Influence of diets containing high and low risk factors for colon cancer on early stages of carcinogenesis in human flora-associated (HFA) rats

Germ-free rats colonised with a human intestinal flora were fed diets containing high risk (HR) or low risk (LR) factors for colorectal cancer, and putative biomarkers were evaluated in the colonic mucosa; (i) proliferation, (ii) 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci and (iii) DMH-induced DNA damage. The HR diet was high in fat (45% of calories) and low in calcium and fibre, reflecting levels characteristic of typical western diets. The LR diet was low in fat (<5% of calories), and high in calcium and fibre. The nutrient/energy ratio of the two diets were similar. Mucosal crypt cell proliferation, assessed after microdissection, was higher on the LR diet (mean number of mitoses per crypt was 2.65 on the LR diet, and 1.62 on the HR diet; P < 0.05). Aberrant crypt foci (ACF) were assessed in the mucosa 12 weeks after DMH treatment. On the HR diet there were significantly more small ACF with 1 and 2 crypts per focus, but fewer ACF with 3, 5 and 7 or more crypts per focus. There was no significant difference in total ACF or the total number of crypts. The effect of diet on DNA damage in the colon was assessed in vivo by the comet assay. Animals were fed a HR or LR diet for 12 weeks before treatment with DMH or saline. For carcinogen-treated animals, DNA damage was significantly higher in colon cells from animals on the HR diet. On the LR diet both DNA damage and the induction of small ACF were reduced despite an increase in cell proliferation. The increase in large ACF on the LR diet may be attributable to elevated crypt cell proliferation possibly increasing crypt fission rates.      

Acoustic neuromas: Gd-DTPA enhancement in MR imaging

Magnetic resonance (MR) imaging examinations were performed in ten patients with 12 acoustic neuromas before and after intravenous administration of 0.1 mmol/kg body weight gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). The degree of enhancement was greatest with the inversion recovery sequence 1,500/500/44 (repetition time [TR]/inversion time/echo delay time [TE]), followed by spin-echo (SE) 544/44 (TR/TE) sequences, then by SE 1,500/44 and SE 1,500/80 sequences. After enhancement there was a 50% reduction for measured T1 values, 33% for T2, and no significant change for proton density. There were no toxic effects on patients. Enhanced CT scans failed to demonstrate lesions in six of 12 cases. Air-CT technique improved sensitivity in four of five cases. Enhanced MR imaging added significant clinical information in two small intracanalicular tumors and in one recurrent tumor.     

Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.     

Ultrasonography guided rectus sheath catheters versus epidural analgesia for open colorectal cancer surgery in a single centre

Introduction

Epidural anaesthesia (EA) has been the accepted standard for postoperative analgesia in open abdominal surgery. However, it is not without significant risk. This study aimed to audit the effect of EA and ultrasonography placed rectus sheath catheters (RSCs) on analgesia as well as the incidence of postoperative complications following open colorectal cancer surgery.

Methods

A three-year retrospective case note review was undertaken of all patients undergoing open colorectal cancer surgery at the Royal Devon and Exeter Hospital NHS Foundation Trust who received either EA or RSC for postoperative analgesia under the care of the senior authors. A single surgeon and single anaesthetist were practitioners.

Results

The case notes of 120 patients were reviewed retrospectively: 85 patients had EA and 24 RSC while 11 patients were excluded from the study. The EA group experienced a significantly higher incidence of hypotension (systolic blood pressure <130mmHg) than the RSC group on the first postoperative day (p=0.0001). There was no significant difference in pain score or opiate sparing properties between the groups (p=0.92). There was no significant difference in postoperative respiratory tract infection, anastomotic leak or wound complications between the groups (p=0.2, p=1.0 and p=0.5 respectively). The RSC group had a higher incidence of ileus than the EA group (4/24 vs 2/85, p=0.026). However, the numbers were too small to draw a reliable conclusion.

Conclusions

The use of ultrasonography guided RSCs has demonstrated effective postoperative analgesia equivalent to EA with the potential benefits of a reduced incidence of hypotension. A prospective randomised trial is now underway to compare RSC and EA in open abdominal and pelvic surgery.     

Effect of niloticin,a protolimonoid isolated from Limonia acidissima L. (Rutaceae) on the immature stages of dengue vector Aedes aegypti L. (Diptera: Culicidae)

The aim of the present study was to evaluate the mosquitocidal activity of fractions and a compound niloticin from the hexane extract of Limonia acidissima L. leaves on eggs, larvae and pupae of Aedes aegypti L. (Diptera: Culicidae). In these bioassays, the eggs, larvae and pupae were exposed to concentrations of 2.5, 5.0, 7.5 and 10.0 ppm for fractions and 0.5, 1.0, 1.5 and 2.0 ppm for compound. After 24 h, the mortality was assessed and the LC₅₀ and LC₉₀ values were calculated for larvae and pupae. Per cent ovicidal activity was calculated for eggs after 120 h post treatment. Among the sixteen fractions screened, fraction 8 from the hexane extract of L. acidissima generated good mosquitocidal activity against Ae. aegypti. The LC₅₀ and LC₉₀ values of fraction 8 were 4.11, 8.04 ppm against Ae. aegypti larvae and 4.19, 8.10 ppm against Ae. aegypti pupae, respectively. Further, the isolated compound, niloticin recorded strong larvicidal and pupicidal activities. The 2 ppm concentration of niloticin showed 100% larvicidal and pupicidal activities in 24 h. The LC₅₀ and LC₉₀ values of niloticin on Ae. aegypti larvae were 0.44, 1.17 ppm and on pupae were 0.62, 1.45 ppm, respectively. Niloticin presented 83.2% ovicidal activity at 2 ppm concentration after 120 h post treatment and niloticin exhibited significant growth disruption and morphological deformities at sub lethal concentrations against Ae. aegypti. The structure of the isolated compound was identified on the basis of single XRD and spectral data (¹H NMR and ¹³C NMR) and compared with literature spectral data. The results indicate that niloticin could be used as a potential natural mosquitocide.