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Biomedical subjects

L D Brown

Publications and source records attributed to L D Brown.

At least 55 records · Page 3Linked to original sources
PubMed1991

Politics and equity in policy-making for the medically uninsured.

A sizable number of Americans (many of low income) lack health insurance, and their ranks grew over the 1980s. One might expect to find vigorous political efforts to redress this inequity. In fact, conflicting normative and practical images of equity have blunted the sense of urgency of the problem, inhibited agreement on the proper division of labor between the market and government, and blocked consensus on strategic models for public policy for the uninsured.

Health Policy↗
PubMed1990

Pyrethroid modifications of the activation and inactivation kinetics of the sodium channels in squid giant axons.

The kinetics of sodium channel activation and inactivation were analyzed in the squid giant axons internally treated with various pyrethroids. Pyrethroids increased the steady-state sodium current in squid giant axons by removing the inactivation. The steady-state sodium conductances in control and pyrethroid-treated axons showed the same voltage dependence, indicating that the removal of inactivation by pyrethroids did not lead to an alteration of gating charge transfer. The pyrethroid-modified sodium channels were activated with a biphasic time course involving the movement of at least two gating particles, and both components were voltage-dependent. The slower component was abolished by treatment with either pronase or N-bromoacetamide. The net elementary charges transported in the electric membrane field were reduced in the course of slow activation of the pyrethroid-induced sodium current. It appears that the 'immobilization' of gating charge is related to the slow activation rather than the inactivation of the sodium channel.

Animals↗
PubMed1990

The medically uninsured: problems, policies, and politics.

The ranks of the medically uninsured have grown significantly in recent years, but no consensus on a policy solution has emerged. After summarizing the characteristics of the uninsured population, this paper reviews diverse policy responses and their troubled political prospects.

Federal Government↗
PubMed1990

Phase II evaluation of infusional etoposide and cisplatin in patients with recurrent astrocytoma.

The purpose of this study was to determine the efficacy of 24-hour concomitant infusions of etoposide (100 mg/m2/day, days 1-3) and cisplatin (45 mg/m2/day, days 2-3) in the treatment of patients with recurrent astrocytoma. All 36 patients entered on this trial had histologic proof of astrocytoma with CT scan evidence of tumor progression despite prior radiotherapy and nitrosourea chemotherapy. At initial diagnosis, three patients had low-grade astrocytoma, but 33 (92%) had high-grade astrocytomas. ECOG performance score was 0-1 in 20 patients and 2-3 in 16 patients. The median age of all patients was 45.5 years. Dose-limiting toxicity was myelosuppression with median leukocyte and platelet nadirs of 2,150/mcL and 56,500/mcL respectively. One life-threatening infection occurred, but there were no treatment-related deaths. Vomiting occurred in 78% of patients, but was severe in only 6%. Peripheral neuropathy occurred in 28% but was severe in only 6%. Six patients (17%; 1 CR, 5 REGR) responded to therapy with median time to progression of 6.0 months (range 1.5-17.7 months). Five additional patients (14%) remained stable greater than 6 months and 1 has not progressed at 17.0+ months. Median time to progression and survival in all patients were 2.7 and 5.8 months, respectively. In conclusion, etoposide and cisplatin at this dose and schedule have limited activity in the treatment of recurrent high grade astrocytomas, although durable responses or periods of stability occurred in some patients. Considering the extent of myelosuppression, near maximal doses of the drugs were given.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Health care coalitions: characteristics, activities, and prospects.

Health care coalitions are an important element in the 1980s' emphasis on private sector cost-containment initiatives. The peak years for the formation of these coalitions were 1982 and 1983. Based on a 1986 telephone survey of 215 health care coalitions, we provide an analysis of the maturing health care coalition movement, focusing on who is in them, what they do, how they are doing, and what they have accomplished. We also propose two life-cycle models that describe most coalitions. One model fits the temporary, outcome-oriented employer-only coalitions, while the second fits the more process-oriented broad-based coalitions. Our data, along with more recent information, suggest that at present the coalition movement is in decline.

Cost Control↗
PubMed1988

Mirex uptake and tissue disposition in intact and adrenalectomized rats.

The toxicity of mirex, an organochlorine insecticide, is increased significantly in adrenalectomized rats. To determine if this might be due to alterations in the tissue distribution of mirex, a disposition study was conducted in intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats. The peak plasma levels of [14C]mirex were shifted from 2 hr in intact and adrenalectomized corticosterone-supplemented rats to 4 hr in the adrenalectomized rats. The initial uptake and disposition of [14C]mirex in the brain of the intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats was essentially the same from 0.5 to 6 hr after dosing. By 48 hr after dosing, the [14C]mirex concentration in the brain of intact and adrenalectomized rats was significantly higher than that in adrenalectomized corticosterone-supplemented rats. Brain to plasma ratios reflected this difference. Corticosterone supplements to adrenalectomized rats decreased the absorption of [14C]mirex in the brain. The uptake of [14C]mirex during the initial 6 hr after dosing in all other tissues studied (liver, kidney, testes, and omental fat) was essentially the same for the three treatment groups. By 48 hr postdose, [14C]mirex concentration per liver was significantly higher in intact than in adrenalectomized and adrenalectomized corticosterone-supplemented rats. The difference in [14C]mirex disposition between the three treatment groups was not due to alterations in metabolism or elimination.

Adrenalectomy↗
PubMed1988

Alterations in the hepatic glucocorticoid response to mirex treatment.

Corticosterone has been shown to be involved in the regulation of mirex-induced adaptive liver growth. To further investigate the role of corticosterone in this response, plasma corticosterone, hepatic tyrosine aminotransferase (TAT) activity, and hepatic cytosolic binding of glucocorticoids were determined in male Sprague-Dawley rats following a single oral dose of mirex (100 mg/kg body wt). Mirex stimulated a significant elevation in plasma corticosterone levels 12 and 24 hr after dosing; however, hepatic tyrosine aminotransferase activity was not induced above control levels 6, 12, or 24 hr after mirex dosing. Mirex does not appear to directly inhibit the enzyme because tyrosine aminotransferase activity was increased in a dose-dependent manner in both intact and adrenalectomized rats when corticosterone supplements (1-50 mg/kg body wt) were given after mirex dosing. In an effort to explain the lack of hepatic TAT induction, the concentration of cytosolic binding sites for [3H]dexamethasone in intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats was measured 12, 24, and 48 hr after mirex dosing. There was a significant decrease in the total concentration of cytosolic binding sites for [3H]dexamethasone 12 and 48 hr after mirex dosing in intact rats, 12 and 48 hr after mirex dosing in adrenalectomized rats, and 12 and 24 hr after mirex dosing in adrenalectomized corticosterone-supplemented rats. There was a significant increase in the apparent dissociation constant (Kd) in intact rats dosed with mirex as compared to the oil controls, but there was no difference in Kd after mirex dosing in the adrenalectomized (ADX) rats when compared to the Kd for the oil-dosed control rats. The maximal binding capacity (Bmax) was not significantly different from oil controls after mirex dosing in either intact or ADX rats. The lack of hepatic TAT induction in the presence of increased plasma levels of corticosterone appears to be related to glucocorticoid receptor alterations in the liver of intact rats.

Adrenalectomy↗
PubMed1988

Phase II studies of bleomycin, cyclophosphamide, doxorubicin and cisplatin, and bleomycin and cisplatin in advanced cervical carcinoma.

In a randomized phase II trial of two cisplatin-based chemotherapy regimens, 45 patients with advanced cervical carcinoma received a combination of bleomycin, cyclophosphamide, doxorubicin, and cisplatin (BCAP), and 45 others received bleomycin plus cisplatin (BP). BCAP was repeated every 4 weeks, and BP was given at 3-week intervals. Although 19 of 43 (44%) evaluable patients receiving BCAP and 16 of 42 (38%) evaluable patients receiving BP experienced tumor regression, only 22% of those receiving BCAP and 21% of those on BP survived 1 year after beginning treatment. Among bidimensionally measurable patients, 15 of 27 (56%) and 8 of 25 (32%) receiving BCAP and BP, respectively, achieved tumor regression. One patient died of bleeding resulting from severe myelosuppression on BCAP, and two others succumbed to pulmonary toxicity of bleomycin on the BP regimen. Although active against cervical carcinoma, these regimens have limited therapeutic value at this advanced stage of the disease.

Adult↗
PubMed1988

Patient-controlled analgesia: an evaluation.

This evaluation was designed and implemented by a special task force created to study the effects of patient-controlled analgesia (PCA) at our institution. Patient satisfaction, evaluation procedures and cost-containment issues were studied. Policies and procedures were established to standardize physician's orders, drug dilutions, narcotic control, documentation, and education. Eighteen patients were studied during a 6 week period. Sixteen patients expressed great satisfaction in being able to take part in controlling their pain relief. Seventeen patients expressed delight over not receiving numerous IM injections. Buprenex was used primarily in the evaluation due to its minimal effects of sedation, nausea and vomiting. An average savings of $16 per patient per day was seen for those patients receiving PCA as compared to those receiving conventional IM dosing. Reaction of the nursing staff to the PCA system was favorable. They regarded the equipment as simple to operate and documentation requirements as minimal, which resulted in tremendous time savings for them. Based on a smooth transition during the evaluation and favorable responses from both patients and staff, this evaluation led to the purchase of six PCA units at our institution.

Analgesia↗
PubMed1987

Activity of tralomethrin to modify the nerve membrane sodium channel.

Deltamethrin is a potent type II pyrethroid insecticide which can modify sodium channel gating kinetics in nerve membranes. The actions of another type II pyrethroid tralomethrin to modify sodium channel kinetics have been ascribed to deltamethrin, to which tralomethrin is known to be converted under certain experimental conditions. The objective of this study was to determine if tralomethrin was intrinsically active in modifying the nerve membrane sodium channel, the major target site of pyrethroids. Experiments were performed using the squid giant axon under voltage-clamp conditions. In axons treated with either pyrethroid, a large sodium tail current was generated upon repolarization from a depolarized level and decayed slowly with a dual exponential time course. The fast time constant for tralomethrin was 165 +/- 110 msec and the slow time constant was 3793 +/- 802 msec. For deltamethrin the time constants were significantly shorter, the fast time constant being 34 +/- 6 msec and the slow time constant being 835 +/- 282 msec. The cumulative dose-response relation of tralomethrin revealed two binding sites with apparent dissociation constants of 0.06 and 5 microM. Deltamethrin appeared to bind to only one site with an apparent dissociation constant of 0.25 microM. It is clear that there are large differences in the gating kinetics of the sodium channels modified by tralomethrin and deltamethrin which are incompatible with the idea that tralomethrin is active only after conversion to deltamethrin. The differences in sodium channel gating kinetics after modification by tralomethrin versus deltamethrin indicate that tralomethrin is intrinsically active in modifying the nerve membrane sodium channels.

Animals↗
PubMed1986

Civil rights and regulatory wrongs: the Reagan administration and the medical treatment of handicapped infants.

Beginning in 1982 the Reagan administration tried to impose federal regulations (based on the civil rights approach of Section 504) on the medical treatment of handicapped newborns in the nation's hospitals. After issuing three sets of regulations, the administration found itself rebuffed by the courts and in ill repute with providers and parts of the public, especially after its widely publicized intervention in the case of Baby Jane Doe illustrated the pitfalls of federal regulation in complex medical decisions. Congress, however, soon enacted legislation employing different means to protect handicapped newborns. The episode offers insights into the dynamics of the U.S. system of separated powers, the limitations of the "civil rights" approach, and the importance of negotiating structures for the resolution of private moral dilemmas with public implications.

Abnormalities, Multiple↗