bluuebunny/crossref_metadata_2025 huggingface dataset:
User involvement in clinical audit: a review of developments and issues of good practice*
Authors: Kelson Marcia
Published: December 2007

There have been considerable political and organizational moves to involve ‘consumers’ (patients, carers, service users, potential users, local communities and the public at large) in the provision, planning and monitoring of health services. Such developments beg the question ‘what constitutes good practice in user involvement?’. Taking user views into account relates not only to obtaining feedback on ’hotel’ aspects of care (issues such as food and cleanliness) but also to the potential for patient input to clinical audit and the standards by which care itself is measured.

Recent policy statements specifically advocate involving users in the process and product of clinical audit. In practice, ‘involvement’ has meant anything from passing on information to full and active participation in partnership with professionals. This paper outlines some of the issues raised in the published literature on user involvement in clinical audit. Suggesting that real involvement refers to users as active participants, not passive recipients, the paper documents the increasing policy commitment to user involvement and considers issues that influence how the rhetoric is put into practice.
The French clinical guidelines and medical references programme: development of 48 guidelines for private practice over a period of 18 months
Authors: Maisonneuve Hervé , Cordier Hélèns , Durocher Alain , Matillon Yves
Published: December 2007

The French medical profession and health insurance organizations have jointly committed themselves to a concept termed the ‘medical regulation’ of care. They decided to promote the quality of health care, judging that an approach based on quality was the best option for reducing the increase in health costs. The Clinical Guidelines and Medical References programme was entrusted to ANDEM (Agence Nationale pour le Développement de l'Évaluation Médicale).

Fifty working groups (669 experts) and 50 reading groups (1643 experts) met from June 1994 to November 1995 to produce guidelines. Learned societies were involved to propose experts. Hospital practitioners, doctors who specialized in the topic in question and those who did not had equal representation in the groups. The method consisted of a review of the literature to determine the level of scientific evidence. ANDEM's Scientific Council suggested modifications to the groups and agreed to disseminate 48 of the 50 texts.

Careful observation of the operation of the groups identified factors that can positively influence the nature of the discussions and help avoid conflict: an abundance of high‐quality literature, an understanding of clinical research methodology, the existence of guidelines from different institutions or different countries tending towards the same conclusions, good initial work carried out by the chairperson and the project manager, a limit to the number of questions asked of the group, the chairperson having good people skills and meeting‐management skills, and an absence of professional and financial consequences for the participants. Good management of working groups is an additional factor in ensuring success. The regulatory medical references programme has led to changes of behaviour within the medical profession.
Patient, physician and presentational influences on clinical decision making for breast cancer: results from a factorial experiment*
Authors: McKinlay John B. , Burns Risa B. , Durante Richard , Feldman Henry A. , Freund Karen M. , Harrow Brooke S. , Irish Julie T. , Kasten Linda E. , Moskowitz Mark A.
Published: December 2007

This study examines the influence of six patient characteristics (age, race, socioeconomic status, comorbiditics, mobility and presentational style) and two physician characteristics (medical specialty and years of clinical experience) on physicians' clinical decision making behaviour in the evaluation and treatment of an unknown and known breast cancer. Physicians' variability and certainty associated with diagnostic and treatment behaviour were also examined. Separate analyses explored the influence of these non‐medical factors on physicians' cognitive processes. Using a fractional factorial design, 128 practising physicians were shown two videotaped scenarios and asked about possible diagnoses and medical recommendations. Results showed that physicians displayed considerable variability in response to several patient‐based factors. Physician characteristics also emerged as important predictors of clinical behaviour, thus confirming the complexity of the medical decision‐making process.
Issues of cost and quality: barriers to an informed debate
Authors: PhD Caryl E. Carpenter , Cornman John M. , PhD A. Douglas Bender , MBA David B. Nash MD
Published: December 2007

Debates over health reform in the United States are hampered by a poorly informed public and misunderstandings about the concepts of quality, cost containment and their relationship to each other. This paper explores the nature and persistence of barriers to an informed public discussion of reform proposals. Those barriers are: (1) multiple definitions of quality, cost and cost containment, (2) the impact of the media on those definitions, (3) a false assumption that cost containment automatically results in diminished quality, and (4) the perceived impact of managed care and for‐profit health firms on that assumption. We suggest a framework for building the understanding and knowledge base necessary to a reform of the nation's health care system.
Shortcomings of the randomized controlled trial: a view from the boondocks
Authors: MD Joseph Herman
Published: December 2007

The randomized controlled trial (RCT), despite its well‐known limitations, continues to be regarded as a gold standard in determining whether an intervention does more harm than good. Some recent evidence suggests that it tends to overvalue the modalities it tests. Moreover, the accuracy with which the disorder under consideration is diagnosed can be critical to the performance of a new intervention designed for it. When technological progress allows us to diagnose milder instances, some therapies, possibly useful in dire circumstances, will appear ineffective if most of a trial population is at low risk. Human individuality makes it impossible to duplicate a RCT. As a result, Popper's criterion of falsifrability may not be met and so the carrying out of a large‐scale therapeutic experiment may not be a scientific activity. Finally, it is doubtful whether group probabilities derived from RCTs can be safely applied to individuals. These and other reservations concerning the applicability of the RCT to clinical practice are discussed.
A model for the development of evidence‐based clinical guidelines at local level ‐ the Leicestershire Genital Chlamydia Guidelines Project
Authors: MRCGP Tim Stokes MPH , MFPHM Rashmi Shukla MRCP , FRCP Paul Schober , FRCGP Richard Baker MO
Published: December 2007

Clinical guidelines can be effective in achieving health gain when they are validly developed, disseminated and implemented appropriately. There is, however, a potential conflict between the need for validity through use of expert resources available at a national level, and implementation, which is undertaken at local level and depends on the local relevance of the guideline. This paper presents a model by which valid guidelines for the management of a given disease (genital chlamydial infection) by general practitioners can be developed at local level using the resources available to a district health authority department of public health. The model has three elements. First, a district‐wide postal questionnaire survey was used to document current clinical practice. Secondly, a critical review of the evidence relating to the management of genital chlamydial infection as it relates to British general practice was performed. Thirdly, the information gained from the critical review and survey was used by a multidisciplinary group to develop evidence‐based guideline recommendations. It is argued that the Leicestershire Genital Chlamydia Guidelines compare favourably with other recently published national guidelines in terms of their development and content. Local guideline development of guidelines for selected topics can be practical and appropriate.
Depot neuroleptic usage in adults with learning disabilities
Authors: Gravestock S.
Published: December 2007

Most previous surveys of depot neuroleptic usage have monitored the consumption of oral psychoactive medications by heterogeneous mental handicap hospital populations. The present study assessed the prevalence, patient, practice and service delivery factors associated with depot neuroleptic usage in community learning disabilities services. The total of 79 adult subjects receiving depot neuroleptics roughly represented 0–5% of local service users. Several significant differences emerged between the factors associated with usage in the 61 (77%) subjects with psychotic disorders and 18 (23%) other subjects. Fitting backward elimination regression models accounted for 67–75% of the depot dosage variance. Comparison of these results with data from previous depot research studies suggested several methodological, clinical, ethical and research issues for future consideration.
Progress in social‐independent functioning of young people with Down's syndrome
Authors: Sloper p. , Turner S.
Published: December 2007

The progress over a 5‐year period in the social‐independent functioning of 96 older children and teenagers with Down's syndrome was examined. A significant increase in scores on the Self‐Sufficiency Index was found, with considerable individual variability. Path analysis was used to trace the factors associated with current levels of self‐sufficiency and the degree of change over time. Earlier level of cognitive development was the strongest predictor of progress in self‐sufficiency, but family factors were also important, particularly mothers’ strategies for coping with child problems and mothers’ levels of social support. For a small number of children with the lowest developmental level, family factors were less important as their self‐sufficiency was more strongly limited by their severe disability. The results suggest that interventions aimed at changing maternal coping strategies and supplementing social support may benefit the development of social‐independent functioning in young people with Down's syndrome.
Clinical predictors of response to recombinant interferon‐α treatment in patients with chronic non‐A, non‐B hepatitis (hepatitis C)
Authors: Davis G. L. , Lindsay K. , Albrecht J. , Bodenheimer H. C. , Balart L. A. , Perrillo R. P. , Dienstag J. L. , Tamburro C. , Schiff E. R. , Carey W. , Payne J. , Jacobson I. M. , Thiel D. H. Van , Lefkowitch J. , Sanghvi B.
Published: December 2007

SUMMARY. Chronic non‐A, non‐B hepatitis (NANBH) is a common and often progressive liver disease. Based on current serological tests, hepatitis C virus (HCV) infection is responsible for most cases. Interferon‐α (IFN) treatment at a dose of 3 × 106 units given three times per week for 24 weeks has been shown to be effective in normalizing serum alanine aminotransferase (ALT) levels and reducing hepatic inflammation in approximately 40% of these patients. The purpose of this study was to identify pretreatment characteristics in patients with chronic hepatitis C(CH‐C) which would best predict a favourable response to IFN treatment (normalization of serum ALT). One hundred and sixty‐three adult patients who had participated in a large multi‐centre treatment trial were included in the study group: 84 had been treated with 3 × 106 units of recombinant IFN‐α‐2b (rIFN) subcutaneously three times per week for 24 weeks and 79 patients had been treated with 1 × 106 units rIFN in the same dosage schedule. Forty‐one pretreatment historical, clinical, laboratory and histological variables were evaluated. In addition, early biochemical improvement during treatment was evaluated as a predictor of ultimate response. Univariate analysis identified six variables (dose, dose m‐2, weight, body surface area, ongoing ethanol use, white blood cell count and the presence of symptoms) as potential predictors of response (two‐tailed, P < 0.15). By multivariate analysis, however, only the 3 × 106 dose of rIFN was independently predictive of response (P < 0.01). When the analysis of response was confined to those patients who received treatment with 3 × 106 units of rIFN, seven variables [body weight, surface area, dose m‐2, current ethanol use, serum albumin and the presence of chronic persistent hepatitis (CPH) on entry liver biopsy] were more frequent in patients who responded to therapy. In a multivariate model, only CPH and body weight predicted an increased likelihood of response (P < 0.01). However, the model was not a sensitive predictor of response as only 18% of the study group had CPH on liver biopsy. A decrease in serum ALT levels within the first 12–16 weeks of rIFN treatment was found to be the strongest indicator of an ultimate response to treatment. Thus, assessment of early response to IFN treatment is the only practical means of predicting complete response and avoiding prolonged and unnecessary therapy in those with little chance of response.
Interferon response pathways—a paradigm for cytokine signalling?
Authors: Müller M. , Ibelgaufts H. , Kerr I. M.
Published: December 2007

SUMMARY. Considerable progress has been made in the past few years elucidating the molecular mechanisms of cytokine signalling. The interferons (IFNs) have provided a singular system allowing the detailed characterization of a specific cytokine signalling pathway. Studies on the IFN signal transduction pathway have identified protein tyrosine kinases (PTKs) that phos‐phorylate signal transducers (STATs) which then bind to DNA promoter sequences and activate gene transcription. Related work has shown that JAKs and STATs are also activated in response to a variety of the cytokines. Thus the novel type of signal transduction pathway identified for the IFNs promises to be more widely utilized than anticipated.
Treatment of chronic hepatitis B
Authors: Lok A. S. F.
Published: December 2007

SUMMARY.Chronic infection with the hepatitis B virus (HBV) is a major cause of worldwide morbidity and mortality. A large number of therapeutic approaches has been tried, including interferon (IFN), nucleoside analogues and immunomodulators. To date controlled clinical trials have shown that only IFN is of long‐term value but many patients fail to respond to treatment. New approaches to treating patients with IFN‐resistant hepatitis B are currently undergoing clinical and experimental evaluation, and it seems likely that new therapeutic agents will be available in the near future.
Hepatitis C virus genotypes in Singapore and Indonesia
Authors: Ng W. C. , Guan R. , Tan M. F. , Seet B. L. , Lim C. A. , Ngiam C. M. , Noer H M Sjaifoellah , Lesmana L.
Published: December 2007

Summary. 5″ untranslated and partial core (C) region sequence of hepatitis C virus (HCV) in 21 Singaporean and 1 5 Indonesian isolates were amplified by reverse‐transcription polymerase chain reaction and sequenced with the use of conserved primer sequences deduced from HCV genomes identified in other geographical regions. The HCV genotypes are predominantly that of Simmonds type 1 and less of type 2 and 3 with the latter genotype currently not detected in Indonesia. The 5″ untranslated sequences are related to HCV‐1, DK‐7 (Denmark), US‐11 (United States of America), HCV‐J4, SA‐10 (South Africa), T‐3 (Taiwan), HCV‐J6, HCV‐J8, Eb‐1 and Eb‐8. When compared with the prototype HCV‐1, insertions are found within the 5″ untranslated region of Singaporean isolates and not in the Indonesians. There are Singaporean and Indonesian isolates that have sequences within the 5″ untranslated region that differ slightly from each other. Microheterogeneity is observed in the core region of two Singaporeans and one Indonesian isolate. Finally, not all HCV isolates can be amplified with the conserved core sequence primers when compared with the ease with which these isolates can be amplified with 5″ untranslated region conserved primers.
Detection of anti‐hepatitis C virus using chemiluminescence
Authors: Ornopia G. L. , Kliramoto K.
Published: December 2007

Summary. To determine if chemiluminescence can be used in an enzyme immunoassay (EIA) format to test for hepatitis C virus (HCV) antibody and to compare sensitivity and specificity of chemiluminescence to a licensed anti‐HCV EIA method, random volunteer donor samples were evaluated. One thousand and seventy‐four random volunteer donor samples were collected during a 2‐week period. Two aliquots of each sample were tested for anti‐HCV. One aliquot was tested using a licensed anti‐HCV 2.0 EIA test. The second aliquot was tested using the research anti‐HCV chemiluminescence assay. Confirmatory testing was done using Recombinant Immuno Blot Assay (RIBA) 2.0 HCV and HCV RNA. Of the 1074 samples, eight were found to be reactive for anti‐HCV. Seven were positive by the anti‐HCV 2.0 EIA and the chemiluminescence system. The eighth sample was chemiluminescence reactive, but EIA negative; when tested by an unlicensed EIA 3.0 HCV test, RIBA 3.0 HCV test and an HCV‐RNA assay, the sample was still negative. The same sample was also tested by RIBA 2.0 HCV and showed a reactive band to SOD. The chemiluminescence assay has a 100% sensitivity and 99.9% specificity compared to EIA and can be used as an alternative to EIA for detecting antibodies to HCV.
Interferon‐α2a for chronic hepatitis B with e antigen or antibody: comparable antiviral effects on wild‐type virus and precore mutant
Authors: Aikawa T. , Kanai K. , Kako M. , Kawasaki T. , Hino K. , Iwabuchi S. , Tsubouchi H. , Takehira Y. , Tsuda F. , Okamoto H. , Miyakawa Y. , Mayumi M.
Published: December 2007

Summary. Recombinant interferon‐α2a (IFN‐α2a) in a total dose of 702 MU was given to 31 patients: nine with wild‐type hepatitis B virus (HBV) and hepatitis B e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild‐type HBV and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA was ultimately lost in four patients in group C, as well as in 10 patients in group D. Thus, patients with HBeAb and infected with precore mutants alone (D) lost serum HBV DNA more often than those with HBeAg and wild‐type HBV (A). Patients with low pre‐treatment levels of HBV DNA cleared virus more frequently, and the response of precore mutant to IFN was comparable with that of wild‐type HBV in patients who had a mixed infection. Based on these results, precore mutants do respond to IFN, and therefore, IFN is indicated in patients with HBeAb, especially those with low serum HBV DNA levels.
Genotypic variation, clinical and histological characteristics of chronic hepatitis C detected at blood donor screening
Authors: Bird G.L.A. , Spence E. , Hillan K.J. , MacSween R.N.M. , Frame D. , Yap P. , Dow B. , McOmish F. , Mills P.R.
Published: December 2007

Summary. Since blood donor screening for the hepatitis C virus (HCV) began in 1991 a large number of seropositive subjects have been detected and several reports have suggested a high prevelance of liver disease. The aim of this study was to evaluate the severity of liver disease in HCV‐positive blood donors in terms of the clinical, biochemical and histological abnormalities and to investigate the relationships between these features and the mode of transmission, duration of infection and viral genotype. We evaluated 54 consecutive blood donors who were positive for HCV both on serological testing and polymerase chain reaction. Twenty‐three (43%) had a history of intravenous drug abuse and 17 (31%) had received blood transfusions. In only two (4%) was no risk factor identified. The mean duration of infection in those with a clear history of HCV exposure was 12 years. Eighty‐three percent were HCV genotypes 1 or 3. All had abnormal liver biopsies with chronic hepatitis and several patients had periportal or portal‐portal fibrous septa, but there was none with architectural distortion or cirrhosis. There was no correlation between severity of liver disease and duration of HCV infection, mode of transmission or viral genotype.

In the majority of HCV carriers detected at donor screening there is a chronic hepatitis with bridging necrosis in one third, but the degree of fibrosis is minimal and cirrhosis was not present in our patients. The long period of infection of many patients suggests that irreversible liver injury does not necessarily develop at an early stage despite persistent infection.
Analysis of hepatitis B virus precore variants in hepatitis B e antibody‐positive patients treated with prednisone plus interferon
Authors: Lopez‐Alcorocho J. M. , Cabrerizo M. , Bartolome J. , Cotonat T. , Carren̄o V.
Published: December 2007

Summary. To assess the effects of prednisone and interferon on the distribution of hepatitis B virus (HBV) precore mutants, nine hepatitis B e antibody (HBeAb)‐positive patients with HBV chronic infection were studied. Patients were treated with prednisone (30 mg day‐1 for 4 weeks, followed by 20 mg day‐1 for 2 weeks and by 10 mg day‐1 for 1 week), followed by recombinant interferon‐α (15 MU thrice per week) for 6 months, without a clearance period. The HBV precore region was amplified by polymerase chain reaction (PCR) and distribution of the precore mutants was determined by hybridization of PCR products. Moreover, the glucocorticoid‐responsive element (GRE) was sequenced to determine whether changes in the sequence were produced at the end of prednisone treatment. During prednisone treatment, changes in alanine transaminase (ALT) were observed in only two patients, in whom ALT decreased to nearly normal values. In three patients ALT normalized at the end of interferon treatment. At baseline, wild‐type HBV alone was detected in one patient, while seven patients were infected by a mixture of wild‐type and precore mutants, predominantly wild type. At the end of prednisone treatment, two patients were infected by only wild‐type HBV. The proportion of precore mutants decreased in three cases, while no changes were observed in three. At the end of interferon treatment, the precore mutant proportion decreased in the three responders, while tending to increase or remain unchanged in the rest. No significant changes in GRE sequence were found as a result of prednisone treatment. Our results would appear to confirm the role of the immune system in the selection of precore mutants.
Approaches to the development of novel inhibitors of hepatitis C virus replication
Authors: Clarke B. E.
Published: December 2007

SUMMARY. Chronic infection with the hepatitis C virus is a major health problem. Conventional therapy, with interferon‐α is effective in only a minority of patients. The failure of current treatments has led to a major initiative to identify new antiviral agents. In the absence of a tissue culture model for hepatitis C infection the phwaceutical industry has been obliged to investigate the basic biology of hepatitis C viral replication. Such studies have identified novel translational regulatory elements and new proteolytic enzymes which may serve as targets for new antiviral drugs.
Coinfection with hepatitis B and C or B, C and δ viruses results in severe chronic liver disease and responds poorly to terferon‐a treatment
Authors: Weltman M. D. , Brotodihardjo A. , Crewe E. B. , Farrell G. C. , Bililus M. , Grierson J. M. , Liddle C.
Published: December 2007

SUMMARY. Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon‐α2b (IFN‐α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P < 0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN‐α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short‐and long‐term responses to doses of IFN‐α that are used to treat HCV are infrequent, but further studies are required to determine whether higher‐dose IFN‐α may benefit patients with combined hepatitis virus infections.
Prolonged therapy of chronic hepatitis C with ribavirin
Authors: Hoofnagle J. H. , Lau D. , Conjeevaram H. , Kleiner D. , Bisceglie A. M. Di
Published: December 2007

Summary. Therapy with ribavirin for 6–12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000–1200mg of ribavirin daily for 24 months. Serum aminotranferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long‐term side‐effects.
In vivo inhibition of hepatitis B viral gene expression by antisense phosphorothioate oligodeoxynucleotides in athymic nude mice
Authors: Zhiqiang Yao , Yongxing Zhou , Xiemei Feng , Chongxin Chen , Jun Guo
Published: December 2007

SUMMARY. Antisense oligodeoxynucleotides strategies have been used both to study normal gene function and to block gene expression therapeutically. We have previously shown that a number of antisense oligonu‐cleotides against hepatitis B virus (HBV) mRNA are able to inhibit viral gene expression in vitro. Here we report the establishment of an animal model producing HBV markers in athymic nude mice and inhibition of HBV gene expression and replication by antisense DNA in vivo. 2.2.15 cells (Hep‐G2 cell line transfected with HBV genomes) were injected subcutaneously (s.c.) into athymic BALB/c nude mice at a total cell number of 0.5–1×108 per mouse. Transplanted tumours developed about 2 weeks after inoculation. Hepatitis B surface and e antigens (HBsAg and HBeAg), as well as HBV DNA, could be detected in the circulation of tumour‐bearing mice. Hepatitis B surface antigen and hepatitis B core antigen (HBcAg) were demonstrated in tumour cells. After 10 days of tumour growth, antisense phosphorothioate oligonucleo‐tide, complementary to the cap site of the SPII promoter of HBV mRNA, were injected by infiltration into or around the tumour as a daily dose of 20 μg per gram body weight. Treatment for a total of 10 days resulted in an effective inhibition of viral replication and gene expression. These results suggest therapeutic potential for antisense oligomers in the treatment of patients who are chronically infected with HBV.
Lack of association between type of hepatitis C virus, serum load and severity of liver disease
Authors: Romeo R. , Colombo M. , Rumi M. , Soffredini R. , Ninno E. Del , Donate M. F. , Russo A. , Simmonds P.
Published: December 2007

SUMMARY. Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription‐polymerase chain reaction (RT‐PCR) with a median level of 1003 × 103 genomic equivalents ml‐1 according to the branched‐DNA assay (b‐DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype la + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non‐progressive liver disease groups. Serum HCV‐RNA levels were similar in the liver diseases groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlying liver damage.
Hepatitis C virus infection and mixed cryoglobulinaemia: assessment of HCV RNA copy numbers in supernatant, cryoprecipitate and non‐liver cells
Authors: Manzin A. , Solforosi L. , Candela M. , Cherubini G. , Piccinini G. , Brugia M. , Gabrielli A. , Clementi M.
Published: December 2007

SUMMARY. The aim of this study was to characterize hepatitis C virus (HCV) infection in patients with mixed cryoglobulinaemia (MC). The HCV RNA copy number was assayed in clinical specimens from 15 consecutive patients with MC and HCV infection. Absolute quantification of HCV RNA molecules was performed using a competitive reverse transcription‐polymerase chain reaction (cRT‐PCR). Specific HCV RNA sequences were detected and quantified in plasma samples from all patients (mean HCV RNA copy number 4.9 times 106 ml‐1 plasma). A high concentration of HCV RNA molecules was detected in the cryoprecipitates of eight of the 15 patients, who had a cryoprecipitate/supernatant ratio higher than 3.0 (range 3.60 to 186.80); in the remain ing seven patients this ratio was close to or lower than 1.0 (range 0.13 to 1.60). Quantitative analysis of HCV RNA molecules in cells other than hepatocytes (i.e. peripheral blood mononuclear cells (PBMCs) and bone marrow cells (BMCs), in which the HCV replicative intermediate was detected using strand specific RT‐PCR, demonstrated that infection is detectable in nearly 60% of these extrahepatic cells. Quantitative analysis of HCV RNA in PBMCs and BMCs revealed low levels of viral nucleic acids.
Interferon‐α2b improves short‐term survival in patients transplanted for chronic liver failure caused by hepatitis B
Authors: Hassanein T. , Colantoni A. , Maria N. De , Thiel D.H. Van
Published: December 2007

SUMMARY.Liver transplantation for cirrhosis caused by hepatitis B virus (HBV) has a poor prognosis. This is primarily a consequence of the near universal reinfection of the allograft, subsequent accelerated hepatic disease while receiving immunosuppression, and a reduced long‐term survival. Because interferon‐α has been shown to have an antiviral effect on HBV, a study was initiated in 1986 to assess the effect of interferon‐α therapy on the course of liver transplantation in HBV‐positive recipients. Twenty‐eight patients with decompensated endstage liver disease caused by HBV were treated with 5, 2.5 or 1.25 million units (MU) of human recombinant interferon‐α2b (r‐IFN‐α2b) daily for a minimum of 14 days prior to transplantation and continuing for 42 days post‐transplantation. HBV antigens, HBV antibodies, HBV DNA and serum transaminase levels were measured throughout the treatment and post‐treatment period. HBV DNA was eliminated in 10 of 19 patients, who survived 3 months or more post‐transplantation, and was associated with a significant flare of hepatitis as detected by symptoms and transaminase levels (P < 0.05). Patients who cleared HBV DNA had lower HBV DNA levels (P < 0.05) at entry compared with those who did not. While four of 10 patients with hepatitis B e antigen (HBeAg) converted to hepatitis B e antibody (HBeAb), no surviving patient cleared hepatitis B surface antigen (HBsAg) on a long‐term basis. Nonetheless, post‐transplant survival was significantly better (P < 0.0001, median follow‐up 42 months) in the IFN‐α treated patients as compared with historical controls, and was similar to that of patients transplanted for all causes of parenchymal liver disease other than HBV cancer. Hence IFN‐α therapy in the perioperative liver transplantation period improves short‐term survival but does not prevent HBV infection of the allograft.
Immunological assays for putative periodontal pathogens
Authors: Zambon Joseph J. , Bochacki Victor , Genco Robert J.
Published: December 2007

Immunological tests including immunofluorescence microscopy, latex agglutination, flow cytometry, and enzyme‐linked immunosorbent assays are being developed for the detection of carcinogenic microorganisms and periodontal pathogens. In the present study, indirect immunofluorescence microscopy was used to examine two hundred eighty‐three subjects for Actinobacillus (“Haemophilus”) actinomycetemcomitans and Bacteroides gingivalis in subgingival dental plaque samples pooled from the mesial surface of the four first molar teeth. Alveolar bone height on panoramic radiographs was measured at each sample site using a Schei ruler and correlated with the results of immunofluorescence microscopy. Over ninety percent of the subjects did not demonstrate either putative periodonlal pathogen or harbored only trace amounts. Only 5% of the subjects demonstrated 2% or greater A. actinomycclemcomitans and no subject harbored more than 5% consistent with the finding that there were no localized juvenile periodontitis patients in this subject group. Nine percent of the subjects revealed 2% or more, and 5% demonstrated 5% or more of the total cell count as B. gingivalis. K. gingivalis levels, however, did exhibit a significant positive correlation with loss of alveolar bone height. The use of immunofluorescence microscopy for B. gingivalis exhibited 19% sensitivity, 96% specificity, 69% positive predictive value, and 69% negative predictive value when correlated with alveolar bone height measurements. The present data indicate that indirect immunofluorescence microscopy is a useful, rapid method for the detection of A. actinomycetemcomitans and B. gingivalis in subgingival dental plaque which can be used in the clinical diagnosis, treatment, and monitoring of periodontal disease. The sensitivity of microbiological assays as indicators of periodontal disease can likely be increased by utilization of additional Immunological tests for other putative periodontal pathogens.
Use and interpretation of microbiological assaysin periodontal diseases
Authors: Genco R. J. , Zambon J. J. , Christersson L. A.
Published: December 2007

This report summarizes the rationale and illustrates the use of microbiological assays for specific microorganisms such as Actinobacillus (Haemophilus) actinomycetemcomitans in periodontal diseases. Data on the prevalence and monitoring of A. actinomycetemcomitans in patients with localized juvenile periodontitis (LJP) are presented. A. actinomycetemcomitans was found in 57 of 60 LJP patients for a prevalence of 95%. Two of the three patients not demonstrating the organism had serum antibodies to A. actinomycetemcomitans suggesting that they were once infected. Large numbers of A. actinomycetemcomitans were found in two‐thirds or more of the periodontally involved sites in the LJP patients. Microbiologic and clinical data illustrates the critical need for complete eradication of this organism in order to ensure successful therapy. The general use of microbiological tests for specific microorganisms in individual periodontitis patients can be applied to: (a) determine the causative agent, (b) assess disease activity for treatment planning, (c) monitor the effects of treatment, and (d) decide on recall intervals. Bacterial culture of the subgingival flora and determination of antibiotic susceptibility is likely to be useful in patients in whom therapy has not been successful. Rapid assays are also useful in examining subjects in epidemiologic studies to determine the prevalence of pathogens in various populations, in longitudinal studies to assess the importance of various microorganisms in the etiology of periodontal disease, and to identify persons at‐risk for either the initial episode of periodontal disease or for recurrent disease.

The data presented here and the review of the relevant literature strongly support the use of microbiological assays for specific microorganisms as adjuncts in the diagnosis and management of periodontal disease. It is clear that meticulous, long‐term supragingival plaque control and root planing to achieve smooth surfaces of the roots is very important for the management of most forms of periodontal disease, however, identification and monitoring of specific microorganisms represents a new approach to the management of periodontal disease and provides a rationale for treatment of the specific infections of the periodontium. Although all of the specific periodontal pathogens have not been defined, a sufficient number of important pathogens are known and testing for these organisms is, therefore, indicated. Furthermore, technologies have developed to the point where rapid microbiological tests are feasible and practical. Future developments will likely provide more efficient and improved tests. In conclusion, the rationale for assessment of several important periodontal pathogens and the present level of technology making such assessment feasible, strongly support the use of microbiologic assays as adjuncts in the clinical management of various forms of periodontal disease.
Studies on the growth of Eikenella corrodens strain 23834
Authors: Progulske A. , Holt S. C.
Published: December 2007

The growth characteristics and nutritional requirements of Eikenella corrodens strain 23834 were studied. Generation times, growth rates, and cell yields were determined employing a basal medium supplemented with yeast extract (YE), vitamins, amino acids, phosphate, nitrogen, and sulfate. Incubation was in a variety of air, CO2, and N2 atmospheres. Incubation statically in air or in 10% CO2+ 90% air did not affect the growth rate, while Na2CO3, bubbling with various atmospheres, shaking, or anaerobic incubation all decreased the growth rate. Atmospheric CO2 was found not to be a requirement for growth. The addition of 1‐2.5% YE decreased the generation time and increased the cell yield. The growth‐promoting factor(s) of YE was a low molecular weight, water‐soluble, dialyzable substance which is stable to and not extractable by chloroform‐methanol. Vitamins and amino acids singly or in combination were slightly growth‐promoting and purines, pyrimidines, and acetate had no effect on Eikenella growth. Increasing concentrations of phosphate inhibited growth, while nitrate but not sulfate proved essential for growth.
Sampling of subgingival plaque: a comparison of two methods using darkfield microscopy
Authors: Strand P. , Palmer R. M. , Wilson R. F.
Published: December 2007

Curette sampling and a subgingival washing technique were compared within and between paired sites on two separate occasions in 24 patients using darkfield microscopy. Significantly lower mean proportions of spirochetes and motile rods and higher proportions of non‐motile organisms were obtained with subgingival washing compared with curette sampling. There were no significant differences in the proportions of bacterial morphotypes between sites in the same patient sampled by the same technique. Although various methods of sampling may be more appropriate in certain clinical circumstances, they may produce quite differing results in both darkfield and cultural studies.
Prevalence and microbiology of localized prepubertal periodontitis
Authors: Sweeney E. A. , Alcoforado G. A. P. , Nyman S. , Slots J.
Published: December 2007

Loss of crestal alveolar bone at primary teeth was ascertained radiographically in a dental school clinical population of 2264 children. 19 patients (0.84%) demonstrated distinct periodontal bone destruction around one or more primary teeth; in only 2 of these patients had periodontal disease been identified in previous clinical examinations. A microbiological study of 35 subgingival samples from 9 available patients revealed a high prevalence of black‐pigmented Bacteroides spp., mainly Bacteroides intermedius. Actinobacillus actinomycetemcomitans and Capnocytophaga spp. were predominant organisms in some samples. The present data indicate that localized prepubertal periodontitis is more common than previously realized and is associated with bacteria generally regarded as major periodontal pathogens.
Characterization and cross‐reactivity of rabbit antisera to plaque toxins
Authors: Levine M. , Movafagh B. F. , Schwartzott D. L.
Published: December 2007

The effects of heat labile, high molecular weight water‐soluble toxins from bacterial plaque on HL60 promyelocytic cells were examined. On gel filtration, four inhibitors of HL60 cell growth and two inhibitors of HeLa cell growth (PT1, PT2) were detected. The first and third HL60 cell inhibitors corresponded to the two HeLa cell inhibitors. The last eluted HL60 cell inhibitor (plaque leuko‐toxin, PL) did not inhibit HeLa cell growth. Anti‐PT2 antibodies reduced the activity of enriched PT2 by 20–50%, but all other antisera tested exhibited no effect. Anti‐PL antibodies detected antigens from Actinobacillus actinomycetemcomitans, although anti‐A. actinomycetemcomitans and anti‐Capnocytophaga sputigena antibodies did not react with plaque extract. These findings suggest that the plaque toxins examined in this study were probably not derived from these two bacteria.
Comparison between different methods for sampling cariogenic microorganisms in persons with exposed root surfaces
Authors: Fure S. , Krasse B.
Published: December 2007

The levels of lactobacilli, mutans streptococci and the group of Actinomyces viscosus and Actinomyces naeslundii in a 15‐s rinse were compared with the levels of these bacteria in paraffin‐stimulated saliva and in pooled plaque from exposed root surfaces. Samples were obtained on 2 occasions from 30 subjects. The levels of lactobacilli, mutans streptococci and Actinomyces spp. in the rinse correlated strongly with the levels in the saliva (r=0.95, r=0.87, r=0.66 respectively). The mean levels of lactobacilli, mutans streptococci and Actinomyces spp. per ml were about 5, 10 and 4 limes higher respectively in the saliva than in the rinse medium. The correlations between the rinse levels and the levels in plaque were O.68, 0.65 and 0.42 but the correlations between saliva and plaque levels were even weaker (0.53, 0.56 and 0.38). The results indicate that a 15‐s oral rinse can be as useful as saliva sampling when discriminating between high and low levels of caries‐associated microorganisms in root surface plaque. The rinse method has definite advantages compared to saliva sampling in persons with low salivary secretion rate or difficulties to chew.
Effect of hemoglobin and of ferric ammonium citrate on the virulence of periodontopathic bacteria
Authors: Mukherjee Sabyasachi , Murphy Richard A. , Wawszkiewcz Edward J.
Published: December 2007

The effect of the iron‐containing substances hemoglobin (Hb) and ferric ammonium citrate (FAC) on the virulence of a strain of Streptococcus sanguis, Actinomyces viscosus, Actinobacillus actinomycetemcomitans, and 2 strains of Bacteroides gingivalis was studied in a guinea‐pig model. The results showed that the addition of Hb or FAC had no effect on the virulence of S. sanguis. However, the addition of Hb but not FAC had an enhancing effect on the virulence of A. viscosus and B. gingivalis. The addition of FAC but not Hb enhanced the virulence of A. actinomycetemcomitans. This study, suggests that the virulence of periodontopathic bacteria could be dependent upon the nature of the iron compound in the host medium.
Penicillin‐induced lysis in fluoride‐resistant mutants of Streptococcus mutans
Authors: Jonooby L. A. , Krai T. A.
Published: December 2007

First‐ and second‐step sodium fluoride‐resistant mutants of Streptococcus mutans GS‐5 were treated with penicillin under optimal lysis conditions to determine if their lytic responses differed from that of the parental strain. First‐step mutants demonstrated lysis values ranging from 54 to 65%, similar to that of the parental strain (64%). Second‐step mutants demonstrated much reduced levels of lysis ranging from 19 to 46%. Since the generation times of the fluoride‐resistant mutants varied, analyses of variance were performed to determine if the observed levels of lysis correlated with the generation times. When the parental strain was grown under conditions resulting in different generation times, there was a statistical correlation between level of penicillin‐induced lysis and generation time. However, no statistical correlation existed between level of lysis and generation time with the fluoride‐resistant mutants. This may indicate that the reduced levels of penicillin‐induced lysis seen in second‐step mutants are associated with the fluoride resistance itself.
Saliva increases serum IgG retention on Streptococcus mutans
Authors: Riviere George R. , Bresnick Steven D. , Miller James N.
Published: December 2007

The purpose of this investigation was to determine if saliva would affect the retention of serum antibodies to S. mutans. A quantitative enzyme‐linked immunosorbent assay (ELISA) was used to estimate total IgM, IgG and IgA after applications of whole saliva and absorbed serum to equal but separate aliquots of S. mutans. Total antibodies were also estimated after the sequential application of saliva and adsorbed serum to the same aliquot of S. mutans. Significantly more IgG, but not IgM or IgA, was retained on saliva‐treated cells than on untreated cells. IgG retention was greatly diminished when saliva was pre‐ab‐sorbed with S. mutans but Streptococcus sanguis was less effective. Most subjects, regardless of caries experience, had IgG that would be retained by saliva‐treated cells but saliva from caries‐resistant subjects promoted IgG retention significantly more than saliva from susceptible subjects.