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.     

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.     

Preliminary investigation of the efficacy of sublingual verapamil in the management of acute atrial fibrillation and flutter

The antiarrhythmic properties of sublingual verapamil were investigated in seven patients with acute fast atrial flutter (n = 2) or fibrillation (n = 5). A rapid and significant (P < 0.05) reduction in the ventricular rate was achieved in all seven patients. The ventricular rate at peak plasma verapamil concentration (+/- s.d.) was significantly slower than on admission (101.6 +/- 11.3 and 159 +/- 5.3 beats min-1 respectively, P < 0.01). The ventricular rate remained controlled for over 4 h. Sublingual verapamil was rapidly absorbed with the maximum peak plasma concentration (153.3 +/- 15.5 ng ml-1) being achieved after 1.21 +/- 0.18 h. Side-effects of sublingual verapamil were limited to one report of a bitter taste. The sublingual administration of verapamil may provide an alternative method for the control of acute fast atrial fibrillation and flutter in selected patients.     

Inhibition of experimental neointimal hyperplasia and thrombosis depends on the type of vascular injury and the site of drug administration

BACKGROUND: Heparin inhibits vascular smooth muscle cell proliferation in tissue culture and limits neointimal hyperplasia after experimental arterial injury but has been ineffective in reducing clinical restenosis. We examined how this discrepancy might reflect suboptimal drug-tissue interactions and/or differences in the vascular response to injury. METHODS AND RESULTS: Intravenous infusion was compared with local administration of heparin to injured rabbit iliac arteries either from drug-impregnated polymeric controlled release matrices in the perivascular space or from drug-releasing endovascular stents. Occlusive thrombosis, seen in 42% of control stent-bearing arteries, and partial thrombosis were virtually eliminated by heparin delivery from any route. Intimal area 14 days after balloon withdrawal denudation alone was reduced to an equal extent by continuous systemic heparin or by perivascular heparin for the first 3 days. In contrast, endovascular stents produced more exuberant neointimal hyperplasia, the inhibition of which required continuous rather than only early heparin administration. Neither perivascular delivery limited to the first 3 days nor stent-based delivery reduced neointimal hyperplasia as effectively. CONCLUSIONS: The antiproliferative and antithrombotic effects of heparin differ markedly, depending on the type of arterial injury and the mode of drug administration. Different forms of injury may require different therapies, and complications of arterial intervention such as excessive neointimal hyperplasia and thrombosis may demand alternate therapeutic regimens. Duration, dose, and site of delivery rather than frank resistance to therapy may explain why experimentally effective antiproliferative and antithrombotic agents fail clinically.