Recent advances in intensive care. More still needs to be known about immunonutrition.
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Critical Care↗
Biomedical subjects
S D Heys
Publications and source records attributed to S D Heys.
Distal proctocolitis and n-3 polyunsaturated fatty acids (n-3 PUFAs): the mucosal effect in situ.
It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.
Animals↗
Distal procto-colitis and n-3 polyunsaturated fatty acids: the mechanism(s) of natural cytotoxicity inhibition.
BACKGROUND: Altered natural killer (NK) and lymphokine-activated killer (LAK) cell activities have been reported with ulcerative colitis (UC). Previously, we have shown that in patients with UC, the n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), specifically inhibit natural cytotoxicity with clinical improvement in disease activity. The aim of this study therefore was to evaluate the possible mechanism(s) involved in this inhibition, and in particular the alteration of production of interleukin 2 (IL2) and the arachidonic acid metabolite leukotriene B4 (LTB4), both known to modulate NK cell activity. MATERIALS AND METHODS: Each patient with procto-colitis received either fish oil extract (EPA 3.2 g, DHA 2.4 g; n = 9) or placebo (n = 9) daily for 6 months. Monthly assessment included disease activity using clinical and sigmoidoscopic scores. Peripheral blood mononuclear (PBMN) cells were isolated and NK cell cytotoxic activity in vitro was measured. Monthly serum samples were analysed for LTB4, IL2 and soluble IL2 receptors (sIL2R). RESULTS: The n-3 PUFAs group had significantly reduced NK cell activity, compared with the placebo group (P < 0.05, Mann-Whitney U-test). In the n-3 PUFA group, incubation of PBMN cells for 72 h with recombinant interleukin 2 (rIL2) reversed the NK inhibition. In patients with active proctocolitis, serum levels of LTB4 correlated positively with NK cell cytotoxicity (r = 0.873, P < 0.05, Kendall's correlation coefficient). After six months of n-3 PUFAs supplementation, serum levels of LTB4 were undetectable with concurrent significant reduction in NK cell cytotoxic activity. The latter was associated with significant reduction of serum IL2 and sIL2R levels (P < 0.05). CONCLUSION: This study has demonstrated both evidence of suppression of immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFAs supplementation. This may have important implications for therapy in patients with UC.
Cytotoxicity, Immunologic↗
Immune-enhancing diets.
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Critical Illness↗
Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy.
PURPOSE: To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. PATIENTS AND METHODS: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. RESULTS: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). CONCLUSION: [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.
Adult↗
Current and potential chemotherapeutic agents used for induction chemotherapy in the treatment of breast cancer.
A substantial proportion of breast cancers are large (<3 cm) or locally advanced (T3, T4, TXN2) at the time of initial presentation. The therapeutic goals that must be achieved in patients with such cancers are to obtain adequate local disease control so that surgery can be performed and to abolish occult distant metastases therefore improving survival. Over the past three decades conventional adjuvant chemotherapy regimens have been employed pre-operatively (neo-adjuvant or primary chemotherapy) to achieve these goals. Studies have now shown that the survival of patients who receive neo-adjuvant chemotherapy is comparable to that of those who receive the same chemotherapy regimen following surgery. It is also apparent that although clinical tumour response rates to neo-adjuvant chemotherapy may be high there is considerable scope for improvement in the corresponding pathological tumour response. Furthermore, data from major studies that have comprehensively evaluated the use of pre-operative chemotherapy now indicates that the pathological response of breast cancers following treatment is of far greater prognostic importance than the clinical response. Recent interests has focoused, therefore, on the implementation of more prolonged or dose intensive chemotherapy regimens with the aims of improving pathological response to treatment and ultimately overall survival. Newer antineoplastic agents are also becoming available that may be used alone or in combination with conventional therapies in order that tumor response may be improved. This review describes current and potential therapeutic agents that may be used for the induction therapy of breast cancer.
Antibiotics, Antineoplastic↗
Comments on the role of fish-oil fatty acids in the prevention of cancer cachexia.
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Cachexia↗
Alterations in polyamine catabolic enzymes in human breast cancer tissue.
High concentrations of acetyl polyamines have been observed in human breast cancer compared with the equivalent normal tissue, however, no explanation as to the reason for the increases has been proposed. In this study, we show that changes in the enzymes responsible for the breakdown of acetyl polyamines occur in breast cancer tissue. Spermidine/spermine N1-acetyltransferase, the first and rate-limiting enzyme in polyamine catabolism, is increased in the tumor tissue whereas polyamine oxidase (PAO) is decreased. The changes in PAO correlate with prognostic factors, and activity decreases as the size and histological grade of tumors increase. The metabolism of polyamines by PAO generates locally high concentrations of hydrogen peroxide, a known inducer of apoptosis; thus, low PAO activity may contribute to the low level of apoptosis seen in tumor cells. Therefore, drugs that induce PAO activity may be a novel means of attacking tumor cells.
Acetylation↗
Minimal modulation of lymphocyte and natural killer cell subsets following minimal access surgery.
BACKGROUND: Trauma, whether accidental or surgically induced, is known to cause significant modulation of the cell-mediated immune response. Minimal access surgery (MAS) has been shown to improve postoperative recovery and enhance rehabilitation. The degree of immunosuppression resulting from two MAS techniques was studied and compared by measuring the circulating T lymphocyte and natural killer (NK) cell subsets. METHOD: This investigation was a randomized prospective study of patients admitted to the Professorial Surgical Unit, Aberdeen Royal Infirmary for elective cholecystectomy. Two methods of MAS were studied-laparoscopy and minilaparotomy. RESULTS: Laparoscopy was found to cause significantly less reduction in the number of cells expressing T lymphocyte phenotypic surface markers (CD2, CD3, CD8, CD4:CD8 ratio), activation markers (CD71 and HLA-DR), and NK cell subsets (CD11b, CD16, CD56 and CD57), when compared with the minilaparotomy technique. CONCLUSIONS: These data show that host defences are less suppressed after laparoscopic cholecystectomy, and this may have important implications for the use of laparoscopic techniques in major surgical resections, especially for malignant disease.
Adult↗
Minimal access surgery for cholelithiasis induces an attenuated acute phase response.
BACKGROUND: Some benefits of laparoscopic (LC) and minilaparotomy (MC) cholecystectomy may reflect attenuation of the acute phase response. The authors examined components of this response. METHODS: Patients were randomized to LC (n = 11) or MC (n = 11). C-reactive protein (CRP), alpha-1-antitrypsin (AAT), retinol-binding protein (RBP), transferrin, and albumin were measured preoperatively and on postoperative days 1, 2, 4, and 7. Interleukin-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor (TNF-alpha) were measured more frequently perioperatively. Peak expiratory flow rate, forced expiratory volume in 1 second, and forced vital capacity were measured daily. RESULTS: The IL-6 increase was more persistent and marked in the MC patients from hour 8 to day 7 postoperatively (P < 0.05). Alterations in CRP, AAT, and albumin were similar. Postoperative deficits of respiratory function correlated with the magnitude of acute phase protein alteration. CONCLUSIONS: Minimal access surgery induces an acute phase response that is less prominent after a laparoscopic technique.
Acute-Phase Proteins↗
Surviving cancer: do psychosocial factors count?
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Humans↗
Psychological factors can predict the response to primary chemotherapy in patients with locally advanced breast cancer.
This study evaluated the possible value of psychological variables in predicting clinical and pathological response to primary chemotherapy. 96 women with newly diagnosed large, or locally advanced, breast cancer (T2 > 4 cm, T3, T4, N2 and M0) participated in a prospective, randomised trial to evaluate the effects of relaxation training with guided imagery and L-arginine on response to primary chemotherapy. Before the first of six cycles of primary chemotherapy, women were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Eysenck Personality Questionnaire (EPQ). The primary outcomes were clinical response (evaluated using standard International Union Against Cancer (UICC) criteria) and pathological response (graded by means of a previously published 5-point scale) following primary chemotherapy. Stepwise linear regressions were used to estimate the predictive value of age, menopausal status, clinical nodal status, tumour size at diagnosis, oestrogen receptor status, dietary supplementation (L-arginine versus placebo), personality (EPQ-L scores), mood (HADS scores) and a psychological intervention. HADS depression score was a significant independent predictor of pathological response to chemotherapy. HADS anxiety score was a significant independent predictor of clinical response. Because the original tumour size before chemotherapy (also a significant predictor of clinical and pathological responses) was taken into account in the analyses, the results cannot be explained in terms of psychobiological factors related to tumour size. This study supports the importance of psychological factors as independent predictors of response to primary chemotherapy in patients with breast cancer. If they can be replicated, these findings have major implications for the management of women with breast cancer. Psychological factors need to be assessed and evaluated in future trials of chemotherapy.
Adult↗
Psychological, clinical and pathological effects of relaxation training and guided imagery during primary chemotherapy.
The diagnosis and treatment of breast cancer are stressful, and stress may be associated with a poorer response to chemotherapy. There is a need, therefore, to develop and evaluate interventions that might enhance quality of life and, possibly, improve treatment response. The effects of relaxation combined with guided imagery (visualizing host defences destroying tumour cells) on quality of life and response to primary chemotherapy, to date, have not been adequately evaluated. Ninety-six women with newly diagnosed large or locally advanced breast cancer (T2 > 4 cm, T3, T4, or TxN2 and M0) took part in a prospective, randomized controlled trial. Patients were randomized following diagnosis to a control condition (standard care) or to the experimental condition (standard care plus relaxation training and imagery). Psychometric tests to evaluate mood and quality of life were carried out before each of the six cycles of chemotherapy and 3 weeks after cycle 6: tests of personality and coping strategy were carried out prior to cycles one and six. Clinical response to chemotherapy was evaluated after six cycles of chemotherapy using standard UICC criteria and pathological response was assessed from the tissue removed at surgery. As hypothesized, patients in the experimental group were more relaxed and easy going during the study (Mood Rating Scale). Quality of life was better in the experimental group (Global Self-assessment and Rotterdam Symptom Checklist). The intervention also reduced emotional suppression (Courtauld Emotional Control Scale). The incidence of clinically significant mood disturbance was very low and the incidence in the two groups was similar. Finally, although the groups did not differ for clinical or pathological response to chemotherapy, imagery ratings were correlated with clinical response. These simple, inexpensive and beneficial interventions should be offered to patients wishing to improve quality of life during primary chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
Peri-operative acute phase response and cytokine releasein women with breast cancer: modulation bypolyadenylic-polyuridylic acid.
AIMS: Acute phase reactants (APRs) are believed to play an important biological role in trauma, sepsis and malignant disease. We have investigated the induction of the APR, C-reactive protein (CRP), by the biological response modifier, polyadenylic-polyuridylic acid (PAPU) during the peri-operative period. METHODS: Twenty post-menopausal women with breast cancer undergoing mastectomy were randomized into a double blind, placebo-controlled, parallel group pilot study. PAPU (150 mg) or placebo was given intravenously the day prior to surgery (D -1), the day of surgery (D 0) and post-operatively on days (D 1, 3, 5, 7 and 14). Blood samples were collected on eight different days (D -2, -1, 0, 1, 2, 4, 6 and 18). CRP was significantly elevated in the PAPU group (P<0.05) on days 2 and 4, when compared with patients receiving placebo. The serum levels of cytokines believed to induce hepatic APRs, were also measured. RESULTS: The serum concentration of IL-6 was elevated on days 1, 2, 4 and 6 (P<0.05), TNF- alpha and IL-1 beta levels were increased on days 1 and 2 (P<0.05), respectively, while the serum level of soluble interleukin-2 receptor (sIL-2R) was elevated above the baseline on days 0, 2, 4, 6 and 18 in the PAPU group, when compared with the baseline. CONCLUSIONS: This modulation of acute phase response may have important implications for patients with cancer undergoing surgery.
Adjuvants, Immunologic↗
Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials.
OBJECTIVE: To conduct a meta-analysis of 11 randomized controlled trials comparing enteral nutritional support supplemented with key nutrients versus standard enteral nutritional support to determine effects on morbidity and mortality rates and hospital stay. BACKGROUND DATA: Recent studies have shown that malnutrition occurs in up to 30% of patients undergoing gastrointestinal surgery, resulting in an increased risk of postoperative complications and death. With the realization that key nutrients can modulate inflammatory, metabolic, and immune processes, enteral nutritional regimens (supplemented with large amounts of key nutrients) have been developed for clinical use. METHODS: Eleven prospective, randomized controlled trials evaluating 1009 patients treated with combinations of key nutrients (Impact, Immun-Aid) were evaluated. Outcome measures examined were the incidences of pneumonia, infectious complications, and death, and length of hospital stay. Meta-analyses were undertaken to obtain the odds ratio and 95% confidence interval for incidences of infectious complications, pneumonia, and death, and the weighted mean difference and 95% confidence interval for length of hospital stay. RESULTS: The provision of nutritional support supplemented with key nutrients to patients with critical illness resulted in a decrease in infectious complications when compared with patients receiving standard nutritional support and a significant reduction in overall hospital stay. Similar results were documented in patients with gastrointestinal cancer. However, there were no differences between patient groups for either pneumonia or death. CONCLUSIONS: This meta-analysis has demonstrated that nutritional support supplemented with key nutrients results in a significant reduction in the risk of developing infectious complications and reduces the overall hospital stay in patients with critical illness and in patients with gastrointestinal cancer. However, there is no effect on death. These data have important implications for the management of such patients.
Abdominal Abscess↗
The management of cancer in the elderly.
The treatment of elderly patients with cancer requires a multidisciplinary approach if optimal locoregional control of disease and survival are to be achieved. Wherever possible, the surgical, radiotherapeutic and chemotherapeutic regimens given to elderly patients with cancer should be comparable with those currently used for the treatment of younger patients with cancer. However, the morbidity (physical and psychological) of therapy must be evaluated against the likely benefits to ensure that elderly patients with cancer receive both optimal management and quality of life.
Aged↗
The accuracy of "one-stop" diagnosis for 1,110 patients presenting to a symptomatic breast clinic.
UNLABELLED: To minimise delay in diagnosis and reduce patient anxiety, triple assessment with immediate reporting has been used in our symptomatic breast clinic since 1991. This article examines the accuracy of the diagnostic modalities used and the efficacy of the "one-stop" diagnostic policy. The data on 1,110 new patients presenting to the symptomatic breast clinic between January and July 1993, were analysed and subsequent three year follow-up and outcome established. Fine needle aspiration cytology (FNAC) gave the highest predictive value (97.3%) with a sensitivity of 93.5% and a specificity of 98.1%. Ultrasonography provided a 97.0% prediction with a sensitivity of 88.9% and a specificity of 97.4%, whereas mammography had a prediction of 96.4% with sensitivity of 93.2% and a specificity of 96.7%. When the mammogram or ultrasound scan were reported as unequivocally benign (M1), there were no missed cancers. The false positive and false negative rates for FNAC were 0% and 1.4%, respectively. Following assessment, a diagnosis was made in 96% of patients. Sixty-two percent of the patients were discharged at the first clinic visit. Four breast malignancies were subsequently diagnosed in the discharged group; two with new microcalcifications due to ductal carcinoma in situ, one with invasive disease in a different quadrant of the breast from that originally investigated, and in one patient the cancer was missed. CONCLUSION: A "one-stop" symptomatic breast clinic provides an accurate and effective means of establishing a correct diagnosis.
Adolescent↗