Search PubMed⌕ Search

Biomedical subjects

S Collins

Publications and source records attributed to S Collins.

At least 19 recordsLinked to original sources
PubMed2001

Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma.

BACKGROUND: Two-thirds of patients with squamous cell carcinomas of the head and neck (SCCHN) at diagnosis have advanced disease with projected 5-year survival rates of 30%. In those patients with distant metastatic or previously treated recurrent disease, response rate to the standard regimen of cisplatin and 5-fluorouracil is approximately 30%. The authors investigated the use of paclitaxel and carboplatin in a limited Phase II study in recurrent or metastatic SCCHN to evaluate tumor response, time to progression, survival, and toxicities of this regimen. METHODS: Patients with recurrent or metastatic SCCHN not amenable to further surgical or radiation therapy were treated with 200 mg/m(2) by 3-hour infusion of paclitaxel followed by carboplatin at an area under the concentration time curve of 6 mg/mL/minute via a 20-30-minute infusion every 3 weeks. RESULTS: Thirty-seven patients were enrolled. Ninety-five percent of patients had received prior surgery and postoperative radiotherapy. The overall response rate was 27% (95% confidence interval, 13-41%) with 1 complete and 9 PRs. Median survival of all patients was 4.9 months, and 1-year survival rate was 16%. There was a 43% response rate and 15.7-month median survival rate in patients with only distant metastatic disease and 38% response rate and a 4.5-month median survival in patients with locoregional and metastatic disease. The response rate for patients with only locoregional recurrence was 7% with a median survival of 4.8 months. Grade 3-4 myelotoxicity occurred in 24% of cycles administered. There were two treatment-related deaths due to neutropenic fever and one additional death on study may have been caused by treatment-induced thrombocytopenia. CONCLUSIONS: The combination of paclitaxel and carboplatin is significantly myelotoxic and ineffective in patients with previously treated locoregionally recurrent SCCHN, whereas it deserves further evaluation in those patients with distant metastatic disease alone. In those patients with locoregional disease, other more innovative treatments are needed.

Adult↗
PubMed2001

Are differences in stage at presentation a credible explanation for reported differences in the survival of patients with colorectal cancer in Europe?

Popular reporting of a comparison of cancer survival rates across 17 European countries, based on data collected by national and regional cancer registries, has left an impression of inadequate treatment of patients in the UK. A subsequent study has suggested that the poor survival rates reported for the UK can, in large part, be explained by more advanced stage at presentation. We believe this conclusion to be unsound and use this study as an example to illustrate the methodological difficulties which may arise during such international comparisons. As the NHS cancer plan aspires to achieve for the UK parity with the best cancer care in Europe, careful thought needs to be given to identifying countries with which the UK can usefully compare itself and the most appropriate indicators for this comparison.

Adenocarcinoma↗
PubMed2001

Changing the way we address severe malnutrition during famine.

This year, yet again, saw widespread food insecurity and famine across the horn of Africa. Again, humanitarian agencies set up operations to implement various relief programmes. Nutritional interventions included general ration distribution to the whole of an affected population; blanket supplementary feeding to all members of an identified risk group; and targeted dry supplementary feeding centres for moderately malnourished and therapeutic feeding centres for the severely malnourished. As is usual in emergencies, many of the therapeutic feeding centres were hard to set up and did not achieve an adequate coverage of all the severely malnourished. This combination of delays and low coverage meant that many therapeutic feeding centres achieved little overall impact on mortality. I believe that the present focus on therapeutic feeding centres as the sole mode of treating severely malnourished people during famine is inappropriate and often counter-productive. A new concept of community-based therapeutic care is necessary to complement therapeutic feeding centres' interventions if famine relief programmes are to address the plight of the severely malnourished in an efficient and effective manner. During an emergency, the community-based therapeutic care approach could quickly provide good coverage and appropriate treatment for large numbers of severely malnourished people. The principles behind community-based therapeutic care are, however, developmental, empowering communities to cope more effectively with crisis and with transition back to normality. This is very different to the therapeutic feeding centres' approach that disempowers communities, requires very large amounts of external staff and resources, and undermines the infrastructure. Although emergency community-based therapeutic care programmes could be large-scale and implemented quickly, they could also evolve into developmental Hearth model nutritional programmes without changing their conceptual basis. Conversely, Hearth programmes, although largely sustainable, could in times of crisis quickly scale-up into rapid effective emergency interventions. Creating such a continuum between emergency and developmental approaches has long been a holy grail of humanitarianism.

Africa↗
PubMed2001

Ecological forecasts: an emerging imperative.

Planning and decision-making can be improved by access to reliable forecasts of ecosystem state, ecosystem services, and natural capital. Availability of new data sets, together with progress in computation and statistics, will increase our ability to forecast ecosystem change. An agenda that would lead toward a capacity to produce, evaluate, and communicate forecasts of critical ecosystem services requires a process that engages scientists and decision-makers. Interdisciplinary linkages are necessary because of the climate and societal controls on ecosystems, the feedbacks involving social change, and the decision-making relevance of forecasts.

Agriculture↗
PubMed2001

Natural history of cervical human papillomavirus infection in young women: a longitudinal cohort study.

BACKGROUND: Laboratory and epidemiological research suggests an association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN). We studied the natural history of incident cervical HPV infection and its relation to the development of CIN. METHODS: We recruited 2011 women aged 15-19 years who had recently become sexually active. We took a cervical smear every 6 months and stored samples for virological analysis. We immediately referred all women with any cytological abnormality for colposcopic assessment, but postponed treatment until there was histological evidence of progression to high-grade CIN. FINDINGS: In 1075 women who were cytologically normal and HPV negative at recruitment, the cumulative risk at 3 years of any HPV infection was 44% (95% CI 40-48): HPV 16 was the most common type. The cumulative risk at 3 years of detecting an HPV type not present in the first positive sample was 26% (20-32). 246 women had an abnormal smear during follow-up, of whom 28 progressed to high-grade CIN. The risk of high-grade CIN was greatest in women who tested positive for HPV 16 (risk ratio 8.5 [3.7-19.2]); this risk was maximum 6-12 months after first detection of HPV 16. All HPV types under consideration were associated with cytologically abnormal smears. Although abnormality was significantly less likely to be associated with low-viral-load samples, the cumulative risk at 3 years of a high-viral-load sample after a low-viral-load sample was 45% (95% CI 35-56). Five women who progressed to high-grade CIN consistently tested negative for HPV. INTERPRETATION: Our findings suggest that attempts to exploit the association between cervical neoplasia and HPV infection to improve effectiveness of cervical screening programmes might be undermined by the limited inferences that can be drawn from the characterisation of a woman's HPV status at a single point in time, and the short lead time gained by its detection.

Adolescent↗
PubMed2001

beta-Adrenergic activation of p38 MAP kinase in adipocytes: cAMP induction of the uncoupling protein 1 (UCP1) gene requires p38 MAP kinase.

Because of increasing evidence that G protein-coupled receptors activate multiple signaling pathways, it becomes important to determine the coordination of these pathways and their physiological significance. Here we show that the beta(3)-adrenergic receptor (beta(3)AR) stimulates p38 mitogen-activated protein kinase (p38 MAPK) via PKA in adipocytes and that cAMP-dependent transcription of the mitochondrial uncoupling protein 1 (UCP1) promoter by beta(3)AR requires p38 MAPK. The selective beta(3)AR agonist CL316,243 (CL) stimulates phosphorylation of MAP kinase kinase 3/6 and p38 MAPK in a time- and dose-dependent manner in both white and brown adipocytes. Isoproterenol and forskolin mimicked the effect of CL on p38 MAPK. In all cases activation was blocked by the specific p38 MAPK inhibitor SB202190 (SB; 1-10 microm). The involvement of PKA in beta(3)AR-dependent p38 MAPK activation was confirmed by the ability of the PKA inhibitors H89 (20 microm) and (R(p))-cAMP-S (1 mm) to block phosphorylation of p38 MAPK. Treatment of primary brown adipocytes with CL or forskolin induced the expression of UCP1 mRNA levels (6.8- +/- 0.8-fold), and this response was eliminated by PKA inhibitors and SB202190. A similar stimulation of a 3.7-kilobase UCP1 promoter by CL and forskolin was also completely inhibited by PKA inhibitors and SB202190, indicating that these effects on UCP1 expression are transcriptional. Moreover, the PKA-dependent transactivation of the UCP1 promoter, as well as its sensitivity to SB202190, was fully reproduced by a 220-nucleotide enhancer element from the UCP1 gene. We similarly observed that increased phosphorylation of ATF-2 by CL was sensitive to both H89 and SB202190, while phosphorylation of cAMP-response element-binding protein was inhibited only by H89. Together, these studies illustrate that p38 MAPK is an important downstream target of the beta-adrenergic/cAMP/PKA signaling pathway in adipocytes, and one of the functional consequences of this cascade is stimulation of UCP1 gene expression in brown adipocytes.

Adipocytes↗
PubMed2001

Electrophoresis separation in open microchannels. A method for coupling electrophoresis with MALDI-MS.

The separation of biological mixtures in open micro-channels using electrophoresis with rapid and simple coupling to mass spectrometry is introduced. Rapid open-access channel electrophoresis employs microchannels that are manufactured on microchips. Separation is performed in the open channels, and the chips are transferred to a matrix-assisted laser desorption/ionization (MALDI) source after the solvent is evaporated. The matrix (2,5-dihydroxybenzoic acid) is placed in the solution with the run buffer before the separation of the analyte components. After separation, the solvent is evaporated and the microchip is ready for MALDI-MS analysis. The microchip is placed directly into a specially designed ion source of an external source Fourier transform mass spectrometry instrument. Separation of simple mixtures containing oligosaccharides and peptides is shown.

Animals↗
PubMed2001

Integration of cytogenetic landmarks into the draft sequence of the human genome.

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.

Chromosome Aberrations↗
PubMed2001

Transcriptional regulation of the mouse uncoupling protein-2 gene. Double E-box motif is required for peroxisome proliferator-activated receptor-gamma-dependent activation.

Uncoupling protein-2 (UCP2) is present in many tissues with relevance to fuel metabolism, and its expression is increased in fat and muscle in response to elevated circulating free fatty acids resulting from fasting and high fat feeding. We proposed a role for peroxisome proliferator-activated receptor-gamma (PPARgamma) as a mediator of these physiological changes in UCP2, because thiazolidinediones also increase expression of UCP2 in these cell types (). To determine the molecular basis for this regulation, we isolated the 7.3-kilobase promoter region of the mouse UCP2 gene. The -7.3-kilobase/+12-base pair fragment activates transcription of a reporter gene by 50-100-fold. Deletion and point mutation analysis, coupled with gel shift assays, indicate the presence of a 43-base pair enhancer (-86/-44) that is responsible for the majority of both basal and PPARgamma-dependent transcriptional activity. The distal (-86/-76) part of the enhancer specifically binds Sp1, Sp2, and Sp3 and is indistinguishable from a consensus Sp1 element in competition experiments. Point mutation in this sequence reduces basal activity by 75%. A second region (-74/-66) is identical to the sterol response element consensus and specifically binds ADD1/SREBP1. However, deletion of this sequence does not affect basal transcriptional activity or the response to PPARgamma. The proximal portion of the enhancer contains a direct repeat of two E-Box motifs, which contributes most strongly to basal and PPARgamma-dependent transcription of the UCP2 promoter. Deletion of this region results in a 10-20-fold reduction of transcriptional activity and complete loss of PPARgamma responsiveness. Point mutations in either E-Box, but not in the spacer region between them, eliminate the stimulatory response to PPARgamma. However, gel shift assays show that PPARgamma does not bind to this region. Taken together, these data indicate that PPARgamma activates the UCP2 gene indirectly by altering the activity or expression of other transcription factors that bind to the UCP2 promoter.

Animals↗
PubMed2001

CCAAT/enhancer-binding protein alpha is required for transcription of the beta 3-adrenergic receptor gene during adipogenesis.

The beta(3)-adrenergic receptor (beta(3)AR) is expressed predominantly in adipocytes, and it plays a major role in regulating lipolysis and adaptive thermogenesis. Its expression in a variety of adipocyte cell models is preceded by the appearance of CCAAT/enhancer-binding protein alpha (C/EBP alpha), which has been shown to regulate a number of other adipocyte-specific genes. Importantly, it has been demonstrated that several adipocyte cell lines that fail to express C/EBP alpha exhibit reduced insulin sensitivity, despite an apparent adipogenic phenotype. Here we show that transcription and function of the beta(3)AR correlates with C/EBP alpha expression in these adipocyte models. A 5.13-kilobase pair fragment of the mouse beta(3)AR promoter was isolated and sequenced. This fragment conferred a 50-fold increase in luciferase reporter gene expression in adipocytes. Two putative C/EBP binding sites exist at -3306 to -3298 and at -1462 to -1454, but only the more distal site is functional. Oligonucleotides corresponding to both the wild-type and mutated -3306 element were inserted upstream of a thymidine kinase luciferase construct. When cotransfected in fibroblasts with a C/EBP alpha expression vector, reporter gene expression increased 3-fold only in the wild-type constructs. The same mutation, when placed into the intact 5.13-kilobase pair promoter, reduced promoter activity in adipocytes from 50-fold to <10-fold. Electrophoretic mobility shift analysis demonstrated that the site at -3306 generated a specific protein-oligonucleotide complex that was supershifted by C/EBP alpha antibody, while a probe corresponding to a putative site at -1462 did not. These results define C/EBP alpha as a key transcriptional regulator of the mouse beta(3)AR gene during adipogenesis.

3T3 Cells↗
PubMed2001

Ammonia uptake and its effects on ionoregulation in the freshwater crayfish Pacifastacus leniusculus (Dana).

Exposure of adult crayfish Pacifastacus leniusculus to Artificial Freshwater (AFW) media containing 1.5 m and 0.15 mmol x l(-1) total ammonia [Tamm; 0.1 x acute lethal concentration (24 h LC50) and 0.01 x 24 h LC50] and adjusted to pH 6.5, pH 8.2 and pH 10.5 resulted in significant increases in haemolymph ammonia over a 24-h period. Ammonia accumulated most rapidly at pH 10.5. These media were chosen to expose animals to a range of different un-ionised ammonia (UIA) [NH3] and ionised ammonia [NH4+] concentrations. From comparisons of measured transepithelial potential differences (PDte) with calculated Nernst potentials (PDNH4+) for the known haemolymph-to-medium gradients of [NH4+], it was deduced that, in pH 8.2 and pH 6.5 AFW, NH4+ was not in thermodynamic equilibrium across the integument (presumably gill epithelium). In pH 10.5 AFW with 1.5 mmol x l(-1) Tamm (predominantly NH3), the accumulation of ammonia in the haemolymph was in the NH4+ form due to haemolymph pH regulation by the crayfish in this alkaline external medium. Measured net fluxes of ammonia (Jamm(net)) were inwardly directed and maximal when [NH3] was the main component externally, but were also significant at pH 8.2 with high [NH4+] ([NH4+]:[NH3] approximately 20:1). Haemolymph Na+ depletion was significant and, over the 24-h exposure period, most rapid in high [NH3] medium but [Cl-] was unaffected. However, paradoxically, sodium uptake (measured JNa(in) on immediate transfer to high Tamm medium) was not significantly inhibited when [NH3] was the predominant ammonia species. In 1.5 mmol x l(-1) Tamm (mainly [NH4+), VNa(in) (the active component of JNa(in)) was significantly inhibited, particularly at low external [Na+]. This inhibition could not be demonstrated as one of competition at an Na+/NH4+ apical gill exchange site. The resultant net efflux of sodium from the animal showed that the ability of the animals to balance sodium losses at low external [Na+] was severely affected. Longer exposure to pH 10.5 AFW with high [NH3] (12 h) resulted in significantly increased JNa(out), while not significantly affecting JNa(in). Analysis of urinary Na+ losses showed that, while urinary flow rate and water reabsorption was most likely unaffected by ammonia exposure, final urine [Na+] was significantly elevated. The resulting urinary Na+ loss accounted for 63% of the increased JNa(out) in high [NH3] medium.

Ammonia↗
PubMed2001

Can models of post-traumatic stress disorder contribute to the application of cognitive therapy by nurse therapists when dealing with individuals affected by the Omagh bombing? An overview.

As mental health professionals practising in an evolving multidisciplinary trauma and recovery team in Omagh, Northern Ireland, the by now infamous Omagh bombing of 15 August 1998 brought abruptly to attention the potential for adverse psychological consequences resulting from exposure to such trauma. As nurse therapists, this event provoked interest in the entity of post-traumatic stress disorder (PTSD) as being one of the possible negative psychological consequences, and the relevance and application of cognitive theory and practice in its treatment. Whilst recognizing that there is no single cognitive theory or model of anxiety disorder, this paper focuses on the approach of Beck and allied approaches when referring to cognitive theory and practice. It is intended to proffer a broad overview of areas the authors consider relevant in order to develop an appreciation of the entity of PTSD, and its evolution, having given a synopsis of the event that provoked interest. Finally, acknowledgement and a brief explication of some of the theoretical models of PTSD to date will be made, and the relevance and application of cognitive theory and principals in the treatment of the disorder will be considered.

Cognitive Behavioral Therapy↗
PubMed2001

Conversation analysis: a method for research into interactions between patients and health-care professionals.

BACKGROUND: It is clear that much of the success of health-care provision depends on the quality of interactions between health professionals and patients. For instance, it is widely recognized that patients are more likely to take medication effectively if they have been involved in discussions about treatment options, and understand and support the decision about what is prescribed (patient concordance). Hence, patient participation is important for the success of medical outcomes. The key is to explore how communicative choices made by health professionals impact on the quality of interactions in general, and of patient participation in particular. However, to date there has not been an appropriate method for investigating this connection or impact. OBJECTIVE: To outline the perspective and method of Conversation Analysis (CA). Developed within sociology and linguistics, CA offers a rigorous method (applicable to large data sets) to the study of interaction in health settings. STRATEGY: The method of CA is illustrated through a review of CA studies of doctor-patient interactions. Two such studies, one from the US and the other from Finland, are reviewed, in order to show how CA can be applied to identifying both forms of patient participation, and the interactional conditions which provide opportunities for patient participation. These studies focus principally on the medical examination and diagnostic stages of the consultation. Further research will examine the forms and conditions of patient participation in decision-making.

Communication↗
PubMed2001

Gerstmann-Sträussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies.

Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and kuru constitute major human prion disease phenotypes. Each has been successfully transmitted in animal models and all are invariably fatal neurodegenerative disorders, with the brains of affected individuals harbouring variable amounts of an abnormal, protease-resistant form of the prion protein (PrPres), which is inextricably linked to pathogenesis and transmissibility. Classical sporadic CJD is the most common human transmissible spongiform encephalopathy (TSE), but recently the variant form (vCJD), first described in the UK in 1996, has drawn considerable attention. In contrast to sporadic CJD, FFI and GSS are almost invariably genetically determined TSEs, caused by a range of mutations within the open reading frame of the prion protein gene (PRNP) on chromosome 20. By definition, the nosologic term FFI is reserved for patients manifesting prominent insomnia, generally in combination with dysautonomia, myoclonus, and eventual dementia, with the predominant pathologic changes lying within the thalami and a specific underlying mutation in PRNP. GSS, however, encompasses a more diverse clinical spectrum ranging from progressive cerebellar ataxia or spastic paraparesis (both usually in combination with dementia), to isolated cognitive impairment resembling Alzheimer's disease. Additional extra-pyramidal features, which may respond to dopaminergic therapy can also be seen. Neuropathological findings are also relatively diverse, partly overlapping with those found in Alzheimer's disease, especially the presence of neurofibrillary tangles (NFTs). Although GSS and FFI in their classical forms are differentiable clinical profiles, such divisions may have no intrinsic biological validity given the considerable intra-familial clinico-pathological diversity so commonly seen. Kuru constitutes a horizontally transmitted prion disease, which after a lengthy incubation period, presents clinically as a progressive cerebellar ataxia associated with tremors. It has now almost disappeared since the cessation of ritualistic endocannibalism in the late 1950s but was previously exclusively endemic amongst the Fore linguistic group and neighbouring tribes in the Eastern Highlands of New Guinea. Uniform topographical central nervous system histopathology includes spongiform change and neuronal loss, with amyloid (kuru) plaques in approximately 75% of cases.

Gerstmann-Straussler-Scheinker Disease↗
PubMed2001

Paenibacillus macerans pseudobacteremia resulting from contaminated blood culture bottles in a neonatal intensive care unit.

Paenibacillus species are gram-positive, rod-shaped, spore-forming aerobes that are abundant in nature and closely related to Bacillus. Between June 24 and June 30, 1999, 8 neonates in our neonatal intensive care unit had positive blood cultures for Paenibacillus macerans. This cluster of positive blood cultures with an unusual pathogen suggested a pseudoepidemic. Investigation revealed that the most likely etiology of the pseudobacteremia was environmental contamination of the rubber stoppers in blood culture bottles. This was confirmed by environmental sampling and simulated inoculation studies. This pseudobacteremia outbreak highlights the importance of adhering to well-established methods for blood culture collection and ongoing infection control surveillance.

Bacillaceae Infections↗