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Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Acute and chronic suppression of leukotriene B4 synthesis ex vivo in neutrophils from patients with rheumatoid arthritis beginning treatment with methotrexate.

OBJECTIVE: To compare the cumulative effects of oral methotrexate (MTX) therapy (after 6-8 weeks) with the acute effects (24 hours after a dose) on arachidonic acid metabolism by the 5-lipoxygenase (5-LO) pathway in neutrophils from patients with active rheumatoid arthritis (RA) who were beginning therapy with MTX. METHODS: Neutrophils and monocytes were isolated from whole blood from 7 patients with RA, immediately before and 24 hours after their first weekly dose of 7.5 mg of MTX, and again after their dose at 6-8 weeks. RESULTS: Total immunoreactive leukotriene B4 (LTB4) formation in neutrophils activated ex vivo with calcium ionophore A23187 was significantly suppressed (by 33%) before the 6-8-week dose, compared with the level before the first dose (mean +/- SEM 8.29 +/- 1.24 ng/10(6) cells at predose 6-8 weeks versus 12.29 +/- 2.13 ng/10(6) cells at predose 1; P = 0.03). Reductions were also observed after the first dose (27%; P = 0.07) and after the 6-8-week dose (43%; P = 0.05) compared with the respective predose levels. MTX treatment produced significant reductions in the total generation of 5-LO pathway products (5-hydroxyeicosatetraenoic acid + 6-trans-LTB4 + LTB4 + omega-oxidation products of LTB4) by calcium ionophore-activated neutrophils, as quantitated by integrated optical density after resolution on reverse-phase high-performance liquid chromatography. Decreases were observed after the first dose (26%; P = 0.025), immediately before the 6-8-week dose (23%; P = 0.05), and after the 6-8-week dose (47%; P = 0.0033) compared with levels before the first dose, and after the 6-8-week dose compared with the level before it (32%; P = 0.04). The generation of LTB4 by calcium ionophore-activated monocytes was not significantly affected by MTX therapy. CONCLUSION: The significant decreases in the formation of omega-oxidation products of LTB4 and in the total generation of neutrophil 5-LO pathway products in the absence of a significant change in the release of 3H-arachidonic acid or the generation of platelet-activating factor suggest that the activity of the 5-LO enzyme in neutrophils is inhibited. We conclude that weekly oral MTX therapy in patients with active RA inhibits neutrophil 5-LO pathway product generation in a pattern consistent with inhibition of the activity of the 5-LO enzyme; an effect is observed after the first dose. The inhibition of 5-LO is cell-selective and cumulative, with a superimposed incremental inhibition observed after the weekly MTX dose.

Adult↗
PubMed1992

Simplified gram stain interpretive method for diagnosis of bacterial vaginosis.

OBJECTIVE: Two methods which only consider bacterial morphotypes and require counting various types of bacteria, for interpreting Gram stains of vaginal secretions for the purpose of diagnosing bacterial vaginosis were previously described. A new interpretative method, which combines clue cells with bacterial morphotypes as diagnostic markers, is offered. STUDY DESIGN: One hundred twenty patients were tested with the new interpretative method and clinical criteria of bacterial vaginosis as the reference standard. RESULTS: The new method was found comparable to older methods when all were compared with clinical diagnostic methods. The sensitivity of the clue cell method was 86.1% and the specificity was 92.8%. The predictive value of a positive test was 83.7% for a population with a prevalence of bacterial vaginosis of 30%. The negative predictive value was 94.0%. CONCLUSION: If clue cells are present and the nonlactobacilli morphotypes exceed lactobacilli morphotypes, bacterial vaginosis can be diagnosed without the need for exact bacterial counts.

Adolescent↗
PubMed1992

Effect of mydriasis on visual field area in retinitis pigmentosa.

PURPOSE: The effect of mydriasis on Goldmann visual field area in patients with retinitis pigmentosa has not been suitably defined. The aim of this study is to determine whether visual field area in these patients varies with pharmacologic mydriasis. METHODS: Fifteen adult patients with retinitis pigmentosa were studied prospectively. Goldmann visual fields with II4e and V4e isopters were obtained in both eyes before and after full pharmacologic mydriasis of the right eye. The isopter areas were quantified and analyzed to determine the effect of mydriasis on visual field area. RESULTS: The difference in the right eye isopter areas was compared with the difference in the left eye isopter areas using paired t tests, where the differences were computed from areas obtained before and after dilation of the right eye. Mydriasis had no significant effect on the visual field in terms of isopter area difference (II4e, P = 0.87; V4e, P = 0.45) and percent change in isopter area (II4e, P = 0.81; V4e, P = 0.24). CONCLUSION: Pharmacologic mydriasis had no appreciable effect on the Goldmann visual field area in a selected group of patients with retinitis pigmentosa. These findings suggest that visual fields of such patients obtained in the dilated or undilated state can be meaningfully compared.

Adult↗
PubMed1992

Cytokine regulation of adenylate cyclase activity in LLC-PK1 cells.

Although several cytokines have been demonstrated to exert pleiotropic responses, there is little information on cytokine regulation of renal tubular epithelial cell function. In the present studies, we find that both T cell-derived (tumor necrosis factor-beta and interleukins 2 and 3) and monocyte/macrophage derived (tumor necrosis factor alpha and interleukin 1 beta) cytokines promote basal, arginine vasopressin- and forskolin-stimulated adenylate cyclase activity in cultured LLC-PK1 cells. No effect of TNF, IL-1 beta, and IL-2 to stimulate protein kinase C activity was observed. TNF-beta, IL-1 beta and IL-2 also modestly stimulated 3H release from 3H-arachidonic acid labeled cells. Mepacrine, a phospholipase A inhibitor, prevented TNF-beta stimulation of 3H release from 3H-arachidonic acid labeled cells and TNF-beta potentiation of adenylate cyclase activity. TNF-beta potentiation of adenylate cyclase activity and stimulation of 3H release from 3H arachidonic acid labeled cells was not prevented by pertussis toxin. These results demonstrate that several cytokines can stimulate adenylate cyclase activity while not affecting protein kinase C activity in cultured renal tubular epithelial cells. The effect of TNF-beta to stimulate adenylate cyclase appears to occur independent of pertussis toxin-sensitive substrate and may involve activation of phospholipase A.

Adenylate Cyclase Toxin↗
PubMed1992

Commentary on NASCIS-2.

Release of results of a clinical study to the public press prior to dissemination in a professional journal is a substantive issue which must undergo continued scrutiny. This report analyzes the second National Acute Spinal Cord Injury Study (NASCIS-2) and its subsequent reportage. NASCIS-2 was an elaborate protocol consisting of the randomized blinded use of methylprednisolone (MP), naloxone or placebo in 487 patients within 12 hours of spinal cord injury. Analysis of the entire population failed to show a significant clinical difference among treatments although data stratification revealed a significant change in patients with a complete loss of function who received MP within 8 hours of injury. The administration of MP was associated with a 7.1% incidence of wound infection. While these results suggested clinical benefit, incomplete data and statistical descriptions reduced assertions. Discrepancies in the report included lack of radiological data or descriptions of time-dependent surgical manipulations and extent of rehabilitative therapy. Justification for the broad 8-hour stratum and multiple hypothesis testing was unclear; incomplete design details included level of statistical significance, study power, stopping rules, trial duration and odds ratio data. The hypothesis that press release prior to publication in a professional journal would result in rapid therapy remained unproven. Reasons for pre-release, including limited peer review, physician familiarity with drug and dosage, and lack of alternative treatment or treatment complications were either unjustified or problematic. Early disclosure to the press resulted in da ta misinterpretation and oversimplification, failure to recognize exclusion or appropriate legal ramifications,and lack of communication to appropriate physicians.

Clinical Trials as Topic↗
PubMed1992

The effect of geriatric evaluation and management on Medicare reimbursement in a large public hospital: a randomized clinical trial.

OBJECTIVE: To study the effect of a geriatric evaluation and management program on health care charges and Medicare reimbursement. DESIGN: Prospective randomized controlled trial during a 1-year study period. SETTING: Large medical school-affiliated public hospital in an urban community. SUBJECTS: Patients at least 70 years old admitted to the medicine service were screened and randomized into two groups of 100 patients each. INTERVENTION: Patients randomized to the experimental group underwent initial comprehensive geriatric evaluation and once discharged from the hospital were enrolled in a geriatric care management and treatment program. The control group received usual care only. The major intervention of this study was in outpatient long-term care. MAIN OUTCOME MEASURE: Total charges for services billed to Medicare Part A and Part B and total Medicare reimbursement. The Medicare charge and reimbursement data were obtained by use of the Medicare Automated Data Retrieval System, a linked Medicare Part A and Part B utilization file. RESULTS: Total charges and reimbursement were greater for the control group but not significantly so. Subset analysis revealed significantly greater inpatient charges (P < 0.03) and Medicare reimbursement (P < 0.005) for the control patients and a greater likelihood of utilization of home health care services in the experimental group (P < 0.01). CONCLUSION: A geriatric evaluation and management program appeared to shift utilization and Medicare expenditures from inpatient services to home health care services. There was no evidence that the experimental program resulted in increased expenditures for Medicare. In selected populations, geriatric evaluation and management programs may contribute to cost containment.

Activities of Daily Living↗
PubMed1992

Hypervitaminosis A and reproductive disorders in rabbits.

Reproductive abnormalities in New Zealand White rabbits at a large commercial rabbitry were linked to an excess of dietary retinyl acetate. Fetal resorptions, abortions, and stillbirths were common in pregnant does. Examination of aborted and stillborn fetuses disclosed hydrocephalus, microencephaly, and cleft palate. Analysis of the commercially prepared feed disclosed a total vitamin A content of 102,278 IU/kg, of which 97,618 IU was retinyl acetate (recommended total vitamin A concentrations are 6,000 to 12,000 IU/kg). Levels of vitamin A in the plasma of does with reproductive disorders were 517 to 1,667 ng/ml (normal level is 300 ng/ml), and liver levels were 2,070 to 12,854 micrograms/g (normal range is 50 to 300 micrograms/g).

Abortion, Incomplete↗
PubMed1992

Marketing dentistry: a pilot study in Dudley.

This study was an attempt to persuade non-users or irregular users of dental services to change their behaviour and visit the dentist more regularly. The task was divided into two main parts. One was a promotion campaign undertaken in the Borough of Dudley in the West Midlands and the other a professional development programme for the dentists practising in the same area. The professional development campaign was designed to make the practitioners aware of the barriers to dental care which are perceived by patients. It was undertaken through a series of workshops on various aspects of practice development and promotion to which the staff of all the dental practices in Dudley were invited. Thirty-nine out of a total of forty-one accepted the invitation and attended some or all of the programme. In addition to the workshops members of the research team visited each of the participating practices regularly to discuss aspects of the programme and to record progress. The practitioners had varied attitudes to marketing and varied learning styles, and therefore they had different expectations of the nature and purpose of professional development. The majority attended solely to learn about the promotion campaign. There were also varying perceptions of patient recruitment and retention. None saw this as a serious problem. However, even before the new National Health Service contract for general dental practitioners there was the growing realisation that in the future there would be competition between practices and that this could be a reason for considering recruitment and the retention of patients more carefully. This was considered by many of the dentists, but not all, to be a problem of patient behaviour, linked with a degree of fatalism, and that nothing much could be done about it. There was a reluctance to change and the fear of the risks involved led a number of the general dental practitioners to identify and emphasise the difficulties in making new developments rather than their benefits. Only one quarter of the practices made any changes and they tended to prefer quick solutions rather than basic development. The experience gained in this part of the study indicated that in the future professional development should be considered in terms of the dentist's perception of the costs and the benefits; direct costs, opportunity costs, and the prospect of effecting change.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Medical apartheid. An American perspective.

The suppressive policies and practices of apartheid in South Africa have directly contributed to preventable morbidity and mortality in black Africans. Due to socioeconomic segregation ("functional apartheid"), America's citizens of color also suffer excess death and disability. Health status measurements in the United States confirm the failure of the current fragmented health care system to recognize or respond to the unmet need or the barriers that exist. Predictably, the changes needed to improve the health status of black South Africans are similar to those that are necessary to remedy the situation in the United States. Community-Oriented Primary Care is a health service provision model that holds promise as a comprehensive community-based strategy that can begin to address some of the shortcomings of the current medical care systems of both nations.

Black or African American↗
PubMed1991

Regulation by forskolin of cyclic AMP phosphodiesterase and protein kinase C activity in LLC-PK1 cells.

Forskolin, a naturally occurring activator of adenylate cyclase, inhibits total and high-affinity cyclic AMP phosphodiesterase activity in soluble and particulate fractions of cultured LLC-PK1 renal epithelial cells. The naturally occurring forskolin analogue 1,9-dideoxyforskolin, which does not stimulate adenylate cyclase activity, is a more potent inhibitor of cyclic AMP phosphodiesterase activity than forskolin. To clarify the structural feature of the forskolin molecule responsible for inhibition of cyclic AMP phosphodiesterase activity, the effects of two agents which share structural identity with portions of the forskolin ring were tested. The steroid 5-pregnenolone, but not the hexose alpha-D-galactose, inhibited cyclic AMP phosphodiesterase activity in LLC-PK1 cells. Forskolin and 1,9-dideoxyforskolin both stimulate protein kinase C activity in LLC-PK1 cells. The effect of 1,9-dideoxyforskolin in stimulating LLC-PK1 protein kinase C activity can be attenuated by staurosporine. Both 5-pregnenolone and alpha-D-galactose also stimulate protein kinase C activity in LLC-PK1 cells. 5-Pregnenolone and the phorbol ester phorbol 12-myristate 13-acetate cause translocation of protein kinase C from a soluble to a particulate fraction, while both 1,9-dideoxyforskolin and alpha-D-galactose increase protein kinase C activity in both soluble and particulate fractions. Our results demonstrate that forskolin exerts diverse enzymic effects in cultured LLC-PK1 cells.

1-Methyl-3-isobutylxanthine↗
PubMed1991

A method for the purification of DNA/protein complexes applied to DNA topoisomerase II cleavage sites.

The object of this study was to devise a purification method for DNA/topoisomerase II complexes, with which to examine the enzyme's cleavage site specificity in cellular differentiation. Retinoic acid-induced differentiation involves topoisomerase II-mediated transient changes in DNA supercoiling, but it is not known whether this occurs at specific sites in the genome. Topoisomerase II forms a covalent DNA enzyme complex as it acts, which can be recovered by the sodium dodecyl sulfate (SDS)/KCl precipitation method, but this method fails to recover significantly more DNA from cells induced to differentiate. This may in part reflect the low numbers of retinoic acid-induced protein-linked breaks in DNA and also the method's relative inefficiency for DNA with few attached topoisomerase molecules. This suggested that an additional purification method would be required to enrich sufficiently for cleavage site DNA to address the issue of site specificity. The principle of our method is to couple poly(ethylene glycol) (PEG) to topoisomerase while it is covalently attached to DNA and then to use phase partitioning in an aqueous two-phase system of PEG and phosphate to separate free DNA from DNA bound to PEG-modified topoisomerases (which have high affinities for the phosphate-rich and PEG-rich phases, respectively). The method can be used in conjunction with DNase protection and, unlike the SDS/KCl method, can fractionate short fragments of DNA to which single protein molecules are attached. Using the SDS/KCl precipitation and new method in series, we have recovered protein-linked DNA from HL60 cells induced to differentiate to the granulocyte lineage (by retinoic acid) or to the monocyte/macrophage lineage (by phorbol myristate acetate) and have demonstrated that specific sequences become protein linked, probably to topoisomerase II, during induced differentiation.

Chemical Fractionation↗
PubMed1991

Separation of cell mixtures by immunoaffinity cell partitioning: strategies for low abundance cells.

The partitioning of cells in aqueous two-phase systems formed by poly(ethylene glycol) (PEG) and dextran can be changed by incubating the cells with a PEG-modified antibody directed specifically against its surface. We have developed a new approach for immunoaffinity cell partitioning (IACP) in which the antibodies are first reacted with tresylated monomethoxy PEG (TMPEG) in sodium phosphate buffer, pH 7.5, the excess TMPEG is quenched by reaction with bovine serum albumin, and the resulting preparation is used directly for incubation with the cells without any isolation of the monomethoxyPEG (MPEG)-antibody conjugates. We have demonstrated the specificity of this IACP method by showing that MPEG-modified anti-human red blood cell antibody increases the partition of human erythrocytes from the interface to the PEG-rich top phase (up to 100%) but not the partitioning of either neutrophils or HL60 cells. Irrelevant antibodies do not affect the partitioning of red blood cells. The partitioning behaviors of erythrocytes and HL60 cells in mixtures varying from 75 to 10% red blood cells subjected to IACP are similar to those of the pure cell population, i.e., erythrocytes ca. 100% and HL60 cells 3% in top phase. Thus, the population of erythrocytes can be almost completely extracted into the top phase in a single step. The contaminant cells represent only a small percentage (less than 5% in most of the cases) of the cell mixture recovered in top phase. Both cell populations can be completely separated by countercurrent distribution (CCD).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Affinity↗
PubMed1991

Carotid endarterectomy for asymptomatic carotid stenosis: a ten-year experience with 120 procedures in a fellowship training program.

Performance of carotid endarterectomy for asymptomatic carotid stenosis has been restricted during recent years because of concern of reported complications in as high as 10-15% of patients, as well as limited long-term data on stroke protection. During the last 10 years, we have studied immediate and long-term results of carotid endarterectomy for asymptomatic disease in 120 patients. Operations were performed by a clinical vascular fellow with a staff surgeon in attendance in 113 (94%) cases with the remainder performed by the staff surgeon. Patients' mean age was 66 years; 82% were men. Risk factors included hypertension (56%), smoking (52%), coronary artery disease (32%), diabetes (24%), and hypercholesterolemia (6%). Arteriographic severity of stenoses was 80-99% in 74%, 60-79% in 22%, and 40-59% in 4% of cases. Postoperative complications included two transient neurological events (1.7%). No permanent strokes or deaths occurred. Using the life table method, cumulative stroke rate was 4.5% for ipsilateral events and 7.3% for contralateral events, confirming the high degree of stroke protection afforded by carotid endarterectomy in this population. Since these results were accomplished in a fellowship training program, we regard adequacy of this experience as the most influential factor in accomplishing this record. Surgeons who are unable to achieve comparable results should consider abandonment of the procedure or an extended period of additional training.

Aged↗
PubMed1991

Leukocyte activation in ischemia-reperfusion injury of skeletal muscle.

Polymorphonuclear leukocyte (PMN) participation in the pathophysiology of the reperfusion injury following skeletal muscle ischemia has become recognized. We measured the activation of PMNs as evidenced by production of superoxide anion (O2-) in the isolated canine gracilis muscle preparation of ischemia-reperfusion injury. PMNs were isolated from the gracilis muscle venous effluent and central venous blood after 6 hr of bilateral gracilis ischemia and 1 hr of reperfusion in five dogs. Baseline samples were obtained prior to ischemia from the central venous circulation. Liberation of O2- from PMNs and from PMNs stimulated by opsonized zymosan was determined by measuring ferricytochrome reduction. Results are expressed as nanomoles of O2- produced/2 x 10(6) PMN +/- SEM. O2- production by unstimulated cells was increased from 0.33 +/- 0.15 nmole in the baseline samples to 0.96 +/- 0.08 nmole in the central venous sample (P less than 0.01). With stimulation by zymosan, production increased from 10.3 +/- 1.4 nmole in the baseline samples to 15.2 +/- 1.1 nmole in the central venous sample (P less than 0.05) and to 15.5 +/- 0.9 nmole in the gracilis venous sample (P less than 0.01). These increases in superoxide production were not seen in the three sham-operated animals. Mean infarct size determined by planimetry was 55%. O2- produced by PMNs from central venous blood correlated with infarct size (r = 0.934, P = 0.02). These data imply that PMNs are activated by muscular ischemia, and the degree of activation is directly related to the extent of the muscle infarction.

Animals↗
PubMed1991

Alcohol consumption in men exposed to the military draft lottery: a natural experiment.

The randomized natural experiment provided by the military draft lotteries of 1970, 1971, and 1972 is used to compare alcohol consumption in men born in the years 1950, 1951, and 1952. Alcohol consumption data are derived from the National Health Interview Survey supplements for 1977, 1983, and 1985. The analysis follows an intention-to-draft paradigm, where draft eligibility is determined solely by randomly assigned lottery numbers. Draft eligibility status is found to be unassociated with alcohol consumption, despite the fact that eligibility for the draft significantly increased the likelihood of military service and that veterans are more likely to report increased alcohol consumption compared to nonveterans. The randomized draft lottery provides an elegant natural experiment that potentially obviates the problem of confounding by premilitary service factors found in previous studies of alcohol consumption among veterans and nonveterans. However, the indirect association between draft eligibility and any health outcome (where military service is an intervening variable), together with the failure of the draft to produce a higher percent of veterans, prohibits application in all but the largest samples.

Alcoholism↗
PubMed1991

Community responsive medicine: defining an academic discipline.

Academic medicine is entering a period of introspection created by changing patterns of health and disease and changing patterns in reimbursement and health policy. To respond to existing health challenges, innovative strategies for health care delivery and education must be devised. The migration of medical education and health care delivery into centralized and frequently difficult-to-access campuses is being reviewed by payors, policy analysts, and purchasers of care. One proposed solution to this problem responds to the identified shortcomings in medical education and some of the failures of our health care delivery system. Community Oriented Primary Care (COPC) and the related discipline of Community Responsive Medicine define health-oriented strategies that blend traditional primary care and public health. The classroom in Community Responsive Medicine is the community. The curriculum is defined by the elements and skills necessary to improve the health status of the target community. The model allows the student and resident to appreciate and experience the entire spectrum of health and disease and to understand the sequence of events that may lead to illness. Tertiary care is a critical curriculum component, but in Community Responsive Medicine the curriculum is balanced between the ambulatory and tertiary care settings. Community Responsive Medicine defines a role for new leadership that can create responsive educational and health care delivery systems accountable to the communities they serve.

Community Medicine↗