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Biomedical subjects

K James

Publications and source records attributed to K James.

At least 91 records · Page 5Linked to original sources
PubMed1996

Continuous thoracic epidural analgesia versus combined spinal/thoracic epidural analgesia on pain, pulmonary function and the metabolic response following colonic resection.

BACKGROUND: The neuroendocrine response following major surgery has not been previously influenced by either regional anaesthetic techniques or opioid analgesia probably due to insufficient intraoperative afferent neural blockade. In this study we attempted to determine whether significant inhibition of these pathways could be achieved by combining preoperative high spinal anaesthesia with postoperative thoracic epidural anaesthesia. In theory too, there may be additional benefits over perioperative thoracic epidural anaesthesia on pain and pulmonary dysfunction. METHODS: 20 ASA 1-3 patients undergoing elective colonic surgery were studied. Gp 1 (n = 10) received a high spinal intraoperative block to T4 using 6mls of 0.5% bupivacaine plus continuous epidural 0.125% bupivacaine/0.0025% diamorphine. Gp 2 (n = 10) patients received epidural 0.5% bupivacaine block to T4 plus continuous epidural infusion of 0.125% bupivacaine/0.0025% diamorphine. We measured a) plasma glucose and cortisol at 0, 1, 2, 3, 4, 8 and 24 h; b) forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak flow rate (PFR) preoperatively, at 8 and 24 h; c) visual analogue pain scores (VAS 0-10) at rest, cough and mobilisation at 8 and 24 h; d) block height every hour for 12 hours then 3 hourly; e) 24-hour urine volumes for dopamine, adrenaline and noradrenaline f) 24-hour PCA morphine requirements. RESULTS: The two groups did not differ in age, sex, height, weight, duration of surgery, blood loss or serum albumin. Pain relief was excellent and similar in both groups. The average 24 hour morphine consumption was 10 mg in both groups with no differences in the block height. All the patients had a 30-50% reduction in FEV1, FVC and PFR (P > 0.05). Metabolically, there was no statistical difference between the 2 groups except a higher rise in glucose in Gp1 at 2 and 3 h (P = 0.0312 and 0.014). 24-hour catecholamine studies showed no differences for noradrenaline (P = 0.8), adrenaline (P = 0.47) and dopamine (P = 0.36). CONCLUSIONS: Thoracic epidural bupivacaine/diamorphine infusion provided excellent postoperative analgesia following colonic surgery. An intraoperative combined spinal/epidural technique conferred no additional benefit on analgesia, pulmonary function and the neuroendocrine response.

Adult↗
PubMed1996

Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: A prospective randomized trial was conducted to determine whether the addition of concurrent cisplatin to preoperative or definitive radiation therapy in patients with muscle-invasive bladder cancer improved local control or survival. PATIENTS AND METHODS: Ninety-nine eligible patients with T2 to T4b transitional cell bladder cancer participated, 64% with cT3b or cT4. Patients and their physicians selected either definitive radiotherapy or precystectomy radiotherapy; patients were then randomly allocated to receive intravenous cisplatin 100 mg/m2 at 2-week intervals for three cycles concurrent with pelvic radiation, or to receive radiation without chemotherapy. Patients were stratified by clinical tumor stage and by radiation plan. The median follow-up duration is 6.5 years. RESULTS: The occurrence of distant metastases was the same in both study arms. However, 25 of 48 control patients have had a first recurrence in the pelvis, compared with 15 of 51 cisplatin-treated patients (P = .036). The pelvic relapse rate in the two groups was significantly reduced by concurrent cisplatin (P = .038, log-rank test) and this effect was preserved in a stepwise Cox regression model of prognostic factors (hazards ratio, 0.50; 90% confidence interval [CI], 0.29 to 0.86; P = .036). The hazard reduction was similar for both radiation plans. Pretreatment leukocytosis and high clinical stage were independent adverse factors in a Cox model of overall survival, but the effect of cisplatin was not significant. CONCLUSION: Concurrent cisplatin may improve pelvic control of locally advanced bladder cancer with preoperative or definitive radiation, but has not been shown to improve overall survival. The use of concurrent cisplatin had no detectable effect on distant metastases.

Adult↗
PubMed1996

A comparison of the performance in vitro of precision cut tissue slices and suspensions of human spleen with special reference to immunoglobulin and cytokine production.

During the past decade our knowledge of the cellular and molecular events associated with key immunological responses has been greatly advanced by the use of isolated subpopulations of immunocompetent cells, cloned cell lines and recombinant derived cytokines. Valuable as these studies have been they do not truly reflect the complex integrative events which take place in both primary and secondary lymphoid tissue both in vivo and in vitro. In order to address this problem we have developed a tissue culture procedure which is a modification of that previously used by others to study T cell maturation in the thymus. This involves culturing precision cut slices of human lymphoid tissue in a sponge culture system. Using this technique we have observed marked differences in both immunoglobulin and cytokine secretion between slices and suspensions of human spleen. In brief, cultured slices (mitogen stimulated or otherwise) consistently secrete higher levels of immunoglobulin, IL-1 beta, IL-6, IL-8 and IL-11 and exhibit much lower proliferation than suspensions of the same tissue. Mitogen stimulated suspensions on the other hand secrete higher levels of IL-2, IL-4, IL-10 and TNF alpha than do slices. These differences are also observed at the intracellular cytokine level. Additional studies reveal that the immunoglobulin and cytokine secretion observed is largely due to the de novo synthesis of these molecules and not as a result of spontaneous secretion of preformed products. Furthermore immunoglobulin secretion in both slices and suspensions can be inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha while IL-6 production can be differentially modulated by a variety of substances. Preliminary studies indicate that close interaction between B cells and stromal cells within explants accounts for some of the observed differences. This review article describes the basic technique, summarises the results we have obtained in this system and outlines the possible basis of the observed differences.

B-Lymphocytes↗
PubMed1995

Organ culture of human lymphoid tissue. I. Characteristics of the system.

The major aim of three-dimensional tissue culture is to preserve the natural architecture of the tissue and thereby allow the cells to retain their original functions during in vitro cultivation. Here we describe a method for the rapid preparation of three-dimensional tissue explants from human lymphoid organs. The precision-cut tissue slices are of uniform size and thickness and can be cryopreserved and stored in liquid nitrogen without substantial loss of viability or functionality of the cells. Upon in vitro culture, cells within the explants survived as well as their counterparts cultured in single cell suspension. However, spontaneous immunoglobulin (Ig) production in explants started more promptly and often reached considerably higher levels than that in suspension cultures run in parallel. Lymphocytes within the slices could be activated by polyclonal stimuli such as PHA, as shown by the upregulation of the activation markers CD23 and CD25 on B and T cells, respectively. However, approximately five-fold higher concentrations of mitogen than those used for suspension cultures were needed. Taken together, the system presented here constitutes a potent tool for the investigation of the complex interactions leading to activation and differentiation of B and T cells in lymphoid organs.

Antibody Formation↗
PubMed1995

Characterisation of melatonin binding sites in the eye of the Japanese quail (Coturnix japonica).

Melatonin binding sites were examined in the quail eye using 2-[125]iodomelatonin. Radioreceptor assays indicated similar binding sites in membrane preparations of neural retina (NR) and choroid-retinal pigment epithelium (C-RPE) eye components. In both tissues binding of the radioligand was specific, saturable, and of high affinity [Kd values NR 50.8 +/- 19.5 pM, C-RPE 98.2 +/- 35.4 pM, mean +/- SEM (n = 4)] and low capacity (Bmax values NR 12.4 +/- 2.7 fmol/mg protein, C-RPE 21.5 +/- 3.2 fmol/mg protein). Kinetic studies demonstrated that association of 2-[125I]iodomelatonin was rapid and further that this binding was reversible upon the addition of 1 microM melatonin. The order of pharmacological potencies of various indoles tested in 2-[125I]iodomelatonin displacement studies was melatonin > 6-chloromelatonin > 6-hydroxymelatonin > N-acetylserotonin >> 5-methoxytryptophol > 5-hydroxytryptamine > 5-methoxytryptamine (5-hydroxytryptamine > 5-methoxytryptophol for C-RPE). Studies with guanine nucleotides indicated that the signal transduction mechanism of the binding site may involve a G-protein linkage. This melatonin binding site displays several pharmacological similarities with those investigated in the retina of other species and with those previously characterised in the quail brain.

Animals↗
PubMed1995

Phase II study to evaluate the toxicity and efficacy of concurrent cisplatin and radiation therapy in the treatment of patients with locally advanced squamous cell carcinoma of the cervix.

Sixty patients presenting with poor prognosis squamous cell cancer of the cervix have been studied in a phase II clinical trial. Patients were treated with radiotherapy and concurrent cisplatin chemotherapy every 10 days. Treatment was well tolerated with all patients completing radiotherapy as prescribed. There was one case of grade 4 acute bowel toxicity. Significant late morbidity was acceptable for this group of patients being restricted to two cases (3.3%) of grade 4 toxicity to the bowel. Pelvic control rates of 78% have been observed. There have been no pelvic recurrences after 26 months, although recurrences beyond the pelvis have occurred up to 4 years later. Actuarial 4-year survival is encouraging at 60%.

Actuarial Analysis↗
PubMed1995

Chronic polychlorinated biphenyls exposure on three generations of oldfield mice (Peromyscus polionotus): effects on reproduction, growth, and body residues.

Effects of chronic dietary exposure to low levels of PCBs (polychlorinated biphenyls) on reproduction, growth and whole body burdens were investigated in three generations of Peromyscus polionotus. Mated pairs were maintained on a diet containing 5 mg/kg PCBs (Aroclor 1254) for 12 months, beginning exposure as young adults; matched controls received a similar diet without PCBs. Offspring were maintained on the parental regime and paired at maturity with non-siblings in the same group. In first and second generation offspring, birth and weaning weights were significantly lower in PCB-exposed animals; in the second generation, there were also significantly fewer mice born/month, longer intervals prior to birth of the first litter, and decreased survival to weaning (25 days) among exposed mice. Whole body residue of PCBs increased significantly with each generation of exposure. This study clearly shows that chronic exposure to PCBs at a dosage of 5 mg/kg depressed fertility, growth and survival in Peromyscus, and that these effects were amplified through multigenerational exposure.

Animals↗
PubMed1995

Production of urinary tumour necrosis factors and soluble tumour necrosis factor receptors in bladder cancer patients after bacillus Calmette-Guérin immunotherapy.

Intravesical immunotherapy for bladder cancer is the most effective form of tumour immunotherapy. Following repeated instillations of bacillus Calmette-Guérin (BCG) organisms into the bladder large quantities of several cytokines are detected in the urine. These cytokines include interleukins IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) and also soluble intercellular adhesion molecule ICAM-1. In the work reported here we simultaneously quantified urinary levels of TNF alpha, TNF beta, TNF receptor I and TNF receptor II by enzyme-linked immunosorbent assay (ELISA) techniques and compared this with bioactive levels of TNF. This was undertaken with a limited number of patients throughout a course of six instillations of immunotherapy. Sequential instillations of BCG induced secretion of TNF alpha and TNF beta into urine. These cytokines were not always secreted simultaneously, perhaps suggesting differential regulation of their synthesis. Maximal concentrations of TNF alpha were 675 pg/ml and TNF beta 47 pg/ml. High levels of both species of soluble TNF receptor were readily identified in urine. Maximal levels of sTNF-RI were 6200 pg/ml (range from 0) and for sTNF-RII 7800 pg/ml (range from 0). Contrasting with earlier published observations concerning cytokine levels, the concentration of soluble receptor did not increase with repeated instillation. In apparent contrast with the ELISA data, very low levels of bioactive TNF were identified by the L929 bioassay (maximum concentration 1 U/ml) despite the elevated concentration of immunoreactive TNF. The large concentrations of soluble TNF receptor in patients' urine samples could account for the apparently low bioactivity as determined by the L929 cytotoxicity assay. The precise nature of the role of TNF in BCG immunotherapy remains undetermined; however, it is thought that proinflammatory cytokines are in part responsible for the clinical efficacy of this therapeutic approach. Whether other cytokines are antogonised by soluble binding proteins remains to be determined. Furthermore, whether TNF is bioactive in the bladder wall and only neutralised in the urine also requires investigation.

BCG Vaccine↗
PubMed1995

Immunomodulatory effects of extracellular secretory vesicles isolated from bovine semen.

We demonstrate that extracellular secretory vesicles isolated from bovine seminal plasma have immunomodulatory properties. They inhibit mitogen induced proliferation of bovine and human peripheral blood lymphocytes in a dose dependent fashion. They also inhibit phagocytosis of latex particles by bovine neutrophils. Phagocytosis of opsonised Staphylococcus aureus however was not affected. Furthermore phorbol ester and chemotactic peptide induced superoxide production was decreased especially when a suboptimal dose of stimulants was used. We suggest that extracellular secretory vesicles may preserve sperm survival in the female reproductive tract.

Animals↗
PubMed1995

Cytokine modulation of epidermal growth factor receptor expression on bladder cancer cells is not a major contributor to the antitumour activity of cytokines.

Epidermal growth factor is a potential mitogen for many different human tumours. Its effect is mediated via a bispecific receptor (EGFR), the expression of which correlates well with invasive disease. We investigated the modulation of EGFR by cytokines produced following bacillus Calmette Guerin (BCG)-immunotherapy. Our data demonstrate the IFN gamma, TNF alpha and IL-1 alpha can decrease the expression of EGFR on some bladder tumour cell lines. IFN gamma reduced EGFR expression on two of eight cell lines (RT4, SD). However, IL-1 and TNF did not share this activity. When cells were treated with a combination of all three cytokines, EGFR was decreased on three cell lines (RT4, RT112, SD) and furthermore, the change in the receptor expression was even more marked. Treatment with phorbol ester (thereby activating protein kinase C) resulted in rapid disappearance of the receptor from the cell surface. Interestingly, the decrease of EGFR expression did not require protein synthesis. Although the cytokines studied could down modulate EGFR, this only occurred on three out of eight cell lines; therefore, it is unlikely that the suppression of proliferative activity caused by cytokine-induced decrease of EGFR expression is central to the antitumour action of BCG therapy, but in a proportion of tumours this mechanism may be involved.

BCG Vaccine↗
PubMed1995

Prediction of amputation wound healing with skin perfusion pressure.

PURPOSE: The purpose of this study was to determine whether laser Doppler skin perfusion pressure (LD-SPP) could accurately predict amputation wound healing. METHODS: We studied a total of 62 limbs in 52 patients (28 men and 24 women) with a mean age of 62.2 years (range 34 to 93 years). From this, 39 limbs underwent major amputation (15 above-the-knee, 24 below-the-knee), and 23 limbs underwent minor amputations (4 transmetatarsal and 19 toes). There were five postoperative deaths, leaving a total of 57 limbs available for analysis. RESULTS: Three of 13 above-knee amputations failed to heal. Twenty-one of 23 below-knee amputations healed. Three of four transmetatarsal amputations failed to heal and eight of 17 toe amputations failed to heal. Binary table analysis showed that an LD-SPP value of 30 mm Hg or greater had a negative predictive value (healing occurred) of 90%. An LD-SPP value of less than 30 mm Hg at the amputation site had a positive predictive value (healing failure) of 75%, (p < 0.001, chi square analysis). For major amputations, negative predictive value was 100%, and positive predictive value was 83%, (p < 0.001). For minor amputations, negative predictive value was 75% and positive predictive value was 66.7%, (p < 0.09). CONCLUSION: These data support the use of the LD-SPP test in the selection of major amputation level consistent with healing in ischemic limbs. Further study of the value of this parameter in the determination of minor amputation wound healing is necessary.

Adult↗
PubMed1995

Interleukin-6 production by bladder tumors is upregulated by BCG immunotherapy.

PURPOSE: To determine whether BCG therapy could upregulate interleukin-6 (IL-6) production in human transitional cell carcinomas (TCC). MATERIALS AND METHODS: Immunohistochemistry of tumor biopsies and urinary cytospins and ELISA studies of urine from bladder cancer patients and TCC cell-line supernatants, before and after exposure to BCG, were performed. RESULTS: Constitutive staining for IL-6 was found in the majority of bladder tumors. Interleukin-6 was detected in the urine of all 13 patients with carcinoma in situ and increased 5-fold during BCG therapy. Levels were variable but were greater in nonresponders (p < 0.01). During therapy both detached bladder urothelial cells and polymorphonuclear leukocytes stained for IL-6. Production of IL-6 increased in only 3 cell lines after exposure to BCG, but all 7 cell lines showed increases after exposure to interferon-gamma (p = 0.015). Grade 3 cell lines showed much greater upregulation than grade 1 and 2 cell lines. CONCLUSIONS: The increase in IL-6 during BCG therapy may be caused by urothelial cells as well as leukocytes. The higher levels seen in nonresponders may be due to either higher grade or persisting tumor.

BCG Vaccine↗
PubMed1995

Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM-1) in bladder cancer patients after bacillus Calmette-Guérin (BCG) immunotherapy.

Intravesical immunotherapy for carcinoma in situ of the bladder is arguably the most effective form of tumour immunotherapy described to date. Following repeated instillations of BCG organisms into the bladder, large quantities of cytokines are detected in patients' urine. This study concerns the production of IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and soluble ICAM-1 (sICAM-1) throughout the six weekly instillations which comprise a therapeutic course. Sequential instillations of BCG induced secretion of IL-1 beta, IL-2, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and sICAM-1 into urine. The responses were heterogeneous between patients and cytokines, but some general trends were evident. Although cytokine levels were initially low, their concentration increased with repeated instillation of BCG. Certain cytokines (e.g. IL-6, IL-8 and IL-10) could be detected after the first instillation, whilst others (e.g. IL-2 and IFN-gamma) were not detected until after the third or fourth instillation. Interestingly, IL-4 was not detected, perhaps suggesting a differential effect on Th2-like responses. Some patients produced particularly elevated or non-detectable levels of cytokines, and a positive correlation was found between the production of various cytokines. The production of a particular cytokine did not correspond with lack of production of another species. Whether monitoring the production of cytokines following therapy may be of prognostic value will be determined in a larger series of patients. However, as these potent immunomodulators are thought to be important for the 75% complete clinical response observed with BCG therapy, there remains the possibility that detection of the products of an activated immune system may correlate with eventual clinical outcome. This study is a necessary forerunner to full prognostic evaluation of such immunological data.

BCG Vaccine↗
PubMed1995

Validation evidence for three coping measures.

Research has shown that the ill effects of stress can be mitigated through the use of appropriate coping strategies. In order to determine which coping strategies are most effective, it must be possible to measure coping strategies accurately. This study investigates the construct validity of 3 coping scales: The Coping Strategy Indicator (Amirkhan, 1990), the Ways of Coping-Revisited (Folkman & Lazarus, 1985), and the COPE (Carver, Scheier, & Weintraub, 1989). Findings from this study indicate that t he data fit the original factor structures reasonably well. In addition, adequate convergent and discriminant validity was found for the revelant scales from each of the 3 coping measures. Finally, these coping measures were correlated with a variety of external criteria, including hassles and uplifts, physical symptoms, satisfaction with life, positive affectively and negative affectivity. Each of these outcome measures was related to at least some of the coping strategies.

Adaptation, Psychological↗
PubMed1994

Conformational change in antithrombin induced by heparin probed with a monoclonal antibody against the 1C/4B region.

A murine monoclonal antibody (MAb) raised against a covalent antithrombin-heparin complex was used to probe the conformational change resulting when the serpin antithrombin binds to heparin. This MAb completely inhibited the progressive activity of antithrombin against thrombin. However, although the MAb remained bound to antithrombin in the presence of heparin, it did not significantly inhibit heparin cofactor activity against thrombin, and increasing concentrations of the antithrombin-binding pentasaccharide progressively unblocked the inhibitory action of the MAb. The MAb bound to antithrombin without affecting either heparin-binding affinity or heparin-induced fluorescence enhancement, and it did not convert antithrombin from inhibitor to substrate. The MAb failed to interact with reduced and S-carboxymethylated antithrombin, indicating the conformational nature of its epitope. Antithrombin variants with N-terminal substitutions (Arg47-->Cys or His, Leu99-->Phe, Arg129-->Gln) modifying heparin binding, and C-terminal substitutions affecting the reactive site (Arg393-->Cys) or resulting in substrate-variant antithrombin (Ala384-->Pro), were all recognized normally, as were normal reactive site cleaved antithrombin and the thrombin-antithrombin complex. However, interaction of the MAb with antithrombin was reduced by several substitution mutations (Phe402-->Cys, Phe402-->Ser, Phe402-->Leu, Ala404-->Thr, Pro407-->Thr) in the 402-407 sequence which codes for amino acid residues of strand 1C and the polypeptide leading to strand 4B. Pro429-->Leu also blocks recognition [Olds et al. (1992) Blood 79, 1206-1212], and this residue is believed to be spatially approximated to strand 1C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗