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Biomedical subjects

K B Hosie

Publications and source records attributed to K B Hosie.

At least 19 recordsLinked to original sources
PubMed2003

A pilot study of adjuvant intraperitoneal 5-fluorouracil using 4% icodextrin as a novel carrier solution.

AIM: This pilot study utilised the sustained intraperitoneal (i.p.) dwell properties of an iso-osmotic solution of 4% icodextrin to investigate the tolerability, toxicity and feasibility of home-based i.p. 5FU adjuvant chemotherapy following resective surgery for colorectal cancer. METHODS: Twenty eligible patients (Dukes' stage B and C with potentially curative resection) underwent perioperative Tenckhoff catheter placement. Ten (6 male, 4 female, aged 46-85; mean 67.5 years) received 5FU chemotherapy. After initial flushing and gradual increase in volumes of 4% icodextrin alone, patients received home-based i.p. 5FU (150-300 mg/m(2)/day given as equal doses at 12-hourly intervals) for 14 days, with a 14-day recovery period, for a maximum of 6 courses. Two incurable patients, treated on compassionate grounds, provided further safety data. RESULTS: Nine of the 10 patients became proficient in self-treatment with 5FU and two completed 6 courses. Frequent abdominal pain was the main dose-limiting toxicity of 5FU, causing withdrawal of three patients after a high (300 mg/m(2)/day) first course and one following a third course at lower doses. I.p. 5FU concentrations (mean>30000 ngml(-1)) were 1000 fold higher than systemic venous levels. Bacterial peritonitis led to two withdrawals but was not a frequent event (microbiologically confirmed incidence of 1 per 27 catheter-months). CONCLUSIONS: Home-based i.p. adjuvant chemotherapy is a feasible treatment option in patients with surgically resected colorectal carcinoma.

Adenocarcinoma↗
PubMed2003

Management of colorectal cancer: variations in practice in one hospital.

AIMS: The Royal College of Surgeons of England and the Association of Coloproctology of Great Britain and Ireland guidelines for the management of colorectal cancer were published in 1996. We audited our practice against these guidelines. METHODS: Data from 211 consecutive patients undergoing colorectal cancer surgery, between September 1999 and September 2000, have been prospectively collected. Preoperative large bowel and liver imaging, assessment by colorectal specialist nurses and median number of lymph nodes resected have been compared between specialist colorectal and non-colorectal surgeons for rectal and colonic cancers. The adequacy of resection and rates of abdomino-perineal resection have been compared for rectal cancers. Following presentation of our findings, we re-audited practice between January and June 2002. RESULTS: There was marked variation in practice within our hospital. Colorectal specialists were more likely to conform to best practice guidelines, performed fewer abdomino-perineal resections and tended to perform more extensive lymphadenectomy. Following presentation of these data, compliance with guidelines was markedly improved and the number of rectal procedures performed by non-colorectal surgeons decreased. CONCLUSIONS: The ability of audit to change practice has been demonstrated. We feel that completion of this audit cycle has improved the quality of service we provide for colorectal cancer patients in our hospital.

Adult↗
PubMed2002

Perianal Hodgkin's lymphoma complicating Crohn's disease.

BACKGROUND: The perianal region is a very rare location for Hodgkin's lymphoma, and clinicians may often neglect the diagnosis in patients with inflammatory bowel disease. PATIENT PRESENTATION: We present a case of perianal Hodgkin's lymphoma in patient with Crohn's disease who was on long-term immunosuppression and whose symptoms would normally be attributed to Crohn's disease. Diagnosis was based on the morphological appearance of atypical cells in the lamina propria and the immunohistochemical profile of Reed Sternberg and Hodgkin's cells, showing co-expression of CD15 and CD30. CONCLUSION: Perianal complaints in patients with inflammatory bowel disease may be a manifestation of other pathology. Hodgkin's lymphoma could be a progression in the chronically inflamed tissue in this unusual location.

Aged↗
PubMed2002

Acute normovolaemic haemodilution in colorectal surgery.

AIMS: Blood transfusions are often given to surgical patients. This study was designed to assess whether acute normovolaemic haemodilution (ANH) reduces exposure to allogeneic blood, affects clinical outcome and hospital stay, and is feasible in colorectal surgery. METHODS: All ASA 1 and 11 patients undergoing colectomies performed between 1997 and 1999 were identified retrospectively from our colorectal cancer database to ascertain our current peri and postoperative transfusion practice. Twenty-six selected patients subsequently underwent ANH during colectomy surgery. The number of patients and units transfused were identified. RESULTS: One hundred and twenty-three of 317 (39%) patients identified from our colorectal cancer database were transfused a total of 328 units (median 2, range 1-7). Of the 26 patients undergoing ANH, 4 (15%) were transfused a total of 13 units (median 3, range 2-5). The reduction in number of patients transfused was statistically significant (P=0.017). ANH increased anaesthetic time by a median of 19 min. There were no complications associated with ANH and the median hospital stay was 9 days (range 6-13). CONCLUSIONS: In this pilot study of selected patients, ANH is a feasible and effective method of reducing allogeneic blood exposure in major colorectal surgery. A prospective randomised controlled trial is now urgently required.

Adult↗
PubMed2001

Randomized clinical trial of intravenous fluid replacement during bowel preparation for surgery.

BACKGROUND: Bowel preparation using purgatives has previously been shown significantly to increase haemoglobin concentration and decrease weight. This prospective randomized study assessed the effects of administering intravenous fluid during bowel preparation. METHODS: Patients having bowel preparation with Picolax for colonic procedures were randomized prospectively to receive no intravenous fluid (group 1) or calculated intravenous crystalloid based on body-weight (group 2) during preparation. Physiological, haematological and biochemical variables were measured before and after bowel preparation. RESULTS: Forty-one patients were recruited with a median age of 69 (range 29-86) years, 22 in group 1 and 19 in group 2. There was no difference between groups in any of the variables measured before bowel preparation. On completion, there was a significant difference between groups in mean weight loss (P = 0.01), postural change in systolic pressure (P = 0.015) and serum creatinine concentration (P = 0.008). In addition there was a significant fall in erect blood pressure after bowel preparation in group 1 (P = 0.02). The mean urine output in group 1 was 982 ml and in group 2 was 1808 ml (P = 0.004). The faeces weight between groups was not significantly different. CONCLUSION: Picolax bowel preparation has a significant dehydrating effect, which can be minimized by administering a simultaneous volume of intravenous fluid (mean 2 litres in this study).

Adult↗
PubMed2000

Prospective audit following the introduction of short-course preoperative radiotherapy for rectal cancer.

BACKGROUND: The value of introducing a short course of preoperative radiotherapy before operation for rectal cancer is still subject to debate. METHODS: One hundred consecutive patients, of mean age 68 (range 29-87) years undergoing pre- operative radiotherapy for rectal cancer between January 1997 and December 1998 at two radiotherapy centres were audited prospectively. RESULTS: The time from referral to radiotherapy was 33 (11-74) days and from radiotherapy to operation 5 (1-42) days. There was a higher than expected anastomotic leak rate (15 per cent) and perineal wound infection rate (18 per cent). Patients waiting more than 7 days were more likely to suffer perineal wound breakdown: 15 per cent (n = 39) versus 30 per cent (n = 10). CONCLUSION: The high anastomotic leak and perineal wound infection rates suggest that the introduction of preoperative radiotherapy combined with total mesorectal excision should be audited carefully or performed as part of the CRO7 trial. Presented to the Association of Coloproctology of Great Britain and Ireland in St Helier, Jersey, June 1998

Adult↗
PubMed2000

Histopathological detection of lymph node metastases from colorectal carcinoma.

AIM: To evaluate whether the assessment of multiple sections from retrieved nodes yields an increased number of metastases compared with the number that would be detected by the commonly applied method of microscopy of a single section of lymph node only. METHODS: A prospective study of 72 colorectal carcinoma resection specimens. Lymph node sampling was based on the current guidelines for the detection of breast cancer metastases in axillary nodes. Lymph nodes up to approximately 5 mm in maximum extent were processed in entirety, without prior sectioning, and assessed histologically at three levels; larger lymph nodes were processed in entirety as multiple sections and histologically assessed at one level. RESULTS: From a total of 72 carcinomas, eight were Dukes's A, 26 were Dukes's B, and 38 were Dukes's C. The mean and median numbers of nodes identified were 13 and 12, respectively (range, three to 44). Of the Dukes's C cases, four contained lymph node metastases identified by our method that might have gone undetected by the current, generally applied method. In one case, this led to the detection of the only nodal metastasis present and therefore "upstaged" the tumour from Dukes's B to C. On average, six extra tissue blocks were processed for each case in applying this method. CONCLUSION: The assessment of multiple sections of lymph nodes from colorectal specimens leads to the detection of only a small number of additional nodal metastases. The method involves increased workload for pathologists and laboratory staff.

Colorectal Neoplasms↗
PubMed1999

Outcome after surgical resection for high-grade anal intraepithelial neoplasia (Bowen's disease).

BACKGROUND: High-grade anal intraepithelial neoplasia (Bowen's disease) may predispose to anal carcinoma. Treatment options include surgical resection but effectiveness remains uncertain. This paper reports long-term follow-up of patients with high-grade anal intraepithelial neoplasia treated by surgical resection. METHODS: Between 1989 and 1996, 46 patients were identified with high-grade anal intraepithelial neoplasia. Thirty-four underwent local excision of all macroscopically abnormal disease and the resulting defect was left open, closed primarily or skin grafted. Regular follow-up subsequently included anoscopy and biopsy of any suspicious lesions. RESULTS: Median follow-up was 41 (range 12-104) months. Total excision was difficult; 19 patients had histological evidence of incomplete excision at the time of initial resection. Some 12 of 19 had histo-logically proven recurrent high-grade intraepithelial neoplasia within 1 year. Even with microscopically complete excision two of 15 patients subsequently developed recurrent high-grade intraepithelial neoplasia at 6 and 32 months after operation. No patient developed carcinoma but five had complica-tions of anal stenosis or faecal incontinence. CONCLUSION: Although no definite recommendations can be made for the treatment of high-grade anal intraepithelial neoplasia, these results illustrate some potential drawbacks of surgical excision with a high potential for incomplete excision and persistent disease, even after complete excision in some patients, and a high morbidity rate.

Anus Neoplasms↗
PubMed1999

Contribution of the MHC region to the familial risk of coeliac disease.

Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.

Celiac Disease↗
PubMed1999

The use of a proforma improves colorectal cancer pathology reporting.

The detail and accuracy of pathological reporting for colorectal cancer is becoming increasingly recognised as important in the overall management of the patient. However, there is criticism of the variable standards of reporting. We assessed how the use of a proforma affected the completeness of reporting within one hospital. Data on all colorectal cancer patients attending one teaching hospital has been collected prospectively over a 15 month period from 1997 to 1998. The Royal College of Surgeons/Association of Coloproctology proforma lists all items considered to be essential for a complete pathological report of colorectal cancer. Its introduction in September 1997 allowed us to compare reporting before the proforma to that after. Of 54 patients, 46 (85%) had one or more items missing from their report before introduction of the proforma compared with only 8/44 (18%) patients after the proforma (P < 0.001). Circumferential resection margins and apical node status were the items most often absent, being significantly more frequently reported after the proforma (P < 0.05 and P < 0.001, respectively). There was no difference in the median number of lymph nodes harvested after proforma introduction. The introduction of the proforma has not only resulted in improvements in reporting, but has increased the dialogue between surgical oncologists and pathologists. These features should result in improved overall management of the colorectal cancer patient.

Colorectal Neoplasms↗
PubMed1998

Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate.

1. Oligonucleotide primers based on the human heart monocarboxylate transporter (MCT1) cDNA sequence were used to isolate a 544 bp cDNA product from human colonic RNA by reverse transcription-polymerase chain reaction (RT-PCR). The sequence of the RT-PCR product was identical to that of human heart MCT1. Northern blot analysis using the RT-PCR product indicated the presence of a single transcript of 3.3 kb in mRNA isolated from both human and pig colonic tissues. Western blot analysis using an antibody to human MCT1 identified a specific protein with an apparent molecular mass of 40 kDa in purified and well-characterized human and pig colonic lumenal membrane vesicles (LMV). 2. Properties of the colonic lumenal membrane L-lactate transporter were studied by the uptake of L-[U-14C]lactate into human and pig colonic LMV. L-Lactate uptake was stimulated in the presence of an outward-directed anion gradient at an extravesicular pH of 5.5. Transport of L-lactate into anion-loaded colonic LMV appeared to be via a proton-activated, anion exchange mechanism. 3. L-Lactate uptake was inhibited by pyruvate, butyrate, propionate and acetate, but not by Cl- and SO4(2-). The uptake of L-lactate was inhibited by phloretin, mercurials and alpha-cyano-4-hydroxycinnamic acid (4-CHC), but not by the stilbene anion exchange inhibitors, 4,4'-diisothiocyanostilbene-2, 2'-disulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulphonic acid (SITS). 4. The results indicate the presence of a MCT1 protein on the lumenal membrane of the colon that is involved in the transport of L-lactate as well as butyrate across the colonic lumenal membrane. Western blot analysis showed that the abundance of this protein decreases in lumenal membrane fractions isolated from colonic carcinomas compared with that detected in the normal healthy colonic tissue.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

The characterization of butyrate transport across pig and human colonic luminal membrane.

1. Luminal membrane vesicles (LMV) were isolated from human and pig colonic tissues. They were characterized in terms of purity and ability to transport [14C]butyrate. 2. The activity of cysteine-sensitive alkaline phosphatase, and the abundance of villin, NHE2 and NHE3 proteins, markers of the colonic luminal membrane, were significantly enriched in the LMV compared with the original cellular homogenate. The LMV were free from contamination by other cellular organelles and basolateral membranes, as revealed by the negligible presence of either specific marker enzyme activity or characteristic immunogenic protein. 3. The transport of butyrate into the luminal membrane vesicles was enhanced 5-fold at pH 5.5 compared with pH 8.0. Butyrate transport was temperature dependent, and was stimulated in the presence of an outward-directed anion gradient in the order of butyrate > bicarbonate > propionate > chloride. Kinetic analysis of increasing substrate concentration showed saturation kinetics with an apparent Km value of 14.8 +/- 3.6 mM and a Vmax of 54 +/- 14 nmol min-1 (mg protein)-1. 4. Butyrate transport was significantly reduced in the presence of short chain fatty acids (SCFA), acetate, propionate and other monocarboxylates (pyruvate and L-lactate). Butyrate uptake was inhibited by several cysteine group modifying reagents such as p-chloromercuribenzosulphonic acid (pCMBS), p-chloromercuribenzoate (pCMB), mersalyl acid and HgCl2, but not by the stilbene anion exchange inhibitors, 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS) and 4,4'-dinitrostilbene-2,2'-disulphonate (SITS). 5. The described properties of butyrate transport across the luminal pole of the colon suggest the involvement of a carrier protein, in the form of a pH-activated anion exchange process. The transporter is distinct from the erythrocyte band-3 type anion exchanger and may belong to the monocarboxylate-type transport proteins (MCT1).

Animals↗
PubMed1997

Linkage analysis of candidate regions for coeliac disease genes.

A strong HLA association is seen in coeliac disease [specifically to the DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account for the increased risk seen in relatives of affected cases. One or more genes at HLA-unlinked loci also predispose to coeliac disease and are probably stronger determinants of disease susceptibility than HLA. A recent study has proposed a number of candidate regions on chromosomes 6p23 (distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3, 19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked susceptibility gene. We have examined these regions in 28 coeliac disease families by linkage analysis. There was excess sharing of chromosome 6p markers, but no support for a predisposition locus telomeric to HLA. No significant evidence in favour of linkage to coeliac disease was obtained for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or 22cen. There was, however, excess sharing close to D15S642. The maximum non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for linkage of coeliac disease to chromosome 15q26 is not strong, the well established association between coeliac disease and insulin dependent diabetes mellitus, together with the mapping of an IDDM susceptibility locus (IDDM3) to chromosome 15q26, provide indirect support for this as a candidate locus conferring susceptibility to coeliac disease in some families.

Celiac Disease↗