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N R Hall

Publications and source records attributed to N R Hall.

At least 19 recordsLinked to original sources
PubMed2006

Melaena as the presenting symptom of gastric mucosal injury due to blunt abdominal trauma.

Blunt abdominal trauma is a common cause of admission to the typical trauma centre. Hollow viscus injury from blunt trauma, however, is unusual and rarely involves the stomach. A 15 year old boy sustained a bicycle handle bar injury to the abdomen and presented to the casualty department four days later with melaena. A computed tomography (CT) scan of the abdomen showed normal findings but endoscopy revealed two "kissing" areas of mucosal ulceration on the anterior and posterior wall of the gastric antrum. The patient received a blood transfusion for anaemia but was otherwise treated conservatively and made a full recovery. The authors believe this to be the first reported case of melaena as the primary presenting symptom of gastric ulceration secondary to blunt abdominal trauma. Diagnosis of hollow viscus injuries due to blunt abdominal trauma requires a high index of suspicion and thorough investigation, particularly if the presentation is delayed.

Abdominal Injuries↗
PubMed2005

How has the 'two-week wait' rule affected the presentation of colorectal cancer?

OBJECTIVE: To assess the impact of the 'two-week wait' rule on the presentation of colorectal cancer. METHODS: A retrospective study of all patients referred to a fast-track clinic in a colorectal cancer centre over an 18-month period, documenting outcome, especially colorectal cancer diagnosis. Comparison was made with patients diagnosed with colorectal cancer presenting via other routes in the same time period. RESULTS: Over an 18-month period, 462 patients were seen in the fast-track clinic and 64 (13.8%) were diagnosed with colorectal cancer. A further 131 patients with colorectal cancer presented to the department in the same time period through other means; 66 via standard out-patient letters, 26 from other departments and 39 (20%) as emergency admissions. Median (range) time to first clinic was 12 (2-28) days for fast-track and 24 (1-118) days for standard referrals (P < 0.0001); median time to first treatment was a further 36 (9-134) and 36.5 (1-226) days, respectively. The fast-track cohort had more advanced staging than those referred by standard letter. There were 19 Dukes' B, 22 Dukes' C and 14 Dukes' D cancers in the fast-track group compared with 28 Dukes' B, 25 Dukes' C and 6 Dukes' D in the standard referral group. After patient interview, only 337 (73%) of 462 fast-track patients appeared to fulfil the referral criteria but of the 64 diagnosed with cancer, 59 (92%) satisfied the criteria. Of the 66 patients with cancer referred by standard letter, 61 (92%) fulfilled the criteria. CONCLUSION: Patients referred to the fast-track clinic were seen quicker than those referred by standard letter, but they tended to have more advanced disease. The fast-track referral criteria were fulfilled by most patients with cancer (whether or not they were referred to the fast track clinic), confirming their validity. After detailed interview in the clinic, a quarter of fast-track referrals were found not to satisfy referral criteria, suggesting that prioritization in primary care could be improved.

Chi-Square Distribution↗
PubMed2001

Colon carcinoma: MR imaging with CO2 enema--pilot study.

Prior to surgery, seven patients with known colonic tumors underwent breath-hold single-shot fast spin-echo magnetic resonance imaging during a CO2 enema. The images were evaluated for depiction of tumor, adjacent structures, and the remaining colon, and findings were compared with findings at surgery. In all seven patients, the tumor was demonstrated, and in four (57%), breach of the muscularis propria was correctly predicted.

Adult↗
PubMed1998

Incidence of DNA replication errors in patients with multiple primary cancers.

PURPOSE: Multiple primary cancers are a feature of hereditary nonpolyposis colorectal cancer in which defects in DNA repair mechanisms result in accumulation of replication errors within tumor DNA. We assessed replication error incidence in multiple primary cancer patients who may have similar genetic defects. METHODS: DNA was obtained from 69 patients from the Yorkshire region who had developed colorectal cancer and one other primary tumor from the hereditary nonpolyposis colorectal cancer tumor spectrum (28 colorectal, 12 stomach, 15 ovary, and 14 uterus). DNA was also obtained from 86 sporadic, single primary cancer patients attending a colorectal cancer clinic. Replication error status was assessed at five microsatellite loci using fluorescent polymerase chain reaction and computer-assisted analysis. RESULTS: The replication error phenotype was observed in 7 of 86 (8 percent) of the sporadic single primary patients. This compared with 23 of 69 (33 percent) of the multiple primary group (P < 0.001). Replication error was also observed more frequently in each subgroup. Even excluding patients from families meeting the Amsterdam criteria (likely to be hereditary nonpolyposis colorectal cancer and have the replication error phenotype), this increased frequency remained in both the multiple primary group (P < 0.005) and multiple colorectal and colorectal/uterine subgroups (P < 0.001). CONCLUSIONS: Results suggest that genetic instability plays an important role in development of multiple primary cancers, particularly from certain cancer subsets. Testing for replication errors may be an appropriate way of identifying individuals at risk of multiple primary cancers.

Aged↗
PubMed1998

Circumferential margin involvement after mesorectal excision of rectal cancer with curative intent. Predictor of survival but not local recurrence?

PURPOSE: This study examines the prognostic significance of circumferential margin involvement by tumor in resected specimens after potentially curative rectal cancer surgery. METHODS: During an eight-year period, all patients with rectal cancer were prospectively audited. For tumors of the middle and lower thirds of the rectum, a total mesorectal excision was performed; for tumor of the upper third, mesorectal excision proceeded at least 5 cm distal to the primary tumor. Resected specimens were subjected to careful histologic assessment, and patients undergoing curative procedures were entered into a surveillance program to detect both local and distant recurrence. RESULTS: Of 218 patients in the cohort, 9 had no resection, 14 underwent local excision, 1 had pre-operative radiotherapy, and 42 patients (20 percent) had palliative resections and were excluded from further analysis. This left 152 patients having a curative resection, of whom 20 (13 percent) had tumor within 1 mm of the circumferential margin. After follow-up until death or a median period of 41 months, recurrent disease was seen in 24 percent of patients with a negative margin and 50 percent with a positive margin. Both disease-free survival and mortality were significantly related to margin involvement (log-rank, P = 0.01 and P = 0.005, respectively). Local recurrence, however, was not significantly different in the two groups (11 and 15 percent, respectively; log-rank, P = 0.38). CONCLUSIONS: When mesorectal excision is performed, circumferential margin involvement is more an indicator of advance disease than inadequate local surgery. Patients with an involved margin may die from distant disease before local recurrence becomes apparent.

Disease-Free Survival↗
PubMed1998

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.

Adult↗
PubMed1996

Hereditary susceptibility to colorectal cancer. Relatives of early onset cases are particularly at risk.

Close relatives of patients with colorectal cancer are at an increased risk of developing a colorectal malignancy themselves. PURPOSE. A study was conducted to compare risks in relatives of patients diagnosed at different ages. METHODS. Family histories were taken from two cohorts of patients with colorectal cancer: Group A, a population group of 65 patients diagnosed at or under 45 (median, 42) years; Group B, 212 patients of all ages (median, 68 years) treated in a single surgeon's practice. RESULTS. Overall relative risk of colorectal cancer in first-degree relatives was 5.2 in Group A and 2.3 in Group B. There was familial clustering of colorectal cancers suggestive of hereditary nonpolyposis colorectal cancer in 13 (20 percent) families in Group A but in only 3 (1.5 percent) families in the second group. Cumulative incidence of colorectal cancer for relatives of the young cohort rose steeply from 40 years, reaching 5 percent at age 50 years and 10 percent at age 70 years. This contrasts with risk for relatives of older patients, in whom the shape of the curve resembles that of the overall population risk, reaching 5 percent at age 70 years and 10 percent at age 80 years. CONCLUSIONS. There appears to be a quantitative and qualitative increase in risk to relatives of patients diagnosed at a young age compared with those diagnosed later in life, at least part of which is likely to be the result of a hereditary susceptibility. Close relatives of early onset cases warrant more intensive endoscopic screening and at an earlier age than relatives of patients diagnosed at older ages.

Adult↗
PubMed1996

The effects of interleukin-1 receptor antagonist protein (IRAP) infusion following spinal cord transection in rats.

A laminectomy was performed at the T5-T6 vertebral level in adult, male, Sprague-Dawley rats and the spinal cord transected with a scalpel. A group of sham animals was subjected to the same surgery without the transection step. A group of unhandled control rats was also included. A subgroup of transected animals received a subcutaneous osmotic minipump that dispensed IL-1 receptor antagonist protein (IRAP) at the transection site for 7 consecutive days. Another transected subgroup received a minipump that infused the vehicle only. IRAP-treated rats displayed a significant reduction in body temperature (p < 0.05) compared with vehicle-treated rats. The IRAP-treated rats were also less active when assessed for locomotor behavior using an HVS computerized tracking system (p < 0.01). IRAP treatment had no effect on serum corticosterone, beta-endorphin levels, Con A, PHA, or LPS-induced splenocyte mitogenesis when compared with vehicle-treated animals. However, half of the IRAP-treated animals exhibited a substantive reduction in the number of reactive astrocytes near the transection site, suggesting a possible effect of IRAP on astrocyte activation.

Animals↗
PubMed1996

Psychological disturbance alters thymic and adrenal hormone secretion in a parallel but independent manner.

Thymosin-alpha 1 (thymosin alpha 1) and cortisol levels were evaluated in juvenile squirrel monkeys to investigate the influence of psychological disturbance on thymic and adrenal hormone activity. Hormone levels were assessed in peripheral circulation following removal of monkeys from their social group to establish the time course of thymosin and cortisol alterations. Thymosin alpha 1 was significantly decreased after social separation in association with increased adrenocortical activity, especially during the first day after being housed alone. The temporal pattern suggested that both hormone systems are involved in the acute inhibition of functional immunity observed following this type of psychological disturbance. A second study verified that the decrement in thymosin alpha 1 levels was replicable and also sensitive to psychosocial factors that influence the level of induced disturbance. In addition, changes in thymosin secretion could be attenuated partially by pharmacological inhibition of the cortisol response and opiate hormone action. Nevertheless, the decrease in thymosin alpha 1 secretion did not appear to be a secondary consequence of adrenocortical secretion, and instead probably emanates from a general shift in neuroendocrine activity.

Animals↗
PubMed1995

Structure of the human MLH1 locus and analysis of a large hereditary nonpolyposis colorectal carcinoma kindred for mlh1 mutations.

Hereditary nonpolyposis colorectal carcinoma is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in at least four genes such as hMSH2, hMLH1, hPMS1, and hPMS2 which encode components of a DNA mismatch repair system. The hMLH1 genomic locus on chromosome 3p has been cloned and shown to cover approximately 58 kilobases of genomic DNA and contain 19 exons. The sequence of all of the intron-exon junctions has been determined and used to develop methods for analyzing each hMLH1 exon for mutations. Using these methods to analyze a 3p-linked hereditary nonpolyposis colorectal carcinoma kindred, we have demonstrated that cancer susceptibility in this family is due to the inheritance of a frame shift mutation in the hMLH1 gene.

Base Sequence↗
PubMed1995

High tie of the inferior mesenteric artery in distal colorectal resections--a safe vascular procedure.

Division of the inferior mesenteric artery flush with the aorta (high tie) allows a tension-free anastomosis in distal colorectal resections but may also diminish the blood supply. Tissue oxygen tension was measured proximal to the resection margin before and after either low or high division of the inferior mesenteric artery in 62 patients undergoing elective colorectal resections. Oxygenation was maintained or improved when the transverse (median change after vs before resection for low tie +9 mmHg (P < 0.05), high tie +8 mmHg (P = 0.3)) and descending colon (low tie +7 mmHg (p < 0.01), high tie +1 mmHg (p = 0.67)) were used for the anastomosis but diminished for sigmoid anastomoses (low tie -4 mmHg (P = 0.42), high tie -9 mmHg (P < 0.05)). Change in oxygenation was significantly affected by location of proximal resection site but not by choice of high or low tie. These results suggest that the marginal artery provides a more than adequate vascular supply to the transverse and descending colon, but that the sigmoid colon is not suitable for anastomosis. We conclude that the sigmoid colon be sacrificed and there should be no hesitation in performing a high tie to avoid tension in low pelvic anastomoses.

Aged↗
PubMed1994

Genetic susceptibility to colorectal cancer in patients under 45 years of age.

A study was conducted to assess the genetic contribution to the development of colorectal cancer in young probands. Of 83 patients aged 45 years or under diagnosed with colorectal cancer in one health region over a 2-year period, 65 or their surviving next of kin were available for interview, from whom were obtained 60 detailed and five limited family histories. Five families fulfilled the Amsterdam criteria and a further eight satisfied less strict criteria for hereditary non-polyposis colorectal cancer, a total of 20 per cent of the cohort. Eleven of these families came from the subgroup of 13 probands who had one or more first-degree relatives with colorectal cancer. Overall the relative risk of colorectal cancer in close relatives was 5.2 (P < 0.0001). This risk was highest for female relatives at 9.7 (P < 0.0001) and relatives of female probands at 6.7 (P < 0.0001). This study highlights the importance of taking a family history in this group of patients. Screening by colonoscopy for all close relatives of young patients with colorectal cancer is recommended.

Adult↗
PubMed1994

Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system. The MSH2 genomic locus has been cloned and shown to cover approximately 73 kb of genomic DNA and to contain 16 exons. The sequence of all the intron-exon junctions has been determined and used to develop methods for analyzing each MSH2 exon for mutations. These methods have been used to analyze two large HNPCC kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that cancer susceptibility is due to the inheritance of a frameshift mutation in the MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other family.

Amino Acid Sequence↗
PubMed1994

Intron splice acceptor site sequence variation in the hereditary non-polyposis colorectal cancer gene hMSH2.

Common but weakly penetrant mutations of certain genes may confer an increased susceptibility to colorectal cancer and account for a proportion of 'sporadic' cases. We analysed DNA from 111 colorectal cancer cases and 114 controls for a specific candidate sequence variation in the hereditary non-polyposis colorectal cancer gene hMSH2. The variant sequence was found in a quarter of individuals, and there was no difference between cancer cases and controls, according to age of development of cancer or presence of family history. It thus appears that this particular sequence variation is a polymorphism rather than a mutation which increases cancer susceptibility.

Adolescent↗
PubMed1994

Genetic linkage in Muir-Torre syndrome to the same chromosomal region as cancer family syndrome.

The Muir-Torre syndrome, in which sebaceous gland tumours occur in association with internal malignancy, is inherited as an autosomal dominant disorder. Many features of the syndrome are similar to those of the Lynch II cancer family syndrome, and thus the two disorders might share a common genetic basis. We typed two large families with DNA markers on chromosome 2p around D2S123, a site recently shown to be linked to the Lynch II syndrome. LOD scores at this locus demonstrated significant and tight linkage to D2S123, suggesting that defects in the same gene might give rise to both syndromes.

Adult↗
PubMed1994

The role of CA-242 and CEA in surveillance following curative resection for colorectal cancer.

This study was undertaken to evaluate the role of a new tumour marker, CA-242, alone or in combination with CEA in the practical management of colorectal cancer patients after potentially curative resection. A cohort of 149 patients who had undergone 'curative' surgery was followed up according to an intensive protocol in order to detect recurrent disease. Over a median tumour marker follow-up period of 24 months there were 25 recurrences in 24 patients. Both CEA and CA-242 alone detected half the local recurrences. The sensitivity of CEA was 84% for distant or mixed recurrence compared with 64% for CA-242. An abnormality of either CEA or CA-242 enabled detection of five out of six local recurrences and 17 out of 19 distant or mixed recurrences with a median lead time of 5 months for each marker. Both markers were elevated concurrently in only one local and 11 distant recurrences. While CA-242 alone is not superior to CEA, their combined use (either abnormal) has a high sensitivity (88%), specificity (78%) and negative predictive value (97%); this may be useful in reducing unnecessary investigations in follow-up programmes and as a guide to the initiation of further treatment for recurrent disease.

Adult↗