EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.

In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

Multidrug-resistant tuberculosis in Russia: clinical characteristics, analysis of second-line drug resistance and development of standardized therapy.

The aim of the study presented here was to identify patients with multidrug resistant tuberculosis (MDRTB) in the Samara region of Russia and to analyze the susceptibility of their isolates to second-line drugs in order to develop an empirical, standard, second-line treatment regimen. Treatment of MDRTB can be individualized based on in vitro laboratory analysis or standardized. In the latter case there is still a need to ascertain local second-line drug-resistance patterns. Described here are the clinical characteristics of 251 MDRTB patients identified in the study and the second-line drug susceptibility of 69 MDRTB isolates obtained from them. Antimicrobial resistance to the following agents was detected in the isolates: rifabutin (88.2%), streptomycin (42.8%), amikacin (7.2%), doxycycline (7.4%), ciprofloxacin (4.3%), clofazimine (2.9%), cycloserine (7.4%), and prothionamide (1.5%). The results of the study indicate it is possible to develop a standard, effective, clinical treatment regimen using ethambutol, pyrazinamide, prothionamide, a fluoroquinolone and amikacin.

Intraocular pressure and pulsatile ocular blood flow after retrobulbar and peribulbar anaesthesia.

AIMS: This study investigated the effect of peribulbar and retrobulbar local anaesthesia on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF), as such anaesthetic techniques may adversely affect these parameters. METHODS: 20 eyes of 20 patients who were to undergo phacoemulsification cataract surgery were prospectively randomised to receive peribulbar or retrobulbar anaesthesia. The OBF tonometer (OBF Labs, Wiltshire, UK) was used to simultaneously measure IOP and POBF before anaesthesia and 1 minute and 10 minutes after anaesthesia. Between group comparisons of age, baseline IOP, and baseline POBF were performed using the non-parametric Mann-Whitney test. Within group comparisons of IOP and POBF measured preanaesthesia and post-anaesthesia were performed using the non-parametric Wilcoxon signed ranks test for both groups. RESULTS: There was no statistically significant IOP increase post-anaesthesia in either group. In the group receiving peribulbar anaesthesia, there was a significant reduction in POBF initially post-anaesthesia which recovered after 10 minutes. In the group receiving retrobulbar anaesthesia, there was a persistent statistically significant reduction in POBF. CONCLUSIONS: Retrobulbar and peribulbar injections have little effect on IOP. Ocular compression is not needed for IOP reduction when using local anaesthesia for cataract surgery. Conversely, POBF falls, at least for a short time, when anaesthesia for ophthalmic surgery is administered via a retrobulbar route or a peribulbar route. This reduction may be mediated by pharmacologically altered orbital vascular tone. It may be safer to use other anaesthetic techniques in patients with ocular vascular compromise.

Trends in antituberculosis drug resistance in Karonga District, Malawi, 1986-1998.

SETTING: Karonga District, Malawi. OBJECTIVES: To examine long term trends in initial and acquired resistance to antituberculosis drugs in a rural area of Africa. DESIGN: Monitoring of all patients with culture-confirmed tuberculosis 1986-1998. RESULTS: Initial drug resistance results were available for 1121 patients. The proportion resistant to any of the first line drugs (streptomycin, isoniazid, rifampicin or ethambutol) was 9.6%, and to isoniazid 7.2%. Initial resistance to at least isoniazid and rifampicin (multidrug resistance) was seen in only six patients. No initial resistance to ethambutol was found. There was no significant change in initial drug resistance over time. Overall, 22/120 (18%) patients with previous treatment were resistant to at least one drug; only one had multidrug resistance. Acquired resistance decreased over the period of the study. There were no associations between age, sex or human immunodeficiency virus (HIV) status and initial or acquired drug resistance. CONCLUSIONS: Changes in acquired resistance may reflect the recent performance of a control programme more quickly than those in initial resistance. It is encouraging that acquired resistance decreased and levels of multidrug resistance were low despite more than a decade of use of rifampicin. The lack of association between HIV and drug resistance confirms findings elsewhere in Africa.

Effects of adenosine receptor antagonists on the responses to contrast media in the isolated rat kidney.

Contrast media can induce both a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR) when administered to both experimental animals and humans. In the present study we have examined the role of adenosine in mediating these effects using the isolated perfused rat kidney. Kidneys were perfused with a 6. 7%-(w/v)-albumin-based perfusate supplemented with glucose and amino acids (n=6 per group). They were exposed to diatrizoate [20 mg of iodine (mgI)/ml; osmolality 1650 mOsm/kg of water] or iotrolan (20 mgI/ml; osmolality 320 mOsm/kg of water) in the presence or absence of theophylline (10.8 microg/ml), or to diatrizoate in the presence or absence of a specific adenosine A(1) receptor antagonist (KW-3902; 2 microg/ml) or a specific A(2) receptor antagonist (KF17837; 6 microg/ml). Diatrizoate (n=6) produced a fall in GFR from 0.65+/-0.04 to 0.42+/-0.03 ml.min(-1).g(-1) (P<0.05); renal perfusate flow (RPF) also declined, from 36.5+/-3.8 to 22.0+/-3.2 ml. min(-1).g(-1) (P<0.05). Iotrolan (n=6) produced a fall in GFR from 0. 64+/-0.02 to 0.48+/-0.04 ml.min(-1).g(-1) (P<0.05) and in RPF from 33.3+/-3.8 to 24.0+/-3.0 ml.min(-1).g(-1) (P<0.05). Theophylline (10.8 microg/ml) prevented the fall in GFR caused by either diatrizoate (baseline, 0.63+/-0.05 ml.min(-1).g(-1); diatrizoate+theophylline, 0. 60+/-0.04 ml.min(-1).g(-1)) or iotrolan (baseline, 0.64+/-0.04 ml. min(-1).g(-1); iotrolan+theophylline, 0.67+/-0.05 ml.min(-1).g(-1)), but did not affect the decreases in RPF caused by either agent. KW-3902 (2 microg/ml) also prevented the fall in GFR produced by diatrizoate (baseline, 0.66+/-0.05 ml.min(-1).g(-1); diatrizoate+KW-3902, 0.61+/-0.05 ml.min(-1).g(-1)), while the fall in RPF remained unaffected. KF17837 (6 microg/ml) had no effect on the decreases in either GFR or RPF induced by diatrizoate (n=6 per group). The results suggest a role for adenosine acting at the A(1) receptor in mediating the decrease in GFR induced by contrast media. This effect is independent of a change in renal vascular resistance, and possibly secondary to mesangial cell contraction causing a decrease in the ultrafiltration coefficient.

Activity against Mycobacterium tuberculosis of alkaloid constituents of Angostura bark, Galipea officinalis.

The activity of an ethanolic extract of Galipea officinalis bark against Mycobacterium tuberculosis was shown to reside mainly in the basic alkaloidal fraction although the major part of the alkaloids present were in the neutral fraction. Six alkaloids were isolated from the bark including two other alkaloids not previously reported from G. officinalis and a new quinoline named allocuspareine, whose structure was determined by spectroscopic methods. 1H- and 13C-NMR spectral data for three of these compounds are reported for the first time. Isolation and testing of fractions and individual alkaloids against ten strains of M. tuberculosis showed that all the alkaloids possessed some activity but that the unidentified most polar basic fraction exhibited the greatest effect.

Randomized controlled trial of a drug regimen that includes ciprofloxacin for the treatment of pulmonary tuberculosis.

The fluoroquinolones are promising new antituberculous agents. A randomized controlled trial of 200 adult patients with sputum smear-positive pulmonary tuberculosis was conducted in Tanzania. Patients received either a trial regimen (HRC) consisting of isoniazid (300 mg), rifampin (600 mg), and ciprofloxacin (750 mg) or a control regimen (HRZE) consisting of isoniazid (300 mg), rifampin (600 mg), pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg). The 168 evaluable patients all had negative smears and cultures by month 6, but the time to conversion to negativity was longer for the HRC group than for the HRZE group because of the poor response of patients infected with human immunodeficiency virus (HIV) to the HRC regimen. Relapse was more frequent in the HRC group. The sterilizing activity of ciprofloxacin does not appear to be equal to that of the combination of pyrazinamide and ethambutol, but the difference in outcome was significant only among HIV-infected patients.

Nitrogenases of Klebsiella pneumoniae and Azotobacter chroococum. Complex formation between the component proteins.

1. Sedimentation velocity analyses of mixtures of highly purified component proteins of Azotobacter chroococcum are consistent with the formation of a tight 1 : 1 complex in the absence of Na2 S2 O4. 1 : 1 complex formation between complementary proteins from A. chroococcum and Klebsiella pneumoniae was also observed. The addition of 5 mM Na2 S2 O4 weakened the interaction between the A. chroococcum proteins and also the interaction between complementary proteins of A. chroococcum and K. pneumoniae. 2. Steady-state kinetic data for acetylene reduction at low protein concentrations have been used to calculate association constants at 30 degrees C for the 1 : 1 protein complexes of nitrogenase proteins from A. chroococcum, K. pneumoniae and mixtures of complementary proteins from both organisms. Values centered around 3 - 10(7) M-1 were obtained. 3. The temperature dependence of the association constant for the complex formed by the K. pneumoniae proteins exhibited a sharp break at 17 degrees C with deltaH = 0 and deltaH = 418 kJ - mol-1 above and below 17 degrees C, respectively. 4. The Arrhenius plot for acetylene reduction by the complex formed by the K. pneumoniae proteins was linear over the range 12-40 degrees C with deltaH = 80 kJ - mol-1.