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[Effect of the leukotriene receptor antagonist montelukast therapy on asthma in childhood].

The authors have summed up the survey results for children with asthma below 14 years of age participating in the Hunair II. surveillance program. This program proves the efficiency of montelucast 5mg treatment in cases of childhood asthma bronchiale. The 255 patients participating in the survey have received 5 mg montelucast therapy for 8 weeks. During the surveillance period they have used questionnaires to record the change of day and night symptoms, decrease of different restrictions and the quantity change of long- and short-acting beta agonists and inhaled steroids. The use of short-acting agonists decreased from 5 inhalations to 1 in 4 weeks. During the leukotriene antagonist montelucast treatment according to symptom scores 61% of the patients have experienced improvements after the 4th week, 80% after the 8th week. To sum up all the survey results--after the 8th week of treatment the daytime restrictions in the everyday lives of children with asthma have decreased by 88.1%, nighttime restrictions by 80.1%. After the 2nd month of the HUNAIR II. surveillance program it could be deduced that montelucast 5 mg therapy used in child populations less then 14 years of age with asthma has proven useful.

Acetates↗

Goal-oriented evaluation as a program management tool.

Health promotion programs, like all human services activities, must be well managed in order to be effective. In an age of reduced financial resources to support new programs and sustain old ones, all program directors must be concerned with the efficiency with which available resources are used to meet program goals and objectives. In times such as these, competition is high for those resources that are available. Programs that can demonstrate both effectiveness in meeting their goals and operational efficiency in doing so are more likely to be successful in the competition for these scarce resources. In this article, practical suggestions for the use and presentation of evaluation data in the analysis of program effectiveness and efficiency are presented. The methodology is based on the contention that program evaluation should be useful to program directors as an integral part of their management of program resources in relation to program goals.

Efficiency↗

[Care of tuberculosis patients at the community level in the state of Chiapas, Mexico].

From August 1989 to August 1990 in the municipio of Chicomuselo, State of Chiapas--an area with a high incidence of tuberculosis--health promoters were trained to carry out priority actions as part of the National Campaign Against Tuberculosis. A program to provide training, semi-monthly evaluation of the work carried out, detection of new cases, treatment supervision, and contact tracing was established utilizing the structure and resources of the Campaign. The health promoters were assigned the following functions: searching for patients with respiratory symptoms and conducting sputum smear examinations, examining postvaccination scars in persons under 15 years of age, and tracing tuberculosis patient contacts. In total, 1,778 doses of BCG vaccine were administered to individuals under 15 years of age in 35 communities; 144 patients with respiratory symptoms were studied; 257 sputum smear examinations were carried out; and 26 cases of tuberculosis were diagnosed. The most affected age group consisted of those 15 to 45 years old. Patients were monitored during treatment through sputum smear examinations. Twenty-nine persons started the treatment and 24 completed it; 24 were cured, five did not complete the treatment, two abandoned it, and three died. There were no treatment failures. The efficiency of the program was 82% and its effectiveness, 100%. The results show that it is possible to utilize the human resources in a community to carry out health programs. The community members' acceptance of and support for the program was due in part to that fact that their interests were taken into account in its implementation.

Adolescent↗

Using force analysis to target collection and analysis of environmental information.

Knowledge of the forces driving and modifying ecosystems can be employed in concert with signal analysis to target the data most likely to yield sensitivity and resilience information. One can optimize return of information per investment of resources by targeting segments of signals that are dominated by the force of interest, coupled with scientific understanding of the system of interest. This force analysis approach is an effective means both to design efficient new monitoring programs and to target relevant information in large data files. We present five example applications of force analysis. Three examples illustrate this approach for an evaluation of whether Canadian rivers might be sensitive to changes in climate. It was concluded that Canadian rivers appear to be sensitive to changing climate. A fourth example illustrates how automated snow pillow data may be evaluated to ascertain the sensitivity of snow accumulation to change in climate. It was concluded that snow accumulation at the site evaluated did appear to be sensitive to changing climate. The fifth example illustrates the assessment of whether a river recovers with the elimination of inputs of iron from an abandoned mine. It was concluded that resilience remained unproven since the river had not as yet restabilized. The force analysis approach focuses data collection or data evaluation on those data required to answer specific resource management questions, greatly reducing collection or consideration of data that are not relevant to that question. This approach is potentially very cost-efficient and therefore is likely to be of interest to hydrologists, climatologists, and environmental data managers.

British Columbia↗

Beef bulls mated to estrus synchronized heifers: Single- vs multi-sire breeding groups.

Beef bulls of approximately 15 months of age were placed with heifers at bull to female ratios (BFR) of 1:20 (n = 3) and 2:40 (n = 3) to compare the breeding efficiency of bulls used in either a single- or a multi-sire group. Prior to the breeding period, each bull was given a breeding soundness exam and two exposures to a libido/serving capacity test. For the purpose of synchronizing estrus, heifers received a nine-day Syncro-Mate-B((R)) (G. D. Searle & Co.) treatment. Twenty-seven hr after removal of the implants, bulls were placed with heifers and sexual activity was observed continuously for the succeeding 30 hr. With the exception of number of services per heifer, the mating performance of bulls and pregnancy rates at both BFR's were not different (P>.05). Heifers in single-sire groups were serviced more times (P<.05) than those in multi-sire groups (4.1 +/- 0.6 vs 2.6 +/- 0.2, respectively). Approximately 50% of heifers in multi-sire groups were serviced by both bulls. Due to the overlap in servicing heifers and the non-significant difference in pregnancy rates between the two BFR's, it was concluded that a single-sire mating program was more efficient.

Journal Article↗

The TestSmart-HPV Program--development of an integrated approach for testing high production volume chemicals.

The TestSmart program was developed in response to the High Production Volume Chemical Challenge, a voluntary initiative under which chemical producers provide basic toxicity data on chemicals produced in greater than one million pounds annually. Specifically, under the Challenge, chemical producers will generate data as needed to complete the Screening Information Data Set (SIDS), as defined by the Organization for Economic Cooperation and Development (OECD). The TestSmart program is a collaborative effort of the Johns Hopkins Center for Alternatives to Animal Testing, the Environmental Defense Fund, Carnegie-Mellon University, and the University of Pittsburgh. The goal of the TestSmart program is to provide a humane and efficient approach to collecting SIDS data. The program has two objectives, one immediate and the other more long term. The immediate objective has been to make recommendations to reduce the number of animals used in collecting SIDS data under the Challenge. This was accomplished, through a group process, by examining the current status of alternative methods for SIDS endpoints and by providing an assessment of the "state of readiness" of current and potential future alternatives. The long-term objective is to provide a model for other programs to follow the TestSmart concept of a more efficient and humane approach to obtain toxicological data of interest to regulators and the public.

Animal Testing Alternatives↗

Preparation of small volume, leuko and erythrocyte very poor platelet concentrates.

Recently developed automated discontinuous flow centrifuge (DFC) separators can produce leuko- and erythrocyte-poor platelet concentrates (PC). According to general experience with these machines it is difficult to obtain more than 4 X 10(11) platelets, though a second program set up by Coffe et al. appears to produce PC containing approximately 5 X 10(11) platelets suspended in a plasma volume of 390 ml. At our center we employed a new Dideco cell separator equipped with the surge pump and a technique developed for the production of small volume, RBC and WBC-very poor PC. In 60 routine procedures we obtained the following results: mean processing time 87 +/- 11 minutes; final volume of PC 136 +/- 19 ml, with a mean platelet yield of 5.21 X 10(11) platelets. WBC contamination was 1.8 X 10(8) (93% lymphocytes) and RBC were 3.1 X 10(8). Plasma volume as well as WBC and RBC contamination were reduced by recirculating PC after the 6th pass. The demand for single donor platelet concentrates (PC) is increasing progressively. Recently developed automated cell separators can produce leukocyte (WBC) and erythrocyte (RBC) poor PC. With these machines it may be difficult to obtain PC containing at least 4 X 10(11) platelets and less than 1 X 10(9) leukocytes (1, 2, 3) since donor variables such as hematocrit, precounts, buffy coat formation and initial plasma light transmission are of paramount importance for the efficiency of the program. At our center a prototype discontinuous flow centrifuge (DFC) cell separator equipped with the surge pump was studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Component Removal↗

Prognosis of functional recovery 1 year after hip fracture: typical patient profiles through cluster analysis.

BACKGROUND: Many investigators have identified distinct medical, demographic and psychosocial prefracture conditions that influence the functional outcome of patients surgically treated for a fracture of the hip. However, to design efficient intervention care programs addressing the needs of these patients, at optimal economic and social costs, more information is required on the typical combinations of prognostic determinants actually encountered. METHODS: Data on specific descriptors of the prefracture status and on mobility and functioning 1 year after surgical intervention were collected by interview from 253 consecutive patients hospitalized for a fracture of the proximal femur. Cluster analysis was used to form homogeneous groups of patients with similar profiles in terms of the 13 predictive variables and the 7 outcome variables significantly interrelated. The modeling procedure generated four clusters of patients with a typical profile sharply contrasted by their structure. RESULTS: Subjects of two clusters could walk without difficulty and were functionally independent prior to their hip fracture. One year later, however, mobility and functioning were only fully recovered by the members of one cluster. The majority of predictors were of less favorable prognostic value for the members of the second cluster. The other two clusters regrouped patients with impaired prefracture mobility that were either unaltered or even aggravated 1 year later. CONCLUSIONS. Cluster analysis identified typical profiles of elderly hip fracture patients. Close scrutiny of their respective global structure, in terms of combined prognostic determinants and outcomes, may help to develop specific management strategies that are more efficiently adapted to these different groups of patients.

Activities of Daily Living↗

Clinical application and dosimetric calibration procedure of the superficial and orthovoltage therapy unit Therapax DXT300.

AIMS AND BACKGROUND: The aim of this study was to configure a new superficial and orthovoltage therapy unit for clinical use and discuss the clinical indications for this kind of energy. There is renewed interest in radiotherapy using photon beams in the range from 40 to 300 kVp, in particular for the treatment of non-neoplastic diseases and superficial lesions. This is due to the fact that the latest units are of good quality, relatively cheap and reliable in comparison with alternative equipment. It is therefore necessary to document the steps involved in the clinical application of this therapeutic equipment. METHODS: The calibration procedure for a new superficial/orthovoltage therapy unit, Therapax DXT300 (Pantak, USA), installed at the Radiotherapy Department of the Mauriziano Hospital in Turin, was carried out by measurement of beam quality (half-value layer, HVL), percentage depth dose (PDD), profiles, internal dosimetry system, dose rate calibration and output factors. The Therapax DXT300 can be programmed to stop treatment either by time or dose, like a linear accelerator. It is equipped with one adjustable collimator (2 x 2 divided by 20 x 20 cm2) for orthovoltage therapy (focus skin distance, FSD = 50 cm) and six fixed applicators for superficial and orthovoltage therapy (FSD = 30 and 50 cm, respectively). Up to eight combinations of generating potential, tube current and added beam filter can be set. RESULTS: In the range of accelerating potentials from 40 to 300 kVp the Therapax provides beams with HVL ranging from 1.48 mm Al to 3.68 mm Cu. As regards the PDD curves, a slight difference between PDD values has been observed with potentials ranging from 200 to 300 kVp. The beam symmetry and flatness are almost the same in Y and X plane directions for accelerating potentials of less than 200 kVp. At higher kVp values these parameters are significantly worse in the anode-cathode axis direction, because the useful X-ray beam is extracted perpendicular to the anode-cathode axis direction: as the energy increases, the bremsstrahlung becomes more forward directed, resulting in a higher dose rate on the anode side. CONCLUSION: The present paper suggests a methodological approach for the clinical application of an orthovoltage/superficial therapy unit and discusses its current indications. It is necessary to maintain the performance of the equipment within predefined limits in order to meet the requirements of an efficient quality assurance program. This unit is particularly useful in the treatment of superficial lesions and non-neoplastic diseases and in palliative care (eg for bone metastases).

Calibration↗

Antigen distribution drives programmed antitumor CD8 cell migration and determines its efficiency.

Understanding both the role of tumor Ag in CD8 cell differentiation and the reasons that CD8 cells may work inefficiently is crucial for therapeutic approaches in cancer. We studied OT-1 CD8 cell responses in vivo in a differential Ag-distribution model that used EG-7, the EL-4 thymoma transfected with OVA. On their initial Ag encounter, OT-1 CD8 cells underwent programmed expansion in the lymph nodes, where they acquired the ability to migrate to the encapsulated tumor site after > or =4 divisions, without continuous antigenic stimulation. This short antigenic stimulation was sufficient to induce the migration differentiation program, which included modulation of chemokine receptor mRNA expression and down-regulation of CD62L. Moreover, Ag quantity determined the behavior of the OT-1 CD8 cells, including their effector functions and sensitivity to apoptosis. Thus, the initial Ag encounter drives the programmed cell migration potencies, but neither effector functions nor cell death can occur without continuous TCR triggering.

Animals↗

Teaching hospital costs: implications for academic missions in a competitive market.

CONTEXT: As the managed care environment demands lower prices and a greater focus on primary care, the high cost of teaching hospitals may adversely affect their ability to carry out academic missions. OBJECTIVE: To develop a national estimate of total inpatient hospital costs related to graduate medical education (GME). DESIGN: Using Medicare cost report data for fiscal year 1993, we developed a series of regression models to analyze the relationship between inpatient hospital costs per case and explanatory variables, such as case mix, wage levels, local market characteristics, and teaching intensity (the ratio of interns and residents to beds). SETTING AND PARTICIPANTS: A total of 4764 nonfederal, general acute care hospitals, including 1014 teaching hospitals. MAJOR OUTCOME MEASURES: Actual direct GME hospital costs and estimated indirect GME-related hospital costs based on the statistical relationship between teaching intensity and inpatient costs per case. RESULTS: In 1993, academic medical center (AMC) costs per case were 82.9% higher than those for urban nonteaching hospitals (actual cost per case, $9901 vs $5412, respectively). Non-AMC teaching hospital costs per case were 22.5% higher than those for nonteaching hospitals (actual cost per differences in case, $6630 vs $5412, respectively). After adjustment for case mix, wage levels, and direct GME costs, AMCs were 44% more expensive and other teaching hospitals were 14% more costly than nonteaching hospitals. The majority of this difference is explained by teaching intensity. Total estimated US direct and indirect GME-related costs were between $18.1 billion and $22.8 billion in 1997. These estimates include some indirect costs, not directly educational in nature, related to clinical research activities and specialized service capacity. CONCLUSIONS: The cost of teaching hospitals relative to their nonteaching counterparts justifies concern about the potential financial impact of competitive markets on academic missions. The 1997 GME-related cost estimates provide a starting point as public funding mechanisms for academic missions are debated. The efficiency of residency programs, their consistency with national health workforce needs, financial benefits provided to teaching hospitals, and ability of AMCs to maintain higher payment rates are also important considerations in determining future levels of public financial support.

Academic Medical Centers↗

Factors associated with tobacco sales to minors: lessons learned from the FDA compliance checks.

CONTEXT: Tobacco products continue to be widely accessible to minors. Between 1997 and 1999, the US Food and Drug Administration (FDA) conducted more than 150,000 tobacco sales age-restriction compliance checks. Data obtained from these checks provide important guidance for curbing illegal sales. OBJECTIVE: To determine which elements of the compliance checks were most highly associated with illegal sales and thereby inform best practices for conducting efficient compliance check programs. DESIGN AND SETTING: Cross-sectional analysis of FDA compliance checks in 110,062 unique establishments in 36 US states and the District of Columbia. MAIN OUTCOME MEASURE: Illegal sales of tobacco to minors at compliance checks; association of illegal sales with variables such as age and sex of the minor. RESULTS: The rate of illegal sales for all first compliance checks in unique stores was 26.6%. Clerk failure to request proof of age was strongly associated with illegal sales (uncorrected sales rate, 10.5% compared with 89.5% sales when proof was not requested; multivariate-adjusted odds ratio [OR], 0.03; 95% confidence interval [CI], 0.03-0.04). Other factors associated with increased illegal sales were employment of older minors to make the purchase attempt (adjusted ORs for 16- and 17-year-old minors compared with 15-year-olds were 1.52 [95% CI, 1.46-1.63] and 2.43 [95% CI, 2.31-2. 59], respectively), attempt to purchase smokeless tobacco (adjusted OR, 2.16 [95% CI, 1.90-2.45] vs cigarette purchase attempts), and performing checks at or after 5 PM (adjusted OR, 1.28 [95% CI, 1. 21-1.35] vs before 5 PM). Female sex of clerk and minor, Saturday checks, type of store (convenience store selling gas, gas station, drugstore, supermarket and general merchandise), and rural store locations also were associated with increased illegal sales. CONCLUSIONS: This analysis found that a request for age verification strongly predicted compliance with the law. The results suggest several ways in which the process of compliance checks might be optimized. JAMA. 2000;284:729-734

Adolescent↗

Prediction of a 12-residue loop in bovine pancreatic trypsin inhibitor: effects of buried water.

The x-ray conformations of 5-, 7-, 9-, and 12-residue loops in bovine pancreatic trypsin inhibitor (BPTI) were predicted by the use of multiple independent Monte Carlo simulating annealing (MCSA) runs starting from random conformations. Four buried water molecules interacted with a 12-residue loop that started at residue 8 and ended at residue 19, and that included the binding region. The final conformation at the end of an MCSA run was characterized. Solvation free energy based on the solvent accessible surface area was included in the energy function at low simulated annealing temperatures. Conformational states were interactively separated by a recently developed algorithm. Computed loops were characterized in terms of total energy, and backbone and side chain root mean square deviations (RMSDs) between computed native loop conformations and the x-ray conformation. The 12-residue loop was computed with and without buried water [called WL12(8-19) and L12(8-19), respectively]. The backbone was reliably and reproducibly computed to within 1.1 A in L12(8-19) and 0.9 A in WL12(8-19). L12(8-19) required significantly more MCSA runs to achieve the same level of reproducibility as WL12(8-19). Based on the size of the cluster of low energy native loop conformations, and the computational effort, WL12(8-19) had greater entropy. In calculations of 7-, 9-, and 12-residue loops without buried water, the effects of buried water became obvious in the 12-residue loop calculation, which interacted with all four buried water molecules. Nearly all conformations of the native loop conformer had a hydrogen bond between the Lys 15 side chain and the backbone of Gly 12, Pro 13, and Cys 14, which may have implications in the rate of exchange of buried water with bulk solvent and in protein folding. The present version of MCSA program was more efficient than earlier versions.

Animals↗

A computer system for coding occupation.

BACKGROUND: Occupation information is widely used in epidemiologic studies and is collected on most death certificates and many birth certificates in the United States. Coding the massive amount of occupation information collected has been a challenge. METHODS: A simple word-matching computer program to code occupation entries from vital records was developed. The accuracy of the program was evaluated by comparing its output to codes assigned by human coders. RESULTS: In routine use in the Washington State Department of Health (DOH), the computer system codes 96-97% of the occupation entries on birth and death records. It assigned the correct code on 89% (95% confidence interval (87%, 91%)) of the records it coded. CONCLUSIONS: The occupation-coding program is both efficient and accurate and can simplify the process of coding occupation entries from vital records. The system is adaptable and can be modified to use occupation classifications other than the one used by DOH.

Birth Certificates↗

Evaluation of stereo-array isotope labeling (SAIL) patterns for automated structural analysis of proteins with CYANA.

Recently we have developed the stereo-array isotope labeling (SAIL) technique to overcome the conventional molecular size limitation in NMR protein structure determination by employing complete stereo- and regiospecific patterns of stable isotopes. SAIL sharpens signals and simplifies spectra without the loss of requisite structural information, thus making large classes of proteins newly accessible to detailed solution structure determination. The automated structure calculation program CYANA can efficiently analyze SAIL-NOESY spectra and calculate structures without manual analysis. Nevertheless, the original SAIL method might not be capable of determining the structures of proteins larger than 50 kDa or membrane proteins, for which the spectra are characterized by many broadened and overlapped peaks. Here we have carried out simulations of new SAIL patterns optimized for minimal relaxation and overlap, to evaluate the combined use of SAIL and CYANA for solving the structures of larger proteins and membrane proteins. The modified approach reduces the number of peaks to nearly half of that observed with uniform labeling, while still yielding well-defined structures and is expected to enable NMR structure determinations of these challenging systems.

Amidohydrolases↗

Caffeine and staurosporine enhance the cytotoxicity of cisplatin and camptothecin in human brain tumor cell lines.

Caffeine and staurosporine have been shown to attenuate G2 delay produced by DNA-damaging agents and to augment the cytotoxicity of these agents in a number of cell lines in vitro. Studies in rodent brain tumor cell lines suggest that modulation of the G2/M transition may not contribute to the enhanced cytotoxicity produced by caffeine in brain tumor cells. To evaluate the impact of agents that decrease G2 delay on the cytotoxicity of chemotherapy in human brain tumor cells, we examined the ability of caffeine and staurosporine to modulate the G2 delay and cytotoxicity produced by cisplatin (CDDP) and camptothecin (CPT) in U251 glioma and DAOY medulloblastoma cells. Synchronized U251 were incubated with 20 microM CDDP in the presence or absence of 2 mM caffeine. DAOY cells were incubated with 100 nM CPT in the presence or absence of 2 nM staurosporine. Caffeine and staurosporine attenuated G2 delay produced by CDDP and CPT, respectively. Clonogenic assays indicated that continuous exposure to 2 mM caffeine substantially lowered the ID50 and ID90 of CDDP in U251 cells without significantly altering plating efficiency. Twenty-four-hour exposure to 2 nM staurosporine lowered the ID50 and ID90 of CPT in DAOY cells without significantly altering plating efficiency. Evaluation of programmed cell death using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay indicated that one mechanism for synergistic cytotoxicty of caffeine with CDDP and staurosporine with CPT in U251 and DAOY cells, respectively, is to promote apoptosis. These results underscore the importance of understanding regulation of G2/M transition in brain tumor cells. Such an understanding may lead to novel therapies that target G2 check points to augment the efficacy of currently available treatments for brain tumors.

Apoptosis↗

An efficient and cost effective nuclear medicine image network.

An image network that is in use in a large nuclear medicine department is described. This network was designed to efficiently handle a large volume of clinical data at reasonable cost. Small, limited function computers are attached to each scintillation camera for data acquisition. The images are transferred by cable network or floppy disc to a large, powerful central computer for processing and display. Cost is minimized by use of small acquisition computers not equipped with expensive video display systems or elaborate analysis software. Thus, financial expenditure can be concentrated in a powerful central computer providing a centralized data base, rapid processing, and an efficient environment for program development. Clinical work is greatly facilitated because the physicians can process and display all studies without leaving the main reading area.

Computer Communication Networks↗

[Preventive medicine in private medical practice].

The basis of preventive medicine for the individual is composed of health education, certain examinations and preventive treatments. A coherent approach is essential for efficiency of a program and avoidance of costly and nonessential expenditures. In the Swiss health system, the doctor's office could become more and more the center of preventive medicine for the individual. It would concern a large part of the population (in the United States, 80% of the men and 90% of the women consult a doctor at least once a year); offering a direct contact with the doctor of choice, advice specific for each case and the possibility of regular examinations by the same doctors. In many situations both public and private sources are involved in preventive medicine (public health services, doctors involved in the educational system, doctors involved in controll of security of working conditions, out-patient clinics, various health organizations). A collaboration among these sources should be organized and a reasonable division of the work established. A list of examinations and preventive treatments is presented.

Physical Examination↗