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Biomedical subjects

E Munoz

Publications and source records attributed to E Munoz.

At least 19 recordsLinked to original sources
PubMed1992

IL-4 and IL-2 selectively rescue Th cell subsets from glucocorticoid-induced apoptosis.

It is well established that T cell maturation and activation are negatively regulated by a mechanism termed apoptosis. We now present evidence that glucocorticoids, known to possess immunosuppressive properties, cause apoptosis in mature Th cells, similarly to what has been reported for thymocytes. Th cells treated with the synthetic glucocorticoid dexamethasone show genome fragmentation into oligonucleosomal fragments, and proliferation of growth factor stimulated Th cells is inhibited by glucocorticoids. We show that IL-4 specifically rescues Th2 cells from dexamethasone-mediated apoptosis, whereas IL-2 and IL-1 are ineffective in these cells. However, IL-2 is the relevant rescue-factor of glucocorticoid-treated Th1 cells. The rescue induced by IL-4 and IL-2 is thought to be mediated by protein kinases (possibly protein kinase C), as evidenced by the fact that the protein kinase inhibitor H7 blocks the action of IL-4 and IL-2 in glucocorticoid-treated cells. Our in vitro data show that mature T cells can be protected by their own growth factors from the deleterious effects of the synthetic glucocorticoid dexamethasone, and suggest that specific interactions occur between lymphokines and naturally produced glucocorticoids in vivo, which may play a role in the regulation of the immune response.

Cell Death↗
PubMed1992

Hospitalisation patterns in children from 10 aboriginal communities in the Northern Territory.

OBJECTIVE: To describe childhood hospitalisation patterns in rural Aboriginal communities in the Northern Territory. DESIGN: Longitudinal data for 1976-1985 were collected retrospectively between March 1986 and December 1987. COHORT: All children born between 1 January 1976 and 31 December 1985 and identified in records at 10 community health centres were included in the study, except for 30 children who were residents of more than one community. Records of hospital admissions were ascertained for the remaining 2254 children until five years of age or 31 December 1985, whichever was earlier. RESULTS: Mean admission rates for Aboriginal children aged 0-1 year were two to three times the national average, and there was a fourfold excess in the number of days in hospital and the number of deaths before the age of five years for Aboriginal infants. Admission rates varied by community, age, year and sex: at 0-6 months of age, rates for communities ranged from a minimum of 0.21 to a maximum of 1.46 admissions per child-year at risk and mean rates increased from 0.50 per year in 1976 to 1.05 in 1985; mean admission rates declined from 0.84 per child-year at age 0-6 months to 0.12 at age 37-60 months. Boys were admitted to hospital more frequently than girls. For communities, hospital stay ranged from a minimum of 2.7 to a maximum of 15.3 hospital days per child-year at risk. CONCLUSIONS: Differences of up to sevenfold in hospitalisation rates between communities highlight the potential for primary and secondary prevention of childhood disease in Aboriginal communities.

Anemia↗
PubMed1992

Social and environmental factors in 10 aboriginal communities in the Northern Territory: relationship to hospital admissions of children.

OBJECTIVE: To identify social and environmental differences associated with differences in admission rates of children from 10 rural Aboriginal communities in the Northern Territory. DESIGN: Between March 1986 and December 1987, records of hospital admissions of the cohort of children for 1976-1985 were examined retrospectively; cross-sectional measurements of 74 historical, social and environmental characteristics of each community were collected. SAMPLE: All 1961 children born between 1 January 1976 and 31 December 1985 and still living in the 10 communities. METHOD: Scores on social and environmental factors for each community were generated by factor analysis. Generalised linear interactive modelling was used to investigate the association between these scores and admission rates. RESULTS: Mean admissions per child-year at risk were higher in Central Australian communities (range, 0.41-0.93) than Top End communities (0.26-0.38). Factor I accounted for 30% of the social and environmental differences between communities: communities with a high score on this factor had more houses, fewer shared toilets, more electrical appliances, better personal hygiene and a history of mission administration. High scores on this factor were predictive of lower admission rates and the factor explained most of the differences in admission rates between the Top End and Central Australian communities. Factor VI, correlated with dilapidated dwellings and fewer Aboriginal Health Workers, explained some differences in admission rates between six Top End communities. CONCLUSIONS: Social and environmental factors correlated with the degree of community development are associated with the health of Aboriginal children. Improved development programs should be community-controlled and evaluated to identify the social, educational, behavioural and environmental changes that are most effective in improving health.

Child, Preschool↗
PubMed1992

Bioavailability of energy, nitrogen, fat, zinc, iron and calcium from rural and urban Mexican diets.

The availabilities of nutrients from a representative rural Mexican diet (RMD) and a representative urban Mexican diet (UMD) were evaluated by balance experiments in sixteen Mexican women. Compared with UMD, the plant-based RMD led to a higher number of defaecations and higher faecal excretion of dry matter, fat, nitrogen and energy. Apparent digestibility of N from RMD was only 67% compared with 90% from UMD. N balance was 0.4 and 2.6 g/d with RMD and UMD respectively (P < 0.001). Apparent digestibility of energy was 89 and 95% from RMD and UMD respectively (P < 0.001). Calculation of the metabolizable energy (ME) using Atwater's (Atwater & Bryant, 1900) general factors overestimates the determined ME in RMD by 8%. The Food and Agriculture Organization/World Health Organization/United Nations University (World Health Organization, 1985) recommended factors for correction of digestibility of fibre intake overestimate energy and protein absorption from RMD. The diets provided similar amounts of zinc, and its apparent absorption from RMD was 0.5 mg/d (4.6%) and its balance was 0.1 mg/d. This compared with values for UMD of 1.6 mg/d (16%) and 1.2 mg/d respectively. Iron intake was higher from RMD (17.4 v. 11.6 mg/d; P < 0.01), but apparent absorption was 17 v. 35% and balance was 2.7 and 3.8 mg/d (P < 0.001) for RMD and UMD respectively. RMD also contained more calcium (745 v. 410 mg/d) but apparent absorption from RMD was negative (-136 v. 15 mg/d) and balance was more negative (-197 v. -77 mg/d; P < 0.05). Thus, the content of these minerals is not low in the rural diet but their bioavailabilities are poor.

Adolescent↗
PubMed1991

Inhibition of dipeptidyl aminopeptidase IV (DP-IV) by Xaa-boroPro dipeptides and use of these inhibitors to examine the role of DP-IV in T-cell function.

Dipeptidyl peptidase IV (DP-IV; dipeptidyl-peptide hydrolase, EC 3.4.14.5) is a serine protease with a specificity for cleaving Xaa-Pro dipeptides from polypeptides and proteins. It is found in a variety of mammalian cells and tissues, including those of lymphoid origin where it is found specifically on the surface of CD4+ T cells. Although the functional significance of this enzyme has not been established, a role in T-cell activation and immune regulation has been proposed. Here we report that Ala-boroPro and Pro-boroPro, where boroPro is the alpha-amino boronic acid analog of proline, are potent and specific inhibitors of DP-IV, having Ki values in the nanomolar range. Blocking the N terminus of Ala-boroPro abolishes the affinity of this inhibitor for DP-IV, while removal of the N-terminal residue, to give boroPro, reduces the affinity for DP-IV by 5 orders of magnitude. The dipeptide boronic acids exhibit slow-binding kinetics, while boroPro does not. We also report here that low concentrations of Pro-boroPro inhibit antigen-induced proliferation and interleukin 2 production in murine T-cell lines but do not inhibit the response of these T cells to the mitogen concanavalin A. These results indicate that DP-IV plays a role in antigen-induced, but not mitogen-induced, activation of T lymphocytes.

Animals↗
PubMed1991

Extracellular Na+ dependency of free cytosolic Ca2+ regulation in aortic vascular smooth muscle cells.

This study examined contribution of Na(+)-dependent processes to the regulation of free cytosolic calcium (Ca2+i) in cultured vascular smooth muscle cells (VSMC) using fura-2. Removal of Na+ from superfusate (replacement with choline) resulted in an increment of Ca2+i that was greatly augmented by pretreatment with ouabain. Under both conditions, Ca2+i increase was followed by partial recovery to a new steady state that was still significantly higher than that seen before removal of external Na+ (Na+o). In ouabain-pretreated cells lowering of Na+o caused progressive increases in Ca2+i. Addition of NiCl2, a Na(+)-Ca2+ exchange inhibitor, completely blocked the increase in Ca2+i produced by removal of Na+o, indicating that the Na(+)-Ca2+ antiporter was responsible for observed Ca2+i changes. Ca2+i increase produced by reduction of Na+o was also seen after depletion of inositol trisphosphate-sensitive Ca2+ stores with repeated pulses of angiotensin II or after blockade of sarcoplasmatic reticulum Ca2+ release with TMB-8 but was not observed in the absence of external Ca2+. These observations indicate that the source of Ca2+i increase in response to changes in the transmembrane Na+ gradient is largely external, and potentiation of the Ca2+i surge by ouabain suggests Ca2+ influx via the Na(+)-Ca2+ exchanger operating in the reverse mode. The relative contribution of a Na(+)-dependent and -independent component of Ca2+i recovery was investigated by superfusing cells with ionomycin in a Na(+)-free medium and later adding Na+ to the medium. This Ca2+ ionophore increased Ca2+i to a peak, and this was followed by a rapid but partial recovery to a new steady state. Readdition of varying amounts of Na+ to the superfusate, in the continued presence of ionomycin, resulted in concentration-related decline in Ca2+i, thereby uncovering a substantial contribution of a Na(+)-dependent mechanism of Ca2+i regulation. Decline of Ca2+i produced by readdition of Na+ was blocked by addition of NiCl2 to the superfusate. Our findings thereby provide evidence for Ca2+i regulation in VSMC via a Na(+)-dependent mechanism, consistent with a Na(+)-Ca2+ exchanger, which acts as a Ca2+ efflux mechanism when Ca2+i is elevated. Na(+)-Ca2+ exchanger acts as a Ca2+ influx mechanism when intracellular Na+ is elevated by prior exposure to ouabain.

Animals↗
PubMed1990

Costs, quality, and the volume of surgical oncology procedures.

We tested the hypothesis that hospital costs and outcome (ie, mortality) would differ for each surgeon by the volume of patients treated per diagnosis related group by individual surgical oncologists. All elective surgical oncologic admissions (N = 2627) to our hospital from 1985 to 1987 were divided into those patients treated by low-volume surgeons vs those patients treated by high-volume surgeons; 11.9% of patients not fitting these categories were excluded. Patients of the 57 low-volume surgeons utilized greater hospital resources (which resulted in losses instead of profits) and had a higher mortality compared with patients of the 17 high-volume surgeons. This was due, in part, to a greater severity of illness. These findings suggest that hospital costs and perhaps outcome may be related, at the individual surgeon level, to the volume of surgical procedures performed, and that the diagnosis related group prospective payment system may provide disincentives for low-volume surgeons.

Academic Medical Centers↗
PubMed1990

Route of admission and hospital costs for urologic patients.

This study of 2,549 urology patients examined resource consumption by route of admission into the hospital. Almost all urologic admissions were more expensive as emergencies. These more expensive emergency urologic admissions had higher diagnostic costs, a longer hospital length of stay, and a greater severity of illness than their less expensive non-emergency counterpart. The more expensive emergency admission had a high referral rate to urology from non-urologic clinical services. These findings suggest that efficiency might be improved in the emergency urologic patients by increasing the speed of diagnosis and admission of patients to the appropriate clinical service (urology).

Costs and Cost Analysis↗
PubMed1990

Economies of scale, physician volume for urology patients, and DRG prospective hospital payment system.

Diagnosis Related Group (DRG) hospital payment has begun to squeeze hospitals financially and is likely to do so in the future. This study analyzed the relationship between the volume of urologic procedures by an individual urologist, hospital costs per patient, and outcome. We used a three-year DRG database of urology patients (N = 2,980) at an academic medical center to analyze these. Low-volume urologists (arbitrarily defined by us) had higher hospital costs per patient, financial losses versus profits under DRGs, and a poorer outcome when compared with high-volume urologists. Pearson correlation showed a positive relationship between cost per patient and physician volume for nonemergency patients (-0.129, p less than 0.0001) and emergency patients (-0.368, p less than 0.0001). This may have been explained (in part) by a greater severity of illness for patients of low-volume urologists. These findings suggest, however, that the volume of urologic procedures per urologist may be related to hospital resource consumption. The health care financing environment of the future should provide substantial interest in this finding for those involved in the consumption of urologic services.

Academic Medical Centers↗
PubMed1990

Regulation of interleukin 6 production in T helper cells.

The cytokine interleukin 6 (IL-6) is a cellular regulatory molecule that is produced by both lymphoid and non-lymphoid cells in response to several stimuli. In this report we present evidence that within the murine T cell compartment T helper type 2 cells (Th2) produce this lymphokine, whereas unprimed CD4+ T cells and a T helper type 1 clone (Th1) do not. Furthermore, IL-6 is not an autocrine growth factor for in vitro cultured Th cells, in contrast to what occurs in freshly isolated CD4+ and CD8+ T cells. We have examined the signal transduction pathways that lead to IL-6 production in activated Th2 cells. We have found that protein kinase C activators, such as PMA, Con A, or IL-1, increase the IL-6 expression in these cells. On the other hand, activation of the cAMP-dependent pathway does not seem to have an effect on the IL-6 production, since forskolin, 8BrcAMP, or TNF-alpha, which in these cells increases the level of intracellular cAMP, do not lead to an accumulation of IL-6 message. These results indicate that the IL-6 gene is more tightly regulated in T cells than in other systems described previously.

Animals↗
PubMed1990

Physicians' patient load per DRG, the consumption of hospital resources, and the incentives of the DRG prospective payment system.

From 1985 through 1987, the authors assessed the relationship between two main variables at a large academic medical center: (1) the numbers (high or low) of patients per diagnosis-related group (DRG) treated by individual physicians and (2) hospital resource consumption of the patients. The patients were classified according to their routes of admission (emergency or non-emergency); the physicians with eight or more patients per DRG were labeled "high-patient-load physicians" (hereafter called "high-load physicians"), and those with five or fewer patients were labeled "low-patient-load physicians," ("low-load physicians"). The resource variables studied were length of stay (LOS) and total hospital cost. For the non-emergency admissions, the low-load physicians' patients had an average LOS that was 56.2% greater and an average hospital cost that was 58.3% greater than were the LOS and cost of the patients of the high-load physicians. (Both LOS and cost per patient were adjusted for DRG weight index.) This was due in part to a greater severity of illness for the patients (as measured by total ICD-9-CM codes per patient) of the low-load physicians. For the emergency admissions, the low-load physicians' patients had an average LOS that was 9.5% greater and an average hospital cost that was 10.5% greater than the LOS and cost of the patients of the high-load physicians. As in the non-emergency admissions group, severity of illness for the patients of the low-load physicians was greater. The only category of patients that was economically profitable to the hospital was the non-emergency admissions group treated by the high-load physicians. Even though these findings were the result of many factors (discussed in the text), they suggest a relationship between hospital resource consumption and the physicians' patient load per DRG.

Academic Medical Centers↗
PubMed1990

Economies of scale, physician volume for neurosurgery patients, and the diagnosis-related group prospective hospital payment system.

Hospitals face an increasingly competitive environment in the era of diagnostic related group (DRG) prospective pricing. Further reductions in Medicare outlays relative to hospital costs are likely, given the looming federal deficit. We analyzed the relationship of individual neurosurgical volume, hospital costs, and outcome. All neurosurgical patients (n = 1002) treated for a 3-year period at our large academic medical center were grouped into those treated by low-volume neurosurgeons versus those treated by high-volume neurosurgeons (arbitrarily defined by us); 95% of patients admitted for neurosurgical procedures fit into one of these two categories. Patients of low-volume neurosurgeons had higher hospital costs (even after correction for DRG case-mix and severity of illness) (P less than 0.01), a much worse financial position under DRGs (P less than 0.01), but a similar outcome for both emergency and nonemergency admissions when compared to patients of higher volume neurosurgeons. Pearson correlation showed an inverse relationship between declining cost per patient and increasing neurosurgical volume for both nonemergency patients -0.340 (P less than 0.0001), and emergency patients, -0.321 (P less than 0.0001). These findings suggest that the volume of neurosurgical procedures performed by an individual neurosurgeon is related to hospital resource utilization. This study also suggests that the DRG prospective payment system could provide incentives that may affect both neurosurgical practice and the access to neurosurgical care.

Academic Medical Centers↗
PubMed1990

Prospective payment experience with DRGs in headache patients.

The new Diagnostic Related Group (DRG) Prospective Hospital Payment System pays a set fee to hospitals depending on the patient's diagnosis. Care of certain patients covered by Neurology DRGs has proven to be unprofitable. The purpose of this project was to study hospital resource consumption for hospitalized patients with a principal or secondary diagnosis of headache. We studied various resource parameters for patients in the three neurology DRGs for headache (#24-seizure and headache, age greater than 69 and/or complicating condition; #25 and #26-seizure and headache age 18-69 without complicating condition, and age 0-17, respectively) by whether or not the patients had a diagnosis of headache. As demonstrated in Table 1, patients with headache had (on average) lower hospital resource utilization than patients in these same DRGs without a headache diagnosis. Headache patients had lesser total hospital costs, a lower severity of illness, and generated profits under DRGs compared to non-headache patients. We found that our headache patients were adequately reimbursed by the DRG hospital payment system and suggest that this could be a financially attractive population to hospitals.

Adult↗
PubMed1990

Economies of scale, physician volume for orthopedic surgical patients, and the DRG prospective payment system.

American hospitals face increasing constraints due to a variety of factors. Federal and state diagnostic-related group (DRG) prospective hospital pricing has caused tremendous fiscal pressure on hospitals; many face substantial financial deficits. We analyzed the volume of orthopedic surgical procedures performed by an individual orthopedic surgeon for all patients (N = 2,134) treated for a 3-year period at a large academic medical center; these surgeons were arbitrarily divided into low volume or high volume. Patients of low volume surgeons had a longer hospital length of stay and hospital cost (after correction for DRG case mix and severity of illness), greater financial risk under DRGs, and a poorer outcome, compared with patients of higher volume orthopedic surgeons. Pearson correlation showed an inverse relationship between cost per patient and physician volume for nonemergency patients -0.201 (P less than .0001), and emergency patients, -0.321 (P less than .0001). Although the reasons for these findings appeared multifactoral, they raise important issues related to orthopedic surgical hospital costs, access, and quality of care. In addition, they suggest that hospital cost for these patients (and perhaps outcome) may be related to orthopedic surgical volume, and that DRG hospital payment (on the margin) may affect future orthopedic surgical practice opportunities.

Academic Medical Centers↗
PubMed1990

The DRG hospital payment system, surgical readmissions and cost containment.

We analyzed all adult surgical patients requiring readmission to the surgical service of an acute care academic hospital for a four-year period (1/1/85-12/31/88). We stratified surgical readmissions by the number of times the patient was readmitted to surgery (from one to five times). For surgical patients 41.1 per cent of the readmission population was readmitted more than once, only 4.4 per cent were readmitted five or more times. Patients requiring three or more admissions generally had the greatest hospital resource utilization, financial risk under DRG payment, and mortality, compared with other surgical readmissions. This analysis suggests that within the surgical readmission population resource parameters may differ by the number of readmissions per patient. Factors were identified which corresponded to a greater likelihood of surgical readmission, and possibly allow the focus of outpatient services which may reduce hospital inpatient costs in the future.

Academic Medical Centers↗
PubMed1989

Health care financing policy for hospitalized pediatric patients.

Prospective hospital payment systems using the federal Medicare DRG payment model are changing hospital reimbursement. Currently, many states have adopted diagnosis related group (DRG) prospective "all payer systems" using the federal model. All payer systems, whereby Medicaid, Blue Cross, and other commercial insurers pay by the DRG mode, prevent cost shifting between payers. New York state has used an all payer system since Jan 1, 1988. This study simulated DRG all payer methods for a large sample (N = 16,084) of pediatric patients for a three-year period using the New York DRG all payer reimbursement system now in effect. Medicaid pediatric patients had (adjusted for DRG weight index) a longer hospital stay and greater total hospital cost compared with pediatric patients from Blue Cross and other commercial payers. Medicaid pediatric patients also had a greater severity of illness compared with patients from Blue Cross and other payers. Pediatric patients in all payment groups (ie, Medicaid, Blue Cross, and other commercial insurers) generated financial risk under the DRG all payer scheme. Medicaid pediatric patients generated the greatest financial risk, however. These data suggest that state and private payers may be under-reimbursing for the care of the hospitalized pediatric patient using the DRG prospective hospital payment scheme. Health care financing policy for pediatric patients may limit both access and quality of care.

Adolescent↗
PubMed1989

Pediatric patients, race, and DRG prospective hospital payment.

The diagnosis related group (DRG) prospective hospital payment system contains inequities in hospital payment for certain groups of patients. Patients of lower socioeconomic status may be underreimbursed by DRGs. We analyzed pediatric patients and hospital resource consumption by race (white, Hispanic, and black) using a DRG prospective payment "all payer" system. All hospitalized pediatric admissions over a 3-year period (N = 14,489) were analyzed by race at a large academic medical center. Mean hospital length of stay and cost per patient (adjusted for DRG weight index) was significantly greater for black and Hispanic pediatric patients compared with whites. Financial risk as measured by outliers and losses under DRGs was greater for blacks and Hispanics compared with whites. Black and Hispanic patients had a higher proportion of emergency admission to the hospital compared with whites, a greater severity of illness (as measured by total International Classification of Diseases, ninth revision, Clinical Modification codes), and (on average) higher diagnostic costs for each episode of illness. Our data suggest that black and Hispanic pediatric patients have a greater hospital resource consumption (adjusted for DRG group case mix) compared with whites, at least at our large medical center in the Northeast. Hospitals that treat greater numbers of black and Hispanic pediatric patients may be at a substantial disadvantage under per-case DRG payment.

Academic Medical Centers↗