Overexpression of protein S100A4 is independently associated with overall survival in stage C colonic cancer but only in cytoplasm at the advancing tumour front.

PURPOSE: S100A4, a multifunctional protein, has been linked to the invasive growth and metastases of several human cancers. This study investigated the association between S100A4 and overall survival and other clinicopathological features in patients with stage C colonic cancer. METHODS: Clinical and pathological data were obtained from a prospective hospital registry of 409 patients who had a resection for stage C colonic cancer. Tissue microarrays for immunohistochemistry were constructed from archived tissue. S100A4 staining intensity and percentage of stained cells were assessed in nuclei and cytoplasm for both the central part of the tumour and at the advancing front. Overall survival was analysed by the Kaplan-Meier method and Cox regression. RESULTS: Only a high percentage of cells with S100A4 cytoplasmic staining in frontal tissue was associated with poor survival (hazard ratio, 1.6; 95 % CI 1.1-2.2; p = 0.008) after adjustment for other prognostic variables. There was no association between frontal cytoplasmic S100A4 expression and any of 13 other clinicopathological variables. CONCLUSIONS: High expression of S100A4 in cytoplasm at the advancing front of stage C colonic tumours indicates a poor prognosis. Whether S100A4 can predict response to adjuvant chemotherapy remains to be investigated in a randomised clinical trial.

Clinical strategies for the management of cytomegalovirus infection and disease in allogeneic bone marrow transplant.

Four clinical strategies are proposed for the management of CMV disease: prophylaxis, suppression, pre-emptive therapy and treatment. The degree of risk of developing CMV disease and the safety profile of the presently available drugs need to be considered when deciding on the most appropriate approach. We conclude that a prophylactic strategy employing a drug with a safe toxicity profile followed by pre-emptive treatment with an effective antiviral drug for failure of prophylaxis gives the best outcome in allogeneic HLA matched bone marrow transplant recipients.

Long-term survival in allogeneic bone marrow transplant recipients following acyclovir prophylaxis for CMV infection. The European Acyclovir for CMV Prophylaxis Study Group.

Recipients of HLA-matched, related or unrelated allogeneic BMT who were CMV seropositive or those receiving unmanipulated marrow from a seropositive donor were randomised to receive one of three treatment regimens, i.v. acyclovir 500 mg/m2 three times a day from 5 days before transplant to 30 days after transplant followed by oral acyclovir 800 mg four times a day for a further 6 months, i.v. acyclovir followed by placebo, or 400 mg oral acyclovir four times a day followed by placebo (control). This paper reports the 1 year data on the same cohort of patients which was previously reported. Intravenous acyclovir (i.v./PCB) significantly reduced the risk of CMV infection when compared to the control group. The frequency of adverse events reported was comparable among the three groups. The mortality rate was significantly reduced by the sequential use of i.v. acyclovir followed by oral acyclovir, resulting in a 19% survival advantage at 1 year from transplant.

A comparison of local and systemic acyclovir in the management of herpetic disciform keratitis.

Forty-three patients with active herpetic disciform keratitis were entered into an open study to compare the efficacy of oral acyclovir (400 mg) with acyclovir ophthalmic ointment (3%) to inhibit viral replication during treatment with 0.05% prednisolone eye drops. All patients, regardless of the mode of therapy, were treated five times a day until they were healed. The mean time to heal in the oral group was 25.9 days and in the topical group was 25.3 days. Resolution of lacrimation was significantly faster in the oral group (12.1 days versus 27.6 days). The patients on tablets also showed a greater improvement in visual acuity. No statistically significant differences were found between the two groups in the incidence of recurrences over a three-year post-treatment period. It is concluded that oral acyclovir treatment is an effective alternative to ophthalmic ointment in the management of herpetic disciform keratitis.

The evaluation of a new technique for anaerobic sampling of deep periodontal pockets.

A new technique for the anaerobic sampling of deep periodontal pockets has been developed and evaluated in vitro and in vivo. The mean percentage difference of total viable counts from pairs of samples from nine deep periodontal pockets was found to be 76.4%. This compared favorably with an established technique for which the equivalent figure was 147.4%. Evidence was obtained that the first sample taken with the new sampler depleted the site. When correction was made for that effect, the mean percentage difference was found to be 31.1%. That value was in good agreement with the variation obtained by taking repeat samples from centrifuged deposits of pure cultures of bacteria.

Determination of trace 2,4-dichlorophenoxyacetic acid in fresh produce by gas chromatography with boron trichloride/2-chloroethanol derivatization.

2,4-Dichlorophenoxyacetic acid (2,4-D) residues in fresh produce is officially analyzed as its methyl ester form by gas chromatography with electron capture detection (GC-ECD). Because of safety concerns with diazomethane, the reagent used to form methyl esters, a less toxic and dangerous reagent, BCl3/2-chloroethanol, was considered. With this alternative reagent, the detecting product is a 2-chloroethyl ester. Compared with the methylester, the 2-chloroethylester has a longer retention time and a better signal-to-noise ratio for trace level analysis by GC-ECD. However, the reagent produces too many unwanted background peaks. If peak retention time is the only information available to identify the residue in case of litigation, the presence of too much background noise increases the ambiguity of identification. Therefore, confirmation by interpretation of the mass spectrum and determination of the compound structure is necessary to ensure the validity of the method. Ten commodities were fortified with 2,4-D at 0.1 ppm. Recoveries of 2-chloroethyl esters and methyl esters were 91 and 92%, respectively. The method is safe, simple, and robust.

Safety and efficacy of using the LigaSure vessel sealing system for securing the pedicles in vaginal hysterectomy: randomised controlled trial.

OBJECTIVE: To assess the safety and efficacy of using the LigaSure vessel sealing system for securing the pedicles during vaginal hysterectomy in comparison with the conventional method of securing the pedicles by suture ligation. DESIGN: Randomised controlled trial. SETTING: Gynaecology Department, Benenden Hospital, Kent. POPULATION: One hundred and sixteen women undergoing vaginal hysterectomy were prospectively randomised to either LigaSure (Group I) or suture ligation (Group II) for securing the pedicles. METHODS: Data of patients were collected prospectively. Statistical analysis was performed using the Mann-Whitney U test, chi(2) and Fisher's exact test as appropriate. MAIN OUTCOME MEASURES: Operating time, operative blood loss and peri-operative complications. RESULTS: The operating time was significantly shorter in the LigaSure group compared with the control group (P < 0.04). There was no statistical significant difference between the two groups in operative blood loss (P= 0.433), but peri-operative haemorrhagic complications were less frequent in the LigaSure group (0%vs 6.8%, P= 0.057). Four patients in the control group required either conversion to laparotomy because of bleeding, return to theatre for immediate post-operative haemorrhage or readmission for vault haematoma, whereas none in the LigaSure group had bleeding from unsecured pedicles. CONCLUSION: The LigaSure vessel sealing system is a safe alternative for securing pedicles in vaginal hysterectomy when compared with conventional suture ligation. Larger studies are required to determine its place in gynaecological surgery.

GC/MIP/AED method for pesticide residue determination in fruits and vegetables.

This research describes the results of a gas chromatography/microwave induced plasma/atomic emission detection (GC/MIP/AED) method performed on a Hewlett-Packard 5921A system for pesticide residue analysis in fruits and vegetables. A total of 6 experiments were conducted: (1) sensitivity and linearity studies for elements S, P, Cl, and N by analyzing dursban; (2) a study of instrument response to Cl concentration in pesticide molecules; (3) organochlorinated pesticide recoveries; (4) organophosphate pesticide recoveries; (5) carbamate pesticide recoveries; and (6) investigation of metallic pesticides with plictran and vendex as standards. The rank according to sensitivity and linearity was found to be as follows: S-181 greater than P-178 greater than Cl-479 greater than N-174. Instrument response to the concentration of chlorine atoms in the pesticide molecule was linear, with a correlation coefficient of 0.89. Recoveries of organochlorinated pesticides were 91.7-109.3%, with the exception of citrus, whose recovery was affected by coeluting interferences. Organophosphate recoveries were 73.2% or higher, except for the cygon oxygen analog, which degraded in the GC system under all circumstances. Carbamate recoveries were inconsistent quantitatively; however, the information generated from elements N and S were useful for qualitative confirmation of other methods, such as LC postcolumn derivatization analysis. Overall, the GC/MIP/AED method is powerful for qualitative confirmation in pesticide residue analysis. The instrument's capability of acquiring multi-elements (Cl and P) selectively and accurately is an alternative method for organochlorinated and organophosphate pesticide residue analyses. In addition, the GC/MIP/AED system is easy to use, simple to maintain, and its chromatograms can be interpreted by any chromatography analyst without much prior training.

The effect of supragingival plaque control on the subgingival microflora.

The effect of plaque control on the apical microflora of deep periodontal pockets was studied. 8 subjects exhibiting signs of chronic periodontitis were chosen for the study, each subject having at least one pocket greater than 6 mm. These subjects were placed on a plaque control programme consisting of 3 visits, during which oral hygiene instructions were given. On two visits, the teeth of these subjects were scaled and polished. Bacteriological samples from the apex of a deep pockets from each subject were collected before the commencement of the plaque control programme and again at 8 and 16 weeks after the last scale and polish. No significant difference in the microbial flora was observed before and after plaque control, but marked fluctuation in bacterial composition was noted at the 3 samplings. It was concluded that supragingival plaque reduction was not sufficient to produce significant changes in the subgingival plaque composition of deep periodontal pockets.

Behaviour of TEM-1 beta-lactamase as a resistance mechanism to ampicillin, mezlocillin and azlocillin in Escherichia coli.

Escherichia coli isolates which synthesised the extremely common 'TEM-1' plasmid mediated beta-lactamase were more resistant to the alpha-aminopenicillins, ampicillin, mezlocillin and azlocillin, than were strains which lacked this enzyme. However, many TEM-1+ isolates remained sensitive to therapeutic concentrations of mezlocillin (less than 64 mg/l), whereas virtually none was susceptible to such levels of ampicillin or azlocillin. Transconjugants of E. coli K12 into which we introduced various TEM-1 coding plasmids similarly acquired lower levels of resistance to mezlocillin than to ampicillin and azlocillin. Those which expressed relatively small amounts of enzyme remained sensitive to 64 mg/l of mezlocillin, whereas they were substantially resistant (MIC greater than 64 mg/l) to the other alpha-aminopenicillins. These data suggested that the enzyme afforded weaker protection against mezlocillin than against azlocillin and ampicillin and we attempted to relate this finding to its hydrolytic activity. Extracted TEM-1 beta-lactamase hydrolysed high concentrations of mezlocillin more rapidly than ampicillin and azlocillin; however, mezlocillin was calculated to be the weakest substrate at the low concentrations which are likely to be obtainable in the bacterial cell. These data may partly account for the residual activity of mezlocillin against enzyme producers, but target and permeability factors probably also contribute.

Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Our aim was to study the prophylactic effect of high-dose intravenous acyclovir given around the time of BMT followed by oral acyclovir on CMV infection and survival. 310 BMT recipients at risk of developing CMV infection were randomised to one of three regimens in a double-blind and double-dummy design: intravenous acylclovir (500 mg/m2, three times a day) for 1 month followed by oral acyclovir (800 mg four times a day for a further 6 months) (intravenous/oral group); intravenous acyclovir followed by oral placebo (intermediate group); or low-dose oral acyclovir (200 or 400 mg, four times a day) followed by placebo ("controls"). Analysis was by intention-to-treat. Intravenous acyclovir significantly reduced the probability of and delayed the onset of CMV infection. There was no further reduction in infection risk with the addition of long-term oral acyclovir. Time to CMV viraemia was delayed in the intravenous/oral acyclovir group compared with controls. Extending the prophylaxis with oral acyclovir significantly improved survival: 79 of 105 recipients were still alive at 7 months compared with 60 of 102 controls (p = 0.012). Although the intravenous/oral acyclovir group did significantly better than controls in terms of survival, the difference between the intravenous/oral acyclovir group and the intermediate group was of borderline statistical significance (p = 0.054). Adverse events that were possibly treatment related were similar in all three groups. The most commonly reported events were nausea, vomiting, elevated creatinine, and renal failure. High-dose intravenous followed by oral acyclovir improved survival and was of benefit in prophylaxis against the effects of CMV after BMT. Interpretation of CMV infection was made difficult because an intermediate treatment (intravenous acyclovir followed by oral placebo) was as effective as high-dose intravenous/oral acyclovir.