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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
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↗
PubMed1997

Nutrient regulation of human intestinal sugar transporter (SGLT1) expression.

BACKGROUND: The activity of most intestinal nutrient transporters is adaptively regulated by the type and amounts of nutrients entering the intestinal lumen. The concentration and activity of the intestinal Na+/glucose cotransporter (SGLT1) are regulated by dietary sugars in most animal species. The activity and abundance of SGLT1 in biopsy specimens removed from human jejunal regions exposed to, and having limited access to, luminal nutrients have been measured and compared. AIMS: To study the effects of luminal nutrients on the expression of SGLT1 in the human intestine. PATIENT AND METHODS: Brush border membrane vesicles (BBMV) were prepared from biopsy specimens removed from the intestine of a 50 year old man who had developed a high output jejunal fistula, and adjacent mucosal fistula, a condition present for 12 months after surgery for a strangulated hernia. BBMV prepared from intestine exposed to luminal nutrients, and from dysfunctional intestine with a limited exposure to nutrients, were used to measure Na+ dependent glucose transport and abundance of SGLT1 protein. RESULTS: The levels of SGLT1 activity and abundance in the BBMV prepared from control biopsy specimens were similar to those found in BBMV prepared from the intestine of healthy individuals. BBMV from the dysfunctional intestine, exposed to limited levels of luminal nutrients, had reduced levels of SGLT1 activity. This reduction in SGLT1 activity and abundance was above that associated with any villus atrophy, as assessed by the abundance/activity of lactase and villin concentrations. CONCLUSIONS: These data indicate that the activity and expression of SGLT1 in human intestine is maintained by the presence of luminal nutrients.

Carrier Proteins↗
PubMed1995

Regression and progression of Barrett's oesophagus after antireflux surgery.

The effects of antireflux surgery on Barrett's oesophagus were studied. Fifty-six patients (45 men and 11 women of median age 48.5 (range 20-78) years) with histologically confirmed Barrett's oesophagus (greater than 3 cm in length) and gastro-oesophageal reflux underwent antireflux surgery. Symptoms were noted and patients underwent manometry and pH recording before and after operation, and annual flexible endoscopy. Fundoplication resulted in a significant improvement in lower oesophageal sphincter pressure (median (interquartile range (i.q.r.)) 8 (5-14) mmHg before operation versus 17 (11-22) mmHg after operation, P < 0.001). Twenty-four of the 56 patients had partial or complete regression of Barrett's oesophagus (median (i.q.r.) length 8 (3-18) cm before versus 4 (0-10) cm after operation, P < 0.001) but nine showed progression (median (i.q.r.) length 6 (3-11) cm before versus 10 (6-15) cm after operation, P < 0.01) (median follow-up 5.5 (range 2.0-10.5) years). Carcinoma developed in one patient. The length of Barrett's oesophagus was unchanged in 23 patients. Regression was more likely to occur in patients who underwent fundoplication with previous or concomitant vagotomy (chi 2 = 7.21, 1 d.f., P < 0.01) and in those with a good symptomatic result (chi 2 = 23.52, 1 d.f., P < 0.001).

Adult↗
PubMed1995

Psychiatric consequences of radical curative surgery for gastric cancer.

Radical resection of gastric cancer offers the best hope of cure, but carries the risk of significant psychological morbidity in addition to the well-documented physical complications. In the case presented, recognition of clinical depression after thoracoabdominal gastrectomy enabled successful psychological intervention.

Anxiety↗
PubMed1994

Long-term results of highly selective vagotomy: a prospective study with implications for future laparoscopic surgery.

Between 1979 and 1984, 141 patients (110 men, 31 women) underwent highly selective vagotomy (HSV) by a standard open technique for duodenal ulcer. All patients had received preoperative treatment with full-dose H2-receptor antagonists. Some 107 of these patients underwent HSV for persistent relapse on withdrawal of H2-receptor antagonists (relapsing responders) and 30 because of non-response to such drugs. After 4 years of follow-up, non-responders were found to be more likely to have symptoms after operation (P < 0.001), but did not have a higher rate of recurrent ulceration. At a median of 11 (range 8-14) years after operation 126 patients were still alive; 115 (91 per cent) of these were followed up. Ten patients (9 per cent) were found to have had endoscopically proven recurrence and eight (7 per cent) still had symptoms without evidence of recurrence. The endoscopic recurrence rate and symptom rate at 11 years were no longer significantly different between relapsing responders and non-responders. The preoperative response to H2-receptor antagonist therapy does not help in predicting the likelihood of ulcer recurrence or long-term symptoms after HSV. Post-operative symptoms do not necessarily predict long-term ulcer recurrence. The long-term endoscopic recurrence rate after HSV is low and, if equally good results can be obtained laparoscopically, this will be an important and cost-effective option in the management of duodenal ulcer.

Adolescent↗