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Biomedical subjects

M A Armstrong

Publications and source records attributed to M A Armstrong.

At least 37 records · Page 2Linked to original sources

CD80 (B7-1) and CD86 (B7-2) expression in multiple sclerosis patients: clinical subtype specific variation in peripheral monocytes and B cells and lack of modulation by high dose methylprednisolone.

Autoimmune activation of T cells by central nervous system (CNS)-derived antigens is hypothesised to underlie neural damage in multiple sclerosis (MS) patients. The role of coreceptor mediated signalling is currently under investigation in order to further elucidate the immunopathogenic mechanisms implicated and to determine possible targets for immune modulation. We have investigated whether differential coreceptor (B7-1/CD80; B7-2/CD86; CD28) expression on circulating lymphocytes and monocytes is (i) a feature of distinctive clinical subtypes of MS (relapsing-remitting in remission/stable-RRMS; relapsing-remitting in relapse/relapsing-RRMS; primary progressive/PPMS), (ii) related to disease activity, and (iii) altered by high dose corticocosteroid treatment. CD80(+) B cells were significantly reduced (P<0.05) in PPMS (4.0+/-0.8%) compared with normal subjects (CON) (9.1+/-1.1%), stable-RRMS (6.7+/-0.7%) and relapsing-RRMS (7.8+/-0.9%) patients. Comparatively fewer monocytes from relapsing-RRMS patients expressed CD86 (relapsing-RRMS 50+/-4.9% vs. stable-RRMS 75.1+/-3.4%, PPMS 77. 7+/-3.2%, CON 72.1+/-3.6%/P<0.05). Otherwise expression of coreceptors did not vary significantly between the groups. A 3-day course of methylprednisolone therapy did not alter coreceptor expression, but did suppress monocyte and B cell HLA-DR expression. There is evidence for differential coreceptor expression on circulating B cells and monocytes in MS disease subtypes. The biological significance of these findings is discussed in relation to alternative theories regarding coreceptor functioning.

Antigens, CD↗

The effect of aprotinin on interleukin-8 concentration and leukocyte adhesion molecule expression in an isolated cardiopulmonary bypass system.

We examined the effect of aprotinin on the production of interleukin-8 and the expression of leukocyte adhesion molecules in an isolated cardiopulmonary bypass circuit. Five healthy volunteers each donated 500 ml blood which was divided into equal portions (A) and (B). Portion A was treated with aprotinin 250000 kallikrein inactivator units and added to a circuit primed with a further 250000 kallikrein inactivator units. Portion B was simultaneously treated with 25 ml normal saline and added to an aprotinin-free circuit. Samples of blood were taken at donation, after addition of a drug and at 30-min intervals throughout isolated cardiopulmonary bypass. The interleukin-8 increase was smaller in the aprotinin group but the difference between groups was not statistically significant (p > 0.05). In contrast, aprotinin inhibited the cardiopulmonary bypass-induced increase in monocyte (p < 0.05) and granulocyte (p < 0.01) CD18 and the increase in granulocyte, but not monocyte, CD11b (p < 0.05). Cardiopulmonary bypass had little effect on expression of L-selectin. These results confirm that aprotinin attenuates leukocyte activation during isolated cardiopulmonary bypass.

Aprotinin↗

Relationship between tumour necrosis factor-alpha (TNFalpha) production and a specific multiple sclerosis (MS) associated TNF gene haplotype.

OBJECTIVE: To determine if monocyte TNFalpha production from patients homozygous for a specific MS associated TNF gene haplotype is different from that produced in patients either heterozygous for, or without this haplotype. BACKGROUND: The balance between pro- and anti-inflammatory cytokines is important in the clinical outcome of inflammatory reactions. Levels of TNFalpha, a pro-inflammatory cytokine, is raised in MS as well as being found in acute and chronic MS lesions. A previous population based study in Northern Ireland with polymorphisms spanning the TNF gene region identified a conserved MS associated haplotype in relation to three markers (130: 118: 127 TNF d:a:b) for which 19 MS patients were homozygous. METHODS: Venous blood collected in EDTA to give a concentration of 10(-3) M was drawn from 16 patients with the conserved MS associated haplotype, 19 patients heterozygous for the haplotype and 17 patients without the haplotype. Mononuclear cells were separated and cultured by standard techniques and levels of TNFalpha and of TNF binding proteins I and II were determined by commercial enzyme-linked immunosorbent assays. RESULTS: There were no significant differences in TNFalpha production in the 3 h (P = 0.28) or 24 h cultures (P = 0.18) or following stimulation with interferon-gamma (P = 0.17) between the group positive for the conserved haplotype and the group negative for this haplotype. There was also no significant difference when compared to the heterozygote group. No association was found between the MS associated haplotype and levels of either TNF binding protein. A greater proportion of patients with the conserved haplotype had a benign clinical course (P = 0.06). CONCLUSION: We conclude that whilst a trend exists, we have found no significant association between peripheral TNFalpha production and a specific MS associated TNF haplotype in this population. Paradoxically this haplotype may also predict a more favourable clinical course.

Cells, Cultured↗

Rehospitalization in the first two weeks after discharge from the neonatal intensive care unit.

BACKGROUND: High-risk newborns are known to have higher than average utilization of services after discharge from the neonatal intensive care unit (NICU). Most studies on this subject report aggregate data over periods ranging from 1 to 3 years postdischarge. Little is known about events that are temporally close to NICU discharge. OBJECTIVES: To characterize rehospitalizations within the first 2 weeks after discharge from six community NICUs. METHODS: We scanned electronic databases and reviewed the charts of rehospitalized infants from six NICUs in the Kaiser Permanente Medical Care Program. We subdivided infants into five groups based on gestational age (GA) and birth hospitalization length of stay (LOS): 1) >/=37 weeks' GA with <4 days LOS (n = 2593); 2) >/=37 weeks' GA with >/=4 days' LOS (n = 1133); 3) from 33 to 36 weeks' GA with <4 days' LOS (n = 545); 4) from 33 to 36 weeks' GA with >/=4 days' LOS (n = 1196); and 5) <33 weeks' GA (n = 587). We performed bivariate and multivariate analyses to identify predictors that might be useful for practitioners. RESULTS: There were 6054 newborns discharged alive from the six study NICUs between August 1, 1992 and December 31, 1995, and 99.5% of these infants remained in the health plan during the 2 weeks after NICU discharge. The overall rehospitalization rate was 2.72%, which is 20% higher than the rate among healthy term newborns in the Kaiser Permanente Medical Care Program (2.26%). The two most common reasons for rehospitalization were jaundice (62/165, 37.6%) and feeding difficulties (25/165, 15.2%). Infants with 33 to 36 weeks' GA and <4 days' LOS were rehospitalized at a significantly higher rate than were all other infants (5.69%); 71% of infants in this group were rehospitalized for jaundice. The following variables predicted rehospitalization in multivariate models: <33 weeks' GA (adjusted OR [AOR]: 1.88; 95% CI: 1.10-3.21), from 33 to 36 weeks' GA with <96 hours' LOS (AOR: 2.94; 95% CI: 1.87-4.62), and birth at facility B, which had the highest rehospitalization rate of the six facilities (AOR: 1.92; 95% CI: 1.39-2.65). CONCLUSIONS: The rate of rehospitalization among NICU graduates is higher than among healthy term infants. Most of the rehospitalizations among infants with from 33 to 36 weeks' GA and <4 days' LOS are for illnesses that are not life-threatening. Collaborative studies and new process and outcomes measures are needed to assess the effectiveness of follow-up strategies in high-risk newborns.

Birth Weight↗

Rehospitalization for respiratory syncytial virus among premature infants.

OBJECTIVES: New interventions to prevent respiratory syncytial virus (RSV) have recently become available. Clinical decisions about the use of these interventions require a better understanding of the incidence of and risk factors for RSV. We sought to characterize the epidemiology of severe RSV disease among premature infants and to identify high-risk subgroups. DESIGN: Retrospective cohort. SETTING: Kaiser Permanente Northern California, July 1992 to April 1996. PARTICIPANTS: One thousand seven hundred twenty-one premature infants born at 23 to 36 weeks who were discharged from a neonatal intensive care nursery (NICU) within 12 months before the December to March RSV season. A secondary analysis included 769 infants discharged during the RSV season. OUTCOME MEASURES: Hospitalization for RSV. RESULTS: Of 1721 infants already home from the NICU at the start of the season, 3.2% were rehospitalized for RSV. In a multivariate model, risk factors for RSV hospitalization included gestation </=32 weeks (odds ratio [OR], 2.6), >/=28 days of perinatal oxygen (OR, 3.7), and NICU discharge during September to November (OR, 2.7). Predicted risk of hospitalization varied by subgroup, ranging from 1.2% to 24.6%. Among 769 infants discharged from the NICU during the RSV season, 3.5% were rehospitalized for RSV during the same season; gestation and perinatal oxygen were not associated with admission. CONCLUSIONS: Most premature infants in this population were at less risk of severe RSV disease than previous studies in other populations have suggested. Preterm infants with a lower gestational age, a prolonged perinatal oxygen requirement, and NICU discharge within 3 months of the RSV season were most likely to require hospitalization for RSV disease. Cost-effectiveness analyses are needed to help define the role of available prophylactic interventions.

California↗

Frequency of neonatal bilirubin testing and hyperbilirubinemia in a large health maintenance organization.

OBJECTIVE: To determine the frequency and interhospital variation of bilirubin testing and identified hyperbilirubinemia in a large health maintenance organization. DESIGN: Retrospective cohort study. SETTING: Eleven Northern California Kaiser Permanente hospitals. SUBJECTS: A total of 51,387 infants born in 1995-1996 at >/= 36 weeks' gestation and >/= 2000 g. MAIN OUTCOME MEASURE: Bilirubin tests and maximum bilirubin levels recorded in the first month after birth. RESULTS: The proportion of infants receiving >/= 1 bilirubin test varied across hospitals from 17% to 52%. The frequency of bilirubin levels >/= 20 mg/dL (342 micromol/L) varied from .9% to 3.4% (mean: 2.0%), but was not associated with the frequency of bilirubin testing (R(2) = .02). Maximum bilirubin levels >/= 25 mg/dL (428 micromol/L) were identified in.15% of infants and levels >/= 30 mg/dL (513 micromol/L) in .01%. CONCLUSIONS: Significant interhospital differences exist in bilirubin testing and frequency of identified hyperbilirubinemia. Bilirubin levels >/=20 mg/dL were commonly identified, but levels >/= 25 mg/dL were not.

California↗

Monitoring women at risk for preterm labor.

BACKGROUND: Preterm birth is a major cause of perinatal morbidity and mortality. Whether the rate of preterm birth can be reduced by frequent contact between nurses and pregnant women or home monitoring of uterine activity is not known. METHODS: We randomly assigned 2422 pregnant women with known risk factors for preterm labor (including 844 women who were pregnant with twins) to receive education and to have one of the following: weekly contact with a nurse, daily contact with a nurse, or daily contact with a nurse and home monitoring of uterine activity. The nurses elicited the women's own assessments of their symptoms and signs of preterm labor. The primary end point was the incidence of birth at less than 35 weeks' gestation. Secondary end points included cervical status at the time preterm labor was diagnosed and birth weight. RESULTS: There were no significant differences among the groups in the incidence of birth at less than 35 weeks (14 percent in the weekly-contact group, 13 percent in the daily-contact group, and 14 percent in the home-monitoring group), in the mean amount of cervical dilatation at the time preterm labor was diagnosed (1.8 cm, 1.5 cm, and 1.4 cm, respectively), or in such neonatal outcomes as birth weights of less than 1500 g or less than 2500 g. However, daily contact with a nurse increased the mean number of unscheduled visits to obstetricians (1.2 in the weekly-contact group, 1.8 in the daily-contact group, and 2.3 in the home-monitoring group) and the proportion of women who received prophylactic tocolytic drugs (12 percent, 14 percent, and 19 percent, respectively). CONCLUSIONS: Women who have daily contact with a nurse, with or without home monitoring of uterine activity, have no better pregnancy outcomes than women who have weekly contact with a nurse.

Adult↗

Structured review of neonatal deaths in a managed care organisation.

We sought to quantify neonatal mortality (< 28 days) in a 10-hospital system, determine what proportion was associated with suboptimal neonatal care and make recommendations on how neonatal mortality rates (NMRs) could be used in quality improvement efforts. Deaths were identified using electronic linkage to the State of California Death Certificate Tapes. Individual fatalities were reviewed by a minimum of two physicians who did not care for the infant. Deaths were classified as either being associated with suboptimal care or not. For deaths where suboptimal care was an issue, emphasis was on delineating the process involved in the death. Subjects were all neonatal deaths among 64,469 babies born in 1990-91 in the 10 birth facilities of the Kaiser Permanente Medical Care Program, Northern California Region. A total of 241 neonatal deaths were identified. Adjusting for prematurity by increasing the follow-up period in preterm babies (included as neonatal deaths if they died up to 40 weeks corrected gestational age + 27.9 days) increased overall mortality rates by 5%. Birthweight-specific NMRs in Kaiser Permanente are similar to those of other published reports. Among the 198 deaths in babies weighing > or = 500 g at birth, only 14 (7%) were possibly associated with suboptimal care. In populations with access to health insurance, reporting only aggregate NMRs is of limited use. The number of deaths that could be ascribed to suboptimal neonatal care is very small and measuring variations in rates of such deaths is difficult. Future measurements of quality of care will require more sophisticated measures, database systems, review strategies and dissemination methods.

Adolescent↗

Alcohol consumption and utilization of health services in a health maintenance organization.

OBJECTIVES: This study examined the relation between alcohol use and utilization of health services during a 3-year period in a sample of 4,264 adult respondents to a member health survey in a health maintenance organization. METHODS: Respondents were categorized as abstainers (no drinks in the past year, n = 1,139), lighter drinkers (less than seven drinks/week, n = 2,330), moderate drinkers (seven to 13 drinks/week, n = 498), and heavier drinkers (> or =14 drinks/week, n = 297). Each drinker group was compared with abstainers on outpatient visits, hospital days, and number of hospitalizations controlling for age, race, and health plan membership. RESULTS: The mean number of outpatient visits was inversely related to the amount of alcohol consumed. Significant differences also were found for mean number of hospitalizations and mean days hospitalized per year. Compared with the three drinker groups, abstainers were significantly higher on both inpatient measures. CONCLUSIONS: These results might be explained by the inclusion in the abstainer group of exdrinkers who quit because of illness, inattention to health problems by heavier drinkers, or lower rates of illness among drinkers. The findings underscore the importance of replicating our study in other cohorts in which problem drinkers can be identified and compared with non-problem drinkers and in which lifelong abstainers can be separated from exdrinkers in the analysis.

Adult↗

Developmentally supportive care in a neonatal intensive care unit: a research utilization project.

PURPOSE: To implement three aspects of developmental care: lower noise levels, decreased light levels, and flexed, midline positioning. DESIGN: Research utilization project. The developmental care interventions were implemented on a daily basis for two hours of "quiet time" during each eight-hour shift. SAMPLE: 49 infants with mean gestational ages of 35.1 +/- 3.2 weeks and mean weights of 2,107 +/- 464 gm. MAIN OUTCOME VARIABLE: Noise levels, light levels, and flexed midline positioning. RESULTS: Mean light levels and mean noise levels decreased during "quiet time" on all three shifts during the project. Optimal positioning was achieved 78 percent of the time during the project period observations.

Child Development↗

Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization.

International comparison data suggest that wine may be more protective against coronary artery disease than beer or liquor. There are potentially protective antioxidants in wine, especially red wine. However, prospective population studies suggest that each beverage type may reduce coronary risk. The role of alcoholic beverage choice in coronary risk remains unresolved. We performed a prospective study of coronary disease hospitalizations among 128,934 adult members of a Northern California prepaid comprehensive health care program. Alcohol data were supplied at health examinations. Using Cox proportional-hazards models with 9 covariates, analyses were performed of the roles of each major beverage type (wine, beer, and liquor) and of drinking only table wine (red, white, or both). Generally, coronary risk traits were most favorable for wine drinkers and least favorable for liquor drinkers. Among 3,931 persons hospitalized for coronary disease, total alcohol drinking was inversely related to risk in both sexes. Uncontrolled for total alcohol, each beverage type showed evidence for coronary protection, weakest for liquor and strongest for beer in men and wine in women. Controlled for total alcohol, these relations were much reduced, and lost statistical significance except for beer in men and both red and white wine (combined) in all persons. We conclude that (1) drinking ethyl alcohol apparently protects against coronary disease, and (2) there may be minor additional benefits associated with drinking both beer and wine, but not especially red wine.

Adult↗

The choice of anesthetic maintenance technique influences the antiinflammatory cytokine response to abdominal surgery.

UNLABELLED: Outcome in some diseases is determined by the relationship between pro- and antiinflammatory cytokines. Surgery may also provoke a cytokine response, which has both pro- and antiinflammatory components. The aim of this study was to ascertain whether anesthetic technique can modify the balance of cytokines associated with abdominal surgery. Twenty patients scheduled to undergo elective abdominal hysterectomy were randomly allocated to receive maintenance of anesthesia with isoflurane (IH group) or propofol (IV group). Venous blood samples for measurement of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1ra) were taken before the induction of anesthesia and at set intervals until 24 h postoperatively. TNF-alpha levels remained low throughout the study; however, all patients showed a significant postoperative increase in IL-6, IL-10, and IL-1ra (P < 0.05). Levels of the proinflammatory cytokine IL-6 were similar in both groups, whereas the antiinflammatory cytokine IL-10 was higher in the IV group at 4 h postoperatively (P < 0.02). The difference between groups in terms of IL-1ra production just failed to reach significance (P < 0.06). We conclude that the cytokine response to abdominal surgery has both pro- and antiinflammatory components and that the choice of anesthetic may modify the balance of these cytokines. IMPLICATIONS: This study demonstrates that in addition to the widely reported proinflammatory cytokine response, elective abdominal surgery provokes an antiinflammatory response, which may be enhanced by total intravenous anesthesia. The ability of anesthetics to modify the cytokine response to surgery may have therapeutic potential.

Adult↗

Peripheral edema.

Distribution of accumulated fluid is the important element in the differentiation of peripheral edema resulting from different etiologies. Isolated upper extremity edema is rare and is usually caused by obstruction of the superior vena cava by a malignancy. The cause of unilateral edema of a lower limb can usually be determined by the history (heart, liver or kidney disease, trauma, malignancy, radiation or surgery), a physical examination (distribution of edema, stigmata of infection, trauma, malignancy or organ failure) and appropriate laboratory and other tests. Determining the etiology of bilateral lower extremity edema requires a similar approach; this condition may be the result of systemic conditions, drug use, lipidema or idiopathic edema, in addition to obstructive causes and chronic venous states. Algorithms, based on the patient's history, physical examination and diagnostic tests, can help guide physicians to the correct diagnosis.

Algorithms↗

The balance of pro and anti-inflammatory cytokines in plasma and bronchoalveolar lavage (BAL) at paediatric cardiac surgery.

During adult cardiac surgery the plasma pro-inflammatory cytokine response is balanced by a phased anti-inflammatory cytokine response. Whether a similar balanced plasma pro- and anti-inflammatory cytokine response occurred in paediatric cardiac surgery was investigated. Changes in intra-pulmonary cytokine balance by measuring bronchoalveolar lavage (BAL) cytokine content were also estimated. Plasma and BAL samples were obtained from 10 children (aged 15 months to 10 years) 10 min after induction of anaesthesia (sample 0), 5 min after the onset of cardiopulmonary bypass (CPB) (sample 1), 10 min after release of the aortic cross clamp (sample 2), and 2 and 24 h after the end of CPB (samples 3 and 4). BAL and plasma was assayed for interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), IL-8, IL-10, interleukin 1 receptor antagonist (IL-1ra) and the TNF soluble receptors (TNFsrs). There was a phased plasma anti-inflammatory response commencing with IL-10 (sample 2), and followed by significant increases in IL-1ra (samples 3, 4 and 5) and TNF soluble receptors (sample 5). Plasma TNF-alpha and IL-1 beta concentrations were not significantly elevated from baseline. Mean baseline plasma IL-8 was 30 (SEM 9) pg/ml. This was significantly elevated at sample 4 (112 (SEM 68) pg/ml). In BAL, only IL-8 and IL-10 were significantly elevated after CPB as compared with baseline. During paediatric cardiac surgery there is a significant increase in plasma and BAL IL-8. This is balanced within the plasma by a phased anti-inflammatory cytokine response, and within the lung by IL-10.

Bronchoalveolar Lavage Fluid↗

Patients' experience of a planned admission program: implications for nursing practice and research.

Various treatment modalities have been used with the population of individuals with serious and persistent mental illness. Variations of day treatment programs, including partial day hospitalization and planned admission programs, are examples of alternatives to extended inpatient treatment. A Veterans Affairs Medical Center initiated a Planned Admission Program. Using qualitative methodology, the researcher interviewed six patients participating in the program to discover information about their experiences in the program. Major themes are identified and discussed, implications for nursing practice and research are articulated.

Adult↗

Immunomodulation: an important concept in modern anaesthesia.

This review summarises evidence for immunomodulatory effect of drugs administered peri-operatively. The clinical significance of the balance of pro- and anti-inflammatory cytokines may be seen in certain disease states, for example, meningococcal meningitis and Lyme arthritis. This balance may be altered peri-operatively. Traditionally, these changes are considered to be due to the stress response of surgery, the response to cardiopulmonary bypass, or endotoxaemia. This review presents in vitro evidence suggesting that drugs modulating this cytokine balance include non-steroidal anti-inflammatory agents, phosphodiesterase inhibitors and opioids, acting through effects on intracellular cyclic nucleotide messenger systems. An important consequence of the pro-inflammatory cytokine activity is increased adhesion of neutrophils. Aspects of this process may be inhibited by avoiding low blood flow states, by reducing adhesion molecule expression (for example by use of pentoxifylline), or by use of negatively charged anions such as heparin. Neutrophil activity is generally depressed by intravenous anaesthetic induction agents, but is enhanced by opioids. Natural killer cell activity, which is involved in immunity against tumour cells and virally infected cells is transiently depressed by volatile anaesthetic agents and opioids. In contrast catecholamines enhance natural killer cell activity. Whereas decrease in immunoglobulin levels occur peri-operatively, this is not thought to be as a result of drugs at clinically used concentrations but rather due to haemodilution.

Anesthesia↗