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Biomedical subjects

A Ross

Publications and source records attributed to A Ross.

At least 19 recordsLinked to original sources

Identification of

[8-vinyl]-Protochlorophyllide a1 was isolated from a Prochloron sp. associated with the host ascidian, Lissoclinum patella. To obtain sufficient amounts for identification of the purified pigment, suitable extraction procedures and HPLC systems were developed. The structure was finally elucidated by UV-VIS and fluorescence spectroscopy, mass spectrometry and NMR (rotating-frame Overhauser enhancement spectroscopy). [8-vinyl]-Protochlorophyllide a was originally detected only as an intermediate in chlorophyll biosynthesis. Although its presence as a light-harvesting pigment was previously suggested in some prochlorophytes and eukaryotic algae, this is the first unequivocal demonstration of [8-vinyl]-protochlorophyllide a in an oxygenic phototroph. We also show that [8-vinyl]-protochlorophyllide a occurs in Prochloron species of four other ascidians as well as in Micromonas pusilla and Prochlorococcus marinus. The possible role of this pigment in photosynthesis is discussed.

Journal Article

Experimentally induced bovine spongiform encephalopathy did not transmit via goat embryos.

Goats are susceptible to experimental challenge with bovine spongiform encephalopathy (BSE). This study set out to investigate whether the transmission of BSE could occur in goats following the transfer of embryos from experimentally infected donor females into uninfected recipient females. The results showed no evidence of transmissible spongiform encephalopathy disease in any of the offspring which developed from embryos from infected donors, nor indeed in any of the recipient females used as surrogate dams. In addition, there was no indication of experimental BSE spreading as either a venereal infection to males used in mating or by maternal transmission to offspring born naturally to experimentally infected donors, although numbers were small.

Animals

Lung epithelial cells are a major site of murine gammaherpesvirus persistence.

It is currently believed that latently infected, resting B lymphocytes are central to gammaherpesvirus persistence, whereas mucosal epithelial cells are considered nonessential. We have readdressed the question of nonlymphoid persistence using murine gammaherpesvirus 68 (MHV-68). To dissect lymphoid from nonlymphoid persistence, we used microMT transgenic mice that are defective in B cells. MHV-68 DNA persisted in the lungs of intact and B cell-deficient mice. Both episomal and linear forms of the virus genome were present in lungs, implying the presence of both latency and productive replication. In situ hybridization for virus tRNA transcripts revealed latent MHV-68 in pulmonary epithelial cells. Infectious virus was recovered from the lungs of microMT mice after T cell depletion, showing that the persisting virus DNA was reactivatable. Finally, using adoptive transfer of B cells into B cell-deficient mice, it was shown that virus persisting in lungs seeded splenic B cells, and virus resident in the spleen seeded the lungs. These results show that mucosal epithelia can act as a nonlymphoid reservoir for gammaherpesvirus persistence, and that there is a two-way movement of virus between lymphoid and nonlymphoid compartments during persistence.

Animals

Early manifestations (pre-AIDS) of HIV-1 infection in Uganda.

OBJECTIVES: To describe the early manifestations of HIV-1 infection before the development of AIDS, in a rural Ugandan population. METHODS: Three monthly follow-up of HIV-1-infected and uninfected participants in an HIV-1 natural history cohort from the start of the cohort in 1990 to the end of 1996. RESULTS: A total of 107 persons with prevalent infection and 104 persons with incident infection were enrolled. Eighty (75%) prevalent and 89 (86%) incident individuals were asymptomatic on enrollment. Of the 91 persons with incident infection seen within 2 years of their estimated date of seroconversion, 51% [95% confidence interval (CI), 40-61] were still asymptomatic 2 years after seroconversion. At 4 and 5 years after seroconversion, only 26% (95% CI, 17-36) and 11% (95% CI, 4-22), respectively, remained asymptomatic. A total of 89 participants entered World Health Organization (WHO) stage 2, and their main stage-defining conditions were weight loss <10% (and > 5%) and minor mucocutaneous manifestations. The median CD4 lymphocyte count for participants entering WHO stage 2 was 516 x 10(6) cells/l (interquartile range, 360-884 x 10(6)/l). A total of 94 participants entered WHO stage 3 and the main reasons were weight loss >10%, unexplained chronic diarrhoea, fever for more than 1 month, and severe bacterial infection. The median CD4 lymphocyte count for participants entering WHO stage 3 was 428 x 10(6) cells/l (interquartile range, 276-736 x 10(6)/l). The rates of all conditions reported under the WHO staging system were significantly more frequent in HIV-positive persons than HIV-negative controls with the exception of fever for more than 1 month and oral hairy leukoplakia (which was seen in only three individuals). CONCLUSION: These are the first data from a non-selected African population describing the early manifestations of HIV infection. The main early manifestations were weight loss, minor mucocutaneous features, chronic diarrhoea, chronic fever and severe bacterial infections. The apparent rapid development of HIV-related signs and symptoms is probably indicative of the high background level of these conditions in our study area, as reflected by the rates of these conditions in the HIV-negative controls.

Adult

Primary care physician compensation method in medical groups: does it influence the use and cost of health services for enrollees in managed care organizations?

CONTEXT: Growth of at-risk managed care contracts between health plans and medical groups has been well documented, but less is known about the nature of financial incentives within those medical groups or their effects on health care utilization. OBJECTIVE: To test whether utilization and cost of health services per enrollee were influenced independently by the compensation method of the enrollee's primary care physician. DESIGN: Survey of medical groups contracting with selected managed care health plans, linked to 1994 plan enrollment and utilization data for adult enrollees. SETTING: Medical groups, major managed care health plans, and their patients/enrollees in the state of Washington. STUDY PARTICIPANTS: Sixty medical groups in Washington, 865 primary care physicians (internal medicine, pediatrics, family practice, or general practice) from those groups and affiliated with 1 or more of 4 managed care health plans, and 200 931 adult plan enrollees. INTERVENTION: The effect of method of primary care physician's compensation on the utilization and cost of health services was analyzed by weighted least squares and random effects regression. MAIN OUTCOME MEASURES: Total visits, hospital days, and per member per year estimated costs. RESULTS: Compensation method was not significantly (P>.30) related to utilization and cost in any multivariate analyses. Patient age (P<.001), female gender (P<.001), and plan benefit level (P<.001) were significantly positively related to visits, hospital days, and per member per year costs. The primary care physician's age was significantly negatively related (P<.001) to all 3 dependent measures. CONCLUSIONS: Compensation method was not significantly related to use and cost of health services per person. Enrollee, physician, and health plan benefit factors were the prime determinants of utilization and cost of health services.

Capitation Fee

Effectiveness of pediatric practice consultation on missed opportunities for immunization.

OBJECTIVE: To evaluate the effectiveness of pediatric practice consultation in reducing missed-opportunity rates at eight pediatric sites in Baltimore, Maryland. The overarching goal was to decrease the occurrence of missed opportunities from 33% to 15% for the first, second, and third diphtheria and tetanus toxoids and pertussis vaccines during visits at which children were eligible for the vaccines. DESIGN: The effect of an in-office educational program alone at four sites is compared with the educational program and a consultation on office vaccination practices at four matched sites. All eight sites received a small grant ($2,000) to fund practice changes. The medical records of children making visits before and after the interventions were audited to determine missed-opportunity rates. The policies and operations and the knowledge, attitudes, and practices of physicians and nurse practitioners at each site were also assessed. RESULTS: The four education-consultation sites experienced a statistically significant 14% net reduction in the missed-opportunity rate relative to the education-only sites. This positive effect, however, was largely due to an increase in missed opportunities at one education-only site. There was a 10% increase in the missed-opportunity rate among the education-only sites and a 4% decrease among the education-consultation sites; neither change was statistically significant. Two of the three sites that reduced missed opportunities were matched health maintenance organizations (HMOs). Shortly after the interventions, both HMOs implemented tracking and follow-up information systems, which were planned before the interventions. CONCLUSIONS: There is no evidence that either the educational program alone or the educational program and consultation combination reduced missed opportunities. The findings suggest that improved tracking and follow-up data systems and vaccination of children at sick visits may reduce missed opportunities.

Baltimore

A hydrophobic interaction site for lysozyme binding to polyethylene glycol and model contact lens polymers.

Proton nuclear magnetic resonance (1H-NMR) spectroscopy is used to identify a preferred binding site for uncharged hydrophilic polymers on the surface of hen egg-white lysozyme. Chemical shift titrations show that exchangeable proton signals from amino acids Arg-61, Trp-62, Trp-63, Arg-73, Lys-96 and Asp-101 are selectively perturbed upon binding of poly(ethylene oxide), poly(ethylene glycol) and poly(ethylene-co-propylene oxide). The greatest binding-induced chemical shift changes are observed for Trp-62, Arg-61 and Arg-73 at the edge of the active site cleft of the protein, consistent with a predominantly hydrophobic interaction mode involving the polymer ethylene moieties. The more hydrophilic species poly(dihydroxypropyl methacrylate) causes similar but substantially smaller chemical shift effects than the other polymers, confirming the nature of the interaction. A dissociation constant of 76+/-5 mM is determined for the poly(ethylene glycol)-lysozyme complex. The relatively low affinity of the protein-polymer interactions compared to oligosaccharide substrate binding suggests that lysozyme activity is minimally affected by these materials.

Binding Sites

Maternal satisfaction with labour analgesia.

Satisfaction with childbirth is a multidimensional issue, of which analgesia is but one component. The importance of analgesia as a contribution to overall satisfaction has been recognized increasingly in the last 50 years, but improvement in quality of available analgesia has not always resulted in commensurate improvement in satisfaction. Satisfaction by its very nature has proved to be difficult both to define and to quantify, and no reliable standards of measurement have been accepted. Pain relief in childbirth is subject to many social and cultural modifiers, which continue to change. Control of pain rather than absolute amelioration is seen by many to provide greater satisfaction. Analgesia issues still do not figure prominently in the overall satisfaction of the birthing process for the vast majority of women, despite the availability of and demand for improved methods of relief. The interpersonal relationships established between patient and healthcare providers may ultimately be of more importance in the determination of satisfaction with management.

Analgesia, Obstetrical

Clonidine suppression test revisited.

BACKGROUND: The diagnosis of pheochromocytoma may be difficult because the clinical picture is variable. OBJECTIVE: The purpose of this paper is to report our experience and to review the published data on the diagnostic significance and risks of the clonidine suppression test in the diagnosis of pheochromocytoma. PATIENTS AND METHODS: 114 patients were evaluated for pheochromocytoma using the clonidine suppression test. RESULTS: The diagnosis was established in four patients. Overall accuracy of the test in our own series was 98% when the normal response to clonidine was defined as total plasma catecholamines of less than 500 ng/L, or less than 70% of the baseline value. No serious complication was noted. CONCLUSION: Our data and the published series demonstrate that the clonidine suppression test is accurate and safe in patients with suspected pheochromocytoma.

Adrenal Gland Neoplasms

Causes of death in a rural, population-based human immunodeficiency virus type 1 (HIV-1) natural history cohort in Uganda.

BACKGROUND: While human immunodeficiency virus (HIV)-related causes of death have been well documented in developed countries, in Africa data are scanty and mainly based on autopsy studies from city hospitals which are highly selective and may not represent causes of HIV-associated deaths in the general population. This study, from a rural population, describes the causes of death in HIV-positive people and their HIV-negative controls. METHODS: A natural history cohort comprising HIV-1 infected participants and HIV-negative controls was established in rural Uganda in 1990. Causes of death were determined by reviewing the premorbid clinical and laboratory findings and from information obtained from relatives. Blindness to the deceased's HIV serostatus was maintained throughout. RESULTS: In all, 78 deaths occurred over a 6-year period: 63 deaths occurred in the HIV-positive cases (53 prevalent and 10 incident cases) and 15 deaths in the HIV-negative controls. Of the prevalent cases, 56%, and 9% the incident cases enrolled died, compared with 7% of the HIV-negative controls. Of the 55 HIV-positive cases with sufficient data to establish cause of death, 52 (95%) were assessed as having HIV-associated deaths and 48 (87%) died in WHO stage 4 (AIDS). The main causes of death were wasting syndrome (31%), chronic diarrhoea (22%), cryptococcal meningitis (13%) and chest infection (11%). CONCLUSIONS: Our results represent an unbiased selection of deaths in a rural area. The HIV-positive cases have high death rates and die of HIV-related pathologies. The main causes of death reflect the WHO clinical case definition of AIDS. Cryptococcal meningitis is also a common cause of death in this population.

Adult

Initiating the first DTP vaccination age-appropriately: a model for understanding vaccination coverage.

OBJECTIVE: Our earlier research found that the strongest predictor of not being up to date on the full series of immunizations by 24 months is failure to receive the first diphtheria vaccine and tetanus toxoid and pertussis vaccine (DTP1) on time. To learn more about the relationship between successful vaccination during the DTP1 age-appropriate (DTP1-AA) period (between 42 and 92 days of life, inclusive) and an infant's early visit to the physician (before 42 days of life), we quantified children's progression through a sequence of provider visits and outcomes. DESIGN: This study analyzed data from 426 children living in the 57 poorest census tracts in Baltimore. For each DTP1-AA visit, we calculated the percentage of times a DTP1-AA vaccination, provider missed opportunity, or deferral for a valid contraindication occurred. Relative and attributable risks were computed to assess associations between DTP1-AA vaccination and early visits and missed opportunities. RESULTS: We found the following: 1) Children who made a visit before 42 days of life were more than twice as likely to receive a DTP1-AA vaccination; 2) the missed opportunity rate for children who did not make an early visit was approximately twice that of the early-visit group; and 3) well visits were more likely to result in DTP1-AA immunization than sick visits. Attributable risk calculations show that DTP1-AA vaccination rates could be increased in this population by one third if all infants had an early visit. CONCLUSIONS: Early in-office visits seem to make DTP1-AA vaccination more likely. These rates may be amenable to intervention by increasing early visits and reducing DTP1-AA missed opportunities. Introduction of the hepatitis B vaccine to the recommended series may place more emphasis on early visits and result in increased DTP1-AA rates and, ultimately, higher vaccination coverage rates.

Age Factors

Effect of compensation method on the behavior of primary care physicians in managed care organizations: evidence from interviews with physicians and medical leaders in Washington State.

The perceived relationship between primary care physician compensation and utilization of medical services in medical groups affiliated with one or more among six managed care organizations in the state of Washington was examined. Representatives from 67 medical group practices completed a survey designed to determine the organizational arrangements and norms that influence primary care practice and to provide information on how groups translate the payments they receive from health plans into individual physician compensation. Semistructured interviews with 72 individual key informants from 31 of the 67 groups were conducted to ascertain how compensation method affects physician practice. A team of raters read the transcripts and identified key themes that emerged from the interviews. The themes generated from the key informant interviews fell into three broad categories. The first was self-selection and satisfaction. Compensation method was a key factor for physicians in deciding where to practice. Physicians' satisfaction with compensation method was high in part because they chose compensation methods that fit with their practice styles and lifestyles. Second, compensation drives production. Physician production, particularly the number of patients seen, was believed to be strongly influenced by compensation method, whereas utilization of ancillary services, patient outcomes, and satisfaction are seen as much less likely to be influenced. The third theme involved future changes in compensation methods. Medical leaders, administrators, and primary care physicians in several groups indicated that they expected changes in the current compensation methods in the near future in the direction of incentive-based methods. The responses revealed in interviews with physicians and administrative leaders underscored the critical role compensation arrangements play in driving physician satisfaction and behavior.

Administrative Personnel

Skin carcinogenicity of condensed asphalt roofing fumes and their fractions following dermal application to mice.

Condensed roofing asphalt fumes, generated at 316 degrees C, were collected by cold trap condensation and fractionated by preparative high performance liquid chromatography. Chemical classes in each of the fractions (A-E) were identified by gas chromatography/mass spectroscopy. The fractions, various combinations of fractions, the raw and heated asphalt, the neat asphalt fume and the reconstituted asphalt were tested for carcinogenicity, and three fractions were tested for cocarcinogenicity and tumor promotion with benzo[a]pyrene (BaP). The skin application carcinogenesis bioassay was conducted by twice weekly application of test materials in 0.05 ml of acetone/cyclohexane (1:1) for 104 weeks to 40 groups of male C3H/HeJ mice (30/group). Fractions were applied at a mass in proportion to their amount in the neat asphalt fumes. In addition, the neat asphalt fume was tested on Sencar mice to determine if this strain was more susceptible to the carcinogenic effects of the fumes. Condensed neat asphalt fumes produced similar and statistically significant increased tumor yields of papillomas and carcinomas in both strains as compared to respective vehicle controls. Recombination of all fractions resulted in a tumor response similar to neat asphalt fumes. Among individual fractions, C was most potent, followed by B. The other single fractions were without significant tumorigenic activity. Combinations containing fractions B and C were most active among the mixtures that were assayed and no evidence of enhancement of tumorigenesis in the mixtures was found. No significant cocarcinogenic or tumor promoting activity was observed with fractions A, D, or E and BaP. Raw unheated asphalt produced a few tumors in C3H mice, but no tumors were seen when raw asphalt heated to 316 degrees C, with the fumes permitted to escape, was applied.

Animals

Expression of RBM in the nuclei of human germ cells is dependent on a critical region of the Y chromosome long arm.

The association of abnormal spermatogenesis in men with Y chromosome deletions suggests that genes important for spermatogenesis have been removed from these individuals. Recently, genes encoding two putative RNA-binding proteins (RBM and DAZ/SPGY) have been mapped to two different regions of the human Y chromosome. Both of these genes encode proteins that contain a single RNA recognition motif and a (different) internally repeating sequence. Y-linked RBM homologues are found in all mammalian species. We have raised an antiserum to RBM and used it to show that RBM is a nuclear protein expressed in fetal, prepubertal, and adult male germ cells. The distribution of RBM protein in the adult correlates with the pattern of transcriptional activity in spermatogenesis, suggesting that RBM is involved in the nuclear metabolism of newly synthesized RNA. RBM sequences are found on both arms of the Y chromosome making genotype-phenotype correlations difficult for this gene family. To address the location of the functional genes and the consequences of their deletion, we examined a panel of men with Y chromosome deletions and known testicular pathologies using this antiserum. This approach enabled us to map a region of the Y chromosome essential for RBM expression. In the absence of detectable RBM expression we see stages of germ cell development up to early meiosis, but not past this point into the haploid phase of spermatogenesis.

Adult

Are immunizations an incentive for well-child visits?

OBJECTIVE: To assess the beliefs of parents and the visit patterns of their children to determine whether immunizations act as an incentive to use well-child care. DESIGN AND METHODS: Medical record audits provided data on immunizations and well-child visits. Two questions from a parent interview were used to identify 4 groups of parents: (1) motivated and (2) unmotivated to keep a well-child care appointment regardless of whether immunizations are scheduled, (3) vaccine-motivated and (4) checkup-motivated (parents who were influenced negatively by the prospect of receiving vaccinations). The percentage of children with a visit at each age window for well-child visits and the percentage up-to-date for their immunizations at given ages were compared across the 4 groups. The 4 groups were also compared for other parental attitudes about immunizations and well-child visits, and on sociodemographic and access characteristics. RESULTS: Most (73.3%) of the 502 parents surveyed were classified as motivated and 5% as unmotivated to keep a well-child care appointment regardless of whether an immunization was scheduled. Only 18.3% were categorized as vaccine-motivated and 3.4% as checkup-motivated. For all 4 groups, there was no discernible difference in attendance between immunization and nonimmunization visits. Attendance in the windows for well-child visits and percentage of children up-to-date on immunizations declined with increasing age. CONCLUSIONS: In this inner-city population, attendance patterns at visits did not support the incentive hypothesis. This finding should reassure clinicians that providing immunizations outside of regular well-child care visits will not necessarily decrease attendance at visits for well-child care.

Baltimore