Hepatitis C virus: Clades and properties

Abstract Hepatitis C virus (HCV) is a member of the virus family Flaviviridae. At present HCV is classified into a discrete hepacivirus genus and is represented by six clades according to genome sequencing. Each clade is further divisible into subtypes, which may prove important for the study of clinical differences and epidemiological studies. Limited homology also exists with hepatitis G/GB viruses, despite the fact that the hepatotropic nature of the latter agents remains contentious. The variability amongst the six HCV clades is less than that observed between the four serotypes of dengue, suggesting that each clade may represent a distinct virus were tests such as plaque neutralization to become available for delineating HCV isolates. The distribution worldwide varies, with Clades 1 and 2 predominating in most regions—an important consideration for the development of any vaccine. In addition, the clade distribution among cohorts may vary according to age. Point source outbreaks of HCV, for example in large numbers of women inadvertently infected with HCV‐contaminated anti‐D globulin, offers an opportunity to study the evolution of HCV genotypes over several decades. Parallel studies in chimpanzees have shown that the hypervariable region of E2 may play a role in HCV immunity, with quasispecies rapidly replacing the predominant subtype as immunity develops to the initiating virus strain. There is some evidence that an IFN‐sensitive motif exists in the NS5 gene which may have some predictive value in determining the likely outcome of IFN treatment. A database is available for all HCV sequences, together with information about their properties and guidance for the evaluation of new isolates ( http://s2as02.genes.nig.ac.jp ). © 2002 Blackwell Publishing Asia Pty Ltd     

Absence of a prosthetic group in a type-specific polysaccharide of pneumococcus

The specific polysaccharide of Type III pneumococcus, with only 0.05 per cent of N and 0.01 per cent of P, still shows almost maximal precipitation of a Type III antipneumococcus rabbit serum and the expected antigenicity in man. There is therefore no evidence that a prosthetic group is involved in these characteristic activities.     

Development of the Hypertonia Assessment Tool (HAT): a discriminative tool for hypertonia in children

Aim The aim of this study was to develop a tool to identify paediatric hypertonia subtypes. Method Items generated by experts were subscaled (spasticity, dystonia, rigidity). The tool was administered to 34 children (19 males, 15 females, mean age 8y 2mo, range 2y 5mo–18y 7mo) with hypertonia and cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels: I, n=7; II, n=5; III, n=7 level IV, n=7; and level V, n=8 level. Kuder–Richardson Formula 20 determined internal consistency. To assess reliability, two physicians administered the tool to 25 additional children with CP (15 males, 10 females; mean age 10y 8mo; GMFCS levels I, n=4; II, n=3; III, n=7; IV, n=4; and V, n=7) on two occasions, 2 weeks apart. To evaluate validity, a third physician diagnosed the hypertonia by neurological examination. Results The internal consistency of the spasticity items was moderate (α=0.58), and dystonia was high (α=0.79). Item reduction eliminated seven of the 14 original items. The agreement of the spasticity and rigidity subscales was adequate (prevalence‐adjusted bias‐adjusted kappa [PABAK] ranging from moderate [0.57] to excellent [1.0]) for validity, test–retest reliability, and interrater reliability. For dystonia agreement was lower, with PABAK ranging from fair (0.30) to good (0.65). Eighty‐seven per cent had spasticity and 78% had dystonia. Interpretation The Hypertonia Assessment Tool has good reliability and validity for identifying spasticity and the absence of rigidity, and moderate findings for dystonia.     

The clinical utility of an SCN1A genetic diagnosis in infantile‐onset epilepsy

Aim Genetic testing in the epilepsies is becoming an increasingly accessible clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are most notably associated with Dravet syndrome. This is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives. Method Participants were identified prospectively from referrals to the Epilepsy Genetics Service in Glasgow and contacted via their referring clinicians. Questionnaires exploring the consequences of SCN1A genetic testing for each case were sent to carers and physicians. Results Of the 244 individuals contacted, 182 (75%) carried a SCN1A mutation. Carers of 187 (77%) patients responded (90 females, 97 males; mean age at referral 4y 10mo; interquartile range 9y 1mo). Of those participants whose children tested positive for a mutation, 87% reported that genetic testing was helpful, leading to treatment changes resulting in fewer seizures and improved access to therapies and respite care. Out of 187 physicians, 163 responded (87%), of whom 48% reported that a positive test facilitated diagnosis earlier than with clinical and electroencephalography data alone. It prevented additional investigations in 67% of patients, altered treatment approach in 69%, influenced medication choice in 74%, and, through medication change, improved seizure control in 42%. Interpretation In addition to confirming a clinical diagnosis, a positive SCN1A test result influenced treatment choice and assisted in accessing additional therapies, especially in the very young.     

FORESTS AND THE COMMUNITY

The main functions of water in firefighting are outlined in this report and an additive which improves its usefulness is described; the effect of the additive is to reduce the rate of evaporation in normal atmospheric conditions, without materially decreasing evaporation when the water contacts burning material.     

Plant pigments for colouring food

During the past few years the food industry has had to adapt to using natural pigments in many foods and beverages in place of artificial colouring materials. This change has been coupled with overall reduced colour intensity of many products in favour of softer pastel shades. This article describes some of the natural extracts which are used and shows how their limitations can be overcome in many instances. The use of natural colours in the European food industry is extensive and all classes of foods are currently being produced containing such colours.     

Pantoprazole and omeprazole in the treatment of reflux oesophagitis: a European multicentre study

Background: Pantoprazole is a new substituted benzimidazole which inhibits gastric H⁺,K⁺-ATPase. Methods: In this double-blind, multicentre study, pantoprazole 40 mg once daily was compared with omeprazole 20 mg once daily in the treatment of grade II and III (Savary–Miller) reflux oesophagitis. Endoscopy was repeated after 4 weeks of treatment, and also after 8 weeks in patients unhealed at 4 weeks. Results: The primary efficacy variable was ulcer healing; after 4 weeks, 81/103 (78.6%) patients in the pantoprazole group and 83/105 (79.0%) patients in the omeprazole group had healed completely. After 8 weeks, the cumulative healing rates were 94.2% and 91.4 % in the pantoprazole and omeprazole groups, respectively (P > 0.05 at 4 weeks and 8 weeks). Both groups experienced rapid relief of the key symptoms: heartburn, acid regurgitation and pain on swallowing. The time course of relief of the individual symptoms was similar in both groups after 2 and 4 weeks (P > 0.05). Both treatments were well tolerated, with only three patients withdrawing owing to adverse events. Conclusion: Pantoprazole has been shown to be as effective as omeprazole in the treatment of reflux oesophagitis.     

PAINFUL THIRD NERVE PALSY: HOW NOT TO MISS AN INTRA-CRANIAL ANEURYSM

Case histories of two patients, each of whom presented to an ophthalmologist with early signs of aneurysm, are presented. Prompt referral of aneurysm patients allows investigation, diagnosis and treatment before catastrophic neurological and ocular sequelae ensue. Patients presenting to an ophthalmologist with diplopia, ptosis or limitation of eye movement due to third nerve paresis or paralysis should be carefully screened for the presence of intra-cranial aneurysm, when pain is an accompanying feature.     

PATTERNS OF COMPLIANCE AND EVASION IN TREATMENT PROGRAMMES WHICH INCLUDE SUPERVISED DISULFIRAM

Examination of the compliance patterns of 84 patients offeredsupervised disulfiram in aqueous suspension, and for whom adequatesupervision by family members, friends or colleagues was possible,showed that 38 took disulfiram regularly and remained abstinentthroughout the minimum six-month period for which it was prescribed.Twenty risked drinking alcohol while taking disulfiram, halfof whom did not experience a significant reaction on doses of200–300 mg daily. In nine patients there was a temporarylapse of supervision. Two patients induced vomiting of disulfiram.Four substituted inert medication. Nine dropped out of treatment—usuallyafter separating from their partner—and two refused tostart disulfiram. Apart from these 11 patients, attempts tosabotage or evade treatment were not necessarily associatedwith a poor response. In most cases it was possible to out-manoeuvrethe patients by increasing the dosage or modifying the supervisiontechniques. Awareness of these possible patient responses isessential if the considerable potential of supervised disulfiramis to be maximised.