals with various levels of exposure to highly active antiretroviral therapy.

The Multispot HIV-1/HIV-2 rapid test detects human immunodeficiency virus type 1 (HIV-1) gp41 antibodies, which can wane over time in some HIV-1-infected populations, resulting in false-negative screening results. Multispot sensitivity was 100% using 248 sera from one such population, and it correctly identified serostatus in individuals who previously tested false negative with rapid testing.

Adult↗
PubMed2005

Usefulness of a rapid human immunodeficiency virus-1 antibody test for the management of occupational exposure to blood and body fluid.

OBJECTIVE: To describe the usefulness of the OraQuick Rapid HIV-1 Antibody Test (OraSure Technologies, Bethlehem, PA) in cases of occupational exposure regarding its use with source-patient sera, effects on post-exposure prophylaxis (PEP) use, potential cost savings, and effects on healthcare worker (HCW) stress reaction symptoms. DESIGN: Before-and-after analysis. SETTING: A 269-bed, tertiary-care medical center with adjacent clinics. PARTICIPANTS: All source-patients and HCWs experiencing an occupational exposure during the study period. METHODS: Use of the OraQuick test with patient sera was validated prior to its use for occupational exposures. Exposures from January 1 through July 10, 2003 (enzyme immunoassay [EIA] group) and July 11 through December 31, 2003 (OraQuick group) were retrospectively reviewed and the use and cost of PEP was compared for each group. Randomly selected HCWs from both groups completed a survey to assess their stress reaction symptoms. RESULTS: After exclusion, there were 71 exposures in the EIA group and 79 in the OraQuick group. OraQuick results were 100% concordant with the reference standard of EIA and Western blot using patient sera. The mean number of doses ingested per course of PEP was significantly higher for HCWs in the EIA group (3.8; range, 0 to 6) compared with the OraQuick group (1.2; range, 0 to 3; P = .016). Cost analysis revealed a mean savings of dollar 6.62 with the OraQuick test per occupational exposure. Although the survey failed to detect an overall reduction in HCW stress reaction symptoms using OraQuick for source-patient testing, 11 HCWs in the EIA group had repetitive thoughts of the exposure compared with 5 in the OraQuick group (P = .049). CONCLUSION: Because of the reduction in ingested doses of unnecessary PEP and reduced cost of occupational exposure management with their use, rapid HIV-antibody tests should be the preferred method for source-patient testing following an occupational exposure.

AIDS Serodiagnosis↗
PubMed2004

Mycobacterium simae outbreak associated with a hospital water supply.

OBJECTIVE: Mycobacterium simiae is found primarily in the southwestern United States, Israel, and Cuba, with tap water as its suspected reservoir. Our institution saw an increase in M. simiae isolates in 2001. An investigation into possible contaminated water sources was undertaken. DESIGN: Environmental cultures were performed from water taps in the microbiology laboratory, patient rooms, points in the flow of water to the hospital, and patients' homes. Patient and environmental M. simiae were compared by PFGE. SETTING: Military treatment facility in San Antonio, Texas. PATIENTS: All patients with cultures positive for M. simiae between January 2001 and April 2002. Medical records were reviewed. RESULTS: M. simiae was recovered from water samples from the hospital, patients' home showers, and a well supplying the hospital. A single PFGE clone was predominant among water isolates (9 of 10) and available patient isolates (14 of 19). There was an association between exposure to hospital water and pulmonary samples positive for the clonal M. simiae strain (P = .0018). Only 3 of 22 culture-positive patients met criteria for M. simiae pulmonary disease. Of them, two had indistinguishable M. simiae strains from tap water to which they were routinely exposed. CONCLUSIONS: This represents an outbreak of M. simiae colonization with one nosocomial infection. It is only the second time that M. simiae has been recovered from hospital tap water and its first presentation in municipal water. This study raises issues about the need and feasibility of eliminating or avoiding exposure to M. simiae from tap water.

Cross Infection↗
PubMed2004

Bilayer thickness modulates the conductance of the BK channel in model membranes.

The conductance of the BK channel was evaluated in reconstituted bilayers made of POPE/POPS (3.3:1), or POPE/POPS with an added 20% of either SPM (3.3:1:1), CER (3.3:1:1), or CHL (3.3:1:1). The presence of SPM, which is known to increase bilayer thickness, significantly reduced the conductance of the BK channel. To directly test the role of membrane thickness, the conductance of the BK channel was measured in bilayers formed from PCs with acyl chains of increasing length (C14:1-C24:1), all in the absence of SPM. Slope conductance was maximal at a chain length of (C18:1) and much reduced for both thinner (C14:1) and thicker (C24:1) bilayers, indicating that membrane thickness alone can modify slope conductance. Further, in a simplified binary mixture of DOPE/SPM that forms a confined, phase-separated bilayer, the measured conductance of BK channels shows a clear bimodal distribution. In contrast, the addition of CER, which has an acyl chain structure similar to SPM but without its bulky polar head group to POPE/POPS, was without effect, as was the addition of CHL. The surface structure of membranes made from these same lipid mixtures was examined with AFM. Incorporation of both SPM and CER resulted in the formation of microdomains in POPE/POPS monolayers, but only SPM promoted a substantial increase in the amount of the high phase observed for the corresponding bilayers. The addition of CHL to POPE/POPS eliminated the phase separation observed in the POPE/POPS bilayer. The decrease in channel conductance observed with the incorporation of SPM into POPE/POPS membranes was, therefore, attributed to larger SPM-rich domains that appear thicker than the neighboring bilayer.

Cells, Cultured↗
PubMed2003

Performance of the OraQuick rapid antibody test for diagnosis of human immunodeficiency virus type 1 infection in patients with various levels of exposure to highly active antiretroviral therapy.

With oral mucosal transudate and serum samples from 101 human immunodeficiency virus type 1 (HIV-1)-infected subjects and 100 HIV-1-negative volunteers, the OraQuick HIV-1 test demonstrated 100% specificity and 96% sensitivity. Four false-negative subjects, who were characterized by early initiation of effective antiretroviral therapy, demonstrated waning serum anti-gp41 titers and Western blot band intensities.

Adult↗
PubMed2003

Chemical burn injury secondary to intraoperative transesophageal echocardiography.

UNLABELLED: We describe a case of a 72-yr-old male who suffered aerodigestive tract chemical injury resulting from a probable post-processing residual of the high-level disinfectant solution Cidex OPA (ortho-phthalaldehyde) used to disinfect the transesophageal echocardiogram probe used for cardiac monitoring during general anesthesia. This case highlights the need for strict adherence to manufacturers' instructions when using chemical disinfectants for transesophageal echocardiogram probe reprocessing. IMPLICATIONS: We describe a case of aerodigestive tract chemical injury resulting from a probable post-processing residual of the high level disinfectant solution Cidex OPA (ortho-phthalaldehyde) used to disinfect the transesophageal echocardiogram probe used during general anesthesia.

Aged↗