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Biomedical subjects

D Stone

Publications and source records attributed to D Stone.

At least 55 records · Page 3Linked to original sources
PubMed1995

Long-term care reimbursement issues.

There have been dramatic changes in long-term care funding recently. Considered only an insignificant part of the continuum of care system just a few years ago, this level of care is now looked to as a wellspring for desperately needed health care cost reductions. Government, insurance companies, intermediaries, large providers, and consumer and physician groups are actively focused on the development and expansion of alternative care provision sites; sub-acute care; hospice; home health care; social, medical, and rehabilitative day care; assisted living and adult congregate care facilities; risk or capitation contracting; expanded health maintenance organizations; alternative care providers; and alternative care approaches. In addition, the improvement in reimbursement is reviewed and is one aspect in ensuring that the economics are right for those needed services to continue to be provided.

Abstracting and Indexing↗
PubMed1994

Human (THP-1) macrophages oxidize LDL by a thiol-dependent mechanism.

The oxidative modification of low-density lipoprotein by macrophages may be an important mechanism in the pathogenesis of atherosclerosis. The human monocytic leukaemia cell line THP-1, when stimulated with phorbol ester, shares many properties with human monocyte-derived macrophages. Oxidation of LDL by these cells was characterised by depletion of alpha-tocopherol, increases in thiobarbituric acid reactive substances and increases in electrophoretic mobility. The LDL particles were also converted to a form which increased accumulation of cholesteryl esters within macrophages. The oxidative mechanism appeared to be dependent upon the presence of thiols in the cellular medium. Oxidation of LDL by THP-1 macrophages, and production of thiols by these cells, were dependent upon the presence of L-cystine in the medium. Furthermore, cellular oxidation of LDL could be partially mimicked by the addition of cysteine to Hams F10 medium. Macrophage-independent oxidation of LDL, mediated by the addition of copper ions, was inhibited by cystine and cysteine in phosphate buffered saline, but not in Hams F10 medium. The glutathione content of THP-1 macrophages was also dependent upon the presence of cysteine or cystine in the medium, but inhibition of glutathione synthesis by buthionine sulfoximine did not prevent the production of thiols or the oxidation of LDL by THP-1 macrophages.

Buthionine Sulfoximine↗
PubMed1993

Changes in mitochondrial matrix free calcium in perfused rat hearts subjected to hypoxia-reoxygenation.

Reperfusion or reoxygenation of ischaemic or hypoxic cardiac tissue results in increases in total cell calcium and cell lysis both of which are dependent on mitochondrial function. Although changes which occur during this period of exposure of the tissue to hypoxia predispose the heart to take up calcium on reoxygenation, the mechanisms involved are not well understood. In the present study we have investigated the effects of hypoxia and reoxygenation on the concentration of intramitochondrial (matrix) free Ca2+ ([Ca2+]m) using mitochondria loaded in the intact heart with fura-2. During periods of up to 80 min hypoxia, total tissue calcium content was unchanged. Over this period [Ca2+]m rose from an initial value of 156 +/- 26 nM to 360 +/- 33 nM and 574 +/- 62 nM at 50 and 80 min of hypoxia, respectively; values that are within the expected physiological range for [Ca2+]m. Reoxygenation after 50 min hypoxia resulted in no further change in [Ca2+]m whereas reoxygenation after 80 min hypoxia resulted in a 10-fold increase in this parameter. These results provide clear evidence that [Ca2+]m increases during hypoxia and suggest that the ability of the cell to maintain Ca2+ homeostasis is lost on reoxygenation after prolonged hypoxia with the result that [Ca2+]m exceeds the normal physiological range.

Adenosine Triphosphate↗
PubMed1993

Detection of HIV-1 by polymerase chain reaction and culture in seronegative intravenous drug users in an inner-city emergency department.

STUDY BACKGROUND: After a health care worker's unprotected exposure to a patient's blood, the current recommendation is to obtain consent from the source for serologic testing for HIV. If the test is negative, no further follow-up of the exposed provider is usually indicated. OBJECTIVE: To determine if patients testing negative for HIV-1 antibody on routine serology harbor occult HIV-1 infection. DESIGN: Cross-sectional, identity-unlinked, patient-related data and blood sample procurement for HIV-1 infection. SETTING: Inner-city university hospital emergency department with high HIV-1 seroprevalence among patients. TYPE OF PARTICIPANTS: IV drug users not known to have HIV-1 infection. MEASUREMENTS: Serum samples were analyzed for HIV-1 antibodies by enzyme immunoassay and Western blot. Peripheral mononuclear cells were analyzed for HIV-1 provirus by polymerase chain reaction and viral culture. MAIN RESULTS: Of 131 patients, 36 (27.5%) were Western blot-confirmed seropositive for HIV-1. Of the 95 seronegative patients, six (6.3%) were polymerase chain reaction positive, and one of these was confirmed with culture. The negative predictive value of standard serology was 93.5% with polymerase chain reaction alone and 98.9% with concordant polymerase chain reaction and culture results. CONCLUSION: There may be a significant number of ED patients in HIV-1 prevalent populations who have occult HIV-1 infection not detectable by serology at the time of a health care provider exposure. Although these data suggest that further prospective study is warranted to better quantify the frequency of this phenomenon, these preliminary data suggest that current Centers for Disease Control recommendations regarding provider exposures may need to be reappraised for certain situations.

Adult↗
PubMed1993

Factors limiting the effectiveness of prenatal screening for anencephaly and spina bifida in a high-risk area.

The effectiveness of a prenatal screening programme in reducing the birth prevalence of anencephaly and spina bifida (ASB) is influenced by three principal factors: the proportion of affected pregnancies screened (uptake), the proportion of affected pregnancies detected on screening (sensitivity) and the proportion of affected pregnancies terminated when detected (compliance). The purpose of the study was two-fold: to develop an epidemiologically-based method for the retrospective monitoring of these three factors and to attempt to quantify their relative importance in relation to the outcome of screening. Data on births and terminations associated with ASB for the period 1976-1986 were obtained from the Glasgow Register of Congenital Anomalies and from the Department of Medical Genetics, Yorkhill Hospitals. Increasing proportions of affected pregnancies screened, detected and terminated were observed, to a greater degree for anencephaly than for spina bifida. The relationships between uptake, sensitivity, compliance and terminations are described in the form of a simple arithmetic expression. In policy terms, further efforts are required to increase all three in order to improve the effectiveness of screening for spina bifida.

Abortion, Therapeutic↗
PubMed1993

Accommodation and chromatic aberration: effect of spatial frequency.

When subjects view an edge in white light, a colour fringe, produced by longitudinal chromatic aberration (LCA) of the eye, is formed at the edge. The colour fringe changes with changes in focus, and serves as a complex colour-coded cue for reflex accommodation. Fincham found that 60% of his subjects failed to accommodate appropriately when the colour fringe was removed with an achromatizing lens or by the use of monochromatic light. Our experiment sought to determine the spatial frequencies at which LCA is most effective. We monitored accommodation in 10 subjects while they viewed sinusoidally moving sine-wave gratings (1-3 D at 0.2 Hz; 1-10.5 c/deg) in a Badal optometer. The targets were 'white' gratings with LCA normal, doubled, neutralized or reversed. Doubling the aberration has minimal effect, removing the aberration reduces gain and increases phase-lag, and reversing the aberration severely disrupts accommodation. Sensitivity to these chromatic cues exists at all spatial frequencies tested, but is most prominent between 3 and 5 c/deg. These results support the view that the system monitors focus by comparing contrast in red-green and perhaps blue-yellow colour-opponent mechanisms.

Accommodation, Ocular↗
PubMed1993

Approaches to the construction of new candidate poliovirus type 3 vaccine strains.

The World Health Organization has called for improvements to oral polio vaccines (OPV), particularly the type 3 component. Our improved understanding of the genetic basis of attenuation and antigenicity of this strain gives rise to possibilities for constructing new derivatives via mutagenesis of infectious cDNA. This article reviews progress made with various approaches to constructing a new type 3 candidate vaccine strain. These include the construction of antigen chimaeras of poliovirus based on the Sabin type 1 strain, the introduction of new genetically stable attenuation mutations into the 5' non-coding region (NCR) of the type 3 poliovirus genome, and the introduction of mutations which may increase the thermostability of the type 3 vaccine.

Antibodies, Viral↗
PubMed1992

Pro-oxidant effects of lipoxygenase-derived peroxides on the copper-initiated oxidation of low-density lipoprotein.

It has been proposed that lipoxygenases, specifically 15-lipoxygenase, may play an important role in promoting the oxidation of low-density lipoprotein (LDL) in the artery wall. It is well known that peroxides are unstable in the presence of transition metals, decomposing to form the alkoxy and peroxy radicals, and so initiating lipid peroxidation. To test whether lipoxygenase-derived peroxides may promote the oxidation of LDL in the presence of copper, the lipoprotein was enriched with lipid peroxides derived from the enzymic action of 5- and 15-lipoxygenases on either linoleic or arachidonic acid. All of these products were found to promote oxidation, whereas the related hydroxy fatty acids had no effect. This suggests that lipoxygenase-derived peroxides associated with the LDL particle may promote peroxidation in the presence of a suitable transition metal catalyst. This result has implications both for the mechanism of the potential pro-oxidant action of lipoxygenases in vivo and for the ex vivo assessment of the oxidizability of LDL samples isolated from different donors.

Arachidonic Acid↗
PubMed1992

The loading of fura-2 into mitochondria in the intact perfused rat heart and its use to estimate matrix Ca2+ under various conditions.

When rat hearts were perfused with a medium containing 10 microM fura-2/AM for 1 hr at 37 degrees C a significant amount of the derived fura-2 could be detected in subsequently isolated mitochondria. This procedure allowed the measurement of matrix free Ca2+ concentration ([Ca2+]m) of mitochondria rapidly isolated from whole hearts by a method which avoids artefactual redistribution of Ca2+. [Ca2+]m in mitochondria prepared from control hearts and incubated with respiratory substrates and EGTA was found to be 172 +/- 23 nM (mean +/- S.E.M.). When hearts were subjected to either increased mechanical work or treatment with 1 microM L-epinephrine (for 2 mins) [Ca2+]m increased to 916 +/- 138 nM and 727 +/- 65 nM respectively. The presence of ruthenium red (2.5 microM) in the perfusion medium prior to and during inotropic intervention diminished these increases in [Ca2+]m(to 316 +/- 28 nM and 218 +/- 18 nM respectively) but did not affect control values. Addition of Na+ ions to incubated mitochondria to enhance mitochondrial Ca2+ egress diminished these increases in [Ca2+]m due to pre-treatment with positive inotropes (compared to controls). These changes in [Ca2+]m were broadly parallelled by changes in the active non-phosphorylated form of pyruvate dehydrogenase (PDH) under all circumstances. These results provide further evidence that the activation of PDH by positive inotropes is accomplished by, and at least in part due to, raised mitochondrial matrix free [Ca2+] and that such increases can be maintained in isolated and suitably incubated mitochondria.

Animals↗
PubMed1992

Correlation of RNA secondary structure and attenuation of Sabin vaccine strains of poliovirus in tissue culture.

Part of the 5' noncoding regions of all three Sabin vaccine strains of poliovirus contains determinants of attenuation that are shown here to influence the ability of these strains to grow at elevated temperatures in BGM cells. The predicted RNA secondary structure of this region (nt 464-542 in P3/Sabin) suggests that both phenotypes are due to perturbation of base-paired stems. Ts phenotypes of site-directed mutants with defined changes in this region correlated well with predicted secondary structure stabilities. Reversal of base-pair orientation had little effect whereas stem disruption led to marked increases in temperature sensitivity. Phenotypic revertants of such viruses displayed mutations on either side of the stem. Mutations destabilizing stems led to intermediate phenotypes. These results provided evidence for the biological significance of the predicted RNA secondary structure.

Base Sequence↗
PubMed1992

Kallmann's syndrome and dilated cardiomyopathy.

A 52-year-old male previously known to have Kallmann's syndrome was admitted with congestive cardiac failure. He was found to have a dilated cardiomyopathy and died despite medical therapy. This report is the first known case of Kallmann's syndrome and dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1991

Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension.

The acute effects of inhaled nitric oxide (NO) (40 ppm in air) on pulmonary (PVR) and systemic (SVR) vascular resistance were compared with those of an intravenous infusion of prostacyclin (24 micrograms/h) in 8 patients with severe pulmonary hypertension and 10 cardiac patients with normal values of PVR. 10 healthy volunteers were studied non-invasively. In the patients with pulmonary hypertension, PVR fell significantly after inhaled NO and after prostacyclin. PVR also fell significantly in the cardiac patients after inhaled NO. Although SVR fell substantially after prostacyclin in patients with pulmonary hypertension, inhaled NO had no effect on SVR in any patient or volunteer. Inhaled NO therefore seems to be both a selective and effective pulmonary vasodilator.

Administration, Inhalation↗
PubMed1991

Reoxygenation-dependent decrease in mitochondrial NADH:CoQ reductase (Complex I) activity in the hypoxic/reoxygenated rat heart.

Reoxygenation of the hypoxic myocardium results in a number of processes, including an O2-dependent increase in total tissue Ca2+ and cell lysis in which mitochondrial electron transport plays a key role. In the present study we have isolated mitochondria from perfused rat hearts subjected to hypoxia and found no change in their respiratory function relative to controls. In contrast, mitochondria isolated immediately after reoxygenation of hypoxic-perfused hearts exhibited a specific and significant decrease in NADH:CoQ reductase (Complex I; EC 1.6.5.3) activity, as measured both polarographically and spectrophotometrically. Isolated cardiomyocytes subjected to a similar protocol of hypoxia/reoxygenation also exhibited a specific decrease in Complex I activity. Myocardial perfusion with media containing Ruthenium Red protected against the reoxygenation-dependent loss of Complex I activity. These observations taken together suggest that mitochondrial Ca2+ uptake on reoxygenation is implicated in the mechanism of the specific loss of Complex I activity.

Animals↗
PubMed1991

Preventability of neonatal cold injury and its contribution to neonatal mortality.

When the body temperature of a small neonate falls below 35 degrees C, lassitude can be noted; severe derangements of cardiovascular, renal, hepatic, immunological, and hematological systems may also occur depending in part on the duration and severity of hypothermia. Diagnosis requires a low-reading thermometer, lacking which the diagnosis can be suspected, but most often is missed. Fatal cases of diagnosed cold injury commonly have terminal pneumonia or sepsis. Prevention involves identification and home visits to high-risk infants; intensive care of those with the diagnosis at Soroka Hospital Medical Center has reduced the case-fatality rate from 30% in 1971 to 3% in 1988-1989. During the same period in our region, the proportion of neonatal deaths occurring in winter months of December, January, and February has dropped from 55 to 27%. The expected proportion is 25%. We hypothesize that excess neonatal mortality during winter months, especially due to pneumonia and sepsis or sudden infant death syndrome (SIDS) is an indicator of missed cold injury syndrome. A preliminary evaluation was made form U.S. data by state, provided by the National Center for Health Statistics, which records no fatalities from cold injury during 1986. Contrasted with this are 26 cold injury deaths in Israel for 1977-1980. In the U.S., though, excess winter neonatal deaths in 1986 from SIDS, pneumonia, and sepsis are reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Cold Temperature↗