Agreement between CBNAAT,liquid culture and line probe assay for detection of Mycobacterium tuberculosis and anti-tubercular drug resistance in extrapulmonary samples

PurposeCartridge based nucleic acid amplification test (CBNAAT) has been endorsed by the WHO as the screening test for diagnosing extrapulmonary tuberculosis (EPTB). In the present study we report the agreement between CBNAAT (Xpert MTB/RIF), liquid culture (LC) and line probe assay (LPA) for diagnosis of Mycobacterium tuberculosis and detection of drug resistance among EPTB cases.MethodsThe EP samples were subjected to CBNAAT (Xpert MTB/RIF, Cepheid, USA) and wherever possible, to LC (MGIT 960, Becton Dickinson, USA) followed sequentially by first line and second line-LPA (FL-LPA, SL-LPA, Hain Lifescience, Germany) on the isolates.ResultsTotal 566/4080 (13.9%) EP samples were detected positive for M. tuberculosis on CBNAAT. Aspirates from lymph nodes were most often positive (11/30; 36.6%), followed by pus (240/873; 27.5%) and CSF samples (166/104; 15.8%). The detection of M. tuberculosis was more in adults than children except in tissue biopsy samples. Rifampicin resistance was also higher among adults except CSF in which resistance was more in children. Total 185 of 566 (32.7%) CBNAAT positive and 770 of 3510 (21.9%) CBNAAT negative samples could be cultured of which 110/185 (59.4%) and 33/770 (4.3%) respectively turned positive. FL-LPA and SL-LPA of 143 culture isolates showed that 27 isolates had drug resistance, of which 3 (2.1%) were XDR, 11 (7.7%) were Pre-XDR (FQ) and 13 (9.1%) were MDR. Of these 27 resistant isolates, 12 were negative by CBNAAT and two were mislabeled as Rifampicin sensitive or indeterminate based on the unique RpoB gene mutation patterns on LPA. The positive and negative agreements between LC and CBNAAT for detection of M. tuberculosis were 67.1% and 92.7% respectively and between LPA and CBNAAT for rifampicin resistance detection were 98.9% and 92.9% respectively.ConclusionsFor EPTB, CBNAAT should be accompanied with LC wherever possible irrespective of the CBNAAT result.     

On the interaction between phenytoin and digoxin

Summary An open, randomized, single-blind cross over trial to investigate phenytoin-digoxin interactions at steady state was performed in 6 healthy male volunteers. Coadministration of phenytoin caused a significant reduction in the elimination half-life of digoxin from 33.9 to 23.7 h and a diminution in AUC_0–48 from 31.6 to 24.4 ng · ml^–1 · h. Renal digoxin clearance was not significantly altered from 135.7 to 120.3 ml · min^–1. Assuming no change in -acetyldigoxin absorption, the in decrease time-course the serum digoxin concentration was due to a significantly increased total digoxin clearance from 258.6 to 328.3 ml · min^–1. An insignificant reduction in the digoxin distribution volume from 749.4 to 668.0 l was also observed. No relevant change in the pharmacokinetic parameters (elimination half-life, area under the serum concentration time-curve, protein binding) of phenytoin was observed when phenytoin and digoxin were co-administered. The data suggest that with this drug combination the serum digoxin concentration should be carefully monitored and, if necessary, the daily digoxin dose should be increased.     

Longitudinal studies of drug abuse in a fifteen-year-old population. 5. Prognostic factors

In an attempt to identify prognostic factors, non-drug users and abusers in the Gothenburg year cohort of 1953 were compared with reference to background data. Individuals with chronic abuse differed most from the "normal" group. Prognostic factors for drug abuse were: member of a multiproblem family, child psychiatric care, contact with the Social Welfare Administration at an early age, truancy, placement in special class, premature drop-out from school, admitted high-frequency drug use in a school questionnaire, for boys early registration for crimes and for girls nervous complaints. The results indicate the necessity of earlier and more effective prevention.     

Personality traits and platelet MAO activity in alcohol and drug abusing teenage boys

The aim of this study has been to investigate whether teenage boys with mixed drug abuse differ from those with pure alcohol abuse as concerns personality traits and platelet monoamine oxidase activity. The series included 1129 consecutive 18-year-old males called to the Enlistment Center in the northern part of Sweden. A special inventory was constructed based on Zuckerman Sensation Seeking Scale (SSS), Eysenck's Personality Inventory (EPI), the Karolinska Scales of Personality (KSP) and questions about alcohol and drug consumption. The subjects with mixed drug abuse (n = 96) had high scores in the two subscales of SSS and KSP related to ability to stand boredom, high scores in both subscales of EPI and KSP related to impulsivity, high scores in Thrill and Adventure Seeking (TAS) and Experience Seeking (ES) of SSS as well as low platelet monoamine oxidase activity. The males with pure alcohol abuse (n = 33) also showed signs of monotony avoidance and impulsivity, but this type of abuse was not clearly related to low platelet monoamine oxidase activity and not to the aspects of curiosity included in the SSS such as TAS and ES. These findings are consistent with the picture earlier found as concerns "Type II" alcoholism which has an early onset, is genetically transmitted, is associated with mixed drug abuse and social complications.     

The Influence of Drugs on Nasal Ciliary Movement

Drugs in nasal preparations, for local use as well as for systemic use, should not interfere with the self-cleaning capacity of the nose, effectuated by the ciliary epithelium. Many drugs and additives, however, have a negative effect on nasal ciliary function. Examples of ciliotoxic agents are lipophilic and mercuric preservatives, local anesthetics, antihistamines, propranolol, and absorption enhancers such as the bile salts. Cholinergic drugs and -adrenergic drugs exert a ciliostimulatory effect. It is the purpose of this review to summarize the present knowledge of ciliotoxicity of drugs and additives and to give recommendations for the use of ciliofriendly drugs in nasal preparations.     

Cervical tissue uptake of all-trans-retinoic acid delivered via a collagen sponge-cervical cap delivery device in patients with cervical dysplasia

The present study was undertaken to evaluate the systemic absorption and cervical tissue uptake of all-transretinoic acid (TRA), delivered via a collagen spongecervical cap delivery device in patients with intraepithelial cervical dysplasia. Ten patients with histologically proven mild or moderate cervical dysplasia were included in this pharmacologic study. The two TRA concentrations (0.05% and 0.372%) selected for study represent the starting and maximally tolerated doses used in phase I clinical trial. All-trans-retinoic-11-³H acid (³H-TRA, 500 Ci) was used to facilitate cervical tissue uptake studies. Cervical biopsies and post-treatment blood samples were obtained from each patient after TRA exposure. The uptake of TRA into cervical tissues four hours after drug administration was significantly increased at the maximally tolerated TRA dose. There was a rapid decrease in cervical tissue concentration of TRA at the 0.372% dose between 4 and 24 h after drug exposure, suggesting a relatively short elimination half-life of TRA in cervical tissues. HPLC analysis of post-treatment blood samples indicate that there was no systemic absorption of TRA after local cervical administration.     

Pharmacokinetic and pharmacodynamic study of the combination of furosemide retard and triamterene

Summary The pharmacodynamics and pharmacokinetics of the combination of furosemide retard (30 mg)/triamterene (50 mg) were compared with furosemide (30 mg) in 18 healthy male volunteers aged 39.3±6.3 years. After the administration of furosemide the onset of its effect was very rapid, reaching a maximum between 1.5 to 3 h, and followed by rebound after 9 to 10.5 h. In contrast the combination furosemide retard/triamterene showed a protracted course with a duration of effect up to 12 h. The general effect over 12 h of the two preparations was equivalent with respect to the excretion of urine, sodium, chloride and calcium, but the combination caused significantly less excretion of potassium (p0.05) than furosemide. After a lag-phase of 33.9±5.4 min the maximum plasma concentration of furosemide was reached after 3.47±0.66 h, and the elimination half-life was approximately 2 h. After a lag-phase of 33.0±17.8 min the maximum plasma concentration of the main metabolite of triamterene, the OH-TA sulphuric acid ester, was reached after 1.7±0.59 h, and its elimination half-life amounted to 1.25±0.37 h. Because of the sustained release of furosemide from the retard-formulation, its principal pharmacokinetic parameters were better adapted to those of triamterene. The consequences were not only a protracted effect but also an improved electrolyte profile, especially with regard to reduced loss of potassium. In the case of renal insufficiency, however, the potassium level in serum might be increased to an undesirable extent.     

Central mediation of the conditioned taste aversion induced in rats by harmaline

The assumption that drugs used as unconditioned stimuli in conditioned taste aversion (CTA) studies act centrally was tested by comparing the effects of systemic and intracerebral injections of harmaline hydrochloride (H) in 340 rats. Intraperitoneal injection of 5–20 mg/kg but not of 2.5 mg/kg H administered 5 min after 15-min saccharin (0.1%) drinking decreased saccharin-water preference in a two-choice retention test, performed 48 h later, from 55% to 20%. Since CTA was not diminished when H (10 mg/kg) was injected into rats anesthetised immediately after saccharin drinking by pentobarbital (40 mg/kg), H (1.7–50 g) was administered intracerebrally to anesthetised rats fixed in the stereotaxic apparatus. Injection of 3–6 g H into the inferior olive elicited CTA comparable to that of systemic injection of 10 mg/kg H. Injections of 6 and 50 g H into cerebellum and bulbar reticular formation elicited weaker CTA while neocortical, hypothalamic and mesencephalic applications were ineffective. CTA could also be elicited when 50 g but not 6 g H was injected into the inferior olive 1 or 2 h after saccharin drinking. This delay-dependent effect and failure of non-contingent H administration to change saccharin preference indicates that the H-induced CTA is not contaminated by a non-specific increase in neophobia. It is concluded that H probably elicits CTA by activation of caudal bulbar structures, including the nucleus of the solitary tract, area postrema and lateral reticular formation.