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Biomedical subjects

K Conway

Publications and source records attributed to K Conway.

At least 19 recordsLinked to original sources

Harmonized French version of the Aging Males' Symptoms Scale.

Interest in clinical investigations about the health-related quality of life (HRQoL) of aging men has increased in recent years. The aim of this paper is to inform the scientific community about a harmonized French Aging Males' Symptoms (AMS) Scale. There were two slightly different French AMS Scales, which both underwent an up-to-date linguistic and cultural translation process, i.e. were valid to be applied in research. However, it was felt to be unfortunate that two versions of one language in one country existed. Therefore, an ad hoc committee of both translation teams were asked to develop a harmonized single French AMS Scale. The harmonization meeting developed a consensus item-by-item and the new French reference scale was agreed upon. It was agreed that only this scale should be published to avoid confusion among future users. The French AMS Scale published in this paper should be used for future research and necessary cultural/linguistic adaptations in the French-speaking world.

Aged↗

Sustained immunological effects of Glatiramer acetate in patients with multiple sclerosis treated for over 6 years.

The availability of a group of multiple sclerosis (MS) patients at the University of Maryland, who had participated in the pivotal Copaxone trial in the early 1990s, provided an opportunity to examine the long-term immunologic effects of Glatiramer acetate (GA) treatment in MS. Forty-eight GA-reactive T-cell lines (TCL) were generated from 10 MS patients who have been receiving GA treatment for 6-9 years. Proliferative responses, cytokine production, and cross-reactivity with myelin basic protein (MBP) and the MBP immunodominant peptide 83-99 were compared to responses obtained from 10 MS patients who were tested pretreatment and after a shorter period of treatment ranging from 1 to 10 months. The results indicate that while long-term treatment with GA results in a 2.9-fold decrease in the estimated precursor frequency of GA-reactive T-cells, the sustained response to GA remains Th2-biased and in part cross-reactive with MBP and MBP (83-99) as measured by proliferation and cytokine release assays. The results indicate that despite a drop in the precursor frequency of GA-reactive T-cells with long-term treatment, the sustained response remains predominantly Th2-biased and cross-reactive with MBP, which is consistent with the anti-inflammatory effects of the drug and bystander suppression.

Biomarkers↗

Altered response of a human squamous cell carcinoma cell line to 1, 25-dihydroxyvitamin D(3) after transfer of a normal chromosome 11.

Previous work in our laboratory using functional assays for tumorigenicity identified a tumor suppressor element on human chromosome 11q for the cutaneous squamous cell carcinoma cell line A388.6TG.c2. In this report, we screened a variety of agents for differential effects on A388.6TG.c2 compared to a growth-suppressed chromosome 11 microcell hybrid of A388.6TG.c2. One of the agents, 1, 25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3); calcitriol), exerted a growth-altering effect on A388.6TG.c2, which formed rounded cell clusters across the surface of the raft by Day 6 of treatment. In contrast, full-length chromosome 11 hybrids of A388.6TG.c2, as well as two other squamous cell carcinoma cell lines (FaDu and A431), when treated with 1,25(OH)(2)D(3), failed to demonstrate this cell-clumping phenotype. To pursue the hypothesis that the growth suppressor element is involved in altering the response to 1, 25(OH)(2)D(3), we tested microcell hybrids carrying t(X;11) chromosomes lacking large portions of 11q. Although these hybrids, like the parent A388.6TG.c2 cells, demonstrated extensive growth in organotypic cultures, they failed to form cell clusters with 1, 25(OH)(2)D(3) treatment. These results suggest that the chromosome 11 element that alters the response to 1,25(OH)(2)D(3) is distinct from the growth-suppressing element. An examination of differentiation marker expression revealed identical patterns of basal and suprabasal markers for A388.6TG.c2 and for a chromosome 11 hybrid with or without treatment with 1,25(OH)(2)D(3). Finally, characterization of candidate tumor suppressor gene PPP2R1B, which encodes for a subunit of protein phosphatase 2A (PP2A), showed seemingly insignificant alterations by cDNA sequence analysis. Collectively, the data suggest that human chromosome 11 contains two different tumor suppressor elements that may account for the two areas of loss of heterozygosity observed on the long arm of this chromosome.

Aged↗

[Evaluation of the quality of life of infants and very young children: validation of a questionnaire. Multicenter European study].

UNLABELLED: In the last few years, evaluating quality of life in children has become possible using specific instruments; nevertheless, there is still an unsolved issue concerning the earliest ages, when the child is not able to give his/her own opinion. QUALIN, a new instrument designed to assess an infant's quality of life (between the ages of three months and three years) was developed from the study of spontaneous criteria used by parents or caregivers (paediatricians or nurses) when they think about the quality of life of a baby (preliminary survey including 800 open-ended questionnaires). PATIENTS AND METHODS: One thousand four hundred and twelve children under the age of three were included in this validation study. QUALIN questionnaire is a 34-item scale and can be completed by parents or caregivers. Two forms are available: one form is designed for children under the age of one and the other is designed for children between the ages of one and three. The QUALIN questionnaire was translated into English, Italian and Spanish, and a European multicentric validation study was conducted in Belgium, France, Italy, Luxembourg, Spain and Switzerland. Data were collected with QUALIN questionnaires from children's parents and paediatricians. RESULTS: The psychometric properties of the scale are satisfactory (acceptability 90%, Cronbach's coefficient alpha over 0.75, correlations between two raters over 0.50, construct validity with principal component analysis showed emerging factors in agreement with the hypotheses linked to the questionnaire construction). The results are interesting, showing significant differences according to the health status of the children and their country of origin. CONCLUSION: The QUALIN questionnaire can be used for studies concerning the quality of life of children less than three years of age.

Child Welfare↗

Lack of association of rare alleles in the HRAS variable number of tandem repeats (VNTR) region with adult glioma.

HRAS rare alleles have been associated with the increased susceptibility to a variety of cancers. In the present study we examined the hypothesis that HRAS rare alleles are a risk factor for adult glioma in a population-based case-control study of adult glioma in six San Francisco Bay Area counties. We compared the prevalence of rare alleles in the variable number of tandem repeats region of HRAS in the germline DNA from 73 white adults who had gliomas with that of 65 controls. Overall, the prevalence of rare alleles in cases was not different from the prevalence of those in controls according to two definitions of rare alleles. We found that 25 of 73 (34%) of cases versus 25 of 65 (38%) of controls had at least one allele that was not 30, 46, 69, or 87 repeats; 4 of 73 (5%) of cases versus 6 of 65 (9%) of controls carried one or more alleles with 33, 39, 42, 53, 59, 63, 68, 105, or 114 repeats. The proportion of rare alleles was somewhat higher among subjects with anaplastic astrocytoma. Among women, cases were less likely than controls to have HRAS rare alleles, whereas among men, cases were slightly more likely to have HRAS rare alleles, but none of these results approach statistical significance. Our data do not suggest an excess of HRAS rare alleles among adult glioma cases.

Adult↗

Te Whanau Cadillac--a waka for change.

Community action research is an effective mechanism to improve the relationship between research and public health practice. The Alcohol and Public Health Research Unit (APHRU) and its Maöri research partner Whariki have developed practice in building partnerships with communities characterized by mutual respect of the different resources the partners bring to public health. A current APHRU/Whariki project focused on youth and drugs is a partnership with six communities in rural and urban areas throughout New Zealand, many predominantly Maöri. This project illustrates a model that aims to bridge the gap between research and practice, and to improve health and well-being through working with communities to increase their capacity to deal with alcohol and drug issues, and to introduce sustainable initiatives.

Adolescent↗

HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer.

PURPOSE: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. PATIENTS AND METHODS: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. RESULTS: Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio ¿OR = 2.2; 95% confidence interval ¿CI, 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P =.06, Fisher's exact test). CONCLUSION: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.

Adult↗

Couples' grief and experience of support in the aftermath of miscarriage.

The aim of this prospective study involving 39 women and 32 partners was to investigate the grief response of both the woman and her partner to miscarriage and to ascertain if support received was adequate and appropriate to their needs. Previous research shows that partners' grief can often be delayed and chronic. Special emphasis is placed on this area in this study. The miscarriage was found to be a significant event and the majority of women and partners still experienced feelings of loss up to 4 months afterwards, describing their reactions as sad or very sad. Scores on the first administration of the Perinatal Grief Scale showed that, in contrast with previous findings, partners scored significantly higher than the women on the three subscales and overall. Partners' scores on the second administration were also higher than those for the women but the difference was not significant. The women tended to receive and welcome social support more than the partners. Support received from health professionals was not always optimal, particularly for partners. Pregnancy subsequent to miscarriage was often viewed with some anxiety. It is argued that the results of the study have important implications for health practice.

Abortion, Spontaneous↗

Community action to reduce rural drink and drive crashes in New Zealand: adapting approaches in dynamic environments.

This paper discusses the evolution of a two-and-a-half year pilot community action project aimed at developing strategies to reduce alcohol-use-related crashes in a rural police district in New Zealand. Formative evaluation aimed to assist an intersectoral coordinating group identify and implement strategies. Initially the idea was to establish community-based committees to mobilize on drinking and driving around the district. However, it became clear that the original concept impeded action. The focus was changed to provide more support to strengthen existing initiatives, particularly those relating to police traffic enforcement and drinking environments. This helped give the project renewed life and direction. The paper focuses on process, organizational, and external community issues affecting the project and the use of formative evaluation to assist the project to respond and adapt to dynamic circumstances.

Accidents, Traffic↗

Risk of breast cancer according to the status of HER-2/neu oncogene amplification.

We examined risk factors for breast cancer after subdividing cases based on the presence of HER-2/neu oncogene amplification in their tumors. Data were from the Carolina Breast Cancer Study, a population-based, case-control study of 577 invasive breast cancer patients, diagnosed during 1993-1996 and ages 20-74 years, and 790 controls frequency-matched on race and age. Information on breast cancer risk factors was obtained from structured personal interviews. About 20% of paraffin-embedded tissues from the breast cancers of cases were identified as positive for HER-2/neu amplification (HER-2/neu+) by differential PCR. Early age at menarche, higher waist:hip ratio, and family history of breast or ovarian cancer were associated with elevated odds ratios (ORs) for both HER-2/neu+ and HER-2/neu- breast cancers. Breastfeeding for at least 1 year was inversely associated with HER-2/neu+ breast cancer [OR, 0.3; 95% confidence interval (CI), 0.1-0.7] more so than HER-2/neu- breast cancer (OR, 0.8; 95% CI, 0.5-1.2). Most of the remaining risk factors had ORs around 1.0 for both HER-2/neu+ and HER-2/neu- breast cancers, although a few exhibited possible associations with one disease subtype in analyses stratified by menopausal status. These study results suggest that most recognized breast cancer risk factors do not operate through HER-2/neu amplification in breast carcinogenesis. Differential effects of long-term breastfeeding by HER-2/neu amplification status have been observed in earlier studies and are provocative; however, the direction and magnitude of the associations have not been consistent.

Adult↗

P57 (KIP2) polymorphisms and breast cancer risk.

A previous report in this journal has suggested that germline deletions in the proline-alanine-rich (PAPA-repeat) region of P57 (KIP2) are associated with increased risk of a variety of cancers, including breast cancer. We have analyzed the association of P57 PAPA-repeat deletion polymorphisms and breast cancer risk as part of a population-based case-control study of breast cancer. We have not observed an association between the presence of one or two copies of deletion polymorphisms in P57 and breast cancer risk (adjusted odds ratio: 1.1, 95% confidence interval: 0.6-2.0). Further investigation is necessary to determine the functional significance of P57 deletion polymorphisms and their potential relationship with disease.

Breast Neoplasms↗

Chemical dehydration of specimens with 2,2-dimethoxypropane (DMP) for paraffin processing of animal tissues: practical and economic advantages over dehydration in ethanol.

Chemical dehydration can be accomplished using 2,2-dimethoxypropane (DMP). In the presence of an acid catalyst, this liquid reacts with water generating methanol and acetone as products. Although DMP is more expensive per milliliter than ethanol and other solvents used for dehydration, it is an economical alternative because a much smaller volume is needed. Slow penetration of DMP was previously thought to restrict its use to tiny specimens, but we now show that pieces of tissue as thick as 2 cm are dehydrated by overnight immersion in acidified DMP. We also show that dehydration in acidified DMP does not impair the staining of RNA or other basophilic components of animal tissues. The temperature and concentrations of methanol and H+ in the chemical dehydrating agent are too low to produce histochemically detectable methylation or nucleic acid extraction.

Animals↗

Localization and characterization of a chromosome 11 tumor suppressor gene using organotypic raft cultures.

The development and progression of human cancer often involves the inactivation of tumor suppressor gene function. Alterations in human chromosome 11 during the development of human cutaneous squamous cell carcinoma suggest the presence of a tumor suppressor gene on this chromosome. Moreover, previous studies in our laboratory demonstrated the presence of a functional tumor suppressor gene on chromosome 11 for the human cutaneous squamous cell carcinoma cell line A388.6TG.c2. In this investigation, we have used organotypic culturing of epithelial cells as a novel in vitro assay for tumor suppression. A388.6TG.c2 and control cells form an abnormal stratified epithelium of 8-12 layers when cultivated on organotypic rafts. In contrast, the chromosome 11 microcell hybrids, HMC 100p4B and HMC 100p5A, form an epithelium of only two to three cell layers. This in vitro growth suppression of the chromosome 11 microcell hybrids in the organotypic rafts correlates well with our previous in vivo skin graft experiments. Comparison of the proliferation and apoptotic indices of cell lines grown on the organotypic rafts suggests that the tumor suppressor gene on chromosome 11 has restricted the ability of the microcell hybrids to stratify but has not significantly altered their ability to undergo cell division or programmed cell death. Furthermore, flow cytometric analysis of cells grown on organotypic raft cultures suggests that the chromosome 11 microcell hybrids are actively progressing through the cell cycle rather than arrested in a particular stage. We have used this novel application of organotypic raft cultures to further localize the chromosome 11 tumor suppressor gene. Introduction of a single der(11)t(X;11) chromosome lacking most of the long arm of chromosome 11 into A388.6TG.c2 does not affect growth on organotypic raft cultures. These data suggest the tumor suppressor gene maps to the long arm of chromosome 11 in the region of 11q13-qter.

Aged↗

Alterations of the p16 gene in head and neck cancer: frequency and association with p53, PRAD-1 and HPV.

Alterations, especially homozygous deletions, of the putative tumor suppressor gene, p16 (p16INK4A, MTS1, CDKN2) have been found in tumor cell lines from a variety of neoplasms. Recent studies have reported frequent p16 gene deletions in cell lines from squamous cell carcinomas of the head and neck (SCCHN), although the prevalence of alterations was variable in primary tumors. This study determined the prevalence of point mutations and deletions of the p16 gene in 33 SCCHN. In addition, the association of p16 gene alterations and abnormalities of p53, PRAD-1 (cyclin D1), and the presence of human papillomavirus (HPV) was examined. We found an overall prevalence of p16 alterations of 36% (nine deletions, three single base substitutions, including one polymorphism). Seven tumors (of 29, 24%) had an alteration of p16 and p53; five (of 33, 15%) had alterations of p16 and PRAD-1; three (of 29, 10%) had alterations of all three genes. In addition, of the five tumors with human papillomavirus detected, only one also had a p16 gene alteration. The results indicate a potentially important role for the p16 gene in head and neck tumorigenesis. In addition, the presence of tumors with multiple somatic gene alterations suggest a possible interaction in the dysregulation of the cell cycle.

Adult↗

p53 mutations in head and neck cancer: new data and evaluation of mutational spectra.

It has been suggested that the frequency, type, and location of p53 mutations (mutational spectra) can be linked to specific exogenous and endogenous carcinogenic agents and processes. Squamous cell carcinoma of the head and neck (SCCHN) provides an excellent tumor model to evaluate the utility of the p53 mutational spectra, given that it has well-defined and strong risk factors (tobacco and alcohol). The purpose of this analysis was to establish the pattern of p53 mutations in SCCHN and evaluate this mutational spectrum in comparison to the spectra for other cancers with similar and different risk factors, including cancers of the esophagus, lung, and colon. p53 mutational data were obtained from head and neck tumors collected at the University of North Carolina Hospitals and the published literature. A total of 14 of 33 tumors from the University of North Carolina Hospitals (42%) were found to have a p53 mutation. The alterations included three transversions, seven transitions, two deletions, and two suspected codon 47 polymorphisms. In general, SCCHN and esophageal cancer share a similar mutational pattern in contrast to colon cancer. These two aerodigestive tract cancers were statistically different from lung cancer, despite sharing tobacco as a major risk factor. For example, G-->T transversions, a mutation type considered to be characteristic of exogenous DNA-damaging agents including tobacco smoke carcinogens, varied among tobacco-related cancer sites (14% SCCHN, 11% esophageal, and 31% lung) in contrast to colon cancer (6%). The comparison of mutational spectra for SCCHN and other cancers indicates that the effects of both tobacco and alcohol exposure may yield a pattern of p53 mutations that reflects elements of both exogenous and endogenous exposures.

Adult↗

Internal sequence variations in the Ha-ras variable number tandem repeat rare and common alleles identified by minisatellite variant repeat polymerase chain reaction.

In this report, we describe the sequence allelotyping of the Ha-ras variable number tandem repeat (VNTR) region using a minisatellite variant repeat (MVR)-PCR approach. This method permits the rapid identification of internal sequence variations among the VNTR alleles, exploiting the presence of two polymorphic sites within the 28-bp repeat subunits that give rise to four distinct repeat types. Using MVR-PCR, 20 to 25 repeats at the 5' end of the VNTR can be sequenced rapidly and reliably. MVR typing of the common alleles a1, a2, a3, and a4 shows that the first six repeats at the 5' end of each allele constitutes an invariant region. Beginning with repeat 7, characteristic "signature" MVR patterns emerge for each common allele. The a1 and a2 common alleles were found to consist of specific repeat types 1, 2, and 3, whereas a3 and a4 contain an additional repeat type 4 not present in the smaller alleles. MVR typing of rare-length alleles indicates that they are comprised of disorganized sequences, although they usually bear a resemblance to one of the common alleles at the 5'-most end. These results suggest that the rare alleles may be generated from recombination or gene conversion-type events involving the common progenitor alleles. MVR typing could, therefore, improve the ascertainment of rare Ha-ras alleles and may provide molecular insights into the genesis of cancer-associated alleles.

Alleles↗

Nursing the physically disabled in a general hospital ward.

Progress in medical treatment over the last three decades has meant that many more people survive either traumatic birth situations or diseases/injuries which would have previously resulted in death, and are leading normal lives with some form of physical disability. Until quite recently, little attention has been given to their longer-term health needs. The following article looks at the attitudes of nurses towards physically disabled patients, the experiences and attitudes of these patients, the interaction between nurse and patient, practical outcomes and future directions. Literature on this subject is not extensive. More empirical research is required focusing on the impact of admission of such people on general hospital ward functioning, the experiences/insights of nursing staff caring for them and the reaction and comments of physically disabled patients.

Attitude to Health↗