Structural and biochemical changes in lungs of 3-methylindole-treated rats

This study compared co-amoxiclav, vancomycin and teicoplanin with and without netilmicin or amikacin for treating experimental subcutaneous fibrin-clot infection in rabbits due to a clinical beta-lactamase-positive methicillin- and gentamicin-resistant Staphylococcus epidermidis strain (MGRSE). MICs (mg/L) for this strain were: oxacillin 125, gentamicin 32, vancomycin 4, teicoplanin 8, netilmicin 1, amikacin 4, amoxycillin 64 with clavulanate at 2 mg/L. In rabbits treated with a single-dose i.v. regimen (netilmicin 8 mg/kg, amikacin 20 mg/kg, vancomycin 30 mg/kg, teicoplanin 15 mg/kg, co-amoxiclav 150-30 mg/kg), the bacterial count 24 h post-dose was reduced whatever the combination used (ANOVA, P < or = 0.001). Regimens were statistically classified in decreasing order of efficacy as follows: co-amoxiclav combined with netilmicin > vancomycin either alone or combined with either netilmicin or amikacin, teicoplanin with netilmicin > netilmicin and co-amoxiclav alone > teicoplanin or co-amoxiclav combined with amikacin, and teicoplanin alone > amikacin > no drug. From these findings, it is concluded that: co-amoxiclav could be useful for the treatment of beta-lactamase-positive and methicillin-resistant S. epidermidis infection; some enzyme-resistant aminoglycoside could be considered for treating gentamicin-resistant but netilmicin/amikacin-sensitive S. epidermidis infection; the combination of co-amoxiclav with netilmicin was synergistic and more rapidly bactericidal than vancomycin in this animal model.     

An improved method for detecting passive pills

One of the principal disadvantages of the passive pill as a telemetric method for measuring various physiological parameters has been its resticted range. The reasons for the restricted range with existing detection methods are discussed. An improved method using a locking spectrometer based on third-order phase-sensitive detection is described and its performance is assessed. A significant increase in the usable range of a high sensitivity passive pill is obtained.     

Radiofrequency catheter ablation of atrioventricular junctional ("AV nodal") reentrant tachycardia in patients with implantable cardioverter defibrillators

Catheter ablation of tachycardias has been undertaken successfully in patients with ICDs without damage to the ICD or lead. Ablation of the slow AV nodal pathway, however, is technically challenging because the lead of the ICD lies close to the ablation site. We report successful ablation of AV junctional reentrant tachycardia (AVJRT) in three patients with ICDs. In all cases, the ablation site was within a few millimeters of the ICD lead. The ablation was successful in all cases and did not cause damage to the ICD or lead. The patients have remained free of recurrence of AVJRT during a mean follow-up of 12 months.     

Rearrangement of immunoglobulin genes in chicken B cell development

Immunoglobulin gene rearrangement in the chicken has evolved not to generate antibody diversity per se but to generate an immunoglobulin variable region which can be diversified by subsequent somatic gene conversion events. While the molecular mechanism of V(D)J recombination in chickens cannot be distinguished from that seen in other species, the way in which this recombination is regulated during chicken B lymphocyte development does differ from the more widely known models of gene rearrangement in humans and rodents. In this review we focus on these differences, relating V(D)J recombination to the progression of chicken B cell development in the bursa of Fabricius.     

Treatment of intracranial ependymomas of children: review of a 15-year experience

PURPOSE: There are still major controversies in the optimal management of children with intracranial ependymomas. To assess the impact of tumor site, histology, and treatment, the outcome of children treated at the Institut Gustave Roussy was reviewed retrospectively. METHODS AND MATERIALS: Between 1975 and 1989, 80 children aged 4 months to 15.8 years were seen at the Institut Gustave Roussy for postoperative management of an intracranial ependymoma. Location of tumor was infratentorial in 63 cases and supratentorial in 17. Surgical treatment consisted of complete resection in 38, incomplete resection in 38 and biopsy only in 4. Postoperative irradiation was done in 65 patients and chemotherapy in 33. Surviving patients have been followed from 12-197 months with a median of 54 months. RESULTS: The 5-year actuarial survival and event-free survival are 56% and 38%, respectively. Thirty-four patients relapsed from 3-72 months after diagnosis (median 25 months). In 20 patients, the only site of failure was the original tumor site. Three patients failed locally and at distance, while 10 others failed only at distance. Survival at 5 years was significantly better for patients who had complete resection of the tumor (75% vs. 41%, p = 0.001) and for those who received radiation therapy (63% vs. 23%, p = 0.003). Event-free survival at 5 years was superior in patients with complete resection of the tumor (51% vs. 26%, p = 0.002) and in patients who received radiation therapy (45% vs. 0%, p < 0.001). Sex and tumor site had no impact on survival or event-free survival. There was no difference in survival, event-free survival, or pattern of failure between patients treated with local field, whole brain or craniospinal irradiation, while severe longterm sequelae were noted predominantly in the latter two groups. CONCLUSION: Considering that failures were predominantly local and that there was no apparent benefit from prophylactic irradiation, we recommend local field irradiation with doses above 50.0 Gy for all children with intracranial ependymomas, without meningeal dissemination at diagnosis. Special considerations are necessary for children < 3 years of age.     

Polymerase chain reaction analysis of allele frequency and loss at the Harvey ras locus in myeloid malignancies

The hypothesis that 'rare' variable number tandem repeat (VNTR) alleles of the Harvey ras (Ha-ras) locus are an inherited predisposing factor in myeloid malignancies has been evaluated. We describe an application of the polymerase chain reaction (PCR) which amplifies the VNTR region at the Ha-ras locus and offers a number of advantages over conventional Southern analysis. Ha-ras VNTR genotypes were assigned to 57 normal subjects, 46 patients with acute myeloid leukaemia (AML), 26 with myelodysplastic syndrome (MDS) and 49 with chronic granulocytic leukaemia (CGL). By comparison with previous reports we found significantly higher frequencies of rare alleles (20.2%) in our normal subjects of whom more than 35% had at least one 'rare' allele. The frequencies of rare alleles in the patient groups was not significantly different from the normal group (chi 2 = 0.54, p = 0.91). In studies of constitutional and leukaemic DNA from patients with AML, we found that allelic loss at the Ha-ras locus was not a common phenomenon. The improved resolution achievable with PCR compared with Southern analysis was demonstrated by the inability of Southern analysis to resolve six out of 34 PCR heterozygotes. We therefore suggest that previous studies showing linkage between rare Ha-ras alleles and susceptibility to malignancy should be reevaluated using our sensitive PCR technique.     

Analysis of solid renal dysplasia by flow cytometry: malignant potential?

The iron-chelating agent desferrioxamine now finds extensive use in the treatment and diagnosis of aluminum-related diseases in renal patients. We review the chemistry and pharmacokinetics of desferrioxamine in chelation therapy for patients on hemodialysis.     

Inhibition of morphine-induced tolerance and dependence by a benzodiazepine receptor agonist midazolam in the rat

We investigated whether midazolam administration influenced morphine-induced antinociception and tolerance and dependence in the rat. Antinociception was assessed by the tail-flick (TF) and the hot-plate test (HP 52 degrees C). Morphine tolerance developed after daily single injections of morphine for 11 days. The effect of midazolam on morphine-induced antinociception and tolerance was assessed by giving daily injections of various doses of midazolam for 11 days. The first injection of saline or midazolam was given intraperitoneally and 30 min later morphine (10 mg/kg body weight) was administered subcutaneously. Antinociception was monitored by measuring TF and HP latencies 60 min after the second injection. Midazolam was injected at four different concentrations: 0.03, 0.1, 0.3, and 3 mg/kg body weight. Chronic administration of morphine resulted in the development of tolerance to antinociception in both TF and HP tests, with rats exhibiting baseline antinociception on Day 9. Animals treated with midazolam alone showed little antinociception on Days 3-9. However, midazolam administration in morphine-treated animals attenuated morphine-induced tolerance to antinociception on Days 1-11 as measured by the tail-flick test. Midazolam also decreased the jumping behavior following naloxone injections in morphine-dependent rats. These results suggest that midazolam may prolong the effects of morphine by delaying morphine-induced development of tolerance to antinociception. Midazolam also attenuated a decrease in weight gain induced by chronic injections of morphine.