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Residual ovarian activity during oral steroid contraception.

Steroid drugs with contraceptive properties have been available in the clinical setting for over four decades and are still subject to improvement. Estrogens, progestins and anti-progestins have been used alone or in various combinations, regimens and routes of administration to favour the balance between efficacy and undesirable effects. One of the most important changes in this respect is the gradual lowering of steroid dosage in commercially available contraceptives. Current steroid contraceptive pills still achieve the goal of suppression of pituitary-ovarian activity, but the margins for error are minimal. In this review the available data on modes of action and the effects on suppressing pituitary-ovarian activity by different forms of oral contraception are reassessed. Although pregnancy rates provide a crude measure of contraceptive efficacy, no benchmark for pituitary-ovarian inhibition is available to test the suppressive potential of contraceptive drugs. Consequently, many studies provide incomplete and/or incomparable results. For the further study of those forms of steroid contraception that rely predominantly on suppression of ovarian activity, prevention of dominant follicles selection should be the objective.

Contraceptives, Oral, Hormonal↗

What lessons can be learned for cancer registration quality assurance from data users? Skin cancer as an example.

BACKGROUND: In cancer registration, data cleaning (i.e. amendments made by data users to datasets released by registries) is potentially informative for quality assurance, but generally underreported. AIM: To assess the scope for learning lessons about cancer registration quality assurance from a data user (using skin cancer as the example). METHODS: The main design features were: (i) A descriptive study identifying, qualitatively and quantitatively, the breadth, depth, and impact of quality assurance issues raised by a user cleaning Merseyside and Cheshire Cancer Registry skin cancer data. Errors were rectified and pitfalls for interpretation were identified. (ii) A nested validation of morphology and site coding on random samples of cutaneous malignant melanomas, basal cell carcinomas (BCC), and squamous cell carcinomas. The 33132-record dataset comprised: all registered skin lesions, except metastases; most recorded variables (about patient, lesion, treatment, outcome); for Merseyside and Cheshire residents diagnosed 1970-1991. RESULTS: (i) Ineligible cases represented 0.3% (97/33132), and were detected best by morphology checks. Most quality assurance issues identified related to local custom and practice, staff training, and computerization, being particularly illustrated by problematic BCC registration practice (e.g. records written over unchallenged by range checks; and idiosyncratic use of variables). (ii) Post-cleaning, morphology coding errors were minimal in the random samples. CONCLUSION: There is great scope for data users to contribute to cancer registration quality assurance. Ultimately, the study dataset appeared fit for epidemiological analysis and important quality assurance messages emerged. Shared explicit standard guidelines for data preparation and validation are needed by users, whose insights could and should be better recognized by cancer registries.

Adult↗

Precise assessment of microsatellite instability using high resolution fluorescent microsatellite analysis.

The instability of microsatellite sequences dispersed in the genome has been linked to a deficiency in cellular mismatch repair. This phenotype has been frequently observed in various human neoplasms and is regarded as a major factor in tumorigenesis. To demonstrate alterations in microsatellite sequences, polymerase chain reaction (PCR) and electrophoretic analysis are techniques often used. However, the electrophoretic profiles of PCR-amplified microsatellite sequences have not been well characterized. Moreover, the conventional method using autoradiography has critical problems in detection characteristics and migration accuracy. We made use of fluorescence-labeled PCR and laser scanning with linear detection characteristics, so as to detect bands quantitatively. Next, we characterized Taq polymerase-dependent modification of the amplified microsatellite sequences, using artificially synthesized microsatellite alleles and we optimized the electrophoretic profiles by enzymatic modification with T4 DNA polymerase. We developed a dual fluorescence co-electrophoresis system, in which both samples derived from cancer and normal tissues are electrophoresed in the same lane, in order to minimize migration errors. These improvements remarkably facilitate precise and objective assessments of microsatellite instability. Analyzing many positive cases in cell lines and tissue specimens, we classified all the patterns of microsatellite alteration and set up new criteria for assessing microsatellite instability.

Adenocarcinoma↗

PlasmID: a centralized repository for plasmid clone information and distribution.

The Plasmid Information Database (PlasmID; http://plasmid.hms.harvard.edu) was developed as a community-based resource portal to facilitate search and request of plasmid clones shared with the Dana-Farber/Harvard Cancer Center (DF/HCC) DNA Resource Core. PlasmID serves as a central data repository and enables researchers to search the collection online using common gene names and identifiers, keywords, vector features, author names and PubMed IDs. As of October 2006, the repository contains >46 000 plasmids in 98 different vectors, including cloned cDNA and genomic fragments from 26 different species. Moreover, the clones include plasmid vectors useful for routine and cutting-edge techniques; functionally related sets of human cDNA clones; and genome-scale gene collections for Saccharomyces cerevisiae, Pseudomonas aeruginosa, Yersinia pestis, Francisella tularensis, Bacillus anthracis and Vibrio cholerae. Information about the plasmids has been fully annotated in adherence with a high-quality standard, and clone samples are stored as glycerol stocks in a state-of-the-art automated -80 degrees C freezer storage system. Clone replication and distribution is highly automated to minimize human error. Infor-mation about vectors and plasmid clones, including downloadable maps and sequence data, is freely available online. Researchers interested in requesting clone samples or sharing their own plasmids with the repository can visit the PlasmID website for more information.

Biological Specimen Banks↗

Activation mechanism of erythrocyte cathepsin E. evidence for the occurrence of the membrane-associated active enzyme.

Activation of the erythrocyte cathepsin E located on the cytoplasmic surface of the membrane in a latent form was studied in stripped inside-out membrane vesicles prepared from human erythrocyte membranes. Incubation of the vesicles at 40 degrees C at pH 4 resulted in increased degradation of the membrane proteins, especially band 3. This proteolysis was selectively inhibited by the inclusion of pepstatin (isovaleryl-Val-Val-statyl-Ala-statine) or H 297 [Pro-Thr-Glu-Phe(CH2-NH)Nle-Arg-Leu] in the incubation mixtures, indicating that cathepsin E, as the only aspartic proteinase in erythrocytes, is responsible for the proteolysis. Two potential active-site-directed inhibitors of aspartic proteinases, pepstatin and H 297, were used to prove the occurrence of the membrane-associated active enzyme. To minimize potential errors arising from non-specific binding, the concentrations of the inhibitors used in the binding assay (pepstatin, 5 x 10(-8) M; H 297, 1 x 10(-5) M) were determined by calibration for purified and membrane-associated cathepsin E. The inhibition of the membrane-associated cathepsin E by each inhibitor, which showed the binding of the inhibitor to the activated enzyme, was temperature- and time-dependent. The binding of each inhibitor to the enzyme on the exposed surface of the membrane at pH 4 was highly specific, saturable, and reversible. The present study thus provides the first evidence that cathepsin E tightly bound to the membrane is converted to the active enzyme in the membrane-associated form, and suggests that this enzyme may be responsible for the degradation of band 3.

Biotransformation↗

Reliability of goniometric measurements and visual estimates of knee range of motion obtained in a clinical setting.

The purpose of this study was to examine the intratester and intertester reliability for goniometric measurements of knee flexion and extension passive range of motion (PROM). In addition, parallel-forms reliability for PROM measurements of the knee obtained by use of a goniometer and by visual estimation was examined. The intertester reliability for visual estimates of the PROM of the knee was also examined. Repeated measurements were obtained on 43 patients in a clinical setting. The intraclass correlation coefficients (ICCs) for intratester reliability of measurements obtained with a goniometer were .99 for flexion and .98 for extension. Intertester reliability for measurements obtained with a goniometer was .90 for flexion and .86 for extension. The ICCs for parallel-forms reliability for measurements obtained with a goniometer and by visual estimation ranged from .82 to .94. The intertester reliability for measurements obtained by visual estimation was .83 for flexion and .82 for extension. Results suggest clinicians should use a goniometer to take repeated PROM measurements of a patient's knee to minimize the error associated with these measurements.

Adult↗

Validity of the Peabody Developmental Gross Motor Scale as an evaluative measure of infants receiving physical therapy.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the validity of the Peabody Developmental Gross Motor Scale (PDMS-GM) as an evaluative measure of infants receiving physical therapy. SUBJECTS AND METHODS: Infants who attended an early intervention program (N = 124) were grouped by diagnosis: cerebral palsy, Down syndrome, hydrocephalus, preterm with developmental delay, full term with developmental delay, and other. The PDMS-GM was administered to each infant three times over a 6-month period by a therapist who did not provide treatment. RESULTS: Mean scaled scores and age-equivalent scores increased for each group. Individual change was examined using the reliable change index. The results indicated that the change in total raw score for 62% of the infants was greater than what could be attributed to measurement error. When minimal clinically important change was defined as 10 scaled score points, the index of responsiveness was equal to 0.5. This finding indicates that a sample size of 68 subjects per group would be needed when the PDMS-GM is used as an outcome measure in research. CONCLUSION AND DISCUSSION: The mean change scores for each group support the use of the PDMS-GM as an evaluative measure. For many infants, particularly infants with cerebral palsy, the PDMS-GM was not responsive to change over a 6-month period. The index of responsiveness suggests that the PDMS-GM should be used only as an outcome measure in large clinical trials. The PDMS-GM is not recommended for evaluating the direct effects of physical therapy but is recommended for providing a global measure of change in motor development as part of a multidimensional assessment.

Cerebral Palsy↗

Epidural anaesthesia and analgesia for surgery: still going strong?

PURPOSE OF REVIEW: The discussion on the value of epidural anaesthesia and analgesia for surgery is fuelled by current controversies regarding effects on postoperative morbidity and mortality, potential benefits for outcome and the fear of rare, but catastrophic neurological complications. This review of the most recent publications on the topic since April 2002 illustrates some of the aspects contributing to the ongoing discussion. RECENT FINDINGS: In contradiction to previous meta-analyses, recent trials could not demonstrate significant improvements of overall morbidity or mortality by epidural anaesthesia and analgesia. However, the technique was shown again to provide superior analgesia and a reduction of perioperative stress response and respiratory complications. Analysis of the current literature strongly supports that epidural anaesthesia and analgesia remains a safe practice with a low rate of severe complications, in particular in paediatric surgery. Several developments in equipment, techniques and especially drugs have been reported, resulting in improved balanced anaesthesia and analgesia and contributing to the safety of this technique. SUMMARY: In an era of evidence-based medicine, further meta-analyses and well-planned large randomized trials have to address the controversial issues of epidural anaesthesia and analgesia and postoperative outcome. In the context of a more holistic 'rehabilitative' management of the perioperative period, this technique might well represent a key factor to improve outcome, reduce hospital stay and thereby healthcare costs. Recent innovations and developments in techniques and drugs as well as established guidelines should further minimize potential errors and harmful complications.

Journal Article↗

Staphylococcal infection under a LASIK flap.

PURPOSE: To report a staphylococcal infection under a laser in situ keratomileusis (LASIK) flap and to discuss the management of this rare and potentially devastating complication. METHODS: A patient was referred to our practice having had bilateral LASIK. She was found to have abscesses under the left corneal flap. Staphylococcus aureus was identified as the infecting organism by corneal scrape and treated with appropriate antibiotics. The cornea improved, and then the abscess recurred. The abscess was again scraped and intensive treatment reinstituted. RESULTS: After successful treatment, the patient recovered excellent visual acuity with only a minimal astigmatic error. CONCLUSION: The possible reasons for the apparent improvement and then recurrence of the abscess are discussed. The management of this case including the need for corneal scrape and antibiotic prophylaxis is discussed in relation to previously reported cases.

Abscess↗

In vivo measurement of proton diffusion in the presence of coherent motion.

Measurement of the self-diffusion coefficient D of water in tissue has been performed traditionally using the technique proposed by Stejskal and Tanner. A variant of that technique is shown here, employing flow-compensated gradients that significantly reduce the sensitivity to small coherent motions that are common in body imaging. An interleaved sequence with four values of diffusion-sensitizing gradient (b) minimizes registration errors. Eddy currents and other systematic errors are reduced, permitting the measurement of standards in an imaging context within 5% of nonimaging values in the literature. The flow-compensated sequence permits the measure of D for tissues in the abdominal cavity of the rat. We present in vivo measurements of D for the following rat tissues; liver, kidney (cortex), kidney (medulla) muscle, brain, fat.

Acetone↗

The brief psychiatric rating scale for children (BPRS-C): validity and reliability of an anchored version.

OBJECTIVE: Because the accuracy of problems reported by referred children may be compromised by their academic, cognitive, or motivational limitations, clinician rating forms may contribute to the accurate assessment of youth adjustment. One such measure, the 21-item Brief Psychiatric Rating Scale for Children (BPRS-C), received psychometric study to estimate its potential contribution to the measurement of symptom dimensions. BPRS-C reliability and concurrent validity were calculated for youths who were receiving psychiatric services within a medical school department. METHOD: Five hundred forty-seven children aged 3 to 18 years were rated by faculty or trainees; a subsample of 90 was concurrently rated by two observers. BPRS-C psychometric performance was demonstrated through interrater agreement, factor analysis, and multivariate analyses of variance across seven diagnosis-based groups. RESULTS: Although items and scales demonstrated substantial reliability and concurrent validity, item factor analysis revealed a few apparent errors in item-to-scale assignment. These errors were minimized by the use of three new second-order factor-derived scales: Internalization, Developmental Maladjustment, and Externalization. CONCLUSIONS: The BPRS-C can be easily integrated into academic clinical practice and is a reliable and valid method of child description. Additional study of three new BPRS-C factor scales and the application of the BPRS-C to the quantification of clinician observation of child symptomatic status are warranted.

Adolescent↗

Review of patients with multiple injuries treated at University Hospital, Kuala Lumpur.

This study has analyzed 260 patients with multiple injuries sustained in road accidents admitted to the University Hospital during the period July 1967 to July 1976, in relation to age, sex, and ethnic distribution. The types of injuries sustained have been discussed to highlight their effects on the community in a developing country. The extremities have been most frequently involved, while head injuries followed closely. The causative factors of multiple injury-producing accidents have been evaluated. The categories of victims most liable to multiple injuries have been discussed. The significance of understanding the mechanism of these accidents and the effect of such knowledge in minimizing diagnostic errors, thus enabling management and the urgent need for regional accident services in developing countries, have been stressed.

Accidents, Traffic↗

An alternative to DRGs. A clinically meaningful and cost-reducing approach.

A statistical methodology based on the Cox proportional hazards model (a survival time analysis method), an alternative to the approach underlying DRGs, is presented. The method is used to obtain an estimate of the length-of-stay (LOS) distribution of a patient incorporating either patient-specific or hospital variables. A percentile of the distribution chosen to minimize prediction error serves as the assigned LOS. Absolute deviation is used as the loss function both to determine the choice of a predicted LOS and to examine how well the scheme works. Multiple assignment schemes may also be developed from this approach. The results of the method, tested on a national probability sample of 4,608 psychiatric patients treated in psychiatric units of general hospitals, suggest that with respect to average absolute deviation, the proposed methodology may provide a scheme that is superior to the present DRG scheme. For the sample, the average percent improvement obtained using the median of the estimated LOS distribution as the predicted LOS over the sample mean of the DRG group is 19%. A two assignment strategy results in average improvements over DRGs of 43%.

Cost Control↗

Reproducibility of a single-sample method for 99Tcm-MAG3 clearance under clinical conditions.

The aim of this study was to assess the intra-individual reproducibility of 99Tcm-mercaptoacetyltriglycine (99Tcm-MAG3) clearance in routine clinical practice in various circumstances using a single-sample method. Three groups of 30 patients each were enrolled in the study. Investigations were repeated on the same day with two different levels of activity (group A), within 1 week (group B), or after 1 year (group C). Blood samples were taken after 20 and 25 min and clearance values were averaged to minimize incidental errors after calculation according to the formula proposed by Bubeck et al. For clearance estimation on the same day, time-dependent background correction for residual activity was carried out. The mean difference was -2.0%, +6.0% and -1.5% (S.D. = 6.3%, 15.7% and 11.7%) for groups A, B and C respectively, taking into account values > 100 ml min-1 only. We demonstrated that 99Tcm-MAG3 clearance is highly reproducible under the same conditions. However, a repeat clearance measurement on a separate day revealed large differences. Therefore, in follow-up studies for evaluation of changing kidney function (e.g. surgery or chemotherapy), differences should exceed 30% (i.e. 2 S.D. of group B) to be statistically significant.

Glomerular Filtration Rate↗

Wavelength-dependent magnification and polychromatic image quality in eyes corrected for longitudinal chromatic aberration.

Theoretical calculations using a simple model eye in combination with achromatizing lenses or artificial pupils show that correcting wavelength-dependent refractive error or its effects can exaggerate wavelength-dependent magnification by up to a factor of 7. These calculations are confirmed experimentally, and their effects on retinal image quality are modeled. Because of the increased wavelength-dependent magnification, gains in polychromatic image quality produced by correcting wavelength-dependent refractive error (or minimizing its effects with small pupils) are generally restricted to a small region of the retina.

Color Perception↗

Frequency of convergence insufficiency in optometry clinic settings. Convergence Insufficiency and Reading Study (CIRS) Group.

PURPOSE: To estimate the frequency of convergence insufficiency (Cl) and its related characteristics among 8- to 12-year-old children randomly selected from 2 optometry clinic populations. METHODS: Clinic records of 620 children were randomly selected and reviewed according to a standard protocol, using a systematic sampling method based on the total number of 8- to 12-year-old children seen over a 1-year period at 2 optometry clinics. Records were reviewed for demographic and clinical data. Data on Cl-related symptoms were obtained at one of the sites. Records that met the eligibility criteria of: good visual acuity (20/30 or better in both eyes); minimal refractive error (-0.50 to +1.00 D and < or = 1.00 D of astigmatism in either eye, and < or = 1.00 D of anisometropia); and no strabismus were evaluated for Cl-related characteristics. Eligible children were classified according to the direction of their near heterophoria and the number of the following clinical signs present: (1) exophoria at near > or = 4 delta than at far; (2) insufficient fusional convergence [i.e., failing Sheard's criterion or minimum normative positive fusional vergence (PFV) of 12 delta base-out (BO) blur/15 delta BO break]; and (3) receded nearpoint of convergence (NPC) of > or = 7.5 cm break or > or = 10.5 cm recovery. Children were then classified as: no Cl (nonexophoric at near or < 4 delta difference between far and near); low suspect (exophoric at near and 1 sign); high suspect (exophoric at near and 2 signs); or definite Cl (exophoric at near and 3 signs). RESULTS: Sixty-seven percent (415/620) of the records met the eligibility criteria and had complete data on phoria, NPC, and PFV. The age (mean +/- SD) of the study population was 10.2 +/- 1.2 years. Ethnicity data were available for 85% of those eligible; the ethnic distribution was 36% African American, 29% Caucasian, 19% Hispanic, and 1% Asian. About one-half of the 415 children were classified as either low suspect (33%); high suspect (12%); or definite Cl (6%). Clinically significant Cl (high suspect and definite categories) was identified in 17.6% of the children. The percentage of children rated as symptomatic increased with the number of Cl-related clinical signs present. CONCLUSIONS: These findings suggest a high frequency of Cl in optometry clinic populations and a potential correlation between patient symptoms and the number of Cl signs present.

Child↗

Frequency of convergence insufficiency among fifth and sixth graders. The Convergence Insufficiency and Reading Study (CIRS) group.

PURPOSE: To estimate the frequency of convergence insufficiency (CI) and its related clinical characteristics among 9- to 13-year-old children. METHODS: Fifth and sixth graders were screened in school settings at three different study sites. Eligible children with 20/30 or better visual acuity, minimal refractive error, no strabismus, and exophoria at near were evaluated according to a standardized protocol to determine the presence and severity of CI. These children were classified according to the presence and number of the following clinical signs: (1) exophoria at near > or =4delta than far, (2) insufficient fusional convergence, and (3) receded nearpoint of convergence. Also, children were classified as accommodative insufficient (AI) if they failed Hofstetter's minimum amplitude formula or had greater than a + 1.00 D lag on Monocular Estimate Method retinoscopy. RESULTS: Of 684 children screened, 468 (68%) were eligible for further evaluation. Of these, 453 had complete data on CI measurements and were classified as: no CI (nonexophoric at near or exophoric at near and < 4delta difference between near and far) (78.6%); low suspect CI (exophoric at near and one clinical sign: exophoria at near > or =4delta than far) (8.4%); high suspect CI (exophoric at near and two clinical signs) (8.8%); and definite CI (exophoric at near and three clinical signs) (4.2%). CI status varied according to ethnicity and study site (p < 0.0005), but not gender. The frequency of AI increased with the number of CI-related signs. For CI children with three signs, 78.9% were classified as also having AI. CONCLUSIONS: These findings suggest that CI (defined as high suspect and definite) is frequent (13%) among fifth and sixth grade children. In addition, there is a high percentage of CI children with an associated AI.

Accommodation, Ocular↗