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Biomedical subjects

L Clayton

Publications and source records attributed to L Clayton.

At least 19 recordsLinked to original sources

Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females.

CONTEXT: Low-grade squamous intraepithelial lesions (LSILs) have been described as a benign cytological consequence of active human papillomavirus (HPV) replication. Several studies have reported that certain behavioral and biological risks exist for LSIL, suggesting that HPV alone is not sufficient for the development of LSIL. However, because most of these studies have been cross-sectional, it is not known whether behavioral and biological risks are simply risks for HPV infection itself. OBJECTIVE: To prospectively examine risks of incident HPV infection in HPV-negative females and of incident LSIL development in females with HPV infection. DESIGN: Prospective cohort study conducted between 1990-2000, with a median follow-up of 50 months. SETTING AND PARTICIPANTS: Females aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area; 496 had prevalent HPV infection and 105 were HPV-negative. MAIN OUTCOME MEASURE: Incident development of HPV infection and LSIL, analyzed by various demographic, behavioral, and clinical risk factors. RESULTS: Fifty-four incident HPV infections occurred in the 105 females who were HPV-negative at study entry (median duration of follow-up for those who remained HPV-negative was 26 months). Multivariable analysis showed that risks of HPV included sexual behavior (relative hazard [RH], 10.10; 95% confidence interval [CI], 3.24-31.50 per new partner per month), history of herpes simplex virus (RH, 3.54; 95% CI, 1.37-9.10), and history of vulvar warts (RH, 2.73; 95% CI, 1.27-5.87). Current use of oral contraceptives had a significantly protective effect (RH, 0.49; 95% CI, 0.28-0.86). Among the 496 individuals who were HPV-positive at baseline or in follow-up, there were 109 incident cases of LSIL during the follow-up interval, with a median follow-up time of 60 months for those who never developed LSIL. Human papillomavirus infection was the most significant risk factor for development of LSIL. The multivariable model showed the following risks for LSIL: HPV infection for less than 1 year (RH, 7.40; 95% CI, 4.74-11.57); HPV infection for 1 to 2 years (RH, 10.27; 95% CI, 5.64-18.69); HPV infection for 2 to 3 years (RH, 6.11; 95% CI, 1.86-20.06); and daily cigarette smoking (RH, 1.67; 95% CI, 1.12-2.48). CONCLUSION: Our results indicate distinct risks for HPV and LSIL. In addition, most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months. These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are, in fact, risks for acquisition of HPV. Cigarette smoking was a risk specific to LSIL, supporting the role of tobacco in neoplastic development.

Adolescent↗

Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import.

The trafficking of macromolecules between cytoplasm and nucleus through nuclear pore complexes is mediated by specific carrier molecules such as members of the importin-beta family. Nuclear pore proteins (nucleoporins) frequently contain sequence repeats based on FG cores and carriers appear to move their cargo through the pores by hopping between successive FG cores. A major question is why some macromolecules are transported while others are not. This selectivity may be generated by the ability to bind FG repeats, a local concentration of carrier-cargo complexes near the entrance to the pore channel, and steric hindrance produced by high concentrations of nucleoporins in the channel.

Active Transport, Cell Nucleus↗

Differences in length of stay for Hospital in the Home patients: comparing simple clinical coding with medical record review.

AIM: To determine whether the apparently longer length of stay (LOS) reported for patients with cellulitis managed in Hospital in the Home (HITH) compared with those managed as inpatients was correct. METHODS: Data, including LOS, from the Victorian In-patient Minimum Database (VIMD) of all patients with cellulitis managed between July 1998 and June 1999 at a large metropolitan teaching hospital were analysed and compared with a retrospective medical record review of the same patients. RESULTS: In the VIMD data, there were 266 episodes of cellulitis during the study period. However, the medical record review found that six episodes were not separate, but rather a continuation of treatment for the same episode of cellulitis, and that 18 were not episodes of cellulitis, but were pilonidal sinus infections. In the VIMD data set, the mean LOS for patients treated in HITH was generally longer than that for inpatients (7.2 days vs 5.1 days, respectively, P = 0.002). However, in the retrospective medical record review, the LOS for patients treated in HITH was similar to inpatients (7.3 days versus 7.0 days, respectively, P = 0.68). CONCLUSIONS: In contrast to the VIMD data, the medical record review demonstrated that, overall, patients with cellulitis had a similar LOS irrespective of whether they were managed at home or in hospital. This study confirms that caution is required in interpreting the VIMD data, highlights the importance of carefully monitoring the introduction of new treatment modalities and indicates areas for further research.

Analysis of Variance↗

The COSTAR wheelchair study: a two-centre pilot study of self-propulsion in a wheelchair in early stroke rehabilitation. Collaborative Stroke Audit and Research.

OBJECTIVE: It is uncertain whether self-propulsion in a wheelchair should be encouraged or discouraged in the early stages of stroke rehabilitation. DESIGN: A two-centre pilot study to assess the feasibility of performing a multicentre randomized controlled trial on this subject. SETTING: Clatterbridge and Aintree Stroke Rehabilitation Units, Merseyside, UK. SUBJECTS: Forty early stroke patients (mean age 67 years) in whom it was uncertain whether self-propulsion in a wheelchair should be encouraged were studied. INTERVENTION: A central randomization service at Newcastle University was used to determine the policy about wheelchair provision and use for each patient. They were allocated to either an 'encouraged to self-propel' or a 'discouraged from self-propulsion group'. OUTCOME MEASURES USED: Independent outcome assessment was performed by postal questionnaire and telephone interview using the Barthel ADL Scale, Nottingham Extended ADL Scales and the shortened General Health Questionnaire (GHQ-12) at 3 and 12 months. Patient's length of stay and their Ashworth tone score were also measured either at three months or when they were discharged from hospital. RESULTS: After considerable preparation time it was possible to conduct a trial on self-propulsion in early stroke rehabilitation in the two-pilot centres. No major differences were found between the pilot groups for any of the outcome measures. CONCLUSIONS: A multicentre randomized controlled trial to assess this question is feasible but further work is being conducted before proceeding, to satisfy the concerns expressed to our group regarding the appropriateness of the intervention and the outcome measures.

Aged↗

Use of nutritional supplements by high school football and volleyball players.

The known use of performance enhancing agents by athletes has occurred throughout history. In the 1960s and 1970s steroids and amphetamines were the supplements most often used. Now athletes are turning to supplements that are either natural or stimulate the release of natural hormones. The purpose of this study is to evaluate the prevalence of use of nutritional supplements among high school football and volleyball players. This study surveyed 495 male football players and 407 female volleyball players from 20 high schools in Northwest Iowa. These athletes completed anonymous surveys and returned them to their coaches. Results showed that 8% of the male athletes and 2% of the female athletes were using supplementation. Supplements used included creatine, androstiendione, HMB, amino acids, DHEA, phosphogen, weight gainer 1850, Tribulus, muscle plus, multivitamins, calcium, GABA, and Shaklee Vita Lea and Physique.

Adolescent↗

The design and analysis of a homeotic response element.

We have shown that the 26 bp bx1 element from the regulatory region of Distal-less is capable of imposing control by the homeotic genes Ultrabithorax and abdominal-A on a general epidermal activator in Drosophila. This provides us with an assay to analyze the sequence requirements for specific repression by these Hox genes. Both the core Hox binding site, 5'-TAAT, and the adjacent EXD 5'-TGAT core site are required for repression by Ultrabithorax and abdominal-A. The Distal-less bx1 site thus fits with the model of Hox protein binding specificity based on the consensus PBX/HOX-family site TGATNNAT[g/t][g/a], where the key elements of binding specificity are proposed to lie in the two base pairs following the TGAT. A single base pair deletion in the bx1 sequence generates a site, bx1:A(-)mut, that on the consensus PBX/HOX model would be expected to be regulated by the Deformed Hox gene. We observed, however, that the bx1:A(-)mut site was regulated predominantly by Sex combs reduced, Ultrabithorax and abdominal-A. The analysis of this site indicates that the specificity of action of Hox proteins may depend not only on selective DNA binding but also on specific post-binding interactions.

Animals↗

Cleaning up. The development of the Alfred/Medseed Wound Imaging System.

This paper describes the rationale, development, functions and applications of a new digital wound imaging system developed at The Alfred Hospital in Melbourne. The system known as The Alfred/Medseed Wound Imaging System (AMWIS) comprises a software package that quantitatively analyses a digital wound photograph and tracks the healing of the wound as a function of the wound care treatment used. The system is designed to enable the wound images and assessment data to be securely transmitted via the internet for review or consultation to any site equipped with the wound imaging system. The AMWIS is capable of being operated at a single site such as a hospital, at remote locations or as a mobile system. We believe that this is the first system of this kind developed in Australia that incorporates sophisticated analytical functions yet retains the flexibility to be used in inpatient, ambulatory or remote settings.

Image Processing, Computer-Assisted↗

The relationship of childhood sexual abuse and depression with somatic symptoms and medical utilization.

BACKGROUND: Previous research suggests that childhood sexual abuse is associated with high rates of retrospectively reported medical utilization and medical problems as an adult. The goal of this study was to determine if abused females have higher rates of medical utilization using self-report and objective measures, compared with non-abused females. A further goal was to determine whether findings of prior research would be replicated when childhood physical abuse level was controlled. This study also examined the moderating impact of depressed mood on current health measures in this population. METHODS: Six hundred and eight women recruited from a health maintenance organization completed self-report measures of health symptoms for the previous month and doctor visits for the previous year. Objective doctor records over a 2 year period were examined for a subset of 136 of these women. RESULTS: Results showed significantly more self-reported health symptoms and more self-reported doctor visits in abused participants compared with those who reported no childhood history of sexual abuse. Objective doctor visits demonstrated the same pattern with abused participants exhibiting more visits related to out-patient surgery and out-patient internal medicine. In addition, persons who were both sexually abused and depressed tended to visit the emergency room more frequently and to have more in-patient internal medicine and ophthalmology visits than sexually abused participants who reported low depressed mood and non-abused controls. CONCLUSIONS: These results replicate prior studies and suggest that current depression may moderate the relationship between sexual abuse and medical problems in adulthood.

Adolescent↗

The effect of body position on arterial oxygen saturation in acute stroke.

BACKGROUND: Evidence suggests that respiratory function is impaired poststroke. Body position is known to influence respiratory function in normal subjects and those with respiratory pathologies. Its effect on respiratory function after stroke has received little attention. However, one study suggests that some positions used in clinical practice may adversely influence respiratory function. This study therefore aimed to identify resting positions that maintain arterial oxygen saturation (SaO2) at optimal levels, changes in SaO2 during time spent in the test position, and differences in SaO2 among the positions investigated. METHOD: A within-subject, two-center clinical study was made. Patients in the first 72 hours following mild to moderately severe stroke were allocated a randomized sequence of four positions. One hour was spent in each position. SaO2 was recorded each minute by pulse oximetry with a finger probe. Mean values for the hour were calculated. RESULTS: Mean arterial oxygen saturation values for all patients were >90% for the hour spent in each test position for all patients. There were no changes in arterial oxygen saturation across the hour spent in the test positions (repeated-measures analysis of variance). No differences in arterial oxygen saturation were identified among positions (analysis of covariance). DISCUSSION: The saturation levels recorded corresponded to those observed in studies of normal elderly persons. The positions tested may be recommended for use in clinical practice to maintain arterial oxygen saturation in patients in the first 72 hours following mild to moderately severe stroke.

Female↗

A role for Rho-like GTPases in the polarisation of mouse eight-cell blastomeres.

Polarisation of cells during mouse preimplantation development first occurs within blastomeres at the eight-cell stage, as part of a process called compaction. Cell-cell contact mediated by the cell adhesion molecule uvomorulin (E-cadherin) and the activity of the microfilament cytoskeleton are important in the development of compaction, which is crucial for establishment of trophoblast and pluriblast (inner cell mass) lineages and for subsequent development. Members of the Rho family of p21 GTPases have been shown to regulate the organisation of the actin cytoskeleton and adhesion in other cell types. The potential role of these proteins in compaction was investigated. Inhibition of Rho with Clostridium botulinum C3-transferase disturbed intercellular flattening at compaction and prevented cytocortical microfilament polarisation of eight-cell blastomeres, in contrast to cytochalasin D which inhibited only adhesion. Microinjection of a constitutively activated recombinant Rho protein into four-cell blastomeres induced cortical microfilament disruption and apical displacement of nuclei associated with polarised clustering of microtubules. Interblastomere adhesion was reduced and E-cadherin was aberrently clustered at remaining cell-cell contacts. Similarly, activated Cdc42 protein induced nuclear displacement with additional cytoplasmic actin bundle formation between nucleus and cell-cell contacts. The effects produced by both of the activated GTPase proteins are indicative of prematurely induced but aberrently organised polarity. These results suggest that Rho family GTPases are involved in the polarisation of early mouse blastomeres.

ADP Ribose Transferases↗

Tropomyosin in preimplantation mouse development: identification, expression, and organization during cell division and polarization.

Tropomyosin is an actin-binding cytoskeletal protein which has been extensively characterized in a variety of cell types and tissues, with the exception of very early developmental stages during which cellular polarization first occurs. We have identified five polypeptides in mouse preimplantation conceptuses which show many of the characteristics of tropomyosin. They form the major portion of the heat-stable cytoskeletal protein fraction of blastomeres and have the characteristic isoelectric and SDS-PAGE migration characteristics on 1-D and 2-D gels. All five polypeptides were synthesized in late 2- and 4-cell, and all 8-cell stages, with three of the five polypeptides showing lower synthetic levels in fertilized eggs and early 2-cell conceptuses. These heat-stable proteins showed specific differences from proteins isolated from mouse 3T3 fibroblasts by the same method, namely higher Mr isoforms were not represented, also some of the isoforms can be labeled by incorporation of [14C]proline. The cellular distribution of tropomyosin in early stage conceptuses was examined using monoclonal and affinity-purified polyclonal antibodies. Tropomyosin becomes associated both with the blastomere cortex postfertilization and with the cleavage furrow during cytokinesis. The interphase cortical association is uniform until the 8-cell stage, when tropomyosin becomes associated with the developing apical pole and is excluded from the basolateral cortex. This polar localization is inherited along with the pole at the 8- to 16-cell division, but experiments in which cell division is artificially prolonged show that tropomyosin localization does not represent a permanent marking of the pole. We conclude that the early mouse conceptus contains a unique and specific set of tropomyosins which respond to polarizing signals.

3T3 Cells↗

The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women.

OBJECTIVES: The objectives of this study were to describe the early natural history of human papillomavirus (HPV) infection by examining a cohort of young women positive for an HPV test and to define within this cohort (1) the probability of HPV regression, (2) the risk of having a squamous intraepithelial lesion, and (3) factors that were associated with HPV regression. STUDY DESIGN: The study was a cohort analytic design. An inception cohort of 618 women positive for HPV participated. HPV testing, cytologic evaluation, and colposcopic evaluation were performed at 4-month intervals. HPV testing was characterized for two groups: low risk (five types rarely associated with cancers) and high risk (nine types most commonly associated with cancers). RESULTS: Estimates provided by Kaplan-Meier curves showed that approximately 70% of women were found to have HPV regression by 24 months. Women with low-risk HPV type infections were more likely to show HPV regression than were women with high-risk HPV type infections (log rank test p = 0.002). The relative risk for the development of high-grade squamous intraepithelial lesion (HSIL) was 14.1 (95% confidence interval: 2.3, 84.5) for women with at least three positive tests for high-risk HPV preceding the development of the HSIL compared with that for women with negative tests for high-risk HPV. However, 88% of women with persistent positive HPV tests have not had HSIL to date. No factors associated with high-risk HPV type regression were identified except for a negative association with an incident history of vulvar condyloma (relative risk = 0.5 [95% confidence interval: 0.3 to 0.8]). CONCLUSION: Most young women with a positive HPV test will become negative within a 24-month period. Persistent positive tests with oncogenic HPV types represented a significant risk for the development of HSIL. However, we found that most young women with persistent positive HPV tests did not have cytologically perceptible HSIL over a 2-year period. Factors thought to be associated with the development of HSIL were found not to be important in HPV regression.

Adolescent↗

Drug calculation competencies of graduate nurses.

This study describes the analysis of the mathematical ability of 220 registered nurses (RNs) from six Victorian universities who applied for a graduate year program at St Vincent's Hospital, Melbourne. Each applicant completed a drug calculation competency test (DCCT) which required them to calculate 11 drug dosages commonly performed by RNs in clinical practice. The results revealed that 58 percent (n = 127) of the 220 applicants were not able to accurately calculate all 11 drug dosages. The results also demonstrated significant differences between applicants from respective universities. The findings suggest that there are fundamental problems with the mathematical competencies of this group of newly graduated nurses. The results may also support the assertion that the educational preparation of these nurses at the undergraduate level could be enhanced in some universities and does not appear to adequately prepare nurses to perform basic drug calculations which are frequently required in the acute setting.

Clinical Competence↗

Genital human papillomavirus infections: knowledge, perception of risk, and actual risk in a nonclinic population of young women.

The purpose of this study was to assess knowledge, beliefs, and attitudes about genital human papillomavirus (HPV) infections in a group of young women in a nonclinic setting and to examine the association between perception of risk and actual risk. One hundred ten women attending a state university participated in the study and were asked to complete a self-administered questionnaire about knowledge and perceptions of risk. They were then offered testing for the virus using a self-administered vaginal method. The mean age was 20 +/- 1.2 years. Ninety (82%) were sexually experienced (SE), with a mean number of lifetime partners of 5.1 +/- 4.3. The mean knowledge score was less than the 68th percentile, reflecting low levels of knowledge about genital HPV infections. The SE group had a higher knowledge score than the sexually inexperienced (p < .02), but there were no differences in knowledge between those who chose to be tested and those who refused testing. The majority of women attributed negative emotion to being hypothetically tested positive for HPV. Emotions selected by > 50% of the group included feeling scared, angry, guilty, anxious, confused, dirty, regretful, and panicky. A greater negative emotion score was associated with refusing HPV testing (p < .002). Of the SE women, 58% (51) perceived themselves at risk, and, of this group, 71% (36) agreed to be tested. Of the women who agreed to HPV testing, 36% who perceived themselves at risk and 35% who did not perceive themselves at risk were, in fact, positive for HPV (p = ns). The majority of women have little knowledge of HPV infections and have attributed many negative emotions associated with infectivity. These negative attributes appear to influence women's decision making concerning HPV testing. The risk of HPV infection in this nonclinic group was substantial, suggesting that even in a nonclinic group, the prevalence of HPV is quite high. Perception of risk was unrelated to actual risk (HPV positive test), reflecting the lack of self-identified risk.

Adolescent↗

CD45 monoclonal antibodies inhibit TCR-mediated calcium signals, calmodulin-kinase IV/Gr activation, and oncoprotein 18 phosphorylation.

The effects of a pan-CD45 mAb (CD45.2) on TCR-mediated signaling pathways were investigated in Jurkat T cells. The simultaneous addition of CD45 mAb with an activating OKT3 mAb had little effect on TCR-stimulated signals. However, when Jurkat cells were exposed to the CD45 mAb for 10 to 20 min before the addition of OKT3, a partial uncoupling of the TCR from intracellular signals was observed. The maximal increase in intracellular calcium was inhibited 47 +/- 10% (n = 11, range 33-67%), whereas no inhibition of inositol trisphosphate production was detected. The transient TCR-mediated activation of the Ca2+/calmodulin-activated kinase IV/Gr was also inhibited by the CD45 mAb, and this was reflected in a 50 to 60% inhibition in the TCR-stimulated generation of the p21 and p23 phosphoisomers of oncoprotein 18, a Ca2+/calmodulin-activated kinase IV/Gr substrate recently implicated in cell cycle regulatory events. Oncoprotein 18 is also a substrate for mitogen- activated protein kinase, but no inhibition by the CD45 mAb of TCR-triggered mitogen-activated protein kinase activation was observed. The CD45 mAb was therefore selective in causing the uncoupling of the TCR from calcium signals and calcium-regulated events without promoting a general inhibition of all TCR-mediated signals. Confocal microscopy revealed that binding of the CD45 mAb caused patching of CD45 molecules at the cell surface and, unexpectedly, a marked redistribution of intracellular CD45. However, no change was observed in the total level of CD45 expressed at the cell surface. Aggregation of CD45 at the cell surface may result in its sequestration from its tyrosine kinase substrates, with a consequent selective uncoupling of the TCR from intracellular signaling pathways.

Antibodies, Monoclonal↗

Experimental manipulations of compaction and their effects on the phosphorylation of uvomorulin.

Compaction of the eight-cell stage mouse embryo is a critical event in the generation of different cell types within the preimplantation embryo. Uvomorulin, a member of the cadherin family of cell adhesion molecules, is important during compaction and its phosphorylation increases early in the eight-cell stage, suggesting that this posttranslational modification may be important for compaction to proceed. We have assessed the importance of the phosphorylation of uvomorulin during compaction by preventing, reversing, or inducing adhesion prematurely. The only condition that affected the overall level of uvomorulin phosphorylation was the prevention of compaction through prolonged exposure of four-cell embryos to low Ca2+. This treatment reduced the level of uvomorulin phosphorylation in eight-cell embryos, and perturbed its localization to regions of cell-cell contact. Thus, whilst the phosphorylation of uvomorulin does not appear to regulate directly uvomorulin's adhesive function, it may be associated with the redistribution of uvomorulin during compaction.

Actins↗