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Biomedical subjects

R Sexton

Publications and source records attributed to R Sexton.

At least 19 recordsLinked to original sources
PubMed2006

Operability and early outcome in 100 consecutive laparotomies for peritoneal malignancy.

BACKGROUND: Peritoneal malignancy is common at the terminal stages of many intra-abdominal neoplasms. In selected patients a novel approach of complete macroscopic tumour removal by extensive surgical cytoreduction, combined with intraperitoneal chemotherapy, provides a possibility of cure. Initial experience with 100 consecutive laparotomies is reported. METHODS: Between 1994 and 2002, 218 patients with peritoneal malignancy were referred to a specialized unit. One hundred underwent laparotomy, of whom 85 had a primary appendiceal tumour. Treatment aims were complete macroscopic tumour excision combined with intraoperative intraperitoneal chemotherapy. RESULTS: Sixty-five patients had complete macroscopic tumour excision, 28 palliative major cytoreduction and seven were inoperable. The overall mortality rate was 8 per cent. The most common complications were pulmonary (25 per cent) and wound (14 per cent) infection. At a median follow-up of 30 (range 3-113) months, 44 of 51 patients with primary appendiceal tumours who had complete macroscopic cytoreduction were alive and 36 were disease free. CONCLUSION: Cytoreduction combined with intraperitoneal chemotherapy is an emerging technique with promising results in selected patients with peritoneal malignancy.

Adult↗
PubMed2005

Elevated tumour markers prior to complete tumour removal in patients with pseudomyxoma peritonei predict early recurrence.

OBJECTIVE: To assess the potential value of pre-operative CEA, CA 125 and CA 19-9 in identifying Pseudomyxoma peritonei (PMP) patients at risk of recurrence following complete cytoreductive surgery and intraperitoneal chemotherapy. METHOD: Between March 1996 and October 2001, 35 patients, with documented pre-operative tumour marker measurements, underwent complete cytoreduction. Outcome in the 32 survivors was recorded. RESULTS: Median age was 53 years (range: 32-74). There were 17[53%] females. In 9/32[28%] all tumour markers were normal. The most common abnormality was elevated CEA level in 14/32[44%]. Median follow up was 23 months (range: 11-74). Recurrence was detected in 8/32[25%]. The 2-year recurrence free interval was 53% in those with elevated CEA compared with 94% with normal CEA. The 2-year disease free intervals were 100% in 9 patients with normal preop markers compared with 66% for the group with at least one abnormal marker. CONCLUSION: PMP patients with elevated CEA, or more than one abnormal serum tumour maker, are at risk of developing recurrent disease.

Adult↗
PubMed2005

Almost all five year disease free survivors are cured following rectal cancer surgery, but longer term follow-up detects some late local and systemic recurrences.

BACKGROUND: The necessity, timing and benefits of follow-up after rectal cancer surgery remain controversial, with two years traditionally considered adequate to detect most local recurrences. This unit has a policy of lifetime follow-up, and this paper investigates, at 23 years, the value of prolonged surveillance. METHOD: Six hundred and sixty consecutive patients undergoing surgery for rectal cancer were prospectively followed-up between 1978 and 2002, and local or systemic recurrence recorded. This analysis was performed on the 509/660 (76%) patients who underwent potentially curative surgery. RESULTS: Total mesorectal excision (TME) was performed in 422/509 (83%) patients, mesorectal transection in 78 (15%), and local excision in 9 (2%). Follow-up ranged from 1 to 23 years (mean = 9.7). Seven (1.4%) patients had local recurrence alone, 11 (2.2%) local plus systemic, and 86 (17%) systemic recurrence alone. Of the local recurrences 3 (17%) became evident within 1 year, 9 (50%) within 2 years, 16 (89%) within 5 years, and 2 (11%) presented after 5 years, at 5.6 and 5.8 years. Of the systemic recurrences 26 (27%) became evident within 1 year, 57 (59%) within 2 years, 93 (96%) within 5 years, and 4 (4%) presented after 5 years at 5.3, 5.3, 5.4 and 7.9 years. CONCLUSION: This long-term surveillance of patients undergoing curative surgery for rectal cancer demonstrates that most local and systemic recurrences occur within 5 years. Almost half occurred more than 2 years after surgery. However, those centres wishing to set standards of care, or evaluate current or new therapies in rectal cancer treatment, should be aware that unexpected late recurrences occasionally develop.

Adult↗
PubMed2003

Optimal preoperative assessment and surgery for rectal cancer may greatly limit the need for radiotherapy.

BACKGROUND: Radiation is being used increasingly in the management of patients with rectal cancer. Over the past decade the Basingstoke Colorectal Research Unit has combined precision total mesorectal excision with the highly selective use of preoperative radiotherapy. METHODS: One hundred and fifty consecutive patients who underwent major surgical excision for cancers of all stages comprised the study group. Preoperative clinical assessment was based largely on tumour size, fixation and distance from the anal verge. Only preoperative radiotherapy was considered and this only for tumours judged to be at high risk of mesorectal fascia involvement. RESULTS: During a 5-year period 35 of 150 patients were selected for preoperative irradiation. In the non-irradiated patients the local recurrence rate after a median follow-up period of 870 (range 51-1903) days was 2.6 per cent (three of 115 patients), compared with 17.1 per cent (six of 35 patients) in those chosen for irradiation. Sixty patients (52.2 per cent) who were not irradiated were node positive. The local recurrence rate for the whole group was 6.0 per cent. CONCLUSION: The great majority of patients undergoing major excision for rectal cancer can be managed without radiation therapy if the preoperative assessment of the mesorectal fascia and surgery are performed optimally.

Adult↗
PubMed2003

Caspase-9 activation in hypoxic human corneal epithelial cells.

The purpose of this study was to determine the effect of hypoxia on caspase-8 and -9 gene and protein expression and activity in corneal epithelium. Non-transformed human corneal epithelial cells (HCEC) were cultured in 2% oxygen. A cDNA expression array coupled with densitometric analysis was used to compare relative mRNA expression levels of 96 apoptosis-related genes in hypoxic and normoxic HCEC. Caspase-8, caspase-9, FLIP, Fas, FasL, and TNFalpha protein expression was assessed further using Western blot analysis and ELISA. Caspase-8 and -9 activities were measured using a fluorometric activity assay. Hypoxia did not affect caspase-8 or -9 gene or protein expression in HCEC, however caspase-9 activity was significantly increased. Hypoxia significantly suppressed the activity of caspase-8. FLIP and Fas gene and protein expression were not significantly altered in hypoxic cells compared to normoxic controls. mRNA and protein levels of TNFalpha and TNFR-1 were significantly decreased, while FasL mRNA and proteins levels were significantly increased in hypoxic HCEC. In corneal epithelium stressed by hypoxia caspase-9 activity is upregulated, suggesting that apoptosis proceeds via the mitochondrial pathway. Caspase-8 activity may be suppressed because the loss of TNFalpha and TNFR-1 gene and protein expression inhibits the initial formation of a death signaling complex.

Apoptosis↗
PubMed2003

A 5-cm colonic J pouch colo-anal reconstruction following anterior resection for low rectal cancer results in acceptable evacuation and continence in the long term.

BACKGROUND: Optimal treatment for low rectal cancer is total mesorectal excision, with most patients suitable for low colo-rectal or colo-anal anastomosis. A colon pouch has early functional benefits, although long-term function, especially evacuation, might mitigate against its routine use. The aim of this study was to assess evacuation and continence in patients with a colon pouch, and to examine the impact of possible risk factors. METHODS: In 1998, all 102 surviving patients with a colon pouch, whose stoma had been closed for more than one year, were sent a postal questionnaire. A composite incontinence score was calculated from questions on urgency, use of a pad, incontinence of gas, liquid or faeces; and a composite evacuation score from questions on medication taken to evacuate, straining, the need and number of times returned to evacuate. RESULTS: The response rate was 90% (50 M, 42 F), with a median age of 68 years (IQR 60-78) and median follow-up of 2.6 years (IQR 1.7-3.9). The anastomosis was 3 cm or less from the anus in 45/92 (49%), and incontinence scores were worse in this group (P = 0.001). There were significantly higher incontinence scores in females (P = 0.014). Age, preoperative radiotherapy, part of colon used for anastomosis, postoperative leak and length of follow-up had no demonstrable effect on either score. CONCLUSION: Gender and anastomotic height were the only variables which influenced incontinence. Ninety percent of patients reported that their bowel function did not affect their overall wellbeing, and none would have preferred to have a stoma.

Aged↗
PubMed2001

Stoma-related complications are more frequent after transverse colostomy than loop ileostomy: a prospective randomized clinical trial.

BACKGROUND: The consequences of leakage from low colorectal or coloanal anastomoses are reduced by the use of a loop stoma to divert the faecal stream. Controversy continues as to whether loop ileostomy (LI) or loop transverse colostomy (LTC) is the optimal method of defunctioning such anastomoses. METHODS: Patients requiring defunctioning following anterior resection and total mesorectal excision were randomized to receive either LI or LTC. Comparison was made between the groups regarding the difficulty of stoma formation and closure, the recovery after stoma closure and stoma-related complications. The minimum follow-up after stoma closure was 6 months (median 36 months). RESULTS: Between October 1995 and August 1999, 70 patients were randomized (LTC 36, LI 34) of whom 63 underwent stoma closure (LTC 31, LI 32). There were no significant differences in the difficulty of formation or closure, or in the postoperative recovery between the groups. However, there were ten complications related directly to the stoma in the LTC group: faecal fistula (one patient), prolapse (two), parastomal hernia (two) and incisional hernia during follow-up (five). None of these complications occurred in the LI group. CONCLUSION: In this randomized study, the frequency of herniation before or after colostomy closure supports the choice of LI as a method of defunctioning a low anastomosis. Both methods appear to provide satisfactory protection for the low anastomosis.

Adult↗
PubMed2000

Analysis of gene promoters for two tomato polygalacturonases expressed in abscission zones and the stigma.

The tomato (Lycopersicon esculentum cv Ailsa Craig) polygalacturonase genes TAPG1 (LYCes;Pga1;2) and TAPG4 (LYCes;Pga1;5) are abundantly expressed in both abscission zones and the pistils of mature flowers. To further investigate the spatial and temporal expression patterns for these genes, the TAPG gene promoters were ligated to beta-glucuronidase (GUS) reporter genes and transformed into tomato. GUS expression with both constructs was similar and entirely consistent with the expression patterns of the native gene transcripts. GUS activity was observed in the weakening abscission zones of the leaf petiole, flower and fruit pedicel, flower corolla, and fruit calyx. In leaf petiole and flower pedicel zones this activity was enhanced by ethylene and inhibited by indole-3-acetic acid. On induction of abscission with ethylene, GUS accumulation was much earlier in TAPG4:GUS than in TAPG1:GUS transformants. Moreover, TAPG4:GUS staining appeared to predominate in the vascular bundles relative to surrounding cortex cells whereas TAPG1:GUS was more evenly distributed across the separation layer. Like the native genes, GUS was also expressed in the stigma. Activity was not apparent in pistils until the flowers had opened and was confined to the stigma and style immediately proximal to it. A minimal promoter construct consisting of a 247-bp 5'-upstream element from TAPG1 was found to be sufficient to direct GUS expression in both abscission zones and the stigma.

Ethylenes↗
PubMed1998

Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997.

OBJECTIVE: To examine the role of total mesorectal excision in the management of rectal cancer. DESIGN: A prospective consecutive case series. SETTING: A district hospital and referral center in Basingstoke, England. PATIENTS: Five hundred nineteen surgical patients with adenocarcinoma of the rectum treated for cure or palliation. INTERVENTIONS: Anterior resections (n = 465) with low stapled anastomoses (407 total mesorectal excisions), abdominoperineal resections (n = 37), Hartmann resections (n = 10), local excisions (n = 4), and laparotomy only (n = 3). Preoperative radiotherapy was used in 49 patients (7 with abdominoperineal resections, 38 with anterior resections, 3 with Hartmann resections, and 1 with laparotomy). MAIN OUTCOME MEASURES: Local recurrence and cancer-specific survival. RESULTS: Cancer-specific survival of all surgically treated patients was 68% at 5 years and 66% at 10 years. The local recurrence rate was 6% (95% confidence interval, 2%-10%) at 5 years and 8% (95% confidence interval, 2%-14%) at 10 years. In 405 "curative" resections, the local recurrence rate was 3% (95% confidence interval, 0%-5%) at 5 years and 4% (95% confidence interval, 0%-8%) at 10 years. Disease-free survival in this group was 80% at 5 years and 78% at 10 years. An analysis of histopathological risk factors for recurrence indicates only the Dukes stage, extramural vascular invasion, and tumor differentiation as variables in these results. CONCLUSIONS: Rectal cancer can be cured by surgical therapy alone in 2 of 3 patients undergoing surgical excision in all stages and in 4 of 5 patients having curative resections. In future clinical trials of adjuvant chemotherapy and radiotherapy, strategies should incorporate total mesorectal excision as the surgical procedure of choice.

Adenocarcinoma↗
PubMed1997

Abdominoperineal excision of the rectum--an endangered operation. Norman Nigro Lectureship.

PURPOSE: This study was undertaken to test the efficacy of an extreme policy of sphincter conservation by combining precise total mesorectal excision with low stapling techniques and endoluminal lavage to guard against implantation. METHODS: A total of 136 consecutive operations for cancer below 5 cm from the anal verge has been prospectively documented and followed for a mean of 7.7 (range, 1-18) years. A total of 105 of the operations were anterior resections (77 percent), and 31 were abdominoperineal excisions (23 percent). RESULTS: The oncologic results in the 105 patients who underwent anterior resections appear greatly superior to those of the patients who underwent abdominoperineal excisions, although the number of abdominoperineal excisions was small (31). Actuarial local recurrence at six years for anterior resection and total mesorectal excision was 1 percent for 85 curative procedures and 4 percent for all cases (n = 100), compared with 33 and 47 percent for abdominoperineal excisions (n = 15 and 31). Only four recurrences were observed below the level of the levators, three in the wound of an abdominoperineal excision and one in a stapled anastomosis after a palliative excision. No cases of nodal metastasis in the ischiorectal fossa were observed. CONCLUSION: In a unit specializing in sphincter conservation, precise total mesorectal excision from above appears oncologically superior to abdominoperineal excision. Three-fourths of patients with carcinoma of the lower one-third of the rectum can be offered sphincter-conserving surgery, although temporary defunctioning is probably prudent in such cases. The wound of an abdominoperineal excision may be a prerequisite for perineal recurrence, which may often be caused by implantation.

Abdomen↗
PubMed1996

Regulation of the iron uptake genes in Pseudomonas fluorescens M114 by pseudobactin M114: the pbrA sigma factor gene does not mediate the siderophore regulatory response.

The iron-regulated PbrA sigma factor dictates the production of the siderophore, pseudobactin M114, and its cognate outer membrane receptor, PbuA, in Pseudomonas fluorescens M114. However, the siderophore molecule also has a role in regulating the expression of the siderophore biosynthetic and siderophore receptor genes in P. fluorescens M114. This is based on the fact that beta-galactosidase levels from lacZ fusions of M114 siderophore promoters (biosynthetic and receptor) were reduced in M114 siderophore biosynthetic mutants compared to wild-type M114. Expression of both promoters was increased by the addition of pseudobactin M114 to the growth medium. This effect was widespread and applicable to all but one of the siderophore negative strains of M114 tested. Furthermore, it was demonstrated that transcription of the pbr A sigma factor gene was not reduced in the siderophore biosynthetic mutants. This excludes the possibility that reduced expression of the siderophore biosynthetic and receptor promoters in the siderophore biosynthetic mutants is mediated at the level of expression of the pbr A gene itself. In addition, it was noted that the siderophore regulated response was applicable to promoters with and without the DNA sequence motif, (G/C)CTAAATCCC, which is required for iron-regulated expression of some pseudomonad promoters.

Bacterial Proteins↗
PubMed1996

Transcriptional regulation of the iron-responsive sigma factor gene pbrA.

In response to the intracellular iron concentration Pseudomonas fluorescens M114 coordinately regulates the production of pseudobactin M114, its cognate receptor PbuA, and a casein protease. Transcriptional initiation of this coordinate iron-stress response requires the sigma factor PbrA. PbrA is a member of the ECF (Extracytoplasmic function) subgroup of the sigma 70 family of eubacterial RNA polymerase sigma factors. Regulatory studies of the pbrA gene utilising promoter-lacZ transcriptional fusions demonstrate that expression of pbrA dictates the cellular response to iron. pbrA is transcribed in all phases of iron-limited growth but maximally at late-logarithmic to stationary phase. pbrA expression is independent of autoregulatory control but is strictly repressed in iron-rich conditions in a Fur-dependent fashion. Constitutive expression of pbrA from an inducible tac promoter permits the induction of PbrA-dependent transcription and pseudobactin M114 biosynthesis in high-iron conditions. A PbrA consensus sequences was derived from significant DNA sequence homologies observed within the "-25 bp" and "-16 bp" regions conserved among all PbrA-dependent promoters. The predicted PbrA target promoter consensus is homologous for the promoter recognition sites for other environmentally responsive ECF sigma factors.

Amino Acid Sequence↗
PubMed1995

The functional neuroanatomy of Tourette's syndrome: an FDG-PET Study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness.

We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioural features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex.

Adult↗
PubMed1995

Iron-responsive gene expression in Pseudomonas fluorescens M114: cloning and characterization of a transcription-activating factor, PbrA.

In response to iron limitation. Pseudomonas fluorescens M114 induces a number of genes including an iron-scavenging siderophore termed pseudobactin M114, its cognate receptor, PbuA, and a casein protease. A Tn5lacZ-induced mutant (M114FA1) was isolated that exhibits a pleiotropic phenotype and lacks the ability to express these iron-regulated genes. A cosmid clone was identified which complements this mutation. This clone is capable of activating a number of iron-regulated promoter fusion constructs from P. fluorescens M114 and Pseudomonas putida WCS358 and can also promote expression of these fusions in Escherichia coli. A series of insertion mutants was constructed by homologous recombination which were unable to transcribe the promoter fusions. DNA sequence analysis of the complementing region identified one open reading frame (ORF) termed pbrA (pseudobactin regulation activation) and the deduced amino acid sequence shows domains with significant homology to a number of ECF (extracytoplasmic function) transcriptional regulators of the sigma 70 sigma factor family, including fecl required for expression of the ferric dicitrate outer-membrane receptor protein of E. coli. Sequences upstream of the pbrA gene suggest that transcription of pbrA may also be iron regulated.

Amino Acid Sequence↗
PubMed1994

Functional brain MR imaging based on bolus tracking with a fast T2*-sensitized gradient-echo method.

Dynamic physiological scanning, based on temporary changes in local field homogeneity during the passage of a contrast agent bolus, has been performed hitherto with echo-planar imaging (EPI) or conventional gradient-recalled techniques (FLASH). Here, it is shown that the T2* sensitivity of conventional FLASH techniques can be improved drastically on a conventional whole body instrument by delaying the gradient-echo until the subsequent TR-period without increasing total imaging time. Examples are given for a full k-space matrix (128 x 256) obtained within 2 s with a TE of 25 ms, resulting in images free of artifacts. The method is applied to bolus tracking through the brain of healthy volunteers during visual stimulation and in the dark. An average increase of regional cerebral blood volume (rCBV) in the visual cortex of 10.9% (n = 9, p = .001) was found.

Blood Volume↗