Search PubMed⌕ Search

Biomedical subjects

J B Mitchell

Publications and source records attributed to J B Mitchell.

At least 145 records · Page 8Linked to original sources
PubMed1994

Physician reaction to price changes: an episode-of-care analysis.

Physicians may respond to fee reductions in a variety of ways. This episode-of-care analysis examines the impact of surgical fee reductions (mandated by the Omnibus Budget Reconciliation Acts [OBRAs] of 1986-87) on the overall pattern and cost of health care services provided in association with the surgical procedure itself. The study focuses on six procedure groups: cataract extractions; total hip replacement; total knee replacement; coronary artery bypass graft (CABG) surgery; upper gastrointestinal (GI) endoscopy; and prostatectomy. Only two of these procedures give significant evidence for the existence of a service volume offset to the fee reductions.

Data Collection↗
PubMed1994

Protection from lethal irradiation by the combination of stem cell factor and tempol.

Cytokines that stimulate growth and differentiation of hematopoietic precursor cells have been used as protectors in vivo against ionizing radiation. Recently, we have shown that the nitroxide tempol is also an effective radiation protector in vivo. The purpose of the present study was to determine if the combination of tempol with stem cell factor (SCF, c-kit ligand) would provide enhanced radiation protection in C57 mice compared with the protection afforded by either agent alone. Mice were exposed to whole-body irradiation and assessed for survival at 30 days after irradiation. No control mice survived doses of more than 9 Gy. Treatment of mice before and after radiation with SCF alone (100 micrograms/kg at -20 h, -4 h and +4 h) protected mice from radiation at doses of as high as 10 Gy (76% survival). Tempol (350 mg/kg) given 10 min prior to radiation was a radioprotector at 9 Gy (55% survival). The combination of SCF and tempol increased the survival of mice exposed to radiation doses up to 11 Gy (32% survival for the combination vs 4% for SCF alone and 0% for tempol alone; P < 0.001 for the combination vs either agent alone). Lower doses of SCF alone (1 microgram/kg) or tempol alone (275 mg/kg) did not protect mice from radiation. However, the combination of these reduced doses of SCF and tempol protected mice from lethal irradiation at 10 Gy. Stem cell factor and tempol given either singly or together were well tolerated by the animals. These data show that SCF and tempol are radiation protectors and that their radioprotective effects are more than additive when the agents are given together.

Animals↗
PubMed1994

The effect of volume ingested on rehydration and gastric emptying following exercise-induced dehydration.

The purpose of this study was to examine the effects of different drink volumes on rehydration, gastric emptying, and markers of fluid balance following exercise-induced dehydration. Nine male subjects (27.3 +/- 5.47 yr of age, 77.8 +/- 7.9 kg) exercised for 90 min (or until 2.5% of initial body weight was lost) on a cycle ergometer in a hot environment (30 degrees C with 60% RH). Following exercise, subjects were moved to a neutral environment (23 degrees C 50% RH) and rested for 30 min prior to beginning a 3-h rehydration period. During rehydration, subjects were serially fed with an electrolyte solution (14.98 mmol.l-1 Na+, 13.51 mmol.l-1 Cl-, and 7.95 mmol.l-1 K+) every 30 min with either 100% or 150% of the fluid lost during exercise. Gastric contents were determined every 15 min using double sampling. Blood samples, urine samples, and body weights were taken before and after exercise and at 1-h intervals throughout rehydration. Blood samples were analyzed for percent change in plasma volume, electrolyte concentration, aldosterone levels, and renin activity. Urine electrolyte concentrations were also measured. The final percent rehydration was 48.11 and 67.90 for the 100% and 150% conditions, respectively. During rehydration, the subjects emptied 98.9 and 86.0% of the fluid ingested, and the % emptied and used for weight gain at the end of rehydration was 55.1 and 54.6 for the 100% and 150% trials, respectively. Urine production was significantly higher in the 150 compared with the 100% condition while renin and aldosterone levels did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Implementing organized delivery systems: an integration scorecard.

Organized vertically integrated health systems are in a key position to play a major role in present health care reform efforts. To demonstrate a competitive advantage in the new health care environment, however, integration efforts must be successful. Based on a national study of nine organized delivery systems, this article develops measures of three types of integration that occur in vertically integrated health systems--functional, physician-system, and clinical. These measures can be used as a "scorecard" to assess progress toward achieving integration objectives.

Comprehensive Health Care↗
PubMed1994

Cycloheximide inhibits the cytotoxicity of paclitaxel (Taxol).

Treatment of human breast (MCF-7) and lung (A549) adenocarcinoma cell lines with 10 micrograms/ml cycloheximide provided substantial protection from paclitaxel-induced cytotoxicity. Addition of cycloheximide to cells at 0, 6, 12 or 18 h into a 24 h exposure to paclitaxel resulted in cytotoxicity similar to that found in cells treated with paclitaxel alone for only 0, 6, 12 or 18 h, respectively. DNA flow cytometry showed that paclitaxel blocked cells in G2/M. Mitotic index studies demonstrated that paclitaxel arrested cells in mitosis and that prolonged exposure to paclitaxel resulted in the development of multiple micronuclei. Concurrent incubation of cells in cycloheximide prevented the development of a G2/M block, mitotic arrest and micronuclei formation. The addition of cycloheximide to cells at 6 or 12 h into a 24 h exposure to paclitaxel reduced the degree of G2/M block to that produced by incubation of cells in paclitaxel alone for only 6 or 12 h. Mitotic index studies confirmed that cells treated with cycloheximide during paclitaxel exposure had a marked reduction in the percentage of cells in mitosis. However, the percentage of paclitaxel-treated cells which had multiple micronuclei was increased in cells treated with cycloheximide. These results indicate that entry into mitosis is a prerequisite for paclitaxel-induced cytotoxicity and that cycloheximide reduces cytotoxicity due to paclitaxel by preventing cells from entering mitosis. However, once cells have entered mitosis in the presence of paclitaxel, protein synthesis is not required for the development of multiple micronuclei and cytotoxicity.

Adenocarcinoma↗
PubMed1994

Using Medicare claims for outcomes research.

Medicare claims databases have several advantages for use in constructing episodes of care for outcomes research. They are population-based, relatively inexpensive to obtain, include large numbers of cases, and can be used for long-term follow-up. However, the sheer size of these claims databases, along with their primarily administrative (as opposed to clinical) nature, requires that researchers take special care in using them. The 10 PORTs using Medicare claims provided information on their approach to several key issues in working with these data, including: 1) identifying the index cases or patient cohorts to be studied; 2) defining the length of the episode; and 3) measuring outcomes. This paper reports the experience and knowledge gained by these PORTs in using these claims to create and analyze episodes of care.

Databases, Factual↗
PubMed1993

Hypoxic mammalian cell radiosensitization by nitric oxide.

The bioregulatory molecule, nitric oxide (NO), was evaluated as a hypoxic cell radiosensitizer. Authentic NO gas was nearly as effective as oxygen in radiosensitizing hypoxic Chinese hamster V79 lung cells as evaluated using clonogenic assays. When NO was delivered to hypoxic Chinese hamster V79 cells using the NO-releasing agent (C2H5)2N[N(O)-NO]- Na+, radiosensitization was also observed with a sensitizer enhancement ratio of 2.4 (1 mM (C2H5)2N[N(O)NO]-Na+). Aerobic radiosensitivity was not affected at this concentration. The hypoxic cell radiosensitization properties of (C2H5)2N[N(O)NO]-Na+, coupled with the vasodilatory effects of NO on tumor vasculature, suggest that such agents open a new avenue of research in radiation oncology.

Animals↗
PubMed1993

Taxol in combination with doxorubicin or etoposide. Possible antagonism in vitro.

BACKGROUND: Taxol is a novel chemotherapeutic agent that promotes microtubule assembly and stabilizes tubulin polymer formation. Clinical evaluation of its antineoplastic activity as a single agent and in combination with other chemotherapeutic drugs is in progress. METHODS: To evaluate the effect of combining taxol with other commonly used antineoplastic agents, clonogenic survival of human breast cancer MCF7 cells, human lung adenocarcinoma A549 cells, and human ovarian cancer OVG1 cells were assayed after an initial exposure to taxol for 24 hours (approximately LD90 for taxol), followed by a 1-hour incubation with varying concentrations of doxorubicin or etoposide (total taxol incubation time, 25 hours). RESULTS: When corrected for taxol-induced cytotoxicity, doxorubicin and etoposide caused less cell killing in the presence of taxol compared with control incubations of doxorubicin and etoposide alone. To determine if a different schedule of drug application resulted in a similar finding, MCF7, A549, and OVG1 cells were exposed to doxorubicin for 1 hour, followed by incubation with varying concentrations of taxol for 24 hours. Less-than-additive cytotoxicity for the combination of taxol and doxorubicin was found. Flow cytometry studies in MCF7 cells showed that taxol caused a G2/M cell cycle block. Fewer cells were found to be in S-phase, which is the most doxorubicin-sensitive phase of the cell cycle. The application of doxorubicin or etoposide to MCF7 cells for 1 hour resulted in partial G1 and G2/M cell cycle blocks. Fewer cells were found to be moving through the cell cycle, which is likely required for taxol cytotoxicity. CONCLUSION: Although direct antagonism of the cytotoxicity of doxorubicin or etoposide by taxol has not been proven, there is less-than-additive in vitro cytotoxicity when taxol is combined with these chemotherapeutic agents. The clinical implications of these findings are unknown; however, these findings generate concern about the combination of these agents in clinical trials and suggest that additional studies to determine optimal scheduling are needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.

Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more carefully the potential synergy between NO and active oxygen species in mammalian cell cytotoxicity, we utilized either hypoxanthine/xanthine cell cytotoxicity, we utilized either hypoxanthine/xanthine oxidase (a system that generates superoxide/hydrogen peroxide) or hydrogen peroxide itself. NO generation was accomplished by the use of a class of compounds known as "NONOates," which release NO at ambient temperatures without the requirement of enzyme activation or biotransformation. When Chinese hamster lung fibroblasts (V79 cells) were exposed to hypoxanthine/xanthine oxidase for various times or increasing amounts of hydrogen peroxide, there was a dose-dependent decrease in survival of V79 cells as measured by clonogenic assays. However, in the presence of NO released from (C2H5)2N[N(O)NO]-Na+ (DEA/NO), the cytotoxicity resulting from superoxide or hydrogen peroxide was markedly abrogated. Similarly, primary cultures of rat mesencephalic dopaminergic cells exposed either to hydrogen peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells.

Animals↗
PubMed1993

Glutathione depletion by L-buthionine sulfoximine antagonizes taxol cytotoxicity.

Taxol is a naturally occurring chemotherapeutic agent that is active against a variety of tumors. Taxol is believed to act by binding tightly to microtubules and preventing their disaggregation. Others have shown that depletion of cellular glutathione results in the disaggregation of microtubules, presumably by allowing the oxidation of some or all of the cysteine residues in tubulins. We studied the effect of glutathione (GSH) depletion by L-buthionine sulfoximine (L-BSO) on taxol cytotoxicity in two human tumor lines. After a 24-h incubation in 5 mM L-BSO, the breast adenocarcinoma line MCF-7 and the lung adenocarcinoma line A549 were exposed to varying concentrations of taxol for 24 h. GSH levels were undetectable in cells treated with L-BSO. At the highest concentrations of taxol (50 nM), control MCF-7 cells had 10% cell survival and control A549 cells had only 1% cell survival as assessed by clonogenic assay. Pretreatment with 5 mM L-BSO resulted in a 3-fold increase in survival of MCF-7 cells and a 10-fold increase in survival of A549 cells. Pretreatment with L-BSO had no effect on taxol uptake into A549 or MCF-7 cells, as assessed by measurement of binding of [3H]taxol to cells. Following exposure to 37 nM taxol for 24 h, both cell lines had over 80% of their population in G2/M and bromodeoxyuridine labeling showed that taxol markedly reduced the percentage of cells in S phase. L-BSO pretreatment had no effect on the cell cycle in either cell line in the absence of taxol. However, in cells treated with taxol, L-BSO increased the percentage of cells in S phase by 3-fold in both cell lines. We conclude that depletion of cellular GSH by L-BSO results in resistance to taxol in MCF-7 and A549 cells. Resistance to taxol mediated by GSH depletion is not due to alterations in cellular uptake of taxol by L-BSO. L-BSO increased the S-phase fraction of taxol-treated cells in both cell lines. These data suggest that GSH depletion interferes with cell cycle changes induced by taxol. The alteration in taxol-induced cell cycle effects may account for the resistance to taxol produced by L-BSO.

Buthionine Sulfoximine↗
PubMed1993

Effect of L-buthionine sulfoximine on the radiation response of human renal carcinoma cell lines.

BACKGROUND: Renal cell carcinoma (RCC) is a progressive and relatively radioresistant disease. Currently, no data are available on the in vitro radiobiologic characterization of renal tumor cells to the authors' knowledge. METHODS: Two RCC were cultured from specimens from previously untreated patients after either surgical resection of the primary tumor or from the malignant ascites. These two cell lines were characterized with respect to cytogenetic abnormalities, gamma radiation survival response, intracellular levels of glutathione and its related detoxification enzymes, and the effect of glutathione depletion on radiation toxicity. RESULTS: The two RCC grew as adherent monolayer cultures with a median doubling time of 29 hours and 37 hours, respectively. Histopathologic analysis of the tumor cells grown in the renal capsule of the athymic mice confirmed their epithelial neoplastic growth. Both cell lines were aneuploid (range, 65-100 chromosomes) and had several marker chromosomes, including those derived from chromosomes 3, 7, and 11. In vitro radiation survival analysis indicated the relative radioresistance (RR; Do, 2.35 Gy) and relative radiosensitivity (RS; Do, 1.42 Gy), respectively, of these tumor cell lines. The levels of intracellular glutathione (GSH) were higher in the RR cells compared with the RS cells. The enzymatic activities of GSH S-transferase, GSH reductase, and the levels of GSH peroxidase and superoxide dismutase were elevated in the RS cells compared with the RR cells. L-Buthionine sulfoximine (BSO) treatment (concentration, 20 microM, applied for 17 hours) resulted in 77% and 63% GSH depletion compared with the untreated RR and RS cells, respectively. Pretreatment with higher concentration of BSO (50 microM for 17 hours) caused a modest radiosensitization of the RR cells (Do, 1.78 Gy). CONCLUSIONS: RCC have a differential pattern of radiosensitivity. BSO treatment causes moderate radiosensitization of the relatively radioresistant renal tumor cells.

Animals↗
PubMed1993

Adenosine-induced suppression of synaptic responses and the initiation and expression of long-term potentiation in the CA1 region of the hippocampus.

The results of several previous studies have suggested that pretreatment with adenosine can block the induction of long-term potentiation (LTP), although other studies have found no effect of adenosine on the induction of LTP. The interaction of adenosine with the induction of LTP in the rat hippocampal slice was investigated. Inhibition of synaptic responses by adenosine either prior to or immediately after high-frequency or theta-burst stimulation did not affect LTP measured after washout of the adenosine. The only conditions under which adenosine blocked the development of LTP was when it was given 3-5 minutes prior to the stimulation train. To understand how it was possible to induce LTP, during the period 1-3 minutes following adenosine when synaptic responses were virtually eliminated, evoked responses during the 100 Hz stimulation train were recorded. Although synaptic responses to low-frequency stimulation were virtually eliminated by adenosine, they reappeared during high-frequency stimulation. These results suggest that although adenosine can depress synaptic responses, an increase in neurotransmission during a high-frequency train can partially overcome this effect of adenosine, and the hypothesis that adenosine can selectively block LTP is not supported.

Action Potentials↗
PubMed1993

Targetted phototherapy with sensitizer-monoclonal antibody conjugate and light.

Photodynamic therapy (PDT) was performed in vitro and in vivo using monoclonal antibody conjugated to hematoporphyrin (HP). The antibody (45-2D9) recognized a cell surface glycoprotein on cells derived from NIH 3T3 cells which were transformed with the ras oncogene (45-342). Radionuclide imaging with either In111 or I125 chelated to 45-2D9 or the isotype identical (IgG1) antibody MOPPC-21 revealed selectivity of 45-2D9 for 45-342 flank tumours in nude mice, and minimal targetting for a 45-342 clone which did not express the cell surface glycoprotein. The 45-2D9-HP conjugate resulted in selective killing of the 45-342 line compared with the parent line in vitro. At HP concentrations of 76 micrograms ml-1, the 45-2D9-HP conjugate resulted in significantly more long-term cures of PDT treated flank tumours compared with free HP at the same concentration. 45-2D9 alone had no effect on tumour growth. The antibody-HP conjugate resulted in significantly less local toxicity compared with standard Photofrin II PDT, and also achieved a greater number of long-term cures. This 'photoimmunotherapy' demonstrates the ability to treat established tumours with greater efficacy and decreased morbidity, probably due to specific sensitizer targetting which allows normal surrounding tissue to be spared upon illumination.

3T3 Cells↗
PubMed1993

Diffusion of new technologies in the treatment of the Medicare population. Implications for patient access and program expenditures.

Patterns of diffusion were analyzed for three pairs of technologies: one of each pair represents a very recent innovation, and the other is more established. Tremendous growth in utilization from 1985-89 was documented, primarily due to more patients obtaining access to the technologies. Nevertheless, disturbing differences in levels of use remain between black and white patients.

Adult↗
PubMed1993

Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.

The cytotoxicity of paclitaxel against eight human tumour cell lines has been studied with in vitro clonogenic assays. The fraction of surviving cells fell sharply after exposure for 24 h to paclitaxel concentrations ranging from 2 to 20 nM; the paclitaxel IC50 was found to range between 2.5 and 7.5 nM. Increasing the paclitaxel concentration above 50 nM, however, resulted in no additional cytotoxicity after a 24 h drug exposure. Cells incubated in very high concentrations of paclitaxel (10,000 nM) had an increase in survival compared with cells treated with lower concentrations of the drug. Prolonging the time of exposure of cells to paclitaxel from 24 to 72 h increased cytotoxicity from 5 to 200 fold in different cell lines. Exponentially growing cells were more sensitive to paclitaxel than were cells in the plateau phase of growth. Cremophor EL, the diluent in which the clinical preparation of paclitaxel is formulated, antagonised paclitaxel at concentrations of 0.135% (v/v). These data suggest that paclitaxel will be most effective clinically when there is prolonged exposure of tumour to the drug. Further, it appears that modest concentrations (i.e., 50 nM) should be as effective as higher concentrations of paclitaxel. Finally, we have noted that Cremophor EL is a biologically active diluent and, at high concentrations (0.135% v/v), can antagonise paclitaxel cytotoxicity.

Adenocarcinoma↗
PubMed1993

The effect of high- and low-intensity warm-up on the physiological responses to a standardized swim and tethered swimming performance.

This investigation was conducted to determine the effect of high- and low-intensity warm-ups on physiological responses, lactate accumulation, and high-intensity freestyle and tethered swimming performance. Ten male collegiate swimmers were tested for maximal oxygen uptake (VO2 max) followed by two series of three warm-up protocols performed in a randomized order at least 2 days apart. The warm-up protocols were: (1) no warm-up (NWU), (2) a 366-m swim at 70% VO2 max (LWU) and (3) four 46-m swims at 1-min intervals at a speed corresponding to 110% VO2 max (HWU). Five minutes after each warm-up in the first series, the swimmers swam a 183-m standardized freestyle swim at a velocity corresponding to 110% VO2 max, and 5 min after each warm-up in the second series the swimmers completed a tethered swim to exhaustion with a weight attached to the tether to elicit fatigue at about 2 min. Three minutes after each warm-up and 3 min after each standardized and tethered swim, a finger-prick blood sample for lactate measurement was obtained. Heart rate and VO2 were also measured during the warm-up and the standardized and tethered swims. The performance times in the tethered swim were not significantly different between the three conditions (116.8 +/- 46.8, 137 +/- 53.3 and 122.94 +/- 37.2 s for the NWU, LWU and HWU, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The management of tracheal rupture using bilateral bronchial intubation.

The management of a patient who required positive pressure ventilation following pharyngolaryngo-oesophagectomy during which tracheal injury was sustained is described. Ventilation with a tracheal tube resulted in a massive pneumoperitoneum. Bilateral bronchial intubation was employed with success.

Bronchi↗