Common Therapeutic Drugs Research Articles

Tuberculosis in Pregnancy - a Summary.

In recent years, the incidence of tuberculosis in pregnancy in the industrialised countries has increased. Tuberculosis in pregnancy is associated with an increased risk for the mother and child. Even if no figures are available for Germany, an increase in the number of tuberculosis cases among pregnant women can be assumed due to the migratory flows; current data from the USA, for example, also show an increasing incidence of tuberculosis in pregnant women in recent years. The physiological and immunological changes that occur during pregnancy are likely to have a negative impact on the course of the disease and may make it more difficult to confirm the diagnosis. There are no internationally standardised recommendations for diagnosing latent tuberculosis infections. When screening for TB is performed in specific risk populations, an Interferon-γ Release Assay (IGRA) should preferably be carried out according to the current study data. If corresponding symptoms are present and an IGRA test is positive, further diagnostics are indicated, also in pregnancy. If tuberculosis is confirmed, the fact that a woman is pregnant must not delay the initiation of anti-tuberculosis therapy, as an early start of therapy is associated with a more favourable outcome for both mother and child. The common first-line therapeutic drugs may also be used during pregnancy and are considered safe. The treatment of latent tuberculosis during pregnancy is disputed.

Forcing ATGL expression in hepatocarcinoma cells imposes glycolytic rewiring through PPAR-\u03b1/p300-mediated acetylation of p53

Metabolic reprogramming is a typical feature of cancer cells aimed at sustaining high-energetic demand and proliferation rate. Here, we report clear-cut evidence for decreased expression of the adipose triglyceride lipase (ATGL), the first and rate-limiting enzyme of triglyceride hydrolysis, in both human and mouse-induced hepatocellular carcinoma (HCC). We identified metabolic rewiring as major outcome of ATGL overexpression in HCC-derived cell lines. Indeed, ATGL slackened both glucose uptake/utilization and cell proliferation in parallel with increased oxidative metabolism of fatty acids and enhanced mitochondria capacity. We ascribed these ATGL—downstream events to the activity of the tumor-suppressor p53, whose protein levels—but not transcript—were upregulated upon ATGL overexpression. The role of p53 was further assessed by abrogation of the ATGL-mediated effects upon p53 silencing or in p53-null hepatocarcinoma Hep3B cells. Furthermore, we provided insights on the molecular mechanisms governed by ATGL in HCC cells, identifying a new PPAR-α/p300 axis responsible for p53 acetylation/accumulation. Finally, we highlighted that ATGL levels confer different susceptibility of HCC cells to common therapeutic drugs, with ATGL overexpressing cells being more resistant to glycolysis inhibitors (e.g., 2-deoxyglucose and 3-bromopyruvate), compared to genotoxic compounds. Collectively, our data provide evidence for a previously uncovered tumor-suppressor function of ATGL in HCC, with the outlined molecular mechanisms shedding light on new potential targets for anticancer therapy.

Interplay between transcription regulators RUNX1 and FUBP1 activates an enhancer of the oncogene c-KIT and amplifies cell proliferation.

Runt-related transcription factor 1 (RUNX1) is a well-known master regulator of hematopoietic lineages but its mechanisms of action are still not fully understood. Here, we found that RUNX1 localizes on active chromatin together with Far Upstream Binding Protein 1 (FUBP1) in human B-cell precursor lymphoblasts, and that both factors interact in the same transcriptional regulatory complex. RUNX1 and FUBP1 chromatin localization identified c-KIT as a common target gene. We characterized two regulatory regions, at +700 bp and +30 kb within the first intron of c-KIT, bound by both RUNX1 and FUBP1, and that present active histone marks. Based on these regions, we proposed a novel FUBP1 FUSE-like DNA-binding sequence on the +30 kb enhancer. We demonstrated that FUBP1 and RUNX1 cooperate for the regulation of the expression of the oncogene c-KIT. Notably, upregulation of c-KIT expression by FUBP1 and RUNX1 promotes cell proliferation and renders cells more resistant to the c-KIT inhibitor imatinib mesylate, a common therapeutic drug. These results reveal a new mechanism of action of RUNX1 that implicates FUBP1, as a facilitator, to trigger transcriptional regulation of c-KIT and to regulate cell proliferation. Deregulation of this regulatory mechanism may explain some oncogenic function of RUNX1 and FUBP1.

Quality, origins and limitations of common therapeutic drug reference intervals.

Therapeutic drug monitoring (TDM) is used to manage drugs with a narrow window between effective and toxic concentrations. TDM involves measuring blood concentrations of drugs to ensure effective therapy, avoid toxicity and monitor compliance. Common drugs for which TDM is used include aminoglycosides for infections, anticonvulsants to treat seizures, immunosuppressants for transplant patients and cardiac glycosides to regulate cardiac output and heart rate. An essential element of TDM is the provision of accurate and clinically relevant reference intervals. Unlike most laboratory reference intervals, which are derived from a healthy population, TDM reference intervals need to relate to clinical outcomes in the form of efficacy and toxicity. This makes TDM inherently more difficult to develop as healthy individuals are not on therapy, so there is no "normal value". In addition, many of the aforementioned drugs are old and much of the information regarding reference intervals is based on small trials using methods that have changed. Furthermore, individuals have different pharmacokinetics and drug responses, particularly in the context of combined therapies, which exacerbates the challenge of universal TDM targets. This focused review examines the origins and limitations of existing TDM reference intervals for common drugs, providing targets where possible based on available guidelines.

Measuring disease similarity and predicting disease-related ncRNAs by a novel method

BackgroundSimilar diseases are always caused by similar molecular origins, such as diasease-related protein-coding genes (PCGs). And the molecular associations reflect their similarity. Therefore, current methods for calculating disease similarity often utilized functional interactions of PCGs. Besides, the existing methods have neglected a fact that genes could also be associated in the gene functional network (GFN) based on intermediate nodes.MethodsHere we presented a novel method, InfDisSim, to deduce the similarity of diseases. InfDisSim utilized the whole network based on random walk with damping to model the information flow. A benchmark set of similar disease pairs was employed to evaluate the performance of InfDisSim.ResultsThe region beneath the receiver operating characteristic curve (AUC) was calculated to assess the performance. As a result, InfDisSim reaches a high AUC (0.9786) which indicates a very good performance. Furthermore, after calculating the disease similarity by the InfDisSim, we reconfirmed that similar diseases tend to have common therapeutic drugs (Pearson correlation γ2 = 0.1315, p = 2.2e-16). Finally, the disease similarity computed by infDisSim was employed to construct a miRNA similarity network (MSN) and lncRNA similarity network (LSN), which were further exploited to predict potential associations of lncRNA-disease pairs and miRNA-disease pairs, respectively. High AUC (0.9893, 0.9007) based on leave-one-out cross validation shows that the LSN and MSN is very appropriate for predicting novel disease-related lncRNAs and miRNAs, respectively.ConclusionsThe high AUC based on benchmark data indicates the method performs well. The method is valuable in the prediction of disease-related lncRNAs and miRNAs.

Patterns and Trends in Scientific Research on Generic Drugs

PurposeThe purpose of this study to investigate the evolution and current status of peer-reviewed publications concerning generic drugs during the past few decades. MethodsScientific articles about generic drugs published until 2012 were retrieved through the PubMed/MEDLINE database, and a content analysis was performed. FindingsOur study revealed an increasing number of publications on generics since 1984. Statins, antiretroviral therapies, and antiepileptics, followed by immunosuppressants and antithrombotic agents, were the most common therapeutic drug categories. ImplicationsAlmost 60% of the generics detailed in studies indexed in MEDLINE were acting on the cardiovascular system as anti-infectives and on the nervous system, which is not surprising considering the leading causes of death and disability worldwide.

Analysis of new designer drugs in post-mortem blood using high-resolution mass spectrometry.

An analytical method was developed and validated for the purpose of detecting and quantifying 37 new designer drugs including cathinones, hallucinogenic phenethylamines and piperazines. Using only 100 µL whole blood, a salting-out-assisted liquid-liquid extraction with acetonitrile was performed to isolate target compounds followed by chromatographic separation using a Waters ACQUITY ultra performance liquid chromatograph coupled to a Waters XEVO quadrupole time-of-flight mass spectrometer. Mephedrone-d3 was used as an internal standard. A gradient elution was used in combination with a Waters ACQUITY HSS C18 column (2.1 × 150 mm, 1.8 µm). Samples were analyzed using the detector in positive electrospray ionization mode with MS(E) acquisition. All compounds of interest were resolved in a 15 min run time and positively identified based on accurate mass of the molecular ion, two product ions and retention time. All analyte calibration curves were linear over the range of 0.05-2 mg/L with most correlation coefficient (r(2)) values >0.98. The limits of detection were within the range of 0.007-0.07 mg/L and limits of quantification within 0.05-0.1 mg/L. All analytes were stable 48 h after extraction and most were stable in blood after 1 week stored in a refrigerator and 3 freeze-thaw cycles. No carryover was observed up to 10 mg/L and no interferences from common therapeutic drugs or endogenous compounds. Recoveries ranged from 71 to 100% and matrix effects were assessed for blank, post-mortem and decomposed blood. All bias and % coefficient of variation values were within the acceptable values of ±15 and ≤15%, respectively (±20 and ≤20% at lower limit of quantification). The method was applied to several forensic cases where the subject exhibited behavior characteristic of designer drug intoxication and where routine screening for a panel of drugs was negative.

Ultra high performance liquid chromatography–electrospray ionization–tandem mass spectrometry screening method for direct analysis of designer drugs, “spice” and stimulants in oral fluid

An ultra high performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS) screening method for the direct analysis in oral fluid (OF) of 24 drugs, including new synthetic cannabinoids and so-called “smart” designer drugs, in a single chromatographic run was set up. Benzylpiperazine, methylone, 5,6-methylenedioxy-2-aminoindane (MDAI), fenproporex, 4-fluoroamphetamine (4-FA), 4-methyl-N-ethylcathinone (4-MEC), 4-methylamphetamine (4-MA), methylbenzodioxolylbutanamine (MBDB), mephedrone, methylthioamphetamine (MTA), methylenedioxypyrovalerone (MDPV), mefenorex, nabilone, furfenorex, clobenzorex, JWH-200, AM 694, JWH-250, JWH-073, JWH-018, JWH-019, JWH-122, HU 210 and CP 47497 were determined in a chromatographic run of 9min only with no sample pre-treatment, after addition of ISs and dilution in mobile phase A. This method is designed to be applied to 250μL of OF sample, anyway is suitable to be used on smaller volumes (till 100μL). LODs vary from 1ng/mL to 20ng/mL. No interfering peaks were observed due to similar analytes, common therapeutic drugs or endogenous compounds. Matrix effect, although present especially for mephedrone, is acceptable, allowing the detection of the compounds at the LODs described. The developed method was applied on 400 real OF samples from on-site tests performed by police officers.

Abstract 269: A novel mechanism of p21 induction by oxaliplatin in p53 deficient cancer cells

Abstract p21(CDKN1A) is a well known cyclin-dependent kinase (cdk) inhibitor. As a critical cell cycle checkpoint of p53 mediated DNA damage response, p21 interferes with cyclin-CDK2 complex, blocking cell cycle at the G1/S interface, thus reducing the risk of DNA damaged cells transforming to cancer cells. Activation of p21 checkpoint by therapeutic agent is often associated with cancer cell cycle arrest and effective tumor suppression. However, many cancer lost wild type p53 while p21 in these cells maintains at a low level. In these cells p21 transcription is mainly controlled by p53-independent mechanisms through various cis-acting elements and these type of cancer are often more likely to resist chemo treatment. In search of effective therapeutic agents against p53 negative and drug resistant cancers we used SKOV3, a p53 deficient cancer cell line, to assess the ability of common therapeutic drugs to induce p21 expression. Promoter-reporter assays suggest p21 promoter is significantly stimulated by Oxaliplatin in SKOV3 cells compared with most common drugs used in chemotherapy. Through the promoter deletion analysis we identified a previously unreported Oxaliplatin responsive cis-acting element located between −237 to −220bp in the p21 promoter. Genomic DNA functional element analysis using ENCODE (Encyclopedia of DNA Elements) Consortium suggests that a vertebrate-conserved element overlaps well with the newly discovered Oxaliplatin responsive element. This conserved promoter element is required for the effective induction of p21 promoter activity by Oxaliplatin and such induction is positively related to drug induced S-phase cell cycle arrest. Finally, the ability of p21 induction of chemotherapy drugs is well correlated with their effectiveness of reducing SKOV3 xenograft tumors in nude mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 269. doi:1538-7445.AM2012-269

Arylamine N-Acetyltransferase 2 (NAT2) Genetic Diversity and Traditional Subsistence: A Worldwide Population Survey

Arylamine N-acetyltransferase 2 (NAT2) is involved in human physiological responses to a variety of xenobiotic compounds, including common therapeutic drugs and exogenous chemicals present in the diet and the environment. Many questions remain about the evolutionary mechanisms that have led to the high prevalence of slow acetylators in the human species. Evidence from recent surveys of NAT2 gene variation suggests that NAT2 slow-causing variants might have become targets of positive selection as a consequence of the shift in modes of subsistence and lifestyle in human populations in the last 10,000 years. We aimed to test more extensively the hypothesis that slow acetylation prevalence in humans is related to the subsistence strategy adopted by the past populations. To this end, published frequency data on the most relevant genetic variants of NAT2 were collected from 128 population samples (14,679 individuals) representing different subsistence modes and dietary habits, allowing a thorough analysis at both a worldwide and continent scale. A significantly higher prevalence of the slow acetylation phenotype was observed in populations practicing farming (45.4%) and herding (48.2%) as compared to populations mostly relying on hunting and gathering (22.4%) (P = 0.0007). This was closely mirrored by the frequency of the slow 590A variant that was found to occur at a three-fold higher frequency in food producers (25%) as compared to hunter-gatherers (8%). These findings are consistent with the hypothesis that the Neolithic transition to subsistence economies based on agricultural and pastoral resources modified the selective regime affecting the NAT2 acetylation pathway. Furthermore, the vast amount of data collected enabled us to provide a comprehensive and up-to-date description of NAT2 worldwide genetic diversity, thus building up a useful resource of frequency data for further studies interested in epidemiological or anthropological research questions involving NAT2.

Microbubble mediated sonoporation of cells in suspension: Clonogenic viability and influence of molecular size on uptake

This work investigates whether the application of sonoporation is limited by the size of a macromolecule being delivered and by the ability of cells to proliferate following uptake. KHT-C cells in suspension were exposed to variations in ultrasound pressure (0–570 kPa) and microbubble shell-type (lipid and protein) at fixed settings of 500 kHz centre frequency, 32 μs pulse duration, 3 kHz pulse repetition frequency and 2 min insonation. Reversible permeability ( P R), defined as the number of cells stained with FITC-dextran and unstained with propidium iodide (i.e., PI-viable), was measured with flow cytometry for marker molecules ranging from 10 kDa to 2 MDa in size. Viable permeability ( P V) defined as the number of permeabilised cells that maintained their ability to proliferate, was measured by clonogenic assay. Comparable intracellular delivery of all sizes of molecules was achieved, indicating that intracellular delivery of common therapeutic drugs may not be limited by molecular size. Maximum P R’s of 80% (at 10 kDa) and 55% (at 10 kDa) were achieved with lipid coated bubbles at 3.3% v/v and protein coated bubbles at 6.7% v/v concentrations. The PI-viability was approximately 80% at 570 kPa in both cases. The maximum P V achieved with both agents was 22%, while inducing a lower overall clonogenic viability with the lipid (39%) compared to the protein (56%) shelled bubbles. This study demonstrates that large macromolecules, up to 2 MDa in size, can be delivered with high efficiency to cells which undergo reversible permeabilisation, maintaining long-term viability in approximately half of the cells.

Lex marks the spot: the virulent side of SOS and a closer look at the LexA regulon

The SOS response that responds to DNA damage induces many genes that are under LexA repression. A detailed examination of LexA regulons using genome-wide techniques has recently been undertaken in both Escherichia coli and Bacillus subtilis. These extensive and elegant studies have now charted the extent of the LexA regulons, uncovered many new genes, and exposed a limited overlap in the LexA regulon between the two bacteria. As more bacterial genomes are analysed, more curiosities in LexA regulons arise. Several notable examples include the discovery of a LexA-like protein, HdiR, in Lactococcus lactis, organisms with two lexA genes, and small DNA damage-inducible cassettes under LexA control. In the cyanobacterium Synechocystis, genetic and microarray studies demonstrated that a LexA paralogue exerts control over an entirely different set of carbon-controlled genes and is crucial to cells facing carbon starvation. An examination of SOS induction evoked by common therapeutic drugs has shed new light on unsuspected consequences of drug exposure. Certain antibiotics, most notably fluoroquinolones such as ciprofloxacin, can induce an SOS response and can modulate the spread of virulence factors and drug resistance. SOS induction by beta-lactams in E. coli triggers a novel form of antibiotic defence that involves cell wall stress and signal transduction by the DpiAB two-component system. In this review, we provide an overview of these new directions in SOS and LexA research with emphasis on a few themes: identification of genes under LexA control, the identification of new endogenous triggers, and antibiotic-induced SOS response and its consequences.

Intercostal nerve mononeuropathy: study of 14 cases

This retrospective study describes 14 cases of intercostal nerve mononeuropathy (INM) found in 5,560 electromyography (EMG) exams performed between January 1991 and June 2004 in our University Hospital. Medical charts of all patients with history of thoracic pain and EMG diagnosis of intercostal mononeuropathy were reviewed. INM was detected in 14 patients; etiology was thoracic surgery in 6 (43%), post-herpetic neuropathy in 4 (28%), probable intercostal neuritis in 2 (14%), lung neoplasia in 1 (7%), and radiculopathy in 1 (7%). From this study, trauma and infection were the main etiologies in intercostal neuropathic pain development. Tricyclic antidepressants and anticonvulsants were the most common therapeutic drugs used.

Assessment of Risks Related to Medicine Dispensing by Nonprofessionals in Colombia: Clinical Case Simulations

Appropriate dispensing is one of the steps for rational drug use, so it is generally advised that the dispenser should have relevant and updated knowledge, skills, and attitudes. To assess pharmacies and nonprofessional employees' (NEs) skills and knowledge, as well as their response to several specific case simulations in Bogota, Colombia. A descriptive cross-sectional study was performed on a random sample of 371 pharmacies in Bogota. Information from each pharmacy was obtained using 2 approaches: (1) direct interview to collect data on organizational aspects of the store and characteristics of NEs, and (2) simulation (both by direct interview and by telephone) to assess dispensing responses in 6 simulated clinical cases. More than half of the simulated clinical situations resulted in inappropriate dispensing (direct simulations 57%; telephone simulations 55%). The proportion of correct answers to theoretical questions regarding a specific therapeutic problem during interviews was higher than the response when a simulation presented that same case and a dispensing act was expected. The educational background of the NEs included in the study points to a specific problem: two-thirds of the individuals selling medicines had completed only secondary-level education and only 2% of the sample had a pharmacist as technical director. Continuing education courses were either directly organized by drug manufacturers (one-third of the courses attended by pharmacists) or sponsored by them (more than an additional one-third). NEs should be considered part of the therapeutic chain and, if appropriately updated or instructed, could play a very important role in the always difficult promotion of rational drug use. Public health institutions and universities should be more actively involved in the provision of independent, unbiased, and essential information on common therapeutic problems, safety concerns, and new drug prescription restrictions.

Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer

P-glycoprotein, encoded by the MDR-1 gene, confers multi-drug resistance against antineoplastic agents and is important for the transmembrane transition of various other common therapeutic drugs. Recently, a number of polymorphisms in the MDR-1 gene were identified and the T/T genotype at position 3435 in exon 26 was found to correlate with intestinal P-glycoprotein expression and bioavailability of digoxin after oral administration. We analysed the allelic frequencies at the polymorphic site C3435T in a group of patients with locally advanced breast cancer treated by preoperative chemotherapy to evaluate its predictive value. Sixty-eight patients diagnosed between 1998 and 2001 were treated by preoperative chemotherapy with anthracyclines or these agents combined with taxanes. From genomic DNA, a 106 bp fragment of MDR-1 exon 26 was amplified and the C3435T genotype was determined by Pyrosequencing methodology. A potential correlation with therapeutic response was calculated with Fisher's exact test. The overall clinical response rate (cCR and cPR) was 68% but only 7 patients (10.3%) achieved pathological complete response (pCR). Heterozygous C3435T occurred in 57% of the subjects and 22% of the analysed individuals possessed only T alleles. Statistical analysis revealed a significant correlation (p=0.029) between clinical complete response to preoperative chemotherapy and the T/T genotype. MDR-1 polymorphism C3435T in exon 26 may co-determine resistance to chemotherapy and provide useful information to individualize therapy.

Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy.

Evidence-based diagnosis and treatment have been proposed recently in various medical fields. Evidence-based diagnostic and therapeutic guidelines for benign prostatic hypertrophy (BPH), one of the most common urological diseases, have been proposed in foreign countries. This paper examines common therapeutic drugs for BPH in Japan from the viewpoint of evidence-based medicine (EBM). The term 'BPH' and drugs indicated for BPH were used as key words to search related articles in the PubMed website. A total of 813 articles extracted as of October 2001 were examined. The articles were ranked in levels ranging from I-V, where Level I indicated a large randomized controlled trial and Level V indicated a non-controlled case accumulation study. Among the 813 articles extracted, 132 clinical articles were suitable for evaluation. There were many reliable articles on the effectiveness of alpha-blockers. However, it seemed necessary to examine further how to choose the optimum alpha-blocker for each clinical case and the combination of antiandrogen drugs with alpha-blockers. It was also considered necessary to evaluate the effectiveness of drugs, such as eviprostat and hachimi-jio-gan, that are available only in Japan. The present study evaluated the effectiveness of commonly available therapeutic drugs for BPH in Japan from a viewpoint of EBM.

Developmental aspects of human hepatic drug glucuronidation in young children and adults.

The liver represents one of the major sites of human glucuronidation. Many therapeutic drugs are substrates for UDP-glucuronosyltransferases (UGT) leading to the formation of usually inactive glucuronides. Hepatic glucuronidation undergoes significant changes during fetal and neonatal development requiring age adapted drug therapy. Regulation of individual UGT genes during hepatic development has not been defined. Expression of 13 UGT genes and glucuronidation activities were analysed in 16 paediatric liver samples (aged 7-24 months), two fetal samples, and 12 adult liver samples (aged 25-75 years) using duplex reverse transcription-polymerase chain reaction, western blot, and specific catalytic UGT activity assays. No UGT transcripts were detected in fetal liver at 20 weeks' gestation. In contrast, UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B4, UGT2B7, UGT2B10, and UGT2B15 transcripts were present without variation in all 28 hepatic samples after six months of age. Significantly lower expression of UGT1A9 and UGT2B4 mRNA was identified in paediatric liver. Hepatic glucuronidation activity in children aged 13-24 months was found to be lower than in adults for ibuprofen (24-fold), amitriptyline (16-fold), 4-tert-butylphenol (40-fold), estrone (15-fold), and buprenorphine (12-fold). An early phase characterised by the appearance of UGT gene transcripts and a later phase characterised by upregulation of UGT expression is demonstrated during human hepatic development. The differential regulation of UGT1A9 and UGT2B4 expression extends beyond two years of age and is capable of influencing hepatic glucuronidation of common therapeutic drugs in children. The development of hepatic UGT activities is significant for paediatric drug therapy and the prevention of adverse drug effects.

Bacteriological survey of diarrheal epidemics in the 1998 Bangladesh floods

In 1998, the worst flood disaster in Bangladesh ravaged more than half of its land and diarrheal epidemics broke out. We examined fecal specimens of diarrheal patients at rural hospitals in Chandpor district located 140 km southeast of Dhaka to analyze the enteric bacterial pathogens in post-flood period October. Of the 76 patients stools examined, Vibrio cholerae O1 biotype El Tor, serotype Ogawa, and Vibrio cholerae O139 Bengal were detected in 25 (33%) and in 14 (18%) respectively. Other enteropathogenic bacteria confirmed were Vibrio cholerae O5, Vibrio fluvialis and Enteropathogenic Escherichia coli O44. Neither Shigella nor Salmonella species was detected in this study. A drug susceptibility test was performed using TC, DOXY, CPFX, NA, and AMPC disks to cholera Vibrios. The O1 Vibrios showed the same susceptible pattern as O139 excluding NA susceptibility. TC resistant strain among the Vibrios was not detected though TC is a common therapeutic drug for diarrhea in this area. Our result clearly suggested that the epidemic potentiality of O139 still existed in rural Bangladesh.

European multicentre evaluation of the Super Aution SA-4220 urinalysis analyser.

A multicentre evaluation of the urine test strip analyser Super Aution-4220 was carried out in six laboratories. The analytical performance of the instrument with regard to imprecision, linearity, detection limit, drift, carry-over and method comparison was studied. Using the Aution stick 8 test strip the pH, glucose, protein, ketones, bilirubin, blood, urobilinogen and leukocyte esterase were analysed. Specific gravity measurements were performed by refractive index method. Within-run and between-run imprecision determined at three levels of analyte were good. No carry-over was observed. Obtained results were linear through all the described analytical range. No significant drift was detected. Method comparison with some quantitative methods was performed and showed a good correlation with most of the analytes. The study of interferences showed minor interferences by common therapeutic drugs with the measurement of some analytes. During the assessment period of about 6 months no breakdown occurred in any laboratory. The Super Aution urine analyser appeared to be a highly automated analyser of urinary test strips. The operation was simple and the maintenance required only a few minutes a day.

Guidelines for the interpretation of analytical toxicology results and unit of measurement conversion factors.

A data compilation has been published on the World Wide Web [http:// www.leeds.ac.uk/acb/annals] which aims to assist in the interpretation of analytical toxicology results in individual patients. 'Therapeutic' or 'normal' plasma/whole blood/urine concentrations, as well as the concentrations associated with serious toxicity (if known), for some 700 analytes of toxicological interest are given together with (when possible) relative atomic or formula masses, and mass/amount and amount/mass concentration conversion factors. This paper gives background and supplementary information which should be borne in mind when providing interpretation or using the Web table. Supplementary tables listing (i) common therapeutic drug monitoring assays and guidelines for interpretation of results, (ii) emergency toxicology analyses which may influence active treatment, (iii) blood carboxyhaemoglobin saturation and clinical features of toxicity, (iv) information important when interpreting the results of toxicology investigations, (v) factors which may affect interpretation of analytical toxicology results, and (vi) conversion factors for volatile compounds are included.