ABSTRACT
INTRODUCTION: Resistance to first-line anti-tuberculosis drugs is a major concern in the treatment of the disease. New strategies, such as the use of efflux pump inhibitors (EPIs), are being investigated to improve the outcome of the treatment. Verapamil (VP), one such inhibitor, was shown to inhibit several efflux pump (EP) Mycobacterium tuberculosis proteins and demonstrate synergic activity with anti-TB drugs.OBJECTIVE: To evaluate the combinatory effect of isoniazid (INH) and VP in M. tuberculosis.METHODS: Minimal inhibitory concentrations and combinatory effects of INH+VP were determined using respectively resazurin microtitre assay plate (REMA) and resazurin drugs combination microtitre assay (REDCA). From the results, we selected three bacilli with different susceptibility profiles and assessed their expression of 10 EP genes through quantitative reverse transcription polymerase chain reaction after exposure to INH, VP and INH + VP for 48 h.RESULTS: A significant reduction of INH MIC was observed in INH-susceptible isolates upon combination with VP. In brief, gene expression assays revealed expression patterns that could be correlated with each resistance profile, presence or absence of gene mutations and combinatory effect with VP.CONCLUSION: Combining VP with INH showed important results in drug-susceptible strains, and clinical trials on combined VP + anti-TB drugs should be discussed.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/pharmacology , Bacterial Proteins/genetics , Gene Expression , Humans , Isoniazid/pharmacology , Membrane Transport Proteins/genetics , Microbial Sensitivity Tests , Mutation , Mycobacterium tuberculosis/genetics , Tuberculosis, Multidrug-Resistant/drug therapy , Verapamil/pharmacologyABSTRACT
OBJECTIVE: To evaluate the effectiveness of the prostatic stenting device--the Urolume--both in terms of relief from urinary outflow obstruction and as a means of reducing waiting lists. PATIENTS AND METHODS: A group of 70 men from the long-term waiting list were chosen for this study. The Urolume, a mesh tube of biomedical superalloy, was successfully introduced in 60 of these patients. The majority had the procedure performed as a day case, under a general anaesthetic. RESULTS: Seventy-two per cent of patients were symptomatically better when assessed at 6 weeks and their mean peak urinary flow rates had doubled. Early problems included haematuria, urge incontinence and dysuria. Stent displacement necessitating removal occurred in 10 patients. CONCLUSION: This technique offers the surgeon a quick and atraumatic method of relieving urinary outflow obstruction. There are, however, a number of problems associated with this technique which will probably be overcome by modification to the Urolume. As a result of our project, the waiting time for prostatic surgery was reduced from 3 years to under 2 years.
Subject(s)
Prostatic Hyperplasia/physiopathology , Prostatic Hyperplasia/surgery , Stents , Urinary Retention/surgery , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Stents/adverse effects , Treatment Outcome , Urethra/physiopathology , Urethra/surgery , Urinary Catheterization/adverse effects , Urinary Retention/physiopathology , UrinationABSTRACT
A series of 30 patients with outflow obstruction underwent treatment with prostatic stents. Most had retention of urine and were unfit for conventional surgery. The prostatic stent was readily inserted under local anaesthesia and successfully relieved obstruction in 80% of patients with acute retention. Minor problems were common but there were few major complications.
