bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged treatment with interferon in patients with histologically mild chronic hepatitis C: a decision analysis
Authors: Davis G. L. , Beck J. R. , Farrell G. , Poynard T.
Published: March 2003

Short courses (6 months) of interferon (IFN) are highly cost‐effective in patients with histologically mild chronic hepatitis C. However, IFN treatment lasting 12–24 months is now the standard of care. We utilized a previously published and validated model of the natural history of chronic hepatitis C and the treatment outcomes from two large multicentre treatment trials of IFN‐α2b, given for 6 months or 18–24 months, to estimate the incremental cost‐effectiveness of prolonged IFN treatment in patients with histologically mild chronic hepatitis C (formerly chronic persistent or mild chronic active hepatitis). In the two treatment trials, pooled analysis of the patients with mild hepatitis showed that 36.4% of them normalized serum alanine aminotransferase and remained virus negative (sustained response) after completing an 18–24 month course of IFN vs 15.3% for a 6‐month course and no response in the absence of treatment. The model then estimated that for patients aged 20–50 years, the discounted marginal cost per year of life gained by long‐term IFN treatment ranged from US $735 to US $8856, and the gain in life expectancy ranged from 4.35 years to 0.75 years, respectively, compared with an untreated age‐matched cohort. Compared with treatment for only 6 months, the incremental marginal cost per life year gained by longer treatment at age 20–50 years ranged from $938 to $9957. The treatment and healthcare costs, sustained response rates and the rate of progression during early disease were identified as significant variables in sensitivity analyses. However, longer treatment always showed a survival benefit compared with 6 months of IFN or no treatment, and the cost of longer treatment is reasonable compared with that for a 6‐month course.
Long‐term retreatment in chronic hepatitis C patients who were non‐responders to an initial course of interferon‐α2b
Authors: Tong M. J. , Blatt L. M. , Tong L. T. , Sayadzadeh K. , Conrad A.
Published: March 2003

Nineteen patients with chronic hepatitis C who were virological non‐responders (seven responder/relapse and 12 no response) to an initial 24‐week course of interferon‐α2b (IFN‐α2b) at a dose of 3million units (MU) thrice weekly were retreated for an additional 48 weeks at the same dosing schedule and followed‐up for another 24 weeks post‐therapy. At the end of follow‐up (week 72), six (32%) of the 19 patients were hepatitis C virus (HCV) RNA negative and were virological complete responders to retreatment. The viral genotypes in these six patients included two each with 1b and 3a, one with 2b, and another with 2a/2b; five of the six virological responder patients had cirrhosis. Significant predictors for successful retreatment included lower baseline HCV RNA concentrations prior to the first course of therapy, 2 log10 reductions in serum HCV RNA during the initial treatment and classification into the virological ‘responder/relapse’ category after the first course of IFN (P < 0.01 for all observations). When the above factors were used to construct a predictive model to determine response to retreatment, it was found that the absence of a 2 log10 drop in HCV RNA concentrations during the first course of IFN therapy was the most reliable indicator of non‐response to retreatment (likelihood ratio = 10, P = 0.0014). In addition, the presence of HCV RNA at week 12 of retreatment was 100% predictive of virological non‐response to the 48‐week course of therapy. Our findings indicate that an additional 48‐week course of IFN‐α2b therapy at 3 MU thrice weekly will achieve a virological complete response in 60% of patients who had a 2 log10 drop in HCV RNA during their first course of treatment, and measurement of week‐12 HCV RNA during retreatment to identify non‐responders is beneficial to patients as well as being cost‐effective. Thus, a second course of IFN remains a viable option in a subgroup of non‐responder patients, regardless of genotype or the presence of compensated cirrhosis.
Clinical evaluation of the branched DNA assay for hepatitis B virus DNA detection in patients with chronic hepatitis B lacking hepatitis B e antigen and treated with interferon‐α
Authors: Habersetzer F. , Zoulim F. , Jusot J. F. , Zhang X. , Trabaud M.‐A. , Chevallier P. , Chevallier M. , Ahmed S. N. S. , Sepetjan M. , Comanor L. , Minor J. , Trépo C.
Published: March 2003

The aim of this study was to evaluate the Chiron branched DNA (bDNA) assay for detection of serum hepatitis B virus (HBV) DNA in patients with chronic hepatitis B lacking hepatitis B e antigen (HBeAg) and undergoing interferon (IFN) therapy. Results obtained with the bDNA assay were compared with those obtained using the Abbott liquid hybridization (LH) assay and the polymerase chain reaction (PCR). Serial samples (274) from 34 patients were analysed. Analysis of variance results indicated that bDNA values were more significantly correlated than LH values with both PCR positive/negative results (probability of artifact (Prob>F) = 0.7 and 0.09 for LH and bDNA assays, respectively) and presence/absence of precore mutations (Prob>F = 0.21 and 0.001 for LH and bDNA assays, respectively). Both bDNA and LH results correlated highly with alanine aminotransferase (ALT) values (both had Prob>F values of 0.0) while PCR was not correlated with ALT (Prob>F = 0.05). In 26 evaluable patients, a model based on a generalized Knodell score was used to predict response to IFN therapy, as defined by normalization of ALT values during therapy. This model discriminated well between non‐responders and responders. The bDNA results correlated well with the generalized Knodell score, while the LH results did not (Prob>F = 0.04 and 0.19 for the bDNA and LH assays, respectively). In conclusion, the bDNA assay appears to be useful for quantification of HBV DNA levels in HBeAg‐negative chronic hepatitis as it correlates with biochemical and histological indications of disease severity as well as with response to IFN therapy.
The natural course of chronic hepatitis C: implications for clinical practice
Authors: Dusheiko G. M.
Published: March 2003

Hepatitis C is an important public health problem with high rates of chronic infection ensuing after viral acquisition. The spectrum of the disease ranges from mild to severe chronic hepatitis, cirrhosis and hepatocellular carcinoma. Extra‐hepatic manifestations may occur. The disease is complex and predictions about long‐term prognosis for individual patients remain difficult. It is generally accepted that 10–20% of patients with chronic hepatitis C will develop cirrhosis within 10 years of first infection: identifying the group of patients at greatest risk remains a primary challenge for clinicians. Older age of infection, duration of infection, degree of liver inflammation at first biopsy and cofactors such as alcohol abuse, all appear to be predictors of a poorer prognosis. The following paper aims to identify some of the features of the natural history of hepatitis C most relevant to the clinician.
Mechanisms of hepatitis C virus NS3 proteinase inhibitors
Authors: De Francesco R. , Pessi A. , Steinkühler C.
Published: March 2003

The NS3 serine proteinase is regarded as one of the preferred targets for the development of therapeutic agents against hepatitis C virus (HCV). Possible mechanisms of NS3 inhibitors include: (i) interference with the activation of the enzyme by its NS4A cofactor; (ii) binding to the structural zinc site; and (iii) binding to the active site. These mechanisms have been explored in detail by structural analysis of the enzyme.

(i) The NS4A cofactor binds to the amino‐terminal β‐barrel domain of the NS3 proteinase bringing about several conformational changes that result in enzyme activation. The interaction betweeen NS3 and NS4A involves a very large surface area and therefore it is not a likely target for the development of inhibitors.

(ii) The NS3 proteinase contains a structural zinc binding site. Spectroscopic studies have shown that changes in the conformation of this metal‐binding site correlate with changes in the specific activity of the enzyme, and the NS3 proteinase is inhibited by compounds capable of extracting zinc from its native coordination sphere.

(iii) Based on the observation that the NS3 proteinase undergoes inhibition by its cleavage products, potent, active site‐directed inhibitors have been generated. Kinetic studies, site‐directed mutagenesis, and molecular modelling have been used to characterize the interactions between the NS3 proteinase and its product inhibitors.
The hepatic flaviviridae: summary
Authors: Sherlock S.
Published: March 2003

Hepatitis C envelope proteins (E1, E2) induce protective neutralizing antibodies. The extent of sequence diversity reflects the host's ability to control viral populations and the response to antiviral therapy. Attempts to prepare effective vaccines against HCV are foiled by lack of prolonged protective immunity. Plasmid vaccines and the use of uninfectious virus‐like particles are being developed. HCV induces a cellular humoral immune response, but this is inadequate to clear the virus and the disease becomes chronic. In any patient, the natural history of HCV infection depends on the age when infected, and the presence of other diseases. The transfusion‐related disease has a worse prognosis than that transmitted by syringes and needles. The outlook in ‘healthy blood donors’ is uncertain. Interferon therapy for 3 or preferably 6 months results in a sustained response in about 30% of patients. Negative serum HCV RNA and normal AST values after 3 months of therapy indicates that there may be a sustained response. Whether or not to stop treatment at that time if HCV is still positive remains a matter of debate. The role of interferon treatment in preventing progression to cirrhosis and hepatocellular cancer is still uncertain. Ribavirin therapy alone reduces transaminases and hepatic histology improves. Improved results follow the combination of ribavirin with interferon. Ribavirin may have immuno‐modularity and anti‐inflammatory actions. Hepatitis G virus (HGV) is unlikely to play a significant role in liver disease in man.
Involvement of Fas system‐mediated apoptosis in pathogenesis of viral hepatitis
Authors: Hayashi N. , Mita E.
Published: March 2003

Enhanced Fas system‐mediated hepatocyte apoptosis is observed in hepatitis C virus (HCV)‐ and hepatitis B virus (HBV)‐associated chronic liver diseases. In these forms of viral hepatitis, liver‐infiltrating lymphocytes that recognize the viral antigen on hepatocytes become activated and express cytolytic Fas ligand (FasL) molecules. In contrast, hepatocytes exhibit enhanced Fas expression and become susceptible to FasL‐mediated death. Augmentation of the Fas system has also been observed in other liver diseases and biliary disorders. Moreover, the Fas system is involved in removing aged hepatocytes. Thus, Fas‐mediated apoptosis plays an important role in several liver diseases and in maintaining normal liver homeostasis.
Histological progression during short‐term follow‐up of patients with chronic hepatitis C virus infection
Authors: Wali M. , Lewis S. , Hubscher S. , Harrison R. , Ahmed M. , Elias E. , Mutimer D.
Published: March 2003

Assessment of prognosis from hepatitis requires liver histology. When the fibrosis stage is known, and if the fibrosis progression rate can be established, time to development of cirrhosis can be calculated. The fibrosis progression rate can be calculated from a single biopsy when duration of infection prior to biopsy is known. Sequential biopsies can also be examined. In this work, we studied histological activity and fibrosis stage in liver biopsies of 157 hepatitis C virus (HCV)‐infected patients, including 92 for whom the approximate duration of infection was known. The mean fibrosis progression rate was 0.09 units per year, and was not influenced by mode of infection or viral genotype. Forty‐six patients who had very mild histological changes in the initial biopsy underwent repeat biopsy 2 years later (with no intervening anti‐viral treatment). Comparison of paired biopsies confirmed a tendency to histological progression and increasing hepatic fibrosis (mean, 0.15 fibrosis units per year). A normal baseline alanine aminotransferase (ALT) value was associated with slow fibrosis progression before baseline biopsy and between biopsies. These data do not differ from published cross‐sectional and longitudinal studies, and suggest that histological progression will be observed during follow‐up of most patients, including those with mild histological changes at time of initial assessment.
Epidemiology of hepatitis A in Asia and experience with the HAV vaccine in Hong Kong
Authors: Sung J.J.Y.
Published: March 2003

Hepatitis A and hepatitis B infections are prevalent throughout Asia. Patients infected with hepatitis B virus (HBV) have a higher morbidity and mortality if superinfected with hepatitis A virus (HAV). In Hong Kong, adolescents and young adults are particularly prone to severe hepatitis infection. Hepatitis A vaccination of patients with or without chronic HBV infection has been shown to be efficacious and associated with a good safety profile.
Hypervariable region 1 quasispecies in hepatitis C virus genotypes 1b and 3 infected patients with normal and abnormal alanine aminotransferase levels
Authors: Asselah T. , Martinot M. , Cazals‐Hatem D. , Boyer N. , Auperin A. , Le Breton V. , Erlinger S. , Degott C. , Valla D. , Marcellin P.
Published: March 2003

The role of hepatitis C virus (HCV) heterogeneity in the severity of chronic hepatitis C infectionremains unclear. Our aim was to study the hypervariable region 1 (HVR1) heterogeneity in patients with chronic hepatitis C infected with genotype 1b or 3 and with normal or abnormal alanine aminotransferase (ALT). HVR1 quasispecies were assessed by single strand conformational polymorphism (SSCP) in 67 patients with chronic hepatitis C, including 35 with persistently normal ALT and 32 with abnormal ALT. Sixty‐two patients underwent a liver biopsy. Among the 67 patients, 40 were infected with genotype 1b and 27 with genotype 3. In univariate analysis, low heterogeneity (≤ 3 bands at SSCP) was significantly associated with normal ALT (P < 0.001), milder histological lesions (activity, P=0.02; fibrosis, P=0.04), and at the limit of significance for genotype 1b (P=0.07). In multivariate analysis, low heterogeneity was significantly and independently associated with normal ALT (P=0.09) and genotype 1b (P=0.03). In patients with chronic hepatitis C, a low viral heterogeneity is significantly and independently associated with normal ALT and genotype 1b. These results are consistent with the view that patients with normal ALT have a different immune response against HCV resulting in a low HCV heterogeneity.
Hepatitis C virus infection in renal failure patients in the absence of anti‐hepatitis C virus antibodies
Authors: Hanuka N. , Sikuler E. , Tovbin D. , Mostoslavsky M. , Hausman M. , Orgel M. , Yaari A. , Shemer‐Avni Y.
Published: March 2003

The magnitude and clinical significance of Hepatitis C virus (HCV) infection in dialysis patients is controversial and underestimated. This study was conducted in order to evaluate the correlation between HCV replication and antibody response to HCV in dialysis patients. HCV infection in dialysis patients was evaluated over a period of 3 years and compared to HCV infection in Liver Clinic patients. Sera were collected from 310 dialysis patients and tested for anti‐HCV and HCV‐RNA. In addition, HCV genotype and HCV viral load were determined in HCV‐RNA‐positive sera. Anti‐HCV was detected in 43 (14%) of the dialysis patients. Of these, 37 (86%) were HCV‐RNA‐positive. Among the 267 HCV‐seronegative dialysis patients, 25 (9%) were found to be HCV‐RNA‐positive in more than one sample during the study. These patients were characterized by low viral load; at least two orders of magnitude lower than in the group of HCV‐seropositives. In contrast, in the Liver Clinic patients, HCV‐RNA was found exclusively in HCV‐seropositive patients. Comparison of the genotype pattern in the two groups did not reveal a difference.  Our results suggest that HCV infection in dialysis units may be underestimated due to cases of low viral load, depending on the method of RNA extraction and sensitivity of the test used. Low viral load might contribute to the lack of humoral immune response seen in some dialysis patients.
Full‐length sequence and functional analysis of hepatitis B virus genome in a virus carrier: a case report suggesting the impact of pre‐S and core promoter mutations on the progression of the disease
Authors: Kajiya Y. , Hamasaki K. , Nakata K. , Nakagawa Y. , Miyazoe S. , Takeda Y. , Ohkubo K. , Ichikawa T. , Nakao K. , Kato Y. , Eguchi K.
Published: March 2003

In chronic hepatitis B virus (HBV) infection, the quiescent immunotolerant phase evolves into the immunoactive phase. The aim of the present study was to clarify the virological alterations relevant to progression. Serial serum samples obtained from a patient with HBV during long‐term follow‐up were analysed by sequencing of the full‐length HBV‐DNA using polymerase chain reaction (PCR). In addition, PCR products of HBV genome from each serum sample were transfected into HuH‐7 human hepatoma cells for the functional analysis of the transfected viral genomes. Based on the HBV‐DNA sequence analysis, the patient had the genotype C virus, and the mutant HBV with common core promoter mutations (T1762A1764) and deletion of the pre‐S region responsible for large surface protein transcription emerged before the onset of hepatitis. When the vigorous host immune response developed (indicated by the flare‐up of hepatitis), the mutant HBV containing common core promoter mutations and another pre‐S deletion causing lack of the surface protein promoter became predominant. The HBV‐DNA sequences, other than pre‐S and core promoter regions were identical to the wild‐type sequence throughout the study. Transfection of PCR products containing the mutant HBV sequences resulted in increased amounts of intracellular replicative intermediates but the decreased secretion of HBsAg and HBeAg into culture media, suggesting accumulation of nonenveloped viral core particles within the cells. These results indicate that pre‐S deletion and core promoter mutations may participate cooperatively in progression of the disease.
Early detection of nonresponse to interferon plus ribavirin combination treatment of chronic hepatitis C
Authors: Castro F. J. , Esteban J. I. , Juárez A. , Sauleda S. , Viladomiu L. , Martell M. , Moreno F. , Allende H. , Esteban R. , Guardia J.
Published: March 2003

We have investigated the value of early hepatitis C virus (HCV) RNA decline (ΔHCV RNA) to predict response to combination therapy in 66 chronic hepatitis C patients treated with IFN‐α2b (3 MU thrice weekly) and ribavirin (800 mg daily) for 12 months [25 sustained responders (SR) and 41 nonresponders or relapsers (NR)]. Serum HCV RNA was retrospectively measured in samples obtained at baseline and 4, 8 and 12 weeks after treatment onset, using a commercially available quantitative RT‐PCR assay. At 4 weeks, serum HCV RNA had decreased a mean of 2.6 ± 0.8 logs among SR as compared with only 0.5 ± 0.8 logs in NR (P < 0.001), and was already undetectable (< 600 IU/mL) in 12 (48%) of the SR but in none of the NR. At 8 weeks, HCV RNA was undetectable in 21 SR and in 2 NR and mean ΔHCV RNA were 4.2 ± 1.3 and 0.8 ± 1.0 logs, respectively (P < 0.001). At week 12 all SR had undetectable HCV RNA as compared with only five NR (P < 0.001). Stepwise logistic regression analysis identified ΔHCV RNA at 12 weeks as the strongest predictor of sustained response. Receiver operating characteristic (ROC) curves of ΔHCV RNA for sustained response prediction identified sensitivity peaks with 100% negative predictive value corresponding to ΔHCV RNA > 1 log at 4 weeks, > 2 logs at 8 weeks and > 3 logs at 12 weeks. Our results show that early changes in the HCV RNA level may reliably identify patients having no chance of a sustained virological response during the first 3 months of combination therapy, thus providing an excellent tool for optimizing antiviral treatment of chronic hepatitis C.
Relationship of clinical and virological factors with hepatitis activity in hepatitis B e antigen‐negative chronic hepatitis B virus‐infected patients
Authors: Sung J. J.‐Y. , Chan H. L.‐Y. , Wong M. L. , Tse C.‐H. , Yuen S. C.‐H. , Tam J. S.‐L. , Leung N. W.‐Y.
Published: March 2003

To investigate the factors associated with active disease among hepatitis B surface antigen (HBsAg) positive/hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B virus (HBV) infection we studied chronic HBV infected patients who had undetectable HBeAg at the first visit. HBV DNA was determined by the cross‐linking assay (NAXCOR) and polymerase chain reaction (PCR). Mutations in the core promoter and precore regions and viral genotypes were studied. Clinical outcome of these patients were followed and categorized as: (i) relapse (ALT > 200 IU/L or three times the previous levels); (ii) active hepatitis (elevated ALT < 200 IU/L with concomitant detectable HBV DNA); or (iii) remission. A total of eighty‐five patients were followed up for 5.5 ± 1.0 years. At first visit, 31 (36.5%) patients had elevated ALT levels, 12 (14.1%) had measurable HBV DNA by the cross‐linking assay and 26 (30.6%) by PCR. Sixteen (18.8%) patients had hepatitis relapse, 13 (15.3%) had active hepatitis, and 56 (65.9%) remained in remission. Core promoter and precore stop codon mutants were found in 27 and 12 patients, respectively. Eleven and 20 had genotype B and C HBV, respectively. Initial elevated ALT and detectable HBV DNA were associated with active liver disease. Patient demographics, viral mutants or genotypes failed to predict disease activity. Hence, serum ALT and HBV DNA levels offer the best prediction of natural course of HBeAg‐negative chronic HBV infection.
Bats in bird nests in Australia: a review
Authors: SCHULZ M.
Published: March 2003

Bats (Microchiroptera) utilize few types of bird nests as roosts. Ten species of bats (Molossidae and Vespertilionidae) were recorded roosting in the enclosed bottle‐shaped mud nests of the Fairy Martin Hirundo ariel; two species (Vespertilionidae) were located in the hanging nests of scrubwrens Sericornis spp. and the Brown Gerygone Gerygone mouki; two species (Vespertilionidae) in the enclosed plant material nests of the Grey‐crowned Babbler Pomatostomus temporalis and Fernwren Oreoscopus gutturalis; and one species (Emballonuridae) was recorded in the open cup‐shaped nest of the White‐rumped Swiftlet Collocalia spodiopygius. No information was available on the importance of bird nests as breeding sites and only one species, the Chocolate Wattled Bat Chalinolobus morio, has been recorded hibernating in a nest. Bird nests in Australia provide roosting habitat for four threatened bats and may be important to the conservation of these species.
The possible fitness benefits of striped coat coloration for zebra
Authors: Ruxton Graeme D.
Published: March 2003

The literature addressing evolutionary reasons for the striped patterns of zebra coats is reviewed here. Possible mechanisms, and the evidence for and against them, are discussed. These mechanisms span four general themes: protection from predators; social functions; thermoregulation; and protection from tsetse flies. The last is the only hypothesis that has been tested experimentally, and the results of these tests are inconclusive. Additionally or alternatively, although stripes apparently increase zebra visibility in daylight, it is at least plausible that they provide effective cryptic protection from predators in poor light, although critical testing has not been attempted. Other related evolutionary questions are raised and suggestions made for future research.
Stomodaeal valve ultrastructure in the sandfly Lutzomyia longipalpis (Diptera: Psychodidae)
Authors: TANG YINSHAN , WARD RICHARD D.
Published: March 2003

The stomodaeal valve and adjacent cardia region of the alimentary canal of the phlebotomine sandfly Lutzomyia longipalpis have been studied using electron microscopy. With the scanning electron microscope (SEM), numerous pit‐like structures of different sizes were found in the surface of the valve of male and female flies. Under the transmission electron microscope (TEM), the cells adjacent to the pores were shown to have numerous mitochondria and to lack neural innervation. It is suggested that the pit‐like structures are probably secretory. A typical basiconic sensilla was found on the inner side of the oesophagus at the junction with the stomodaeal valve, with at least one dendrite which extended to the tip, indicating a chemosensory role. It is likely that this type of sensilla may control the movement of the stomodaeal valve after contact with fluids entering the mid‐gut and may be responsible for diverting the sugar meal to the crop by closure of the valve.
Comparison of bednets treated with alphacypermethrin, permethrin or lambdacyhalothrin against Anopheles gambiae in the Gambia
Authors: JAWARA  , MCBEATH  , LINES  , PINDER  , SANYANG  , GREENWOOD
Published: March 2003

In the Gambian village of Saruja, where malaria is transmitted mainly by mosquitoes of the Anopheles gambiae complex, a trial was undertaken of the acceptability and efficacy of bednets treated with one of three pyrethroid insecticides – alphacypermethrin 40 mg/m2, permethrin 500 mg/m2 and lambdacyhalothrin 10 mg/m2. Fewer mosquitoes were found alive under nets treated with insecticide than under control nets. Significantly more dead mosquitoes were found under nets treated with alphacypermethrin than under nets treated with permethrin or lambdacyhalothrin. Side‐effects were reported by a proportion of the users of nets treated with each of the insecticides, but none were severe and their prevalence was similar between treatment groups. Unwashed nets treated with alphacypermethrin were more effective at killing anopheline mosquitoes in bioassays than nets treated with permethrin or lambdacyhalothrin. Killing activity was reduced when nets were washed, irrespective of which insecticide was used. Bednets treated with alphacypermethrin are well accepted, effectively killed anopheline mosquitoes and should therefore be evaluated for personal protection against malaria transmission.
Responses of the biting midge Culicoides impunctatus to acetone, CO2 and 1‐octen‐3‐ol in a wind tunnel
Authors: Bhasin A. , (luntz) A. J. Mordue , Mordue W.
Published: March 2003

Responses of host‐seeking female Culicoides impunctatus (Goetghebuer) (Diptera: Ceratopogonidae) to acetone, carbon dioxide and 1‐octen‐3‐ol were measured in a wind tunnel. Carbon dioxide, presented as a filamentous plume, increased upwind flight in a dose‐dependent manner, up to 0.09% concentration. A homogenous CO2 plume elicited similar upwind responses at concentrations up to 0.09%, whereas higher plume concentrations (> 0.1%) induced erratic responses with a suppression of upwind flight. Bovine equivalent concentrations of acetone (1.5 × 10−6 g/l) and 1‐octen‐3‐ol (1.3 × 10−8 g/l) failed to induce any significant upwind response when tested alone. In the presence of CO2, however, 1‐octen‐3‐ol showed highly significant increases in upwind responses at concentrations of 1.3 × 10−10−10−8 g/l. Mixtures of CO2 + acetone also enhanced upwind flight at 1.5 × 10−9 g/l. High tunnel concentrations of both 1‐octen‐3‐ol and acetone inhibited upwind responses. These findings are discussed in relation to host finding by C. impunctatus and known mechanisms by which upwind flight is initiated and arrested at high odour concentrations.
Suspected intestinal myiasis due to Dryomyza formosa in a Japanese schizophrenic patient with symptoms of delusional parasitosis
Authors: Chigusa Y. , Shinonaga S. , Koyama Y. , Terano A. , Kirinoki M. , Matsuda H.
Published: March 2003

A third‐stage larva of Dryomyza formosa (Wiedemann) (Diptera: Dryomyzidae) was found in the fresh stool of a 27‐year‐old Japanese woman resident of Shiobara, 150 km north of Tokyo, on 16 November 1998. This is the first record of myiasis due to Dryomyza. Detection of this maggot (2 cm long) by the patient herself was associated with her longstanding delusion of abdominal parasitosis as a symptom of chronic schizophrenia. Circumstantial evidence agreed with this being a genuine case of intestinal myiasis, apparently due to accidental ingestion of the insect, with no signs that the patient had contrived the report, nor that the maggot had invaded the stool post‐defaecation. This case draws attention to the likelihood that some personality states are predisposed to noticing and reporting myiasis, when it occurs. We review other conditions (mental and physical) that are more prone to myiasis.
Shared salinity tolerance invalidates a test for the malaria vector Anopheles farauti s.s. on Guadalcanal, Solomon Islands
Authors: Foley D. H. , Bryan J. H.
Published: March 2003

Among the Punctulatus Group of Anopheles mosquitoes (Diptera: Culicidae), first‐instar larvae of the medically unimportant freshwater Anopheles farauti species No. 7 survives a seawater tolerance test (STT) that was previously thought to be diagnostic for the saltwater‐tolerant malaria vector species, An. farauti Laveran s.s. Salt tolerance in these two closely related isomorphic species appears to be a shared derived character within the Farauti Complex. Failure to differentiate An. farauti s.s. from An. farauti No.7 will overestimate potential malaria vector numbers and waste limited larval control resources. Use of the STT should therefore be discontinued on Guadalcanal and other techniques such as allozyme electrophoresis used instead.
Educational needs of internal medicine residency graduates: general internist versus subspecialists
Authors: Baker  , Scofield
Published: March 2003

Residency training is inadequate with respect to the needs of general internal medicine doctors in several areas. We undertook this study to determine the practice habits and educational requirements of general versus subspecialty internists.

A survey was mailed to 138 doctors who had completed at least a three‐year university‐based internal medicine post‐graduate training.

Sixty‐three (46%) responded, of whom 32 completed additional training in a subspecialty of internal medicine. Many (14 of 32) subspecialists described their practice as general internal medicine (GIM) with a subspecialty emphasis. GIM was as important to their practice as it was to the general internists. General internists saw non‐internal medicine disciplines as important but subspecialists did not. General internists frequently performed procedures that were not formally taught during training, while subspecialists rarely if ever performed a procedure outside the scope of their fellowship training.

Internal medicine training programmes should be able to individualize training based on the career choices of trainees such that training will more fully prepare trainees for practice.
Flexible training opportunities in the European Union
Authors: Maingay John , Goldberg Ilfra
Published: March 2003

This paper compares the opportunities for flexible (part‐time) specialist training in the UK and elsewhere in the EU in the overall context of the rising numbers of women doctors across Europe. Few other EU countries appear to provide the same opportunities for flexible training as the UK, despite high percentages of women medical students and women medical graduates. There are important differences in training patterns across the EU and some reasons are proposed for why flexible training may be more difficult to implement or may not be required elsewhere in the EU. Reasons include less centralized health care systems and more rigidly structured training programmes. In the context of four main factors affecting medical manpower – medical unemployment, contracted working hours, maternity provisions and duration of training – both the health authorities' need to implement flexible training and the trainee doctors' demand for it would appear to be greater in the UK than in other EU countries.
Establishing community‐orientated medical schools: key issues and steps in early planning
Authors: Hamad Bashir
Published: March 2003

Objectives

To describe briefly the process of early planning and establishment of community‐based medical schools with highlights of the key issues and milestones.

Design

After outlining some basic concerns and provisos for the Dean and suggested strategies for setting the stage (preparing the ground) for the innovation, three phases of early planning and action steps within each are listed to serve as a guide and a general checklist.

Setting

University of Gezira, Sudan and UAE University, AL‐Ain.

Conclusion

As the curriculum with its implications constitutes the driving force for establishing the schools, it has been given due emphasis and greater share in planning. The communication is concluded with further advice to founding Deans through the proposition of a five‐star Dean.
Make induction day more effective – add a few problems
Authors: Mitchell  , Laidlaw
Published: March 2003

Introduction

Induction courses are important to introduce Pre‐Registration House Officers (PRHOs) to their new place of work. Traditionally, such programmes employ lectures, small group discussion and demonstrations. They let PRHOs meet members of various hospital disciplines and services. Since 1991, an interactive induction programme has been held each August for new PRHOs in the Eastern Region of Scotland taking up posts in Dundee Teaching Hospitals NHS Trust.

Design

Feedback from participants allows the course to be refined each year. In 1995, three paper‐based patient management problems (PMPs) were included in the induction programme. Response was favourable. Most of the participants (82%) suggested the PMPs should be used again, but that more time should be allocated to enable them to tackle the problems. By August 1996, we aimed to provide a relevant and interactive programme that encouraged PRHOs to make immediate use of hospital resources. Two PMPs, in print format described likely case histories, with tasks that mirrored the junior doctors’ forthcoming responsibilities. Healthcare team members and laboratory staff provided support as did study boards displaying written sheets of relevant clinical information.

Results

In the subsequent evaluation, the PMP component was rated highly by participants. They effectively triggered PRHOs to interact with hospital staff.

Conclusions

We conclude that PMPs provide a valuable learning experience for junior doctors and are a useful addition to an induction day programme. We plan to refine and increase the use of PMPs in undergraduate and postgraduate settings.
Why? What? and How? IT provision for medical students in general practice
Authors: Hagdrup N A , Edwards M , Carter Y H , Falshaw M , Gray R W , Sheldon M G
Published: March 2003

Objectives

The aim of this paper is to discuss the increasing use of computers in undergraduate medical education and explore the why, what and how of providing IT facilities to undergraduate medical students when they are on placement in general practice. Adequate computing facilities are usually available within hospitals and medical schools, however, major changes are taking place in undergraduate education resulting in more teaching being undertaken in the community. Students will therefore need access to comparable facilities whilst in primary care settings in order for their training not to be compromised.

Setting

This paper describes one initiative addressing this need: the University Linked Practices (ULP) project in the Department of General Practice and Primary Care at St. Bartholomew’s and the Royal London School of Medicine and Dentistry.

Design

We discuss the ways in which computers are currently being used in medical education and discuss some of the merits and drawbacks that are associated with this increasing drive to computerization.
RAPD markers of mitochondrial origin exhibit lower population diversity and higher differentiation than RAPDs of nuclear origin in Douglas fir
Authors: AAGAARD J. E. , KRUTOVSKII K. V. , STRAUSS S. H.
Published: March 2003

We developed a method of screening RAPD markers for the presence of organelle DNA products using enriched organelle DNA probes, then used these markers to compare the structure of nuclear and mitochondrial RAPD diversity in Douglas fir. Of 237 screened RAPD fragments from 25 primers, 16% were identified as originating in the mitochondrial genome and 3% in the chloroplast genome. The mitochondrial DNA probe correctly distinguished fragments with known maternal inheritance (which is exclusive for the mitochondrial genome in the Pinaceae), and neither of the organelle probes hybridized to biparentally inherited fragments. Mitochondrial RAPD markers exhibited low diversity within populations compared to nuclear RAPD diversity (HS = 0.03 and 0.22, respectively), but were much more highly differentiated than were fragments of nuclear origin at both the population (GST = 0.18 and 0.05, respectively) and racial levels (GST = 0.72 and 0.25, respectively). Both nuclear and mitochondrial DNA based phylogenetic analyses identified the varieties as monophyletic groups; the nuclear RAPD markers further separated the north and south interior races.
The patterns of genetic diversity in Carpentaria acuminata (Arecaceae), and rainforest history in northern Australia
Authors: SHAPCOTT
Published: March 2003

Carpentaria acuminata occurs in monsoon rainforest and is endemic to the Northern Territory, Australia. The genetic diversity of C. acuminata populations was surveyed across the geographical range of the species using isozyme analysis. Genetic diversity within C. acuminata populations (HE = 0.143) was typical of rainforest species and woody angiosperms generally. Genetic diversity was not correlated with rainforest patch size. However, there was significant heterogeneity among populations (FST = 0.379), with infrequent effective gene flow among populations (Nm = 0.39). Genetic diversity was negatively correlated with increasing distance between neighbouring C. acuminata populations, but geographical distance was not a good predictor of genetic similarity. C. acuminata is a favoured food of mobile frugivores such as Torres Strait pigeons and flying foxes. The decreased diversity with decreasing density of populations indicated that seed dispersal by frugivores has been important for the maintenance of diversity in this species. Populations known to have originated on relatively young, Holocene landforms were not necessarily genetically depauperate. Gene flow by pollen is apparently limited because C. acuminata populations are significantly inbred regardless of genetic diversity (F = 0.641). The distribution and diversity of rare alleles, i.e. those occurring in few populations, is consistent with the theory of rainforest contraction during the Pleistocene.
Estimating null allele frequencies at a microsatellite locus in the oystercatcher (Haematopus ostralegus)
Authors: VAN TREUREN R.
Published: March 2003

A significant heterozygote deficiency was found for microsatellite locus 20H7 among adult breeding birds in four populations of the oystercatcher (Haematopus ostralegus). Genotype frequencies at seven other loci were according to Hardy–Weinberg equilibria. Deviations between observed and expected genotype numbers decreased substantially when the data were corrected based on the estimated frequency of a putative null allele at locus 20H7. However, no null homozygotes were observed in the total sample of 378 individuals. The probability that, because of chance effects, null homozygotes were not represented in the sample (n=230) from the most intensively studied population (Schiermonnikoog) was estimated to be less than 1%. Parent–offspring comparisons from Schiermonnikoog showed that observed genotype numbers in the offspring were in accordance with expected values based on the estimated frequency of the putative null allele in the population. Moreover, a null homozygote was observed among the nestlings. The combined results indicated that a null allele is present at locus 20H7 in oystercatchers and that the inheritance is according to normal Mendelian segregation. If the absence of null homozygotes among adult animals cannot be ascribed to statistical effects, null homozygotes may suffer a selective disadvantage during the juvenile stage.
Genetic variation in a freshwater bryozoan. I: Populations in the Thames basin, UK
Authors: HATTON‐ELLIS TRISTAN W. , NOBLE LESLIE R. , OKAMURA BETH
Published: March 2003

In spite of increasing interest in metapopulation dynamics, the genetic consequences of a metapopulation structure remain poorly understood. Here we examine the metapopulation genetic structure of the colonial, facultatively sexual freshwater bryozoan Cristatella mucedo, in the Thames basin of southern England, UK. Populations from nine sites were sampled and colonies genetically characterized using random amplified polymorphic DNA (RAPD)–PCR. A total of 78 different clones was detected over all sites. Despite the large number of clones, genetic distances among clones both within and among sites were very small. Nonetheless, no clone was present at more than one site even though C. mucedo has an asexual dispersal propagule, and clones strongly clustered by sites. No consistent pattern of clonal structure was evident, with both the number and equitability of clones varying greatly among sites. Although sites were genetically distinct, population genetic regions were absent, and a Mantel test indicated that there was no relationship between geographical distances among sites and genetic distances among populations. Our results indicate that C. mucedo exists as a classical metapopulation in the Thames basin, with dispersal independent of distance and all sites contributing to the genetic diversity of the metapopulation.
Character compatibility of molecular markers to distinguish asexual and sexual reproduction
Authors: MES
Published: March 2003

Particularly in polyploids, the potential of the high variability of dominant markers such as random amplified polymorphic DNA fragments (RAPDs) and amplified fragment length polymorphisms (AFLPs) in population genetic studies and analysis of breeding systems is reduced due to their dominant nature. In contrast, the criterion of character compatibility is hindered neither by dominance nor by polyploidy as allelic interpretation is not necessary. Character compatibility, which can be used to detect events of genetic exchange (or recombination), is particularly informative if these events are expected to be rare such as in taxa with extensive vegetative reproduction or apomixis. Binary unordered characters such as presence and absence of anonymous DNA markers are incompatible if all four pairwise combinations of character states are present among the individuals studied. Because incompatible character state distributions defy any progenitor–derivative relationship among individuals, they provide strong evidence for genetic exchange. Both the absolute number of incompatible character combinations and the probability of compatibility can be used as a measure of incompatibility. Although these measures may not directly relate to the frequency of genetic exchange, they provide a useful tool to heuristically explore data sets. The most commonly used input for multivariate analyses and analysis of molecular variance in population genetic studies of (dis)similarity of marker distributions are amalgamates of mutation and recombination. Character compatibility can be used to complement these traditional methods of analysis. Advantages and disadvantages of character incompatibility relative to multilocus analysis of modes of reproduction and population genetics are demonstrated with data from RAPDs, isozymes, and restriction fragment length polymorphisms (RFLPs) of the nuclear ribosomal and chloroplast genome.
Microgeographic population genetic structure in the northern water snake, Nerodia sipedon sipedon detected using microsatellite DNA loci
Authors: PROSSER MELANIE R. , LISLE GIBBS H. , WEATHERHEAD PATRICK J.
Published: March 2003

We describe the isolation and genetic characterization of eight microsatellite DNA loci from the northern water snake, Nerodia sipedon sipedon and use these loci to analyse levels of genetic differentiation between local (<2km apart) populations of these snakes in Ontario. These loci are variable, with expected heterozygosities ranging from 0.28 to 0.91, and can correctly exclude nonsires in parentage analyses with a high probability (0.998). Population analyses reveal significant deviation from expected heterozygosity levels for one population, probably a result of a null allele(s) at a single locus and small but significant levels of genetic differentiation among all three populations. This demonstrates that microgeographic genetic structure exists in this species, possibly due to limited dispersal.
Genetic variability and structure of Canadian populations ofChondrostereum purpureum, a potential biophytocide
Authors: Gosselin Lyne , Jobidon Robert , Bernier Louis
Published: March 2003

Genetic diversity was studied in four Canadian ecological populations, each corresponding to a Canadian ecozone, ofChondrostereum purpureum, including 93 isolates of various host origin. Pseudo‐allelic frequencies were estimated at each of 22 putative RAPD loci by scoring for presence or absence of amplicons in haploid mycelial cultures. The analysis of the hierarchical population structure did not reveal any trend with regard to ecological or host origin. Total gene diversity (HT† = 0.288) was mostly attributable to diversity within populations (HS† = 0.269). In addition, theAMOVAanalysis detected most of the molecular variability within subpopulations (89.3%;P< 0.001), whereas a significant (7.3%;P= 0.001) proportion of the gene diversity was found among subpopulations, within ecozones. The results indicate thatC. purpureumis a highly heterogeneous pathogen with a continuously distributed population across Canada (GST† = 0.048), and underscore the importance of considering the population structure in the process of its registration as a microbial control agent. A genotype isolated in either central or eastern Canada (ecozones 2, 4 and 5 populations) and selected for its potential as a biophytocide should be considered indigenous in any of these regions of intended use.
Contribution of calystegine catabolic plasmid to competitive colonization of the rhizosphere of calystegine‐producing plants by Sinorhizobium meliloti Rm41
Authors: Guntli D. , Heeb M. , Moënne‐Loccoz Y. , Défago G.
Published: March 2003

Calystegines are plant secondary metabolites produced by the roots of a few plant species, and the ability to catabolize calystegines is infrequent in rhizosphere bacteria. In Sinorhizobium meliloti Rm41, the endosymbiont of the legume Medicago sativa, this ability results from the presence of the genes cac (for calystegine catabolism) located on the nonsymbiotic plasmid pRme41a. The effect of the cac catabolic plasmid pRme41a on the ability of Rm41 to colonize the rhizosphere of calystegine‐positive plants was studied using derivatives of Rm41 with or without cac catabolic plasmid. When strains were inoculated alone, the presence of a cac catabolic plasmid had no effect on their colonization of the rhizosphere, regardless of whether plants produced calystegines or not. However, a spontaneous rifampicin‐resistant mutant of Rm41 containing a cac catabolic plasmid reached population levels in the rhizosphere of calystegine‐positive plants that were several orders of magnitude higher than those of the same strain without the plasmid, when each was co‐inoculated with a derivative of Rm41 cured of pRme41a. In contrast, the cac catabolic plasmid provided little or no selective advantage in the rhizosphere of calystegine‐negative plants. In conclusion, the cac catabolic plasmid pRme41a can contribute to the ability of S. meliloti Rm41 to colonize the rhizosphere of alternative, nonlegume plant hosts producing calystegines.