Characterization of antimicrobial resistance among Escherichia coli O111 isolates of animal and human origin

Fifty isolates of Escherichia coli serogroup O111 recovered from humans and various animal species over a 24-year period (1976-1999) were examined for typical virulence-associated factors and susceptibilities to antimicrobials of human and veterinary significance. Nine H (flagellar) types were identified including nonmotile (n = 24), 32 (n = 12), negative (n = 5), and 56 (n = 3). Thirty-five (70%) isolates possessed at least one Shiga-toxin-producing E. coli (STEC)-associated virulence determinants (eae, stxl, stx2, hlyA) via PCR analysis. Of these 35 isolates, 20 possessed eae, stxl, and hlyA genes, whereas three isolates possessed eae, stxl, stx2, and hylA genes. Multiple antibiotic resistance was observed in 70% of the 50 E. coli O111 isolates. The majority of isolates displayed resistance to streptomycin, sulfamethoxazole, tetracycline, and kanamycin. Bacterial resistance to ampicillin, gentamicin, chloramphenicol, trimethoprim and apramycin was also observed. Integrons were identified in 23 (46%) of the E. coli isolates assayed, with a 1-kb amplicon being most frequently observed. DNA sequencing of these integrons revealed the presence of the aadA gene, encoding resistance to streptomycin. Two integrons of 1.5 and 2 kb contained the aadA2 and either dfrI or dfrXII genes, encoding resistance to streptomycin and trimethoprim, respectively. Integrons were also identified from isolates dating back to 1982. Isolates were further genetically characterized via ribotyping, which identified 15 distinct ribogroups, with 62% of isolates clustering into four major ribogroups. Certain riboprint patterns from different animal species, including humans, were observed in isolates spanning the 24-year collection period, suggesting the dissemination of specialized pathogenic O111 clones.     

Tumor antigens and antigen-presenting capacity in breast cancer.

AIMS: Cancer cells frequently express antigens capable of being recognized by the host immune system; however, any resultant immune response is often ineffective. This may be related in part to tumor-induced defects in antigen presentation. We screened for dendritic cell infiltration, tumor MHC II expression and associated lymphocytic reaction in the context of three established breast tumor antigens. METHODS: Forty primary breast tumors were evaluated by immunohistochemical techniques for expression of her2/neu, p53, and MUC1 and MHC class II molecules. Twenty-five samples were further analyzed for p53 mutations by PCR-SSCP analysis and DNA sequencing. The phenotype of tumor-infiltrating inflammatory cells was evaluated using the following markers: CD1a, MHC Class II, CD3, CD45, and CD45RO. RESULTS: Tumors with p53 mutations and overexpression, but not her2/neu or MUC1 overexpressing tumors, more frequently harbored marked CD1a+ dendritic cell infiltrates. An overall correlation between CD1a+ cell infiltrates and HLA class II expression on tumor cells (p = 0.0008) was also observed and these tumors had greater CD45RO+ lymphocytic infiltrates. CONCLUSIONS: In breast cancer, p53 mutations may present a more visible signal to the immune system and hence provide a better target for immunotherapy. Infiltrating CD1a positive cells are associated with a more dense tumor lymphocytic infiltrate and tumor cell expression of MHC II molecules.     

Seat belt-induced trauma to the small bowel

Thirty-two patients with seat belt-induced injuries to the jejunum and ileum are reviewed. These patients are classified into 3 groups according to the nature and mechanism of injury. Group I consists of 4 patients with complete transection of the proximal jejunum caused by deceleration forces. Injuries commonly associated include spleen rupture and perforation of the transverse colon and splenic flexure. Group II consists of 6 patients with infarcted ileum caused by crushing forces. Associated injuries include tears to the cecum, aorta, and inferior vena cava. Group III consists of 22 patients with blowout perforations of the jejunum and ileum. These injuries are caused by transmitted forces. There are no associated specific injuries related to this group.

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Resumen Se revisaron treinta y dos casos de lesiones del yeyuno y del íleon por cinturones de seguridad (automotrices). Los pacientes fueron clasificados en tres grupos de acuerdo a la naturaleza y mecanismo de la lesión. El grupo I consistió de 4 pacientes con transección completa del yeyuno proximal causada por fuerzas de desaceleración. Como lesiones frecuentemente asociadas aparecieron la ruptura del bazo y la perforación del colon transverso y del ángulo esplénico. El grupo II consistió de 6 pacientes con infarto del íleon causado por fuerzas de machacamiento. Como lesiones asociadas se encontraron desgarros del ciego, de la aorta y de la vena cava inferior. El grupo III consistió de 22 pacientes con perforación por estallido del yeyuno y del íleon. Estas lesiones son causadas por fuerzas transmitidas a partir de la pared anterior del abdomen, los cuales causan una elevación repentina en la presión intraluminal del intestino delgado. No se encontraron lesiones específicas asociadas en este grupo de pacientes. La mortalidad por lesiones del intestino delgado causadas por trauma abdominal cerrado ha sido principalmente atribuida a diagnóstico tardío. Los síntomas iniciales pueden ser mínimos. El neumoperitoneo puede aparecer radiográficamente sólo en el 50% de los casos; la determinación de la amilasa sérica generalmente ha demostrado ser poco confiable. En nuestra serie la mortalidad reflejómás bien la presencia de lesiones asociadas que diagnóstico tardío. Creemos que el examen e historia clínicos cuidadosos y un buen conocimiento de los mecanismos de lesión del intestino delgado pueden alertar al cirujano para lograr un diagnóstico correcto en la mayoría de los casos.

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Résumé Trente-deux observations d'accidentés présentant des lésions intestinales dues au port de la ceinture de sécurité sont rapportées. Elles se classent en trois groupes en fonction de la nature et du mécanisme des lésions. Le groupe I concerne 4 accidentés qui présentaient une section complète du jéjunum proximal provoquée par la décélération. Des lésions associées comprenaient la rupture de la rate, la perforation du colon transverse et de l'angle splénique. Le groupe II répond à 6 blessés qui présentaient un infarcissement iléal provoqué par l'écrasement. Les lésions associées répondaient à des déchirures du coecum, de l'aorte et de la veine cave inférieure. Le groupe III intéresse 22 accidentés qui présentaient des perforations du jéjunum et de l'iléon par brusque distension due elle-même à la force de la contusion, ce type de lésions par rupture ne s'accompagnant pas de lésion spécifique associée.

     

T-antigen expression by peanut agglutinin staining relates to mucosal dysplasia in ulcerative colitis

Staining of 326 rectal mucosal biopsies from ulcerative colitis patients with peanut agglutinin (PNA), which binds to the T-blood group antigen and has been claimed to reflect a cancer-associated mucin alteration, showed highly significant direct associations with mucosal dysplasia (P less than 0.001), disease activity (P less than 0.001), and subsequent development of rectal cancer in a smaller series of patients (P = 0.005). Staining for normal colonic mucin by the Dolichos biflorus (DBA) lectin related significantly and inversely to dysplasia. Intense normal colon mucin staining by DBA related significantly (P less than 0.025) to long disease duration and to subsequent development of cancer (P = 0.02). The latter association is based on a small number of patients only and is not considered conclusive evidence, but may provide a link with goblet-cell hyperplasia. The authors conclude that although T-antigen expression relates to dysplasia, the findings of "false" positive and negative rates of 22 and 33 percent respectively, make it unlikely that staining of biopsy sections for the T-antigen by peanut agglutinin will contribute materially to routine assessment for dysplasia and cancer risk prediction in patients with ulcerative colitis.     

Gastric cancer and survival

The survival of patients with cancer of the stomach in a Melbourne series showed no improvement over a 20-year period. Of 246 patients, 8.1% survived for a period of five years, and 4.8% survived for 10 years after presentation. A further plea is made to establish a "100%" register of cancer.     

Navigating on the medical management freeway

Ready or not, the role of the medical group manager is rapidly expanding and only those who are well prepared and in control will survive. The views of a medical management consultant are presented in this entertaining article on a critical subject, along with guidelines for developing formal organizational goals.     

Thio TEPA pharmacokinetics during intravesical chemotherapy and the influence of Tween 80

Summary A pharmacokinetic study of randomised crossover design was carried out in which eight patients with recurrent stage pTa or pT1 transitional cell carcinoma of the bladder were given thio TEPA (30 mg) in distilled water or in 10% (v/v) Tween 80 (30 ml) intravesically for 2 h, followed 3 months later by the alternative treatment. Thio TEPA and its primary metabolite, TEPA, were measured in plasma and urine using a sensitive and specific chromatographic assay. Large differences between patients were observed in the proportion of thio TEPA absorbed, ranging from 20%–78%. Peak plasma levels of thio TEPA were observed within 1 h of intravesical administration. By 2 h after administration the plasma levels of TEPA were similar to those of thio TEPA and, in contrast to those of the parent compound, remained at a similar level over the next 4 h. The rate of absorption of thio TEPA was not influenced by Tween 80, but it did cause statistically significant increases in mean peak plasma levels (from 101 to 154 ng/ml) and mean AUC values (from 0.376 to 0.496 g h per ml) and a decrease in the mean half-life (from 1.83 to 1.25 h). To obtain plasma levels similar to those achieved after instillation with thio TEPA alone, the dose should be reduced with Tween 80.     

Neuropsychologic status in multiple sclerosis after treatment with glatiramer

BACKGROUND: Glatiramer acetate (Copaxone) therapy reduces clinical disease activity in relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To study the effect of glatiramer therapy on neuropsychologic function as part of a randomized, placebo-controlled, multicenter trial. METHODS: Two hundred forty-eight patients with relapsing-remitting MS and mild to moderate disability (Expanded Disability Status Scale score, <5.0) were tested before and 12 and 24 months after randomization to administration of glatiramer acetate, 20 mg/d, or matching placebo. Neuropsychologic tests examined 5 cognitive domains most often disrupted in patients with MS: sustained attention, perceptual processing, verbal and visuospatial memory, and semantic retrieval. RESULTS: Baseline neuropsychologic test performance was similar in both treatment groups and was within normal range, except for impaired semantic retrieval. Mean neuropsychologic test scores were higher at 12 and 24 months than at baseline, and no differences were detected between treatment groups over time. No significant interactions were detected between treatment and either time or baseline impairment. CONCLUSIONS: Our 2-year longitudinal study showed no effect of glatiramer therapy on cognitive function in relapsing-remitting MS. Although it is possible that glatiramer therapy has no effect on cognitive function, the lack of measurable decline in cognitive function in both patient groups for 2 years limits the opportunity for glatiramer to demonstrate a therapeutic effect by minimizing such decline. Emerging treatments for MS should continue to be examined for their effect on cognitive impairment because it can be a critical determinant of disability. A greater understanding of the natural history of cognitive decline in MS is essential for a rational design of these drug trials.     

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.