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Biomedical subjects

R Cox

Publications and source records attributed to R Cox.

At least 55 records · Page 3Linked to original sources

Comparison of cytogenetic damage in cultured cells from cobalt-60 gamma-radiation and the Auger emitter zinc-65.

PURPOSE: To assess the ability of the Auger-emitting nuclide, zinc-65 (65Zn), relative to gamma-irradiation, to cause chromosomal aberrations in cultured rat prostate cells. MATERIALS AND METHODS: Rat prostate adenocarcinoma cells in culture were exposed to doses of 1, 2, 3 or 5 Gy of external gamma-irradiation for 24h or incubated with 0.7, 1.5, 1.8 or 2.8 MBq of 65Zn for 24 h. The uptake by and clearance from cells of 65Zn was measured. Metaphase spreads prepared from washed cells were scored for chromatid- and chromosome-type aberrations. RESULTS: Following exposure to 65Zn or gamma-irradiation, chromatid-type damage was more commonly observed than chromosome-type aberrations. The relationship between induced chromatid damage and gamma dose (to 3 Gy) was best fitted by a second-order polynomial function, while the activity response relationship for chromatid damage caused by 65Zn appeared to be best fitted by a straight line. Measurements of the uptake of 65Zn by cells showed that average concentrations within cells were about 100 times the concentration in the culture medium. Assuming uniform distribution of 65Zn within cells, with 36% in the nucleus, the dose was estimated as 0.70 Gy per MBq added 65Zn, with Auger electrons contributing most (93%) of the dose. Assuming that 20% of cellular zinc was localized in the nucleus, based on previous measurements, the dose to the nucleus was calculated as 0.44 Gy per MBq added 65Zn. RBE values for chromatid damage induced by 65Zn compared to gamma-radiation range from about 1 to 3 based on a uniform dose throughout the cell and from about 2 to 5 based on 20% of 65Zn in the cell nucleus. CONCLUSION: The observed radiotoxicity of 65Zn is consistent with its behaviour as an Auger-emitting radionuclide that is localized to some extent in the nucleus.

Adenocarcinoma↗

Optimal outcome measures, research priorities, and international cooperation.

The participants in the Eriksholm Workshop on "Measuring Outcomes in Audiological Rehabilitation Using Hearing Aids" debated three issues that are reported in this article. First, it was agreed that the characteristics of an optimal outcome measure vary as a function of the purpose of the measurement. Potential characteristics of outcome self-report tools for four common goals of outcome measurement are briefly presented to illustrate this point. Second, 10 important research priorities in outcome measurement were identified and ranked. They are presented with brief discussion of the top five. Third, the concept of generating a brief universally applicable outcome measure was endorsed. This brief data set is intended to supplement existing outcome measures and to promote data combination and comparison across different social, cultural, and health-care delivery systems. A set of seven core items is proposed for further study.

Correction of Hearing Impairment↗

The X-ray structure of a chitinase from the pathogenic fungus Coccidioides immitis.

The X-ray structure of chitinase from the fungal pathogen Coccidioides immitis has been solved to 2.2 A resolution. Like other members of the class 18 hydrolase family, this 427 residue protein is an eight-stranded beta/alpha-barrel. Although lacking an N-terminal chitin anchoring domain, the enzyme closely resembles the chitinase from Serratia marcescens. Among the conserved features are three cis peptide bonds, all involving conserved active site residues. The active site is formed from conserved residues such as tryptophans 47, 131, 315, 378, tyrosines 239 and 293, and arginines 52 and 295. Glu171 is the catalytic acid in the hydrolytic mechanism; it was mutated to a Gln, and activity was abolished. Allosamidin is a substrate analog that strongly inhibits the class 18 enzymes. Its binding to the chitinase hevamine has been observed, and we used conserved structural features of the two enzymes to predict the inhibitors binding to the fungal enzyme.

Acetylglucosamine↗

A randomized controlled trial of strapping to prevent post-stroke shoulder pain.

OBJECTIVE: To determine whether strapping the shoulder in hemiplegic stroke patients: (1) prevents the development, or reduces the severity, of shoulder pain, (2) preserves range of movement in the shoulder, and (3) improves the functional outcomes for the arm and patient overall. DESIGN: A prospective, randomized, single-blind controlled trial of shoulder strapping versus no strapping. SETTING: Care of the elderly wards in a teaching hospital, Christchurch, New Zealand. SUBJECTS: All patients admitted with an acute hemiplegic stroke, who had persisting weakness of shoulder abduction. INTERVENTION: The treatment group had their affected shoulder strapped for six weeks from randomization in addition to standard physiotherapy. MAIN OUTCOME MEASURES: All subjects were assessed at entry (week 0), at end of the treatment phase (week 6) and two months later (week 14). A visual analogue scale (VAS) was used to assess shoulder pain severity whereas shoulder range of movement to the point of pain (SROMP) assessed passive range of movement and pain. Functional Independence Measure (FIM), Motor Assessment Scale (MAS) and Rankin Disability Index measured functional outcomes. RESULTS: Ninety-eight subjects participated (49 strapped, 49 controls). Intention to treat analysis showed no significant difference in pain, range of movement or functional outcomes after the intervention phase or at the final assessment. However there were trends for less pain at six weeks (VAS, p = 0.11) and better final upper limb function (MAS, p = 0.16) in strapped patients. Skin reactions were uncommon (6.1%). The presence of neglect or sensory loss, but not subluxation, at baseline was independently associated with poor outcome. Range of movement was lost early (mean difference SROMP between hemiplegic and contralateral shoulders at baseline = 15.2 degrees (95% CI 10.9-19.5)) and continued throughout the study. Shoulder strapping did not alter the rate at which range of movement was lost. CONCLUSIONS: No significant benefit with shoulder strapping was demonstrated and reasons for this are discussed. Range of movement in the hemiplegic shoulder is lost very early and any preventive treatments need to begin within the first 1-2 days after a stroke.

Aged↗

Studies of the oestrous cycle, oestrus and pregnancy in the koala (Phascolarctos cinereus).

As an integral part of the development of an artificial insemination programme in the captive koala, female reproductive physiology and behaviour were studied. The oestrous cycle in non-mated and mated koalas was characterized by means of behavioural oestrus, morphology of external genitalia and changes in the peripheral plasma concentrations of oestradiol and progestogen. The mean (+/- SEM) duration of the non-mated oestrous cycle and duration of oestrus in 12 koalas was 32.9 +/- 1.1 (n = 22) and 10.3 +/- 0.9 (n = 24) days, respectively. Although the commencement of oestrous behaviour was associated with increasing or high concentrations of oestradiol, there were no consistent changes in the morphology or appearance of the clitoris, pericloacal region, pouch or mammary teats that could be used to characterize the non-mated cycle. As progestogen concentrations remained at basal values throughout the interoestrous period, non-mated cycles were considered non-luteal and presumed anovulatory. After mating of the 12 koalas, six females gave birth with a mean (+/- SEM) gestation of 34.8 +/- 0.3 days, whereas the remaining six non-parturient females returned to oestrus 49.5 +/- 1. 0 days later. After mating, oestrous behaviour ceased and the progestogen profile showed a significant increase in both pregnant and non-parturient females, indicating that a luteal phase had been induced by the physical act of mating. Progestogen concentrations throughout the luteal phase of the pregnant females were significantly higher than those of non-parturient females. Parturition was associated with a decreasing concentration of progestogen, which was increased above that of basal concentrations until 7 days post partum.

Animals↗

Natural and artificial methods for inducing the luteal phase in the koala (Phascolarctos cinereus).

An experiment was conducted in which female koalas were mated for different durations of intromission and ejaculation to confirm that the luteal phase of the oestrous cycle in koalas is induced by the physical act of mating. Results showed that induction of a luteal phase in the koala usually required a complete duration of penile thrusting behaviour from the male. It is proposed that induction of a luteal phase in koalas may involve a copuloceptive reflex, triggered by the thrusting of the male's penis into the female's urogenital sinus. Although interrupted mating in koalas may be used to induce a luteal phase in preparation for an artificial insemination programme, this study showed that there is a 12.5% probability that pregnancy will result from semen prematurely emitted by the teaser male. A dose of 250 iu hCG was administered intramuscularly to eight oestrous females to determine whether it was possible to induce a luteal phase artificially. In contrast to control females, which received sterile saline injections, all females injected with hCG showed a significant increase in progestogen concentration above that of basal values, indicating that a luteal phase had been induced successfully.

Animals↗

Somatic cell hybrids for high-density mapping of chromosome 2 breakpoints in radiation-induced myeloid leukemia cell lines from inbred mice.

Chromosome 2 (chr 2) deletions are recurrent abnormalities in acute myeloid leukemia (AML) induced by ionizing radiation in the mouse. The localization of deletion sites has proven extremely useful in providing information on the molecular mechanisms of leukemogenesis. The models available for the study of AML are mostly represented by inbred mouse strains, in which the molecular resolution of breakpoints is problematic. In this study, we have examined five leukemic cell lines exhibiting hemizygous chr 2 loss, derived from CBA, C3H, or (C57BLxCBA/H) F1 mice in which AML had been induced by a whole-body dose of radiation. By application of a somatic cell hybridization technique, we have generated interspecific cell hybrids retaining the deleted murine chr 2 homologue. This strategy permitted a very detailed genetic analysis allowing the utilization of any genetic marker on chr 2 without a requirement for polymorphism. Somatic cell hybrid clones were subjected to a high-density polymerase chain reaction-based microsatellite screening using 62-106 informative markers for each cell line. Detailed maps accurately defining chr 2 breakpoints were obtained. The identification of critical breakpoint markers allowed the construction of partial yeast artificial chromosome contigs across chr 2 breakpoints. These maps represent an essential resource for cloning of the breakpoint regions.

Animals↗

Clonidine toxicity in an adolescent patient.

Clonidine is a central acting a2-agonist used primarily as an antihypertensive agent. Recently, it has been used for the treatment of attention deficit hyperactivity disorder in children and adolescents. When taken in excess, it can produce profound CNS depression, apnea, bradycardia and hypotension. A transient period of hypertension can sometimes occur. Treatment is primarily supportive, including respiratory support, atropine for bradycardia, and fluids and dopamine for hypotension. The CNS depression sometimes responds to naloxone. Young children are very sensitive to the toxic effects of clonidine. A case of an 11 year old adolescent who took an overdose of his clonidine is described to illustrate the toxicity of this agent.

Accidents, Home↗

AUDIX: a knowledge-based system for speech-therapeutic auditory discrimination exercises.

AUDIX is a knowledge-based multimedia system for auditory discrimination exercises. The aim of AUDIX is to provide patients with a computer-based therapy system which they can use between sessions with the human therapist, at home on an 'on-demand' basis. It is centered around computer based cognitive rehabilitation therapy whereas most existing programs in this area are only used for assessment. The auditory discrimination exercise system is designed for adult people who are speech-impaired as a result of a stroke. These people have auditory perceptual problems. The nature of the perceptual problem is an inability to perceive differences between phonemes. This requires a type of therapy called auditory discrimination training. The system provides computer-based auditory discrimination training. Through the knowledge-based design the domain dependent therapy knowledge is separated from the system core and provides a way for the therapist to add new knowledge, as new stimuli, or to create a new knowledge base to provide special exercises for an individual patient. The AUDIX architecture is described and the advantages of computer-based therapy are discussed.

Adult↗

Nurse managers' use of a computer decision support system. Differences in nursing labor costs per patient day.

To control nursing labor cost, nurse managers (NMs) need access to productivity indicators and financial performance information on a daily basis. Labor cost and hour reports after the fact are no longer acceptable for making crucial management/labor decisions. The purpose of this study was to determine if there was a mean difference in nursing labor cost per patient day (PPD) when a nurse manager used a labor computer decision support system (CDSS) compared to an NM who did not use this system. This descriptive study was implemented on a study and comparison unit in both a psychiatric and a medical hospital. The CDSS provided the NMs with daily labor cost information on which to base labor decisions. Study findings indicate that with the use of the labor CDSS, nurse managers achieved better cost performance per patient day compared to the nurse managers who did not use the labor CDSS.

Computer User Training↗

Physical map and characterization of transcripts in the candidate interval for familial chondrocalcinosis at chromosome 5p15.1.

The gene for familial chondrocalcinosis (MIM 118600; gene symbol CCAL2) has been localized to a 0.8-cM interval on the short arm of chromosome 5, between the polymorphic microsatellite markers D5S416 and D5S2114. We have undertaken the physical and transcript mapping of this interval, as well as regions telomeric to the interval, in an attempt to define ultimately the gene for this disorder. The physical map is composed of YAC, BAC, PAC, and cosmid resources and spans a physical distance of approximately 0.3 Mb. Using cDNA selection, we have identified eight novel transcripts in and around the interval; two of the selected transcripts reside in the candidate interval. We have also more precisely placed several expressed sequence tags (ESTs) that were previously mapped by radiation hybrid analysis and were reported to reside in or near the candidate interval. Two of the ESTs analyzed overlap with the selected cDNAs that reside in the candidate interval. All of the selected cDNAs are expressed partial transcripts, as determined by Northern blot analysis, and using RT-PCR analysis, we have determined that the cDNAs that reside in the candidate interval are expressed in cartilage and synovium, tissues that are presumably relevant to the chondrocalcinosis phenotype.

Adult↗

Voluntary ethanol drinking during the first three postnatal weeks in lines of rats selectively bred for divergent ethanol preference.

BACKGROUND: Using a procedure first developed by Hall (1979), we examined ethanol self-administration in preweanling pups from Wistar rats and in lines of rats selectively bred for divergent ethanol preference (alcohol-preferring P, alcohol-nonpreferring NP, high-alcohol-drinking HAD-1 and -2, and low-alcohol-drinking LAD-2) to determine if factors contributing to high and low alcohol intakes are present early in development. METHODS: From postnatal days 5 to 20, nondeprived male and female rat pups received 30 min daily access to either water or a 15% (v/v) ethanol solution. In each daily session, pups were placed in a heated chamber containing Kimwipes soaked with a water or ethanol solution. Pups were weighed before and after each session, and intake levels were calculated as a percentage of body weight change. RESULTS: Similar to previous reports, Wistar pups exhibited over a 2-fold higher level of ethanol ingestion than water on postnatal days 9 through 14, with ethanol intakes approaching 3 g/kg body weight. When the drinking patterns of the selected lines were examined, only the HAD replicate lines showed a comparable preference for ethanol versus water during the preweanling period. The ethanol consumption of P, NP, and LAD lines was not consistently distinguishable from water intake levels. To reveal whether early ethanol exposure would influence later ethanol drinking behavior, a subset of HAD and LAD rat pups received free-choice ethanol access upon weaning. Although the divergent ethanol preference between high- and low-alcohol-drinking lines was evident within the first 4 days of access (>4 g/kg/day for HAD; <2 g/kg/day for LAD), preweanling ethanol exposure did not alter the acquisition or maintenance of ethanol drinking in either line. CONCLUSIONS: Overall, these results suggest that (a) the enhanced ethanol ingestion observed during the middle portion of the preweanling period is a robust phenomenon and generalizes across nonselected strains of rats, (b) selective breeding for divergent alcohol preference has arrested this age-specific effect in all but the HAD lines of rats, and (c) early ethanol exposure does not alter genetic dispositions for later high or low alcohol preference.

Alcohol Drinking↗

Molecular mapping of chromosome 2 deletions in murine radiation-induced AML localizes a putative tumor suppressor gene to a 1.0 cM region homologous to human chromosome segment 11p11-12.

Radiation-induced acute myeloid leukemias (AMLs) in the mouse are characterized by chromosome 2 deletions. Previous studies showed that a minimal deleted region (mdr) of approximately 6.5 cM is lost from one homologue in chromosome 2-deleted AMLs. An AML tumor suppressor gene is proposed to map within this mdr. In this study, we refine the mdr to a I cM interval between markers D2Mit126 and D2Mit185 by microsatellite analysis of 21 primary radiation-induced F I AMLs. The construction of a partial yeast artificial chromosome (YAC) contig spanning the mdr and the location of six known genes indicated that the 1 cM mdr is homologous to human 11p11-12, a region implicated in some human AMLs. Screening of five cell lines derived from primary radiation-induced AMLs for homozygous loss of microsatellites and genes mapping within the mdr revealed loss of both copies of the hemopoietic tissue-specific transcription factor Sfpi1(PU.1/Spi1) in one cell line. Studies of primary and F1 AMLs failed to implicate Sfpi1 as the AML tumor suppressor gene. YAC contig construction, together with data suggesting that the critical gene flanks Sfpi1, represents significant progress toward identifying an AML tumor suppressor gene.

Animals↗

Crystallization and preliminary X-ray analysis of a chitinase from the fungal pathogen Coccidioides immitis.

Chitinase is necessary for fungal growth and cell division and, therefore, is an ideal target for the design of inhibitors which may act as antifungal agents. A chitinase from the fungal pathogen Coccidioides immitis has been expressed as a fusion protein with gluathione-S-transferase (GST), which aids in purification. After cleavage from GST, chitinase was crystallized from 30% PEG 4000 in 0. 1 M sodium acetate pH 4.6. The crystals have a tetragonal crystal lattice and belong to space group P41212 or P43212 and diffract to 2. 2 A resolution. The unit-cell parameters are a = b = 91.2, c = 95.4 A; there is only one chitinase molecule in the asymmetric unit.

Chitinases↗