A review of major trauma admissions to a tertiary adult referral hospital over a ten year period: fewer patients, similar survival.

BACKGROUND: Trauma is an important cause for presentation to the emergency department, representing a significant number of emergency surgical admissions. Societal changes result in alterations in the epidemiology of trauma. OBJECTIVES: This study aimed to review patients admitted to a tertiary referral hospital as a result of traumatic injuries, assessing for changes in admission epidemiology. METHODS: Trauma admissions over two year-long periods a decade apart were reviewed. The Trauma Audit and Research Network (TARN) audit system identified admissions and transfers between June 2006 and May 2007. The Hospital In-Patient Enquiry (HIPE) system identified those fulfilling TARN criteria a decade earlier. Comparative analysis was performed on the dataset. RESULTS: There were 367 trauma admissions between June 2006 and May 2007: 88 road traffic accidents (RTAs), 201 falls and 77 other injuries, with 627 admissions a decade earlier: 286 RTAs, 247 falls and 94 others. Males comprised 72% and 69% of RTA admissions in both periods respectively. Firearm-related injuries increased significantly (p = 0.015). Neurosurgical transfers decreased from 256 to 150 with a slight increase in unadjusted overall mortality from 8.5% to 10.9%. Admissions of patients aged less than 19 reduced from 150 to 59 (p = 0.0031) with a similar trend in those aged between 20 and 29 years from 149 to 78. CONCLUSION: Admissions resulting from RTAs and of patients aged under 30 reduced significantly, however, young males remain the most affected sub-group. Firearm injuries increased significantly, a worrying trend in view of the severity of injury sustained by these victims.

Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in sporadic colorectal adenomas with demographic and clinicopathologic characteristics.

In colorectal tumorigenesis, Ki-ras proto-oncogene mutation often occurs early in the adenoma-adenocarcinoma sequence, whereas mutation of the p53 gene is associated with late progression to carcinoma. We evaluated the relationship of demographic and clinicopathologic characteristics to Ki-ras mutation and p53 gene product overexpression in 1,093 baseline sporadic colorectal adenomas from 926 individuals enrolled in a phase III recurrence prevention trial. Ki-ras mutation was found in 14.7% of individuals and p53 overexpression was found in 7.0% of those tested. Multivariate analysis found older age, rectal location, and villous histology to be independently associated with Ki-ras mutation. Individuals with an advanced adenoma (>or=1 cm or high-grade dysplasia or villous histology) had a 4-fold higher likelihood of Ki-ras mutation [odds ratios (OR), 3.96; 95% confidence intervals (CI), 2.54-6.18]. Ki-ras mutations in codon 12 and of the G-to-A transition type were more frequent in older individuals, whereas G-to-T transversion was more frequent in rectal adenomas than in the colon. Multivariate analysis showed that previous history of a polyp (P = 0.03) was inversely associated with p53 overexpression. Large adenoma size (>or=1 cm), high-grade dysplasia, and villous histology were independently associated with p53 overexpression, with the strongest association for advanced adenomas (OR, 7.20; 95% CI, 3.01-17.22). Individuals with a Ki-ras mutated adenoma were more likely to overexpress p53 (OR, 2.46; 95% CI, 1.36-4.46), and 94.8% of adenomas with both alterations were classified as advanced (P

Differing DNA methylation patterns and gene mutation frequencies in colorectal carcinomas from Middle Eastern countries.

PURPOSE: The epidemiology of colorectal carcinoma is well known to differ among countries but the molecular characteristics are usually assumed to be similar. International differences in molecular pathology have not been studied extensively but have implications for the management of patients in different countries and of immigrant patients. EXPERIMENTAL DESIGN: We evaluated the CpG island methylator phenotype pathway characterized by concordant methylation of gene promoters that often silences transcription of the genes, the microsatellite instability pathway, and K-ras and p53 gene status in 247 colorectal carcinomas from the three selected Middle Eastern countries of Egypt, Jordan, and Turkey. RESULTS: Colorectal carcinoma from Egypt had the lowest frequencies of methylation. In multinomial logistic regression analysis, Jordanian colorectal carcinoma more frequently had methylation involving the p16 tumor suppressor gene (odds ratio, 3.5; 95% confidence interval, 1.2-10.6; P = 0.023) and MINT31 locus (odds ratio, 2.3; 95% confidence interval, 1.0-5.1; P = 0.041). The K-ras proto-oncogene was more frequently mutated in colorectal carcinoma from Turkey (odds ratio, 2.9; 95% confidence interval, 1.2-6.7; P = 0.016), but p53 overexpression was more common in both Jordanian and Turkish colorectal carcinoma than in Egyptian cases (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = 0.019; and odds ratio, 3.6; 95% confidence interval, 1.8-7.1; P = 0.0003, respectively). The findings in Turkish colorectal carcinoma were most similar to those reported for Western cases. CONCLUSIONS: Colorectal carcinoma from Middle Eastern countries have differing gene methylation patterns and mutation frequencies that indicate dissimilar molecular pathogenesis, probably reflecting different environmental exposures. These molecular differences could affect prevention strategies, therapeutic efficacy, and transferability of clinical trial results.

Hematologic parameters and leukocyte histogram patterns in infectious mononucleosis.

Blood samples from 60 patients with serologically positive infectious mononucleosis were analyzed on the Coulter S-Plus IV. Hemoglobins and platelet counts were essentially normal, and leukocyte counts were elevated in less than half the cases. Reactive lymphocytes were present on blood smears from all patients. The S-Plus IV automated three-part leukocyte differentials showed significantly lower numbers of lymphocytes and more mononuclears and granulocytes than manual microscopic differentials. On the leukocyte histograms, lymphocyte peaks were consistently wider than normal and asymmetrical. The instrument generated R2 flags on 43 of 60 (72%) of the samples. Using a combination of "R" flags, mononuclear backlighting, and "H" flags, the Coulter S-Plus IV identified 59 of 60 infectious mononucleosis samples as requiring further review.

MGMT promoter methylation and field defect in sporadic colorectal cancer.

BACKGROUND: Sporadic colorectal cancers often arise from a region of cells characterized by a "field defect" that has not been well defined molecularly. DNA methylation has been proposed as a candidate mediator of this field defect. The DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal cancer. We hypothesized that MGMT methylation could be one of the mediators of field cancerization in the colon mucosa. METHODS: We studied MGMT promoter methylation by three different bisulfite-based techniques in tumor, adjacent mucosa, and non-adjacent mucosa from 95 colorectal cancer patients and in colon mucosa from 33 subjects with no evidence of cancer. Statistical tests were two-sided. RESULTS: MGMT promoter methylation was present in 46% of the tumors. Patients whose cancer had MGMT promoter methylation also had substantial MGMT promoter methylation in apparently normal adjacent mucosa. This methylation was seen with a quantitative assay in 50% (22/44; 95% confidence interval [CI] = 34% to 65%) of normal samples with MGMT promoter methylation in the adjacent tumors, 6% (3/51; 95% CI = 1% to 16%) of samples without MGMT methylation in adjacent tumors, and 12% (4/33; 95% CI = 3% to 28%) of control samples (P < .001 for comparison between each of the latter two groups and the first group). MGMT methylation was detected with a more sensitive assay in 94%, 34%, and 27% of these samples, respectively (P < .001). In grossly normal colonic mucosa of colon cancer patients, methylation was detected 10 cm away from the tumor in 10 of 13 cases. Tumors with MGMT promoter methylation had a higher rate of G-to-A mutation in the KRAS oncogene than tumors without MGMT promoter methylation (10/42 versus 3/46, P = .03). Using a sensitive mutant allele-specific amplification assay for KRAS mutations, we also found KRAS mutations in 12% (3/25; 95% CI = 2.5% to 31%) of colorectal mucosas with detectable MGMT methylation and 3% (2/64; 95% CI = 0.4% to 11%) of colorectal mucosas without MGMT methylation (P = .13). CONCLUSION: Some colorectal cancers arise from a field defect defined by epigenetic inactivation of MGMT. Detection of this abnormality may ultimately be useful in risk assessment for colorectal cancer.

Pheromonal activity of single castoreum constituents in beaver,Castor canadensis.

Behavioral activity of single components of beaver castoreum was demonstrated for the first time. In four experiments samples were presented to free-ranging beaver in their family territories. First, responses to whole castoreum and anal gland secretion (AGS) from males and females were tested. Second, 24 compounds, known to be constituents of beaver castoreum, were individually screened for activity. Four of these consistently released immediate responses during the observation periods. These are the phenols 4-ethylphenol and 1,2-dihydroxybenzene and the ketones acetophenone and 3-hydroxyacetophenone. In the most complete responses, the beaver sniffed from the water, were attracted to the odor, swam toward its source, went on land, and then approached, sniffed, pawed, and scent-marked the artificial scent mound. 4-Ethoxyphenol, a compound not yet found in castoreum, also released these responses. Five additional compounds resulted in a few delayed visits to the samples during the night following the observations, as evidenced by destroyed scent mounds. These are 4-methyl-1,2-dihydroxybenzene, 4-methoxyacetophenone, 5-methoxysalicylic acid, salicylaldehyde, and 3-hydroxybenzoic acid. Third, mixtures of 24 and six compounds were tested. Responses to these mixtures could be as strong as those to whole castoreum. Fourth, the four regularly active compounds were tested in two additional beaver populations and proved to be active there, too. The response was strongest in the densest beaver population.

The identification of alpha-adrenergic receptors in adipose tissue by [3H]dihydroergocryptine binding.

The 3H-labelled alpha-adrenergic antagonist dihydroergocryptine has been found to bind specifically to hamster white adipocyte membranes. Binding is rapid and is inhibited by alpha but not beta antagonists. In addition, adrenergic agonists compete for this binding site in order of affinities equal to their activity as alpha-adrenergic agonists. The (-) stereoisomer of adrenaline is 10 times more potent than the (+) stereoisomer in inhibiting binding.

Phenotypic and molecular characteristics of hyperplastic polyposis.

BACKGROUND & AIMS: Patients with hyperplastic polyposis are reported to have multiple and/or large hyperplastic polyps (HPs) and an increased risk of colorectal cancer, but the phenotype and genetic alterations in hyperplastic polyposis have not been studied in detail. METHODS: We evaluated clinical-pathological and molecular characteristics of 129 HPs, 6 serrated adenomas, and 3 admixed hyperplastic-adenomatous polyps from 13 patients with hyperplastic polyposis (more than 20 HPs), 5 patients with a large HP (>/=1 cm in diameter), and 5 patients with multiple HPs (5-10 HPs). RESULTS: HPs in the right colon in contrast to the left colorectum had more frequent topographic dysregulation of p21(Waf-1/Cip1) expression (94% vs. 76%, P = 0.03) and of proliferation (92% vs. 53%, P = 0. 0001), but less frequent allelic loss of chromosome 1p (4% vs. 17%, P = 0.03). K-ras mutation was present in 8% of HPs, p53 gene product overexpression in none, and microsatellite instability in 3% without relationship to microsatellite instability in synchronous cancer. Patients with a large HP differed from those with multiple HPs in having a high frequency of right-sided HP (63% vs. 22%, P = 0.01) and of right-sided colon cancer (100% vs. 8%, P = 0.003). Hyperplastic polyposis was associated with a family history of colorectal cancer (P = 0.01) and with loss of chromosome 1p in HP (21% vs. 0%, P = 0.001). CONCLUSIONS: A hyperplastic polyp/dysplasia-to-adenocarcinoma sequence can be manifested in 3 distinct phenotypes consisting of patients with hyperplastic polyposis and chromosome 1p allelic loss in some HPs, in contrast to patients who have large, right-sided HPs or small numbers of HPs that lack 1p loss.

Cytogenetic evidence for involvement of erythroid progenitors in a child with therapy linked myelodysplasia.

A 6-year-old male with prior metastatic retinoblastoma developed a therapy linked myelodysplastic syndrome. Whole bone marrow cytogenetics showed monosomy 7 and a marker chromosome. To determine the progenitor level of origin of the malignant clone, we studied the karyotypes of marrow erythroid and granulocyte/macrophage colonies grown in methyl cellulose. All erythroid and granulocyte/macrophage colonies had an abnormal karyotype with 45 chromosomes (monosomy 7) and several colonies contained the marker chromosome. These findings give direct evidence that this patient's myelodysplastic syndrome involved an early stem cell which was capable of both erythroid and granulocyte differentiation.

Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients.

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours.