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Biomedical subjects

R N Brown

Publications and source records attributed to R N Brown.

At least 19 recordsLinked to original sources
PubMed2006

Rejection with hemodynamic compromise: objective evidence for efficacy of photopheresis.

BACKGROUND: Photopheresis therapy (photo) has been advocated as a therapy to improve outcome after recalcitrant or severe rejection, but objective evidence of a beneficial effect has been elusive. This study examined the hypothesis that photo provides protection against rejection, rejection with hemodynamic compromise (HC), and death from rejection after cardiac transplantation. METHODS: Between 1990 and 2003, 36 adult patients (from 343 adult transplant recipients) received at least 3 months of photo (2-day treatment every 3 to 6 weeks for a target of 18 months) after HC rejection (n = 12), recurrent/recalcitrant rejection (n = 20), or as prophylaxis in the presence of anti-donor antibodies (n = 4). Survival and risk factors were examined by analysis using multivariate hazard function modulated renewal function. RESULTS: Patients selected for photo were at greater risk for rejection (p < 0.0001) and HC rejection (p < 0.0001) than non-photo patients. After 3 months of photo therapy, rejection risk was decreased (p = 0.04). More importantly, the hazard for subsequent HC rejection or rejection death was significantly reduced toward the risk-adjusted level of lower-risk non-photo patients (p = 0.006). CONCLUSIONS: This study provides objective evidence that photo reduces the risk of subsequent HC rejection and/or death from rejection when initiated for patients with high rejection risk. Photopheresis is recommended as an important therapeutic modality after rejection with hemodynamic compromise, although further studies are needed to define the precise mechanism of the effect and the potential for benefit in other patient sub-sets.

Adult↗
PubMed2006

Utility of long-term surveillance endomyocardial biopsy: a multi-institutional analysis.

BACKGROUND: The utility of long-term endomyocardial biopsy surveillance in heart transplant recipients has been questioned. This study was undertaken to identify risk factors for late rejection and to examine the impact of different biopsy surveillance protocols on outcomes using the registry of the Cardiac Transplant Research Database. METHODS: The study group consisted of all adult patients who underwent heart transplantation at the 33 centers participating in this investigation between January 1, 1993 and January 1, 2002, survived past the second post-transplant year, and were followed-up by a defined surveillance biopsy protocol. RESULTS: During a follow-up that consisted of 24,137 patient-years, 1,626 late rejections occurred. Shorter time since transplant, history of rejection, younger age and African-American ethnicity of the recipient were strong risk factors for late rejection. The practice of surveillance biopsy varied among institutions. Continued surveillance increased the rate of diagnosis of late rejection (RR = 1.3, p = 0.002). There was no reduction in the incidence of hemodynamically compromising rejection and no increase in survival in patients with long-term vs intermediate-term surveillance. Short-term surveillance was associated with an increased incidence of hemodynamically compromising rejection, particularly among high-risk patients, and increased mortality in African-American patients. CONCLUSIONS: There are no apparent benefits from surveillance biopsy beyond 5 years post-transplant. Surveillance biopsy between 2 and 5 years post-transplant was found to reduce mortality in African-American recipients. Non-African-American recipients at high risk for late rejection will likely benefit from surveillance up to 5 years post-transplant.

Adult↗
PubMed2006

Sylvatic maintenance of Borrelia burgdorferi (Spirochaetales) in Northern California: untangling the web of transmission.

Lyme borreliosis is associated with several genospecies of Borrelia burgdorferi sensu lato (s.l.) (Spirochaetales), but human disease has been associated only with Borrelia burgdorferi sensu stricto (s.s.) Johnson, Schmid, Hyde, Steigerwalt & Brenner in the western United States. Restriction fragment length polymorphism (RFLP) analysis of rrf-rrl amplicons from 124 tick and mammalian isolates from various habitats yielded 13 RFLP patterns. Of these patterns, six were patterns previously associated either with Borrelia bissettii Postic, Marti Ras, Lane, Hendson & Baranton or Borrelia burgdorferi s.s., and the remaining seven patterns belonged to diverse and previously uncharacterized Borrelia spp. Uncharacterized Borrelia spp. were cultured most frequently from Ixodes spinipalpis Hadwen & Nuttall and California kangaroo rats, Dipodomys californicus Merriam, inhabiting grasslands, and B. bissettii from I. spinipalpis and dusky-footed woodrats, Neotoma fuscipes Baird, associated with oak woodlands or chaparral. B. burgdorferi s.s. typically was isolated from host-seeking Ixodes pacificus Cooley & Kohls collected in dense oak woodlands, woodland-grass, or redwood forests. Although some isolates of B. burgdorferi s.s. were cultured from woodrats, there was no clear association of this human pathogen with any vertebrate host. These findings, along with recent evidence indicating that the western gray squirrel, Sciurus griseus Ord, may be an important reservoir of B. burgdorferi s.s. in Californian oak woodlands, suggest that our earlier hypothesis implicating an enzootic cycle involving woodrats and I. spinipalpis is insufficient to account for observed patterns of infection in nature.

Animals↗
PubMed2005

To induce or not to induce: do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy?

BACKGROUND: Induction immunosuppression utilizing lymphocytolytic agents in the early peri-operative period has a number of theoretical and practical advantages and disadvantages. However, the efficacy of cytolytic agents as induction therapy remains unproven. METHODS: To assess the current impact of induction therapy in heart transplantation, we queried a multi-institutional database regarding the frequency of use, type of agent, duration of therapy and outcomes of 6,553 patients transplanted from 1990 to 2001. A study group of 5,897 patients were identified who survived the first 48 hours post-transplant and received either no induction therapy (n = 4,161) or induction with OKT3 or anti-thymocyte preparations (n = 1,736). RESULTS: By multivariate analysis, risk factors for rejection death were identified and then applied to a model of overall mortality. Among patients with a 1-year risk of rejection death at >5%, induction therapy provided a survival advantage, but survival with induction was decreased when the risk of rejection death was <2%. Specific patient sub-sets that received a survival benefit in the current era with induction included younger patients of black race with >/=4 HLA mismatches and long-term (>6 months) support on a ventricular assist device (VAD). CONCLUSIONS: Use and application of induction therapy continues to be controversial in heart transplantation. At present, this approach appears to be beneficial in selected patients who are at high risk for rejection death, but likely detrimental in patients who are at low risk for rejection death. Those with a combination of longer term VAD support, of black ethnicity, and having extensive HLA mismatching are most likely to benefit from cytolytic induction therapy.

Adult↗
PubMed2003

RAPD markers linked to eastern filbert blight resistance in Corylus avellana.

A total of 1,110 decamer primers were screened for RAPD markers linked to a dominant allele in hazelnut ( Corylus avellana) that confers resistance to eastern filbert blight caused by Anisogramma anomala. Twenty RAPD markers linked in coupling, and five markers linked in repulsion, were found. A seedling population was used to construct a linkage map of the region flanking the resistance locus. The map spans 46.6 cM, with 14 markers on one side of the resistance locus and eight on the other side. Eleven markers showed less than 3% recombination with resistance, including three that showed no recombination. Seven of these 11 markers are sufficiently robust to allow their use in marker-assisted selection. These include AA12(850) which shows no recombination, and six markers on one side of the resistance locus: 173(500), 152(800), 122(825), 275(1130), H19(650) and O16(1250). Marker 268(580), which flanks the resistance locus on the other side, is also suitable for use in marker-assisted selection, but shows 5.8% recombination with resistance. Other markers are less suitable for marker-assisted selection because of sensitivity to changes in primer or MgCl(2) concentration, or the long time required for electrophoresis to separate bands of similar size. The 16 markers closest to the resistance locus were cloned and sequenced. The W07(365) marker, which showed no recombination with the resistance locus but is difficult to score, includes a CT microsatellite repeat. The sequence information will allow the design of SCAR primers and eventual map-based cloning of the resistance allele.

Base Sequence↗
PubMed2000

Differences in the epidemiology of theileriosis on smallholder dairy farms in contrasting agro-ecological and grazing strata of highland Kenya.

A prospective cohort study was conducted in five purposively-sampled agro-ecological zone (AEZ)-grazing system strata in Murang'a District, Kenya, between March 1995 and June 1996. The study strata were selected based on a preliminary characterization study to represent the widest range of risks to East Coast fever (ECF) in the District and included zero-grazing and open-grazing farms. In total, 225 calves from 188 smallholder farms were examined from birth to 6 months of age and visited within the first 2 weeks of life and thereafter at bi-weekly intervals for up to 14 visits. The purpose of the study was to characterize the differences in epidemiology (risks of infection, morbidity and mortality) and potential control of ECF between the selected strata. Evidence of Theileria parva infection was assessed by increased antibody levels as measured in an indirect ELISA assay by the percent positivity (PP) of serum samples relative to a strong positive reference serum. Sero-conversion risks of T. parva were highest in the open-grazing strata. Antibody prevalence in adult cattle and ECF morbidity and mortality risks were also highest in open-grazing strata. While different, all five AEZ-grazing strata were considered to be endemically unstable for ECF. East Coast fever challenge was low in all zero-grazing strata and this challenge is likely to remain low due to continuing intensification of smallholder farming in the central highlands. In the open-grazing strata, there was higher challenge and a greater impact of ECF.

Animals↗
PubMed1999

First trimester umbilical venous Doppler sonography in chromosomally normal and abnormal fetuses.

In 342 singleton pregnancies in which the patients were undergoing chorionic villus sampling at 11 to 14 weeks of gestation, color Doppler sonography was used to obtain waveforms from the umbilical cord. The prevalence of pulsatile flow in the umbilical vein was higher in the 18 fetuses with trisomy 18 or 13 (16 of 18; 88.9%) than in the 18 fetuses with trisomy 21 (6 of 18; 33.3%) or the 302 chromosomally normal fetuses (73 of 302; 24.2%).

Aneuploidy↗
PubMed1996

Ixodes (Ixodes) jellisoni and I. (I.) neotomae (Acari:Ixodidae): descriptions of the immature stages from California.

Nymphal and larval stages of Ixodes (Ixodes) jellisoni Cooley & Kohls and I. (I.) neotomae Cooley are described for the first time. These 2 tick species occur only in the western United States, predominantly in California. The primary host for I. jellisoni is the California kangaroo rat, Dipodomys californicus (Merriam); that for I. neotomae is the dusky-footed woodrat, Neotoma fuscipes Baird. The etiologic agent of Lyme disease Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt & Brenner has recently been isolated from both tick species, and I. neotomae was proven a competent enzootic vector of the Lyme disease spirochete.

Animals↗
PubMed1996

Reservoir competence of four chaparral-dwelling rodents for Borrelia burgdorferi in California.

Aspects of the reservoir competence of four rodents for the Lyme disease spirochete, Borrelia burgdorferi, were evaluated in California. Rodents were live-trapped and ear-punch biopsies were cultured during each season. A second set of biopsies was cultured from representative individuals after 2-3 weeks of captivity and the results of culturing biopsies taken on both dates were compared with the results of feeding Ixodes pacificus larvae on hosts xenodiagnostically. The prevalence of infections did not differ significantly between dusky-footed woodrats (Neotoma fuscipes) and California kangaroo rats (Dipodomys californicus) nor among seasons. Combined results of the three tests showed that 85.7% of dusky-footed woodrats (n = 21) and 78.6% of California kangaroo rats (n = 14) were infected with B. burgdorferi. In contrast, only 22.2% of brush mice (Peromyscus boylii) (n = 14) and 7.1% of pinyon mice (P. truei) (n = 9) were infected. The sensitivity of culturing ear-punch biopsies as an assay for borrelial infection was significantly greater when biopsies were taken after a short period of captivity (0.89) rather than on the day of capture (0.52). Tick xenodiagnosis, in which I. pacificus was used as the vector, revealed borrelial infections in 90.3% of infected rodents. Spirochetes were observed in 37.7% of 239, 45.2% of 155, 60.0% of 10, and 7.1% of 14 cultures of nymphal I. pacificus fed as larvae on naturally infected woodrats, kangaroo rats, brush mice, and a pinyon mouse, respectively. The mean prevalence of infection in xenodiagnostic ticks varied significantly among host species with a greater proportion of ticks infected while feeding on woodrats and kangaroo rats than on mice. This study reconfirms previous reports that implicated woodrats and kangaroo rats as reservoirs of B. burgdorferi in California.

Animals↗
PubMed1994

Vector competence of Ixodes pacificus and Dermacentor occidentalis (Acari: Ixodidae) for various isolates of Lyme disease spirochetes.

The vector competence of the western black-legged tick, Ixodes pacificus Cooley & Kohls, and the Pacific Coast tick, Dermacentor occidentalis Marx, for the Lyme disease spirochete (Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner) was compared. Rabbits, hamsters, and the deer mouse, Peromyscus maniculatus (Wagner), were injected with cultured spirochetes or infected tick-suspensions, or were fed upon by spirochete-infected ticks. Five of seven isolates used as inocula were reisolated from vertebrates with the ear-punch biopsy technique. Three isolates (CA4, 5, 7) that were infectious for both vertebrates and ticks possessed prominent low-molecular-weight protein bands that had relative mobilities of approximately 24-26 kd. The ability of ticks to acquire and maintain various inocula of B. burgdorferi was evaluated by feeding uninfected larvae xenodiagnostically on all three hosts 0-63 d postinjection. Low percentages (0-10.6%) of the I. pacificus and none of the D. occidentalis became infected. By contrast, 33% of I. pacificus and 40% of Ixodes scapularis Say (= I. dammini Spielman, Clifford, Piesman & Corwin) that fed on hamsters infected by tick-bite acquired and transstadially passed spirochetes; 10% of D. occidentalis fed on infected hamsters similarly acquired but did not maintain spirochetes. Ixodes pacificus nymphs efficiently transmitted B. burgdorferi to deer mice and a hamster. Feeding by one spirochete-infected nymph was sufficient to produce patent infections in each of five mice.

Animals↗
PubMed1994

Natural and experimental Borrelia burgdorferi infections in woodrats and deer mice from California.

Sequestration of spirochetes and concurrent histopathologic lesions were evaluated in tissues of Borrelia burgdorferi-infected dusky-footed woodrats (Neotoma fuscipes) and deer mice (Peromyscus maniculatus). Rodents were either wild-caught and naturally infected or were experimentally infected by tick bite, by intramuscular (i.m.) injection of cultured spirochetes, or by i.m. injection of tick suspensions. Samples of host tissues, including skin, blood, ear, brain, eye, heart, lung, liver, spleen, kidney, and urinary bladder, were removed from up to 21 woodrats and four deer mice and cultured in BSK II medium. Borreliae-positive cultures of ear punch biopsies were obtained from 10 of 11 woodrats and from all of four deer mice. Additionally, positive cultures were obtained from three of 36 skin biopsies of woodrats, and from one of 36 cultures of woodrat blood. In contrast, spirochetes were not observed in 505 cultures of internal organs or whole blood. Samples of tissues from seven naturally infected woodrats, four experimentally infected woodrats, and nine experimentally infected deer mice also were examined for histopathologic lesions. Nonsuppurative cellular infiltrates were recognized in samples from most tissue types from woodrats, but few lesions were observed in tissues from deer mice. Recognized lesions in woodrats that were consistent with infections of Lyme borreliosis in other species included synovitis, myositis, and myocarditis. Such lesions were more common in woodrats than in deer mice. Inflammatory lesions, especially synovitis, were more common in woodrats with long-term infections than in woodrats with relatively short-term infections. No clinical signs of disease were observed in either species of rodent.

Animals↗
PubMed1993

Genetic diversity among Borrelia burgdorferi isolates from wood rats and kangaroo rats in California.

Twenty-nine Borrelia burgdorferi isolates, obtained from dusky-footed wood rats (Neotoma fuscipes) and California kangaroo rats (Dipodomys californicus) in California, were analyzed genetically. Chromosomal DNA was examined by restriction endonuclease analysis (REA) and gene probe restriction fragment length polymorphism. Pulsed-field gel electrophoresis was used to analyze the plasmid profiles of the isolates. REA, the method with the greatest discrimination, disclosed 24 distinct restriction patterns among the 29 isolates. These restriction patterns were sorted into four restriction fragment length polymorphism groups on the basis of their gene hybridization patterns. Results of the REA and plasmid profile analysis supported this grouping. The degree of genetic diversity among Californian isolates demonstrated by our findings is greater than that previously reported among other groups of North American isolates and is similar or greater than the diversity reported among European isolates.

Animals↗
PubMed1992

Lyme disease in California: a novel enzootic transmission cycle of Borrelia burgdorferi.

Knowledge of zoonotic transmission cycles is essential for the development of effective strategies for disease prevention. The enzootiology of Lyme disease in California differs fundamentally from that reported from the eastern United States. Woodrats, not mice, serve as reservoir hosts, and Ixodes neotomae, a nonhuman-biting tick, maintains the agent of Lyme disease, Borrelia burgdorferi, in enzootic cycles. The western black-legged tick, Ixodes pacificus, is the primary vector to humans, but it appears to be an inefficient maintenance vector. Isolates of B. burgdorferi from California exhibit considerable antigenic heterogeneity, and some isolates differ strikingly from isolates recovered from this and other geographic regions.

Animals↗
PubMed1992

First isolation of Borrelia burgdorferi in southern California.

The Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was isolated from the blood of a dusky-footed wood rat, Neotoma fuscipes Baird, in the San Bernardino Mountains of southern California. Antigenic, protein, and molecular analyses demonstrated that the isolate varied slightly from most isolates of B. burgdorferi from northern California and was clearly distinct from other species of Borrelia that are endemic to the state. This is the first reported isolate of B. burgdorferi from southern California and demonstrates that the Lyme disease spirochete is enzootic in mountains near the major human population center of the state.

Animals↗
PubMed1991

Wood rats and kangaroo rats: potential reservoirs of the Lyme disease spirochete in California.

The etiologic agent of Lyme disease, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was isolated repeatedly from dusky-footed wood rats, Neotoma fuscipes Baird, and California kangaroo rats, Dipodomys californicus Merriam, in northern California. All animals were collected in a region endemic for Lyme disease but for which the natural reservoir of B. burgdorferi was unknown. Similar attempts to isolate spirochetes from lizards, other species of rodents, jack rabbits, and deer between 1987 and 1991 were unsuccessful. Spirochetes isolated from wood rats and kangaroo rats were antigenically similar to strains of B. burgdorferi that had been isolated previously from the western black-legged tick, Ixodes pacificus Cooley & Kohls, in California. Similar enzootic cycles involving wood rats or kangaroo rats should be sought in other regions of the United States where the reservoirs of this spirochete are unknown.

Animals↗