bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined index of heart rate variability and oximetry in screening for the sleep apnoea/hypopnoea syndrome
Authors: Raymond Ben , Cayton R. M , Chappell M. J.
Published: March 2003

Many sleep centres employ a preliminary screening test in order to reduce the number of polysomnographies required in the routine diagnosis of the sleep apnoea/hypopnoea syndrome (SAHS). We investigated the combination of heart rate and oximetry information as a means of performing this test. A retrospective study of 100 patients with suspected SAHS was made. All patients had in‐hospital polysomnography on one night. We estimated the number of respiratory event‐related arousals by counting the number of autonomic arousals (assessed on the basis of changes in the heart interbeat interval) that were coincident with a rise in oximetry. The hourly index of such events was denoted the ‘cardiac‐oximetry disturbance index’ (CODI). The median apnoea/hypopnoea index (AHI) was 16.5 (range 1.0–93.6) h−1. The CODI correlated significantly with the AHI (Spearman correlation coefficient rs = 0.88, P < 0.01), and the area (± standard error) under the receiver operating characteristic (ROC) was 0.94 ± 0.05. Oximetry alone (based on 4% dips) was a less effective screening test (rs = 0.80, P < 0.01; area under ROC 0.83 ± 0.06). Using 2% dips in oximetry offered comparable performance with the CODI (rs = 0.91, P < 0.01; area under ROC 0.93 ± 0.04). The CODI was better correlated with the electroencephalograph arousal index (rs = 0.84, P < 0.01) than was oximetry (2% dips, rs = 0.57, P < 0.01). The CODI algorithm also offers an informal measure of self‐validation: a large discrepancy between the number of autonomic arousals and the number of rises in oximetry indicates the presence of autonomic arousals without changes in oximetry (or vice versa). This self‐validation mechanism identified several patients in this study, and may be useful in identifying sleep disruption due to chronic pain or other causes.
Concentration of enrofloxacin and its active metabolite in alveolar macrophages and pulmonary epithelial lining fluid of dogs
Authors: Hawkins  , Boothe  , Guinn  , Aucoin  , Ngyuen
Published: March 2003

The purpose of this study was to determine the concentration of enrofloxacin and its active metabolite, ciprofloxacin, in alveolar macrophages (AM) and epithelial lining fluid (ELF) of the lungs in comparison to plasma concentrations in healthy dogs. Eleven dogs were given a single oral dose (5 mg/kg) of enrofloxacin. Four hours later, plasma and bronchoalveolar lavage (BAL) fluid were collected. Cells were separated from the BAL fluid and lysed for determination of drug concentrations within AM. Supernatant was used to determine concentrations of drugs in ELF. Drug assays were performed by high‐performance liquid chromatography.

 The concentration of enrofloxacin (mean ± SD) was 0.33 ± 0.14 μg/mL in plasma, 3.34 ± 2.4 μg/mL in AM and 4.79 ± 5.0 μg/mL in ELF. The concentration of ciprofloxacin was 0.42 ± 0.26 μg/mL in plasma, 1.15 ± 1.03 μg/mL in AM and 0.26 ± 0.26 μg/mL in ELF. Mean concentrations of both drugs in AM were greater than in plasma (AM to plasma ratio, 10.3 for enrofloxacin and 4.7 for ciprofloxacin). Mean concentrations of enrofloxacin, but not ciprofloxacin, in ELF were greater than in plasma (ELF to plasma ratio, 13.5 for enrofloxacin and 0.52 for ciprofloxacin). Enrofloxacin concentrations in AM and ELF largely exceeded the MICs of the major bacterial pathogens and surpassed by about two times the breakpoint MIC of that drug, and ciprofloxacin concentrations in AM surpassed the MIC of many susceptible organisms. These results suggest that sufficient antimicrobial activity is present in AM and ELF of dogs following oral administration of enrofloxacin to be effective in the treatment of lower respiratory tract infections involving susceptible organisms.
The pharmacodynamics of thiopental, medetomidine, butorphanol and atropine in beagle dogs
Authors: Grimm K.A.. , Thurmon J.C. , Olson W.A. , Tranquilli W.J. , Benson G.J.
Published: March 2003

This study evaluated the quality of anaesthesia and some of the haemodynamic effects induced by a combination of thiopental, medetomidine, butorphanol and atropine in healthy beagle dogs (n = 12). Following premedication with atropine (ATR, 0.022 mg/kg intravenously (i.v.)) and butorphanol (BUT, 0.22 mg/kg i.v.), medetomidine (MED, 22 μg/kg intramuscularly (i.m.)) was administered followed in 5 min by thiopental (THIO, 2.2 mg/kg i.v.). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) were monitored continuously with an ECG and direct arterial blood pressure monitor. Atipamezole (ATI, 110 μg/kg i.v.) was administered to half of the dogs (n = 6) following surgery to evaluate the speed and quality of arousal from anaesthesia. Anaesthesia was characterized by excellent muscle relaxation, analgesia and absence of purposeful movement in response to surgical castration. Arousal following antagonism of mede­tomidine was significantly faster (P < 0.05) than in unantagonized dogs. Recoveries were smooth but recovery times following atipamezole administration were highly variable among dogs (sternal time range 6–38 min, standing time range 9–56 min). Medetomidine caused a significant (P < 0.05) increase in SBP, DBP and MBP. Atropine prevented the medetomidine induced bradycardia. In conclusion, this combination provided adequate surgical anaesthesia in healthy beagle dogs. At the dosages used in this study, it seems prudent that this combination should be reserved for dogs free of myocardial disease.
Norfloxacin pharmacokinetics in lactating cows with sub‐clinical and clinical mastitis
Authors: Gips M. , Soback S.
Published: March 2003

Single‐dose pharmacokinetics of norfloxacin after intravenous administration of norfloxacin nicotinate at 10 mg norfloxacin/kg body weight was investigated in cows with healthy udders and in cows with chronic subclinical and postacute clinical mastitis. An HPLC method was used to determine the norfloxacin concentrations in serum and milk. Significant differences were observed in norfloxacin pharmacokinetics when administered to cows with infected udder quarters. The clearance (Cl) values were 10.4 ± 2.5, 13.2 ± 1.9 and 14.2 ± 2.1 mL/min/kg (mean ± SD) in the control (healthy udder) cows and in cows with subclinical and postacute clinical mastitis, respectively. There appeared to be a trend of increasing clearance according to severity of the disease. The volume of distribution at steady state (Vss) in the respective groups was 3.1 ± 0.7, 2.2 ± 0.6 and 1.3 ± 0.2 L/kg. The volume of distribution was significantly decreased in the cows with postacute clinical mastitis. The half‐lives (t1/2) and mean residence times (MRT) of norfloxacin were 353, 206 and 115 min (harmonic means) and 306 ± 76, 168 ± 39 and 95 ± 9 min in control cows or in cows with subclinical and postacute clinical mastitis, respectively. The half‐lives in the clinical mastitis group were significantly shorter than in the control group and the mean residence times were significantly shorter in the two mastitis groups when compared to the control group.

 Norfloxacin concentrations in milk were extremely high when compared to the respective serum concentrations. The area under the concentration vs. time curve (AUC) of norfloxacin in milk was 23899 ± 6206 mg/L×min in the control cow group. The AUC in milk was significantly lower in the infected udder quarters of the mastitis groups (5075 ± 1887 mg/L×min and 7484 ± 4645 mg/L×min in the subclinical and the clinical group). The AUC values were significantly lower in milk from the infected udder quarters of the cows with chronic subclinical and postacute clinical mastitis when compared to the values in milk from the healthy quarters of the same udder.

 Norfloxacin was marginally bound to serum protein. The binding was concentration dependent and was 19, 13 and 6% at 0.2, 1.0 and 8.4 mg/L, respectively. Binding to milk protein was 46–51% and concentration independent. An in vitro dialysis model was used to simulate drug transport between serum and milk as a function of protein binding. The results showed that the rate of norfloxacin disposition from milk to serum was slower than from serum to milk, which was in agreement with the findings obtained in the pharmacokinetic study. Norfloxacin was poorly soluble in organic solvents and our results suggest that changes in the degree of ionization of the drug in different body fluids considerably affect its disposition.
Comparative study of the plasma pharmacokinetics and tissue concentrations of danofloxacin and enrofloxacin in broiler chickens
Authors: Knoll  , Glünder  , Kietzmann
Published: March 2003

The plasma pharmacokinetics of danofloxacin and enrofloxacin in broiler chickens was investigated following single intravenous (i.v.) or oral administration (p.o.), and the steady‐state plasma and tissue concentrations of both drugs were investigated after continuous administrationviathe drinking water. The following dosages approved for the treatment of chickens were used: danofloxacin 5 mg/kg and enrofloxacin 10 mg/kg of body weight. Concentrations of danofloxacin and enrofloxacin including its metabolite ciprofloxacin were determined in plasma and eight tissues by specific and sensitive high performance liquid chromatography methods. Pharmacokinetic parameter values for both application routes calculated by noncompartmental methods were similar for danofloxacin compared to enrofloxacin with respect to elimination half‐life (t1/2; ≈ 6–7 h), mean residence time (MRT; 6–9 h) and mean absorption time (MAT; 1.44 vs. 1.20 h). However, values were twofold higher for body clearance (ClB; 24 vs. 10 mL/min. kg) and volume of distribution at steady state (VdSS; 10 vs. 4 L/kg). Maximum plasma concentration (Cmax) after oral administration was 0.5 and 1.9 μg/mL for danofloxacin and enrofloxacin, respectively, occurring at 1.5 h for both drugs. Bioavailability (F) was high: 99% for danofloxacin and 89% for enrofloxacin. Steady‐state plasma concentrations (mean ±  SD) following administrationviathe drinking water were fourfold higher for enrofloxacin (0.52 ± 0.16 μg/mL) compared to danofloxacin (0.12 ± 0.01 μg/mL). The steady‐stateAUC0–24hvalues of 12.48 and 2.88 μg.h/mL, respectively, derived from these plasma concentrations are comparable with corresponding area under the plasma concentration‐time curve (AUC) values after single oral administration. For both drugs, tissue concentrations markedly exceeded plasma concentrations, e.g. in the target lung, tissue concentrations of 0.31 ± 0.07 μg/g for danofloxacin and 0.88 ± 0.24 μg/g for enrofloxacin were detected. Taking into account the similarin vitroactivity of danofloxacin and enrofloxacin against important pathogens in chickens, a higher therapeutic efficacy of water medication for enrofloxacin compared to danofloxacin can be expected when given at the approved dosages.
Cytotoxicity in pig hepatocytes induced by 8‐quinolinol, chloramine‐T and natamycin
Authors: Martínez‐Larrañaga  , Anadón  , Fernandez‐Cruz  , Díaz  , Martinez  , Frejo  , Martínez  , Tafur
Published: March 2003

The potential cytotoxic effects of the compounds 8‐quinolinol, chloramine‐T and natamycin have been studied in isolated pig hepatocytes. The relative cytotoxicity of these compounds was evaluated on the basis of the leakage of cytosolic lactate dehydrogenase (LDH), 3‐(4,5 dimethyl)thiazol‐2‐yl,‐2,5‐diphenyl tetrazolium bromide (MTT) reduction by mitochondrial dehydrogenases, uptake of neutral red (NR) by cytosolic lysosomes, glutathion (GSH) depletion and oxidized glutathion (GSSG) efflux after 24 h exposure. Evaluation of the 20%, 50% and 80% reduced absorbance data obtained from the parameters NR20, NR50, and NR80, and MTT20, MTT50 and MTT80 enabled us to rank these compounds in decreasing order of cytotoxicity: 8‐quinolinol > natamycin > chloramine‐T. Also for the parameters LDH and GSH, chloramine‐T appears to be less cytotoxic than natamycin and 8‐quinolinol. Our study demonstrated that pig hepatocytes may be a useful model for examining cytotoxic events of drugs to be used in pigs, therefore avoiding possible extrapolation problems due to species differences.
Milk depletion of dicloxacillin residues in cows and sheep following intramammary administration
Authors: RONCADA P. , TOMASI L. , STRACCIARI G. L. , ERMINI L. , STROCCHIA A.
Published: March 2003

The excretion rate of dicloxacillin from milk was studied after intramammary administration of a suspension of the drug active in vegetable oil. Eight cows and eight sheep, four of each group in low and four in high milk production, were dosed with 200 mg dicloxacillin/quarter in cows and 100 mg dicloxacillin/quarter in sheep, three times at 12 h intervals. The dicloxacillin concentrations in milk were quantified by high performance liquid chromatography (HPLC). In cows, time until dicloxacillin was undetectable was 48 h and no difference was observed between the groups. In sheep, dicloxacillin was undetectable 72 h and 84 h after the treatment in low and in high milk production groups, respectively. The implications of several factors affecting the possible milk withdrawal period were studied. The results indicated that the pharmaceutical vehicle and the coefficient of lipid solubility exerted major effects on depletion time.
Comparative disposition of tripelennamine in horses and camels after intravenous administration
Authors: Wasfi I. A. , Abdel Hadi A. A. , Elghazali M. , Boni N. S. , Alkatheeri N. A. , Barezaig I. M. , Al Muharami A. M. , Hamid A. M.
Published: March 2003

The pharmacokinetics of tripelennamine (T) was compared in horses (n=6) and camels (n=5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half‐lives were 2.39 (1.91–6.54) and 2.08 (1.31–5.65) h, total body clearances were 0.97 (0.82–1.42) and 0.84 (0.64–1.17) L/h/kg. The volumes of distribution at steady state were 2.87 (1.59–6.67) and 1.69 (1.18–3.50) L/kg, the volumes of the central compartment of the two compartment pharmacokinetic model were 1.75 (0.68–2.27) and 1.06 (0.91–2.20) L/kg. There was no significant difference (Mann–Whitney) in any parameter between camels and horses. The extent of protein binding (mean±SEM) 73.6±8.5 and 83.4±3.6% for horses and camels, respectively, was not significantly statistically different (t‐test).

Three metabolites of T were identified in urine samples of camels. The first one resulted from N‐depyridination of T, with a molecular ion of m/z 178, and was exclusively eliminated in conjugate form. This metabolite was not detected after 6 h of T administration. The second metabolite, resulted from pyridine ring hydroxylation, had a molecular ion of m/z 271, and was also exclusively eliminated in conjugate form. This metabolite could be detected in urine sample for up to 12 h after T administration. The third metabolite has a suspected molecular ion of m/z 285, was eliminated exclusively in conjugate form and could be detected for up to 24 h following T administration. T itself could be detected for up to 27 h after i.v. administration, with about 90% of eliminated T being in the conjugated form.
Metabolism of prostaglandin F2α during fasting in prepubertal gilts
Authors: Holst H. , Kindahl H.
Published: March 2003

The study was conducted to investigate a possible mechanism behind earlier observations of fasting‐induced increases of blood concentrations of prostaglandin (PG) F2α metabolite (P‐PG) in gilts. Six animals were fasted for 28 h, then administered i.v. PGF2α (500 ng/kg body weight). Blood samples were withdrawn at 1, 3, 5, 7, 10, 15, 20, 30, 40, 60 min, 2 and 3 h after the injection. A control group followed an identical protocol, except that they were fed during the corresponding 28 h‐period. P‐PG increased as previously observed during the 28 h of fasting. The P‐PG increase in terms of area under the concentration time curve (AUC) following injection was significantly larger in the fasted than in the non‐fasted gilts. In the fasted animals, the mean P‐PG maximum concentration (Cmax) was 7145 pmol/L, the corresponding value for the non‐fasted animals was 4566 pmol/L. PGs are metabolised through β‐oxidation in the liver. The results of this study imply that reduced 15‐ketodihydro‐PGF2α breakdown in the liver might contribute to the fasting‐induced increases in P‐PG.
Study of the plasma pharmacokinetics and faecal excretion of the prodrug olsalazine and its metabolites after oral administration to horses
Authors: KNOLL U. , STRAUHS P. , SCHUSSER G. , UNGEMACH F. R.
Published: March 2003

Olsalazine sodium (Dipentum*) has been used therapeutically against inflammatory bowel disease in human medicine as an alternative to sulphasalazine over the past 20 years. Bacteria in the colon split this prodrug into two molecules of the locally effective 5‐aminosalicylic acid (5‐ASA). Considering the potential therapeutic use in equine colitis, the pharmacokinetics of olsalazine (OLZ) after single oral administration to six horses at a dosage of 30 mg/kg was investigated. Plasma concentrations of OLZ, 5‐ASA, and its main metabolite N‐acetyl‐5‐aminosalicylic acid (Ac‐5‐ASA) were analysed by high‐performance liquid chromatography methods. Evaluation of the plasma pharmacokinetics revealed a rapid, but low extent of absorption of OLZ (peak concentrations around 1 μg/mL at 0.5–1.5 h), and a delayed minimal absorption of 5‐ASA (concentrations < 0.2 μg/mL, at 11–35 h), which is immediately metabolized to Ac‐5‐ASA. As indicators of the local availability in the colon, high faecal water concentrations of 5‐ASA and Ac‐5‐ASA (mean Cmax about 300 and 130 μg/mL, respectively), but only traces of OLZ were found in faeces excreted 18–50 h after dosing. Of the administered OLZ dose 26% could be recovered from faeces, almost completely as 5‐ASA and Ac‐5‐ASA.

Routine clinical examination of the horses and assay of standard haematological and serum chemistry parameters before and after OLZ administration confirmed that a single dosage of 30 mg/kg was well tolerated.

To estimate the systemic availability of 5‐ASA liberated from OLZ, 5‐ASA was administered i.v. at a dosage of 1.5 mg/kg to four horses and plasma concentrations of 5‐ASA and Ac‐5‐ASA were determined. The pharmacokinetic evaluation showed a very low bioavailability of 2.4% for 5‐ASA, released from orally administered OLZ.

Furthermore, in an in vitro experiment, the metabolic transformation of 5‐ASA to Ac‐5‐ASA mediated by bacteria in the caecal content of horses was determined at 38 °C for 31 h and compared with the metabolism data of the in vivo study. The markedly lower degree of acetylation in vitro supports the assumption that biotransformation of 5‐ASA in vivo occurs not only by colonic bacteria, but also at other sites.
Quantitative hepatitis B virus DNA assessment by the limiting‐dilution polymerase chain reaction in chronic hepatitis B patients: evidence of continuing viral suppression with longer duration and higher dose of lamivudine therapy
Authors: Honkoop P. , De Man R. A. , Niesters H. G. M. , Main J. , Nevens F. , Thomas H. C. , Fevery J. , Tyrrell D. L. , Schalm S. W.
Published: March 2003

Lamivudine, a novel cytosine analogue, exhibits potent antiviral activity against hepatitis B virus (HBV) in vitro and in vivo. The standard HBV DNA hybridization assay used in phase II clinical studies has a low sensitivity, the detection limit of HBV DNA levels being ≈ 107 genome equivalents per ml (geq ml–1). In this work we used a semiquantitative polymerase chain reaction (PCR) assay (detection limit ≈ 103 geq ml–1) to determine HBV DNA levels during a 24‐week study of lamivudine in 51 stable chronic hepatitis B patients who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Patients were randomly allocated to receive oral doses of 25, 100 or 300 mg lamivudine once daily. At week 24 the median serum concentration of HBV DNA had fallen from 108 to 104 geq ml–1, a 4‐log median reduction. A trend towards more profound suppression of viral replication with an increased dose of lamivudine was observed. After 12 weeks of therapy, 12% of patients had an HBV DNA level that was undetectable in the PCR assay; this increased to 26% after 24 weeks, while in an additional 20% of patients, HBV DNA decreased to the level of detection of the PCR assay. We conclude that a 24‐week course of lamivudine decreases serum HBV DNA to the level of PCR detection in 46% of patients. Such additional viral suppressive activity with higher doses and more protracted lamivudine may be of clinical utility prior to liver transplantation. Further studies are needed to define the degree of virus suppression required in clinical practice, and methods are required to increase the efficacy of virus suppression.
Current aspects of hepatitis B surface antigen mutants in Singapore
Authors: Oon C. ‐J. , Chen W. N.
Published: March 2003

Mutations occurring on the major antigenic ‘a’ determinant of hepatitis B surface antigen (HBsAg) have been detected in immunized Singapore children, despite immunoprophylaxis with hepatitis B immune globulin and HBV vaccine. These vaccine‐escape HBsAg mutants display a predominance of the Gly145‐to‐Arg145 mutation in the antigenic ‘a’ determinant. Our latest follow‐up studies indicate the stability of this as well as other vaccine‐escape HBsAg mutants over time. We have also identified HBsAg mutants in immunized children with amino acid substitutions outside the ‘a’ determinant. Transmission of various vaccine‐escape HBsAg mutants have been shown in our epidemiological studies. Detection of HBsAg mutants, carrying amino acid changes at various position of the ‘a’ determinant in random population, points to their emergence in Singapore before the implementation of the vaccination programme. Of significant interest is the recent identification of vaccine‐escape HBsAg mutants in hepatocellular carcinoma.
The influence of host factors on the natural history of chronic hepatitis C viral infections
Authors: Minuk G. Y.
Published: March 2003

The natural history of hepatitis C is variable, with some patients progressing rapidly to cirrhosis and others showing no significant fibrosis over many decades. A number of studies have examined the factors that influence disease progression. Age at time of infection, gender, alcohol abuse and, perhaps, route of transmission, appear to have the greatest influence on the natural history of the hepatitis C virus with the possible exception of alcohol, the mechanism whereby these factors influence disease progression has yet to be determined.
Prediction of relapse or sustained response in biochemical responders by serum hepatitis C virus RNA monitoring during interferon therapy
Authors: Colloredo G. , Roffi L. , Brunetto M. R. , Leandro G. , Brugnetti B. , Bissoli F. , Scalori A. , Mancia G. , Civardi E. , Idéo G. , Bonino F. , Bellati G.
Published: March 2003

Normalization of serum aminotransferase levels is achieved in ≈ 50% of chronic hepatitis C patients treated with interferon (IFN); however, in about one‐half of these patients the hepatitis relapses after therapy. In this study we investigated the efficacy of serum hepatitis C virus (HCV) RNA monitoring during IFN therapy to predict the outcome of a biochemical end‐of‐treatment (ETR) response. Eighty patients with chronic hepatitis C received leucocyte (natural) IFN‐α (13 patients) or recombinant IFN‐α2a (67 patients). Antiviral therapy was given for 12 months to 43 (53.7%) responders and this group was analysed further. During follow‐up, 15 relapsed and 28 showed a sustained response (median follow‐up 50 months, range 39–67 months). Viraemia was monitored at baseline, and at months 1, 3, 6, 9 and 12 of treatment, by nested polymerase chain reaction (PCR) (sensitivity 10–100 copies ml–1). A combination of positive nested PCR and HCV RNA values at the 3rd and 6th months of treatment was 100% predictive of relapse (sensitivity, 66.6%; specificity, 100%). A combination of negative nested PCR and HCV RNA values at the 1st and 3rd months of treatment was 100% predictive of sustained response (sensitivity, 39.3%; specificity, 100%). In conclusion, serum HCV RNA monitoring is an appropriate and reliable tool for predicting early outcome of the biochemical ETR response after IFN discontinuation. This could be useful in the modulation of therapeutic management of chronic hepatitis C.
Immunogenetics of hepatitis C virus
Authors: McKiernan S. , Kelleher D.
Published: March 2003

Hepatitis C is a complex disease and a significant public health problem. The long‐term outcome of HCV infection is difficult to predict, as the virus may be eliminated or may persist to establish a chronic infection. Further investigation is required to clarify factors that determine or influence the outcome of infection, although unique host factors appear to significantly affect the prognosis for infected patients.
Increased effective immunogenicity to high‐dose and short‐interval hepatitis B virus vaccination in individuals with chronic hepatitis without cirrhosis
Authors: De Maria N. , Idilman R. , Colantoni A. , Van Thiel D. H.
Published: March 2003

Hepatitis B virus (HBV) vaccination is recommended for individuals with chronic liver disease. However, the response to standard doses of hepatitis B vaccines in such individuals has been poor. The aim of the present study was to assess the response to high‐dose short‐interval HBV vaccination in individuals with chronic liver disease of different aetiologies. A total two hundred and 24 subjects with chronic liver disease (138 chronic active hepatitis and 86 cirrhosis) and 26 healthy controls were vaccinated using a high‐dose (40 μg) short‐interval (monthly for 3 consecutive months) HBV vaccination schedule.

One hundred and thirty‐eight of the 224 subjects with chronic liver disease (62%) seroconverted to anti‐HBs antibody positivity (>10 mIU/mL) after the third dose of vaccine as compared with 24 of the 26 controls (92%) (P < 0.01). The response rate was reduced in individuals with cirrhosis (36/86, 42%), particularly in alcohol‐induced cirrhosis (2/17, 12%), as compared with individuals with chronic hepatitis (102/138, 74%) (P < 0.001). No significant HBV vaccination‐related adverse effects were seen in individuals with or without cirrhosis as well as in the controls.

High‐dose short‐interval HBV vaccination is safe and efficacious in individuals with chronic liver disease. The response to HBV vaccination is reduced in cirrhotics, particularly those with alcoholic cirrhosis. These data suggest that HBV vaccination should be accomplished early in an individual cause of chronic liver disease prior to the development of cirrhosis.
Diagnosis and management of pre‐core mutant chronic hepatitis B
Authors: Papatheodoridis G. V. , Hadziyannis S. J.
Published: March 2003

Chronic hepatitis due to pre‐core hepatitis B virus (HBV) mutants presents as hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (CHB). HBeAg‐negative CHB represents a late phase in the natural course of chronic HBV infection that develops after HBeAg loss and seroconversion to anti‐HBe. It is usually associated with pre‐core stop codon mutation at nucleotide 1896 (mainly selected in non‐A HBV genotypes), but also with other pre‐core changes or with mutations in the basic core promoter region (mainly in HBV genotype A). In chronic HBV infections, pre‐core mutants can be detected both in patients with HBeAg‐negative CHB and in inactive hepatitis B surface antigen (HBsAg) carriers. The diagnosis of HBeAg‐negative CHB is based on HBsAg positivity, HBeAg negativity, and mainly on increased alanine aminotransferase (ALT) and serum HBV‐DNA levels and exclusion of other causes of liver disease. The differential diagnosis between patients with CHB and inactive HBsAg carriers can be made only by close follow‐up of aminotransferase activity and viraemia levels, although the cut‐off level of serum HBV DNA has not been definitely determined. IgM anti‐HBc levels have also been suggested as an index that increases the diagnostic accuracy for transient hepatitis flares, while liver biopsy confirms the diagnosis and evaluates the severity of the liver disease. Interferon‐α (IFN‐α) and lamivudine are the two drugs that have been tried, mainly in the management of HBeAg‐negative CHB. A 12‐month course of IFN‐α achieves sustained biochemical remission in about 20% of patients, which has been associated with improvement in the long‐term outcome of this subset. A 12‐month course of lamivudine is rather ineffective, maintaining remission in less than 15% of patients after cessation of therapy. Long‐term lamivudine is associated with progressively increasing rate of virological and subsequent biochemical breakthroughs due to YMDD mutants, with approximately 30% of patients remaining in remission in the third year of therapy. Several other antiviral agents are currently being evaluated in this setting with combined regimens being the most reasonable step for the near future.
A possible role of hypervariable region 1 quasispecies in escape of hepatitis C virus particles from neutralization
Authors: Korenaga M. , Hino K. , Katoh Y. , Yamaguchi Y. , Okuda M. , Yoshioka K. , Okita K.
Published: March 2003

We examined serial changes in the hypervariable region 1(HVR1) quasispecies both in immune and nonimmune complexed hepatitis C virus (HCV) particles from 12 patients with chronic hepatitis C to elucidate the mechanism by which genetic diversification of HCV during the course of infection allows escape of virus from the humoural immune response. Immune and nonimmune complexes were separated by differential flotation centrifugation and immunoprecipitation, and their HVR1 quasispecies were determined by subcloning and sequencing. The presence of a specific antibody against a specific viral clone in serum was examined in two patients by Western blotting of the corresponding recombinant HVR1 protein. The distribution of HVR1 quasispecies in both immune and nonimmune complexes conspicuously changed over time in most of the patients studied. In seven patients, various HCV clones serially shifted from nonimmune complexes to immune complexes. In four of them, a group of clones with similar HVR1 sequences to each other remained predominant in nonimmune complexes, whereas minor clones with sequences considerably divergent from the predominant clones shifted from nonimmune complexes to immune complexes. These results suggest a mechanism for persistent infection of HCV, in which major HCV clones escape from neutralization by anti‐HVR1 antibodies by generating considerably divergent minor ‘decoy’ clones which may be preferentially neutralized.
Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection
Authors: Westin J. , Lagging L. M. , Spak F. , Aires N. , Svensson E. , Lindh M. , Dhillon A. P. , Norkrans G. , Wejstål R.
Published: March 2003

Although excessive alcohol consumption in combination with hepatitis C virus (HCV) infection is known to increase the risk of liver cirrhosis, the effect of moderate alcohol intake remains to be elucidated. The aim of this study was to evaluate the effect of moderate alcohol consumption on fibrosis progression in HCV infection. A group of 78 patients with HCV infection and moderate alcohol consumption were analysed retrospectively. All patients had undergone two liver biopsies, with a median time between biopsies of 6.3 years, and had not received any antiviral therapy. Their lifetime drinking history was recorded. All patients except one had daily alcohol consumption below 40 g of ethanol (median 4.8 g/day, interquartile range 1.1–11.6 g/day) during the period between the biopsies. The patients whose liver fibrosis had deteriorated had a higher total alcohol consumption and higher drinking frequency between the biopsies. The degree of fibrosis progression was greater in patients with a total alcohol intake and drinking frequency above the median level for the group. A multiple logistic regression analysis showed that drinking frequency and time between biopsies were independently associated with fibrosis progression. Hence, even moderate alcohol intake seems to increase fibrosis progression in HCV‐infected patients. From that point of view, total abstention ought to be recommended. If this is not achieved, occasional use of alcohol is probably less harmful than daily drinking for patients with low or moderate alcohol consumption.
Cerebral dysfunction in chronic hepatitis C infection
Authors: Forton D. M. , Taylor‐Robinson S. D. , Thomas H. C.
Published: March 2003

summary. A number of studies have reported an association between chronic hepatitis C (HCV) infection and significant impairments in health‐related quality of life (QOL), which are independent of the severity of liver disease. There are numerous reports documenting the prevalence of symptoms such as fatigue and depression in chronic HCV infection, which may in part account for the reductions in quality of life. Although there are a large number of potential explanations for these symptoms, including depression and anxiety associated with the diagnosis of HCV infection or substance abuse, there has been recent interest in the possibility of a biological effect of HCV infection on cerebral function. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be attributed to substance abuse, coexistent depression or hepatic encephalopathy. In vivo magnetic resonance spectroscopy and neurophysiological studies have suggested that a biological mechanism may underlie these cognitive findings. The recent detection of HCV genetic sequences in post mortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.
Distribution and conservation of the Gaur Bos gaurus in the Indian Subcontinent
Authors: CHOUDHURY ANWARUDDIN
Published: March 2003

The Gaur Bos gaurus ranges from India to peninsular Malaysia. Its distribution, status and conservation in the Indian subcontinent are reviewed here on the basis of available information, both published papers and unpublished census reports of forest departments, and field survey data from north‐eastern India and parts of Bhutan and Nepal. The Gaur is found in three disjunct regions, south‐western India, central India and north‐eastern India (including Nepal, Bhutan and Bangladesh). Within these regions the distribution is highly fragmented and includes a number of small non‐viable isolated populations. The habitat in north‐eastern India is still contiguous with that in Bhutan, Myanmar and Bangladesh and to some extent with Nepal. Although the estimated population of the Gaur is 23 000–34 000, it is declining alarmingly. Populations outside the protected areas may not last long. An action plan has been proposed for its conservation.
Evolution of group size in the superfamily Delphinoidea (Delphinidae, Phocoenidae and Monodontidae): a quantitative comparative analysis
Authors: Gygax Lorenz
Published: March 2003

Predictors of group size in Delphinoidea were investigated in a comparative study. Possible predictors included phylogenetic variables, variables of the physical environment, the diet, correlates of predation pressure and life‐history parameters. The strongest predictors were the variables species and subfamily, which explained most of the observed variation in group size. Group size also increased with openness of the habitat and showed a U‐shaped relationship with temperature. In conclusion, phylogeny seems to play the most crucial role in the evolution of group size in Delphinoidea. The simplest interpretation of this result is that group size resulted from a historical (random) process and has only been marginally shaped by direct selection.
Sugar feeding and fluid destination control in the phlebotomine sandfly Lutzomyia longipalpis (Diptera: Psychodidae)
Authors: TANG YINSHAN , WARD RICHARD D.
Published: March 2003

Sandfly feeding behaviour and destination of coloured sugar meals in the gut of Lutzomyia longipalpis were investigated with particular attention to the role of the crop. Sandflies were able to ingest sugar from liquid drops, microcapillaries, a slice of pear and even sugar powder. In most cases the flies adopted a ‘sugar feeding mode’ with raised palps. As the fruit dried, flies of both sexes fed by piercing the tissue with the proboscis. All sugar‐fed flies had a full crop plus a small amount of sugary fluid in the thoracic mid‐gut, i.e. past the stomodaeal valve. Dissections of flies interrupted during feeding showed that the very first trace of sugar passed through the stomodaeal valve, but that the rest of the meal was diverted into the crop. This suggests that closure of the stomodaeal valve is initiated only after a small volume of sugar solution has passed through it.
Population structure of Andean Triatoma infestans: allozyme frequencies and their epidemiological relevance
Authors: DUJARDIN  , SCHOFIELD  , TIBAYRENC
Published: March 2003

Triatoma infestans (Hemiptera: Reduviidae) from 22 Andean localities in Bolivia (n=968) and Peru (n=37) were analysed by multi‐locus enzyme electrophoresis. Among 12 gene–enzyme systems analysed, GPD, 6GPD and PGM were polymorphic, ACON, G6PD, GPI, 1DH, LAP, MDH, ME, PEP‐A and PEP‐B were monomorphic. Allozyme frequencies were analysed in relation to geographical and climatic factors, and the presence or absence of Trypanosoma cruzi infection. At one locality (Vallegrande, Bolivia), the frequency of 6Pgd‐1 was significantly higher in infected (41% of 85) than in uninfected (17% of 83) adult T. infestans, although no such difference was found among nymphs (n = 347). From other localities, only insects infected with T. cruzi were subjected to isozyme analysis. Populations of T. infestans within villages showed panmixia, while genetic differentiation of T. infestans between villages was correlated with the distance between them. The genetic structure of T. infestans natural populations followed an ‘isolation by distance’ model, involving a series of founder effects followed by genetic drift, rather than adaptation in response to differential selection pressures. This conforms with circumstantial evidence that T. infestans spread, mainly in association with recent human migrations, from a source, probably in southern Bolivia. Isoenzyme characterization of populations of T. infestans could be used to infer sources of re‐infestation during the surveillance phase of control programs.
Mesocyclops longisetuseffects on survivorship ofAedes aegyptiimmature stages in car tyres
Authors: Manrique‐Saide Pablo , Ibáñez‐Bernal Sergio , Delfín‐González Hugo , Tabla Victor Parra
Published: March 2003

Abstract.The effect of the introduction of the entomophagous copepod Mesocyclops longisetus (Acuacultura F.C.B. strain) on the survival of Aedes aegypti immature stages in car tyres was evaluated under semi‐natural conditions in the municipality of Merida, Yucatan, Mexico. Life tables were constructed for the immature stages of the mosquito in the presence and absence of M. longisetus, and the survival data were compared using log–linear models. The data set was adjusted using the GLIM statistical package and the quality of adjustment was evaluated with a chi‐squared test. Survivorship curves were constructed for each treatment.

In the absence of M. longisetus, the survivorship of Ae. aegypti immature stages averaged 9%. The highest mortality rate was observed during the fourth larval instar (54%) and the resulting survival pattern corresponded to a type II survivorship curve. The mortality rate of Ae. aegypti first‐instar larvae (fifty per tyre) increased more than 200‐fold in the presence of M. longisetus (twenty per tyre) and the highest mortality was during the first two larval instars, where it reached 98.9%, with a resulting survivorship of 0.2%. Overall mortality was sixfold greater in the presence of the copepod than in its absence. The survival pattern of immature stages of Ae. aegypti in the presence of the copepod corresponded to a type III survivorship curve. As M. longisetus was so effective against Ae. aegypti immature stages in tyres under semi‐natural conditions, its long‐term effectiveness should be evaluated under socially and ecologically realistic field conditions in Mexico.
Abundance of house dust mites in relation to climate in contrasting agricultural settlements in Israel
Authors: Mumcuoglu K. Y. , Gat Z. , Horowitz T. , Miller J. , Bar‐Tana R. , Ben‐Zvi A. , Naparstek Y.
Published: March 2003

The correlation between climatic conditions and mite numbers in houses from rural areas was studied in 13 agricultural communities (kibbutzim and moshavim) in nine geo‐climatic subregions of Israel. Mites were present in 97% of the dust samples. The average number of mites per gram of dust in the different localities ranged between 84 and 2053. The maximum number of mites (7440/g dust) was found in a carpet from a house in Geva Carmel in the northern coastal region. The most prevalent species of mites were Dermatophagoides pteronyssinus and Dermatophagoides farinae, which were found in 85.6% and 71.3% of the samples, respectively. The house dust mites D. pteronyssinus, D. farinae and Euroglyphus maynei constituted 94.8% of the mites. Most of the mites were isolated from the carpets and sofas (37.0% and 33.7%, respectively), and a smaller number from beds (29.3%). The smallest number of mites (≤ 250/g dust) were found at a minimum relative humidity (RH) of 30% and lower, with a maximum temperature of 32°C and higher, i.e. in the Jordan valley and Negev mountains. A greater number of mites (250–500/g dust) were found at a minimum ambient RH of 35–40% and a maximum temperature of 32°C and higher, i.e. the Hula valley. A large number of mites (500–1000/g dust) were found at a minimum RH of 35–40% with a maximum temperature of 30°C and lower, i.e. in the Judean and Samarian range, as well as in upper Galilee. The largest number of mites (1000–2000/g dust) was found at a minimum RH of 45% and higher, with a maximum temperature ranging between 30 and 32°C. These conditions occur in the coastal strip, the coastal plain and in the Judean and Samarian foothills. A monthly examination of two houses in Zova, a kibbutz in the Judean hills next to Jerusalem, and two houses from Palmachim, a kibbutz in the coastal region, revealed that the highest prevalence of mites was found in the months April–November and May–November, respectively. In Zova, the highest number of mites were found during the months of June and July while the highest concentrations of D. pteronyssinus‐antigen (Der p I) were measured during the month of September. A positive correlation between mite numbers and the quantity of Der p I in house dust was found.
Diapause, pupation sites and parasitism of the horn fly, Haematobia irritans, in south‐eastern Brazil
Authors: Mendes J. , Linhares A. X.
Published: March 2003

In order to verify the occurrence of diapause, preference for pupation sites and hymenopteran parasitism, the pupae of the horn fly, Haematobia irritans (Diptera: Muscidae), were collected from undisturbed cattle dung pats in pastures, and adults of the fly were sampled from cattle in São Paulo State, south‐eastern Brazil, from April 1993 to July 1994. Diapause was verified in 7.7% of pupae sampled from pastures in June and July of 1993 and in 9.9% of those sampled in May, June and July of 1994 (overall rate of 9.1%). Approximately 8.3% of the pupae were parasitized by microhymenopterans, mostly Spalangia nigroaenea and S.cameroni (Hymenoptera: Pteromalidae). Horn fly pupae were found almost exclusively inside the pat or in the soil immediately beneath and adjacent to it, and very few were collected elsewhere. Pupa mortality was 54.4% and did not change significantly during the year, but mortality was greater among pupae collected in pastures when compared to those obtained from experimental pats, lacking natural enemies.
Scanning electron microscoscopy of the second‐instar larva of Gasterophilus nasalis
Authors: Leite A. C. R. , Scott F. B.
Published: March 2003

The second‐instar larva of the bot fly Gasterophilus nasalis (L.) (Diptera: Gasterophilidae) is described for the first time, based on scanning electron microscope (SEM) studies. On the pseudocephalum the larva bears an anteno‐maxillary sensory complex formed by the antenna (coeloconic sensilla) and the maxillary palp with a set of six coeloconic sensilla and four basiconica sensilla. The oral opening is latero‐posteriorly limited by small spines, and exhibits strongly ornamented maxillae and mandibles. The thoracic and abdominal segments are circled by two bands, each with two rows (except the last segment that has one row) of backwardly pointed spines, and have cuticular depressions. Trichoid and campaniform sensilla surround the larval segments. The anterior spiracular opening is a small aperture. The terminal end of the eighth abdominal segment shows a spiracular cavity, lateral tubercles, eight basiconic and two trichoid sensilla. Each spiracular plate has two slightly curved slits, each with a serrated rima. There is a probable ecdysial scar. The findings of this ultrastructural study are compared with those other of larval flies.
Elevated oxidase and esterase levels associated with permethrin tolerance in Anopheles gambiae from Kenyan villages using permethrin‐impregnated nets
Authors: Vulule J. M. , Beach R. F. , Atieli F. K. , Mcallister J. C. , Brogdon W. G. , Roberts J. M. , Mwangi R. W. , Hawley W. A.
Published: March 2003

The permethrin tolerance (PT) of a population of the mosquito Anopheles gambiae (Diptera: Culicidae) increased following the introduction of permethrin‐impregnated nets for malaria control in certain villages near Kisumu, western Kenya. Using a biochemical test that indirectly measures oxidases associated with permethrin resistance, we found that this population had higher oxidase levels than a comparison population from villages without impregnated nets. Mosquitoes from a colony of An. gambiae selected for PT, the RSP (reduced susceptibility to permethrin) strain, were exposed to permethrin with or without the oxidase inhibitor piperonyl butoxide (PB). Significantly higher mortality rates occurred when permethrin was synergized by PB, presumably by suppression of oxidases responsible for PT. An unselected (UNS) colony of An. gambiae that was more susceptible than RSP in a permethrin‐susceptibility bioassay (i.e. LT50 22 min for UNS, vs. 42 min for RSP) was compared with the RSP colony for levels of oxidases and esterases. The levels of both enzymes were very significantly higher in the RSP strain (P < 0.0001). We speculate that use of impregnated nets selected for higher oxidase and esterase levels in An. gambiae to metabolize permethrin acquired from the nets. Both oxidase and esterase mechanisms could confer cross‐resistance to other pyrethroids.