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Biomedical subjects

C Knowles

Publications and source records attributed to C Knowles.

At least 19 recordsLinked to original sources
PubMed2002

Accuracy of set-up of thoracic radiotherapy: prospective analysis of 24 patients treated with radiotherapy for lung cancer.

In thoracic radiotherapy, a number of factors hinder the use of portal films and electronic portal imaging devices for measuring field placement errors (FPEs). The aim of this study was to assess the accuracy of treatment set-up using simulator check films (SCFs) in radiotherapy for lung cancer. Prospective evaluation was performed on 24 patients. During their radiotherapy, patients returned to the simulator weekly for a minimum of four SCFs, for which the parameters from the original simulator planning film were set, positioning being achieved without fluoroscopy. A total of 96 SCFs were taken. FPEs in left-right (L-R) and superior-inferior (S-I) direction, as well as coronal rotational errors, were measured. The mean absolute FPE was 0.35 cm in the L-R axis and 0.43 cm in the S-I axis. Statistically, the FPEs in the S-I direction were greater than those in the L-R direction (p<0.001). A margin of 0.93 cm between the clinical target volume and the planning target volume would cover 95% of FPEs in the L-R direction, whilst a margin of 1.13 cm is needed for this degree of certainty in the S-I direction. Mean coronal rotational error was 1.6 degrees. Systematic errors were greater than random errors. This study demonstrated that the FPEs were within clinical tolerance (< or = 0.7 cm) in 84.9% of the measurements. The planning margins used in our clinical practice compare favourably with the FPEs in this study.

Adult↗
PubMed2001

Vanilloid receptor 1 immunoreactivity in inflamed human bowel.

Vanilloid receptor 1 (VR1) is expressed by sensory neurons. Once activated, these neurons evoke the sensation of burning pain and release neuropeptides that induce neurogenic inflammation. We used immunoblotting and immunostaining to estimate the density of VR1 in colonic tissues of patients with inflammatory bowel disease and of controls. Our study results indicate that VR1 immunoreactivity is greatly increased in colonic nerve fibres of patients with active inflammatory bowel disease. Thus, the discovery of new drugs that can bind the VR1 receptor, or antagonise endogenous inflammatory substances that activate this receptor, could lead to new therapies for pain and dysmotility.

Humans↗
PubMed2001

Increased acid-sensing ion channel ASIC-3 in inflamed human intestine.

OBJECTIVES: Acid-sensing ion channels (ASICs) are expressed by rat sensory neurons and may mediate pain associated with tissue acidosis after inflammation or injury. Our aim was to examine the molecular forms and localization of ASICs in human intestine and dorsal root ganglia using immunochemical techniques, and to measure the effects of inflammation and injury. DESIGN AND METHODS: Inflamed Crohn's disease intestine and injured human dorsal root ganglia, with appropriate controls, were studied by Western blotting and immunohistochemistry, using specific affinity-purified ASIC antibodies. RESULTS: In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers. There was a corresponding trend for an increased immunoreactive density and increased number of ASIC-3-positive neurons in the myenteric and sub-mucous plexus of inflamed intestine. In dorsal root ganglia, immunoreactivity for all ASICs was restricted to a sub-population (about 50%) of small-diameter (nociceptor) sensory neurons, and was generally less intense after injury. CONCLUSIONS: Increased ASIC-3 in inflamed intestine suggests a role in pain or dysmotility, for which ASICs represent new therapeutic targets.

Acid Sensing Ion Channels↗
PubMed2001

A randomised controlled trial of the effectiveness of combining video role play with traditional methods of delivering undergraduate medical education.

OBJECTIVE: To determine the effectiveness of video role play with structured feedback in improving undergraduate communication skills and application of knowledge in genitourinary medicine. DESIGN: A blind, randomised, controlled trial. SUBJECTS AND SETTING: Fourth year undergraduates attending a 5 week attachment in genitourinary medicine during 1997 at a London medical school. INTERVENTION: A randomly selected sample group of undergraduates were filmed in the role of a doctor interviewing a patient (played by an actor) presenting with a genitourinary (GU) problem. Structured feedback by a GU physician and an educational psychologist was given a week later. The control group of undergraduates did not receive this training intervention. OUTCOME MEASURES: Student performance in two stations of an objective structured clinical examination (OSCE), administered at the end of their attachment. This tested communication skills and knowledge in GU settings. RESULTS: 132 undergraduates were assessed in the OSCE. 40 of these were in the sample group who received training using video role play with feedback and 92 were in the control group. The sample group scored significantly higher marks than the control group (p<0.001). CONCLUSIONS: Video role play with structured feedback is effective in improving undergraduate communication skills and application of knowledge in GU medicine settings.

Education, Medical, Undergraduate↗
PubMed2001

Abnormal platelet function and calcium handling in Dahl salt-hypertensive rats.

The effect of dietary salt on platelet function and Ca(2+) homeostasis was studied in Dahl (DS) rats, a genetic model of salt-sensitive hypertension. DS rats were fed a high-salt (DSHS) or a low-salt diet (DSLS) for up to 4 weeks, and the effects of salt loading on systolic blood pressure, platelet P-selectin expression, and platelet Ca(2+) homeostasis were measured. The high-salt diet increased blood pressure and markedly increased the amount of ionomycin (IM)-releasable Ca(2+) in platelet intracellular stores (Ca(2+)/IM). The alteration in Ca(2+) stores was not prevented when the hypertension was prevented by treatment with hydralazine and reserpine. The Ca(2+) store filling during platelet exposure to 1 mmol/L Ca(2+) for 5 minutes and the rate of sarcoplasmic/endoplasmic Ca(2+) ATPase-dependent Ca(45) uptake were higher in DSHS compared with that in DSLS. There was a decrease in thrombin-induced Ca(2+) influx in platelets from DSHS; consistent with this, agonist-induced P-selectin expression was decreased. In DSLS, nitric oxide accelerated reloading of platelet Ca(2+) stores after their emptying by thrombin but failed to do so in DSHS. These results indicate that in DS rats, a high-salt diet increases sarcoplasmic/endoplasmic Ca(2+) ATPase activity and the Ca(2+)/IM but decreases the reuptake of Ca(2+) caused by nitric oxide. Decreases in Ca(2+) influx and platelet P-selectin expression might be explained by changes in intracellular Ca(2+) stores in DSHS rats, which apparently is a heritable response to a high-salt diet.

Analysis of Variance↗
PubMed2001

Variation in size and position of the planning target volume in the transverse plane owing to respiratory movement during radiotherapy to the lung.

Movement of thoracic tumours with respiration poses a real dilemma in terms of the accuracy of delivering radical radiotherapy in patients with carcinoma of the lung. Movements in the craniocaudal direction have previously been described. This technical note describes ten patients planned for radical lung radiotherapy using CT. The study assesses the maximum impact of respiration on the planning target volume in the transverse plane by comparing the planning CT appearances during quiet respiration with those during full inspiration and full expiration. The study demonstrated the potential impact of respiratory movement on the planning target volume and, hence, implications for local tumour control.

Humans↗
PubMed2000

Burger King, Dunkin Donuts and community mental health care.

This paper describes the patchwork of cottage industries and human warehousing composing Montréal's 'community mental health care' system. It examines the ways in which this system's clients assemble a collage of ad hoc facilities including homeless shelters, rooming houses, food banks and soup kitchens through which they pursue the fragmented task of daily survival. In their various forms of transit around the city, released psychiatric patients, who rotate in and out of the local psychiatric wards, construe the grammar of urban space. In examining their use of key city sites - malls, fast food outlets, churches and the streets - it becomes apparent that the 'mad' have a particular relationship to these places which they pass through and use on certain terms. Examining the nature of their journeys, the scenes on which they are set and the social relationships of space in play, it is evident that the 'mad' have a particular (dialogical) relationship to the city: a relationship which they share with other, multiply disenfranchised people. This raises significant social questions concerning the politics of city space, and the kinds of fragmented lives and forms of subjectivity that they produce.

Adolescent↗
PubMed1999

Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene.

Endothelial nitric oxide synthase (eNOS) has been identified in human platelets. Although platelet-derived nitric oxide (NO) has been shown to inhibit platelet recruitment in vitro, its role in the regulation of the hemostatic response in vivo has not been characterized. To define the role of platelet-derived NO in vivo, we studied mice that lacked a functional eNOS gene (NOSIII). Surface P-selectin expression in platelets from eNOS-deficient mice was not significantly altered; however, bleeding times were markedly decreased in eNOS-deficient versus wild-type mice (77.2+/-3 versus 133.4+/-3 seconds, P<0.00005). To determine the contribution of endothelium- versus platelet-derived NO to the bleeding time, isolated platelets from either eNOS-deficient or wild-type mice were transfused into a thrombocytopenic eNOS-deficient mouse and the bleeding time was measured. The bleeding times in mice transfused with eNOS-deficient platelets were significantly decreased compared with mice transfused with wild-type platelets (Deltableeding time, -24.6+/-9.1 and -3.4+/-5.3 seconds, respectively; P<0.04). Platelet recruitment was studied by measuring serotonin release from a second recruitable population of platelets that were added to stimulated platelets at the peak of NO production. There was 40.3+/-3.7% and 52. 0+/-2.1% serotonin release for platelets added to wild-type or eNOS-deficient platelets, respectively (P<0.05). In summary, mice that lacked eNOS had markedly decreased bleeding times even after endothelial NO production was controlled. These data suggest that the lack of platelet-derived NO alters in vivo hemostatic response by increasing platelet recruitment. Thus, these data support a role for platelet-derived NO production in the regulation of hemostasis.

Animals↗
PubMed1999

Cocaine effects on immunocompetent cells: an observation of in vitro cocaine exposure.

This study investigated in vitro effects of cocaine on the function of T and B lymphocytes, natural killer cells and macrophages in a mouse model. In mature C57BL/6J mice (60-90 day-old), splenocytes were cultured with cocaine at different concentrations ranging from 4 to 64 microg/ml for 24 h. The exposure to cocaine in vitro was found to affect (1) T cell function, with reduced responses to stimulation of Con-A, PHA and Interleukin 2, and decreased production of gamma-IFN; (2) B cell function, with reduced response to LPS; (3) natural killer cell function, with attenuated killing capacity; (4) monocyte-macrophage function, with decreased ability to inhibit the growth of tumor cells. The results of the study indicated a direct cocaine effect on four major immune competent cells, and the generally suppressive effects of in vitro cocaine exposure may be related to its in vivo action on the immune system.

Animals↗
PubMed1998

Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure.

This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.

Animals↗
PubMed1997

Selective autonomic and sensory deficits in slow transit constipation.

Chronic idiopathic constipation is likely to be a heterogeneous condition. Our previous studies on the stimulated sweating response suggested that autonomic dysfunction may be a cause in a subset of patients. Our aims were to test selectively the neural and sweat gland components of the sweat response and to test unmyelinated sensory fibres so as to determine whether a small fibre neuropathy is present. Twelve female patients with proven slow transit constipation and nineteen age-matched healthy volunteers took part in the study. The sensory tests included thermal thresholds and axon reflex vasodilatation in response to intradermal capsaicin, measured with a laser Doppler. Direct and axon reflex sweating was induced with intradermal methacholine and nicotine, respectively, and measured with an evaporimeter. Non-parametric tests were used for statistical comparison with a group of seven control subjects. Results are expressed as medians and range. All four patients who reported constipation from childhood had a selective deficit of unmyelinated afferent fibre function in the feet, with markedly elevated thresholds to warm sensation (controls 5.2; 4.3-10.6, patients 13.8; 11.8-16.1 delta T (degree C), P < 0.02) and heat pain (controls 10.6; 8.2-14.7, patients 18.1; 13.9-22.6 delta T (degree C), P < 0.05) and a reduced response to capsaicin (controls 47.0; 24-117, patients 13.5; 12-30 delta Flux (V), P < 0.005). In contrast, patients with adult onset constipation (n = 7) had a selective neural sweating deficit (controls 49.8; 32.0-61.8; patients 27.7; 7.3-44.3 g/m2 h, P < 0.05), indicating dysfunction of post-ganglionic sympathetic cholinergic fibres. Patients from both groups were shown to have normally functioning sweat glands in direct response to methacholine. Our findings suggest that patients with severe chronic idiopathic constipation may have selective small fibre neuropathies, of which constipation is a manifestation.

Adult↗
PubMed1997

Genetic control of platelet activation in inbred mouse strains.

Platelet activation in inbred mouse strains was studied using expression of P-selectin as a marker of activated platelets. P-selectin expression in response to no added stimulus (spontaneous activation) or in response to adenosine diphosphate (ADP) and epinephrine or thrombin, was assessed using a flow cytometric assay. Wide variation in the responsiveness of different strains was observed with strains SJL and AKR in particular showing very high levels of spontaneous activation. Genetic studies suggest that this phenomenon is under control of a small number of genes and that the same loci are probably responsible for the high activation of both SJL and AKR. Bone marrow transplant experiments show that the trait is expressed in the platelet itself. Screening of SWXJ and AKXD recombinant inbred lines suggests that one of the responsible genes is located on chromosome 3.

Journal Article↗
PubMed1997

Managing pressure relief in a special needs nursing scheme.

People admitted to the Royal Devon and Exeter Hospital, who require continued long term nursing care and fulfil at least one of seven identified criteria, can be referred to a special needs scheme for placement in a private local nursing home supported by education, free loan of electronic pressure-relieving equipment and visits to monitor progress. A clinical nurse specialist in tissue viability is also available for advice and the supply of equipment to any residents with tissue viability problems who are referred by nursing home staff. From a total of 293 referrals during the first four years of this scheme, 155 patients have been supported in nursing homes through the scheme. At the time of placement, 71 patients (46%) had pressure sores, all of whom received the free loan of an electronic mattress. A further 21 patients, whose skin integrity was at high risk, also received mattresses. The sores ranged from Grade 2 to Grade 4 (Stirling grading scale). During the study period, only four patients placed under the scheme suffered deterioration in their sores (all immediately prior to death). Over the three years before the scheme began, 14 patients per year were admitted from private nursing homes to an acute hospital with a primary diagnosis of pressure sore. Since the introduction of the scheme this figure has been reduced to nil.

Aged↗
PubMed1995

In vivo biotinylation demonstrates that reticulated platelets are the youngest platelets in circulation.

In both mice and humans, a subset of platelets can be identified that shows increased labeling with nucleic acid-specific fluorescent dyes, such as thiazole orange. Termed "reticulated platelets," they have been postulated to be platelets that have recently entered the circulation. Their numbers appear to reflect the rate of new platelet production in a number of clinical and experimental situations. To determine whether reticulated platelets really are the youngest platelets in circulation and to estimate the length of time that they are identifiable after entering the circulation, we have employed a technique of "in vivo biotinylation" in mice that labels the entire cohort of circulating cells with covalently bound biotin. Blood samples can then be double-labeled with fluorescent avidin derivatives and thiazole orange, permitting correlated measurement of both surface biotin content and nucleic acid content. The biotinylation occurs rapidly, is complete within 30 minutes, is stable for several days, and does not appear to alter platelet function. The results show that within 24 hours after in vivo biotinylation, platelets appear in the circulation with decreased levels of biotinylation and that these are the reticulated platelets. The estimated lifespan of reticulated platelets is 1.8 days, and the lifespan of all platelets by this method is 4.5 days, which is in agreement with estimates made by other methods.

Animals↗