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C Clelland

Publications and source records attributed to C Clelland.

At least 19 recordsLinked to original sources
PubMed2001

Carrier rate of APC I1307K is not increased in inflammatory bowel disease patients of Ashkenazi Jewish origin.

Colorectal cancer (CRC) occurs with an increased incidence in individuals with chronic inflammatory bowel disease (IBD) of the colon. Recent data suggest that a family history of colorectal cancer is an independent risk factor for CRC in IBD, an observation that implies that genetic factors are relevant to the development of CRC in this context. Among the genetic defects associated with CRC, the APC I1307K mutation has been detected nearly exclusively in individuals of Ashkenazi Jewish (AJ) origin, occurring in 6%-7% of the AJ general population and in 10%-28% of AJ with a either a personal or family history of CRC or adenomatous polyps. These findings, together with the increased incidence of IBD in AJ, prompted the current analysis of the contribution of the APC I1307K variant of CRC in AJ IBD patients. APC I1307K carrier frequencies were determined in 306 AJ individuals affected with IBD and 308 of their unaffected relatives ascertained from a family collection obtained for the identification of IBD susceptibility genes. Prevalence of the I1307K variant was not significantly different among individuals with IBD, Crohn's disease, ulcerative colitis, and unaffected relatives (6.9%, 7.6%, 4.7%, and 6.2%, respectively), and the mutation was detected in only one of five IBD-affected individuals with a diagnosis of CRC. These results reveal that IBD patients of AJ origin carry the APC I1307K variant at the same rate as individuals within the general AJ population. Lack of an increased APC I1307K carrier rate suggests that this mutation does not account for the increased CRC susceptibility associated with IBD.

Adult↗
PubMed2000

Immunohistochemical analysis of endothelial-monocyte-activating polypeptide-II expression in vivo.

Endothelial-monocyte activating polypeptide (EMAP)-II is a novel molecule with cytokine-like pro-inflammatory properties, inducing procoagulant activity on the surface of endothelial cells and monocyte/macrophages in vitro, as well as up-regulating E- and P-selectin expression. EMAP-II is chemotactic for monocytes/macrophages and neutrophils, and stimulates myeloperoxidase release from neutrophils. Injection of EMAP-II into the mouse footpad induces an acute inflammatory response, although some regression occurs in response to direct injection of EMAP-II into murine tumors. Very little is known about the expression of EMAP-II in normal tissues of mice or humans, or about its function in vivo. We developed polyclonal antibodies against EMAP-II using recombinant protein produced in Escherichia coli, and used these antibodies to carry out an immunohistochemical study of the occurrence and distribution of EMAP-II in human tissues. The distribution of EMAP-II protein is relatively restricted, occurring primarily in endocrine organs, in cells of neuroendocrine origin, but also in tissues with high turnover. EMAP-II is strongly expressed in secretory epithelial cells of the thyroid, pancreas, adrenal and salivary glands, among others, as well as in neurons and subsets of monocytes/macrophages. It is also found in the epithelium of the small and large intestines. We conclude that EMAP-II expression is usually, but not always, associated with tissues that display high turnover and high levels of protein synthesis.

Cardiovascular System↗
PubMed1998

Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium-dependent relaxants.

The pig is increasingly being used in medical research, both as a model of the human cardiovascular system, and as a possible source of organs for xenotransplantation. However, little is known about the comparative functions of the vascular endothelium between porcine and human arteries. We have therefore compared the effects of two endothelium-dependent vasorelaxants, acetylcholine (ACh) and the Ca2+-ATPase inhibitor, cyclopiazonic acid (CPA) on the porcine and human isolated pulmonary artery using isometric tension recording. ACh and CPA produced endothelium-dependent relaxations of both the human and porcine pulmonary arteries. In the porcine pulmonary artery, the cyclo-oxygenase inhibitor, flurbiprofen had no effect on relaxations to ACh (Emax: control 67.8+/-8.8% versus 72.4+/-9.5% (n=11)) or CPA (Emax: control 79.6+/-5.0% versus 94.0+/-10.6% (n=7)). The nitric oxide synthase inhibitor, L-NAME converted relaxations to both ACh and CPA into contractile responses (maximum response: ACh 30.0+/-11.1% (n = 10); CPA 80.4+/-26.2% (n = 8) of U46619-induced tone). These contractile responses in the presence of L-NAME were abolished by flurbiprofen. In the human pulmonary artery, L-NAME and flurbiprofen partly attenuated relaxations to ACh (Emax: control: 45.1+/-12.1%; flurbiprofen: 33.4+/-13.5%; L-NAME: 10.1+/-7.2%) and CPA (Emax: control: 78.1+/-5.5%; flurbiprofen: 69.6+/-7.2%; L-NAME 37.9+/-10.7% of U46619-induced tone). These responses were abolished by the combination of both inhibitors. We have demonstrated that while the release of nitric oxide is important in responses to endothelium-dependent vasorelaxants in both human and porcine pulmonary arteries, in the human arteries, there is an important role for vasorelaxant prostanoids whilst in the porcine arteries, vasoconstrictor prostanoids are released.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

An experimental study of intra aortic balloon pumping within the intact human aorta.

OBJECTIVE: Intra-aortic balloon pumping is a therapeutic technique which carries a significant morbidity related to the interaction between the balloon catheter and the aorta. The aim of this study was to visualise directly the dynamic action of the balloon catheter within the cadaveric human aorta in an artificial circulation. METHODS: An artificial circulation was constructed using of PVC tubing, a filter and a roller pump. A series of five intact cadaveric human aortas were then individually studied by placing each in series within the circuit. A balloon catheter was advanced via the left common iliac artery into the descending aorta under direct angioscopic vision. Balloon pumping was then commenced. The circuit was perfused with normal saline at a flow rate of 3 l/min. Pump actions of 1:1 and 1:2 were simulated. Each aorta at the end of the experiment was subjected to histological examination. RESULTS: The balloon only appeared to make direct contact with the wall of the aorta during deflation when it was swept to one side by the circulating fluid. During maximal inflation the only points of contact were the tip of the catheter and the entry site. Side branches of the aorta were not occluded by the balloon. There was considerable atheromatous debris visualised within the lumen of the aorta. Atheromatous plaques were seen to fissure and disrupt by a pressure wave action and not by direct contact with the balloon. CONCLUSION: The balloon catheter moves relative to the wall of the aorta during inflation and deflation. Contact between the balloon and the aorta only occurs during deflation. Side branches of the aorta are not occluded by the catheter. Plaque disruption and embolus formation appear to result from pressure wave action rather than direct contact with the balloon. This may have implications for future balloon design. Further investigation of this poorly understood interaction between the balloon and the aortic wall is required.

Adult↗
PubMed1997

Restoration of limb alignment in total knee arthroplasty: evaluation and methods.

Obtaining adequate alignment is critical in the proper performance of total knee arthroplasty (TKA). This study prospectively evaluates 350 patients who had previous TKA. Its goals are to establish the best method of measuring limb alignment as well as the best method of restoring ideal alignment. Intramedullary alignment techniques were compared with extramedullary, and alignment of each limb was evaluated by both long (scanogram) and short films (14 inches x 17 inches). Conclusions reached were (1) that only data obtained from full limb radiographs are accurate for determining and reporting limb alignment in TKA, (2) that alignment values should be reported relative to the mechanical axis of the limb because of the variability of the femoral anatomic angle, (3) that intramedullary femoral guides are required to make accurate femoral bone cuts, (4) that extramedullary tibial guides permit accurate cuts of the proximal end of the tibia, and (5) that tibial intramedullary guides are not only unnecessary but also potentially misleading.

Biomechanical Phenomena↗
PubMed1997

A comparison of the cytology of endomyocardial biopsy washings from heart transplants with biopsy histologic study and peripheral blood lymphocyte counts.

Cytospin preparations of endomyocardial biopsy washings were examined on 117 occasions from 13 heart transplant recipients and categorized according to the pattern of cell types observed. Twenty-nine percent of samples were acellular, a further 10% too bloodstained for analysis, and 61% were cellular. Eight lymphocytic samples were found and in all cases there was at least grade 1B rejection (four grade 1B, three grade 2, and one grade 3A) on histologic study. However, histologic study showed at least 1B rejection in 48% of cases when cytospins showed mixed inflammatory cells, 33% of cases when cytospins were histiocytic and in 35% when cytospins were bloodstained or acellular. Furthermore 16 of these rejection episodes with nonlymphocytic cytospins were grade 2. Although the recovery of a lymphocytic cytospin was specific for rejection, the sensitivity of the test was poor. Even when the sample is adequate, this method of biopsy washings will predict only one third of cases of significant acute rejection (grade 2 or worse). The large proportion of unsuitable samples also severely limits the utility of endomyocardial biopsy washings for the diagnosis of rejection. Histiocytic cytospins were seen in 63% of samples when previous biopsy sites were reported on histologic study and also in all three samples when histologic study showed ischemic injury. A mixed inflammatory cell pattern was seen to a lesser extent (31% of samples) in relation to previous biopsy sites. High peripheral blood lymphocyte counts were found when endomyocardial biopsy washings were lymphocytic or mixed inflammatory and also when histologic study showed endocardial lymphocytic infiltration (Quilty effect).

Biopsy↗
PubMed1996

Preoperative medical evaluation in patients having joint replacement surgery: added benefits.

Elderly patients having elective total joint replacement surgery are at increased perioperative risk because of comorbid conditions. To show the importance of the preoperative medical evaluation for total joint replacement, we reviewed the records of 238 patients who had screening for total joint replacement surgery in 1994. Of these 238 patients, 76 (32%) benefited from findings on the preoperative medical evaluation. Four percent of these patients were found to have a condition that warranted the postponement or cancellation of surgery, and others were found to have a condition that was immediately treatable. Some patients required referral to their primary care provider or to a specialist. This study emphasizes the importance and added benefits of the preoperative medical evaluation for elderly patients having elective total joint replacement surgery.

Adult↗
PubMed1996

Simultaneous bilateral total knee replacement versus unilateral replacement.

Over a 5-year period the two authors performed 213 simultaneous (sequentially) bilateral total knee arthroplasties (426 knees). A matched series of 107 unilateral arthroplasties was performed within this time frame, and the two groups of patients were evaluated based on postoperative complications and functional improvements. The patients in both groups were primarily osteoarthritics with an average age of 70 years. Knee function according to Hospital for Special Surgery (HSS) scores showed no significant difference, with the postoperative scores for the bilaterals and unilaterals averaging 93.6 and 93.4, respectively. The complication rate in the bilateral series was not increased over the unilaterals; it was less. These results lead to the conclusion that in patients with bilateral arthritis, both knees should be operated on under a single anesthetic, providing the surgical team is able to carry out the operative procedure expeditiously.

Aged↗
PubMed1995

Distinct phenotypes of infiltrating cells during acute and chronic lung rejection in human heart-lung transplants.

To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung rejection, as diagnosed by clinical data and histopathological investigation. TBBs without rejection and normal lung tissue specimens served as controls. Distinct phenotypes of inflammatory cells were found in acute and chronic lung rejection. T cells were present both in acute and in chronic rejection, but did not differentiate between them. In contrast, B cells with antibody deposition were mainly present in chronic rejection and not in acute rejection. Activated macrophages were present only in acute rejection and not in chronic rejection. In nonrejecting lung transplants, perivascular infiltrating cells were virtually absent. In the biopsy specimen, vessels had to be available for analysis, because the cell phenotypes were best recognized in perivascular infiltrates. The analysis of specific phenotypes of inflammatory cells by immunohistochemistry supports the diagnosis of acute and chronic lung rejection, in particular in those cases in which TBB provides limited tissue without airways.

Antibodies, Monoclonal↗
PubMed1993

Bronchoalveolar lavage and transbronchial lung biopsy during acute rejection and infection in heart-lung transplant patients. Studies of cell counts, lymphocyte phenotypes, and expression of HLA-DR and interleukin-2 receptor.

The total and differential cell counts of 135 bronchoalveolar lavages (BAL) in 48 heart-lung transplant (HLT) patients were compared with the histologic findings in concurrent transbronchial lung biopsies (TBBs). Counts of CD3+, CD4+, and CD8+ lymphocytes were recorded, and a semiquantitative assessment of HLA-DR and interleukin-2 receptor (IL-2R) expression was made on 29 occasions. There were five diagnostic categories: normal (n = 8), acute rejection (ALR) (n = 57), treated rejection (TR) (n = 19), infection (INF) (n = 24), and chronic rejection (CR) (n = 24). Total cell counts in INF were significantly higher than counts in all the other diagnostic groups. The highest BAL lymphocyte counts, significantly higher than in INF, were found in ALR because of increased CD8+ cells, exceeding 15% in 13 of 57 BALs. TBBs in ALR by contrast showed significantly increased numbers of both CD8+ and CD4+ cells. High dose corticosteroid treatment of ALR caused a fall in cellularity of BAL and TBB specimens but not always to values seen when patients were well. During INF and CR, significantly increased numbers of PMNs were seen in the BAL. HLA-DR and IL-2R expression was enhanced in cells of BAL and TBB in all complications. BAL can only supplement at present histologic examination of TBB in the diagnosis of complications after HLT.

Acute Disease↗
PubMed1992

Delay in fixation does not affect the immunoreactivity of proliferating cell nuclear antigen (PCNA).

The effect of delayed fixation on the immunoreactivity of proliferating cell nuclear antigen (PCNA) was investigated using eight breast carcinomas. Topologically shuffled samples of each tumour were immersed in fixative at times of 0.5, 1, 2, 4, 6, 18, and 24 h after surgical removal. In addition to a PCNA index (percentage of positive cells per 1200 tumour cells), a semi-quantitative PCNA grading system was used, based on estimates of more than or less than 50 per cent of positive tumour cells at each time interval. The PCNA index of six tumours increased by a mean of 10 per cent with a fixation delay of 24 h. The PCNA grade of all eight tumours showed no change with delayed fixation.

Antigens, Neoplasm↗
PubMed1992

Intimal proliferation in an organ culture of human internal mammary artery.

OBJECTIVE: Intimal smooth muscle cell proliferation is an early feature of atherosclerosis. Its progression is difficult to monitor in humans and previous studies have mostly relied on necropsy material. The aim of this study was therefore to establish whether intimal proliferation occurred in an organ culture of human internal mammary artery. METHODS: Segments of freshly isolated internal mammary artery were maintained din standard tissue culture medium containing 30% calf serum for 14 d. Tissue viability (measured by ATP concentration) was maintained during processing and throughout the culture period [211(SEM 28) nmol ATP.g-1 wet weight on d 1 v 208(27) on d 14]. RESULTS: Histological transverse sections of cultured internal mammary artery showed the development of a neointima containing smooth muscle cells identified by immunocytochemistry for alpha actin. Pulse labelling of cultures with [3H]-thymidine showed proliferating cells predominantly in a neointimal layer with few dividing cells in the media. Cultured de-endothelialized vessels showed less neointimal thickening than cultured freshly isolated vessels [16(3) v 36(5) microns, p < 0.0025] as well as a reduced number of dividing cells per mm of neointimal length [3.1(0.6) v 5.5(1.1), p < 0.05]. CONCLUSIONS: Intimal proliferation occurred in organ culture of internal mammary artery. There is evidence for a factor derived from the endothelium, which may be important in the development of intimal proliferation.

Aged↗
PubMed1992

Diurnal variation in FEV1 after heart-lung transplantation.

We have examined the diurnal variation in forced expiratory volume in one second (FEV1) in 25 heart-lung transplantation patients over a four week period in order to study the pathophysiological mechanisms underlying the increased mortality and morbidity which occurs at night in asthma. These patients do not have pulmonary autonomic nervous reflexes, but often have muscarinic receptor hypersensitivity. They also develop mixed cell infiltration of the lung tissue in the course of infection or rejection. Thus, they show many features in common with asthma. Seventeen patients (68%) showed a significant diurnal variation in airway calibre (mean amplitude of FEV1 was 4.6% (SD 3.7%)), which is similar to that reported in normal adults. One patient had a diurnal variation of 34.5% during an episode of rejection. This variation fell to 6.9% after steroid therapy, a change often seen in asthma. There was a correlation between increased amplitude of the variation and the presence in transbronchial biopsies of airway submucosal eosinophils and lymphocytes, associated with a histological diagnosis of acute rejection and with epithelial damage. No association was seen with muscarinic receptor sensitivity. The variation in FEV1 showed no alteration from the normal day/night synchronization, and the peak values were around 1300 h. We conclude that the diurnal variation in FEV1 after heart-lung transplantation is not dependent on autonomic nerve reflexes or muscarinic receptor sensitivity, but is related to the consequences of inflammation described above.

Adult↗
PubMed1990

Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome.

A comparison has been made between the endothelium-dependent relaxation of pulmonary arteries (PA) obtained at heart-lung transplantation from 4 patients with Eisenmenger's syndrome and secondary pulmonary hypertension, and PA obtained at lobectomy from 4 patients with lung carcinoma, the controls. All vascular rings were studied immediately after lung excision. PA rings from control patients dose-dependently relaxed to cumulative doses of acetylcholine (ACh, 10(-10) to 10(-5) M), achieving a maximal relaxation of 80 +/- 5% (mean +/- s.e. mean) from precontraction with phenylephrine. By contrast, PA rings from Eisenmenger's syndrome patients achieved a maximal relaxation of only 34 +/- 12% (P less than 0.05, unpaired t test), with even paradoxical contraction at high doses of ACh (10(-6) to 10(-5) M). Sodium nitroprusside (10(-4) M) relaxed all PA rings, with and without endothelium (carefully removed before study), obtained from both control and Eisenmenger's syndrome patients. These results provide the first evidence that endothelium-dependent relaxation of PA mediated by endothelium-derived relaxing factors is impaired in Eisenmenger's syndrome patients with secondary pulmonary hypertension.

Acetylcholine↗
PubMed1990

Lung function associated with histologically diagnosed acute lung rejection and pulmonary infection in heart-lung transplant patients.

A group of 34 heart-lung transplant patients were studied with serial pulmonary function measurements, chest radiographs, and transbronchial biopsies from the time of surgery. These investigations were carried out routinely at 3 and 6 months and then annually after transplantation as well as on clinical suspicion of acute lung rejection or infection. A total of 61 transbronchial biopsies and concurrent lung function and chest radiographs were obtained. Of the biopsies, 30 (49.2%) showed histologic evidence of lung rejection, 12 (19.7%) demonstrated various opportunistic infections, and 19 (31.1%) were normal. Compared to during episodes of normal biopsies, FEV1 decreased significantly with lung rejection (p less than 0.001) and with infection (p less than 0.01). Vital capacity (VC) and DLCO also fell with these acute lung complications. Using histologic diagnosis as a standard, lung function testing had a sensitivity of 86% in detecting lung rejection in the first 3 months postoperation and 75% in the subsequent period. Its sensitivity for detecting lung infection was 75%. Although not distinguishing between these two complications, lung function had a specificity of 84% for detecting occurrence of an acute lung complication. Chest radiographs, although of similar sensitivity in the first 3 months postsurgery, had a sensitivity of only 19% for rejection in subsequent months and 58% for infection. Its specificity was 100%. Lung function testing changes in a predictable fashion with lung rejection and infection, offers an improvement over chest radiographs, and provides a quantitative measurement to aid the decision of when to undertake transbronchial lung biopsy.

Biopsy↗
PubMed1990

Acetylcholine and adenosine diphosphate cause endothelium-dependent relaxation of isolated human pulmonary arteries.

Endothelium-dependent vasorelaxation mediated by endothelium-derived relaxing factors (EDRF) has been extensively studied in animals but only limited studies in man are available. Demonstration of EDRF-mediated dilatation of human vessels is fundamental for understanding the mechanisms of vascular diseases in man. We have investigated endothelium-dependent relaxation of isolated human pulmonary arteries. Vascular segments, taken from uninvolved regions of resected lung from eight patients undergoing lobectomy for lung carcinoma, were cut into rings. In rings precontracted with phenylephrine, both acetylcholine (ACh) and adenosine diphosphate (ADP) induced dose-dependent relaxation in the presence of endothelium but not when the endothelium had been carefully removed. The rings without endothelium relaxed completely with sodium nitroprusside, a vasodilator agent acting directly on vascular smooth muscle. Pre-incubation with indomethacin, a cyclo-oxygenase inhibitor which blocks production of prostacyclin, did not alter the vasorelaxant responses to ACh and ADP, suggesting that one (or several) non-prostanoid EDRF(s) are responsible for the endothelium-dependent relaxation of isolated human pulmonary arteries.

Acetylcholine↗