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Use of steroid hormone treatments prior to superovulation in Nelore donors.

The objective of this study was to evaluate the effectiveness of synchronization of follicular wave emergence using steroid hormone treatments in Nelore cows. Donors were placed into three groups. Those that were between days 9 and 12 of their cycle (estrus=day 0) formed the TI group (n=60), whilst those that were in any other stages of their estrus cycle constituted groups TII (n=60) and TIII (n=60). TI donors were submitted to a standard protocol of superovulation, however, TII and TIII donors were treated with the Syncro-Mate-B (SMB) or Controlled Internal Drug Releasing Device (CIDR-B) programs, respectively. Superovulation was induced with p-FSH, divided into eight decreasing doses at intervals of 12h. The donors received cloprostenol 48h after the beginning of the treatment and progestagens were removed 12h later. Artificial inseminations (AI) were done at 12 and 22h after the initiation of estrus and the embryo collections were done 7 days after AI. In the donors which displayed behavioral estrus, mean (+/-S.E.M.) total ova and viable (transferable) embryos were 15.8+/-1.4 and 8.3+/-1.0 (TI, n=56); 15.6+/-1.3 and 8.9+/-1.0 (TII, n=56); 17.3+/-1.0 and 9.9+/-0.9 (TIII, n=57), respectively, with no significant difference (P > or =0.05) among groups. In those animals that did not displayed behavioral estrus, the mean values of total ova and viable embryos were 3.5+/-1.6 and 0.7+/-0.5 (TI, n=4); 11.5+/-3.9 and 9.0+/-4.4 (TII, n=4); 8.7+/-5.0 and 5.0+/-2.9 (TIII, n=3), respectively, with no significant differences (P > or =0.05) among groups. Pregnancy rates of 62.2% (TI, n=235); 66.4% (TII, n=284) and 65.1% (TIII, n=244) were obtained with embryos transferred from these collections and did not differ significantly (P > or =0.05) among groups. It was concluded that the synchronization of the emergence of follicular waves in Nelore donors is usable and does not harm the efficiency of embryo transfer programs. In addition, in contrast to the standard superovulation protocol, this method permits the use of a large number of donors in a short time period, at any stage of the estrus cycle, minimizing the costs of embryo transfer.

Animals↗

A genetic map of chromosome 1: comparison of different data sets and linkage programs.

We have used 22 chromosome 1 loci to construct a genetic linkage map of this autosome using the Venezuelan Reference Pedigree. These markers formed two linkage groups separated by an interval of more than 30 cM. Linkage maps were constructed separately using the computer programs LINKAGE and MAPMAKER to determine their relative speed, efficiency, and accuracy. We found that both programs generated maps with the same order and distances, although the LINKAGE program derived more information from the data, allowing placement of one additional marker. Many of the probes have previously been mapped using the CEPH pedigrees. However, the current map is generated from a different data set and so can be used to increase the certainty of locus order and map position. Ultimately, the generation and confirmation of a 1-cM map of this chromosome will require such multiple data sets.

Alleles↗

Health care for persons with non-insulin-dependent diabetes mellitus. The German experience.

A structured treatment and education program for patients with non-insulin-dependent diabetes mellitus (NIDDM) who are not taking insulin was developed, evaluated, and implemented at the primary health care level throughout Germany. The program is based on the definition of individual and pragmatic therapeutic goals for each patient, primarily using nondrug treatment, which includes systematic glycosuria self-monitoring by the patients and four structured sessions of group education held in a general practitioner's office. After documentation of the program's efficacy in a randomized, controlled trial and several pilot projects, the program has been officially incorporated into the general German health care scheme and includes payment to practicing physicians for each patient treated. More than 12,500 primary health care physicians have participated in special 2-day postgraduate courses given by diabetologists; these courses are a precondition to participating in the program. As part of the primary health care scheme, the NIDDM program will be continuously monitored for quality control and efficiency. Currently, similar structured treatment and education programs targeted to primary health care physicians are being introduced for both insulin-treated NIDDM and arterial hypertension.

Diabetes Mellitus, Type 2↗

Use of explicit criteria and implicit judgments in a drug-use review program.

The degree of agreement between implicit and explicit judgments made by a pharmacist in a drug-use review program in an ambulatory-care setting was studied. During a six-month period in 1980, all prescriptions for a group of 19 drugs were reviewed for appropriateness of indication, dosage, and length of therapy by a pharmacist using implicit judgment. The same prescriptions were then reevaluated according to explicit criteria that had been approved by the prescribing physicians. A sample of prescriptions that did not meet either implicit or explicit criteria for use was subjected to review by a committee of four physicians to validate whether these prescriptions were indeed inappropriate. Of the 935 prescriptions evaluated, 36.8% were judged inappropriate by the explicit criteria and 23.5% were judged inappropriate by implicit judgment. The explicit and implicit approaches yielded concordant results for 95.5% of the observations. The proportion of true deviations as validated by the review committee was estimated at 80% for the implicit method and 74.4% for the explicit method. The implicit judgments of a pharmacist appear to be as effective as explicit drug-use criteria for identifying inappropriate prescribing in a drug-use review program. These judgments could be used to increase the efficiency of a drug-use review program when explicit criteria are not available.

Drug Utilization↗

The use of steroid hormones in superovulation of Nelore donors at different stages of estrous cycle.

The objective of the present study was to evaluate the superovulatory response and ova/embryo recovery from Nelore donors following treatment with a controlled internal drug releasing device and estradiol benzoate (CIDR-B program) at different stages of the estrous cycle. The control group (TI; n=40) received a standard superovulation protocol with females of this group being between days 9 and 12 of the estrous cycle (estrus = day 0). The donors that received a CIDR-B program containing 1.9 g progesterone and an intramuscular injection of estradiol benzoate (2 mg) were at day 0 (TII; n=30), between days 2 and 6 (TIII; n=30), days 7 and 12 (TIV; n=30), days 13 and 16 (TV; n=30) and days 17 and 20 (TVI; n=30) of the estrous cycle. Superovulation was induced with 400 IU of p-FSH, divided into eight decreasing doses (80/80; 60/60; 40/40; 20/20) at intervals of 12h. The donors received PGF2alpha (Cloprostenol) 48 h after beginning the treatment and CIDRs were removed 12h later. Artificial inseminations (AI) were performed 12 and 22 h after the initiation of estrus and embryos were collected 7 days after AI. The mean numbers (+/-S.E.M.) of total ova and embryos, viable (transferable) and degenerated embryos were 14.2+/-11.3, 7.4+/-6.9 and 3.2+/-3.5 (TI), 13.3+/-10.4, 7.1+/-6.2 and 3.3+/-4.3 (TII), 13.5+/-7.0, 8.1+/-6.7 and 2.3+/-3.0 (TIII), 17.4+/-9.9, 9.4+/-6.9 and 4.0+/-4.4 (TIV), 16.9+/-8.8, 9.8+/-8.1 and 2.7+/-2.5 (TV) and 13.0+/-7.8, 7.2+/-6.9 and 2.3+/-2.5 (TVI), with no significant differences (P>/=0.05) among groups. Pregnancy rates of 67.1% (TI; n=86/128), 60.8% (TII; n=59/97), 62.5% (TIII; n=73/115), 64.1% (TIV; n=84/131), 72.3% (TV; n=81/112) and 60.6% (TVI; n=63/104) were obtained with embryos transferred from these collections and did not differ significantly (P>/=0.05) among groups. The results of the present study allow us to conclude that a combination of steroid hormones may be used prior to superovulation in Nelore donors, at any stage of the estrous cycle without affecting the efficiency of embryo transfer programs.

Administration, Intravaginal↗

The challenge of evaluating programs in a large health sciences centre.

This article illustrates how the logic model and a course on program evaluation at a large health sciences centre were instrumental in preparing staff to evaluate their own programs. Staff and physicians need basic skills in program evaluation. The logic model is a simple yet useful tool in helping to identify key measurables. A short course to teach the theory and practice of logic models, evaluation design, choice and design of measures, and data analysis has been shown to be a practical solution in preparing staff and physicians to evaluate their own programs.

Efficiency, Organizational↗

Evaluation of a program to overcome vitamin A and iron deficiencies in areas of poverty in Minas Gerais, Brazil.

Randon samples of children from both sexes from Belo Horizonte, the capital City, and from Turmalina, Jequitinhonha Valley, Minas Gerais, Brazil, were submitted to nutritional evaluation before and after the intervention "Program to Overcome Vitamin A and Iron Deficiencies in Areas of Poverty in Minas Gerais, Brazil". After the first examination, all the children received, with an interval of 180 days, a single oral dose of vitamin A, oral iron sulfate during 50 days, and 200 mg of Mebendazol/day for three days. Thirty days after ending administration of the third dose of medicine, the children were subjected to a new evaluation. In Belo Horizonte, the first evaluation revealed a high prevalence of deficient and low values of vitamin A in preschool children (21.5%) and school children (21.7%). A small prevalence of low hematocrit values was also observed in both groups. Deficient and low values of hemoglobin were found as well in 21.5% of preschool children and in 17.5% of school children. The second evaluation, practiced 30 days after the third dose of medicine, showed a small incidence of low vitamin A values (4.3% in preschool children and 2.9% in school children) and low hemoglobin values (6.5% in preschool children and 2.9% in school children). No deficient values of hemoglobin and vitamin A were observed. Concerning the hematocrit value, only one school child presented a low value at the second evaluation. On the other hand, in Jequitinhonha Valley, five cases of Bitot spot with conjunctival xerosis, two cases of corneal xerosis, and one case of keratomalacia were detected at the first examination. Thirty days after ending the third dose of medicine, only one corneal scar was observed. Only a small number of children with deficient and low levels of vitamin A and hemoglobin was found in the final evaluation (less than 8%), while this number was high at the first evaluation (above 38 and 12%, respectively). These results show the efficiency of the intervention Program in relation to hypovitaminosis A and iron anemia prevention. The Program is now being implemented by the Brazilian Ministry of Health.

Adolescent↗

A follow-up comparative study of two modes of learning human anatomy: by dissection and from prosections.

Two groups of medical students (traditional and experimental), who had studied the gross anatomy of the lower limb by different methods (by dissection and from prosections, respectively) 5 years earlier, were re-assessed without warning. The objective was to determine whether or not the learning mode had any implications for the subsequent recall of the material studied. Three tests were administered: a 100-item two-choice theory paper, a practical test consisting of 18 time stations with specimen-based questions, and a standardized oral examination. Both qualitative and quantitative assessments were made in the practical and oral examinations. Although the numerical scores gained by both groups in the practical test were statistically similar, the incidence of random guesswork was significantly less among students on the experimental program. The same group was also adjudged to have performed better in the oral examination by two of the investigators who were blind to the group affiliations of the students. The results suggest that on testing 5 years after a practical learning experience in gross anatomy, the numerical scores gained by students who had studied from prosections were similar to those of their peers who had carried out dissections but that, by some qualitative considerations, the recall ability of the non-dissecting students was superior. Furthermore, the program of study from prosections lasted only 74% of the duration of the dissection course and is thus more efficient. The results recommend the program to institutions faced with unfavorable student-to-cadver ratios. The time it liberates may be dedicated to such other imaginative pedagogical purposes as autonomous student learning, clinical demonstrations, and problem-solving team exercises.

Anatomy↗

Parametric receiver operating characteristic curve analysis using mathematica.

Several computer programs have been written to perform receiver operating characteristic (ROC) curve analysis, and are available in the public domain. Here, the author provides the theory and description for 'rocMath', a Mathematica program that performs parametric ROC curve analysis. The 'rocMath' program has some advantages over other ROC curve programs, including the ability to provide, through optional arguments: (a) user-specified pointwise confidence limits, as well as default 95% limits, on ROC curve area and on true-positive rates; (b) ROC curve plots with data points, a fitted curve, and user-specified pointwise confidence bands; and (c) ROC curve areas, tables, and plots based on a logistic distribution as well as on a standard normal distribution. In addition, the code of 'rocMath' can be modified to address additional ROC curve applications. The program uses Mathematica's ability to operate on purely symbolic as well as numeric data to achieve substantial coding efficiency. Limitations of the 'rocMath' program are also discussed.

Mathematical Computing↗

Managed care for preventive services: a review of policy options.

In summary, the managed care system we propose for preventive services is designed to limit the potential for overcare under FFS payment and for undercare under capitation and comprehensive fixed fees. It bases payment on the provision of a complete set of preventive services, thus limiting the tendency of physicians to provide only the relatively high-profit services, such as screening tests, while neglecting the lower-profit services, such as counseling. It also allows primary care providers to outsource selected services to lower-cost providers, such as laboratories, health educators, and counselors, and community-based health promotion programs, thus encouraging greater efficiency. In addition, the proposed system funds both primary and high-risk preventive case management to ensure that individuals receive preventive services appropriate to their age, sex, and risk factors. Finally, the proposed system monitors the use of preventive services, relying on physician reminders to stimulate the appropriate provision of preventive care and denying payment for unauthorized care. Existing research suggests that none of the individual strategies for managed care can be expected to achieve all of the goals of managing and promoting the appropriate use of preventive services as defined by the U.S. Preventive Services Task Force (1989). To be most effective, we conclude that the strategies need to be coordinated and integrated into the current health care delivery practices of HMOs, PPOs, and point-of-service plans. In addition, the strategies require additional provider training in preventive care. With this support, the proposed model has the potential to improve quality, control costs, and increase the appropriate use of preventive care. While many of the individual components of the proposed managed care model have been evaluated for preventive services, a great deal more research is needed to evaluate the effect of combining these elements into a coordinated and comprehensive approach to managing preventive care. Research is also needed on workable ways to invite people not currently receiving medical care into the health care system to receive preventive care. To inform policy development, the impact of the proposed managed care model--both on preventive services utilization for specific screening, immunization, and counseling services, and on total health care costs and patient health status outcomes--needs to be evaluated.

Cost Sharing↗

Implications for health care policy. A social and demographic profile of hemodialysis patients in the United States.

Before 1973, selection of patients with end-stage renal diseases (ESRD) for treatment was necessary because of inadequate medical and financial resources. Patients were selected based partly on social worth rather than medical suitability. In 1973 ESRD patients became eligible for Medicare benefits, eliminating the financial barrier to treatment. Using data from two national surveys of hemodialysis patients in 1967 and 1978, two social and demographic profiles of patients illustrate the effect of extension of Medicare benefits on composition of the dialysis patient population. These data indicate that problems of patient selection have been resolved, and ESRD patients now have equal access to medical care. Nevertheless, there is growing pressure for cost efficiency for the ESRD program in the tightening economic climate. This may lead again to some form of restriction for future access to dialysis therapy.

Adolescent↗

Is the periodic health examination worthwhile?

Periodic health examinations is a primary tool in the practice of preventive medicine. It has been identified as such and promoted for health maintenance and disease control since the early 1900s. And yet, it has never been proved cost-effective. In fact, recently is has become fashionable for certain physicians to challenge the professional time and public money spent on examinations of asymptomatic adults as nonproductive and wasteful, urging medical care only in the presence of complaints suggesting illness. A balanced assessment of the value of periodic health examinations requires definition of the content and method of the examination, the individuals to be examined, and the frequency with which the examination is performed. Some procedures have no or very little yield under any circumstances. Most procedures will be more effective for certain groups of examinees, particularly with reference to age and family and environmental factors. During the past decade, methods for health hazard or risk factor analysis have been developed which enable design of more efficient periodic health examination programming, targetting those population subgroups most apt to be harboring presymptomatic disease. It can be anticipated that refinement of risk-related examination methods in the next decade will firmly establish the value of periodic health examination as a basic tool in medical practice.

Adult↗

Capillary electrophoretic bioanalysis of therapeutically active peptides with UV and mass spectrometric detection after on-capillary preconcentration.

An earlier developed capillary electrophoresis (CE) system with an on-capillary adsorptive phase is investigated for its suitability to quantitate low concentrations of angiotensin II and gonadorelin in plasma. An off-line solid-phase extraction is used for sample preparation. The on-line preconcentration CE system allows multiple capillary volumes of sample solution to be injected, increasing the concentration sensitivity of CE with 3-4 orders of magnitude. Furthermore, possible influence of matrix salts can be ruled out by employing a rinsing step after sample application. Using short-wavelength UV detection, reproducibility and linearity in the low nanomolar range were satisfactory. The capillary could be efficiently regenerated using a programmed between-run rinsing procedure, allowing 20-30 large injections of sample extracts. Coating of the capillary improved the robustness of the method. Mass spectrometric detection via a previously reported sheathless interface increased the selectivity and sensitivity substantially. Recommendations are provided for the sample preparation process, the most critical part of the system. Further purification of the sample is required to allow the loading of larger sample volumes and to optimize the system's robustness.

Angiotensin II↗

Conformational analysis of a dinucleotide photodimer with the aid of the genetic algorithm.

The solution structure of the photodimer cis,syn-dUp[]dT is derived with the aid of the genetic algorithm. The conformational space available for the molecule is sampled efficiently using the computer program DENISE and tested against a set of constraints available from nmr experiments. The dominant conformation in solution found with this approach can be described by the following combinations of sugar-phosphate backbone torsion angles: epsilon(t), zeta(t), alpha(+), beta(-ac), and gamma(t). The conformation of the sugars and glycosidic torsion angles are S type and syn, respectively. The cyclobutane ring and pyrimidines are puckered. In addition, other conformations that exist in equilibrium with the first are found. It is concluded that the cyclobutane-pyrimidine system is rigid, whereas the sugar-phosphate backbone is flexible. The solution structures are compared with the crystal structure of the strongly related cyano-ethyl ester of cis,syn-dTp[]dT.

Algorithms↗

A key developmental switch during Norway spruce somatic embryogenesis is induced by withdrawal of growth regulators and is associated with cell death and extracellular acidification.

The biotechnology of somatic embryogenesis holds considerable promise for clonal propagation and breeding programs in forestry. To efficiently regulate the whole process of plant regeneration through somatic embryogenesis, it is of outmost importance to understand early developmental events when somatic embryos are just formed. In Norway spruce, somatic embryos transdifferentiate from proembryogenic masses (PEMs). This work describes the developmental dynamics (frequency distribution of PEMs and early somatic embryos) of the whole embryogenic suspension culture growing in the presence and absence of plant growth regulators (PGRs), auxin and cytokinin. The experiments have shown that PEM-to-somatic embryo transition is a key developmental switch that determines the yield and quality of mature somatic embryos and ultimately plant production. This switch was induced by the withdrawal of PGRs in cell suspension leading to a rapid accumulation of early somatic embryos (to a maximum of 75% of the entire population of suspension culture) and concomitant degradation of PEMs. The latter was evident from increased level of cell death measured through spectrophotometric Evans blue staining assay. Proembryogenic mass-to-embryo transition and concomitant activation of cell death were mediated by strong extracellular acidification. Therefore, buffering PGR-free culture medium at high (pH 5.8) or low (pH 4.5) levels of pH inhibited both PEM-to-embryo transition and cell death. The yield of mature somatic embryos on abscisic acid (ABA)-containing medium was increased up to 10-fold if the suspension culture had been pretreated for 1 to 9 days in unbuffered PGR-free medium. In this case a large proportion (75%) of the total number of mature embryos was formed within a short, 5-week, contact with ABA. The latter is practically important because prolonged contact with ABA suppresses the growth of somatic embryo plants. Based on these results, an improved method for regulating somatic embryogenesis was set up and tested for nine genotypes of Norway spruce. Over 800 plants regenerated from all tested genotypes demonstrated a good performance in the greenhouse and they were transferred to the field.

Apoptosis↗

Modeling of Cdc25B dual specifity protein phosphatase inhibitors: docking of ligands and enzymatic inhibition mechanism.

The Cdc25 dual specificity phosphatases have central roles in coordinating cellular signalling processes and cell proliferation. It has been reported that an improper amplification or activation of these enzymes is a distinctive feature of a number of human cancers, including breast cancers. Thus, the inhibition of Cdc25 phosphatases might provide a novel approach for the discovery of new and selective antitumor agents. By using the crystal structure of the catalytic domain of Cdc25B, structural models for the interaction of various Cdc25B inhibitors (1-13) with the enzyme were generated by computational docking. The parallel use of two efficient and predictive docking programs, AutoDock and GOLD, allowed mutual validation of the predicted binding poses. To evaluate their quality, the models were validated with known structure-activity relationships and site-directed mutagenesis data. The results provide an improved basis for structure-based ligand design and suggest a possible explanation for the inhibition mechanism of the examined Cdc25B ligands. We suggest that the recurring motif of a tight interaction between the inhibitor and the two arginine residues, 482 and 544, is of prime importance for reversible enzyme inhibition. In contrast, the irreversible inhibition mechanism of 1-4 seems to be associated with the close vicinity of the quinone ring and the Cys473 catalytic thiolate. We believe that this extensive study might provide useful hints to guide the development of new potent Cdc25B inhibitors as novel anticancer drugs.

Cell Cycle Proteins↗

Computing conditional recombination probabilities given marker information.

When a parent is homozygous, it is not possible to determine directly whether offspring share an allele identical by descent (IBD) from that parent. However, an IBD probability can be computed using information from linked loci where the parent is heterozygous. To solve this problem for the phase-known case, probability equations and a computer program were developed for efficient computation of conditional probabilities under a Sturt model of chiasma interference. Data are analyzed and contrasted with and without taking interference into account. The effect of failing to account for interference is very small, but the computational cost is also small.

Alleles↗

Evaluation of trained midwives in a copper-T IUD insertion Program in Isfahan, Iran.

From four centers in Isfahan, data from 252 insertions of the Cu-T-200 made by midwives and 646 insertions of the same device made by doctors are compared. Although the net cumulative one-year continuation rate for women who had a copper-T inserted by a midwife is significantly lower than for women who had a copper-T inserted by a doctor there are no significant differences between the one-year event rates for the two groups of patients. These data suggest that an expanded role for midwives in IUD insertion programs would be an efficient use of health personnel.

Copper↗