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Biomedical subjects

C D Black

Publications and source records attributed to C D Black.

At least 19 recordsLinked to original sources

A population-based health information system.

The authors introduce the Population Health Information System, its conceptual framework, and the data elements required to implement such a system in other jurisdictions. Among other innovations, the Population Health Information System distinguishes between indicators of health status (outcomes measures) and indicators of need for health care (socioeconomic measures of risk for poor health). The system also can be used to perform needs-based planning and challenge delivery patterns.

Canada

Utilization of hospital resources.

A population-based approach was used to analyze the utilization patterns of hospital care by Manitoba residents during the fiscal year 1991/1992. Patterns were analyzed for eight administrative regions, with use assigned to the patient's region of residence, regardless of the location of the hospitalization. Regional boundaries consistent with those used for presentation of data on health status and socioeconomic risk permitted integration of findings across the Population Health Information System. Marked differences in acute hospital use were found. Residents of the urban Winnipeg ("good health") region had the lowest rates of use of acute care overall, and northern rural ("poor health") regions had significantly higher rates of use. However, almost one half of hospital days by Winnipeg residents were used in long-stay care (60+ days), while rural residents were more likely to use short-stay hospital care. Despite a concentration of surgical specialists in Winnipeg, there were only small regional differences in overall rates of surgery.

Adult

Utilization of physician resources for ambulatory care.

This article describes the utilization of ambulatory physician services by Manitoba residents during the fiscal year 1991/1992. Care was assigned to the patient's residence in one of eight administrative regions, whether the care was received in or out of the region of residence. Disparities in physician supply across regions did not correspond with differences in the use of services: the Winnipeg region had twice as many physicians per 1000 residents as the largely rural non-Winnipeg regions and was home to most specialists. With their rich supply of physicians, particularly specialists, Winnipeg residents had somewhat higher contact rates (16%), and the province spent 26% more per resident providing physician services, despite the fact that our indicators of health status and socioeconomic risk suggest no increased need for physician services among Winnipeg residents. Despite the concentration of physicians in Winnipeg, there was remarkably good access to physicians across the province, with 78% or more of the residents in every region making at least one contact with a physician during the year. The differences in use between Winnipeg and non-Winnipeg residents were almost entirely accounted for by intensive users, (individuals making eight or more visits per year). Although residents 75 years of age and older (6% of the population) made twice as many visits per capita compared to younger adults, their actual demand on the system was small, accounting for just less than 10% of expenditures on physician services. Population-based health information provides important insight for needs-based planning of physician services.

Adolescent

The Population Health Information System: data analysis and software.

This article describes the software developed in the process of creating the Population Health Information System. The software can be applied to a range of administrative data and provides standardized data on the health status and health care use of populations by generating population-based rates of discrete events. The standardized approach permits construction of a comprehensive, comparative picture for residents of defined geographic regions. The addition of a user friendly graphic interface will permit regional planners to do their own data analyses and allow out-of-province researchers to adopt the system for their own uses.

Community Health Planning

Stability and trends over 3 years of data.

Because the health status of a population does not usually respond immediately to interventions, whether social or medical, the ability to analyze change over time is important. Therefore, patterns of change and stability in health status and health care use of Manitoba residents during a 3-year period from 1990 to 1992 were analyzed using the Population-based Health Information System. This article presents summary findings and discusses methodological and policy issues arising from the analyses. A small but significant decrease in premature mortality (the primary health status indicator) was observed in most regions of the province, but two remote, northern regions, those whose residents scored at high socioeconomic risk, remained distinguished for their poor health status. These "poor health" regions also had the highest contact rates with primary caregivers, raising questions about the role of the health care system in improving the health of the population. A persistent increase in surgery was observed in several regions, led by increases in outpatient surgery over and above increases in the elderly population and beyond substitution for inpatient procedures. This trend (not obvious before these analyses) is important as hospitals move to expand their outpatient facilities in response to restraints on inpatient care.

Adolescent

A population-based approach to monitoring adverse outcomes of medical care.

A population-based approach to monitoring quality of care combining small-area analysis and outcomes assessment is proposed. While adverse outcomes due to poor surgical technique have long been targeted for quality-of-care review, in this study, giving similar attention to adverse outcomes produced by high rates of interventions is proposed. A population-based approach will strengthen traditional review efforts that currently begin and end at the hospital door. Excluded from these reviews have been questions such as the following: Should the procedure have been performed in the first place? Did the benefits outweigh the risks? Were there other patients not operated on who might have benefited more? Traditional approaches can identify less competent hospitals or practitioners: population-based approaches can identify the surgical enthusiasts who may pose equal risks to the populations of the areas they serve. Applying a population-based approach to review of coronary artery bypass graft surgery for Medicare patients in five cities in the United States demonstrates that at least as many deaths could have been prevented by decreasing surgical rates to the U.S. average as by improving the technical quality of care with which the procedure was performed. A similar population-based analysis of complications (as judged by re-admissions within 30 days of surgery) associated with hysterectomy across regions of Manitoba, Canada, is presented. In summary, negligent acts in the delivery of health care in institutions are rare and are difficult to detect because medicine is an inexact science and because adverse outcomes are more likely in high-risk patients, regardless of the quality of care. However, from a population perspective, adverse events are predictable, occur relatively frequently, and are directly related to the frequency of a population's exposure to surgical intervention. Efforts to improve quality of care could be made more effective by including the rates at which populations are exposed to treatments and the technical quality of care delivered.

Adult

Maslach Burnout Inventory: factor structures for pharmacists in health maintenance organizations and comparison with normative data for USA pharmacists.

This study compared the factor structure and burnout scores obtained on the Maslach Burnout Inventory from 84 pharmacists in Health Maintenance Organizations (HMO) with the normative data for USA pharmacists. Results provided empirical support for the reliability and validity of the inventory to measure burnout within the profession of pharmacy. Values of Cronbach coefficient alpha for subscales of Emotional Exhaustion, Depersonalization, and Personal Accomplishment were similar to those obtained with the normative sample. Factor analysis was conducted to yield the best three-factor solution. Derived factor loadings matched the three hypothesized subscales. On Personal Accomplishment the mean subscale score for HMO pharmacists was significantly higher than the normative score. Given limitations of the small sample, research is indicated to substantiate use of the inventory among HMO pharmacists.

Adult

Fc-receptor-mediated targeting of antibody-bearing liposomes containing dideoxycytidine triphosphate to human monocyte/macrophages.

Liposomes bearing surface-attached antibody (L-Ab) molecules can be used for various purposes including the immunospecific delivery of drugs or other materials to antigenic target cells. In this study, L-Ab were prepared to deliver an anti-human immunodeficiency virus (HIV) drug, dideoxycytidine triphosphate (ddCTP) to human monocyte/macrophages. Cells of the monocyte/macrophage lineage are an important reservoir of HIV-1. A mouse monoclonal antibody IgG2a was labelled with 125I and modified using N succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a heterobifunctional reagent in order to conjugate with liposomes to produce a covalent bond (thioether). SPDP-modified antibody was incubated with liposomes containing 5 mol% of maleimido phenyl butyrate phosphatidylethanolamine (MPB-PE) at room temperature (21 degrees C) for 24 h. L-Ab were separated from free and aggregated antibodies by centrifugation. L-Ab were characterized by measuring particle size and binding to anti-mouse IgG-sepharose. Ninety five per cent of the liposomal (L-Ab) lipid label was bound to anti-mouse IgG-sepharose, whereas only 7% of plain liposomes were bound, indicating non-specific binding. Uptake of L-Ab was measured in human monocyte/macrophages as a function of time and compared with that of plain liposomes. The uptake increased with time and it was 4-6 times greater than that of plain liposomes although part of that effect may have been due to unreacted MPB groups.

Antibodies, Monoclonal

Two cases of suspected immunologic-based hypersensitivity reactions to etoposide therapy.

OBJECTIVE: To report two cases of suspected immunologic-based hypersensitivity reactions to etoposide therapy. DATA SYNTHESIS: Two cases are presented that differ from the majority of reported hypersensitivity reactions to etoposide. One patient, who tolerated etoposide during his first three-day chemotherapeutic dosage regimen, developed a hypersensitivity reaction to etoposide upon re-exposure to the drug during the first day of a subsequent three-day cycle. Another patient experienced a hypotensive episode on the first day of an initial three-day regimen, which did not recur on the two subsequent days of the cycle. However, when the patient was re-exposed to etoposide four weeks later, he experienced a severe reaction within minutes of drug infusion. Both patients were premedicated with corticosteroids and neither reported prior drug allergies. CONCLUSIONS: Based upon these cases and other literature reports, we believe these reactions primarily represent a type II or immunologic-based hypersensitivity reaction to etoposide.

Aged

Ability of nifedipine to prolong parturition in rats.

Rats were randomly assigned to treatments: (i) no surgery control; (ii) saline control; (iii) 0.25, 0.5, 1.0 or 2.0 micrograms nifedipine kg-1 min-1; or (iv) 5.0 micrograms ritodrine kg-1 min-1. All drug treatments increased the interval between pup deliveries compared with the no surgery and saline controls. Apparent complete tocolysis was observed in 20, 60, 80 and 80% of the animals receiving 0.5, 1.0 or 2.0 micrograms nifedipine kg-1 min-1 or 5.0 micrograms ritodrine kg-1 min-1, respectively. A positive pharmacodynamic relationship was observed for the nifedipine doses. Analysis of pup viability showed no statistically significant difference among treatments. Treatment with 2.0 micrograms nifedipine kg-1 min-1 gave a delay in pup delivery comparable to that with ritodrine.

Animals

Semidehydroascorbic acid as an intermediate in norepinephrine biosynthesis in chromaffin granules.

We investigated whether semidehydroascorbic acid was an intermediate in norepinephrine synthesis in chromaffin granules and in electron transfer across the chromaffin granule membrane. Semidehydroascorbic acid was measured in intact granules by electron spin resonance. In the presence of intragranular but not extragranular ascorbic acid, semidehydroascorbic acid was formed within granules in direct relationship to dopamine beta-monooxygenase activity. However, semidehydroascorbic acid was not generated when granules were incubated with epinephrine instead of the substrate dopamine, with dopamine beta-monooxygenase inhibitors, without oxygen, and when intragranular ascorbic acid was depleted. Experiments using the impermeant paramagnetic broadening agents [K3 [Cr(C2O4)3].3H2O] and Ni(en)3(NO3)2 provided further evidence that semidehydroascorbic acid was generated only within granules. We also investigated semidehydroascorbic acid formation in the presence of intragranular and extragranular ascorbic acid. Under these conditions, semidehydroascorbic acid was formed on both sides of the granule membrane, and formation was coupled to dopamine beta-monooxygenase activity. These data indicate that dopamine beta-monooxygenase is reduced by single electron transfer from intragranular ascorbic acid, that transmembrane electron transfer occurs by single electron transfer, and that transmembrane electron transfer is directly coupled to formation of intragranular semidehydroascorbic acid via dopamine beta-monooxygenase activity.

Adrenal Medulla

Kinetics of superoxide production by stimulated neutrophils.

Oxygen-derived active species and superoxide radical in particular are generated and excreted upon granulocyte activation and are instrumental in host defense against bacterial and fungal infections. Associated with the activation of neutrophils is an apparent transitory oxy-radical production. Evidence from independent methods has previously suggested that radical production peaks shortly following neutrophil stimulation and decays within minutes. However, since neutrophil function in the body might reasonably be expected to last beyond the few minutes following stimulation, cessation of the production of oxy-radicals is unexpected. In an attempt to reconcile this discrepancy, the formation kinetics of superoxide by stimulated human neutrophils was reinvestigated by three independent methods: electron spin resonance, chemiluminescence, and ferricytochrome c reduction. The present results demonstrate that under appropriate experimental conditions stimulated neutrophils have the capacity to produce superoxide for several hours. The reasons for the previously reported "apparent" ephemeral nature of oxy-radical formation are discussed.

Electron Spin Resonance Spectroscopy

On radical production by PMA-stimulated neutrophils as monitored by luminol-amplified chemiluminescence.

The means by which neutrophils within the body ward off infectious and neoplastic processes by the activation of molecular oxygen, as well as how such mechanisms dysfunction, is the subject of extensive ongoing research. Most previous studies of neutrophil activation indicate that there is a transient production of reactive oxygen species. Luminol-amplified chemiluminescence surveillance of O2-. and H2O2 supported these general findings. Yet, recent studies showed that production of reactive oxygen species by PMA-stimulated neutrophils is not transient but persistent; however, luminol-dependent methods do not corroborate such findings. The kinetics of O2-. production by human neutrophils were studied using luminol-amplified chemiluminescence (CL), spin trapping combined with electron spin resonance detection, and ferricytochrome c reduction. The effects of pH and O2 level on luminol-amplified CL were determined using hypoxanthine/xanthine oxidase to produce O2-. and H2O2 in cell-free systems. As we have found by electron spin resonance and ferricytochrome c reduction, stimulated neutrophils continued to generate O2-. for several hours, yet when luminol-amplified CL was used to continuously follow radical production, CL was shortly lost. Similar loss of CL was observed with continuous enzymatic formation of O2-. and H2O2. The failure of the CL assay to report O2-. and H2O2 formation results from some luminol reaction product which interferes with the light reaction. Our results show that the cells are operative for long periods indicating that cell exposure to prolonged O2-. fluxes does not terminate radical production, and even when pH, [O2], and reagents are optimized, the use of luminol-amplified CL is not a valid assay for continuous monitoring of O2-. and H2O2 generated by either stimulated neutrophils or in cell-free systems.

Cell-Free System

Superoxide production by stimulated neutrophils: temperature effect.

Activation of neutrophils results in a one-electron reduction of oxygen to produce the superoxide anion and other oxygen-derived, microbicidal species. Evidence from many kinetic studies of oxygen-derived radicals generated by stimulated neutrophils in vitro shows that radical production is optimal at 37 degrees C but only lasts several minutes and then rapidly subsides. These findings support the widely held perception that the neutrophil's "oxidative burst" is a transitory event that peaks within minutes of stimulation and ends shortly thereafter. However, while some studies have shown that under controlled conditions stimulated neutrophils can generate superoxide continuously for several hours, others have observed that the superoxide formation by neutrophils stimulated in buffer at 37 degrees C does not persist. To reconcile the conflicting findings and to better understand neutrophil function, we have reinvestigated the effect of temperature on the kinetics of radical generation by PMA-stimulated cells. Electron paramagnetic resonance spectroscopy coupled with spin-trapping and SOD-inhibitable ferricytochrome c reduction were used to monitor superoxide production by neutrophils stimulated at either 25 degrees C or 37 degrees C in RPMI 1640 medium or in Hank's balanced salt solution. When oxygen was supplied continuously, neutrophils stimulated at 25 degrees C in buffer or in medium generated superoxide for several hours but at 37 degrees C, particularly in HBSS, O2- formation strikingly and rapidly decreased. This cessation of superoxide generation was reversible by lowering the temperature back to 25 degrees C. These data imply that in vivo neutrophils may be capable of generating oxy-radicals for prolonged periods. In part, our results may also explain the often observed termination of neutrophil-derived radical formation in vitro and help to dispel the perception that neutrophil-derived oxy-radical production is an ephemeral phenomenon.

Cyclic N-Oxides

Inhibition of HIV-1 in monocyte/macrophage cultures by 2',3'-dideoxycytidine-5'-triphosphate, free and in liposomes.

The antiviral effects of 2',3'-dideoxycytidine (ddC), 2',3'-dideoxycytidine-5'-triphosphate (ddCTP) and liposome-encapsulated ddCTP [L(ddCTP)] were compared in cultured human monocyte-macrophages (M/M) infected with HIV-1. These treatments inhibited virus replication at nanomolar drug levels with activities in the order ddC greater than ddCTP = L(ddCTP). Studies on drug stability and uptake suggest that a large part of the free ddCTP is dephosphorylated before entering the cells, whereas L(ddCTP) remains stable over days and is taken up, probably by endocytosis. The response to L(ddCTP) suggests that the capability of liposomes for targeting drugs to macrophages in vivo could potentially be exploited to improve the therapeutic index of dideoxynucleoside drugs.

Acquired Immunodeficiency Syndrome

Nitroglycerin delivery through a polyethylene-lined intravenous administration set.

Adsorption and delivery of nitroglycerin through a new polyethylene-lined (PEL) i.v. administration set was compared with adsorption and delivery through an identical set composed of polyvinyl chloride (PVC) rather than PEL tubing. The new delivery system consisted of PEL tubing, a transparent PVC chamber, and a silastic segment for insertion in a peristaltic pump. Nitroglycerin was prepared in concentrations of 50, 125, and 200 micrograms/mL in 0.9% sodium chloride injection and run through both administration sets at flow rates of 12 and 60 mL/hr. Samples were obtained at 0, 0.5, 1, 2,4, and 8 hours from each of three sites: bottle, junction before silastic segment, and distal end of tubing. Nitroglycerin content was assayed using a modified high-performance liquid chromatography technique. A slight but significant average loss of nitroglycerin (2.3 +/- 9.3%) was observed at the distal end with the PEL set, whereas the PVC set showed a significant average nitroglycerin loss of 39.7 +/- 12.7% at the distal end. These differences were independent of infusion rate, nitroglycerin concentration, or time of sampling. Flow rate, concentration, and time had no significant effect on nitroglycerin adsorption with the PEL set, but all three had a significant effect on nitroglycerin adsorption with the PVC set. An unexpected finding was the approximately 14% loss of nitroglycerin from the admixture bottle over time. This phenomenon, which has been observed by other investigators, needs further investigation to determine its cause. It appears that a partially PVC-based administration set should provide consistent delivery of i.v. nitroglycerin to the patient.

Chemistry, Pharmaceutical

Hydroxyl radical production by stimulated neutrophils reappraised.

Release of active oxygen species during the human neutrophil respiratory burst is thought to be mandatory for effective defense against bacterial infections and may play an important role in damage to host tissues. Part of the critical bacterial and host tissue damage has been attributed to hydroxyl radicals produced from superoxide and hydrogen peroxide. Because of the short life time of the very reactive hydroxyl radical, direct study of hydroxyl radical production is not possible; therefore, indirect detection methods such as electron spin resonance (ESR) coupled with appropriate spin-trapping agents such as 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) have been used. Superoxide production during the oxidative burst has been unambiguously demonstrated. Recent reports claim that hydroxyl radicals are not made during neutrophil stimulation and offer as an explanation the presence of granular components that interfere with hydroxyl radical production. When using the spin-trap agent DMPO, absence of the relatively long-lived adducts DMPO-OH and DMPO-CH3 has been assumed to be prima facie evidence for lack of hydroxyl radical participation. We show that high superoxide flux produced during stimulation of human neutrophils rapidly destroys both DMPO-OH and DMPO-CH3. In accord with previous implications, our results provide an alternative explanation for the absence of .OH adduct in spin-trapping studies and corroborate results obtained using other methods that implicate hydroxyl radical production during neutrophil stimulation.

Cyclic N-Oxides