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Biomedical subjects

P W Davies

Publications and source records attributed to P W Davies.

18 recordsLinked to original sources

Pancreatobiliary diversion enhances experimental pancreatic carcinogenesis.

Since compensatory hyperplasia promotes experimental carcinogenesis in the gut, we tested the ability of two surgical models of pancreatic growth to promote pancreatic carcinogenesis. Male Wistar rats (n = 60) weighing 250-300 g underwent pancreatobiliary diversion (PBD), 90% small bowel resection (PSBR) or triple transection and reanastomosis of the small intestine (controls). Postoperatively, each group received azaserine (20 mg kg-1 wk-1 i.p.) for 6 weeks. Surviving rats were killed at 6 months, pancreatic wet weight was measured and histological sections were examined for atypical acinar cell foci (AACF), the putative precursor of carcinoma. Median relative pancreatic weight (mg pancreas/g body weight) was 2.20 for controls (n = 18), 4.08 for PSBR (n = 11) (P less than 0.001) and 6.86 for PBD (n = 16) (P less than 0.001). PSBR did not affect the development of acidophilic AACF, but PBD produced an enormous increase in their number per cm3 (median 96 vs. 0; P less than 0.001) and a 7-fold increase in their volume (P less than 0.001). Both operations cause pancreatic growth, but only PBD promotes carcinogenesis, possibly because of its unique hormonal effect.

Animals↗

Effect of defunction on cytokinetics and cancer at colonic suture lines.

An intestinal suture line potentiates experimental carcinogenesis in its vicinity, probably due to adaptive hyperplasia. By contrast, a defunctioning colostomy causes distal hypoplasia, and fewer tumours develop. Male Sprague-Dawley rats (n = 160) were used to study adaptation (assessed by a stathmokinetic technique) and carcinogenesis (induced by azoxymethane) at an end-to-end anastomosis that was raised in either functioning or defunctioned left colon. Controls had no procedure and other rats had proximal colostomy alone. Defunction had a profound antitropic effect on the colon, reducing bowel length and weight and crypt cell production rate (CCPR) by 22-56 per cent. Anastomotic CCPR was increased by a factor of 2.6 over controls: mean(s.e.m.) values of 12.71(2.85) versus 4.87(0.41) cells/crypt/h (P less than 0.01), but defunction reduced this by 76 per cent to a mean(s.e.m.) value of 3.00(0.52) cells/crypt/h below that in the intact colon. In the left colon, 39-50 per cent of tumours were sited at the anastomosis. Compared with controls there were 77 per cent fewer tumours in defunctioned colon, but they still favoured the site of anastomosis. Neoplasms at the colostomy site accounted for 74-77 per cent of all right-sided tumours. Anastomosis and defunction have powerful but contrasting effects on colonic adaptation and carcinogenesis; when combined they tend to cancel each other out.

Adaptation, Physiological↗

The polyphasic nature of the respiratory process at the mitochondrial level.

The kinetics of oxygen consumption by rat liver mitochondria, respiring under a variety of metabolic conditions, have been studied. Respiration was initiated by injecting oxygen into anaerobic suspensions of mitochondria. It was found that, irrespective of the metabolic state of the mitochondria and the nature of the respiratory substrate, the rates of electron flow and oxygen consumption follow the pattern of a polyphasic reaction. The rates of oxygen uptake during the first phase are extremely fast and depend on oxygen concentration. The second phase represents a transition in which net oxidation of cytochrome-c oxidase stops and the rates of oxygen consumption suddenly decrease. The third phase is characterized by its changeability. Depending on initial conditions the rates may increase, decrease, or remain constant, although the reaction is not one of zero order. During the last phase, the rates decrease and the oxidase becomes increasingly reduced. It is postulated that the mitochondrial respiratory process is basically a cyclic event in which the redox state of the membrane and the rates of oxygen consumption oscillate with amplitudes and frequencies conditioned by the energy demand and energy-yielding capacity of the cell.

Aerobiosis↗

Perioperative blood transfusion increases the risk of recurrence in colorectal cancer.

A retrospective study was conducted on 519 patients undergoing curative resection for colorectal carcinoma between 1969 and 1980. Recurrence was diagnosed in 214 patients (41.2 percent), 179 of whom (34.5 percent) had received blood transfusions and 35 of whom (6.7 percent) had not (P less than .001). Exclusion of the right-sided colonic tumors still showed that recurrence was more common in transfused than nontransfused patients (135 [47.2 percent] vs. 25 [22.5 percent]; P less than .001). Recurrence in patients transfused only during surgery (N = 201) was higher than in nontransfused patients (P less than .001) and, similarly, all patients transfused during surgery (N = 297) had an increased risk (P less than .001). Among patients with rectal cancer, transfusion increased the risk of recurrence in those treated by abdominoperineal resection (P less than .02), but this was not the case in those treated by sphincter-saving resection (P = .2). Hierarchical log linear analysis of all dependent factors (Dukes' stage, histologic grade, age, sex, site, elective, or emergency procedure) showed that Dukes' stage and blood transfusion had the most significant effects on the development of recurrence (chi 2 = 54.04, df = 6, P less than .0001 and chi 2 = 13.93, df = 3, P less than .003). The risk of recurrence following curative surgery for colorectal cancer is markedly increased by blood transfusion on the day of operation.

Adult↗

The use of CA-50 radioimmunoassay inhibition test in the differential diagnosis of benign and malignant breast disease.

The role of the tumour marker CA-50 has been studied in the differential diagnosis of benign and malignant breast disease. Serum levels of CA-50 were determined by radioimmunoassay using a level of 17 units/ml as a cut-off. All 50 normal subjects and 22 of 24 patients (92%) with benign breast disease had CA-50 levels below 17 units/ml. By contrast, 15 of 36 patients (42%) with breast carcinoma had serum CA-50 levels above 17 units/ml (P less than 0.001). There was no clear correlation with tumour stage. The data suggest that CA-50 levels may help to differentiate benign and malignant diseases of the breast.

Adolescent↗

Inhibition of intestinal carcinogenesis by dietary supplementation with calcium.

Dietary supplementation with calcium reduces colonic crypt cell production rates in both normal and hyperplastic mucosa. Calcium can bind intraluminally with bile salts and fatty acids thus reducing their mitogenic effect. The protective role of oral calcium on intestinal carcinogenesis (induced by azoxymethane) was tested in 60 male Sprague-Dawley rats submitted to either 80 per cent mid jejuno-ileal resection (n = 30) or jejunal transection (n = 30). Half the rats in each group received calcium lactate 24 g/l added to their drinking water. Rats were killed 25-27 weeks postoperatively. Enterectomy increased colonic tumour yield by 60-106 per cent (P = 0.002-0.005) and duodenal tumour yield by 70-86 per cent. Calcium abolished this effect at both sites, halving intestinal tumour yields in rats with both transection and resection (P less than 0.05). Doubling the dietary intake of calcium inhibits experimental carcinogenesis.

Adenoma↗

Effect of hypothermia on intestinal adaptation and carcinogenesis in the rat.

Postoperative hyperplasia enhances experimental intestinal carcinogenesis, but the effects of nonsurgical adaptation are uncertain. The tropic and tumour-promoting potentials of moderate hypothermia were tested in two groups of male Sprague-Dawley rats housed at 10 degrees C for 30 weeks. One group (n = 10) received a 6-week course of azoxymethane (total dose 90 mg kg-1). The second group (n = 7) acted as hypothermic controls. Another 2 groups maintained at 22 degrees C received azoxymethane (n = 15) or served as normothermic controls (n = 15). Overall food intake was 42% higher in the hypothermic groups, yet at sacrifice mean body weight was 13% lower (P less than 0.01). Hypothermia and azoxymethane combined to produce the following increases in crypt cell production rate (CCPR), as determined stathmokinetically: duodenum 170%, jejunum 172%, ileum 74%, proximal colon 227% (P = 0.05-0.01). Independently hypothermia had no effect, but azoxymethane produced 76-156% increases in CCPR throughout the large intestine. Although hypothermia did not affect overall tumour yield, the mean diameter of proximal colonic tumours was increased by 65% (P less than 0.05). In rats receiving azoxymethane, hypothermia stimulates cell proliferation in the small bowel as well as in the proximal colon, where it has a correspondingly mild cocarcinogenic effect.

Adaptation, Biological↗

Intraoperative antegrade lavage and anastomotic healing in acute colonic obstruction.

The management of acute distal colonic obstruction remains controversial. The advent of intraoperative colonic irrigation has allowed primary anastomosis to be performed in obstructed bowel. Fifteen patients, with acute distal obstruction due to carcinoma, diverticulitis or sigmoid volvulus were managed by primary resection and anastomosis. There were two leaks (14 percent) and the duration of operation was prolonged. In an experimental study of anastomotic healing after acute obstruction, intraoperative irrigation improved early anastomotic colonic collagen content (P less than 0.02) and perianastomotic proximal and distal collagen content (P less than 0.002, P less than 0.05). Intraoperative lavage is a useful technique to permit safer primary resection and anastomosis in obstructed colon.

Acute Disease↗

Do magnetic fields influence soft tissue wound healing?--A preliminary communication.

Magnetic fields have been considered for treating many ailments over man's history. There have been many anecdotal unsupported claims for successful treatment of soft tissue injury although reports have been more substantive in the orthopaedic field. The widespread clinical and veterinary use of a light self-adhesive magnetic foil in Europe prompted this trial of experimental wound healing. One hundred and sixty Sprague-Dawley rats had a linear 2.5 cm incision or a circular 1 cm skin defect made over the mid-dorsal spine. Equal numbers were randomised to receive either a magnetic foil or a dummy (control) dressing. At three, seven, 10 or 14 days linear wounds were distracted using a tensiometer; open defects were measured, excised and assayed for collagen content; 14-day wounds were examined histologically. Although wound tensile strengths increased and open wounds decreased in size with increase of hydroxyproline, there were no statistically significant differences between treated or control animals. Although easy to apply the alternate magnetic foil (giving 400 Gauss at 7 mm) conferred no statistically significant effect on soft tissue healing.

Animals↗

An experimental study of the influence of magnetic fields on soft-tissue wound healing.

The influence of magnetized foil strips (Energy-Pak Ltd., Wolfhalden, Switzerland) on soft-tissue healing in the skin of laboratory rats was studied. Linear sutured wounds healing by primary intention have been assessed for tensile strength using Instron tensiometry, and open full-thickness defects healing by secondary intention have been analyzed for collagen content, histologic appearance, and rate of healing. Wounds were covered by the alternate magnetic Energy-Pak foil or by a dummy control. No differences in tensile strength, collagen content, histologic studies, or rate of healing were seen between the treated and control groups.

Animals↗

Relative effects of ileal resection and bypass on intestinal adaptation and carcinogenesis.

Since ileal resection and ileal bypass are commonly performed in man and might stimulate colonic hyperplasia, their co-carcinogenic potential was explored in male Sprague-Dawley rats (n = 135). One week after 33 per cent distal small-bowel resection, 33 per cent distal small-bowel bypass or distal ileal transection (control), animals started a 6-week course of azoxymethane injections (total dose 90 mg/kg ip). Findings in rats killed at 20 and 25 weeks were similar: bypass produced a higher yield of colorectal tumours (4.0 +/- 0.6 per rat: mean +/- s.e.) than controls (2.4 +/- 0.4; P less than 0.05), but resection caused maximal enhancement (5.2 +/- 0.5: P less than 0.01). In rats killed at 30 weeks, however, tumour yields were almost identical. Overall, resection increased colonic tumour yield by 55 per cent (P less than 0.02) and bypass by 32 per cent. Stathmokinetic measurements of crypt cell production rate (CCPR) at 20 weeks showed similar increases after resection and bypass both in residual functioning small bowel (109-200 per cent: P less than 0.01) and in colorectum (63-100 per cent: P less than 0.05). At 30 weeks these adaptive effects persisted, despite an overall increase in CCPR with age. Loss of functioning ileum enhances experimental colorectal carcinogenesis principally by reducing the latent period for tumour development. Resection has a greater effect than bypass probably by producing earlier hyperplasia, though later adaptive effects are similar.

Adaptation, Physiological↗

Adaptation and carcinogenesis in defunctioned rat colon: divergent effects of faeces and bile acids.

Because the composition of faeces modulates colorectal carcinogenesis, promotional effects of the secondary bile salt sodium deoxycholate (SDC) were compared with those of dilute homogenised faeces (12.5% w/v) or saline alone in rat colon isolated from the faecal stream as a Thiry-Vella fistula (TVF). Each fluid was used to irrigate a group of TVFs 3 times per week for 12 weeks. Other rats had TVF without irrigation or colonic transection and reanastomosis (sham TVF). Operations followed a 6-week course of azoxymethane injections. At sacrifice 15 weeks postoperatively crypt depth and tumour yield were reduced to the same extent in both the non-irrigated TVFs and the SDC-irrigated TVFs, when compared to shams. Irrigation with faeces and saline completely restored crypt depth and partly restored tumour yields to the levels in shams. Tumours were smaller in the SDC group than in the other 4 groups. While tumours developed mainly in the left colon of shams, there was significantly more even distribution in the TVFs. Exclusion of the colon from the faecal stream leads to mucosal hypoplasia and impaired carcinogenesis. Irrigation with faeces or saline partly reverses these changes. Deoxycholate has no such effect and clearly is not co-carcinogenic in this model.

Animals↗

Intestinal adaptation and experimental carcinogenesis after partial colectomy. Increased tumour yields are confined to the anastomosis.

Small-bowel resection enhances experimental colorectal carcinogenesis, probably by stimulating epithelial cell proliferation. The possibility that similar mechanisms might explain metachronous large-bowel cancers in man was tested in Sprague-Dawley rats submitted to partial colectomy before or after a five-week course of azoxymethane (total dose 50 mg/kg). The timing of operation did not affect tumour yields at 40 weeks. Caecal resection augmented mucosal mass in the ileum and right colon but did not affect carcinogenesis. Right hemicolectomy only increased ileal segmental weight (by 22%); left hemicolectomy increased the protein and DNA contents of the residual right colon by 18-42%. Large-bowel tumours in 84 rats were distributed as follows: proximal colon 36, colonic anastomosis 51, distal colon 87, rectum 43. Consistent with this left-sided predominance, left hemicolectomy reduced the number of large-bowel tumours. A twofold increase in distal tumours after both transection and right hemicolectomy simply reflected the high incidence of anastomotic tumours. Furthermore, one rat given vehicle as opposed to carcinogen developed an invasive mucinous adenocarcinoma at the colorectal anastomosis, after left hemicolectomy. The large bowel shows limited adaptation to partial resection and is not at increased risk of carcinogenesis, except in the region of the suture line.

Adaptation, Physiological↗

Intermittent claudication: is a supervised exercise class worth while?

Twenty-one patients (19 men and two women) with disabling exercise-related leg pain attended a physiotherapy department on one afternoon each week for an exercise training programme lasting one month. The clinical diagnosis of intermittent claudication and localisation of the atherosclerotic occlusions were confirmed in all but one case by pulse volume recordings and segmental Doppler systolic pressure measurements. Two patients whose symptoms worsened underwent arterial reconstruction. Post-training assessment at six months showed that the remaining 18 patients walked 80% further and performed 75% more step-ups. They also felt much healthier, having unduly restricted their activities before because they had feared the onset of ischaemic leg pain. These results suggest that supervised exercise training is a simple and effective method of treating patients with intermittent claudication.

Blood Pressure↗