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Biomedical subjects

L D Brown

Publications and source records attributed to L D Brown.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lessons learned in institutionalization of quality assurance programs: an international perspective.

A sustainable quality assurance (QA) program depends on development of a QA structure, ongoing standard setting, routine monitoring, quality improvement activities and the development of a culture of quality. A review of QA implementation in five countries identifies some practical guidelines for successful institutionalization of QA. These experiences underscore the importance of organizational assessment and provide insight about the advantages and disadvantages of an initial QA assessment. Developing a methodology that is both standardized and flexible is stressed, as well as a training strategy that integrates classroom learning, coaching and application. Gradual development of QA structure, based closely on existing systems, is recommended. Issues relating to gaining and sustaining political support, dealing with personnel changes, using appropriate incentives and dissemination are also discussed. Finally, the definition and dimensions of quality are put forth as the foundation for a culture of quality, which develops as individuals and groups commit themselves to their quality ideal.

Developing Countries↗
PubMed1995

Phase II evaluation of recombinant interferon alpha and BCNU in recurrent glioma.

The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus recombinant interferon-alpha (IFN-alpha) in patients with recurrent glioma. As single agents, both BCNU and IFN-alpha can cause tumor regression in patients with recurrent glioma. In vitro studies suggest synergy between the two agents. Thirty-five patients in whom computerized tomography (CT) or magnetic resonance (MR) evidence was obtained of progressive astrocytoma, oligoastrocytoma, or oligodendroglioma received recombinant IFN-alpha 2a (12 x 10(6) U/m2 intramuscularly) on Days 1 through 3 and BCNU (150 mg/m2 intravenously) on Day 3 of each 6-week cycle. All patients had tumor progression despite radiation therapy and had received no prior chemotherapy. Response was assessed by CT or MR evidence and by neurological examination while the patients were on a regimen of stable or decreasing doses of corticosteroids. All patients could be evaluated for response and toxicity. Twenty-nine percent of the patients demonstrated objective tumor regression; 37% remained stable for more than 6 months and 25% were stable for less than 6 months. The median duration of response to IFN-alpha and BCNU was 9.9 months and the median survival for all patients was 13.3 months. Toxicity consisted primarily of moderate myelosuppression, venous irritation, vomiting, flulike symptoms, and transient reversible exacerbation of underlying neurological symptoms. The use of BCNU plus IFN-alpha is a safe, active regimen in the treatment of patients with recurrent glioma who have failed to respond to prior radiation therapy. The contribution of IFN to the antitumor activity observed in this study compared with that previously described with BCNU alone cannot be assessed from this trial.

Adult↗
PubMed1994

The F1 genes of the F1F0 ATP synthase from the acidophilic bacterium Thiobacillus ferrooxidans complement Escherichia coli F1 unc mutants.

An atp gene cluster from the extreme acidophile Thiobacillus ferrooxidans was able to complement Escherichia coli F1 unc mutants for growth on minimal medium plus succinate. Complementation with all four E. coli F1 mutants tested was observed and subunits for the F1 portion of the T. ferrooxidans ATP synthase formed a functional association with the F0 subunits of the E. coli enzyme. In addition, a hybrid F1 enzyme in which some units were derived from E. coli and some from T. ferrooxidans was partially functional. No clones capable of complementing E. coli F0 unc mutants were isolated. The nucleotide sequence of the gene cluster was determined and the genes for the F0 and the F1 ATP synthase subunits were found to be physically linked.

Amino Acid Sequence↗
PubMed1994

Transdermal clonidine for ameliorating post-orchiectomy hot flashes.

To determine the efficacy of transdermal clonidine for alleviating post-orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was designed including 70 men with a history of prostate cancer who had undergone a medical or surgical orchiectomy and were suffering from hot flashes. The results of this study demonstrated that clonidine did not significantly decrease hot flash frequency or severity. Future research is necessary to find effective means of alleviating hot flashes in post-orchiectomy patients.

Adult↗
PubMed1993

The role of G protein in muscarinic depolarization near resting potential in cultured hippocampal neurons.

Cultured neurons from the CA1 and CA3 regions of the rat hippocampus were studied by using the whole-cell version of patch clamp. Application of acetylcholine (5-10 microM) or muscarine (20 microM) to a neuron with a holding potential of approximately -70 mV produced a slow inward current. This inward current was inhibited by atropine (1-2 microM). Loading the cell with GTP gamma S caused a change in the muscarinic response. In the control cells the muscarine-induced inward current recovered by 89%. On the other hand, in the GTP gamma S-loaded cells the inward current recovered by only 30%, indicating some irreversibility. Pertussis toxin treatment did not change the muscarine-induced slow inward current. Loading the cells with cyclic AMP (100 microM) plus IBMX (1 mM) (an inhibitor of phosphodiesterase) did not occlude the effect of muscarine. We conclude that the slow inward current is mediated through a pertussis toxin-insensitive G protein, and that cyclic AMP is not a part of the signal transduction cascade. The finding that the GTP gamma S-loaded cells did not show complete irreversibility was discussed in relation to the results of Benson et al. (J. Physiol., 404 (1988) 479-496), which showed that there are two ionic mechanisms responsible for the muscarine-induced depolarization. Occasionally cells were encountered, in which muscarine (or acetylcholine) evoked a large and rapid inward current, followed by the usual slow inward current. The time course of this rapid response was not affected by GTP gamma S.

Acetylcholine↗
PubMed1993

Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma.

PURPOSE: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and PCNU with those of RT and carmustine (BCNU) in patients with malignant glioma. PATIENTS AND METHODS: A total of 346 patients with histologically verified supratentorial grade 3 and grade 4 astrocytoma were studied. After surgery, patients were randomly assigned to receive RT 60 Gy in 30 fractions and either PCNU 100 mg/m2 or BCNU 200 mg/m2 every 7 weeks for 1 year and every 10 weeks for the second year. RT and chemotherapy were started within 72 hours of randomization and usually on the same day. Of 334 assessable patients, 72% had partial or radical resection and 71% had grade 4 tumors. Median age was 59 years, and 85% had performance scores of 0 to 2 (Eastern Cooperative Oncology Group [ECOG]). The follow-up duration of 51 living patients ranged from 10.3 to 63.2 months, with a median of 36.2 months. RESULTS: The median survival duration in each group was 47 weeks, and median time to progression was 28 weeks. PCNU produced significantly more leukopenia and thrombocytopenia, whereas BCNU produced significantly more nausea, vomiting, and irritation. CONCLUSION: PCNU has no therapeutic advantage at this dose and schedule and does not warrant further study as a single agent for patients with high-grade glioma.

Adult↗
PubMed1993

Dogmatic slumbers: American business and health policy.

For more than a decade students of health policy have predicted a revolution waged by corporate purchasers of health care who would rise in demand of public policy cures for increasing and burdensome health care costs. This forecast has been largely disappointed, however, as the business sector has remained oddly diffident in its demands for health policy reform. There are three reasons for business's reticence--the economic stakes of the corporate sector in health reform are uncertain, organizational encumbrances hamper business activism in this arena, and ideological convictions make business wary of governmental solutions. Although business is sometimes said to manipulate the policy process for its own material ends, in the health sphere the most likely road to reform may reverse this image: a newly activist federal government may have to mobilize business support for reforms that advance both corporate interests and larger social goals.

Commerce↗
PubMed1993

Commissions, clubs, and consensus: Florida reorganizes for health reform.

This paper explores the political dynamics by which a health reform leader state--Florida--engineered an ambitious reorganization of state health agencies as an expected prelude to bolder policy measures before the end of 1994. Demographic and fiscal pressures spurred the state to action, but its success at innovation demands a political explanation. This narrative highlights Florida's patient quest, by means of commissions and task forces, for common ground among parties of diverse dispositions; the sagacity of would-be innovators in wielding a potent policy "club"--the prospect of a single-payer system--to encourage a search for common centrist ground; and the consensus- and coalition-building skills of the state's leading executive and legislative figures. Florida's political skill has sustained impressive departures, but the hardest questions--how to finance universal coverage, how to secure universal access, and how to keep it all affordable--remain to be answered.

Budgets↗
PubMed1992

Modulation of nerve membrane sodium channel activation by deltamethrin.

Deltamethrin is a highly potent pyrethroid insecticide that causes hypersensitivity, choreoathetosis, tremors, and paralysis in mammals. It is known to modify the sodium channel in such a way as to prolong the tail current associated with step repolarization following a depolarizing pulse. Using the axial-wire voltage-clamp technique with the giant axon of the squid Loligo pealei, we have demonstrated that deltamethrin also greatly slows the opening of the sodium channel. This was first observed as a decrease, by as much as 80%, in the peak sodium current flowing during a short, 10 ms depolarization. Current flowing through these slowly opening deltamethrin modified sodium channels was observed during the first depolarizing pulse after deltamethrin exposure and developed with a time constant of 320 ms. This supports the idea that deltamethrin can modify sodium channels when they are in the closed or resting state. Further, evidence of this hypothesis was provided by experiments using 0.1 and 10 microM deltamethrin and measuring the tail current amplitude after depolarizing pulses of varying duration (1-1200 ms). The mean time constant for the increase in tail current amplitude was almost concentration independent; 253 ms at 0.1 microM and 193 ms at 10 microM. We conclude that deltamethrin modifies the activation kinetics of sodium channels in such a way as to slow opening and that this modification occurs predominantly when channels are in the closed or resting state.

Animals↗
PubMed1992

Political evolution of federal health care regulation.

Although federal regulation of health care faces cultural obstacles and skepticism among policymakers, it has grown markedly over the past two decades. Beginning in the 1970s with decentralized programs aimed at regulating provider behavior (Health Systems Agencies and certificate of need) and budgets (state rate setting), health care regulation grew more centralized in the 1980s as federal policymakers expanded their influence on behavior (peer review organizations and medical practice guidelines) and budgets (Medicare prospective payment and the resource-based relative value scale). Behavioral regulation has increased the heavy micromanagement that providers face in the United States, while budgetary regulation falls well short of the fiscal macromanagement (global budgets, for example) that other Western nations use. As cost increases intensify, the coalitions that supported limited regulation as a compromise designed to forestall more threatening intrusions may yield to political pressure for firmer central budget controls.

Delivery of Health Care↗
PubMed1992

Policy reform as creative destruction: political and administrative challenges in preserving the public-private mix.

As political pressure for affordable universal coverage intensifies, various proposals have been crafted to improve the system without sacrificing the role of the private sector. Some analysts view the preservation of a mixed public-private system as an exercise in incrementalism, avoiding disquieting departures from familiar arrangements. A review of the political and administrative challenges of several main options--market innovation, tax credits, play or pay, and Medicaid expansion--suggests that the path to true reform is a slippery slope. Over time, changes in particular sectors, such as insurance, employers, government, and providers, will very likely implicate the others too. Although redefining the public-private mix may be more incremental than (say) adoption of a Canadian model, it will also entail considerable "creative destruction" of existing patterns and cannot fail to disturb the institutional status quo substantially.

Financing, Government↗
PubMed1991

Capture and culture: organizational identity in New York Blue Cross.

This article explores the changing corporate culture of New York's Blue Cross and Blue Shield plan in its first fifty years. As the plan grew, corporate culture evolved over four sequential phases: the plan first had the character of an experiment, then that of a movement, a business, and, most recently, a corporate agglomerate. Accompanying this evolution has been an identity crisis, as the need to adapt to a turbulent environment has challenged the plan's settled understanding of its core values, namely, voluntarism, community, and cooperation.

Blue Cross Blue Shield Insurance Plans↗