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J Craven

Publications and source records attributed to J Craven.

At least 19 recordsLinked to original sources
PubMed2002

The effects of body composition on the pharmacokinetics of subcutaneously injected ivermectin and moxidectin in pigs.

Macrocyclic lactones are characterized by their long persistence in animals because of their extensive distribution into fat. This study examined the influence of body condition on the disposition of ivermectin (IVM) and moxidectin (MXD) in blood and fat following subcutaneous (s.c.) drug administration. 'Fat' and 'thin' lines of pigs were established using two different diets. All animals were then injected with either MXD or IVM at 300 microg/kg and blood samples were taken at regular intervals until slaughter. Two IVM-treated animals from each diet group were slaughtered at either 3 days or 3 weeks posttreatment. Two MXD-treated animals from each diet group were slaughtered at 3 days, 3, 6 or 9 weeks after treatment. Samples of backfat were taken from all animals at slaughter. Fluorescence HPLC was used to determine the concentrations of MXD or IVM in the plasma and fat samples. The plasma IVM concentration peaked more rapidly in the thin IVM treated pigs compared with the fat pigs. The concentration of IVM in backfat was significantly lower in the thin animals slaughtered 3 weeks after treatment. The MXD plasma concentration peaked within the first hour in both the thin and fat groups, but from 12 h posttreatment there was a higher MXD concentration in the plasma of the fat pigs resulting in MXD being detectable in these pigs for 28 days compared with only 17 days in the thin pigs. Despite this difference in plasma persistence no differences were seen in the MXD concentration of backfat between fat and thin animals. Body condition influenced the kinetic disposition of IVM and MXD following s.c. drug administration with both drugs being less persistent in thin compared with fat animals.

Adipose Tissue↗
PubMed2002

Does the rate of fat deposition influence the pharmacokinetic disposition of subcutaneously administered moxidectin and ivermectin in pigs?

Body condition has been shown to affect the pharmacokinetics of subcutaneously administered macrocyclic lactone anthelmintics but the underlying mechanism is unknown. This study examined the effect of different rates of fat deposition on the pharmacokinetics of moxidectin (MXD) and ivermectin (IVM). All animals initially received a diet with a high linoleic acid content for 7 weeks. One group of animals then received a normal grower diet while the other half received a maintenance ration. Within each diet group, animals were treated with either IVM (n = 4) or MXD (n = 4) or remained as untreated controls (n = 2). There was no difference in the proportion of linoleic acid between the drug treated groups and the untreated controls at any time throughout the study. At 4 and 9 weeks after treatment there was a significantly lower proportion of linoleic acid in the pigs fed the normal ration indicating a greater fat deposition in these animals compared with those that received the maintenance diet. There was an increased persistence of MXD in the plasma of pigs fed the normal ration compared with those fed the maintenance ration. No differences were seen in the kinetic disposition of IVM between pigs fed the maintenance or normal ration. Reducing the rate of fat deposition influenced the pharmacokinetic disposition of the highly lipophilic MXD but did not influence the pharmacokinetic disposition of the less lipophilic IVM.

Adipose Tissue↗
PubMed2001

Pharmacokinetics of moxidectin and ivermectin following intravenous injection in pigs with different body compositions.

Macrocyclic lactones (ML) are highly effective anthelmintics that provide a long protective period after administration because of their extensive distribution into fat. This study examined whether the body composition of the animal at the time of treatment had any influence on the pharmacokinetics of two MLs, moxidectin (MOX) and ivermectin (IVM). 'Fat' and 'lean' lines of pigs were established using two different diets, with weekly determination of liveweight and backfat thickness confirming the difference in body condition between the groups. Blood samples were taken at regular intervals following i.v. injection of IVM or MOX at a dose of 300 microg/kg and the plasma was analysed using fluorescence high performance liquid chromatography (HPLC) to determine the concentration of IVM or MOX in the samples. Regardless of body composition IVM and MOX kinetics were very different with MOX having a greater apparent volume of distribution, longer distribution and elimination half-lives and a slower clearance rate than IVM, which led to MOX being detectable in plasma for >40 days compared with only 8-10 days for IVM. Altering body composition had no detectable influence on the kinetic disposition of IVM in this study. In contrast, although there was no difference in AUC or the volume of distribution, MOX was distributed within and eliminated from the lean animals more rapidly than from the fat animals.

Animals↗
PubMed2000

Use of a migration assay for the separation of adult pyrantel-susceptible and -resistant oesophagostomum dentatum.

A migration assay was used to separate a pyrantel-susceptible and -resistant isolate of the pig nematode, Oesophagostomum dentatum. The experiment had three steps. In the first step, LD(50) values for pyrantel of the two isolates in the assay were established. In the second step, susceptible and resistant worms were mixed in various proportions prior to exposure to a fixed concentration of pyrantel and thereafter assayed. The inhibition of migration showed to be linearly correlated with the proportion of resistant worms in a sample. In step three, this line was used as a standard curve to predict the number of resistant worms in samples from pigs infected with mixed samples of susceptible and resistant larvae.

Animals↗
PubMed2000

That smile.

Explore the source record for details and available documents.

Adult↗
PubMed2000

Sample size calculation for clinical trials: the impact of clinician beliefs.

The UK Medical Research Council (MRC) randomized trial of gastric surgery, ST01, compared conventional (D1) with radical (D2) surgery. Sample size estimation was based upon the consensus opinion of the surgical members of the design team, which suggested that a change in 5-year survival from 20% (D1) to 34% (D2) could be realistic and medically important. On the basis of these survival rates, the sample size for the trial was 400 patients. However, this trial was exceptional in the way that a survey of surgeons' opinions was made at the start of the trial, in 1986, and again before results were analysed but after termination of the trial in 1994. At the initial survey, the three surgeons from the trial steering committee and 23 other surgeons experienced in treating gastric carcinoma were given detailed questionnaires. They were asked about the expected survival rate in the D1 group, anticipated difference in survival from D2 surgery, and what difference would be medically important and influence future treatment of patients. The consensus opinion of those surveyed was that there might be a survival improvement of 9.4%. In 1994, prior to closure of the trial, and before any survival information was disclosed, the survey was repeated with 21 of the original 26 surgeons. At this second survey, the opinion of the trial steering committee was that 9.5% difference was more realistic. This was in accord with the opinion of the larger group, which remained little changed since 1986. The baseline 5-year D1 survival was thought likely to be about 32%, which corresponded closely to the actual survival of recruited patients. Revised sample size calculations suggested that, on the basis of these more recent opinions, between 800 and 1200 patients would have been required. Both surveys assessed the level of treatment benefit that was deemed to be sufficient for causing surgeons to change their practice. This showed that the 13% difference in survival used as the study target was clinically relevant, but also indicated that many clinicians would remain unwilling to change their practice if the difference is only 9.5%. The experience of this carefully designed trial illustrates the problems of designing long-term, randomized trials. It raises interesting questions about the common practice of basing sample size estimates upon the beliefs of a trial design committee that may include a number of enthusiasts for the trial treatment. If their opinion of anticipated effect sizes drives the design of the trial, rather than the opinion of a larger community of experts that includes sceptics as well as enthusiasts, there is likely to be a serious miscalculation of sample size requirements.

Bayes Theorem↗
PubMed1999

A comparison of in vitro tests and a faecal egg count reduction test in detecting anthelmintic resistance in horse strongyles.

This study reports a comparison between faecal egg count reduction test (FECRT), egg hatch assay (EHA) and larval development assay (LDA) for detecting anthelmintic resistance in equine strongyles. Resistance to benzimidazoles was demonstrated in 33 of 42 (79%) farms tested by FECRT and in 32 (62%) of the 52 farms tested by EHA. As the reference strain used was not fully susceptible to benzimidazoles it was not possible to determine the level of resistance by LDA. Pyrantel resistance was indicated on three of 15 farms by faecal egg count reduction. Resistance was also indicated by LDA for one of these farms. In addition resistance was indicated by LDA on two more farms that were not tested by FECRT. Further testing is needed to confirm if these findings are truly indicative of resistance. Generally, correlations between the tests were poor and it was not possible to use the outcome of one test to predict the outcome of another.

Animals↗
PubMed1999

Patient survival after D1 and D2 resections for gastric cancer: long-term results of the MRC randomized surgical trial. Surgical Co-operative Group.

Controversy still exists on the optimal surgical resection for potentially curable gastric cancer. Much better long-term survival has been reported in retrospective/non-randomized studies with D2 resections that involve a radical extended regional lymphadenectomy than with the standard D1 resections. In this paper we report the long-term survival of patients entered into a randomized study, with follow-up to death or 3 years in 96% of patients and a median follow-up of 6.5 years. In this prospective trial D1 resection (removal of regional perigastric nodes) was compared with D2 resection (extended lymphadenectomy to include level 1 and 2 regional nodes). Central randomization followed a staging laparotomy. Out of 737 patients with histologically proven gastric adenocarcinoma registered, 337 patients were ineligible by staging laparotomy because of advanced disease and 400 were randomized. The 5-year survival rates were 35% for D1 resection and 33% for D2 resection (difference -2%, 95% CI = -12%-8%). There was no difference in the overall 5-year survival between the two arms (HR = 1.10, 95% CI 0.87-1.39, where HR > 1 implies a survival benefit to D1 surgery). Survival based on death from gastric cancer as the event was similar in the D1 and D2 groups (HR = 1.05, 95% CI 0.79-1.39) as was recurrence-free survival (HR = 1.03, 95% CI 0.82-1.29). In a multivariate analysis, clinical stages II and III, old age, male sex and removal of spleen and pancreas were independently associated with poor survival. These findings indicate that the classical Japanese D2 resection offers no survival advantage over D1 surgery. However, the possibility that D2 resection without pancreatico-splenectomy may be better than standard D1 resection cannot be dismissed by the results of this trial.

Adenocarcinoma↗
PubMed1998

A questionnaire survey on nematode control practices on horse farms in Denmark and the existence of risk factors for the development of anthelmintic resistance.

A questionnaire survey to obtain information on endoparasite control practices and management on 68 Danish horse farms was undertaken in 1995. The study revealed that foals, young horses and adults were on average, annually treated 4.3, 4.0 and 3.7 times, respectively. The most commonly used drug from 1993-1995 was ivermectin. On average 2.4 different drugs were used annually. The most used method of weight estimation was eye measure: for foals by 78%, for youngsters by 81% and adults by 82% of the herd owners. The most commonly used weight in the dosing of anthelmintics was individual weights of the horse: 72% of the herd owners dosed their foals this way. 76% their youngsters and 75% their adults. Sixty two percent of the herd owners treated at turn out, 47% at housing, 57% treated when buying new horses, 26% treated when stabling visiting horses, 78% applied pasture change and 18% performed alternate/mixed grazing. Sixty one percent of the herds had experienced problems with diarrhoea and in 18% of the cases the suspected cause was considered to be endoparasites. 33% of the farms performed disease registration and on 25% Faecal Egg Count Reduction tests had been performed before entering this study. The herd owners obtained their formation about endoparasite control from veterinarians, meetings and papers in that order of importance.

Animal Husbandry↗
PubMed1998

Survey of anthelmintic resistance on Danish horse farms, using 5 different methods of calculating faecal egg count reduction.

This study reports on the prevalence of anthelmintic resistance in strongyles of horses in Denmark. Of 5 methods used for the calculation of faecal egg count reduction (FECR) the method recommended by the World Association for the Advancement of Veterinary Parasitology, for the detection of resistance in sheep was the most sensitive procedure for detecting resistance. Using this method benzimidazole resistance was detected on 33 of 42 farms (79%) examined. Pyrantel was tested on 15 farms and FECR tests indicate resistance on 3 (30%) farms. On 2 farms on which resistance to pyrantel was detected resistance to benzimidazoles was also detected. On one of 16 farms examined ivermectin resistance was indicated at Day 14 but not at Day 19. On the 15 remaining farms ivermectin was effective. Due to the high prevalence of anthelmintic resistance in Danish horse herds it is recommended that tests of anthelmintic efficacy be conducted routinely to monitor the effectiveness of the strongyle control programmes.

Animals↗
PubMed1997

In vitro characterization of lines of Oesophagostomum dentatum selected or not selected for resistance to pyrantel, levamisole and ivermectin.

Lines of Oesophagostomum dentatum artificially selected or not selected for resistance to pyrantel, levamisole and ivermectin were used in this study. From the 10th generation of selection eggs were collected from each line and subjected to an in vitro larval development assay (LDA) and an egg hatch assay (EHPA). Significant differences were observed between an unselected line of O. dentatum and the lines selected for resistance to levamisole or pyrantel in both assays. The LDA was more sensitive than EHPA in detecting anthelmintic resistance in O. dentatum. The results obtained from the LDA confirmed side-resistance between levamisole and morantel/pyrantel. The in vitro tests failed to show significant differences between ivermectin-sensitive and resistant lines.

Animals↗
PubMed1996

Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. The Surgical Cooperative Group.

BACKGROUND: In Japan the surgical approach to treatment of potentially curable gastric cancer, including extended lymphadenectomy, seems in retrospective surveys to give better results than the less radical procedures favoured in Western countries. There has, however, been no evidence from randomised trials that extended lymphadenectomy (D2 gastric resection) confers a survival advantage. This question was addressed in a trial involving thirty-two surgeons in Europe. METHODS: In a prospective randomised controlled trial, D1 resection (level 1 lymphadenectomy) was compared with D2 resection (levels 1 and 2 lymphadenectomy). Central randomisation (200 patients in each arm) followed a staging laparotomy. FINDINGS: The D2 group had greater postoperative hospital mortality (13% vs 6.5%; p=0.04 [95% Cl 9-18% for D2, 4-11% for D1] and higher overall postoperative morbidity (46% vs 28%; p<0.001); their postoperative stay was also longer. The excess postoperative morbidity and mortality in the D2 group was accounted for by distal pancreaticosplenectomy and splenectomy. In the whole group (400 patients), survival beyond three years was 30% in patients whose gastrectomy included en-bloc pancreatico-splenic resection versus 50% in the remainder. INTERPRETATION: D2 gastric resections are followed by higher morbidity and mortality than D1 resections. These disadvantages are consequent upon additional pancreatectomies and distal splenectomies, and in long-term follow-up the higher mortality when the pancreas and spleen are resected may prove to nullify any survival benefit from D2 procedures.

Adenocarcinoma↗
PubMed1991

Eating disorders and intentional insulin undertreatment in adolescent females with diabetes.

Intentional undertreatment with insulin was found to be a common method of inducing weight loss or preventing weight gain in female adolescents with insulin-dependent diabetes mellitus (IDDM) and eating disorders. More than half of those with eating disorders intentionally omitted insulin to produce hyperglycemia and weight loss. Individuals with eating disorders were also less compliant with other aspects of IDDM management and had poorer metabolic control than the rest of the sample. It is suggested here that intentional undertreatment with insulin in some individuals with IDDM may be regarded as an equivalent to purging, with similar purpose and consequences.

Adolescent↗
PubMed1991

The Endstage Renal Disease Severity Index (ESRD-SI).

Measures of disease severity are required as experimental, control and outcome variables in studies of the psychosocial aspects of physical illness. The Endstage Renal Disease Severity Index (ESRD-SI) was developed for these purposes during a prospective study of patient adjustment to dialysis and endstage renal disease (ESRD). It was found to have adequate inter-rater reliability, test-retest reliability, and construct and predictive validity in two subsamples (total N = 233) of dialysis patients. The ESRD-SI is suitable as a sensitive indicator of disease severity in these patients.

Adaptation, Psychological↗
PubMed1990

Psychiatric aspects of lung transplant. The Toronto Lung Transplant Group.

Psychiatric problems in a consecutive series of lung transplant applicants (n = 116), candidates (n = 57) and recipients (n = 42) are reported. Fifty percent of all the applicants for lung transplantation reported a history of psychiatric disorder including organic brain syndrome (19%), major depressive episode (16%), panic or anxiety disorder not otherwise specified (11%) and alcohol or substance abuse (11%). In most cases, psychiatric problems had occurred in these patients as a complication of endstage lung disease. The most common new diagnoses in candidates awaiting surgery were adjustment disorder with anxious mood and anxiety disorders. Organic brain syndromes developed in over 50% of the recipients during the first two post-operative weeks. The type and prevalence of these disorders have implications for the management of lung transplant patients and those with chronic pulmonary disease.

Adaptation, Psychological↗