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Biomedical subjects

M H Fox

Publications and source records attributed to M H Fox.

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

The effects of newborn early discharge on hospital readmissions.

The objective of this study is to determine the effects of early newborn hospital discharge policy on hospital readmission for Medicaid infants. It is a multiple year, retrospective study in which early hospital discharges were followed using Medicaid claims data to determine the rate of readmissions for newborns during 1989-1992, the years in which this policy became widespread in Maryland. Analysis compares early discharges, using chi 2 tests, and calculates odds ratios to estimate the risk of readmissions. Our results found significant increases in early discharges for Medicaid newborns over time among sick newborns. The odds of readmissions for normal babies discharged early were about the same as for those kept longer, but for sick babies discharged early they were significantly greater, especially during the early study years. Findings from this natural experiment indicate that early discharge of Medicaid newborns with physical problems increases their likelihood of readmissions. Careful attention to the needs of these higher risk infants must be a part of any hospital or managed care program implementing early discharge policy.

Humans↗
PubMed1994

Isolation and characterization of a Chinese hamster ovary cell mutant with improved staining for indo-1.

Chinese hamster ovary (CHO) 10B2 cells do not stain well with indo-1 and thus cannot be used for experiments to measure intracellular calcium using this dye. We have isolated a mutant CHO cell line (CHO IS1) that stains quite well with indo-1 and that has virtually identical growth characteristics and heat sensitivity as the parent line. The mutant was isolated by sorting individual mutagenized cells with high indo-1 fluorescence and cloning them. Since it has been reported that cells with multiple drug resistance (MDR+) can pump out various fluorescent dyes, the mutant and parent lines were characterized for Hoechst 33342 staining, Adriamycin toxicity, and P-glycoprotein expression, which are markers of the MDR phenotype. P-Glycoprotein was measured with the C219 antibody using flow cytometry. Multidrug-resistant cells (CHRC5) were used as positive controls. The IS1 cells stained as well with Hoechst 33342 as fixed 10B2 cells, and much better than unfixed 10B2 cells. The IS1 cells were 10- to 30-fold more sensitive to Adriamycin than the 10B2 cells, and both cell lines were much more sensitive than the CHRC5 cells. The amount of P-glycoprotein was similar in both 10B2 and IS1 cell lines, but was about fivefold lower than the CHRC5 cells. Thus, the poor staining for indo-1 in the 10B2 cells may not be caused by the P-glycoprotein MDR pump, but by a different efflux pathway. Alternatively, the P-glycoprotein may be altered and less efficient in the CHO IS1 cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Impact of heterogeneity in the predictive value of kinetic parameters in canine osteosarcoma.

Intratumoral heterogeneity has been identified as a potential problem in the efficacy of predictive assays. Canine osteosarcoma is an extremely heterogeneous solid tumor that has been shown to be an excellent model for the human disease. Intratumoral heterogeneity of kinetic parameters and the effect of heterogeneity on predicting outcome of treatment (time until metastasis) were studied in dogs with naturally occurring osteosarcoma. Dogs were treated with amputation or tumor excision and limb-sparing followed by chemotherapy with cisplatin. Kinetic parameters evaluated included v, duration of DNA synthesis (Ts), and potential doubling time (Tpot), determined using in vivo labeling with bromodeoxyuridine and flow cytometry. In 30 tumors, multiple samples were obtained and evaluated. There was significantly more variation between tumors from different dogs than intratumoral variation of v, Ts, and Tpo. Variations in v, Ts, and Tpot within a tumor were associated with both sample location and tumor subpopulation. Time to metastasis was determined in 51 dogs with tumors sampled for kinetics. Multiple samples were available from 25 of these tumors. Cox proportional hazard analysis was performed using either the fastest or slowest Tpot from each sample. The fastest available Tpots were highly significant (P < 0.001) for prediction of outcome. The slowest available Tpots were also significant predictors, although the statistical strength was compromised (P = 0.024). Obtaining at least two samples in large tumors known to be heterogeneous is recommended to improve the predictive ability of Tpot. v is a more limited predictor but can useful when Tpot is not available. In canine osteosarcoma, an extremely heterogeneous tumor, kinetic parameters were shown to be predictors of outcome.

Animals↗
PubMed1994

Low pH suppresses synthesis of heat-shock proteins and thermotolerance.

Chinese hamster ovary (CHO) cells heated for 10 min at 45 degrees C became thermotolerant to a second heat exposure at either pH 7.3 or 6.6. However, low pH delayed the development of thermotolerance and suppressed the rate of synthesis of all proteins, including heat-shock proteins (HSPs). Low-pH-tolerant mutant CHO cells (PHV2) in pH 6.6 medium were also delayed in both the development of thermotolerance and protein synthesis, though less than CHO cells in pH 6.6 medium. The rate of synthesis of inducible HSP-70 under the three conditions paralleled the kinetics of the development of thermotolerance. The intracellular pH (pHi) of CHO cells in pH 6.6 medium, whether heated or not, was far lower than CHO cells in pH 7.3 medium, and the pHi of PHV2 cells in pH 6.6 medium was close to that of CHO cells in pH 7.3 medium after the initial heat shock. Amiloride enhanced the effect of low-pH medium on pHi HSP synthesis and development of thermotolerance. The concentration of HSP-70 was also measured by flow cytometry. The level of HSP-70 was not altered within the first 4 h after a 10-min 45.0 degrees C initial heat treatment during which the major portion of thermotolerance developed, though the level of HSP-70 increased rapidly after 4 h. Low pH caused a further delay in the increase in HSP-70. We conclude that low-pH medium may inhibit the synthesis of HSPs in part by lowering pHi, but the delay and suppression of development of thermotolerance is not primarily due to the inhibition of HSP synthesis.

Animals↗
PubMed1994

Using Medicaid claims data to evaluate a large physician fee increase.

OBJECTIVE: This study demonstrates the use of Medicaid claims data in order to evaluate a threefold fee increase in physician fees for deliveries ($265 to $795), which the Maryland Medicaid program implemented in 1986. DATA SOURCES AND STUDY SETTING: The study used Maryland Medicaid claims data for years of service 1985-1988, and was done at the Maryland Department of Health and Mental Hygiene with the help of a Robert Wood Johnson, Health Care Financing and Organization (HCFO) grant. STUDY DESIGN: Overall, our design is that of a pre-test, post-test with multiple observation points both before and after the fee increase. We measured participation in three ways, corresponding to three different units of analysis. With the county-quarter year as unit of analysis, we followed a panel of providers over 16 quarters for each county in the state to determine changes in the number of delivering providers. With the individual provider as the unit of analysis, we identified effects on their Medicaid caseload between years that may have been influenced by the fee increase. Finally, we looked at continuously enrolled Medicaid women who delivered to determine the effects of the fee increase on site and volume of prenatal care. DATA COLLECTION/EXTRACTION METHODS: Analytic files for each unit of analysis were compiled from previously extracted Medicaid claims files using standard statistical software packages. PRINCIPAL FINDINGS: Using techniques described, we were able to get an in-depth picture of overall responsiveness to the intervention. We found a moderate influence of the fee increase on overall participation, less than what we would have predicted. CONCLUSIONS: Administrative data can be used to construct efficient, yet sophisticated evaluations of major policy changes. Findings from our evaluation suggest a moderate effect of the fee increase on overall participation. However, raising fees to the level of private third party payers does not in itself guarantee equal access to private physician health care for Medicaid mothers.

Adolescent↗
PubMed1993

Measurement of intracellular pH using flow cytometry with carboxy-SNARF-1.

The new intracellular pH (pH(i)) dye carboxy-seminaphthorhodafluor (SNARF-1) was compared to the established dye 2,3-dicyanohydroquinone (DCH) using flow cytometry. Both dyes give high-resolution pH(i) measurements. SNARF-1 remains trapped within cells much longer than DCH, so that pH(i) can be monitored during and after treatments with chemicals or hyperthermia. The toxicity of the dyes is similar, and both dyes can be used at concentrations that result in low toxicity to cells. Adequate staining of cells with SNARF-1 is dependent on the cell concentration. The absolute pHi values indicated by SNARF-1 are higher than values measured with DCH. However, the trends measured by both dyes are consistent, and both are useful for making pH(i) measurements.

Animals↗
PubMed1993

Acadesine prevents oxidant-induced damage in the isolated guinea pig heart.

Acadesine is a cardioprotective nucleoside that can attenuate postischemic contractile dysfunction in the isolated heart even if administered at reperfusion, thereby implying an effect on a reperfusion-induced component of injury. Consequently, the effects of acadesine on the maintenance of cardiac function were evaluated in isolated guinea pig hearts in which the perfusion buffer was subjected to electrolysis to produce a mixture of free radicals and oxidants that have been implicated in reperfusion injury. A reduction of left ventricular developed pressure to 38 +/- 3% at 10 min after electrolysis was prevented by acadesine in a concentration-dependent manner (EC50 1 microM). Hypochlorous acid (HOCl) is a principal oxidizing species implicated in electrolysis-induced myocardial damage, and it is a major oxidant produced by neutrophils. Isolated hearts, perfused with HOCl to induce damage, were also protected by acadesine (EC50 1-3 microM). In addition, acadesine protected alpha 1-antiproteinase (alpha 1-AP) against inactivation by 30 microM HOCl with an EC50 of approximately 10 microM, demonstrating that acadesine reacts rapidly enough with HOCl to protect important biological targets. Additionally, acadesine scavenged the hydroxyl radical with a second-order rate constant of 5.0 x 10(9) M-1 s-1. In contrast, acadesine had no effect on superoxide anions generated from either xanthine-xanthine oxidase or hydrogen peroxide-mediated peroxidation. The free base of acadesine 5-amino-4-imidazole carboxamide (AICA) also reduced HOCl and attenuated the electrolysis-induced cardiac injury. However, unlike the parent molecule acadesine, AICA was not protective in the isolated heart subjected to ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoimidazole Carboxamide↗
PubMed1993

The role of intracellular pH changes in heat sensitization by procaine.

Although it has been known for many years that procaine sensitizes cells markedly to hyperthermia, the mechanism by which this occurs is not yet understood. The recent finding in our laboratory that procaine caused an intracellular acidification following heating prompted further studies using carboxy-SNARF-1 to measure the intracellular pH of cells during heating. We found that procaine actually causes an intracellular alkalinization during heating and the intracellular pH is lowered immediately after the extracellular procaine is removed. These results suggest that procaine causes acid loading analogous to ammonium chloride (NH4Cl) loading. Sensitization could not be attributed entirely to this acid shock, since a comparable acid shock with NH4Cl loading following heating caused only a slight sensitization compared to procaine. Heated cells acidified with NH4Cl loading recovered rapidly from the low intracellular pH, whereas the cells acidified with procaine loading did not. Cell sorting demonstrated that the cells which were unable to recover from acidification by procaine had significantly lower survival than those that recovered. Thus, in addition to causing an intracellular acidification following heating, procaine alters cellular processes responsible for recovery from an acid shock.

Adaptation, Physiological↗
PubMed1992

Effect of Medicaid payment levels on access to obstetrical care.

Across the nation, the number of providers serving pregnant Medicaid clients has dropped precipitously. In an effort to retain providers, in 1986 the Maryland Medicaid program tripled reimbursement fees for deliveries. This raised Medicaid payments for perinatal care to levels roughly comparable to those paid by private insurers. Providers' participation can be measured using two criteria: the total number of participating providers in a given country and the number of deliveries performed by targeted providers. The fee increase was associated with an overall stabilization in the number of providers performing deliveries. Providers performed slightly more deliveries after the fee increase, relative to predictions derived from statistical models. One-quarter of all providers increased their participation on a scale commensurate with the fee increase.

Delivery, Obstetric↗
PubMed1992

The effect of intramyocardial pH on functional recovery in neonatal hearts receiving St. Thomas' Hospital cardioplegic solution during global ischemia.

The experiments in the present study were designed to address two issues: Is it possible to manipulate intramyocardial pH in neonatal hearts with different buffers in cardioplegic solution and, if so, do differences in intramyocardial pH during ischemia influence functional recovery? Isolated working hearts from 7- to 10-day-old rabbits underwent 60 minutes of cardioplegic arrest at 37 degrees C with cardioplegic washouts at the onset of ischemia and at 30 minutes. Hearts were reperfused with oxygenated physiologic saline solution (pH = 7.4), returned to the working mode for 30 minutes, and hemodynamic measurements were obtained to compare with baseline values. Intramyocardial pH was held constant during the ischemic interval by infusing cardioplegic solution containing different buffers: histidine (pK 6.0 at 37 degrees C), bicarbonate (pK 6.4), or tromethamine (pK 8.1). The intramyocardial pH was measured continuously with a Khuri glass electrode system (Vascular Technology, Inc., North Chelmsford, Mass.). Cardioplegic solutions buffered to pH values of 6.0 (histidine), 7.4 (bicarbonate), and 8.0 (tromethamine) were associated with ischemic intramyocardial pH values of 6.3 +/- 0.03, 7.02 +/- 0.05, and 7.88 +/- 0.06, respectively. Functional recovery was best in the acidic (histidine) and worst in the basic (tromethamine) groups. Recoveries of developed pressure, the rate of rise of pressure over time, and aortic flow were significantly better for each parameter in the bicarbonate-treated compared with the tromethamine-treated hearts (p less than 0.005). Recovery in the histidine group, however, was superior to that in both the bicarbonate-treated and the tromethamine-treated hearts (p less than 0.005). Regression analysis demonstrated that a significant inverse relationship existed between functional recovery and intramyocardial pH, supporting the conclusions that intramyocardial pH is an important determinant of functional recovery in the neonatal heart and that acidic conditions during normothermic ischemia optimize preservation of myocardial function.

Animals↗
PubMed1992

Heat-induced changes in the membrane fluidity of Chinese hamster ovary cells measured by flow cytometry.

Flow cytometry was used to measure the fluorescence polarization of the lipid probe trimethylammonium-diphenylhexatriene as an indicator of plasma membrane fluidity of Chinese hamster ovary (CHO) cells heated under various conditions. Fluorescence polarization was measured at room temperature about 25 min after heating. When cells were heated for 45 min at temperatures above 42 degrees C, fluorescence polarization decreased progressively, signifying an increase in plasma membrane fluidity. The fluorescence polarization of cells heated at 42 degrees C for up to 55 h was nearly the same as for unheated control populations, despite a reduction in survival. The fluorescence polarization of cells heated at 45 degrees C decreased progressively with heating time, which indicated a progressive increase in membrane fluidity. The fluorescence polarization distributions broadened and skewed toward lower polarization values for long heating times at 45 degrees C. Thermotolerant cells resisted changes in plasma membrane fluidity when challenged with subsequent 45 degrees C exposures. Heated cells were sorted on the basis of their position in the fluorescence polarization distribution and plated to determine survival. The survival of cells which were subjected to various heat treatments and then sorted from high or low tails of the fluorescence polarization histograms was not significantly different. These results show that hyperthermia causes persistent changes in the membrane fluidity of CHO cells but that membrane fluidity is not directly correlated with cell survival.

Animals↗
PubMed1992

The effect of 45 degrees C hyperthermia on the membrane fluidity of cells of several lines.

The membrane fluidity of cells of human (AG1522 human foreskin fibroblasts), rodent [Chinese hamster ovary (CHO) and radiation-induced mouse fibrosarcoma], and feline (Crandall feline kidney) cell lines after heating at 45 degrees C was measured by flow cytometry. In addition, a heat-resistant variant of radiation-induced mouse fibrosarcoma cells and two heat-sensitive CHO strains were studied. Fluorescence polarization of the plasma membrane probe trimethylammonium-diphenylhexatriene was used as a measure of membrane fluidity. The sensitivity of all cell lines to 45 degrees C hyperthermia was compared. The baseline membrane fluidity varied among the cell lines, but did not correlate with sensitivity to hyperthermia. However, CHO cells, especially the heat-sensitive mutants, had the largest increase in membrane fluidity after heating at 45 degrees C, while the heat-resistant mouse fibrosarcoma variants and Crandall feline kidney cells resisted changes in fluidity. In general, the more resistant the cell line was to killing by heat, the more resistant it was to changes in membrane fluidity.

Animals↗
PubMed1991

Spatial and temporal distribution of DNA replication sites localized by immunofluorescence and confocal microscopy in mouse fibroblasts.

The temporal course of replication monitored by 2- or 5-min pulses of bromodeoxyuridine (BrdUrd) incorporation in synchronized 3T3 cells was mapped by high-resolution light microscopy employing a charge-coupled device (CCD) camera and a confocal laser scanning microscope (CLSM). The cells were labeled simultaneously with monoclonal antibodies directed against BrdUrd and nuclear lamin, and stained with the A+T-specific dye 4',6-diamidino-2-phenylindole (DAPI). Stereoscopic reconstructions of cells showing both the lamin and BrdUrd distributions demonstrate that DNA replication occurs at discrete sites in the nucleus, the locations of which progress through a programmed sequence during S phase. Replication begins in a small number of sites in the interior of the nucleus exclusive of the nuclear membrane and proceeds rapidly in early S phase to encompass a relatively large number of small, discrete sites located throughout the nucleus, with the exception of the condensed heterochromatic regions. Replication is primarily confined to the condensed heterochromatic regions in mid-to-late S phase, and to the nuclear periphery at the end of S phase. These distinctive patterns demonstrate a programmed control of replication sites in the spatial domain in differentiated cell nuclei.

Animals↗
PubMed1991

Effects of procaine on the intracellular pH of Chinese hamster ovary cells heated at 42.0 or 45.0 degrees C.

The local anesthetic procaine greatly sensitizes cells to hyperthermia. Though it is generally accepted that procaine is a membrane-active agent that increases membrane fluidity in cells, the mechanism by which it potentiates heat killing is unknown. In this paper we report changes in intracellular pH (pHi) of Chinese hamster ovary (CHO) cells heated at 42.0 or 45.0 degrees C in the presence of procaine. The pHi was measured with flow cytometry using the dye 1,4-diacetoxy-2,3-dicyanobenzene (ADB). Studies were carried out using cells grown at normal pH (7.3) or cells placed in low-pH (6.6) medium 4 h prior to and during heating (acute low-pH treatment). Low-pH-adapted cells (PHV2), which were obtained previously by continuous culture in pH 6.6 medium, were also used. Normal cells heated in the presence of procaine at pH 7.3 underwent a large decrease in pHi compared to cells heated without procaine. Procaine had little additional effect on the intracellular pH of cells in medium with a pH of 6.6 for 4 h before and during 30 min of heating. PHV2 cells exposed to chronic low-pH conditions were resistant to acidification when heated with or without procaine. The surviving fraction of cells heated with procaine was significantly lower under all pH conditions than that of cells heated without procaine. Cells heated at 42.0 degrees C with procaine also became greatly acidified and their survival was reduced. These data suggest that the reduction in pHi caused by procaine may be part of the mechanism of heat sensitization, but cannot account for it entirely. Furthermore, the degree of procaine sensitization and intracellular acidification is dependent on the extracellular pH, with a larger effect occurring at pH 7.3 than at pH 6.6.

Adaptation, Physiological↗
PubMed1991

Recovery of the neonatal heart after normothermic ischemia. Effect of oxygen and catalase.

The objective of this study was to determine the effect of oxygen and the oxygen radical-scavenging enzyme catalase on the neonatal rabbit heart exposed to global ischemia. The experiments were performed with an isolated neonatal (7 to 10 days of age) working heart model in which normothermic (37 degrees C) ischemia was produced for 60 minutes. Left ventricular developed pressure, ratio of change of ventricular pressure to change in time, and aortic flow were measured before ischemia and 30 minutes after reperfusing the hearts with physiologic saline solution. In the control group (ischemia only), developed pressure and ratio of change of ventricular pressure to change in time recovered to 27% +/- 3% (mean +/- standard error of the mean) and 24% +/- 7% of baseline; the hearts were incapable of ejecting (aortic flow = 0). Treatment of hearts before and after ischemia with catalase (150 units/ml of perfusate) was studied in a second group (control plus catalase), but functional recovery (developed pressure = 32% +/- 1%; ratio of change of ventricular pressure to change in time = 24% +/- 2%, and aortic flow = 0) was not significantly different from the control group. The effect of washout midway through the ischemic period with a low oxygen (oxygen concentration less than 35 mm Hg) solution was measured in a third group (hypoxic physiologic saline solution). Functional recovery (developed pressure = 13% +/- 3%; ratio of change of ventricular su pressure to change in time = 13% + 2%; aortic flow = 0) was not significantly different from the control and control plus catalase groups. In marked contrast were the effects of washout with an oxygenated (oxygen concentration greater than 500 mm Hg) solution (oxygenated physiologic saline solution) in which functional recovery (developed pressure = 78% +/- 3%; ratio of change of ventricular pressure to change in time = 80% +/- 3%; aortic flow = 39% +/- 9%) was significantly better than in the control, control plus catalase, and hypoxic physiologic saline solution groups. Use of modified St. Thomas' Hospital cardioplegic solution (cardioplegic solution group) during the ischemic period also resulted in substantial functional recovery (developed pressure = 80% +/- 3%; ratio of change of ventricular pressure to change in time = 78% +/- 5%; aortic flow = 64% +/- 7%) that did not differ significantly from that in the oxygenated physiologic saline solution group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Comparison of DNA aneuploidy of primary and metastatic spontaneous canine osteosarcomas.

Spontaneous canine osteosarcomas were analyzed for DNA aneuploidy and percentage of S phase cells using flow cytometry. Forty-eight dogs were studied in which both a primary tumor and subsequent metastases were available. The DNA index distributions for the primary tumors and the metastases were quite similar. However, when individual primary tumors and metastases derived from them were compared, many of the cases had different ploidy values. The tumor cells were also analyzed for percentage of S phase. The diploid metastases had less than 17% S phase cells, whereas the aneuploid metastases had up to 40% S phase cells. There was a direct correlation between the DNA index and the percentage of S phase in the metastases.

Aneuploidy↗