Biomedical subjects

C Thomas

Publications and source records attributed to C Thomas.

At least 73 records · Page 4Linked to original sources

PubMed2002

Informal carers in cancer contexts.

This paper considers some of the challenges involved in studying informal carers in cancer contexts. It reviews current knowledge by examining, first, the dominant psycho-oncological research tradition that focuses on psychological distress among carers and, second, the more recent sociologically informed body of work examining what carers actually do and the contribution that they make to patient care. The authors suggest that this second sociologically informed approach offers an important counter-weight to the psycho-oncological perspective. The developing research agenda for a sociology of cancer caring is briefly outlined.

Caregivers↗

PubMed2002

The need to know: informal carers and information.

There is a growing recognition that the carers of cancer patients require information. A key source of this information is the formal health care system that patients, and thus carers, encounter. However, the research literature suggests a lack of clarity on the part of service providers concerning the type, amount, timing and purpose of information for carers. This lack of clarity is reflected in the ways carers have been 'tacked on' to patients and thus are often treated as co-clients. That carers are also an active participants in the illness scenario is not always fully recognized, resulting in failure to provide appropriate information. Carers' interactions with health service providers are complex and context bound, and entail potential tensions of allegiance in the arena of information exchange. This article suggests that the following research and practice is required: a clearer understanding of the informational needs of carers in variable situations, specific ways to address these needs, where carers 'fit in' to the health care system, and how processes of information exchange with carers can be improved.

Access to Information↗

PubMed2002

Culturability, injury and morphological dynamics of thermophilic Campylobacter spp. within a laboratory-based aquatic model system.

AIMS: To study the survival processes of thermophilic Campylobacter spp. within a modelled aquatic system and particularly the involvement and survival potential of viable but non-culturable forms. METHODS AND RESULTS: The survival and morphological characteristics of populations of thermophilic Campylobacter species exposed to simulated aquatic conditions were examined using a combination of cultural and microscopic techniques. Populations underwent progressive decay when exposed to simulated aquatic conditions. The rates of population decay were observed to be significantly greater at the higher temperature (20 degrees C) with a rapid transition of the dominant sub-populations from non-stressed to dead cells occurred within 3 days. At 10 degrees C the rate of culturability loss was much reduced with substantial development (approx. 80% of total population) of viable but non-culturable (VBNC) populations by all species within 3 days, declining to represent approximately 5-25% of the total population at day 60. Significant differences (P < 0.001) were identified between decay rates as a consequence of different species, sub-populations and temperature but not between sub-populations of different species. Morphological variants including spiral, elongated spirals and rods, short rods and coccoid forms were identified. The endpoints of morphological transition were temperature-independent and isolate-specific yet the rate of morphological transition was directly related to temperature and approximately equivalent between species. CONCLUSION: The VBNC state is a transitory stage in the degeneration of Campylobacter population within the aquatic environments simulated during this study. SIGNIFICANCE AND IMPACT OF THE STUDY: VBNC cells form the most persistent, viable, potentially pathogenic sub-population of Campylobacter populations exposed to aquatic stress conditions.

Bacteriological Techniques↗

PubMed2002

Effects of vaginal distension on urethral anatomy and function.

OBJECTIVE: To determine the effect of repeated and prolonged vaginal distension on the leak-point pressure (LPP) and urethral anatomy in the female rat, as prolonged vaginal distension has been clinically correlated with signs of stress urinary incontinence (SUI). MATERIALS AND METHODS: Sixty female rats were placed into one of five groups; four groups underwent one of four vaginal distension protocols using a modified 10 F Foley catheter, i.e. prolonged (1 h), brief (0.5 h), intermittent (cycling inflated/deflated for 0.5 h) or sham distension. All animals had a suprapubic bladder catheter implanted 2 days after and were assessed urodynamically 4 days after vaginal distension. The fifth group of rats acted as controls and did not undergo vaginal distension, but did have a suprapubic bladder catheter placed and urodynamics assessed. To measure LPP the rats were anaesthetized with urethane, placed supine and the bladder filled with saline (5 mL/h) while bladder pressure was measured via the bladder catheter. LPPs were measured three times in each animal by manually increasing the abdominal pressure until leakage at the urethral meatus, when the external abdominal pressure was rapidly released. Peak bladder pressure was taken as the LPP and a mean value calculated for each animal. Immediately after measuring LPP the urethra was removed and processed routinely for histology (5 micro m sections, stained with haematoxylin/eosin and trichrome). The means (sem) were compared using a Kruskal-Wallis one-way anova on ranks, followed by a Dunn's test, with P < 0.05 indicating a significant difference. RESULTS: Both LPP and the external increase in abdominal pressure were significantly lower after prolonged distension, at 31.4 (1.7) and 19.8 (1.2) cmH2O, than in the sham group, at 41.1 (3.2) and 32.0 (4.7) cmH2O, respectively. There were no significant differences in LPP or in the increase in abdominal pressure between the brief, intermittent and sham groups. Qualitative histology showed that prolonged distension resulted in extensive disruption and marked thinning of urethral skeletal muscle fibres. Brief and intermittent distension showed mild and focal disruptions, respectively. CONCLUSIONS: As observed clinically, prolonged vaginal distension results in a lower LPP, greater anatomical injury and increased severity of SUI. These results suggest that ischaemia is important in the development of SUI after prolonged vaginal distension.

Animals↗

PubMed2002

Cancer and faith. Having faith--does it make a difference among patients and their informal carers?

This research considers the impact of having a religious faith on the cancer experience of patients and informal carers, focusing primarily on the association between faith and psychosocial needs. A questionnaire survey of 1000 patients in the north-west of England returned 402 completed questionnaires; around two-thirds of patients indicated they had an informal carer. Using logistic regression analysis, we examine the relationship between the importance of 48 needs and faith for 189 paired patients and carers, while controlling for the effect of eight socio-demographic and clinical variables. Patients with expressed faith identified fewer psychosocial needs than those without faith. In contrast, carers with expressed faith identified more needs than those without faith in relation to support from family and neighbours. Carers also needed more help with finding a sense of purpose and meaning, and help in dealing with unpredictability. Not surprisingly, both patients and carers with faith identified a greater need for opportunities for personal prayer, support from people of their own faith and support from a spiritual adviser. Various explanations of these differences between patients and carers are proposed. The crucial point is that one should not too readily assume that the cancer experience is shared in the same way by patients and carers. In understanding the faith dimension, one needs to consider both the spiritual and secular aspects of having a religious faith.

Adaptation, Psychological↗

PubMed2002

Dissipation of chlorpyrifos from tap, river and brackish waters in glass aquaria.

Persistence of Dursban 2E formulation of chlorpyrifos was studied in aerated and unaerated tap, river and brackish water, under laboratory conditions. Adsorption of residues onto a glass surface over 12-24 h was 12%. The half-lives of the residues in aerated and unaerated (data in parenthesis) tap, river and brackish waters were 23 and (403) h, 3.2 and (60) h, and 5.8 and 232 h, respectively. The kinetics of dissipation of residues from aerated and unaerated tap, river and brackish waters suggested a linear relationship for most of the data sets, and could not be ascribed to distinct first- or second-order models.

Chlorpyrifos↗

PubMed2002

[Computer-assisted development of epitheses after optical recording of facial defects].

A major drawback of conventional impression techniques used for customizing facial prostheses is the fact that pressure applied deforms soft tissue, thus reducing accuracy and causing patient discomfort. A possible solution is the use of optical 3-D coordinate measuring techniques, such as the fringe projection technique, which enables precise and contact-free recording of facial surfaces. The application of this method is demonstrated on a patient who lost his left eye and part of the jaw bone during surgery for cancer. 3-D CAD software that supports the construction of a facial prosthesis from the data obtained has been developed. For this purpose, spline functions are used to define border curves, and the intact half of the face is used as a model for the prosthetic surface. The resulting digital data are used to construct first a model made of synthetic resin, and then a final wax model with the aid of rapid prototyping techniques.

Computer-Aided Design↗

PubMed2002

Automated colorimetric screen for apyrase inhibitors.

Apyrases are enzymes that efficiently hydrolyze ATP and ADP and may operate both inside and outside the cell. Although apyrases are important to a variety of cellular mechanisms and uses in industry, there are no available apyrase-specific inhibitors. Colorimetric assays based on the Fiske-Subbarow method for measuring inorganic phosphate are able to detect the release of inorganic phosphate from ATP and other nucleotides. We found that this type of assay could be automated and used to screen for apyrase-inhibiting compounds by assaying for a reduction in released phosphate in the presence of potential inhibitors. The automation of this assay allowed for the successful screening of a commercially available compound library. Several low molecular weight compounds were identified that, when used at micromolar concentrations, effectively inhibited apyrase activity.

Apyrase↗

PubMed2001

In vivo and in vitro modulation of HLA-DM and HLA-DO is induced by B lymphocyte activation.

Ag presentation via HLA class II molecules in B lymphocytes depends on the coordinated action of HLA-DM, the catalyst of class II-peptide loading, and HLA-DO, a pH-dependent modulator of DM, the expression of which is almost completely restricted to B lymphocytes. The relative expression levels of both class II modulators are critical for the composition of the HLA class II peptide repertoire. The data in this work demonstrate that DO and DM expression are both dependent on the cellular activation status in primary human B lymphocytes. In vivo low-density activated primary human B lymphocytes show a prominent reduction in DO and DM expression when compared with high-density resting primary B lymphocytes. In vitro, reduction of DO and DM expression can be induced by B lymphocyte activation via the B cell receptor or by use of the phorbol ester, PMA. Specific inhibition of protein kinase C resulted in a significant reduction of HLA-DO and is potentially due to protein degradation in lysosomal compartments as the phenomenon is reversed by chloroquine. Thus, the expression of the dedicated HLA class II chaperone DM and its pH-dependent modulator DO is regulated and tightly controlled by the activation status of the B lymphocyte.

Antigens, Differentiation, B-Lymphocyte↗

PubMed2001

Mutations in the sterol-sensing domain of Patched suggest a role for vesicular trafficking in Smoothened regulation.

The tumor suppressor gene patched (ptc) encodes an approximately 140 kDa polytopic transmembrane protein [1-3] [corrected] that binds members of the Hedgehog (Hh) family of signaling proteins [4-6] [corrected] and regulates the activity of Smoothened (Smo), a G protein-coupled receptor-like protein essential for Hh signal transduction [7-9] [corrected]. Ptc contains a sterol-sensing domain (SSD) [10, 11] [corrected], a motif found in proteins implicated in the intracellular trafficking of cholesterol [12] [corrected], and/or other cargoes [13-15] [corrected]. Cholesterol plays a critical role in Hedgehog (Hh) signaling by facilitating the regulated secretion and sequestration of the Hh protein [16] [corrected], to which it is covalently coupled. In addition, cholesterol synthesis inhibitors block the ability of cells to respond to Hh [18, 19] [corrected], and this finding points to an additional requirement for the lipid in regulating downstream components of the Hh signaling pathway. Although the SSD of Ptc has been linked to both the sequestration of, and the cellular response to Hh [16, 20, 21] [corrected], definitive evidence for its function has so far been lacking. Here we describe the identification and characterization of two missense mutations in the SSD of Drosophila Ptc; strikingly, while both mutations abolish Smo repression, neither affects the ability of Ptc to interact with Hh. We speculate that Ptc may control Smo activity by regulating an intracellular trafficking process dependent upon the integrity of the SSD.

Amino Acid Sequence↗

PubMed2001

Conjugative metabolism of 1,2-dibromoethane in mitochondria: disruption of oxidative phosphorylation and alkylation of mitochondrial DNA.

1,2-Dibromoethane (DBE) is an environmental contaminant that is metabolized by glutathione S-transferases to a haloethane-glutathione conjugate. Since haloethane-glutathione conjugates are known to alkylate nuclear DNA and cytoplasmic proteins, these effects were investigated in isolated rat liver mitochondria exposed to DBE by measuring guanine adducts and several aspects of oxidative phosphorylation including respiratory control ratios, respiratory enzyme activity, and ATP levels. Mitochondrial large-amplitude swelling and glutathione status were assessed to evaluate mitochondrial membrane integrity and function. When exposed to DBE, mitochondria became uncoupled rapidly, yet no large-amplitude swelling or extramitochondrial glutathione was observed. Mitochondrial GSH was depleted to 2-53% of controls after a 60-min exposure to micromolar quantities of DBE; however, no extramitochondrial GSH or GSSG was detected. The depletion of mitochondrial glutathione corresponded to an increase of an intramitochondrial GSH-conjugate which, based on HPLC elution profiles and retention times, appeared to be S,S'-(1,2-ethanediyl)bis(glutathione). Activities of the NADH oxidase and succinate oxidase respiratory enzyme systems were inhibited 10-74% at micromolar levels of DBE, with succinate oxidase inactivation occurring at lower doses. ATP concentrations in DBE-exposed mitochondria in the presence of succinate were 5-90% lower than in the controls. The DNA adduct S-[2-(N(7)-guanyl)ethyl]glutathione was detected by HPLC in mtDNA isolated from DBE-exposed mitochondria. The results suggest that respiratory enzyme inhibition, glutathione depletion, decreased ATP levels, and DNA alkylation in DBE-exposed mitochondria occur via the formation of an S-(2-bromoethyl)glutathione conjugate, the precursor of the episulfonium ion alkylating species of DBE.

Adenosine Triphosphate↗

PubMed2001

Factors altering the sleep of burned children.

Although few studies have been conducted on burn patients, they indicate that sleep of burned children is altered. We suggest in this review, on the basis of the limited data available that factors contributing to sleep disruption in burned individuals may be broadly categorized as pathophysiological responses to the injury, the pain and discomfort experienced by the patient and medications used to treat these symptoms, and the physical environment in the Burns Intensive Care Unit. The responses to thermal injury include alterations in circulating neuropeptides, hormones, and immune-active substances, many of which are known to regulate/modulate sleep. Medications for the management of pain and for treating symptoms of various injury-induced stress and anxiety disorders may also alter sleep. Finally, frequent disruptions of the patient by medical staff is but one of the many environmental factors that may contribute to disrupted sleep. Severe burns induce a hypermetabolic response that may result in peripheral wasting, that depletes substrates necessary for tissue repair, and is associated with reduced growth hormone. Burn-induced growth hormone insufficiency is aggressively treated to counteract peripheral wasting and to aid in wound healing of skin graft donor sites. We speculate that improvement of sleep quality would result in a less severe reduction in growth hormone due to the well documented relationship between slow-wave sleep onset and growth hormone secretion. Such improvement in spontaneous growth hormone secretion patterns may aid in recovery by supporting tissue repair and by minimizing the hypermetabolic response to thermal injury. The experiments to test such hypotheses remain to be conducted, yet the results of such experiments may provide the basis for beginning to answer the question of whether or not sleep aids in recovery from injury.

Adolescent↗

PubMed2001

Sensitivity of human melanoma cells to adherent leukocytes depends on the ratio between them, the activation status of adherent leukocytes and the metastatic potential of tumor cells.

This study examined the interaction of the poorly metastatic human melanoma cell line M4Be and the highly metastatic clone 4 derived from M4Be, with respect to fresh adherent leukocytes (AL) isolated from 17 different healthy blood donors. These AL contained 80% (73%-93%) monocytes, 15% (6%-20%) B lymphocytes and 5% (1%-8%) T lymphocytes. The survival of these tumor cells against the stress exerted by these AL was estimated with a clonogenic assay where isolated tumor cells were co-cultured for 14 days in contact with AL and lipopolysaccharide (LPS). For a given blood donor, AL either stimulates or inhibits the colony formation of the tumor cells (T) depending on the AL/T ratio, the AL activation status and the metastatic potential of tumor cells. At low AL/T ratios (< 10/1) in the presence of low (8 ng/ml) and trace (8 pg/ml) levels of LPS, hydrogen peroxide (H2O2) release is significantly reduced, and tumor cells significantly increase their colony formation; the feeder effect of AL is suggested to be due to low concentrations of soluble tumor necrosis factor-alpha (TNF-alpha). At high AL/T ratios (> 10/1), whatever the characteristics of the blood donor, clone 4 is significantly more sensitive than M4Be to AL activated with medium containing low (8 ng/ml) or high (1,000 ng/ml) levels of LPS; this killing effect is suggested to be due to TNF-alpha, both soluble and membrane-bound, but not to be due to release of H2O2. These data suggest that the regulatory role of AL, which remove the majority of human melanoma cells and stimulate the colony formation of a small fraction of them, is partly due to TNF-alpha.

Adult↗

PubMed2001

Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells.

Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal DNA particles similar to double-minute chromosomes. The cells contained two other gene mutations that are associated with high-grade astrocytic tumors: extra-chromosomal amplification of the cyclin-dependent kinase-4 (CDK4) gene and a homozygous mutation within the PTEN tumor suppressor gene. Immunoblots revealed very high levels of EGFR, moderately increased expression of CDK4, and no detectable PTEN protein. The overexpressed SKMG-3 EGFRs responded to exogenous ligand and resembled normal rather than mutant receptors. A heterozygous mutation of the p53 gene (p53R282W) correlated with failure of radiation to induce the expression of cyclin-dependent kinase inhibitor p21waf1 or an early G1 cell cycle arrest. Although each of these gene mutations occurs in GBMs, SKMG-3 cells had an unusual genotype in that a p53 gene mutation co-existed with amplified EGFR genes. Nonetheless, the SKMG-3 cell line can be exploited as a model to study how oncogenic EGFR signals in GBM cells interact with over-expressed CDK4 and loss of PTEN to confer the malignant phenotype.

Blotting, Southern↗

PubMed2001

The significant unmet needs of cancer patients: probing psychosocial concerns.

'Significant unmet needs' are those needs that patients identify as both important and unsatisfied. In this article we ask whether the overall needs of cancer patients are actually being met. We believe that the range of unmet need, and the kinds of patients who are more likely to claim unmet need, should be carefully identified. The needs responses of a series of 295 cancer patients in a cross-sectional survey were analysed. The majority expressed the opinion that information and good relationships with health care professionals were important, and few expressed dissatisfaction with these aspects of need. Similarly, needs items about support from family and friends were largely rated as important and satisfied. For a sizeable minority of patients, items of significant unmet need cluster around aspects of managing daily life, emotions, and social identity. The distribution of significant unmet needs is not random but is more likely to be experienced by patients who are younger, have a long-standing illness or disability, do not own/have use of a car, and/or have no religious faith. Furthermore, significant unmet needs relate to patients' ability to talk freely to a carer about the cancer, the degree to which the cancer interferes with social activities, and whether financial difficulties are experienced. Most of the significant unmet need is beyond the remit of services primarily designed for the treatment of disease. We consider whether multidisciplinary cancer teams can be expected to deal with all aspects of the cancer experience.

Activities of Daily Living↗

PubMed2001

A study of occlusal variation in the primary dentition of Australian twins and singletons.

In this study, we quantified the extent of variation in different occlusal features of Australian children of European descent with complete primary dentitions, but no permanent teeth present in the mouth. The study group consisted of 412 individuals, aged between 3 and 7 years, including 70 monozygous (MZ) twin pairs, 68 same-sexed dizygous (DZ) twin pairs, 11 opposite-sexed DZ twin pairs, and 114 singletons. Occlusal traits, including inter-dental spacing, incisal overbite and overjet, arch breadth and arch depth, were obtained directly from dental casts or indirectly from photocopies or impressions of the casts. Descriptive statistics summarised the data and indicated that distributions were similar to those published for other populations. Univariate genetic analysis, using the structural equation modelling package Mx, was carried out on the quantitative data using the normal assumptions of the twin model. Genetic modelling indicated that a model incorporating additive genetic (A) and unique environmental variation (E) was the most parsimonious for interdental spacing, overbite, overjet and arch dimensions. Estimates of heritability for interdental spacing ranged from 0.62 to 0.81. Estimates for overbite and overjet were 0.53 and 0.28, respectively, and estimates for arch dimensions ranged from 0.69 to 0.89. These results indicated a moderate to relatively high genetic contribution to observed variation.

Australia↗

PubMed2001

Evidence that regenerating optic axons maintain long-term growth in the lizard Ctenophorus ornatus: growth-associated protein-43 and gefiltin expression.

In the lizard, Ctenophorus ornatus, the optic nerve regenerates but animals remain blind via the experimental eye, presumably as a result of axons failing to consolidate a retinotopic map in the optic tectum. Here we have examined immunohistochemically the expression of the growth-associated protein GAP-43 and the low-molecular-weight intermediate filament protein gefiltin, up to one year after optic nerve crush. Both proteins were found to be permanently up-regulated, suggesting that regenerating axons are held in a permanent state of re-growth. We speculate that, in the lizard, the continued expression of GAP-43 and the failure to switch from the expression of low- to high-molecular-weight intermediate filament proteins are associated with the inability to consolidate a retinotopic projection.

Animals↗

PubMed2001

Influence of gangliosides or LPS-like gangliosides on the tumoricidal activity of adherent leukocytes.

We previously showed that highly metastatic clones derived from the poorly metastatic human melanoma cell line M4Be are very radiosensitive provided that they are deficient in complex gangliosides. Here, we report that the highly metastatic clone 4 appears more sensitive to activated adherent leukocytes than M4Be via a transmembrane TNF-alpha-dependent mechanism. Adherent leukocytes (AL) were freshly isolated from different blood donors and were activated with Esherichia coli lipopolysaccharide (LPS). These AL contain 80% (73-93%) monocytes, 15% (6-20%) B lymphocytes and 5% (1-8%) T lymphocytes. The tumour cell survival following contact with AL was estimated with a clonogenic assay where isolated tumour cells were plated for 14 days with AL. We show on the one hand that either exogenous bovine brain GM1 gangliosides or Campylobacter jejuni LPS with GM1-like structure (LPS-like GM1) significantly decrease the hypersensitivity of clone 4 to AL. On the other hand, the cleaving with neuraminidase of more than 50% of the sialic residues bound to endogenous gangliosides in resistant M4Be cells significantly increases their sensitivity to AL. Thus, our highly metastatic cells appear both very sensitive to activated AL when they are deficient in complex gangliosides and resistant to AL when they are transiently exposed to exogenous gangliosides or LPS-like gangliosides. These in vitro data may reflect the paradoxidal behaviour of highly metastatic cells in vivo which appear both very sensitive to physiological stresses and able to survive to form secondary tumours.

Adult↗