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Biomedical subjects

S D Heys

Publications and source records attributed to S D Heys.

At least 91 records · Page 5Linked to original sources
PubMed1995

Effect of essential fatty acids on natural cytotoxicity in patients with colorectal cancer.

Essential fatty acids (EFAs), have been shown to modulate lymphocyte reactivity and destroy various tumour cells in vitro. Natural cytotoxicity, mediated by NK and LAK cells, is believed to play an important anti-cancer role in vivo. The effect of EFAs, given orally as dietary supplementation, on NK and LAK cell cytotoxic activity in patients with localized (n = 10) and advanced (n = 20) colorectal cancer has been studied, using in-vitro 51Cr release cytotoxicity assays with K562 (NK) and DAUDI (LAK) cells. The activity of effector cells was expressed as lytic units. NK cell activity showed no significant change following 15 days ingestion of EFAs in the group with localized cancer, but was significantly reduced in the group with advanced disease and continued to decline, reaching minimal levels following 6 months supplementation (P = 0.017). LAK cell activity showed no overall alteration after 15 days ingestion of EFAs in patients with localized cancer, but in the group with advanced disease, the reduction in the activity occurred at day 15 and steadily declined on prolonged intake, reaching significant minimal levels after 6 months of supplementation (P = 0.05). Cell surface marker analysis (FACS-CD MABs) revealed reduced absolute numbers of CD16+, CD56+ and CD57+ lymphocytes (P < 0.05) in the patients with advanced colorectal cancer. More importantly, the cytotoxicity of NK and LAK cells returned to the pre-supplementation values, 3 months after cessation of EFA intake. Furthermore, there was no alteration in the cytotoxic activity of NK and LAK cells in the control group (advanced colorectal cancer without EFA supplementation) during the 6 months period of evaluation. These results suggest that prolonged EFA supplementation, in the doses used in this study, may have detrimental effects on natural anti-cancer cytotoxic mechanisms in patients with malignant disease.

Aged↗
PubMed1995

Positron emission tomography: 2-deoxy-2-[18F]-fluoro-D-glucose uptake in locally advanced breast cancers.

Fifteen patients with locally advanced breast cancers were studied using the radiopharmaceutical 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) with positron emission tomography (PET). Five patients were sequentially imaged before and after two pulses of chemotherapy. In 14 of 15 tumours increased uptake of FDG was observed which correlated with the clinical site of the tumour. The PET images were compared with the mammographic and ultrasonomammographic appearances of the tumours in selected patients. In two patients with normal mammograms PET imaging detected the tumour and in a further four patients, with suspicious but not conclusively malignant mammographic changes, a well-defined area of increased FDG uptake was demonstrated by PET. In all five sequentially imaged tumours, following chemotherapy, there was a decrease of the FDG tumour: normal breast uptake ratio. In four patients who completed a full chemotherapeutic course this change preceded a pathological response of their tumours. These findings suggest that this technique may be of benefit in imaging carcinomas in the breasts of pre-menopausal women which may appear dense on mammography and moreover, that sequential imaging may have a role in the prediction, at an early stage, of the response of locally advanced carcinomas to chemotherapy.

Adult↗
PubMed1995

Superimposition of PET images using 18F-fluorodeoxyglucose with magnetic resonance images in patients with pancreatic carcinoma.

Six patients with histologically proven adenocarcinoma of the pancreas were studied using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) using positron emission tomography (PET), and magnetic resonance imaging (MRI). In all six cases there was avid accumulation of 18F-FDG within the pancreatic tumour and clear visualization of the tumour on the MRI images. Delineation of the tumours was aided by superimposition of the images from the two imaging methods, which was achieved by using a system of surface markers.

Adenocarcinoma↗
PubMed1995

Acute phase proteins and recombinant IL-2 therapy: prediction of response and survival in patients with colorectal cancer.

Twenty-four patients with metastatic colorectal cancer were treated with recombinant IL-2 (rIL-2) by continuous intravenous infusion for 5 days (18 x 10(6) U/m2 per 24 h), followed by three injections of 5-fluorouracil (600 mg/m2) and folinic acid (25 mg/m2) at weekly intervals. The response to treatment was assessed using standard UICC criteria (partial or complete response, stasis or progression of disease). The serum concentrations of the acute phase proteins; C-reactive protein (CRP), retinol binding protein (RBP), alpha 1-antitrypsin (alpha 1-AT), transferrin (TF) and albumin were measured. A response to therapy occurred in the tumours of seven (29%) of the 24 patients (two complete and five partial responses). All patients who demonstrated a response to treatment had a serum albumin level of > 37 g/l and a CRP level of < or = 10 mg/l. In contrast, of the 17 patients who did not respond to therapy, 12 (71%) had a serum albumin of less than 37 g/dl and a CRP of greater than 10 mg/l. Examination of the survival times of the 12 patients who had a pretreatment serum albumin level of less than 37 g/l revealed that all had died within 12 months of cessation of therapy. However, 58% of patients with pretreatment serum albumin levels of greater than 37 g/l survived for longer than 12 months. These results have shown that (i) patients who respond to rIL-2-based therapy and (ii) those patients who have prolonged survival times, can be identified by pretreatment measurement of serum levels of acute phase proteins.

Acute-Phase Proteins↗
PubMed1995

Preliminary clinical evaluation of a combined optical Doppler ultrasound instrument for the detection of breast cancer.

Mammography is widely used for imaging the breast, but is known to be less effective in evaluating the younger dense breast. In this study the ability of telediaphanography in conjunction with Doppler ultrasound (TDDU) to detect breast carcinomas was assessed. Light absorption, determined by the number of blood cells per unit volume of breast, results in the detection of an opaque lesion. Subsequent Doppler ultrasound detects the neovascularization at the periphery of tumours. In total, 178 patients were investigated without prior knowledge of the mammographic findings. This consisted of 69 patients presenting to the symptomatic breast clinic with normal mammograms and 109 patients with mammographic detected abnormalities (mean age 54 years). There were 95 neoplastic lesions. The sensitivity and specificity were: telediaphanography alone 73% and 82%; TDDU 61% and 92%, respectively. TDDU was less sensitive for small and impalpable tumours, and did not detect ductal carcinoma in situ (26 false negatives, mean diameter of 1.1 cm (SD of 0.3 cm)). Subsequent Doppler ultrasound did not further increase the sensitivity of the examination, but did increase the specificity. Patients with locally advanced breast cancers showed dramatic changes on repeated optical/Doppler examinations, in concordance with response to chemotherapy. The combined optical/Doppler instrument, with its low sensitivity, is not suitable for screening, even in the young dense breast, but may have a role in assessing the response of large tumours to chemotherapy.

Adolescent↗
PubMed1995

Surgical management of the septic complications of diverticular disease.

This retrospective study has reviewed the surgical management of the septic complications of diverticular disease involving the left colon in 77 patients who presented between 1980 and 1992. Over this period, Hartmann's resection continued to be the predominant surgical procedure. The overall mortality and morbidity rates in the study period were 10% and 31%, respectively. However, a marked improvement in survival was recorded in the latter half of the study (17% vs 6%). The mortality from Hartmann's resection was also reduced substantially in the second half of the study (24% vs 7.5%). These improvements occurred despite having a higher number of poor-risk patients (APACHE II score) with more severe pathology (generalised peritonitis, 35% vs 50%; faecal peritonitis, 9% vs 25%) in the latter half. There was a significantly worse survival in patients who were over 70 years of age (P < 0.03), those who had a severe concomitant medical illness (P < 0.02), those who had a generalised peritonitis (P < 0.02), and in those patients who had an APACHE II score of over 11 (P < 0.05) (Fisher's exact test). There was no difference in outcome (morbidity, mortality) between the various grades of surgeon involved in performing the emergency surgical procedures.

Adult↗
PubMed1995

Mesenteric ischaemia: prognostic factors and influence of delay upon outcome.

The case records of 43 patients with acute mesenteric ischaemia who presented to the Professorial Surgical Unit, Aberdeen Royal Infirmary between January 1982 and December 1992 were examined. Principal presenting clinical symptoms were acute abdominal pain (100%) with diarrhoea in 44% of patients. Abdominal examination revealed diffuse non-specific tenderness in 48%, with signs of peritonitis in 52% of patients. In 22 of the 43 (51%) patients there was a delay in diagnosis (greater than 12 h from the onset of pain). The overall mortality was 70%, and three significant prognostic factors were identified--surviving patients had a delay in diagnosis of less than 12 h, a normal chest radiograph and a higher arterial paO2, (10.0 +/- 1.0 vs 7.7 +/- 1.2, P < 0.05, vs non-survivors), on admission to the surgical unit. Twenty-five of the 29 non-surviving patients had extensive infarction of small and large intestine, compared with only 1 of the 14 surviving patients (P < 0.05).

Acute Disease↗
PubMed1994

Prognostic factors and survival of patients aged less than 45 years with colorectal cancer.

Colorectal cancers in 92 patients aged 45 years and under presenting over a 20-year period (1970-1990) were studied. A delay of more than 4 months in presentation was seen in 27 per cent of patients. All underwent surgery, 14 per cent emergency and 86 per cent elective, and follow-up was available for 91 patients. Overall, 14 per cent of patients had Dukes A tumours, 32 per cent Dukes B, 36 per cent Dukes C and 18 per cent Dukes 'D'. Local recurrence occurred in eight (9 per cent) of the 92 patients and overall 5- and 10-year survival rates were 61 and 59 per cent. Multivariate analysis identified independent risk factors for local recurrence to be mucinous carcinoma (relative effect 4.9) and the presence of intramural vascular invasion by tumour (relative effect 9.4). For overall survival, independent risk factors were involvement of the regional lymph nodes by tumour (relative effect 2.0), extramural invasion by tumour cells (relative effect 3.0), tumour size (relative effect 1.8) and the presence of metastatic disease at initial diagnosis (relative effect 3.7).

Adolescent↗
PubMed1994

Effect of essential fatty acids on circulating T cell subsets in patients with colorectal cancer.

The effect of essential fatty acids (EFA), given orally as dietary supplements, on the responsiveness in vitro of peripheral blood lymphocytes (PBL), to the mitogen concanavalin A have been studied in 10 patients with localized and 14 patients with advanced colorectal cancer. The degree of lymphocyte activation was assessed by measuring the amount of tritiated [3H]thymidine incorporated into newly synthesised lymphocyte DNA. The results were expressed as stimulation indices. T cell responses to concanavalin A stimulation showed a significant reduction of stimulation indices following EFA supplementation, in both the localized (P = 0.026) and advanced (P = 0.016) tumour groups, when compared with pretreatment activity in vitro. Mixing experiments, using EFA-supplemented and non-EFA-supplemented lymphocytes with concanavalin A, suggest no enhancement of T suppressor cell activity. Cell surface marker analysis (fluorescence-activated cell sorting for CD phenotyping) revealed a reduction of absolute numbers of CD4+ and CD8+ lymphocytes following EFA supplementation. The stimulation indices returned to pre-supplementation values 3 months following cessation of EFA intake. There was no significant change of these indices in the control (no EFA supplementation) advanced tumour group tested. This study suggests that EFA supplementation in patients with colorectal cancer selectively reduces circulating PBL, and T cell subset (including suppressor cells) numbers and/or activity. Such effects may have an important outcome in patients with malignant disease.

Administration, Oral↗
PubMed1994

Dietary supplementation with L-arginine in patients with breast cancer (> 4 cm) receiving multimodality treatment: report of a feasibility study.

L-Arginine has been shown, in human breast cancers, to increase protein synthesis and the number of cells in the growth phase of the cell cycle. L-Arginine, therefore, may potentiate the response of breast cancers to cell cycle-specific cytotoxic agents. This phase II pilot study assessed the clinical, radiological and pathological responses in 44 patients with breast cancers > 4 cm in diameter (46 tumours: T2, n = 6; T3, n = 22; T4, n = 19), who received oral L-arginine 30 g day-1 for 3 days prior to each cycle of CHOP chemotherapy, followed after 4-6 cycles by radiotherapy. Following this treatment, 95% of patients had a clinical response: complete response in 30% and partial response in 65%. Imaging, ultrasound and mammography revealed response rates of 91% and 76% respectively. Surgery was performed in 43 patients. Histological examination revealed that in 18% of cases there was no residual evidence of tumour. Furthermore, if residual tumour was identified, the degree of destruction was graded as 'severe' in 36% and 'moderate' in 30% of cases. Further studies are now required to evaluate the potential beneficial use of nutritional pharmacology in combination with existing treatment regimens.

Adult↗
PubMed1994

In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses.

Recombinant interleukin 2 (rIL-2), when given to patients with advanced malignant disease, induces a limited beneficial effect, with only 20-30% of patients with solid tumours responding. This present study has identified those patients with advanced colorectal cancer most likely to respond to rIL-2 therapy, by analysis of serum cytokine levels, prior to and during rIL-2 treatment, documented in responders and non-responders. Responders were found to have significantly lower pretreatment serum IL-6 and soluble IL-2 receptor levels (sIL-2R) than non-responders (P < 0.01 and P < 0.05 respectively). During rIL-2 infusion, responders developed high circulating levels of IL-6 and had low constant levels of prostaglandin E2 (PGE2). Non-responders failed to produce IL-6 and demonstrated elevated serum concentrations of PGE2, during infusions of rIL-2. Thus, an enhanced ongoing IL-6 and sIL-2R response, prior to therapy, was detrimental to subsequent treatment with rIL-2. Differential production and/or release of cytokines and prostaglandins, during therapy, further determined the likelihood of response to rIL-2.

Biomarkers↗
PubMed1994

Tumour and host tissue responses to branched-chain amino acid supplementation of patients with cancer.

1. Rates of protein synthesis have been measured from the incorporation of 57 mg of L-[1-13C]leucine/kg for 90 min into muscle tissue and colorectal tumours removed at surgery from cancer patients. 2. For the 20 h preceding surgery and during the measurement of protein synthesis, the patients received intravenous saline, conventional intravenous nutrition (0.2 g of N and 103 non-protein kJ/kg body weight) or intravenous nutrition enriched with the branched-chain amino acids leucine, isoleucine and valine (0.2 g of N with 30% from branched-chain amino acids and 103 non-protein kJ/kg body weight). 3. Conventional intravenous nutrition resulted in a significant stimulation of the rate of protein synthesis in both muscle tissue (2.64 +/- 0.75%/day versus 1.78 +/- 0.51%/day in saline control, means +/- SD) and tumour tissue (43.9 +/- 10.3%/day versus 22.6 +/- 5.6%/day in saline control). 4. Pre-operative nutrition enriched with branched-chain amino acids was less effective than conventional intravenous nutrition in stimulating protein synthesis in both muscle and tumour. The rates of protein synthesis were 2.12 +/- 0.41%/day in muscle and 33.7 +/- 5.3%/day in the tumours. 5. The expression of proliferating cell nuclear antigen in sections of the tumours showed changes with intravenous feeding of the two different amino acid mixtures that were similar to the changes in protein synthesis, and these two variables were significantly correlated. This is evidence that feeding with conventional mixtures and mixtures enriched with branched-chain amino acids stimulates tumour growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Lymphocyte protein synthesis in vivo: a measure of activation.

1. The 'flooding' dose technique was used to measure rates of lymphocyte protein synthesis after infusion of [1-13C]leucine (20 atoms % enrichment, 4 g/70 kg body weight). Lymphocyte protein synthesis was measured in healthy subjects and in patients with metastatic colorectal cancer before and during infusion of recombinant interleukin-2. Rates of protein synthesis were compared with thymidine uptake in vitro and phenotypic analysis of lymphocytes. 2. The median rate of lymphocyte protein synthesis in four healthy subjects was 9% (range 7.2-11.4%/day) and in seven patients with colorectal cancer was 6.4% (range 4.2-8.2%/day). After recombinant interleukin-2 treatment the median rate of lymphocyte protein synthesis was 27.8% (range 25.2-33.7%/day). 3. The increased rates of lymphocyte protein synthesis in vivo, after recombinant interleukin-2 infusion, corresponded with increased rates of thymidine uptake and changes in the phenotypic expression of lymphocytes, but these were less consistent than the measured rates of protein synthesis. 4. It is concluded that lymphocyte activation is accompanied by a marked increase in lymphocytic protein synthesis which may have important implications for whole body protein metabolism. Furthermore, measurement of lymphocyte protein synthesis may provide a determination of lymphocyte activation in vivo.

Adult↗
PubMed1994

Renal impairment associated with the pre-operative administration of recombinant interleukin-2.

1. The T-cell-derived cytokine interleukin-2 may be used to reverse the immune suppression associated with major surgery. However, both major surgical procedures and recombinant interleukin-2 therapy are known to induce renal dysfunction. 2. Eighteen patients were randomized to receive either recombinant interleukin-2 (18 x 10(6) i.u./day) or placebo, given subcutaneously for 3 days before undergoing curative colorectal cancer surgery. Indices of renal function were determined pre-operatively and for 21 days after surgery. 3. Pre-operative recombinant interleukin-2 was found to significantly increase, compared with placebo controls, N-acetyl-beta-D-glucosaminidase [peak levels 28 (SEM 2) versus 11 (SEM 3) i.u./mmol of Cr] and gamma-glutamyltransferase [peak levels 5.3 (SEM 0.6) versus 2.4 (SEM 0.2) i.u./mmol/l] and decrease urinary fractional excretion of sodium [peak difference 0.32 (SEM 0.06) versus 0.76 (SEM 0.08)] (all P < 0.05). Significantly increased urinary excretions of creatinine, N-acetyl-beta-D-glucosaminidase and gamma-glutamyltransferase were also identified after surgery. All variables returned to pretreatment limits by the seventh day post-operatively, except N-acetyl-beta-D-glucosaminidase, which was still significantly elevated 21 days after surgery. No differences in the serum concentrations of sodium, creatinine or urea were observed before or after surgery in either group. 4. Recombinant interleukin-2, when given in the preoperative period, was associated with significant renal dysfunction. However, routine monitoring of serum indices (i.e. sodium, urea, creatinine and albumin) failed to detect such renal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗