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Biomedical subjects

S D Heys

Publications and source records attributed to S D Heys.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1992

Nutrition and malignant disease: implications for surgical practice.

Malignant disease is often associated with weight loss and malnutrition. Nutritional support is frequently provided to patients with cancer in an attempt to improve nutritional status and reverse weight loss, with the aim of reducing morbidity and mortality rates. This review evaluates the effect of supplemental nutrition on morbidity and mortality in patients with malignancy undergoing treatment with surgery, chemotherapy or radiotherapy. It also assesses the effect nutritional supplementation has on host defence mechanisms and how nutrients affect tumour cell growth. The evidence suggests that perioperative nutritional support, if given for at least 10 days, reduces morbidity and mortality in patients with biochemical evidence of severe malnutrition, manifest as a low serum albumin concentration and excessive weight loss. In contrast, there is no evidence that parenteral nutritional support benefits patients undergoing chemotherapy or radiotherapy, in terms of either an increased tumour response rate or prolongation of survival. Current research on malignant disease is highlighting the role of specific nutrients (amino acids, essential fatty acids and polyribonucleotides) as key regulators of both anticancer host defence mechanisms and the control of nitrogen metabolism and tumour growth. Arginine, essential fatty acids and ribonucleotides have all been demonstrated to stimulate antitumour host defence mechanisms and some also modulate tumour cell metabolism. Dietary manipulation offers exciting possibilities for the innovative management of malignant disease.

Adult↗
PubMed1992

Immunopathological changes in the skin following recombinant interleukin-2 treatment.

The systemic administration of the cytokine recombinant interleukin-2 (rIL-2) is associated with a number of toxic effects, including dermatological complications. The clinical, histological, and immunopathological changes occurring in the skin of six patients receiving rIL-2 for metastatic colorectal carcinoma have been studied. All of the patients developed a diffuse erythema shortly after initiation of the treatment. In one patient, generalized erythroderma and photosensitivity developed. The initial biopsy revealed patchy spongiosis, focal exocytosis, and focal basal layer damage with a perivascular chronic inflammatory cell infiltrate. With further treatment there was progressive thickening of the epidermis. Immunohistochemistry revealed changes in the expression of CD1, CD3, CD4, and CD25, particularly on perivascular cells. Additionally, there was an increase in the expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes in the basal and mid-layers of the epidermis, endothelial cells, and perivascular cells. It is hypothesized that the expression of ICAM-1 by the epidermal keratinocytes may be the important event in initiating the cutaneous manifestations associated with rIL-2 administration.

Aged↗
PubMed1992

Recombinant interleukin-2 treatment in patients with metastatic colorectal cancer: effect on natural cytotoxicity.

Natural cytotoxicity (natural killer, NK, and lymphokine-activated killer, LAK, activity) was documented in 12 patients with metastatic colorectal cancer, both before and after a 5-day course of continuous therapy with intravenous recombinant interleukin-2 (rIL-2). Treatment induced a substantial increase in circulating CD56+ lymphocytes (pretreatment: 12.1 +/- 6.9%, mean +/- SD; posttreatment: 39.2 +/- 6.9%. Maximal NK cell activity was induced by treatment with rIL-2 but only suboptimal augmentation of LAK cell cytotoxicity was obtained. This study indicates that although continuous infusion of rIL-2 does have a significant effect on natural cytotoxicity, this is suboptimal and further studies are necessary to define the most efficacious immunity-enhancing regimens of therapy, thereby hopefully improving clinical outcome of rIL-2 treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Interleukin 2 therapy in cancer: identification of responders.

C-reactive protein (CRP) levels in serum were measured in fifteen patients with metastatic colorectal carcinoma, prior to and during treatment with a continuous intravenous infusion of rIL.2. Patients were subsequently classified as responders or non-responders to this therapy. Baseline serum CRP levels, prior to treatment, were significantly lower in the responders (range < 2-8 mg l-1) when compared with the non-responders (range 7.5-116 mg l-1), P = 0.004. Furthermore, the responding patients demonstrated significantly and grossly elevated CRP stimulation indices (SI) compared with non-responders at different time intervals during the rIL2 infusion. At the cessation of rIL2 therapy, the CRP stimulation index was 31.3 +/- 9.3 in the responders, and only 1.6 +/- 0.3 in the non-responders (means +/- s.e.m, P = 0.014). These findings suggest that it is possible to predict those cancer patients who are most likely to respond to and benefit from rIL2 therapy, either prior to the commencement of or during the first course of rIL2.

Adult↗
PubMed1992

Stimulation of human breast cancers by dietary L-arginine.

1. The amino acid L-arginine has been shown to enhance immune mechanisms and inhibit tumour growth in experimental animals, but although many of the immunological effects of arginine have been reproduced in man there have been few studies of its effects on human tumours. In this study the effects of arginine on human breast cancers were determined by measuring tumour protein synthesis and comparing this with immunohistochemical assessments of cell proliferation. 2. Patients with breast cancer were randomized to receive either a standard diet or arginine supplementation. At the time of surgery, the rate of tumour protein synthesis was measured by the incorporation of the stable isotope [1-13C]leucine into tumour protein. Tumours were also assessed histologically and by staining for the presence of the activation antigen Ki67. 3. The median rate of tumour protein synthesis was 10%/day (range 5.5-15.8%/day) in the control patients and 25.6%/day (range 9-37%/day) in the patients receiving arginine supplements (P less than 0.005, Wilcoxon rank sum test). The rates of protein synthesis correlated with Ki67 expression within these tumours (r = 0.78, P less than 0.001). A double-staining technique confirmed that tumour cells, rather than tumour-infiltrating lymphoreticular cells, expressed Ki67. 4. This study demonstrates that, in contrast to animal studies, L-arginine stimulates human tumours in vivo. This represents the first direct evidence that a single amino acid can modulate the behaviour of a human cancer.

Administration, Oral↗
PubMed1992

Pattern of 2-deoxy-2-[18F]-fluro-D-glucose accumulation in liver tumours: primary, metastatic and after chemotherapy.

Eight patients with liver metastases from adenocarcinoma of the colon or rectum, two with suspected hepatic metastases and one with primary hepatoma were studied with 2-deoxy-2-[18F]-fluro-D-glucose (18F-FDG) using positron emission tomography (PET). In five of the patients with metastatic tumour a second examination was performed four weeks after treatment with recombinant interleukin-2 (rIL2) and fluorouracil (5FU). In all tumours (one primary and eight metastatic) the radioactivity was seen to accumulate in a rim around each tumour with a large central area showing no uptake. In the five cases imaged after treatment with rIL2, the appearance of the tumour uptake was the same as before treatment. In the two cases of suspected but not proven metastases, no abnormal accumulation of 18F-FDG was seen.

Adenocarcinoma↗
PubMed1992

Protein synthesis rates in colon and liver: stimulation by gastrointestinal pathologies.

Rates of protein synthesis in vivo in normal and pathological tissues of the gastrointestinal tract, were measured using the 'flooding dose' technique with the stable isotope L-[1-13C] leucine. The rate of protein synthesis in normal colonic mucosa was 9.4 (1.2)% (mean (SEM)) per day but was significantly raised in benign and malignant colorectal tumour tissue, and in colonic mucosa from patients with inflammatory bowel disease (p less than 0.001). Furthermore, the rate of protein synthesis was significantly greater in benign colorectal tumour tissue, 36.7 (2.5)% per day, than that in either malignant tumour tissue, 21.7 (1.9)% per day, or in inflammatory bowel disease mucosa, 24.7 (2.5)% per day (means (SEM) p less than 0.001). Liver protein synthesis rates were also measured in separate groups of patients with benign disease of the gastrointestinal tract, in patients with colorectal carcinoma, and in patients with inflammatory bowel disease. The fractional rate of liver protein synthesis was 20.7 (1.9)% per day in patients with benign disease and 23.1 (1.6)% per day in patients with colorectal cancer. In patients with inflammatory bowel disease, however, liver protein synthesis was significantly increased to 35.4 (2.3)% per day (means (SEM) p less than 0.01).

Adult↗
PubMed1992

Bilateral carpal tunnel syndrome associated with interleukin 2 therapy.

We report the development of synchronous bilateral carpal tunnel syndrome in a woman with metastatic colorectal cancer, undergoing treatment with recombinant interleukin 2. A carpal tunnel decompression was carried out on the hand which was more severely affected, with a gradual recovery in median nerve function. To the best of our knowledge, this is the first reported case of carpal tunnel syndrome in association with recombinant interleukin 2.

Aged↗
PubMed1992

The relevance of tumor draining lymph nodes in cancer.

Involvement of RLN by tumor cells is a prognostic index of survival and a biologic indicator of more distant metastatic disease. In most solid tumors in humans, removing the draining lymph nodes seems to have little impact on survival, although it may be important in local control of disease. Although data from animal studies suggest that tumor draining RLN may have an important antitumor role (particularly in the early stage of tumor growth), there is a shortage of evidence in humans to substantiate such a supposition. At the time of operation, alterations in nodal microarchitecture with an expansion of T and B lymphocyte compartments is well documented. The findings of immunologic studies, however, reveal a general hyporeactivity, inappropriate humoral and cell mediated responses to antigens associated with tumors and a low or absent natural cytotoxicity. Failure of host defenses, possibly induced by tumors, may be responsible for progressive growth of tumor and spread of tumor to the RLN, resulting in dissemination of the tumor cells, establishment of metastatic deposits and concurrent growth of tumor in lymph nodes. Regional lymphatics may have an important antitumor role at the early stage of the development of a tumor (as yet unproved in humans). With progressive growth of tumor, the lymphatics are unlikely to be beneficial, not only because of a failure of nodal anticancer defenses, but because they provide a possible preferred biologic environment for tumor cell proliferation and an anatomic route for dissemination to distant tissues and organs.

B-Lymphocytes↗
PubMed1991

Stimulation of protein synthesis in human tumours by parenteral nutrition: evidence for modulation of tumour growth.

Eighteen patients with localized colorectal carcinoma were randomized to receive intravenous nutrition or to be fasted during the 24 h before surgery. Protein synthesis, an index of tumour growth, was then measured by the incorporation of [13C]leucine into tumour protein immediately before surgery. The mean (s.e.m.) rate of tumour protein synthesis in patients receiving nutrition (42.7(3.5) per cent per day) was 89 per cent higher than the rate in the fasted group (22.6(1.9) per cent per day) (P = 0.002). As tumours consist of a variety of different cell types, in vitro rates of protein synthesis were measured in malignant cells isolated from colorectal tumours and cultured with autologous serum obtained from the patient in either the fasted or the fed state. There was a mean increase of 81 per cent in protein synthesis when fed rather than fasted serum was used (P less than 0.02), indicating that the malignant cells themselves respond to nutrient supply. This increase in tumour protein synthesis provides the first evidence in vivo that the exogenous supply of nutrients can modulate the rate of growth of a human tumour.

Aged↗
PubMed1991

Measurement of tumour protein synthesis in vivo in human colorectal and breast cancer and its variability in separate biopsies from the same tumour.

1. A method is described for measuring the rates of protein synthesis in vivo in human colorectal and breast tumours by the intravenous injection of L-[1-13C]leucine as a 'flooding dose'. 2. The incorporation of isotope into colorectal tumour protein was measured in six patients, whose tumours were biopsied after the injection. Fractional rates of protein synthesis were calculated from the enrichment of leucine in protein and the average free leucine enrichment in plasma. The range of rates obtained was 17.2-33.9%/day, with a mean rate (+/- SEM) of 22.5 +/- 2.6%/day. 3. Tumour protein synthesis rates were also measured in 15 patients with breast cancer. The range of rates obtained was 5.3-15.9%/day, with a mean rate (+/- SEM) of 10.3 +/- 0.8%/day. These rates are significantly lower than those obtained with colorectal tumours (P less than 0.001). 4. In 9 of the breast cancer patients, protein synthesis was measured in multiple random biopsies taken from the same tumour. The mean (+/- SEM) difference between the highest and lowest rates in biopsies from the same tumour was only 1.1 +/- 0.3%/day. Only 13% of the variation in protein synthesis between separate tumours could be explained by sampling error because of variation within the tumour itself, the remainder being genuine variation between individual tumours.

Adult↗
PubMed1991

Measurement of protein synthesis in human skeletal muscle: further investigation of the flooding technique.

1. The rate of protein synthesis in quadriceps muscle of healthy subjects estimated from the incorporation of L-[1-13C]leucine given by continuous infusion was 1.1%/day. The estimate of protein synthesis from the incorporation of a flooding amount of labelled leucine was 1.8%/day (SD 0.65). The possibility that the higher rate obtained with the flooding technique arose from stimulation of protein synthesis by the large amount of leucine is unlikely. 2. The same rate of protein synthesis (1.7%/day, SD 0.3) was obtained with a flooding amount (0.05 g/kg) of a different amino acid, L-[1-13C]phenylalanine, as was obtained with leucine. 3. Incorporation of L-[1-13C]phenylalanine was not affected by simultaneous injection of leucine (1.7%/day, SD 0.7) or valine (1.6%/day, SD 0.4). 4. Protein synthesis, assessed in a completely different way from the proportion of polyribosomes isolated from the skeletal muscle, was unaltered by the injection of 0.05 g of L-leucine/kg (44.6%, SD 8.5 versus 43.8%, SD 7.7). 5. Good agreement in estimates of protein synthesis was observed in subjects in whom both legs were measured with both L-[1-13C]leucine (mean difference 0.16%/day) and L-[1-13C]phenylalanine (mean difference 0.2%/day).

Adult↗
PubMed1991

Organ-specific measurements of protein turnover in man.

Methods that were originally developed for animal studies have now been modified for measuring tissue protein turnover in man with stable isotopes. Of the three techniques which have been discussed, only the arterio-venous difference method has the capacity to measure both the synthesis and degradation. This technique is, however, difficult to perform and has a number of potential sources of error, one of the most important being the assessment of precursor labelling. Constant infusion of a labelled amino acid with measurement of the incorporation into protein of a biopsy is a simpler and more precise technique for measuring synthesis in patients as well as volunteers, but the most appropriate means of assessing the precursor labelling still remains to be worked out. The flooding-dose procedure aims to minimize the difficulty of assessing precursor labelling and there is no evidence that the unphysiological dose of labelled amino acid given influences the synthesis rate which is measured. It is rapid to perform and is very well suited to measurements in patients, in whom a wide range of tissues can be studied. These advances in techniques have been facilitated particularly by improvements in mass spectrometry, which have allowed the use of stable in place of radioactive isotopes, and have enabled measurements of isotopic enrichments to be made in small samples of tissue. These techniques for assessing the dynamics of protein metabolism in individual tissues are now being used to answer nutritionally and clinically important questions in human volunteers and patients.

Amino Acids↗
PubMed1991

Strangulated femoral hernia: the persisting clinical trap.

Five cases of strangulated femoral hernia, all with a delay in establishing the diagnosis, are reported here. These cases illustrate the continuing difficulties experienced, both in primary care and hospital practice, in making this diagnosis despite the clinical awareness of this condition.

Aged↗
PubMed1991

Femoral hernia: mortality and morbidity following elective and emergency surgery.

A retrospective study of 95 patients undergoing elective or emergency surgical repair of femoral herniae over the period 1980-1990 was performed. The patients undergoing emergency surgical repair had an increased incidence of pre-existing serious 'medical' diseases and were significantly older (P less than 0.001) when compared with those patients undergoing elective repair. The duration of hospital stay was significantly less in the elective group (P less than 0.001). Although there were no deaths or bowel resections in the elective group, emergency surgery was associated with a mortality rate, albeit low, of 5% (2 of 44 patients), and bowel was resected in 9% of cases (4 of 44 patients). The delay in diagnosis, before emergency surgery was carried out, was short with a mean time of only 1.4 days. Longer delays were associated with an increased morbidity and mortality.

Age Factors↗
PubMed1990

Baseline measurements for stable isotope studies: an alternative to biopsy.

Studies of protein metabolism with stable isotopes require determination of the 'natural' isotopic enrichment in tissues. This has previously been determined by taking a pre-test muscle biopsy or by using the isotopic enrichment of a separate control group of subjects. In this study we have measured and compared the 'natural' 13C enrichment of leucine in plasma protein and muscle protein in 14 subjects. The mean enrichment of leucine (delta 13CPDB) in muscle protein, -26.627, was not significantly different from that in plasma protein, -27.152. The data indicate that the 13C enrichment of leucine in plasma protein reflects that of muscle protein and provides an attractive alternative to an additional muscle biopsy in studies of protein metabolism with stable isotopes.

Adult↗