Search PubMed⌕ Search

Biomedical subjects

O Eremin

Publications and source records attributed to O Eremin.

At least 109 records · Page 6Linked to original sources
PubMed1994

Modulation of cytokine production in vivo by dietary essential fatty acids in patients with colorectal cancer.

1. The effects of essential fatty acids (gamma-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid), at a dose of 4.8 g/day, given in combination as dietary supplements, on cytokine production were investigated in patients with colorectal cancer. 2. Total serum cytokines--interleukin (interleukin-1 beta, 2, 4 and 6), tumour necrosis factor-alpha and interferon-gamma--were analysed using the enzyme-linked immunosorbent assay technique at different time intervals during the course of essential fatty acid supplementation. 3. Fatty acid uptake and patient compliance were confirmed by a significant increase in serum levels of gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid in all three fractions: tricylglycerol, cholesterol and phospholipid. 4. There was no significant alteration in total serum cytokine concentration/levels in the first 2 months of essential fatty acid ingestion, but the levels of serum cytokines steadily declined thereafter, reaching minimum levels after 6 months of essential fatty acid supplementation. 5. Essential fatty acids, at the dose and duration (6 months) used in this study, reduced total serum interleukin-1 beta levels by 61% (P = 0.044), interleukin-2 by 63% (P = 0.05), interleukin-4 by 69% (P = 0.025), interleukin-6 by 83% (P = 0.030), tumour necrosis factor-alpha by 73% (P = 0.040) and interferon-gamma by 67% (P = 0.050). 6. Three months after cessation of essential fatty acid intake, however, these cytokine levels returned to presupplementation values. 7. This present study has shown that long-term n-3 and n-6 EFA ingestion results in a significant reduction in circulating key cytokines. The precise mechanism of this reduction is unclear.

Aged↗
PubMed1994

Correlation of serum cytokine and acute phase reactant levels with alterations in weight and serum albumin in patients receiving immunotherapy with recombinant IL-2.

Recombinant IL-2 (rIL-2) has been used alone or in combination with other chemotherapeutic agents to enhance host defences against cancer. Prolonged administration of high doses, required for clinical efficacy, may precipitate serious dose-limiting toxicity. rIL-2-induced 'vascular leak syndrome' leads to hypotension, renal insufficiency, respiratory disturbances and other organ dysfunctions. Serial measurements of serum cytokines and the acute phase protein C-reactive protein (CRP) were performed on nine patients who received high-dose i.v. continuous therapy with rIL-2. The influence of these immunological parameters upon alterations in patients' weight and serum albumin, as indicators of toxicity, was assessed. All patients experienced weight increases during the cycle (3-11% of total body weight). The serum levels of tumour necrosis factor (TNF-alpha) and CRP were highly predictive of alterations in patients' weight (both P < 0.001), while no correlation was found with IL-6 and weight change. Serum albumin fell linearly throughout the infusion cycle, but this showed no correlation with variations in serum levels of IL-6, TNF-alpha, or CRP. The complement components C3 and C4 were significantly reduced at the end of the infusion, suggesting a possible role for this cascade system in mediating these clinical changes. The strong association between serum TNF-alpha and weight change, not previously documented, further supports the hypothesis that TNF-alpha is a key mediator in the pathogenesis of the 'vascular leak syndrome'.

Acute-Phase Proteins↗
PubMed1994

Reversal of Hartmann's colostomy.

From January 1980 to December 1992, sixty-two Hartmann's procedures were performed for septic complications of sigmoid diverticular disease, in the Professorial Unit at Aberdeen Royal Infirmary. Colorectal continuity was subsequently restored in 53% of the fifty-three surviving patients. The overall morbidity and mortality was 34% and 0% respectively. There were two anastomotic leaks (7%) while two patients (7%) developed anastomotic stenoses requiring multiple dilations. Closure of Hartmann's colostomy was carried out by consultants (48%), senior registrars (38%) and registrars with consultant supervision (14%). Fifteen anastomoses were hand sewn and fourteen were stapled. Twenty-one per cent of patients had closure of colostomy in less than 3 months, 48% between 3 and 6 months and 31% of reversals were carried out more than 6 months following their formation. The grade of surgeon had no influence on the outcome of reversal. Although the numbers were small, the morbidity was found to be highest in those patients in whom colostomy closure was carried out within 3 months of colostomy formation. Also, there was an increased incidence (7%) of anastomotic stenoses in the stapled anastomosis group.

Adult↗
PubMed1994

Essential fatty acids and malignant disease.

EFAs have shown promising anti-tumour effects in cell culture studies and in animal models. However, it is also clear that in man EFAs can have marked immunomodulatory effects, in particular, inhibiting certain aspects of host anti-tumour defence mechanisms (natural cytotoxicity and cytokine production). Further careful studies are required to evaluate more precisely the role of EFAs in the treatment of malignant disease in man.

Animals↗
PubMed1994

Diet and oxidative stress in breast, colon and prostate cancer patients: a case-control study.

OBJECTIVE: To study the changes in pro-oxidant-antioxidant status in breast, colon and prostate cancer patients as compared to respective controls. DESIGN: Cross-sectional case-control study. The pro-oxidant status was measured by analysing alkanes (ethane and pentane) in exhaled air and lipid peroxidation (as malonaldehyde) in blood samples. The antioxidant capacity was measured by studying blood glutathione concentration, vitamin concentrations and serum antioxidant capacity in liposomes in vitro. SETTING: Aberdeen hospitals. SUBJECTS: Breast, prostate and colon cancer cases, and age- and sex-matched control patients (hospitalized for a benign disease). Breast cancer patients were females, prostate cancer patients were males and colon cancer patients were both males and females. Controls were age-matched to within 5 years, sex-matched and matched for smoking habits. RESULTS: The dietary study suggested a higher monoene and polyene fat intake in prostate cancer than in controls while in other cancer patients no significant differences were found. Breast and colon cancer patients tended to have lower vitamin intakes than controls. Pentane concentration in exhaled air increased in breast cancer patients as compared to respective controls. In serum total antioxidant capacity no significant differences were found. Both breast and colon cancer patients showed decreased C18:2 and C20:4 fatty acid concentrations in red blood cells while C22:6 concentration was elevated in breast cancer patients. CONCLUSIONS: Oxidative stress may be associated with malignant diseases, suggesting the importance of simultaneous analysis of pro- and antioxidation in the search of mechanistic parameters leading to the tumour formation.

Adult↗
PubMed1994

Interleukin 2 treatment in colorectal cancer: current results and future prospects.

Recent interest in the treatment of advanced colorectal cancer with immunotherapy has focused on the use of recombinant interleukin 2 (rIL2). These studies have shown that rIL2 used alone, in combination with lymphokine-activated killer (LAK) cells or tumour-infiltrating lymphocytes (TILs), has little anti-tumour activity, with low, short-lived clinical responses being documented. However, phase I and II studies evaluating rIL2 in combination with 5-fluorouracil (5FU) or 5FU and leucovorin (LV) have been more encouraging, with response rates of up to 46% being reported. Only one randomized, controlled study, however, has compared rIL2 combined with 5FU/LV vs 5FU/LV alone. Although there was no difference in tumour response rates between the two groups, there was a doubling in the median survival of those patients in the poor performance status group (ECOG 1). Also, studies have evaluated the effects of rIL2, given in the peri-operative period, on reversing the immunosuppression that occurs following 'curative' resection for colorectal cancer. These studies have shown an abrogation of immune suppression induced by surgery and an enhancement of host anti-tumour defence mechanisms in the peri-operative period, a time when active tumour dissemination has been shown to occur. These results may have important implications for the management of those patients with malignant disease who are undergoing major curative surgery.

Animals↗
PubMed1994

Natural cytotoxicity in breast cancer patients receiving neoadjuvant chemotherapy: effects of L-arginine supplementation.

Certain cytotoxic drugs have been shown to suppress host anti-cancer defence mechanisms. The amino acid L-arginine can significantly enhance natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity in patients with locally advanced breast cancer. In this study, the effect of L-arginine supplementation on natural cytotoxicity was determined in patients with breast cancer receiving CHOP chemotherapy. This cytotoxic regimen caused a transient immunosuppression, maximal on day 14 of each cycle (P < 0.001); this was not cumulative during the four cycles of treatment. Those patients receiving L-arginine supplementation (30 g/day for 3 days prior to each course of chemotherapy) had a smaller and delayed onset of immunosuppression (day 14), compared with those patients who had CHOP only (day 9). L-Arginine was able to repeatedly stimulate NK and LAK cell cytotoxicity in patients who were receiving CHOP chemotherapy (P < 0.003). In conclusion, further studies are required to determine the optimal use of chemotherapeutic agents, alone or in combination with immunostimulators, to avoid inhibition of host anti-cancer defence mechanisms.

Adult↗
PubMed1994

L-arginine and malignant disease: a potential therapeutic role?

The beneficial effects of L-arginine on nitrogen metabolism, wound healing and host defences demonstrated in animal studies have been shown to be significant in patient studies as well. With tumours, interacting effects on neoplastic cells and host defence mechanisms indicate strategies for beneficial use in cancer patients, especially in association with chemotherapy.

Animals↗
PubMed1994

Colorectal cancer in young patients: a review of the literature.

Colorectal cancer in patients under 45 years of age accounts for approximately 4% of all cases of colorectal cancer. The stage of disease at presentation is comparable with that of older patients. Histological evaluations of the cancers in the younger age group of patients reveal that approximately four times as many tumours are of the mucinous type and this is associated with an increased risk of local recurrence. Dukes staging and vascular invasion by tumour are prognostic indicators for overall patient survival. However, survival rates for young patients with colorectal cancer are comparable to those of older patients, when considering equivalent Dukes stages.

Adult↗
PubMed1994

L-arginine stimulates host defenses in patients with breast cancer.

BACKGROUND: The amino acid L-arginine is known to have immunostimulatory effects in animals and healthy human volunteers. We have studied the effect of dietary supplementation with L-arginine (30 gm/day for 3 days) on host defenses in patients with breast cancer. METHODS: Mitogenic responses of peripheral blood lymphocytes to concanavalin A, phytohemagglutinin, and pokeweed mitogen and phenotype analysis of lymphocyte subsets and activation markers were assessed before and after 3 days of L-arginine supplementation. The effect of L-arginine supplementation on natural killer and lymphokine-activated killer cell cytotoxicity and serum levels of the cytokines interleukin-1 beta and 2, interferon-gamma, and tumor necrosis factor-alpha were also measured. RESULTS: L-arginine significantly increased lymphocyte mitogenic reactivity to concanavalin A, phytohemagglutinin, and pokeweed mitogen (mean percentage increases: 64% [p < 0.001], 65% [p < 0.001], and 48% [p < 0.05], respectively). Natural killer and lymphokine-activated killer cell cytotoxicity was also significantly enhanced after L-arginine intake (mean percentage increase, 81% and 107% [p < 0.001]). However, no corresponding increase in circulating CD16+ and CD56+ cells was obtained: Arginine supplementation did not increase the level of serum cytokines. CONCLUSIONS: Dietary supplementation with L-arginine in patients with breast cancer significantly enhances host defenses and therefore may have a role in adjuvant treatment.

Aged↗
PubMed1993

Outcome in colorectal adenocarcinoma: two seven-year studies of a population.

OBJECTIVE: To record every patient with proved colorectal adenocarcinoma presenting from a defined population over two years in 1968-9 and during 1980-2, and to compare treatment and outcome over seven years. DESIGN: Retrospective in 1968-9 and prospective in 1980-2. SETTING: Aberdeen general hospitals. SUBJECTS: Every patient presenting to the four general surgical units with histological proof of colorectal adenocarcinoma. MAIN FINDINGS: On average, one new patient presented each week per 100,000 population. The proportion of patients aged 65 and over rose from 67% to 71%. An operation was performed on 385 patients in 1968-9 and on 399 during 1980-2. At laparotomy the proportion of patients who seemed to be curable and had a radical operation rose slightly, from 56% to 61%, and operative mortality fell from 9% to 5%. In all there were 421 survivors of curative surgery, and seven years later three quarters were either alive (51%) or had died without recurrence (25%). In both studies some 40% of patients were considered incurable when they presented, but the number who had a palliative resection rose from 59% to 85%. CONCLUSIONS: The contribution of radical surgery to the treatment of colorectal adenocarcinoma is substantial, with three quarters of patients so treated showing no evidence of recurrence after seven years. Operative mortality in an elderly population is now low, and improvement in late outcome is more likely to come from developments in adjuvant therapy than in operative technique. A continuing problem is that 40% of patients are not curable when they present, although palliative resection can now be offered to over 80%.

Adenocarcinoma↗
PubMed1993

Interleukin 2 therapy: current role in surgical oncological practice.

The use of recombinant interleukin 2 (rIL-2) in clinical practice has opened up new and beneficial avenues in the treatment of certain malignant diseases. Although rIL-2 can stimulate a range of host antitumour defence mechanisms, only 30-40 per cent of patients who are treated will respond to such therapy as assessed by a reduction in tumour volume. The effect of rIL-2-based treatment schedules on delaying progression of disease and on overall survival in comparison with standard current treatments and chemotherapeutic regimens is not clear. Randomized clinical trials are required to evaluate precisely the role of rIL-2 in various therapeutic combinations and to ascertain the optimum therapeutic regimens for individual tumour types. Studies currently under way should provide more insight into the possible beneficial effects of immunotherapy with rIL-2. More basic research is required to ascertain how rIL-2 may produce its antitumour effects and why the therapeutic results obtained in humans have been so selective and less beneficial than those in experimental animals.

Cytokines↗
PubMed1993

Lithium clearance measurements during recombinant interleukin 2 treatment: tubular dysfunction in man.

Renal tubular function was evaluated in nine patients undergoing recombinant interleukin 2 (rIL2) treatment for metastatic colorectal carcinoma. A lithium clearance technique was used and the activities of the lysosomal enzyme N N-acetyl-beta-D-glucosaminidase were also measured in the patients' urine, before treatment, during treatment, and then 2 days and 23 days after rIL2 therapy had finished. Significant reductions in clearances of creatinine, sodium, and lithium were observed. The fractional excretions of sodium and lithium were also reduced. Twenty-three days following cessation of rIL2 treatment, there was still a significant reduction in creatinine clearance compared with pretreatment values (p < .01). The clearances of sodium and lithium were also reduced compared with pretreatment values although this did not achieve significance. The fractional reabsorption of sodium and water by the proximal nephron increased during rIL2 treatment, from 0.707 +/- 0.030 (pretreatment) to 0.793 +/- 0.043. This increased reabsorption of sodium and water persisted, rising to 0.849 +/- 0.029, 2 days following cessation of treatment (p < .001, means +/- SEM). Twenty-three days later this had returned toward the pretreatment value, being 0.781 +/- 0.036. The fractional reabsorption of sodium by the distal nephron was also significantly elevated, both during and 2 days after completing rIL2 treatment. Twenty-three days after cessation of rIL2, this value had returned to the pretreatment value. However, in contrast, the fractional reabsorption of water by the distal nephron demonstrated no change during rIL2 treatment, but 2 days posttreatment was significantly reduced and remained low for a further 3 weeks.

Acetylglucosaminidase↗
PubMed1993

In vitro primary immunization of B lymphocytes for producing human monoclonal antibodies against tumor-associated antigens.

The selective cytotoxicity of the lysosomotropic leucine methyl ester and its lysosomal condensation product leucyl-leucine methyl ester have been used to investigate their effect on a range of lymphocyte subsets and on the cellular proliferation and secretion by immunoglobulin-secreting B cells from axillary regional draining lymph nodes of breast cancer patients. CD2+, CD3+, and CD8+ lymphocyte subsets were selectively reduced by the leucyl-leucine methyl ester treatment (CD2: 84.2-67.5%; CD3: 76.1-62.3%; and CD8: 8.0-3.4%), but there was no significant reduction in the CD4+ and CD19+ subsets (CD4: 68.2-64.7%; and CD19: 22.6-33.2%). In the presence of mouse splenic macrophages as antigen-presenting cells, rIL-2, IFN-gamma, and pokeweed mitogen-stimulated lymphocyte supernatant, leucyl-leucine methyl ester-treated lymphocytes showed a significant increase in 3H-thymidine incorporation and in the number of immunoglobulin-secreting B cells following coculture with the breast tumor cell line MCF-7. In this study, we have characterized some of the cellular and cytokine factors that are necessary for in vitro immunization of human B lymphocytes. Hopefully, this will enable human MAbs to be produced in vitro against tumor-associated antigens.

Animals↗
PubMed1993

Multimodality treatment in the management of locally advanced breast cancer.

Forty-two patients with locally advanced breast cancer were treated with multimodality therapy comprising neoadjuvant chemotherapy (cyclophosphamide, vincristine, doxorubicin and prednisolone) and radiotherapy to the breast and lymph-draining areas, followed by tamoxifen and then selective surgery. The objective response rate (UICC criteria) of the primary tumours to chemotherapy alone was 72%, which increased to 83% following radiotherapy. The patients have been followed up for 13-56 months and the probability of local control at 36 months was 0.83. The probabilities of distant disease-free survival and overall survival were 0.50 and 0.65 respectively, at 36 months. However, if the patients' breast cancers had shown a response to chemotherapy/radiotherapy then the distant disease-free survival and overall survival of these subgroups of patients were 0.61 and 0.83 respectively, at 36 months. Toxicity included nausea, vomiting, alopecia, and peripheral neuropathies (two patients), but with no episodes of severe infection or bleeding. This multimodality therapy has achieved good local control and satisfactory overall and distant disease-free survivals with excellent patient compliance.

Adult↗