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Biomedical subjects

R K Phillips

Publications and source records attributed to R K Phillips.

At least 55 records · Page 3Linked to original sources

Upper gastrointestinal disease in patients with familial adenomatous polyposis.

BACKGROUND: Upper gastrointestinal disease has become an important aspect in the management of patients with familial adenomatous polyposis (FAP). METHODS: A review of the literature was carried out using Medline. Epidemiology, pathology and treatment options are considered. RESULTS AND CONCLUSION: Despite the fact that over 90 per cent of patients with FAP develop duodenal adenomas, only 5 per cent go on to develop cancer. In the absence of methods to detect who is at risk of cancer, all patients undergo regular endoscopic surveillance at present. Chemoprevention in the form of drug therapy may be the answer to controlling the disease.

Adenomatous Polyposis Coli↗

A survey of phenotypic features in juvenile polyposis.

Solitary juvenile polyps are quite frequent in children, but juvenile polyposis (JP) is a rare autosomal dominant trait characterised by the occurrence of numerous polyps in the gastrointestinal tract. Extracolonic phenotypic abnormalities are well documented in patients with familial adenomatous polyposis and Peutz-Jeghers syndrome and can allow a clinical diagnosis to be made before the bowel pathology becomes available. Though described, characteristic extracolonic abnormalities have not been clearly defined in juvenile polyposis. We sought to determine whether there are consistent extracolonic phenotypic abnormalities in JP patients and how frequently this would allow diagnosis of one of the genetic syndromes known to be associated with juvenile polyposis. Twenty-two JP patients underwent clinical examination and data from one patient were obtained from case notes. Those consenting to further investigations had x rays of the skull, chest, and hands and an echocardiogram if clinically indicated. Significant extracolonic phenotypic abnormalities were present in 18 patients (14 male and four female), and included dermatological (13), skeletal (16), neurological (5), cardiopulmonary (4), gastrointestinal (3), genitourinary (4), and ocular (1) features. In five patients the diagnosis of a genetic syndrome was possible: two had Bannayan-Riley-Ruvalcaba syndrome, two had Gorlin syndrome, and one had hereditary haemorrhagic telangiectasia (HHT, also known as Osler-Rendu-Weber syndrome). Other patients had some features of these conditions and of Cowden and Simpson-Golabi-Behmel syndromes, but these were not sufficient to allow a definitive diagnosis.

Adult↗

The use of 32P-postlabelling in studies of the nature and origin of DNA adducts formed by bile from patients with familial adenomatous polyposis and from normal patients.

32P-postlabelling is a highly sensitive technique for the detection of DNA adducts. It is unique in that it requires no prior knowledge of the nature of adducts or adduct-forming species under investigation. In the past, we have used this technique to investigate the role of bile in the production of foregut adenomas in patients with familial adenomatous polyposis (FAP). We have found that bile contains constituents that form DNA adducts directly, and after metabolic activation, and that the bile of FAP patients has an increased capacity for adduct formation with DNA in vitro, in human cell lines in culture, and in the gastrointestinal tract of rats given bile by gavage. The sensitivity of 32P-postlabelling is such that it is difficult to obtain sufficient quantities of DNA adducts for chemical analysis. The nature of the adducts produced by bile, or of the bile constituents that produce them is as yet undetermined. In the present studies, we have combined 32P-postlabelling with indirect methods to gain some insight into the nature of DNA adducts produced by bile and the properties of the reactive species that form them. Firstly, bile was incubated with synthetic monodeoxynucleotides or polydeoxynucleotides. Bile did not produce adducts when incubated with monodeoxynucleotides or single-stranded polydeoxynucleotides. However, it did produce adducts when incubated with double-stranded polydeoxynucleotides. The pattern of adduct formation suggested that human bile forms a mixture of adenine and guanine adducts. Secondly, bile was fractionated by extraction with blue cotton or with neutral, acid or alkaline organic solvent. Blue cotton, which efficiently and selectively absorbs mutagens having 3 or more fused aromatic rings, did not absorb biliary constituents that could form adducts with DNA in vitro or with DNA of MCL-5 cells, a metabolically competent human cell line. This suggests that biliary DNA adduct precursors are polar compounds that contain fewer than 3 aromatic rings or are non-aromatic. Acidic organic extracts of human bile produced much higher levels of DNA adducts in vitro or with DNA of MCL-5 cells than did neutral or alkaline organic extracts, suggesting that constituents of bile that form DNA adducts are acidic in nature.

Adenomatous Polyposis Coli↗

Sphincteroplasty for incontinence after surgery for idiopathic fistula in ano.

Between 1990 and 1992, external sphincter repair was performed in 20 patients rendered faecally incontinent after earlier fistula surgery. All were improved, 13 (65%) achieving Grade 1 or 2 continence. Postoperative ultrasound was useful in explaining the sub-optimal outcome of 3 patients who still had defects. Clinical outcome in female patients was better than in male patients. Clinical outcome was not related to the results of preoperative manometry, the site of external sphincter damage, the use of a stoma, or the occurrence of wound complications. External sphincter repair for faecal incontinence after fistula surgery achieves good results in the majority of patients.

Adult↗

Patterns of prolapse in women with symptoms of pelvic floor weakness: assessment with MR imaging.

PURPOSE: To show the magnetic resonance (MR) imaging patterns of prolapse and to correlate them with symptoms in patients with constipation or fecal incontinence. MATERIALS AND METHODS: Thirty women underwent MR imaging with fast spoiled gradient-recalled acquisition in the steady state. The women were divided into three groups: 10 were asymptomatic volunteers, 10 had constipation, and 10 had fecal incontinence. Visceral prolapse and the configuration of the pelvic floor muscles were identified at rest and during straining. Visceral descent was compared between the three groups. RESULTS: Visceral prolapse was seen at multiple sites, most frequently in constipated patients. There was significantly greater bladder base descent (P < .01), uterocervical descent (P < .001), and puborectalis muscle ballooning (P < .05) in the group of constipated patients when compared with the group with fecal incontinence or the asymptomatic group. The degree of anorectal junction descent was significantly greater (P < .05) in the group of incontinent patients when compared with the asymptomatic group. CONCLUSION: MR imaging clearly shows pelvic visceral prolapse and pelvic floor configuration on straining. Prolapse frequently involves multiple sites in constipated patients, which is suggestive of global pelvic floor weakness. In contrast, the weakness is frequently posterior in fecally incontinent patients.

Adult↗

MR appearances of desmoid tumors in familial adenomatous polyposis.

OBJECTIVE: The purpose of this study was to investigate the ability of MR imaging to show desmoid tumors in patients with familial adenomatous polyposis, to document the appearances of these tumors, and to identify possible predictors of growth. SUBJECTS AND METHODS: CT and MR imaging of 15 patients with familial adenomatous polyposis and known abdominal wall or intraabdominal desmoid tumors were performed. Nine patients underwent follow-up CT and MR imaging, and four patients had undergone CT within the previous 12 months. Unenhanced and gadolinium-enhanced T1-weighted MR imaging sequences and T2-weighted MR imaging sequences were performed, as was unenhanced and IV contrast-enhanced helical CT. The CT and MR images were independently assessed. RESULTS: CT revealed 35 desmoid tumors: 22 were intraabdominal and 13 were in the abdominal wall. MR imaging revealed 21 of the 22 intraabdominal desmoid tumors and 13 of the 13 abdominal wall desmoid tumors. MR imaging and CT findings agreed precisely on the site and margin of the intraabdominal and abdominal wall desmoid tumors. CT was more effective in revealing their relationship to the bowel. Contrast enhancement was more easily identified on MR images than on CT scans, especially when enhancement was inhomogeneous. High signal intensity on T2-weighted images was seen in eight desmoid tumors, all of which showed significant growth on follow-up scans. CONCLUSION: MR imaging can show both intraabdominal and abdominal wall desmoid tumors in patients with familial adenomatous polyposis. High signal intensity on T2-weighted images was seen from desmoid tumors that had shown marked growth on follow-up imaging.

Adenomatous Polyposis Coli↗

p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis.

BACKGROUND: The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients. METHODS: Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.

Adenoma↗

Advanced nursing practice with the Indian Health Service.

Work with the US Indian Health Service is an exciting and rewarding experience. It allows family nurse practitioners the opportunity to use a wide range of skills and to develop true family and community involvement.

Health Services Needs and Demand↗

Magnetic resonance imaging of the pelvic floor in patients with obstructed defaecation.

BACKGROUND: Evacuation proctography and measurements of anorectal physiology are frequently used to clarify the pathophysiology of obstructed defaecation. In some patients these tests are normal, despite convincing clinical evidence of defaecatory difficulty. The aim of this study was to determine whether magnetic resonance imaging (MRI) could reveal pelvic floor abnormality in patients with obstructed defaecation. METHODS: Eleven women with obstructed defaecation, in whom evacuation proctography and anorectal physiology were normal, were examined by MRI, using a fast gradient echo sequence. Measurements of pelvic visceral and muscular descent were taken at rest and during straining, and compared with those obtained from 13 asymptomatic volunteers. RESULTS: Patients with obstructed defaecation had significantly greater pelvic visceral descent (P < 0.05), levator muscle descent (P = 0.04), levator plate angle change (P = 0.003) and increase in the area of the pelvic floor hiatus (P = 0.0002) than asymptomatic volunteers. CONCLUSION: MRI demonstrated marked pelvic visceral and levator muscle descent in women with obstructed defaecation, despite normal evacuation proctography and anorectal physiology. MRI should be considered if these examinations have been normal.

Adolescent↗

Topical glyceryl trinitrate in the treatment of chronic anal fissure.

The aetiology of anal fissure is unclear, but there is an association with high maximum resting pressure (MRP). Internal sphincterotomy reduces MRP and heals fissure through an increase in local blood supply. Glyceryl trinitrate (GTN) is a nitric oxide donor which contributes to internal anal sphincter relaxation via a non-adrenergic non-cholinergic pathway. GTN ointment was applied topically in different concentration to the anal margin in patients with chronic anal fissure to monitor its effect primarily on MRP and secondarily on fissure healing. Nineteen patients with chronic anal fissure were treated with ointment containing increasing concentrations of GTN (0.2-0.8 per cent) to produce a reduction in MRP of greater than 25 per cent. The actual dose of GTN varied as no standard delivery system has been developed, but a 'typical amount' of GTN ointment weighed about 200 mg. In 15 of 19 patients, a concentration greater than 0.2 per cent was required to lower the MRP by at least 25 per cent. The minimum concentration of GTN that reduced the resting pressure by at least 25 per cent was prescribed and local application was carried out by the patient twice daily for 6 weeks. At 6 weeks, nine patients had healed, six required sphincterotomy and four were lost to follow-up. Eight of the nine patients with healed fistula required a GTN concentration of 0.3 per cent or more. Sixteen patients were resistant to the usually effective does of 0.2 per cent GTN. In three there was tachyphylaxis and the duration of action of GTN was less than the 12 h described previously in control patients. Two patients did not fulfil the study because of headache.

Administration, Topical↗

Desmoids in familial adenomatous polyposis.

Clinical desmoid disease affect approximately 10 per cent of patients with familial adenomatous polyposis (FAP); the subclinical rate is unknown. Desmoids are probably neoplastic rather than regenerative in origin and may arise in association with germline or somatic mutations at or beyond codon 1444 of the APC gene. Intra-abdominal desmoids behave unpredictably but are an important cause of death in those with FAP. Signal intensity on magnetic resonance imaging reflects tumour cellularity, which in part determines progression, and this may help management. Surgical treatment of advanced desmoids is hazardous, but medical treatments have limited success. Chemotherapy with doxorubicin and dacarbazine is currently under evaluation.

Adenomatous Polyposis Coli↗