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Biomedical subjects

R K Phillips

Publications and source records attributed to R K Phillips.

At least 91 records · Page 5Linked to original sources
PubMed1995

Gender differences in incidence of idiopathic fistula-in-ano are not explained by circulating sex hormones.

The observed increased incidence of idiopathic anal fistulae in men compared with women cannot be explained by the cryptoglandular hypothesis alone. Male predilection is even more pronounced in neonates and is also seen in the canine population. Investigations into hormonal aspects of hidradenitis suppurativa suggest a possible influence of androgens in its pathogenesis. In order to investigate the possibility of a similar effect in fistula-in-ano, we have compared a range of circulating sex hormones in 15 male and 12 female patients with anal fistulae with those in equal numbers of age-matched controls. There were no differences in levels of any measured hormones between male patients and healthy controls. There was no evidence of increased androgenisation of female patients. Women with fistulae had higher levels of circulating oestradiol (253 vs 163 pmol/l, medians, P = 0.03) and lower levels of progesterone (1.05 vs 3.0 nmol/l, medians, P = 0.039) than healthy women. Further work is merited to investigate the possibility of increased local androgen conversion in anal glands.

Adult↗
PubMed1995

A peroperative comparison of Western and Oriental colonic anatomy and mesenteric attachments.

It has been suggested that the Oriental colon is easier to colonoscope than its Western counterpart. The aim of this study was to investigate possible differences in colonic anatomy between Western and Oriental patients that might explain this observation. Measurements of colonic length and mesenteric attachments were taken according to a set protocol from 115 Western (Caucasian) and 114 Oriental patients at laparotomy. Sigmoid adhesions were found more frequently in Western (17%) compared to Oriental (8%) patients, P = 0.047. A descending mesocolon of > or = 10 cm occurred in 10 (8%) Western patients but only 1 (0.9%) Oriental patient, P = 0.01. The splenic flexure was more frequently mobile in Western patients (20%) compared to Oriental (9%) patients, P = 0.016. In 29% - of Western patients the mid-transverse colon reached the symphysis pubis, or lower when pulled downwards in contrast to 10% of Oriental patients, P < 0.001. There was no significant difference in total colonic length comparing Western (median = 114 cm, range 68-159 cm) to Oriental (median = 111 cm, range 78-161 cm) patients. Western patients have a higher incidence of sigmoid colon adhesions and increased colonic mobility when compared to Orientals. These findings support the observation that colonoscopy is a more difficult procedure in Western patients.

Adult↗
PubMed1995

Minimally raised end colostomy.

The traditional maturation of the mucocutaneous junction of an end colostomy often leads to a stoma with no significant projection above the skin. We describe a simple method which allows a small spout to be easily created. This technique has been used in 30 patients and is believed to diminish leakage. A raised stoma is easier for the patient to see and Stoma care nurses prefer them.

Colostomy↗
PubMed1995

Adjuvant radiotherapy and anastomosis in rectal cancer--disturbing evidence from animal studies.

PURPOSE: Adjuvant radiotherapy is used increasingly in the management of rectal cancer. However, ionizing radiation is mutagenic, and, superimposed on a background of increased cellular proliferation as seen around anastomoses and in colorectal cancer patients, there is the potential for enhanced metachronous cancer risk. METHOD: The influence of preoperative irradiation on both carcinogenesis and cellular proliferation at colonic anastomoses was explored in 180 adult male F344 rats. Orthovoltage x-rays were delivered to the distal descending colon by parallel opposed fields. Ninety rats received 16 Gy in one fraction; the remainder received 36 Gy in two fractions one week apart. In each irradiation group 18 rats either acted as controls or one week after radiotherapy underwent distal colotomy and repair. RESULTS: We found the descending colon susceptible to radiation carcinogenesis; 26 colorectal tumors developed in the low-dose irradiation group and 47 in the high-dose group (P = 0.0008; Mann-Whitney U test, 16 vs. 36 Gy). Preferential tumor development was seen in the anastomotic region. In those animals that underwent surgery and irradiation, among the low-dose irradiation group only 3 of 72 had tumors within the descending colon compared with 21 of 72 at the anastomotic site (McNemar's test chi-squared = 40.9; P < 0.001), and in the high-dose irradiation group 5 of 72 had tumors within the descending colon compared with 36 of 72 at the anastomotic site (McNemar's test chi-squared = 22.0; P < 0.001). Anastomotic crypt cell production rates were increased for at least three months following exposure to irradiation (16 Gy: f = 15.1, P < 0.005; 32 Gy: f = 9.4, P < 0.005). CONCLUSIONS: Radiation carcinogenesis is greatly enhanced at colonic anastomoses and may result from altered anastomotic proliferation. This has potentially disturbing implications in view of the increasing use of adjuvant radiotherapy for rectal carcinoma.

Adenocarcinoma↗
PubMed1995

Influence of soluble suture factors on in vitro macrophage function.

Suture materials may interact with immune competent cells and thereby affect localized immunity. Macrophages are central to the inflammatory response and coordinate wound healing. They are also involved in the clearance of foreign material, bacteria and malignant cells. We studied the influence of soluble factors associated with silk, steel, nylon, polyglactin, polydioxanone and chromic catgut sutures on macrophage adherence, phagocytosis and the production of lysozyme and tumour necrosis factor. Soluble factors from suture materials influenced macrophage behaviour in vitro causing cellular activation, functional impairment and alterations in secreted levels of the cytokine tumour necrosis factor and the bactericidal agent lysozyme. Of the six materials studied, polyglactin had the most extreme effect, causing significant inhibition of cell adherence and lysozyme production. Silk also exerted a considerable effect on macrophages, significantly inhibiting adherence. In contrast, steel and polydioxanone media caused minimal inhibition of macrophage function although, as with all materials, they did activate the cells. This study has demonstrated that sutures release immunotoxic factors which considerably influence macrophage behaviour in vitro. These effects may have important clinical implications.

Animals↗
PubMed1995

Caffeine phenotyping of cytochrome P4501A2, N-acetyltransferase, and xanthine oxidase in patients with familial adenomatous polyposis.

Patients with familial adenomatous polyposis (FAP) and age and sex matched controls were tested for cytochrome P4501A2 (CYP1A2), N-acetyltransferase, and xanthine oxidase activities using caffeine urinary metabolites as a discriminator. FAP patients showed significant underactivity of N-acetyltransferase (which inactivates some carcinogens) and significant overactivity of CYP1A2 (which activates some carcinogens). Xanthine oxidase activity, which can generate free radicals and cause cellular damage, was significantly increased in the FAP patients. All but one of the FAP patients had undergone colectomy. A separate group of six patients was therefore assessed before and at an average time of eight weeks after colectomy. No effect on enzyme activity was seen. The differences in enzyme activities detected in this study could produce an excess of active carcinogenic metabolites in the bile of FAP patients and contribute to the high risk for intestinal cancer in FAP.

Acetyltransferases↗
PubMed1995

High pH reduces DNA damage caused by bile from patients with familial adenomatous polyposis: antacids may attenuate duodenal polyposis.

Patients with familial adenomatous polyposis (FAP) develop periampullary duodenal tumours, suggesting that bile contributes to their formation. The hypothesis that bile contains carcinogens has been tested by looking for DNA adducts (markers of carcinogen exposure) in the duodenum of patients with or without FAP and by determining whether bile can produce DNA adducts in vitro. Using 32P-postlabelling to detect adducts, there was an excess (compared with unaffected patients) of DNA adducts in the duodenum of FAP patients and an excess of DNA adducts in the small bowel of rats treated with FAP bile, while bile from FAP patients formed significantly more DNA adducts in vitro than did bile from controls. In this study it is shown that the excess of adduct labelling produced by FAP bile in vitro depends on the pH of the incubate. While adduct labelling at pH 6-8 did not differ significantly between bile from six FAP patients and six controls, at pH 4-5 FAP bile, but not control bile, produced a near threefold excess of adduct labelling over that at pH 6-8. Therapy that increases duodenal pH may therefore alleviate duodenal polyposis.

Adenomatous Polyposis Coli↗
PubMed1994

Surgical assessment of acute anorectal sepsis is a better predictor of fistula than microbiological analysis.

Twenty-two patients with acute anorectal sepsis were examined prospectively to compare surgical assessment with microbiological analysis as predictors of the aetiology of the sepsis. Culture of gut organisms was a sensitive method of detecting an underlying fistula but was not particularly specific (80 per cent). Demonstration of sepsis in the intersphincteric space in association with an anorectal abscess was 100 per cent sensitive and 100 per cent specific for detection of an underlying fistula. The demonstration was facilitated by a radially placed incision.

Abscess↗
PubMed1994

Life-table analysis of stomal complications following ileostomy.

Stomal complications of ileostomy may occur many years after construction. An actuarial analysis of complications of 150 permanent end ileostomies constructed over a 10-year period is reported. By 20 years the incidence of stomal complications approached 76 per cent in patients operated on for ulcerative colitis and 59 per cent in those with Crohn's disease (P < 0.05). Revisional surgery rates were higher in patients with ulcerative colitis than in those with Crohn's disease (28 versus 16 per cent), albeit not significantly. The four commonest complications were skin problems (cumulative probability 34 per cent), intestinal obstruction (23 per cent), retraction (17 per cent) and parastomal herniation (16 per cent). Closure of the lateral space did not reduce the probability of developing intestinal obstruction (18 per cent at 20 years in those with closure versus 3 per cent in those without, P > 0.1). Fixation of the mesentery did not reduce the probability of developing prolapse of the ileostomy (11 per cent in those with fixation versus none in those without, P < 0.1). The incidence of parastomal herniation was not reduced by sitting through the rectus abdominis (21 per cent in those sited through the body of the rectus abdominis versus 7 per cent in those sited through the oblique muscles, P < 0.1). Some of the surgical dogmas relating to ileostomy construction are not supported by the results of this study.

Adolescent↗
PubMed1994

Haemorrhoids: pathology, pathophysiology and aetiology.

Haemorrhoidal disease is the consequence of distal displacement of the anal cushions, which are normal structures with an important role in continence. The causes of haemorrhoidal disease are unknown; constipation and abnormal bowel habit are commonly blamed despite largely contrary evidence. The most consistently demonstrated physiological abnormality is an increased maximum resting anal pressure. Most evidence points to this being a secondary phenomenon rather than the cause of haemorrhoidal disease. Among the many unexplored areas are the function of the longitudinal muscle in relation to haemorrhoidal disease, the description and pharmacological responsiveness of the anal subepithelial muscle, and the clinical role of specific pharmacological agents that might reverse some of the observed physiological changes.

Anal Canal↗
PubMed1994

Factors affecting continence after surgery for anal fistula.

Anorectal physiology and continence were assessed prospectively before and after surgery in 50 patients with chronic perianal sepsis. Functional and physiological parameters were unchanged after surgery in 13 control patients who had sepsis but who did not undergo division of the anal sphincter. Group 1 comprised 22 patients with internal sphincter division alone (15 intersphincteric, seven trans-sphincteric treated by a loose seton technique) and group 2 consisted of 15 patients with a trans-sphincteric fistula laid completely open. In group 1 the median (interquartile range (i.q.r.)) resting pressure in the distal 1 cm of the anal canal was reduced from 68 (60-90) cmH2O before surgery to 44 (35-60) cmH2O after operation (P < 0.001); squeeze pressure was less affected, but function deteriorated in 11 of the 22 patients. The median (i.q.r.) resting pressure in group 2 patients also fell, from 68 (34-84) cmH2O before operation to 28 (20-54) cmH2O afterwards (P = 0.003); median (i.q.r.) maximum squeeze pressure decreased more, from 124 (76-170) cmH2O to 72 (48-112) cmH2O (P = 0.002). Functional deficit occurred in eight of the 15 patients. Incontinence was related to low resting pressure, reflecting internal sphincter integrity, and to local epithelial electrosensitivity (reflecting scarring), but not to squeeze pressure, fistula type or surgical treatment.

Adult↗
PubMed1994

'Reversible chemical sphincterotomy' by local application of glyceryl trinitrate.

Nitric oxide has emerged as one of the most important neurotransmitters mediating internal anal sphincter relaxation. The effect of glyceryl trinitrate, a nitric oxide donor, on anal tone was examined. Maximum resting pressure, predominantly a function of the smooth muscle internal anal sphincter, was measured before and 20 min after application of 0.2 per cent glyceryl trinitrate ointment in ten patients. Pressure decreased by a mean of 27 per cent (95 per cent confidence interval 18-36 per cent) (P = 0.0004) after administration of the drug. A further 20 patients were then randomized to either active or placebo ointment. Anal pressure was significantly decreased (P = 0.002) in those who received 0.2 per cent glyceryl trinitrate, but there was no significant reduction in the control patients. Mild headache occurred in two patients who were given the active preparation and in one who received placebo. Manometry was repeated 9h after application of glyceryl trinitrate and showed a sustained decrease in pressure in two patients. Topical glyceryl trinitrate may have a role in the treatment of anal fissure, haemorrhoids, certain types of constipation and anal pain. It may also reduce injury to the internal sphincter during peranal operations.

Administration, Topical↗
PubMed1994

Detection of free malignant cells in the peritoneal cavity before and after resection of colorectal cancer.

PURPOSE: This study was designed to select the best monoclonal antibody to stain malignant cells in peritoneal wash fluid, and to investigate the incidence of free malignant cells in preresection and postresection colorectal cancer peritoneal washings using a combination of conventional cytology and immunocytochemistry. METHODS: Peritoneal washings were taken from 35 consecutive patients undergoing colorectal cancer resection. RESULTS: Malignant cells were isolated on a density gradient and identified by conventional cytology and an indirect immunoperoxidase stain. Malignant cells were identified in peritoneal washings from 15 patients (preresection only n = 3, postresection only n = 4, both n = 8). The origin of free malignant peritoneal cells in 11 preresection-positive washings must be the serosa. The origin of these cells in the four postresection-positive patients is uncertain: serosal and luminal spillage were considered unlikely and no circulating cells were found in the mesenteric vessels near the tumor. CONCLUSION: Tumor cells may have leaked out from lymphatics cut during the dissection.

Aged↗
PubMed1994

Life table analysis of stomal complications following colostomy.

PURPOSE: This study was designed to evaluate the long-term complication rate of left iliac fossa end sigmoid colostomies and to determine etiologic factors. METHODS: A retrospective chart review and actuarial analysis were performed. RESULTS: The crude and actuarial risks of paracolostomy complications in 203 patients were 51.2 percent and 58.1 percent at 13 years, respectively. Paracolostomy hernia was the most common complication (36.7 percent at 10 years). Siting the stoma through the belly of the rectus abdominis muscle did not reduce the risk of hernia, but an extraperitoneal course had a significantly lower risk of herniation when compared with a transperitoneal course and intestinal obstruction was marginally less frequent. Paracolostomy hernias were otherwise more likely in the elderly, and in those with other abdominal wall hernias. Mesenteric fixation did not reduce the subsequent chance of prolapse. The reduction in the risk of intestinal obstruction when lateral space closure was employed was not statistically significant (4 percent vs. 10 percent, P < 0.1), and all three patients with stomal retraction had had lateral space closure. CONCLUSION: The evidence in this study that spans a 22-year period questions much surgical technical dogma and raises the possibility that parastomal hernias may, like inguinal hernias, represent a failure in the transversalis fascia that might technically be avoidable.

Adult↗
PubMed1994

Magnetic resonance imaging of fistula-in-ano.

PURPOSE: Successful management of anal fistulas depends upon accurate assessment of the primary tract and any secondary extensions. Preoperative imaging has, to date, been disappointing. METHODS: A prospective study of 35 patients with a clinical diagnosis of fistula-in-ano was performed comparing magnetic resonance imaging with the independently documented operative findings. Magnetic resonance imaging was also compared with anal endosonography in 20 patients. RESULTS: Magnetic resonance imaging is accurate and demonstrates pathology missed at surgery by experienced coloproctologists. Magnetic resonance imaging is superior to anal endosonography. CONCLUSIONS: Magnetic resonance imaging is advocated as the method of choice when imaging is required for anal fistulas.

Adult↗
PubMed1994

Results of Delorme's procedure for rectal prolapse.

PURPOSE: This study was designed to examine the results of Delorme's procedure. METHODS: Thirty-two patients (24 males and 8 females, mean age, 70 years) underwent Delorme's procedure between 1978 and 1990 following symptoms lasting between two weeks and ten years. Thirteen patients had had 21 previous operations for prolapse. RESULTS: The mean operation time was 65 minutes. No blood transfusions were needed, there was no operative mortality, and only two patients had complications (one chest infection and one anastomotic dehiscence). No patients were lost to follow-up. Over a mean follow-up of 24 months (4 months to 4 years), 9 patients died of unrelated conditions. There were four recurrences (12.5 percent), two in patients who had each had two previous procedures. Incontinence improved in 46 percent. No patient became constipated and 50 percent of those constipated preoperatively improved. CONCLUSION: Although abdominal rectopexy is safe and has a low recurrence rate (< 5 percent), it involves the hazards of a laparotomy. In addition, up to 40 percent of patients become constipated after rectopexy which may be debilitating. Delorme's procedure has a low morbidity, results in good bowel function, and has a low recurrence rate. It can be performed on unfit patients with possible advantages over rectopexy and perhaps should be used more readily.

Adolescent↗