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Biomedical subjects

D B Gough

Publications and source records attributed to D B Gough.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1996

Nutritional pharmacology and malignant disease: a therapeutic modality in patients with cancer.

It is now established that certain nutrients have a significant effect on cellular metabolism and growth, tissue repair and regeneration, and modulation of host defences. So far, however, potential clinical benefits have been difficult to demonstrate. Nevertheless, the use of nutrients in combinations seems to have promise and may be associated with a reduction in infectious complications and length of hospital stay. Nutritional pharmacology in the future may be able to improve tumour response to chemotherapy and may minimize the metabolic effect of cachexia.

Animals↗
PubMed1996

Metabolic disturbance and sensitivity to endotoxin in patients with advanced cancer: relationship to lymphocyte reactivity, tumour necrosis factor (TNF) production and survival.

Increased TNF production and impaired lymphocyte function have been individually linked with metabolic disturbance, endotoxaemia and mortality in humans. The inter-relationship between these observations was investigated in humans with cancer. In 13 patients with metastatic colorectal cancer and seven healthy volunteers, observations (n = 23) included peripheral blood mononuclear cell (PBMC) TNF production, IL-2 production and phytohaemagglutinin (PHA) response; the acute-phase protein response (APPR) (serum C-reactive protein (CRP), albumin, CRP/albumin ratio), and survival. APPR correlated with survival (CRP, r = -0.689, P = 0.006; CRP/albumin, r = -0.758, P = 0.002; albumin, r = 0.655, P = 0.011), but not with TNF production. TNF production in response to in vitro endotoxin correlated with impaired lymphocyte function in patients (r = 0.567, P = 0.043) and in the whole group (r = 0.65, P = 0.001). The ratio (basal PBMC TNF production)/(lymphocyte function) correlated with CRP (r = 0.569, P = 0.042), CRP/albumin (r = 0.617, P = 0.025), endotoxin sensitivity (r = 0.567, P = 0.043) and survival (r = -0.545, P = 0.038) in patients, and the whole group (P < 0.002). Impaired lymphocyte function may influence TNF production, endotoxin sensitivity and metabolic disturbance in humans with cancer. (r = Spearman correlation coefficient.)

Adult↗
PubMed1995

High-dose interleukin 2 promotes bacterial translocation from the gut.

Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) therapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be important. Fifty-one male rats were randomised to receive rIL-2 by intraperitoneal injection at doses (IU) of 10(5) (n = 15), 10(4) (n = 8), 10(3) (n = 8) or 10(2) (n = 8) twice daily, or a saline bolus (n = 12). After 5 days, ileal histomorphology was assessed and the mesenteric lymph node complex cultured. Results showed that colonisation of mesenteric lymph nodes with Escherichia coli occurred in all rats treated with 10(5) IU of rIL-2, and in 62%, 37% and 12% of rats treated with decreasing doses of rIL-2. No translocation was observed in control animals. An increase in submucosal lymphatics and occasional mucosal disruption was seen only in the group receiving 10(5) IU. These data show that rIL-2 promotes bacterial translocation and suggests a mechanism that may fuel high-dose rIL-2 toxicity in man.

Animals↗
PubMed1994

Resection of hepatic and pulmonary metastases in patients with colorectal cancer.

Nine consecutive patients underwent surgery for liver and lung metastases from colorectal cancer (Dukes' stage B in five, C in one and 'D' in three) between 1980 and 1991. A total of 21 procedures were performed: 16 thoracotomies with six lung lobectomies and 17 lung wedge resections, ten laparotomies with nine hepatectomies and six liver wedge resections. No operative or hospital deaths occurred and the mean(s.d.) postoperative hospital stay was 10(7) days per procedure. Perioperative blood transfusions for all nine patients amounted to a total of 7 units. The median survival after completion of liver and lung surgery was 27 (range 10-62) months. Median survival from resection of the first liver or lung metastasis was 30 (range 12-62) months and from excision of the primary colorectal tumour 46 (range 30-78) months. Two patients were alive and well 11 and 62 months after liver and lung resections; seven have died with metastases. This controversial aggressive treatment resulted in longer survival times than most alternative therapies in these highly selected and well motivated young patients, with no hospital mortality and only moderate morbidity.

Adult↗
PubMed1994

Pseudomyxoma peritonei. Long-term patient survival with an aggressive regional approach.

OBJECTIVE: The aims of this study were to analyze the natural history of patients with pseudomyxoma peritonei (PMP), evaluate clinical and pathologic variables as prognostic indicators, and review the authors' experience with different treatments. SUMMARY BACKGROUND DATA: PMP is an unusual form of intra-abdominal neoplasm that presents with large amounts of extracellular mucin. Diffuse peritoneal spread occurs in most patients with PMP, and distant metastasis is infrequent. Debulking surgery, radiation therapy (radioisotope and external beam), and chemotherapy (both intraperitoneal and systemic) have all been advocated for optional patient management, but the variability of patients studied, the small patient numbers, and the prolonged course of this disease make the evaluation of results difficult. METHODS: Fifty-six patients were treated for PMP at the Mayo Clinic between 1957 and 1983. The data were collected retrospectively. Univariate (log-rank test) and multivariate (Cox regression model) analyses were performed for disease recurrence and patient survival. RESULTS: Most patients with PMP had carcinomas of the appendix (52%) or ovary (34%). All gross tumor could be removed only in the 34% of patients with limited disease. Although tumor progression occurred in 76% of patients, the 1-, 5-, and 10-year survival rates were 98%, 53%, and 32%, respectively. Adverse predictors of patient survival included weight loss (p = 0.001), abdominal distention (p = 0.004), use of systemic chemotherapy (p = 0.005), diffuse disease (p = 0.038), and invasion of other organs (p = 0.04). Intraperitoneal chemotherapy (p = 0.009) and radioisotopes (p = 0.0043) both were effective in prolonging the recurrence time of symptomatic PMP. CONCLUSIONS: Although PMP is an indolent disease, aggressive surgical debulking followed by intraperitoneal radioisotopes and/or chemotherapy should be considered because of the diffuse peritoneal involvement.

Adolescent↗
PubMed1994

Simple method for comparing reliability of two serum tumour markers in breast carcinoma.

AIMS: To compare the two breast tumour markers, CA15-3 and mucinous-like carcinoma associated antigen (MCA), using Receiver Operating Characteristic (ROC) curve analysis. METHODS: One hundred and ninety six patients "presenting" with breast carcinoma had serum CA15-3 and MCA concentrations measured. RESULTS: Using these markers as indicators of stage IV disease at the recommended laboratory level, true positive rates (TPR) and false positive rates (FPR) were obtained as follows: CA15-3 TPR = 75%, FPR = 7.4%, MCA TPR = 80%, FPR = 59.1%. By increasing the CA15-3 cutoff level to 45 U/ml, a TPR and FPR of 75% and 0.6%, respectively were obtained. By increasing the MCA cutoff level to 23 U/ml, a TPR and FPR of 65% and 2.3%, respectively, were obtained. CONCLUSIONS: Using ROC curve analysis shows that CA15-3 is a superior indicator of metastatic breast disease than MCA at recommended laboratory levels, and by altering the cutoff points, the specificity and sensitivity for both these markers can be improved.

Antigens, Neoplasm↗
PubMed1993

A 50-year experience of male breast cancer: is outcome changing?

During the period 1933-1983, 124 men (median age 62.5 years, range 33-86 years) were treated for breast carcinoma. Median length of follow-up was 6.7 years and was complete for 93% of patients. Presenting complaints were most frequently a mass (95%) or pain (31%) while physical examination revealed the tumour to be central in 95% of patients with nipple or skin retraction in 36% and associated gynaecomastia in 12%. Twenty-seven per cent of the patients had a positive family history of breast cancer, 6% noted previous breast trauma and 7% had prior chest wall irradiation. Mean tumour size was 2.5 cm, and the pathological stage was 0 in 3%, I in 17%, II in 22%, III in 35%, IV in 11%, and unknown in 12%. Ninety-four per cent were ductal carcinoma. Histological grading of tumours was 2% grade 1, 10% grade 2, 33% grade 3 and 48% grade 4. Ninety-two per cent of patients underwent mastectomy (41% radical, 39% modified radical and 12% simple), while adjuvant irradiation was used in 44% and chemotherapy in 9%. Median disease-free patient survival was 5 years (36% of patients developed tumour recurrence). Median overall patient survival was 6.3 years (57% at 5 years and 31% at 10 years). Tumour size (P < 0.05), pathological stage (P < 0.04), and tumour grade (P = 0.007) were adverse factors for recurrence, while pathological stage (P < 0.02), tumour size (P < 0.03), pain (P < 0.05) and age (P < 0.02) were associated with a decreased survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Regulation of tumor necrosis factor production in healthy humans and in patients with cancer.

To study the factors that influence cytokine release, the effect of endotoxin on in vitro tumor necrosis factor production by monocytes from debilitated patients with cancer (n = 6) was compared with that from healthy controls (n = 5). Spontaneous and endotoxin-stimulated monocyte tumor necrosis factor production was similar in patients with cancer and controls. However, with total peripheral blood mononuclear cells, enhancement of tumor necrosis factor production by endotoxin in patients with cancer (46 +/- 12, mean +/- SEM) was greater than in controls (0% +/- 7%). This enhanced response correlated with reduced peripheral blood mononuclear cell blastogenesis in response to phytohemagglutinin (r = .66) and could be partially reversed in vitro by addition of exogenous interleukin 2. Thus, a component of total peripheral blood mononuclear cells (probably T cells) seems to influence monocyte cytokine production in response to endotoxin. Moreover, this regulatory component is decreased in patients with cancer, correlates with decreased peripheral blood mononuclear cell blastogenesis, and can stimulated with interleukin 2.

Adult↗
PubMed1992

Impaired cell-mediated immunity in experimental abdominal sepsis and the effect of interleukin 2.

A murine model of experimental sepsis, ie, cecal ligation and puncture, was used to determine the potential effects of infection on in vitro cell-mediated immunity. Following cecal ligation and puncture, in vitro responses of mouse splenocytes to mitogens (phytohemagglutinin and concanavalin A), the effects of in vitro interleukin 2 on these responses, and the impact of in vivo interleukin 2 on survival were studied. Compared with controls (sham cecal ligation and puncture), phytohemagglutinin responses 1 day after cecal ligation and puncture were enhanced (43% +/- 17%, n = 9), phytohemagglutinin and concanavalin A responses at day 4 were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%), and, by day 7, phytohemagglutinin and concanavalin A responses were approaching values in mice treated by sham cecal ligation and puncture. Suppressed phytohemagglutinin responses at day 4 after cecal ligation and puncture were restored to normal with in vitro interleukin 2 (61,052 +/- 3407 cpm for cecal ligation and puncture and 64,643 +/- 4727 cpm for sham cecal ligation and puncture). Mortalities following cecal ligation and puncture were identical at day 1 after cecal ligation and puncture (6/20) for both interleukin 2- and vehicle-treated groups; thereafter, interleukin 2-treated groups fared better. At day 1 after cecal ligation and puncture, the mean spleen cell phytohemagglutinin response was enhanced (43.8% +/- 17%, n = 9) compared with sham cecal ligation and puncture (= 10). By day 4, the responses to both concanavalin A and phytohemagglutinin were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%, respectively). Responses at day 7 approached those of controls given sham cecal ligation and puncture. Sepsis causing a temporary impairment of cell-mediated immunity may be a factor in the frequent coexistence of altered cell-mediated immunity and sepsis, and interleukin 2 may have a role in limiting the adverse effects of sepsis.

Abdomen↗
PubMed1992

Effects of in vivo endotoxin infusions on in vitro cellular immune responses in humans.

Studies of the immune response of patients following major injury have identified significant abnormalities, some of which may be due to the effects of endotoxin. To evaluate the effect of endotoxin on the immune system without conflicting variables, we studied 18 normal, healthy male volunteers each on two occasions. In one study, Escherichia coli endotoxin was administered intravenously at a dose of 4 ng/kg. In the other, saline was given. Blood for immune function studies was obtained at either 0, 4, or 24 hr (seven volunteers), 0, 1, and 4 hr (five volunteers), or 0, 4, and 6 hr (six volunteers) postinfusion. Peripheral blood mononuclear cells (PBMC) were isolated and adjusted to the same concentration. Measurements following endotoxin infusion were compared with those of the same volunteers following saline infusion and with those from normal ambulatory laboratory volunteers. Interleukin 1 (IL-1) production by adherent cells was significantly reduced at 1 hr post endotoxin infusion. Significant decreases in number of mononuclear cells, response to phytohemagglutinin (PHA), and production of IL-2 and IL-1 were observed by 4 hr after endotoxin infusion. No significant changes in percentages of monocytes, lymphocytes, or CD3, CD4, or CD8 lymphocytes were observed at any time. By 24 hr postinfusion all values had returned to normal or, in some cases, supranormal levels. Response to PHA by PBMC from volunteers 4 hr following endotoxin was completely restored by in vitro addition of recombinant human IL-2 but was only marginally improved by IL-1. In vitro addition of indomethacin to PBMC cultures responding to PHA reduced the suppression observed after in vivo endotoxin but also was not as effective as IL-2. In a fourth study, seven volunteers were treated as above either with two doses (800 mg each) of the cyclooxygenase inhibitor ibuprofen before endotoxin infusion or with ibuprofen alone. Ibuprofen pretreatment completely restored the PBMC response to PHA to normal and caused a significant decrease in the endotoxin-induced suppression of IL-2 production. However, the decrease in circulating PBMC number and adherent cell secretion of IL-1 was not affected by inhibition of the cyclooxygenase pathway. These results suggest that endotoxin has immunomodulatory effects on both adherent mononuclear-cell and T-lymphocyte function and that more than one mechanism is involved.

Adult↗
PubMed1992

The relationship between a nutritional index and acute physiology score in critical illness.

Prognostic indices derived from available physiological data (SAPS), complex nutritional and biochemical tests (PNI), grip strength and serum albumin were calculated in 16 critically ill patients receiving intravenous nutrition over a six week period. The aim was to compare these independently derived prognostic indices, to assess their response to feeding, and to determine suitability for use in Irish intensive care units. Mean SAPS (7.6 +/- 0.92), PNI (3.1 +/- 0.29), serum albumin (30.3 +/- 1.03 g/l) and grip strength (17.9 +/- 1.3%) were all suggestive of an "at risk" group. Significant associations were found between the accepted SAPS index and both PNI (r = 0.6, p < 0.001, n = 35) and grip strength (r = -0.68, p < 0.001, n = 44) but not with serum albumin. No consistent improvement was seen in response to feeding in any of the derived indices. The close correlation between prognostic indices derived from either physiological, nutritional or grip strength data in this study and the failure of prognostic indices to improve during hyperalimentation would support a common mechanism, e.g. endogenous mediators, for metabolic and physiological disturbance in critical illness. It suggests that the role of hyperalimentation is supportive rather than therapeutic and re-iterates the importance of managing underlying disease processes. Simple grip strength may be a useful alternative to complex nutritional indices.

Critical Illness↗
PubMed1992

Suppressor T-cell levels are unreliable indicators of the impaired immune response following thermal injury.

The presence of increased levels of suppressor T cells after thermal injury and their relevance remain controversial. It is unclear whether suppressor T cells are the cause or result of sepsis complicating thermal injury. Spleen cells from a standardized murine burn model and sham burn controls were studied and the relationship between the levels of suppressor cytotoxic T cells (CD8, Lyt-2+), helper T cells (CD4, L3T4+), response to concanavalin A (ConA) and to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production was examined. Mortality following infection via cecal ligation and puncture (CLP) of matched controls was also studied. At day 7 postburn, mean ConA (70 +/- 12% of control) and PHA response (58% +/- 5.2% of controls) and IL-2 production (43% +/- 5.4%) were significantly less than sham burn values (100%; p less than 0.05). However, the mean percentage of cells staining with anti-Lyt-2 and anti-L3T4 (9.1 +/- 0.59 and 13.9 +/- 0.65) was similar to the mean percentage in sham burn animals (9.4 +/- 0.65 and 16.6 +/- 1.1). Furthermore, no significant differences were observed between burned mice and controls in helper (17.3% +/- 1.8% burn vs. 21.2% +/- 1.7% sham) or suppressor cell levels (7.8% +/- 1.2% burn vs. 8.6% +/- 0.7% sham) or helper-suppressor ratios on day 10 postburn. Mortality of 20 litter-matched controls subjected to CLP on day 10 postburn was 90%, which was significantly greater than the sham burn mortality of 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Transhiatal oesophagectomy in the management of advanced oesophageal carcinoma.

Thirty-seven patients have undergone transhiatal oesophagectomy for tumours in the upper (n = 3), middle (n = 12) and lower (n = 22) thirds of the oesophagus. Four tumours arose in association with Barrett's oesophagus. Dysphagia for solids was the presenting symptom in 95% of cases. Orringer's technique was used and all cervical anastomoses were hand-sewn. The median duration of surgery was 2.9 (range 1.5-4.0) h and the 30-day hospital mortality rate was 16% (six patients). Respiratory complications were considerable (48%) and accounted for three deaths. Median postoperative stay was 21 (range 13-53 days) while median stay in the intensive care unit was 8.5 days. The majority (97%) of patients had stage III disease and 14 (38%) had lymph node involvement. The actuarial survival was 56% at 1 year and 31% at 2 years. Of the operative survivors, 90% resumed normal swallowing although 17 (55%) required outpatient dilatation. Transhiatal oesophagectomy provides safe and efficient palliation while mortality and 1-year survival rates compare with the transthoracic approach.

Aged↗