PubMed Health⌕ Search

Biomedical subjects

B Kearney

Publications and source records attributed to B Kearney.

18 recordsLinked to original sources
PubMed2001

An LC-MS-MS method for the determination of indinavir, an HIV-1 protease inhibitor, in human plasma.

A method for the determination of indinavir (IDV) (L-735 524) in human plasma by LC-MS-MS is discussed, and the validation data is presented. The analyte and internal standard are isolated from plasma by a simple acetonitrile precipitation of plasma proteins followed by centrifugation. LC-tandem mass spectrometry in positive ion, multiple reaction monitoring mode used pairs of ions at m/z of 614/421 for indinavir and 628/421 for internal standard, respectively. The calibration curve had a linear range from 3.0 to 12320 ng/ml when linear least square regression weighing 1/x was applied to the concentration versus peak area plot. The advantages of this method are the fast sample preparation, wide dynamic assay range and quick analysis taking only 5 min for each sample run. The robust nature of this assay has been further verified during routine use over several months involving multiple analysts.

Calibration↗
PubMed2001

Heart transplantation in patients seventy years of age and older: A comparative analysis of outcome.

OBJECTIVE: Advanced age has traditionally been considered a contraindication for heart transplantation because of the reported adverse effect of increased age on long-term survival. However, as the field of transplantation continues to evolve, the criteria regarding the recipient's upper age limit have been expanded and older patients are being considered as potential candidates. We analyzed the outcome of heart transplantation in patients 70 years of age and older and compared these results with those in younger patients (<70 years) over a 4-year period. METHOD: We retrospectively analyzed the results of 15 patients 70 years of age and older who underwent heart transplantation between November 1994 and May 1999 and compared them with results in 98 younger patients undergoing transplantation during the same period RESULTS: The older age group had a higher preoperative left ventricular ejection fraction (P =.02), higher incidence of female donors (P =.02), and longer cardiac allograft ischemic time (P =.01). No differences were found regarding incidence of diabetes mellitus, donor age, donor/recipient weight ratio, and mismatch (<0.80). The 30-day or to-discharge operative mortality was similar in both groups (0% in the older vs 5.1% in younger patients). Actuarial survival at 1 year and 4 years was not statistically different between the older and younger patients (93.3% +/- 6.4% vs 88.3% +/- 3.3% and 73.5% +/- 13.6% vs 69.1% +/- 5.8%, respectively). The length of intensive care unit stay and total post-transplantation hospital stay, incidence of rejection, and incidence of cytomegalovirus infection were similar between the groups. CONCLUSIONS: Heart transplantation in selected patients 70 years of age and older can be performed as successfully as in younger patients (<70 years of age) with similar morbidity, mortality, and intermediate-term survival. Advanced age as defined (> or =70 years) should not be an exclusion criterion for heart transplantation. The risks and benefits of transplant surgery should be applied individually in a selective fashion.

Adolescent↗
PubMed2001

Combined heart-kidney transplantation with single-donor allografts.

OBJECTIVES: Combined heart-kidney transplantation with allografts from the same donor has been long proved to be a feasible approach for selected patients with coexisting end-stage cardiomyopathy and renal disease. The purpose of this retrospective study is to analyze our long-term results and compare these results with heart-only transplantation over a 7-year period. METHODS: Between June 1992 and April 1999, 10 patients underwent combined heart-kidney transplantation at Cedars-Sinai Medical Center. They were all men from 44 to 70 years old (mean age, 59 +/- 8.3 years) who had a mean left ventricular ejection fraction of 19.4% +/- 5.0% (range, 9%-25%) and a mean creatinine clearance of 25.4 mL/min (range, 10-39 mL/min). Four patients underwent pretransplantation dialysis. RESULTS: There was no operative mortality. The actuarial survival at 1, 2, and 5 years was 100%, 88% +/- 11.7%, and 55% +/- 20.1%, respectively. By comparison, the operative mortality of 169 patients who underwent heart-only transplantation during the same time interval was 2.4%, with an actuarial survival at 1, 2, and 5 years of 92% +/- 2.1%, 84% +/- 2.8%, and 71% +/- 3.9%, respectively (P =.37). Eight patients showed no evidence of significant (> or =1B) cardiac allograft rejection postoperatively, and the actuarial freedom from rejection at 30 days, 1 year, and 2 years was 90% +/- 9%, 80% +/- 13%, and 80% +/- 13%, respectively. Renal allograft survival was 90% at 1 and 2 years. CONCLUSIONS: Combined heart-kidney transplantation yields satisfactory long-term results similar to those for heart-only transplantation, with a low incidence of cardiac allograft rejection and renal allograft survival when both allografts are from the same donor. This approach effectively expands the selection criteria for heart-only and kidney-only transplantation in potential candidates with coexisting end-stage cardiac and renal disease.

Actuarial Analysis↗
PubMed1999

Failure to detect nelfinavir in the cerebrospinal fluid of HIV-1--infected patients with and without AIDS dementia complex.

OBJECTIVE: To assess the penetration of the HIV-1 protease inhibitor, nelfinavir, into cerebrospinal fluid (CSF). DESIGN: Nelfinavir, a commonly used HIV-1 protease inhibitor (PI), is highly effective for reducing plasma viral load. It is deployed clinically in combination with other antiretroviral agents, including nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). Despite its potency based on plasma HIV-1 RNA results, its effectiveness in reducing HIV-1 RNA levels (i.e., viral load) in the central nervous system (CNS) is less certain. We sampled the CSF as a surrogate for brain because this fluid also is separated from the blood by a barrier to free diffusion, the blood-CSF barrier (BCB), which shares properties with the blood-brain barrier (BBB). These studies of nelfinavir CSF pharmacokinetics exploited the multiple CSF samples derived from individual study subjects who were enrolled in studies the primary objective of which was to compare viral kinetics in CSF and blood in response to antiviral therapy. METHODS: Six study subjects, four with and two without AIDS dementia complex, underwent multiple lumbar punctures (LP). Intervals of CSF sampling after drug dosing were varied (from 0.48 hours to 10.3 hours after nelfinavir administration) to quantitate nelfinavir concentrations throughout the steady-state dosing interval. In four study subjects, CSF sampling was accompanied by assessment of nelfinavir levels in plasma before and after LP, whereas in the other two subjects, a single plasma sample was obtained before or after the LP. In total, 25 CSF samples were analyzed. Nelfinavir concentrations in CSF and plasma were determined using an high-performance liquid chromatography (HPLC) method with a limit of quantitation of 25 and 50 ng/ml, respectively. RESULTS: Plasma concentrations before and after LP averaged 2420+/-1365 ng/ml and 2528+/-1132 ng/ml, respectively. Nelfinavir was not detected in any of the CSF samples and levels >25 ng/ml were not present in the CSF. Thus, standard therapy with nelfinavir does not result in CSF drug concentrations at or exceeding the IC95 level for most HIV-1 isolates. However, study subjects with high CSF viral loads experienced a marked reduction in the context of the combination-drug regimen including nelfinavir with two subjects showing a comparable CSF response with that in plasma. CONCLUSIONS: Nelfinavir does not appreciably penetrate into the CSF. The clinical importance of this observation is not certain, in that in four study subjects who initiated nelfinavir in combination with other antiretroviral therapy, a comparable degree of viral suppression was obtained in both the CSF and the blood when sampled 4 weeks or later after initiating therapy.

AIDS Dementia Complex↗
PubMed1997

Health technology assessment in Australia: the role of AHTAC. Australian Health Technology Advisory Committee.

This paper outlines and discusses the field of medical technology assessment and the role of the Australian Health Technology Advisory Committee (AHTAC) in that process. Developments in medical technologies have altered the way in which health care is practised and delivered. The policy task is a complex one; attempting to balance the need for cost containment whilst at the same time ensuring that the processes of innovation into Australia, and diffusion occur in a manner which maximises the benefit and minimises any harm to the Australian community.

Australia↗
PubMed1996

Spontaneous and induced mutations in a single open reading frame alter both virulence and avirulence in Xanthomonas campestris pv. vesicatoria avrBs2.

Molecular characterization of the avrBs2 locus from Xanthomonas campestris pv. vesicatoria has revealed that expression of this gene triggers disease resistance in Bs2 pepper (Capsicum annuum) plants and contributes to virulence of the pathogen. Deletion analysis and site-directed mutagenesis established the avrBs2 gene as a 2,190-bp open reading frame encoding a putative 80.1-kDa protein. Two classes of Xanthomonas pathogens evading Bs2 host resistance and displaying reduced fitness were found to be specifically mutated in avrBs2. Members of one class contained a 5-bp insertion, while the second class was distinguished by a divergent 3' region of avrBs2; both mutant classes were complemented in trans by a plasmid-borne copy of avrBs2. A divergent avrBs2 homolog was cloned from the Brassica pathogen X. campestris pv. campestris. The predicted AvrBs2 proteins from the two Xanthomonas pathovars were strongly conserved and had predicted sequence similarity with both Agrobacterium tumefaciens agrocinopine synthase and Escherichia coli UgpQ, two enzymes involved in the synthesis or hydrolysis of phosphodiester linkages. On the basis of homology with agrocinopine synthase and UgpQ and the dual phenotype of avirulence and virulence, several models for the function of AvrBs2 are proposed.

Alleles↗
PubMed1996

Health technology assessment.

This paper discusses the role of technology assessment in health care. The definition of health technology and its effect on health care in the Australian setting is reviewed. In particular, emphasis is placed on the work of the Australian Health Technology Advisory Committee and its approach to providing advice to clinicians on technology based healthcare services. Specific issues relating to laparoscopic services, radiation oncology, ultrasound, molecular biology and gene therapy, telemedicine and magnetic resonance imaging are outlined. The issue of the explosion of growth in the diagnostic services is also outlined.

Australia↗
PubMed1990

Widespread distribution and fitness contribution of Xanthomonas campestris avirulence gene avrBs2.

Disease-resistance genes introduced into cultivated plants are often rendered ineffective by the ability of pathogen populations to overcome host resistance. The bacterial pathogen Xanthomonas campestris pathovar vesicatoria causes bacterial spot disease of tomato and pepper, and this pathogen has been shown to overcome disease resistance in pepper (Capsicum annuum) by evading the recognition and defence response of the host plant. Numerous resistance genes to bacterial spot have been identified in pepper and its wild relatives, each providing resistance to specific races of X.c. vesicatoria. The resistance gene Bs1, for example, provides resistance to X.c. vesicatoria strains expressing the avirulence gene avrBs1; Bs2 provides resistance to stains expressing avrBs2 and so on. We now report that avr Bs2 is highly conserved among strains of X.c. vesicatoria, and among many other pathovars of X. campestris. Furthermore, we find that avrBs2 is in fact needed for full virulence of the pathogen on susceptible hosts. This implies that plants carrying Bs2 can recognize an essential gene of the bacterial pathogen, which may explain why Bs2 confers the only effective field resistance to X.c. vesicatoria in pepper.

DNA, Bacterial↗
PubMed1990

Characterization of IS476 and its role in bacterial spot disease of tomato and pepper.

IS476 is an endogenous insertion sequence present in copper-tolerant strains of Xanthomonas campestris pv. vesicatoria. Sequence analysis has revealed that the element is 1,225 base pairs in length, has 26-base-pair inverted repeats, and causes a 4-base-pair target site duplication upon insertion into the avirulence gene avrBs1. Comparison of the full-length sequence with sequences in the National Biomedical Research Foundation and National Institutes of Health data bases showed that one of the predicted IS476 proteins is partially homologous to the putative transposase of IS3 from Escherichia coli, and the inverted repeats of IS476 have significant homology to the inverted repeats of the IS51 insertion sequence of Pseudomonas syringae pv. savastanoi. A transposition assay based on the insertional inactivation of the sacRB locus of Bacillus subtilis was used to demonstrate that one of the three copies of IS476 residing on the 200-kilobase copper plasmid pXVCU1 is capable of transposition in several strains of Xanthomonas campestris. The position of IS476 insertion in several avrBs1 mutants was established and was shown to influence both induction of hypersensitivity and bacterial growth in planta.

Base Sequence↗
PubMed1978

Genetic counselling.

This article outlines the modes of inheritance of genetic disease, its risk of recurrence and the information the doctor needs in order to give accurate genetic counselling. Consideration also is given to the role of environmental factors in producing congenital defects. Suggestions are made as to how parents can be given the most reliable and humane help in understanding such conditions.

Abnormalities, Drug-Induced↗
PubMed1973

Dietary intake of linoleic acid in multiple sclerosis and other diseases.

The linoleic acid intake of patients with multiple sclerosis is not significantly different from that of healthy control subjects. This is true both in absolute terms and when linoleic acid intake is expressed as a percentage of total fat intake. In the other categories of illness, included as control groups, linoleic acid intake was significantly decreased only in patients with acute non-neurological illness and in this case only when considered in absolute terms. In all groups studied the daily linoleic acid intake was in excess of 1·7% of the total calorie intake and in the case of multiple sclerosis was 2·7% of the total calories ingested. Since other workers have shown that linoleic acid absorption is not altered in multiple sclerosis and we have shown that the diet is not deficient, it seems that the decrease in linoleic acid content is due to some process occurring after the absorption of this essential fatty acid.

Adult↗
PubMedDate not supplied

Unbalanced translocation t(15;22) in "severe" Prader-Willi syndrome.

A 13-year-old girl with an unbalanced karyotype 45,XX,-15,der(22)t(15;22)(q13;q13.3) de novo had Prader-Willi syndrome (PWS), (score 13.5), but with features of mental and physical retardation more severe than usually seen in PWS. The clinical diagnosis of PWS was confirmed by methylation analysis that showed absence of the paternal band. With GTG banding, the cytogenetic breakpoint on chromosome 15q13, with 15q14 intact, encompassed the PWS region, while the breakpoint on 22q was terminal. Investigations with FISH utilised ten different probes/combinations, namely SNRPN/PML, TUPLE1/22q13.3, TUPLE/ARSA, GABRB3, three YAC clones and one cosmid for specific regions within chromosome 15q, painting probes for the long arm of chromosomes 15 and 22 and a pantelomere probe. Deletion of SNRPN,TYAC 9 (at 15q11-12), TYAC19 (at 15q13) and GABRB3 (within the PWS locus), was evident on the derivative (22) chromosome, while TYAC10 (at 15q22), cos15-5 (at 15q22) and PML (15q22) were not deleted. On the der(22), 22q13.3 and ARSA were not deleted, but the most distal non specific pantelomeric probe was deleted. Thus, the severe phenotype could be attributable to deletion on chromosome 15q extending beyond q13 to q14, (further than the usual chromosome 15q deletion (q11-13) in PWS), or be related to loss of the very terminal 22q region (from ARSA to the pantelomere) or be due to genetic factors elsewhere in the genome.

Adolescent↗
PubMedDate not supplied

Performance evaluations of physician executives. Interview by Barbara J. Linney.

Six senior physician executives were interviewed to see how they were doing or not doing performance reviews in their organizations. There seems to be a trend toward doing them, but it is in the beginning stages. Of the physician executives surveyed, the experience ranges from formal lengthy evaluations with rating scales to reviewing a short list of goals. Several are in the process of developing new systems or revising old ones. Probably the most useful part of a performance evaluation is the conversation between the physician executive and the person he or she reports to. If you can stop approaching performance evaluations as passing negative judgments on people, but as having a conversation to hear their concerns, learn what their goals are, and offer ways to help them achieve their potential, they can be useful, enjoyable experiences for both people.

Employee Incentive Plans↗