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Biomedical subjects

S D Heys

Publications and source records attributed to S D Heys.

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

The separate and combined effect of leucine and insulin on muscle free amino acids.

The effect of insulin and leucine on amino acid and protein metabolism in muscle is not fully understood. To characterize their separate and combined effects on free amino acids in muscle and plasma, 11 volunteers received an infusion of either leucine (1 g h-1, Group 1) or glucose (20 g h-1, Group 2) for 2 h followed by a combination of the two infusions for an additional 2-h period. In muscle both the leucine infusion and the leucine plus glucose infusion increased the concentration of free leucine significantly, while the sum of the other branched chain amino acids (BCAA), of the aromatic amino acids and of the basic amino acids decreased. Glucose infusion alone decreased the sum of the essential amino acids, the BCAA and the aromatic amino acids. The combination of leucine and glucose augmented the decreases, while the concentrations of glutamate, glutamine and alanine were unaffected. In plasma the leucine infusion doubled the leucine concentration and decreased alanine, valine, methionine, tyrosine, phenylalanine and the sum of the aromatic amino acids. Glucose infusion decreased methionine, serine, isoleucine and the sum of the essential amino acids and of the BCAA. The combination of leucine infusion and hyperinsulinaemia augmented the decreases. The plasma concentrations of the keto acids of valine and isoleucine decreased by the leucine infusion while the concentrations of the keto acid of leucine and isoleucine decreased by glucose infusion. The combination of leucine and glucose had an additive effect. These effects are attributed to a specific effect of leucine on the other two BCAA and a depression of muscle proteolysis by both leucine and insulin, resulting from glucose infusion.

Adult↗
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

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

Alleviation of experimental cyclosporin A nephrotoxicity by low dose aspirin in the rat.

Groups of male Sprague-Dawley rats received either cyclosporin A (CsA; 25 mg/kg by gavage), low dose aspirin (ASP; 20 mg/kg by gavage), a combination of both, or the appropriate drug vehicles daily for 14 days. Renal structure and function were assessed on day 0 (pretreatment) and on days 7 and 14. Compared to pretreatment results, CsA nephrotoxicity was characterized by increased plasma urea and creatinine concentrations and by moderate to severe microcalcification (MC) at the corticomedullary junction by day 14. The development of nephrotoxicity was also associated with a 5-fold increase in urine thromboxane B2 (TxB2) excretion by day 10, while that of 6-ketoprostaglandin F1 alpha remained relatively constant. Although both ASP and saline (ASP vehicle) -cotreated animals demonstrated significantly lower plasma urea and creatinine concentrations compared to treatment with CsA alone, the severity of MC observed on day 14, was reduced only in the ASP cotreatment group. Though whole blood CsA concentrations were similar at around 2400 ng/mL in all experimental groups. In addition, although a 2-fold increase in urine TxB2 excretion was observed on days 7 and 10 following treatment with CsA/ASP, levels were significantly reduced compared to treatment with either CsA alone or CsA/saline (both P < 0.05).

6-Ketoprostaglandin F1 alpha↗
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

Clenbuterol, a beta-adrenoceptor agonist, increases relative muscle strength in orthopaedic patients.

1. The sympathomimetic agent clenbuterol has a muscle-specific anabolic effect in normal and wasted muscles from animals. This trial was designed to examine the effect of the drug on the recovery of muscle strength and area after open medial meniscectomy. 2. A double-blind, completely randomized, placebo-controlled study was carried out on 20 healthy male patients. Muscle strength and cross-sectional area were determined before and after surgery. Patients were treated with drug or placebo for 4 weeks postoperatively and there was a 2 week washout period. 3. The results suggest that, in the operated leg, clenbuterol treatment is associated with a more rapid rehabilitation of strength in knee extensor muscles; in the unoperated leg, knee extensor strength increased above the initial values after 6 weeks (P = 0.01). However, in terms of absolute strength the differences were not significant between the two groups. 4. It is concluded that the data lend support to the proposition that clenbuterol has therapeutic potential in the treatment of muscle-wasting conditions.

Adult↗
PubMed1993

Acute mesenteric ischaemia: the continuing difficulty in early diagnosis.

Five cases of acute intestinal ischaemia due to occlusion of the superior mesenteric artery, all with a delay in diagnosis, are reported here. These cases illustrate the continuing difficulties, in clinical practice, in recognizing mesenteric ischaemia before intestinal infarction has occurred, despite the clinical awareness of this condition.

Acute Disease↗
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

Chronic cyclosporin A (CsA) nephrotoxicity in the rat: the effect of calcium blockade with verapamil.

Renal structure and function were assessed in groups of male Sprague-Dawley rats, either surgically intact (SI) or nephrectomized (N), treated with either CsA alone (20 mg/kg, p.o.) or in combination with verapamil (VER; 10 mg/kg/day, i.p.) daily for up to 28 days. Compared to vehicle treated controls, reduced creatinine clearance rates (CCR, mean +/- s.e.m.) were noted following CsA treatment in Sl animals on days 21 and 28 (279 +/- 4 vs 196 +/- 20 and 296 +/- 13 vs 122 +/- 13 ml/h/kg, respectively, both P < 0.05). However, CCR was around 60% of pretreatment values in all N animals from day 7 onwards. A two to three-fold elevation in urinary N-acetyl-beta-D-glucosaminidase activity was noted from day 7 to 28 in all CsA treated animals. In addition, a similar severity of both renal tubular basophilia and corticomedullary microcalcification (but not proximal tubular vacuolation), was noted at all time points in animals receiving CsA alone. Co-treatment with VER reduced the severity of microcalcification in CsA groups, particularly N animals, increased CCR on day 14 in the Sl (196 +/- 23 vs 391 +/- 64) and days 21 and 28 in N (141 +/- 14 vs 357 +/- 32 and 152 +/- 28 vs 261 +/- 20) groups, respectively but had no effect on the magnitude of enzymuria, despite significantly increased trough whole blood CsA levels (20-30%) in both Sl and N groups. These results indicate that calcium blockade reduces both structural and functional features of chronic CsA nephrotoxicity.

Animals↗