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Biomedical subjects

L D Brown

Publications and source records attributed to L D Brown.

At least 19 recordsLinked to original sources

Nonuniform distribution of myosin light chains within the thick filaments of lobster slow muscle: Immunocytochemical study.

The in situ distribution of the alpha and beta myosin light chains was investigated at the subsarcomeric and subfilament levels in individual fibers of the superficial flexor muscle (SFM) of the lobster, Homarus americanus. Polyclonal antibodies were produced against the two classes of myosin light chains and used for subsequent immunolocalization on thin sections of sarcomeres and on isolated filaments from both the medial and lateral fiber bundles of the SFM. The beta myosin light chains were uniformly distributed within the crossbridge region of sarcomeres of both medial and lateral bundles. The alpha myosin light chains were uniformly distributed within the crossbridge region of sarcomeres from the medial bundle, but were nonuniformly distributed over the crossbridge region of lateral bundle sarcomeres. In the latter, the number of alpha myosin light chains was highest toward the center of the thick filaments, diminishing towards the ends. Similar distributions of alpha light chains were found in isolated myosin filaments. These data demonstrate that heterogeneity in protein composition extends to the level of the myosin filament and suggest that the myosin filament substructure in lobster may be different than that found in vertebrate skeletal muscle.

Animals↗

A-band architecture in vertebrate skeletal muscle: polarity of the myosin head array.

Despite extensive knowledge of many muscle A-band proteins (myosin molecules, titin, C-protein (MyBP-C)), details of the organization of these molecules to form myosin filaments remain unclear. Recently the myosin head (crossbridge) configuration in a relaxed vertebrate muscle was determined from low-angle X-ray diffraction (Hudson et al. (1997), J Mol Biol 273: 440-455). This showed that, even without C-protein, the myosin head array displays a characteristic polar pattern with every third 143 A-spaced crossbridge level particularly prominent. However, X-ray diffraction cannot determine the polarity of the crossbridge array relative to the neighbouring actin filaments; information crucial to a proper understanding of the contractile event. Here, electron micrographs of negatively-stained goldfish A-segments and of fast-frozen, freeze-fractured plaice A-bands have been used to determine the resting myosin head polarity relative to the M-band. In agreement with the X-ray data, the prominent 429 A-spaced striations are seen outside the C-zone, where no non-myosin proteins apart from titin are thought to be located. The head orientation is with the concave side of the curved myosin heads (containing the entrance to the ATP-binding site) facing towards the M-band and the convex surface (containing the actin-binding region at one end) facing away from the M-band.

Animals↗

An evaluation of the impact of training Honduran health care providers in interpersonal communication.

OBJECTIVE: To evaluate the impact of interpersonal communication (IPC) training on practice and patient satisfaction and to determine the acceptability of this training to providers in a developing country. DESIGN: The study used a pre-post design with treatment and control groups. Data collection methods included interaction analysis of audio-taped clinical encounters, patient exit interviews, and a self-administered questionnaire for health providers. STUDY PARTICIPANTS: Interaction analysis was based on an experimental group of 24 doctors and a control group of eight with multiple observations for each provider). Exit interviews were carried out with 220 pre-test patients and 218 post-test patients. All 87 health providers who received training responded to the self-administered questionnaire. INTERVENTION: A brief in-service training programme on interpersonal communications was presented in three half-day sessions; these focused on overall socio-emotional communication, problem solving skills and counselling. MAIN OUTCOME MEASURES AND RESULTS: The IPC intervention was associated with more communication by trained providers (mean scores of 136.6 versus 94.4; P = 0.001), more positive talk (15.93 versus 7.99; P = 0.001), less negative talk (0.11 versus 0.59; P = 0.018), more emotional talk (15.7 versus 5.5; P = 0.021), and more medical counselling (17.3 versus 11.3; P = 0.026). Patients responded by communicating more (mean scores of 113.8 versus 79.6; P = 0.011) and disclosing more medical information (54.7 versus 41.7; P = 0.002). Patient satisfaction ratings were higher for providers who had received the training and providers reported training to be relevant and useful. CONCLUSIONS: Further validation of IPC skills and simplification of assessment methods are needed if IPC is to be an area for routine monitoring and quality improvement.

Ambulatory Care↗

Primary central nervous system non-Hodgkin's lymphoma (PCNSL): survival advantages with combined initial therapy? A final report of the North Central Cancer Treatment Group (NCCTG) Study 86-72-52.

PURPOSE: We herein report updated survival and toxicity data on the entire cohort of 53 eligible patients treated on North Central Cancer Treatment Group (NCCTG) protocol 86-72-52, which is now closed. METHODS AND MATERIALS: An initial report was published in this journal in 1995. No substantive changes in the conclusions of that report were identified in this analysis. Median survival was 9.6 months for the entire cohort; median survival for the 20 patients who completed the prescribed protocol treatment was 20.7 months. The hematologic and non-hematologic toxicity distributions are virtually the same as those reported in the original paper. RESULTS: Results are given for the entire group and for subsets defined by age < or = 60 versus > 60 years, and < 70 versus > or = 70 years of age. CONCLUSIONS: No significant differences were observed in any of the outcome variables by age group. There was, however, a nonsignificant suggestion of poorer outcome in those who were > 60 years of age.

Adult↗

The consequences of treatment and disease in patients with primary CNS non-Hodgkin's lymphoma: cognitive function and performance status. North Central Cancer Treatment Group.

Per protocol, patients with primary CNS non-Hodgkin's lymphoma in an intergroup phase II trial conducted by the North Central Cancer Treatment Group and the Eastern Cooperative Oncology Group had their cognitive functions measured using the Folstein and Folstein Mini-Mental Status Examination (MMSE) and their physical functions measured using the Eastern Cooperative Oncology Group Performance Score (PS) at study entry, at each treatment evaluation, and at quarterly intervals thereafter until disease progression or death. Of the 53 eligible participants who began therapy, 46 (87%) had baseline MMSE scores recorded, 36 (68%) had at least one follow-up MMSE, and 32 (60%) had both, while 52 (98%) had baseline PS, 49 (92%) had at least one follow-up PS, and 48 (91%) had both. Patterns of MMSE and PS values over time were studied in each individual, in the group as a whole, in the 20 patients who completed the study regimen, in the 23 who survived more than a year, and in patients who were classified as nonprogressors at each key evaluation. For each patient, all recorded values were plotted versus time, with dates of disease progression and death included, to look for signs of decline in cognitive or physical function preceding adverse events. Long-term declines in scores of both cognitive and physical function were observed in many treated patients with primary CNS non-Hodgkin's lymphoma. Nearly all patients who were alive more than 52 weeks after study entry had a demonstrable decline in cognitive and physical functionality. Such declines may occur before disease progression is documented; they may also occur in some patients who have long-term follow-up without evidence of disease progression. Declining MMSE and PS was a poor predictor of disease progression. There was no association of PS and toxicity. The data from this study demonstrated the considerable difficulties we encountered conducting an ancillary study such as this within a multicenter clinical trial. Firstly, the test instruments written into the protocol were unable to tell if the declines seen were due to disease, treatment, co-morbidity, or other factors. Secondly, the missing data created difficulties in interpreting outcome.

Adult↗

Nothing exceeds like success: managed care comes to Medicaid in New York City.

Nearly every state is encouraging or requiring Medicaid beneficiaries to enroll in managed care delivery systems. In New York City, Medicaid officials began with an incremental, but not insignificant, managed care initiative. Buoyed by its success, New York policy makers tried, and failed, to accelerate the transition to managed care. The legacy of that failure still plagues them. A comparison of such initiatives in other states indicates that most state officials have remembered what New York's leaders temporarily forgot, namely, that Medicaid managed care is a complex exercise that demands consultation and consensus building.

Health Care Reform↗

Management by objection? Public policies to protect choice in health plans.

Consumer choice is a watchword of the market reforms now sweeping the U.S. health care system. Policy makers, however, must grapple with an important ambiguity; is the objective to expand choice or protect choosers, and what should be done if the two goals conflict? Concerns about health care market malfunctions trigger a politics of consumer protection that may emphasize regulatory standards over market flexibility. To complicate matters further, hopes that deluging consumers with information can ensure that choices are at once ample and prudent are likely to be disappointed.

Choice Behavior↗

Implementing Medicaid managed care: the New York City story.

Across the nation, public officials are encouraging or requiring Medicaid beneficiaries to enroll in managed care. In this article, we report on a study of the implementation of Medicaid managed care in New York City. Several findings are clear. First, government officials need to treat health plans as partners rather than adversaries; in New York, the relationship between the state and the plans is far too adversarial. Second, effective managed care requires good management information systems; New York officials are collecting an enormous amount of data but not much useful information. Third, effective implementation of Medicaid managed care is slow going; New York's effort to dramatically accelerate the enrollment process did not work.

Health Policy↗

Urban health policy.

Explore the source record for details and available documents.

Financing, Government↗

Exceptionalism as the rule? U.S. health policy innovation and cross-national learning.

American health care reformers, who often look to other nations for models of desirable health systems, are often surprised nowadays by cross-national infatuation with health policy innovations minted in the United States. American innovations appeal to policy makers abroad as they struggle with cost pressures, distinguish knowledge about how health systems work, and deal with changing images of what constitutes good public policy. These strategems are adapted, not adopted; however, the premises and practices with which other nations follow American directions differ deeply from those in the United States. Ironically, even cross-national experiments may end up offering instructive policy "rules" to the exceptionalist United States.

Cost Control↗

The effect of developmental care on preterm infant outcome.

Using a retrospective comparative design, the investigators evaluated the effects of training 10% of a nursing staff in the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP) on preterm infant outcomes. A convenience sample of 25 preterm infants (< 1500 grams) cared for during the NIDCAP implementation and training period were matched by birth weight and gestational age to infants born before NIDCAP implementation. Outcome measures collected through chart review showed NIDCAP infants had significantly fewer and less severe intraventricular hemorrhages, fewer days of ventilatory support, shorter hospitalizations, and greater rate of weight gain. Findings suggest that benefits of developmental care are achievable with only a portion of the staff being NIDCAP trained.

Female↗

Pharmacokinetics and kinetic-dynamic modelling of aminophenones as methaemoglobin formers.

Methaemoglobin, the oxidized form of haemoglobin, can be formed by a variety of agents, most of which act to oxidize haemoglobin directly or indirectly. Cyanide has a higher affinity for methaemoglobin than for mitochondrial cytochromes, making methaemoglobin formation a basis for the treatment of cyanide poisoning. We used the beagle dog model to investigate the relationship between drug concentration and methaemoglobin levels for two candidate anti-cyanide compounds. The compounds studied were the aminophenones p-aminopropiophenone (PAPP) and p-aminoheptylphenone (PAHP). Both PAPP and PAHP were given as intravenous boluses and as two different oral formulations. The kinetics of both compounds appeared to follow a three-compartment open model for intravenous bolus administration and a two-compartment open model for oral administration. The first distribution phase seen with the intravenous administration was obscured by the absorption phase during oral administration. Bioavailability for all formulations varied between 20 and 47%. For both compounds there was a delay between the appearance of drug in the plasma and the appearance of methaemoglobin (counter-clockwise hysteresis) which is suggestive of an active metabolite causing methaemoglobin formation. The pharmacodynamics were fit with an effect-compartment kinetic-dynamic model linked to a sigmoid Emax pharmacodynamic model. Maximum amounts of methaemoglobin occurred between 2 and 4 h for PAHP and between 1 and 3 h for PAPP. When administered intravenously estimates of EC50 were lower than the estimates of EC50 from oral administration for both compounds. This might be because of oral first-pass inactivation or a 'first-pass' activation through the lungs contributing to the formation of an active metabolite. The phenones as a class appear to have the drug cleared and methaemoglobin return to near baseline within 12 h. Both compounds seem to produce sufficient methaemoglobin to treat acute cyanide poisoning and to serve as prophylactic agents against acute cyanide poisoning in a military setting.

Administration, Oral↗

Using lot quality assurance sampling to assess measurements for growth monitoring in a developing country's primary health care system.

BACKGROUND: Local supervisors used lot quality assurance sampling (LQAS) during routine household visits to assess the technical quality of Costa Rican community-based health workers (CHW): measuring and recording weights of children, interpreting their growth trend and providing nutrition education to mothers. METHOD: Supervisors sampled 10 households in each of 12 Health Areas (4-8 hours per area). No more than two performance errors were allowed for each CHW. This LQAS decision rule resulted in judgments with a sensitivity and specificity of about 95 percent. RESULTS: Three categories of results are reported: (1) CHW adequately weighed children, calculated ages, identified children requiring nutritional services, and used the growth chart. (2) They needed to improve referral, education, and documentation skills. (3) The lack of system support to regularly provide growth cards, supplementary feeding to identified malnourished children, and other essential materials may have discouraged some CHW resulting in them not applying their skills. CONCLUSIONS: Supervisors regularly using LQAS should, by the sixth round of supervision, identify at least 90 percent of inadequately performing CHW. This paper demonstrates the strength of LQAS, namely, to be used easily by low level local health workers to identify poorly functioning components of growth monitoring and promotion.

Child↗

Primary central nervous system non-Hodgkin's lymphoma: survival advantages with combined initial therapy?

PURPOSE: Results of multiple radiation, chemotherapy, and combined treatment trials have shown that the fate of primary central nervous system lymphoma (PCNSL) patients is very different from that of patients with similarly treated systemic IE non-Hodgkin's lymphoma. This study was designed to improve the survival of PCNSL patients by the use of combined initial therapy. METHODS AND MATERIALS: Forty-six eligible primary PCNSL patients were treated with whole brain irradiation and adjuvant chemotherapy consisting of preirradiation cyclophosphamide-adriamycin-vincristine-prednisone (CHOP) and postirradiation high-dose cytosine arabinoside (HDAC) as part of an ongoing Phase II Mayo/North Central Cancer Treatment Group/Eastern Cooperative Oncology Group (M/NCCTG/ECOG) intergroup effort, which opened in April 1986. RESULTS: This cohort consisted of 23 men and 23 women with median age 63.5 years (range 24 to 75 years). Only 5% were under age 40; 36% were age 40 to 59, 37% were age 60 to 69, and 22% were age 70 and over. Forty-six percent had good performance scores of ECOG 0-1 at time of study entry. Forty-six patients were evaluable for treatment outcome as of October 6, 1993. Of these, 10 were still alive. Estimated median survival and 21-month survival were 45.3 weeks and 29%, respectively. There were four early deaths ranging from Day 9 to Day 15 (three drug-related, one from other complications), and two CHOP responders died at 32 and 35 days, soon after Cycle 2 of CHOP (one probably drug-related, one from other complications). There was no significant difference in survival according to baseline performance status. However, survival was consistently worse for patients > 60 years old than for the younger patients (< or = 60 years). With deaths recorded for 21 of 21 older patients, but only 9 of the 14 younger patients, 21-month survival for older vs. younger was 14 vs. 50% based on the 35 patients who entered the study at least 21 months ago (p = 0.0365). Of the 46 patients evaluable for response, 63% had objective remissions on CHOP and another 20% remained stable. CONCLUSION: Combined modality therapy in this study did not produce an overall survival advantage in treating PCNSL. The 50% 21-month survival of younger patients may be a reflection of age only.

Adult↗