Diagnostic accuracy of Doppler ultrasound for detecting hepatic artery stenosis after liver transplantation.

AIM: To evaluate the diagnostic accuracy of Doppler ultrasound (DUS) in detecting hepatic artery stenosis (HAS) after liver transplantation using computed tomography angiography (CTA) as the reference standard. MATERIALS AND METHODS: This study included data from January 2005 to November 2017, where DUS of the hepatic artery of living and deceased donor liver grafts were compared with the reference standard, CTA. DUS parameters, such as intrahepatic artery (IHA) peak systolic velocity (PSV), resistive index (RI), systolic acceleration time (SAT); and extrahepatic artery (EHA) PSV were taken. The optimum cut-off was estimated using area under the receiver operating characteristic curve (AUC). Multivariable logistic regression analysis was developed to predict HAS. RESULTS: Ninety-nine liver transplant cases were retrieved, 50 met the inclusion criteria where nine patients had significant HAS. HAS patients had a significantly low IHAPSV with a cut-off of 35.1 cm/s (sensitivity 53.8%, specificity 78.4%, AUC 0.701). IHARI had a significantly low RI with a cut-off 0.585 (sensitivity 86.7%, specificity 85.4%, AUC 0.913). The IHASAT cut-off was 0.045 seconds (sensitivity 80%, specificity 91.4%, AUC 0.857). The EHAPSV cut-off was 197.4 cm/s (sensitivity 50%, specificity 99.1%, AUC 0.648). The prediction model using DUS parameters IHARI and IHASAT demonstrated good discrimination with an AUC of 0.930 (95% CI: 0.843, 1.000; sensitivity 93.3%, specificity 88%). CONCLUSION: A prediction model using the DUS parameters IHARI and IHASAT showed good diagnostic accuracy of 88.6% for monitoring liver transplant patients. If validated externally, this DUS model could be utilised to diagnose HAS in liver transplant recipients.

Alternatives to antibiotics in a One Health context and the role genomics can play in reducing antimicrobial use.

BACKGROUND: This review follows on from the International Conference on One Health Antimicrobial Resistance (ICOHAR 2019), where strategies to improve the fundamental understanding and management of antimicrobial resistance at the interface between humans, animals and the environment were discussed. OBJECTIVE: This review identifies alternatives to antimicrobials in a One Health context, noting how advances in genomic technologies are assisting their development and enabling more targeted use of antimicrobials. SOURCES: Key articles on the use of microbiota modulation, livestock breeding and gene editing, vaccination, antivirulence strategies and bacteriophage therapy are discussed. CONTENT: Antimicrobials are central for disease control, but reducing their use is paramount as a result of the rise of transmissible antimicrobial resistance. This review discusses antimicrobial alternatives in the context of improved understanding of fundamental host-pathogen and microbiota interactions using genomic tools. IMPLICATIONS: Host and microbial genomics and other novel technologies play an important role in devising disease control strategies for healthier animals and humans that in turn reduce our reliance on antimicrobials.

Extrapancreatic findings of IgG4-related disease.

IgG4-related disease is a systemic fibro-inflammatory condition, which includes autoimmune pancreatitis as part of the disease spectrum. Imaging has been demonstrated to play a major role in the diagnosis of autoimmune pancreatitis. Recognizing the wide spectrum of extrapancreatic manifestations of IgG4-related disease coupled with a high clinical index of suspicion will allow for an accurate and timely diagnosis to be made, thus avoiding unnecessary invasive procedures and ensuring that early effective corticosteroid therapy is commenced. This review aims to serve as a concise reference tool for both clinicians and radiologists in the diagnosis of extrapancreatic IgG4-related disease.

Difficulties with prenatal diagnosis of the Walker-Warburg syndrome.

We describe a postnatally diagnosed case of Walker-Warburg syndrome--a form of congenital muscular dystrophy with lissencephaly and eye abnormalities. We reviewed the literature to highlight its clinico-radiological diagnostic features and discuss the difficulties encountered with prenatal diagnosis, especially in cases with no positive family history. An increased awareness of this rare but lethal condition, and a high index of suspicion during routine antenatal ultrasound, could prompt further advanced fetal ultrasonography and magnetic resonance imaging, and aid in timely prenatal diagnosis, management, and counseling.

Audit of diagnostic and interventional craniocervical catheter angiographic procedures at the Singapore General Hospital.

INTRODUCTION: Catheter angiography is an established imaging modality of evaluating cerebral and head and neck vascular diseases. It is, however, an invasive procedure with a small risk of complications. The aim of our study was to evaluate the prevalence of peri-procedural complications in a local hospital setting. MATERIALS AND METHODS: A total of 88 patients underwent diagnostic and interventional craniocervical procedures over 6 months in our department. The casenotes of 83 patients were retrospectively reviewed for complications arising from a total of 99 procedures carried out. RESULTS: A new focal neurological deficit developed in 3 different patients after a procedure, giving a prevalence of 3.0%. All these occurred in diagnostic procedures and were permanent deficits with correlative computed tomography (CT) or magnetic resonance (MR) imaging findings of acute cerebral infarction. All these occurred in high-risk patients who had severe underlying cerebrocarotid vascular compromise. There was 1 case of contrast medium-induced nephropathy (1.0%), occurring in a patient with pre-existing renal impairment. Local complications included 1 case of iatrogenic external iliac artery dissection (1.0%) and 5 cases (5.1%) of small and uncomplicated puncture site groin haematomas. CONCLUSION: The most significant complication associated with a craniocervical angiographic procedure was the development of post-procedural stroke in patients with significant preexisting cerebrocarotid vascular compromise. In the absence of this risk factor, craniocervical catheter angiography is a relatively safe procedure.

Association between two tumour necrosis factor intronic polymorphisms and HLA alleles.

The gene for tumour necrosis factor (TNF) lies at the telomeric end of the class III region of the major histocompatibility complex (MHC). Polymorphisms within this gene have been implicated in the genetic background of a large number of common human diseases. Recently two polymorphisms, TNF +489 and +691, have been described in the first intron of TNF (+489, G to A transition; +691, G deletion) and disease associations have been reported; however, the pattern of linkage disequilibrium with other MHC alleles has not been studied. We have therefore studied the association of TNF alleles with HLA-DR, -DQ and -B alleles in 216 healthy individuals from the north of England. The frequencies of the uncommon alleles were 0.08 (+489A) and 0.05 (+691Gdel). The +489A allele is associated with carriage of DRB1*1104, DQB1*0301, B18 and B35. The +691Gdel allele is associated with carriage of DRB1*13 *11, DQB1*0301 and B44. Knowledge of the pattern of association, indicating probable linkage disequilibrium, between these TNF alleles may be useful in studies aimed at determining the role of this locus in the genetic background of the large number of diseases which show genetic associations with MHC haplotypes.

TNF +489 polymorphism does not contribute to susceptibility to rheumatoid arthritis.

OBJECTIVES: To determine if a tumour necrosis factor (TNF +489) polymorphism is associated with susceptibility to rheumatoid arthritis (RA). METHODS: Two European populations were studied: 217 controls and 238 patients from the north of England and 145 controls and 179 patients from Spain. HLA-DRB1 and TNF +489 markers were typed using polymerase chain reaction based methods. RESULTS: Strong associations were demonstrated with shared epitope (SE) encoding HLA-DRB1 alleles in the English (OR = 2.9 [2.2-3.9]) and Spanish (OR = 2.3 [1.6-3.3]) populations, however no association was found with TNF +489 alleles. Furthermore carriage of TNF +489A was not associated with the presence of radiological erosions, rheumatoid nodules or rheumatoid factor. CONCLUSION: The role of the TNF locus in the genetic background of RA is unclear, however, our data does not support the previous reported association of the TNF +489A allele with RA susceptibility or severity.

Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy.

Long-term antibiotic treatment offers a rare opportunity to study the evolution of bacteria within the same individual. The appearance of new variants has been suggested to take place via the selection of enhanced resistance in compartments of the body in which the antibiotic concentration is low. Laboratory models of protected compartments have elegantly demonstrated their potential in selecting novel variants. However, comparable data from patients have been rare. In this study, extended antibiotic therapy in a single patient suffering from multiple infected liver cysts has provided the opportunity to observe and analyse the molecular evolution of antibiotic resistance. Each isolate has the same basic ompC gene sequence that is distinct from other Escherichia coli isolates, which suggests that they derive from the same founder population. However, the isolates differ in their auxotrophic markers, in the pI values of their dominant beta-lactamase activities and in the mutations in the promoter region of the ampC gene leading to increased expression of the AmpC enzyme. The data provide strong evidence for a single focal infection expanding via parallel pathways of evolution to give a range of antibiotic-resistant isolates. These data suggest that the infected cysts provide numerous protected environments that are the foci for the separate development of distinct variants.

Pharmacopoeial quality of drugs supplied by Nigerian pharmacies.

BACKGROUND: The quality of medicines available in some less-developed countries is inadequate in terms of content of active ingredient. Reasons for the poor quality of drugs include widespread counterfeiting of medicines in less-developed countries, excessive decomposition of active ingredient as a result of high temperature and humidity, and poor quality assurance during the manufacture of medicinal products. Our aim was to investigate the quality of different drugs obtained from retail pharmacies in two urban areas of Nigeria, and, in instances of poor quality, to ascertain the reason why. METHODS: We randomly collected 581 samples of 27 different drugs from 35 pharmacies in Lagos and Abuja in Nigeria. We analysed the medicines for drug content by validated chromatographic methods, and compared our results with pharmacopoeial requirements. FINDINGS: 279 (48%) samples did not comply with set pharmacopoeial limits, and this proportion was uniform for the various types of drugs tested. Although some preparations contained no active ingredient, most had amounts just outside the pharmacopoeial limits. We identified samples with both too much and too little active drug content. INTERPRETATION: The most probable cause of the poor quality of drugs is absence of adequate quality assurance during manufacture. Substandard drugs sold in the pharmacies of less-developed countries could contribute to global microbial resistance and therapeutic failure of infectious diseases.

Analysis of proguanil and its metabolites by application of the sweeping technique in micellar electrokinetic chromatography.

The method of applying large sample volumes in micellar electrokinetic chromatography termed sweeping is applied to determine the conservative limits of detection of some basic drugs in plasma and urine. The biguanides proguanil, 4-chlorophenylbiguanide and cycloguanil are used as models of basic drugs and the limits of detection obtained compared with those previously reported for capillary zone electrophoresis using field-amplified sample injection (FASI) and also by LC using off-line preconcentration. It is found that the sweeping method can be applied to extracts of such biological matrices. The limits of detection obtained by sweeping are improved over FASI for plasma but not for urine and the limits of detection are higher than those reported for LC, for these compounds.

An HPLC assay for the determination of ketoconazole in common pharmaceutical preparations.

An HPLC method is described using octadecylsilica (3 microns) with an acetonitrile phosphate buffer mobile phase containing diethylamine which is capable of separating ketoconazole [(+/-)-cis-1-acetyl-4-(4[2-(dichlorophenyl)-2- (1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)pi perazine] from four related compounds, (R049223, R063600, R053165 and R039519) and from excipients in tablets, cream and shampoo. The method was validated using an external calibration method for tablets, shampoo and creams and a standard addition method for cream. The limits of detection for the related compounds in the presence of ketoconazole are also reported.

Chemoprophylaxis compliance in travelers with malaria.

Much effort and resources have been focused on improving or evolving antimalarial prophylactic regimens in order to reduce the increasing problems of malaria infection in nonimmune travelers to malaria endemic regions. Falciparum malaria in travelers returned from Africa has been attributed to reduced efficacy of chloroquine against chloroquine-resistant strains of Plasmodium falciparum (CRPF). Reported prophylaxis use by tourists from East Africa suggests only 52% admit taking their chemoprophylaxis without any missed doses. The effect of noncompliance with chloroquine (CQ) or proguanil (PG) in East Africa has been estimated as equivalent to taking no prophylaxis at all. The influence of poor compliance and/or parasite resistance on the changing pattern of malaria among travelers needs to be understood if methods of reducing morbidity are to be identified. In a number of studies, prophylaxis compliance in travelers has been collected by self-administered questionnaires from which prophylaxis efficacy of drug regimens has been calculated. The interpretation of drug efficacy has hinged on drug compliance and is controversial. We have addressed the role of chemoprophylaxis compliance in travelers with malaria using a prospective study of 368 malaria patients attending the Hospital for Tropical Diseases by examining their travel history and reported prophylaxis compliance compared to their actual plasma drug levels. This has enabled us to characterize the role of CRPF and poor compliance in the etiology of breakthrough malaria in travelers.

Determination of opiates in urine by capillary electrophoresis.

A method for the separation of a mixture of opiates comprising pholcodine, 6-monoacetylmorphine, morphine, heroin, codeine and dihydrocodeine by capillary electrophoresis using a running buffer of 100 mM disodium hydrogenphosphate at pH 6 is described. The characteristics of an analytical method based on this separation for the determination of these drugs following extraction from urine and using levallorphan as internal standard are reported. Detection limits in the region of 10 ng cm-3 are achieved when using electrokinetic injection. A comparison is made of the sensitivity and reproducibility of electrokinetic and hydrodynamic injection for these drugs. Data are presented to show the results obtained when the proposed method is applied to urine spiked with all the above opiates and also to urine from a subject following consumption of dihydrocodeine and pholcodine. The concentrations found are compared with those obtained by LC.

Analysis of common opiates and heroin metabolites in urine by high-performance liquid chromatography.

A separation of heroin, 6-monoacetylmorphine, codeine, pholcodine, dihydrocodeine and morphine using a 200 x 2 mm I.D., 3 microns silica column with dichloromethane-pentane-diethylamine-methanol mobile phase is described. Data on the determination of these compounds in a urine matrix based on this separation using a solid-phase pretreatment with Bond Elut Certify cartridges and nalorphine as an internal standard are shown. The compounds listed can be quantified at levels below that generally accepted as the cut-off level for the screening for opiates by enzyme immunoassay (EMIT) with detection limits for the different opiates ranging from 4 to 20 ng ml-1. Comparative data are shown of subject urine samples assayed for opiates by both the enzyme immunoassay and the proposed method. The utility of the method for the elimination of so-called false positives detected by EMIT due to the presence of medically prescribed and non-prescription opiates in urine is discussed.

Traveller's diarrhoea; a controlled study of its effect on chloroquine and proguanil absorption.

The potential for traveller's diarrhoea to impair proguanil and chloroquine absorption and cause chemoprophylaxis failure was investigated in a study involving recently returned travellers who were either asymptomatic or presented with diarrhoea. A routine dose of chemoprophylaxis was administered to 12 travellers with diarrhoea and 12 asymptomatic subjects. The subjects undertook a lactulose-mannitol intestinal permeability test and were bled hourly after prophylaxis ingestion. Plasma analysis of chloroquine and proguanil from serial samples revealed a significantly lower proguanil Cmax (146 ng/mL vs. 196 ng/mL, P = 0.05), and longer tmax (3.1 h vs. 2.6 h, P = 0.05) in the diarrhoea cohorts. The absorption coefficient was lower for proguanil (0.57 vs. 0.76) but the difference did not quite reach levels of significance. Chloroquine kinetics were similar in both groups. The diarrhoea cohort had a three-fold higher lactulose absorption, influencing the mean lactulose mannitol:ratio, 0.114 +/- 0.17 compared to the control ratio of 0.02 +/- 0.01 (P = 0.04). Symptomatic subjects had impaired mucosal function which reduced the absorption of proguanil but not chloroquine, a phenomenon which may reduce prophylactic efficacy.

Determination of clavulanic acid by a sensitive HPLC method.

A new HPLC method is described for the estimation of clavulanic acid. It should be of use for further studies on the penetration of clavulanic acid into body tissues and fluids. It utilizes standard HPLC equipment and UV detection, but provides at least ten-fold increased sensitivity (less than 0.008 mg/l) over previously published methods by using solid phase extraction with imidazole derivatization and subsequent pre-concentration of the sample, and a microbore chromatographic column with a conventional detection system.