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Biomedical subjects

R Day

Publications and source records attributed to R Day.

At least 199 records · Page 11Linked to original sources

Intratester and intertester reliability of the cervical range of motion device.

The purpose of this study was to investigate the intratester and intertester reliability of the Cervical Range of Motion instrument (CROM) for measuring cervical flexion, extension, lateral flexion, and rotation. Twenty able-bodied subjects were tested by two testers on two different occasions. Pearson product-moment correlations for intratester reliability ranged from .63 to .90 for tester one and from .62 to .91 for tester two. Intertester reliability was good. Coefficients ranged from .80 to .87 for session one and .74 to .85 for session two. Paired data t-tests showed that there were no significant differences between testers or sessions (p = .01). The results suggest that the CROM has acceptable intratester and intertester reliability. The CROM has many benefits including ease of application and reliability. More research is needed on patients with cervical dysfunction.

Adult↗

Direct relationship between remission duration in acute myeloid leukemia and cell cycle kinetics: a leukemia intergroup study.

Cell cycle characteristics including labeling indices (LI), duration of S-phase (Ts), and total cell cycle time (Tc) were determined in 54 standard-risk, newly diagnosed patients with acute myeloid leukemia following an infusion of bromodeoxyuridine. Remission induction therapy consisting of cytosine arabinoside and daunomycin was then administered to all patients, followed by three courses of consolidation to those who achieved complete remissions (CR). Older patients appeared to have more rapidly cycling cells (P = .003). No unique cell cycle characteristics were identified for patients who achieved remission versus those who had resistant disease. However, the pretherapy cell cycle characteristics were a strong prognosticator for remission duration. CR patients were divided into those whose leukemic cell Tc were above median (A) and below median (B). Among 14 B patients, median duration of response was 211 days, and all relapsed by day 600. Among 18 A patients, the median has not as yet been reached, with nine patients in continuous complete remission (log rank P = .007, Wilcoxon P = .04). We conclude that cell cycle characteristics of leukemic cells play a role in determining remission duration, perhaps because the leukemic cells of the former patients regrow slowly between courses of chemotherapy.

Bone Marrow↗

Evaluation of tetrazolium-based semiautomatic colorimetric assay for measurement of human antitumor cytotoxicity.

A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay was developed and compared with 51Cr release from different adherent tumor cell targets (human squamous cell carcinoma lines of the head and neck established in our laboratory, melanoma, and colorectal carcinoma) using 5-7-day human lymphokine-activated killer cells and monocyte-depleted peripheral blood lymphocytes as effectors. With adherent tumor cell targets, MTT colorimetry was more sensitive than the 51Cr release assay in measuring the antitumor activity of effectors: median, 4385 (range, 988-8144) versus median, 1061 (range, 582-7294) lytic units (the number of effector cells required to lyse 20% of 5 x 10(3) targets)/10(7) effectors (P less than 0.01). Background effects (without effector cells) were comparable in 4-h assays (9% versus 10%) between MTT colorimetry and 51Cr release. In 24-h assays, MTT colorimetry showed higher antitumor activity (70-100% versus 40-60% lysis at 1:1 effector:target cell ratio) but lower background effects (6% versus 38%) than 51Cr release assay. Thus, MTT colorimetry was more sensitive, did not use radiolabeled targets, required fewer effector cells, and was easier, less expensive, and better adaptable to serial monitoring of effector cell function in cancer patients. This colorimetric assay is especially well suited to adherent tumor cell targets. The use of adherent tumor cell monolayers, as opposed to trypsinized single cell suspensions, provides an opportunity to measure interactions of effector cells with enzymatically unaltered solid tumor targets. Because of the greater sensitivity of the colorimetric assay, the transformation of MTT data into lytic units, as commonly used for 51Cr release assays, required an adjustment to avoid the extrapolation based on the exponential fit equation.

Carcinoma, Squamous Cell↗

Regulation of striatonigral prodynorphin peptides by dopaminergic agents.

The primary purpose of this study was to examine the regulation of prodynorphin peptides by dopaminergic agents in the central nervous system. The indirectly acting catecholamine agonist D-amphetamine sulfate (AMPH) and the dopamine receptor antagonist haloperidol (HAL) were administered to rats across a variety of treatment schedules and drug doses. The striatum, substantia nigra and hippocampus were dissected and examined by radioimmunoassay for 5 different prodynorphin peptides, covering all 3 opioid domains in the prodynorphin precursor: dynorphin A(1-8) and dynorphin A(1-17) of the dynorphin A domain, dynorphin B(1-13) of the dynorphin B domain, and alpha-neo-endorphin and beta-neo-endorphin of the neo-endorphin domain. In addition, the proenkephalin peptide Met-enkephalin-arg6-gly7-leu8 (MERGL) was examined in the striatum. AMPH administered one hour prior to sacrifice caused a dose-dependent depletion of prodynorphin peptides in both the striatum and substantia nigra. In animals treated with AMPH once each day for 7 days and sacrificed 24 h later, a dramatic dose-dependent increase in prodynorphin peptides was observed in these brain regions. Animals treated with AMPH once each day for 7 days and sacrificed one hour after the final injection showed no changes in prodynorphin peptides. In addition to changes in individual prodynorphin peptides, AMPH treatment caused alterations in the relationships between intermediate peptides (dynorphin A(1-17) and alpha-neo-endorphin) and their immediate products (dynorphin A(1-8) and beta-neo-endorphin). AMPH caused no consistent changes in prodynorphin peptides in the hippocampus, or in MERGL in the striatum. Taken together these data suggest that acute dopaminergic activation causes depletion of dynorphins from striatonigral prodynorphin neurons, presumably due to dopamine-dependent release of these peptides; repeated activation causes repeated release, with a rebound increase in biosynthesis. HAL, in contrast to AMPH caused relatively subtle changes in striatonigral prodynorphin peptides. Although no significant changes in individual prodynorphin peptides were observed, HAL treatment caused a change in the relationship between dynorphin A(1-17) and dynorphin A(1-8), a change opposite in direction to that observed with AMPH treatment. As has been previously reported, repeated HAL administration caused a dose-dependent increase in the proenkephalin peptide MERGL. The relatively subtle effects of HAL on prodynorphin peptides suggests that tonic dopamine activity is not important in the regulation of striatonigral prodynorphin neurons. The potential functional and behavioral significance of the present results are discussed.

Animals↗

Natural killer cytotoxicity in the diagnosis of immune dysfunction: criteria for a reproducible assay.

Current evidence indicates that natural killer (NK) cells, which are large granular lymphocytes that mediate non-major histocompatibility complex (MHC)-restricted cytotoxicity and antibody-dependent cytotoxicity and that are involved in multiple regulatory, developmental, and immunologic processes, are important in health. Immunodeficiency states presenting with low NK activity are often associated with malignancies, chronic viral infections, or autoimmune diseases. Monitoring of NK function appears to be indicated as an aid to diagnosis, prognosis, and follow-up after therapy. Reliable performance of NK assays in a clinical laboratory requires that uniform criteria be established and followed for the acceptability of results. Statistical analysis of daily variability can be of great assistance in identifying and tracking sources of error, but routine statistical adjustments are not generally advisable. The quality control program described here provides a degree of assurance that this cytotoxicity assay can be dependable whether performed at one time point or serially. The successful implementation of this program requires laboratory resources, biostatistical support, and interpretative skills, all of which are available in a modern clinical laboratory.

Cytotoxicity Tests, Immunologic↗

Partial biventricular repair for double-outlet right ventricle with left ventricular hypoplasia.

The presence of left ventricular hypoplasia in double-outlet right ventricle may increase the risk of biventricular repair and Fontan procedures. The hypoplastic left ventricle of an 11-year-old girl with complex double-outlet right ventricle was successfully incorporated in a modified biventricular repair by Dacron patch closure of the ventricular septal defect, diversion of venous return of the inferior vena cava to the mitral valve with an intraatrial baffle, insertion of a left ventricular apex to pulmonary artery valved aortic homograft, and diversion of residual systemic venous return directly to the lungs with a bidirectional superior vena cava to pulmonary artery shunt. Postoperatively, the systemic venous atrial pressure was 6 mm Hg and the pulmonary artery pressure was 14 mm Hg. This method is proposed as a partial biventricular repair hemodynamically superior to the Fontan procedure, although aortic homograft revision may be required in the future.

Blood Vessel Prosthesis↗

Antimalarials in rheumatic diseases.

The antimalarials hydroxychloroquine and chloroquine remain established and effective agents for the treatment of rheumatoid arthritis and systemic lupus erythematosus. Although the mechanisms of action remain uncertain, evidence is accumulating that the antirheumatic and immunological effects of the antimalarials are related to their massive distribution into the cellular acid-vesicle system. These drugs are attracting new interest because their relative safety recommends their use in early rheumatoid arthritis and as a component of second-line antirheumatic drug combinations. The absence of data examining the effect of antimalarials upon radiological progression of rheumatoid arthritis needs to be rectified. Recent understanding of the pharmacokinetics of these drugs reveals that steady-state concentrations are not achieved for at least 3-4 months. Preliminary information also suggests a relationship between blood concentrations and effect. Taken together, these data suggest that more effective dosage regimens will be possible when therapeutic concentration ranges are properly established.

Antimalarials↗

Marked sex differences on a fine motor skill task disappear when finger size is used as covariate.

Purdue Pegboard performance of 16 male and 25 female right-handed college students were compared, and results were replicated with 25 male and 28 female subjects. In agreement with the literature, women performed significantly better than men. When measures of index finger and thumb thickness were used as covariate, all significant sex differences in performance disappeared. Negative correlations between performance and finger size were observed in both sexes. Sex differences in fine manual dexterity tasks may therefore be confounded by sex differences in finger size.

Female↗

MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia.

The expression of the MDR1 gene was studied by Northern blot analysis in leukaemic cell specimens obtained from 74 patients with acute myelogenous leukaemia (AML). No relationship was found between MDR1 RNA levels and FAB type of leukaemia or patient age. Transcript levels tended to be highest in the leukaemic cells of patients with a history of toxic exposure or preleukaemia compared with 'standard risk' patients at diagnosis but the differences were not significant (P = 0.07). Patients whose leukaemic cells contained high MDR1 transcript levels were difficult to induce into remission and, if remission was induced, the remissions were short. Hence high levels of MDR1 expression may explain, at least in part, the ineffectiveness of anthracycline antibiotic containing treatment regimens in some patients with AML.

Adolescent↗

Proenkephalin messenger RNA is expressed both in the rat anterior and posterior pituitary.

The presence of proenkephalin (PENK)-derived opioid peptides in the pituitary gland is well known. However, the cellular sources of their biosynthetic origin in all three pituitary lobes are less clear. In this study we identified the potential sites of synthesis by localizing the mRNA coding for PENK in the rat pituitary gland using in situ hybridization histochemistry. Numerous cells containing PENK mRNA were detected throughout the anterior lobe. Although suggested by previous reports, no mRNA signal could be detected in the intermediate lobe. Surprisingly, high levels of PENK mRNA were found in the posterior lobe. The cellular distribution in the neural lobe implies that pituicytes, a special class of glial cells, may express PENK mRNA.

Animals↗

Relatives' expressed emotion and the course of schizophrenia in Chandigarh. A two-year follow-up of a first-contact sample.

A two-year follow-up was conducted of a subsample of the Chandigarh cohort of first-contact schizophrenic patients from the WHO Determinants of Outcome project. The patients were those living with family members who had been interviewed initially to determine their levels of expressed emotion (EE). The interview was repeated for 74% of the relatives at one-year follow-up. A dramatic reduction had occurred in each of the EE components and in the global index. No rural relative was rated as high EE at follow-up. Of the patients included in the one-year follow-up, 86% were followed for two years. In contrast to the one-year findings, the global EE index at initial interview did not predict relapse of schizophrenia over the subsequent two years. However, there was a significant association between initial hostility and subsequent relapse. The better outcome of this cohort of schizophrenic patients compared with samples from the West is partly attributable to tolerance and acceptance by family members.

Attitude to Health↗

A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma.

This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously.

Adolescent↗

Sertoli cells are the primary site of prodynorphin gene expression in rat testis: regulation of mRNA and secreted peptide levels by cyclic adenosine 3' ,5'-monophosphate analogs in cultured cells.

Prodynorphin is one of three endogenous opioid peptide genes expressed in testis. Through the use of cell fractionation procedures and Northern blot analysis, Sertoli cells were found to be the primary site of prodynorphin mRNA synthesis in rat testis. In situ hybridization of a prodynorphin cRNA probe to fixed adult tissue confirmed this result. Treatment of primary cultures of rat Sertoli cells with a cAMP analog, 8-(4-chlorophenylthio)cAMP, resulted in a transient 5.6-fold increase in steady state prodynorphin mRNA levels relative to those in control cells. This increase was maximal at 48 h of treatment, after which mRNA levels gradually declined. Treatment of Sertoli cells with cAMP analogs resulted in concurrent 2.6-fold decreases in sulfated glycoprotein-2 mRNA levels. Culture medium from Sertoli cells showed a 3.1-fold increase in secreted dynorphin immunoreactivity after treatment with 8-(4-chlorophenylthio)cAMP. Chromatographic analysis indicates that the majority of the immunoreactive dynorphin peptide synthesized in Sertoli cells is present as high mol wt species, with some processing to bioactive peptides.

Animals↗