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Biomedical subjects

D B Gough

Publications and source records attributed to D B Gough.

27 records · Page 2Linked to original sources
PubMed1992

The prognostic value of nucleolar organiser regions in colorectal cancer: a 5-year follow-up study.

Nucleolar organiser regions (AgNORs) are loops of ribosomal DNA which reflect the cellular activity or malignant potential of the cell and are identified by a specific staining technique. The purpose of this study was to assess the prognostic value of AgNORs in colorectal cancer and to compare it with other accepted prognostic methods. We studied 164 patients who were surgically staged for colorectal cancer and who had complete follow-up data available for 5 years. Using a highly specific silver staining and counting technique each patient was given an AgNOR score. There were 5 Dukes' C tumours, 108 were Dukes' B and 5 were Dukes' A. No cancer deaths occurred in patients with Dukes' A tumours. The incidence of well-differentiated, moderately-differentiated and poorly-differentiated tumours was 37.2%, 53.7% and 9.1%, respectively. Non-survivors had significantly higher AgNOR scores compared with survivors (mean value +/- SD, 14.2 +/- 0.9 vs 8.2 +/- 0.6, P less than 0.0001). In a regression analysis model AgNOR score was the most significant individual variable for predicting survival (chi 2 = 15, P less than 0.01) when compared with Dukes' classification, histological grade, tumour depth or vascular invasion.

Adult↗
PubMed1992

CA15-3: a reliable indicator of metastatic bone disease in breast cancer patients.

Carcinoma of the breast is the most common malignancy in women and is frequently associated with metastatic bone disease and its associated osteolytic morbidity and mortality. Traditional radiological methods for mass screening bony secondaries are not cost-effective. We examined the value of the tumour marker 'CA15-3' as an alternative to conventional isotope bone scintigraphy. A total of 218 patients with breast cancer was evaluated over a 4-year period. Venous CA15-3 levels were obtained at 3-monthly intervals and bone scintigraphy annually or if the patient developed locomotor symptoms or exhibited elevated CA15-3 levels. Of these patients, 33 with metastatic breast carcinoma had an elevated tumour marker level at the time of diagnosis of their metastases; bone metastases alone = 15/17 (88%), soft tissue metastases alone = 2/6 (33%), simultaneous bony and soft tissue metastases = 7/10 (70%). The preponderance of an elevated CA15-3 in metastatic bone disease, be it in isolation or in combination with non-bone metastases, yields a sensitivity, specificity and positive predictive value of 81.5%, 66% and 92%, respectively. Although 22 of the 27 patients had an elevated CA15-3 at the time of diagnosis of their bone metastases, the remaining five patients (with tumour marker levels in the normal range) showed a similar, albeit a delayed, increase (median = 3 months). Thus, all metastatic bone disease patients demonstrated elevated marker levels. We recommend CA15-3 as a simple, reliable and inexpensive screening method for detecting bone metastases in the patient with breast carcinoma.

Antigens, Neoplasm↗
PubMed1991

The role of prostaglandin E2 in immune suppression following injury.

It has been thought for some time that prostaglandin E2 (PGE2) released from activated monocytes/macrophages may contribute to the suppression of immunity seen after burns and major injury because PGE2 inhibits the activation of T lymphocytes. To clarify this issue, we studied 15 patients with total body surface area burns of 20% to 90% (mean, 48%). Peripheral blood mononuclear cells (PBMC) were obtained from these patients one to two times each week for 1 month after burn and were stimulated with the T-cell mitogen phytohemagglutinin (PHA). On 14 occasions the PBMCs from eight patients were significantly suppressed (30% or more) in their response to PHA (suppressed [sup] burn) as compared with PBMCs from normal controls. In 38 instances PBMCs from 12 patients were not significantly suppressed in PHA (nonsuppressed [nonsup] burn). Sup burn PBMCs and control PBMCs were cultured with or without the addition of the cyclooxygenase (CO) inhibitor indomethacin (Indo, 1 microgram/mL) and studied for PHA response and the production of the stimulatory cytokine interleukin-2 (IL-2). Indo partially restored the PHA response of sup burn PBMCs to normal. Sup burn PBMCs also were deficient in production of IL-2. Indo increased IL-2 production by sup burn PBMCs significantly more (160% +/- 20%, p less than 0.005) than control (57% +/- 5%) and nonsup PBMCs (67% +/- 8%). Next inhibition of the PHA response of PBMCs from 12 burn patients and 17 controls was studied by exogenous PGE2. At all time periods after burn injury, patients' PBMCs were significantly more sensitive to inhibition by PGE2 (50% inhibition at 10(-8) mol/L [molar] PGE2) than PBMCs from normal controls (50% inhibition at 10(-6) mol/L PGE2) with maximum sensitivity occurring 8 to 14 days after injury. Peripheral blood mononuclear cells from patients with more than 40% burns were significantly (p less than 0.05) more sensitive to PGE2 than those from patients with lesser burns. Interleukin-2 was added to cultures of sup burn PBMC, nonsup burn PBMC, and controls containing 10(-7) mol/L PGE2. Interleukin-2 totally reversed PGE2 inhibition of the PHA response in PBMC from both controls and burn patients. Because endotoxin leak from the gut has been implicated as a trigger for a number of the metabolic and immunologic abnormalities following injury, the authors looked for the effect of a bolus infusion of Escherichia coli endotoxin (Endo, 4 ng/kg) in seven normal healthy volunteers on the response of PBMC to PHA and on the production of PGE2 and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Pulse oximetry: a new non-invasive assessment of peripheral arterial occlusive disease.

Peripheral skin perfusion reflects the level of vascularity and viability of a limb and may help in planning the site of amputation or bypass surgery in patients with vascular disease. This study used peripheral pulse oximetry in 20 healthy volunteers and in 20 patients with limb ischaemia. Pulse oximetry saturation levels (Psa,O2) were compared with ankle artery Doppler pressures and transcutaneous oxygen measurements (Ptc,O2). Recordings were taken at two standard sites distally and referenced to finger and forearm to calculate an index. A significant correlation was found between Ptc,O2 and Psa,O2 in patients with ischaemia (r = 0.68, P less than 0.01). A further group of 12 patients with acute limb ischaemia was similarly assessed before and after revascularization. After revascularization mean(s.d.) Ptc,O2 increased from 38(13) to 44(1) mmHg (P greater than 0.05) and mean(s.d.) Psa,O2 increased from 86(3) to 90(4) per cent (P less than 0.01). These data suggest that pulse oximetry is a more sensitive index of peripheral perfusion than Ptc,O2 or ankle artery Doppler pressure and that, because of its accuracy and simplicity, it merits further use.

Angioplasty, Balloon↗
PubMed1990

Free radical inhibition and serial chemiluminescence in evolving experimental pancreatitis.

Oxygen free radical activity and inhibition were examined in experimental pancreatitis. Twenty-five rats were randomized to five groups: controls received intravenous saline, to simulate pancreatitis one group received intravenous caerulein (5 micrograms kg-1 h-1), and three groups received sodium taurocholate via the pancreatic duct (0.2 ml, 5 per cent), either alone, following allopurinol or immediately before superoxide dismutase. Chemiluminescence (a phenomenon based on the emission of light during chemical reactions and which is dependent on oxygen free radical activity) was used as an index of oxygen free radical activity and was measured in tissue samples at 5-min intervals following induction of pancreatitis. The control mean(s.e.m.) serum amylase level 1 h after induction of pancreatitis was 635(13) units. It was significantly elevated in caerulein-induced pancreatitis, 1833(118) units (P less than 0.05) and exceeded 3000 units in all taurocholate-infused animals. Mean(s.e.m.) chemiluminescence ranged from 44 (8) mV 100 mg-1 at time zero to 404(113) mV 100 mg-1 at 1 h in controls. In caerulein-induced pancreatitis mean(s.e.m.) chemiluminescence peaked at 20 min (1399(239) mV 100 mg-1, P less than 0.02) and in taurocholate-induced pancreatitis at 15 min (2316(95) mV 100 mg-1, P less than 0.004). Superoxide dismutase significantly reduced chemiluminescence and hyperamylasaemia in taurocholate groups. Increasing oxygen free radical activity paralleled evolving pancreatitis. Superoxide dismutase may have a therapeutic role in pancreatitis.

Allopurinol↗
PubMed1988

Recombinant interleukin-2 (rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice.

Impaired immune competence leading to decreased resistance to sepsis is a major cause of death in burn patients. We have previously shown that increased mortality from a septic challenge correlated with impaired splenocyte interleukin-2 (IL-2) production and response to T cell mitogens in mice subjected to a 25% surface area scald burn. We report now that the addition of recombinant (r) IL-2 (100 U/ml) in vitro to splenocytes from burned animals restored mitogen responses to normal. Burned mice intraperitoneally received 16,000 U of rIL-2 (selected on the basis of dose-response experiments) once daily in 0.5 ml 5% dextrose (5% D) on days 1 through 6 after thermal injury and were compared with burned mice treated with only 5% D. Both groups were subjected to cecal ligation and puncture 10 days after burn; 4 days later, there were no survivors in the 5% D group, whereas 45% of the rIL-2 group remained alive (p = 0.001; Gehan statistic). We found that rIL-2 treatment at the dose selected resulted in no apparent toxicity in burned mice. Finally, splenocytes from rIL-2-treated burned mice showed improved responses to T cell mitogens in vitro compared with 5% D-treated controls. We conclude that rIL-2 therapy may have a role in the restoration of immune competence after thermal injury.

Animals↗
PubMed1988

Temporal correlation of impaired immune response after thermal injury with susceptibility to infection in a murine model.

Suppression of cellular immunity and increased susceptibility to sepsis frequently accompany thermal injury. However, a convincing association between the two has been difficult to establish in human beings. Therefore we chose to investigate the relationship of impaired cell-mediated immunity with susceptibility to sepsis in an animal model. We studied the response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production by splenocytes from mice subjected to a standard 25% scald burn and killed at intervals of 3, 5, 7, 10, 14, and 25 days after thermal injury. Burned mice were compared in all instances to sham-burn animals (i.e., animals that had been anesthetized and shaved but not burned). We also studied mortality after cecal ligation and puncture (CLP), as a septic challenge, in burned and control animals at the same postburn intervals. We found maximal suppression (50% to 55%) of the PHA response at 10 to 14 days after injury and maximum suppression (68%) of IL-2 production at 7 days. Both of these parameters returned to normal by postinjury day 28. Mortality after CLP increased gradually from control levels after thermal injury up to a maximum of 88% on postburn day 10 and also returned to control levels after 28 days after burn. Significant correlations were found between mortality after CLP in the postburn period and suppression of the PHA response, on the one hand, and the suppression of IL-2 production, on the other (r = 0.89 and 0.91, respectively; p less than 0.05). This result implies a causal relationship between impaired cell-mediated immunity and susceptibility to sepsis after burn injury.

Animals↗
PubMedDate not supplied

Diverse clinical and pathologic features of gastric carcinoid and the relevance of hypergastrinemia.

The etiology, prognosis, and optimal management of primary gastric carcinoids remain controversial. Records of 36 consecutive patients with gastric carcinoid (15 men) were reviewed retrospectively between 1975 and 1990. Follow-up was complete in 97% of cases. Mean age at diagnosis was 58.4 years (range 24-82 years). The clinical presentations included anemia (72%), pain (69%), and carcinoid syndrome (11%). Associated autoimmune and endocrine abnormalities were common and included atrophic gastritis (67%), pernicious anemia (58%), hypothyroidism (39%), diabetes (19%), Addison's disease (6%), and hyperparathyroidism (6%). Lesions were nonantral in 78%, involving only the corpus in 42%, the fundus in 28%, and only the antrum in 8%; 42% were multiple. Urinary 5-hydroxyindoleacetic acid (5-HIAA) and serum gastrin levels were elevated in 17% and 50% of those tested, respectively. Histologic examination revealed that 28% of lesions were > or = 2 cm, and 33% had liver metastases on presentation or developed them during follow-up. Eight patients (22%) died of tumor with a median survival of 39 months. The presence of metastases, atypical histology, serosal involvement, and size > 2 cm were adverse prognostic factors. In patients without hypergastrinemia (n = 6), 66% developed metastases, 60% had elevated 5-HIAA, and 50% died of carcinoid tumor. In sharp contrast, those patients with hypergastrinemia and "typical" gastric carcinoids (n = 15), metastases and death did not occur (p < 0.003 and p < 0.005, respectively, compared with eugastrinemic patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗