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Biomedical subjects

M H Davies

Publications and source records attributed to M H Davies.

At least 19 recordsLinked to original sources
PubMed2004

Spread of marker bacteria from the hides of cattle in a simulated livestock market and at an abattoir.

The spread of microbial contamination on the hides of beef was investigated at two stages in the meat chain: (i) in a simulated livestock market ("the market") using 33 animals, and (ii) in the unloading-to-skinning area of a commercial abattoir using 18 animals. At both stages, harmless bacterial markers (nalidixic acid-resistant Escherichia coli K-12; rifampicin- and nalidixic acid-resistant Pseudomonas fluorescens; and a tetracycline-resistant E. coli) were inoculated on the hides of a small number of selected animals, and their transfer to other animals and the environment was examined. At the market, the initial prevalence of animals positive for the hide markers (9.1% in each phase) introduced in the presale pen, sale ring, and postsale pen changed to 39.4, 15.1, and 54.5%, respectively, by the end of the market process. In addition, widespread contamination of the market environment with the hide markers was observed. At the abattoir, the initial prevalence of animals positive for the hide marker (11.1%) inoculated at unloading increased to 100% (hide before skinning) and 88.8% (skinned carcass). In addition, another marker inoculated on environmental surfaces in lairage pens, races, and stunning box was detected on 83.3% (hide before skinning) and 88.8% (skinned carcass). These results, although obtained with a relatively small number of animals, demonstrate that both the livestock market process and the unloading-to-skinning process at abattoirs can facilitate the extensive spread of microbial contamination on hides not just within, but also between, batches of animals.

Abattoirs↗
PubMed2003

Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding.

UNLABELLED: The management of bleeding gastric varices has not been standardized. Although transjugular intrahepatic portosystemic shunt (TIPS) is used in most centers, endoscopic treatment with N-butyl-2-cyanoacrylate (cyanoacrylate) glue has recently been shown to be effective. Cost-effectiveness analyses of these methods are lacking. METHODS: We performed a retrospective review of patients with bleeding gastric varices treated either by TIPS or cyanoacrylate glue injection. Economic analysis was based on direct costs for a fixed financial year. The two groups were compared for a period of 6 months follow-up, to liver transplantation, or death for each patient. RESULTS: Between January, 1995 and December, 1999, 20 patients with bleeding gastric varices had TIPS; 23 patients had cyanoacrylate glue injection from January, 2000 to October, 2001. There were no significant differences between the two groups in patient characteristics, transfusion requirement, and gastric variceal anatomy. In the TIPS group, 15/20 patients had the procedure performed within 24 h of hemorrhage, and 90% of stent insertions were successful. Complications consisted of two cases of pulmonary edema, two cases of severe encephalopathy, and a 15% stenosis rate at 6 months. In the glue group, there were 3 +/- 1.5 endoscopies and 2 +/- 1 injections per patient, with a 96% initial hemostasis. There was one case of (glue) pulmonary embolism and one blocked front endoscope lens, which required repair. The initial rebleed rate was significantly lower in patients who had TIPS (15% vs 30%, p = 0.005). The inpatient stay was shorter in the glue group (13 +/- 1 vs 18 +/- 2 days, p = 0.05), but there was no difference in the overall mortality rate. The median cost within 6 months of initial gastric variceal bleeding was $4,138 US dollars ($3,009-$8,290 US dollars) for glue versus $11,906 US dollars ($8,200-$16,770 US dollars) for TIPS (p < 0.0001). CONCLUSION: In this comparable group of patients, cyanoacrylate glue injection was more cost effective than TIPS in the management of acute gastric variceal bleeding. A prospective, randomized trial would be required to confirm our analysis.

Acute Disease↗
PubMed2000

The species-dependent metabolism of efavirenz produces a nephrotoxic glutathione conjugate in rats.

Efavirenz, a potent nonnucleoside reverse transcriptase inhibitor widely prescribed for the treatment of HIV infection, produces renal tubular epithelial cell necrosis in rats but not in cynomolgus monkeys or humans. This species selectivity in nephrotoxicity could result from differences in the production or processing of reactive metabolites, or both. A detailed comparison of the metabolites produced by rats, monkeys, and humans revealed that rats produce a unique glutathione adduct. The mechanism of formation and role of this glutathione adduct in the renal toxicity were investigated using both chemical and biochemical probes. Efavirenz was labeled at the methine position on the cyclopropyl ring with the stable isotope deuterium, effectively reducing the formation of the cyclopropanol metabolite, an obligate precursor to the glutathione adduct. This substitution markedly reduced both the incidence and severity of nephrotoxicity as measured histologically. Further processing of this glutathione adduct was also important in producing the lesion and was demonstrated by inhibiting gamma-glutamyltranspeptidase with acivicin pretreatment (10 mg/kg, IV) prior to dosing with efavirenz. Again, both the incidence and severity of the nephrotoxicity were reduced, such that four of nine rats given acivicin were without detectable lesions. These studies provide compelling evidence that a species-specific formation of glutathione conjugate(s) from efavirenz is involved in producing nephrotoxicity in rats. Mechanisms are proposed for the formation of reactive metabolites that could be responsible for the renal toxicity observed in rats.

Alkynes↗
PubMed2000

Production factors that influence the hygienic condition of finished beef cattle.

A survey was conducted at five UK abattoirs to trace the source of dirty beef cattle and identify factors in the production chain that contributed to their dirtiness. The Meat Hygiene Service Clean Livestock score categories were used and the animals' histories were traced back to their farm of origin. Comprehensive information was collected relating to the farm, transport and lairage phases for 675 cattle from 85 batches. The mean score of the animals on arrival at the abattoir was 1.57, with 2.8 per cent in categories 3 and 4, and none in category 5. Regression analysis, blocking the data by farm of origin, revealed that age, feed type, coat length, clipping, journey distance and time, and abattoir were the six principal factors that affected the scores. Cattle under 20 months of age were cleaner than older cattle. Dry diets resulted in lower scores than wet diets. 'Shorthair' cattle were cleaner than 'medium' or 'longhair' cattle, and cattle which had been clipped were cleaner than unclipped animals. The cattle which had travelled over 150 miles (15 per cent) were dirtier than the others. Within each abattoir there were variations in score between 1 and 4, and the mean scores of the five abattoirs ranged from 1.19 to 1.76. A significant part of this variation could only be accounted for by unmeasured variables such as abattoir management practice, assessors' categorisations and climate.

Abattoirs↗
PubMed2000

Hepatocellular carcinoma in the cirrhotic liver: double-contrast MR imaging for diagnosis.

PURPOSE: To measure the sensitivity and accuracy of double-contrast magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC) in the cirrhotic liver. MATERIALS AND METHODS: Twenty-seven patients with MR features of dysplastic nodules and/or HCC were examined. T2-weighted spin-echo and T1-weighted gradient-echo imaging was performed before and after superparamagnetic iron oxide (SPIO) administration and immediately followed by T1-weighted gradient-echo imaging at 10, 40, and 120 seconds after bolus injection of a gadolinium-based contrast material. Nonenhanced, nonenhanced plus SPIO-enhanced, and nonenhanced plus SPIO-enhanced plus gadolinium-enhanced images were reviewed. Alternative-free response receiver operating characteristic (ROC) methodology was used to analyze the results, which were correlated with histopathologic findings after transplantation in 15 patients and at biopsy in 12. Lesions visualized with all three techniques were characterized as a dysplastic nodule or HCC, and ROC analysis was performed. RESULTS: For all observers, SPIO-enhanced MR imaging (mean accuracy, 0.76) was more accurate than nonenhanced MR imaging (mean accuracy, 0.64) (P <.04), and double-contrast MR imaging (mean accuracy, 0.86) was more accurate than SPIO-enhanced imaging (P <.05). Both types of lesions were correctly characterized with all three techniques, although observer confidence for lesion characterization was greatest with double-contrast MR imaging. CONCLUSION: Double-contrast MR imaging significantly improves the diagnosis of HCC compared with SPIO-enhanced and nonenhanced imaging (P <.01).

Adult↗
PubMed1999

Pretransplant prediction of prognosis after liver transplantation in primary sclerosing cholangitis using a Cox regression model.

Liver transplantation remains the only treatment for patients with end-stage primary sclerosing cholangitis (PSC); however, selection criteria for the procedure and its timing remains uncertain. The aim of this study was to identify pretransplant variables associated with survival after transplantation and to devise a Cox regression model for prediction of post-transplant survival. We studied 118 patients transplanted for PSC at the Queen Elizabeth Hospital, Birmingham, UK, being followed for up to 91/4 years after the procedure. The association between pretransplant data and the post-transplant survival up to 1 year was studied using the logrank test (univariate analyses) and Cox multiple regression analysis. Univariate analyses showed the following variables to be associated with a decreased post-transplant survival: high serum creatinine, high serum bilirubin, biliary tree malignancy, previous upper abdominal surgery, hepatic encephalopathy, ascites, and Crohn's disease, whereas ulcerative colitis was associated with increased post-transplant survival (all P </=.05). The final multiple Cox regression model included the following significant variables: inflammatory bowel disease, ascites, previous upper abdominal surgery, serum creatinine, and biliary tree malignancy (all P <.03). Biliary tree malignancy could be omitted from the Cox model with only slight loss of information. The results were validated using the data of 30 independent PSC patients from another center. These results can improve selection of patients with PSC for liver transplantation. The developed prognostic model for transplantation can be used in parallel with previously published prognostic models for nontransplantation. The obtained prognostic estimates will provide additional information that is useful for optimal timing of liver transplantation in the individual patient.

Adult↗
PubMed1999

Tacrolimus in liver transplantation.

Tacrolimus has been in clinical use for ten years. It was launched in a hail of publicity following the successful treatment of cases with apparently irreversible rejection using conventional immunosuppressive therapies. Since that time, the overall experience with the drug has increased considerably. The purpose of this article is to review tacrolimus comprehensively, including evidence derived from major clinical trials, to enable the reader to become familiar with its clinical role, including a comparison with its main competitor, cyclosporin. Tacrolimus was discovered in 1984, it predominantly acts via inhibition of T-cell mediated immunity, and to a lesser extent B-cell humoral immunity. The agent was introduced into clinical medicine in 1989 and was soon shown to be a highly effective immunosuppressive agent, receiving approval in 1994 by the Food and Drug Administration (FDA) for primary immunosuppression in adult and paediatric liver transplantation. Tacrolimus has proved to be a major development in transplantation. Whilst the available data have been hindered to some extent by deficiencies of trial design in the major studies, there is still more comparative clinical data available for tacrolimus than for any of its predecessors. The overall balance of risk benefit is considered by many to be tipped in favour of tacrolimus; it is likely that with more long-term follow-up results becoming available in liver and other solid organ transplants, the benefits will appear clearer.

Journal Article↗
PubMed1996

Exogenous interferon delays luteal regression in red deer hinds (Cervus elaphus) by suppressing steroid-induced endometrial oxytocin sensitivity.

Three groups of intact hinds (n = 10-18) and one group of ovariectomized hinds were treated with progesterone by mean, of Controlled Internal Drug Releasing (CIDR) devices for 13 days (device removal = Day 0). Group 1 served as controls; group 2 received injections of 4 mg recombinant bovine interferon-alpha,1 twice daily from Days 13 to 21; group 3 was run with a stag from Days 0 to 3, and all hinds were subsequently diagnosed pregnant; group 4 (ovariectomized) was treated with CIDR devices and estradiol to mimic steroid secretion during the estrous cycle. Progesterone profiles were determined from thrice-weekly plasma samples from Days -13 to 28. Rectal temperature was measured in a subset of groups 1 and 2 from Days 9 to 21. Oxytocin-induced prostaglandin F2 alpha release was measured in a subset of groups 1, 2, and 4 on Days 2, 4, 10, 16, and 18. Data are presented as means +/- SEM. Exogenous interferon delayed luteolysis (> or = 28 vs. 21.2 +/- 0.55 days, P < 0.0005) and induced transient pyrexia after the first injection (39.89 +/- 0.11 vs. 38.88 +/- 0.19 degrees C, p < 0.0005). Incidence of oxytocin-induced PGF2 alpha release in control hinds was greater on Days 2 and 18 than on Days 4 and 10 (8/8 and 7/8 vs. 3/8 and 0/8, respectively; p < 0.05) and was greater in control than in interferon-treated hinds on Days 16 and 18 (5/8 and 7/8 vs. 1/8 and 1/8, respectively; p < 0.05). Profiles of plasma progesterone concentration and oxytocin sensitivity in steroid-treated ovariectomized hinds did not differ from those in control hinds. These results suggest that steroid-controlled uterine oxytocin sensitivity is important in luteolysis and is suppressed by the administration of interferon, the putative embryonic pregnancy recognition signal in red deer.

Administration, Intravaginal↗
PubMed1995

Sulphoxidation and sulphation capacity in patients with primary biliary cirrhosis.

We have previously reported an association of impaired S-oxidation with primary biliary cirrhosis. In order to confirm and further define this relationship, we retested S-oxidation capacity via three metabolic pathways and sulphation capacity via a fourth pathway. Metabolism of S-carboxymethyl-L-cysteine is polymorphic -20% of healthy individuals being poor S-oxidisers. We found 26% with primary biliary cirrhosis were poor S-oxidisers, compared with 36% with other liver disease and 25% of healthy controls. Differences were not statistically significant. S-oxidation of ranitidine is dependent upon flavin mono-oxygenases. We showed a non-significant trend toward less S-oxide in primary biliary cirrhosis and other liver disease, compared with healthy controls, with no significant difference between disease groups. Conversion of cysteine to sulphate depends predominantly on cysteine dioxygenase. Impaired activity may be reflected by decreased plasma sulphate and elevated cysteine. We found that the plasma cysteine: sulphate ratio was significantly elevated not only in primary biliary cirrhosis (p < 0.0001), but also in other liver disease (p < 0.0001), compared with healthy individuals. Sulphation capacity was studied by analysing paracetamol metabolism. Paracetamol sulphate and sulphate: glucuronide ratio were reduced in primary biliary cirrhosis compared with normal individuals, (p < 0.05). A trend towards less sulphate in primary biliary cirrhosis compared other liver disease was not significant (p = 0.42). We conclude that although sulphation and some sulphoxidation pathways are impaired in primary biliary cirrhosis, we can currently find no evidence to substantiate the hypothesis that primary biliary cirrhosis is a disease specifically associated with poor S-oxidation, as assessed via these metabolic pathways.

Acetaminophen↗
PubMed1995

Fetal mortality associated with cholestasis of pregnancy and the potential benefit of therapy with ursodeoxycholic acid.

Cholestasis of pregnancy is associated with increased fetal morbidity and mortality and should be treated actively. The significance attached to pruritus in pregnancy is often minimal, but it is a cardinal symptom of cholestasis of pregnancy, which may have no other clinical features. Eight women with previous cholestasis of pregnancy were referred to The Liver Unit within a 12 month period for advice concerning future pregnancies. Thirteen pregnancies had been affected by cholestasis of pregnancy and 12 had been treated expectantly with resultant perinatal morbidity or mortality in 11 (one normal delivery), including; eight stillbirths, two premature deliveries with fetal distress (one died in perinatal period), and an emergency caesarean section for fetal distress. The other pregnancy was treated actively and delivery was uncomplicated. Subsequently, three of these cases with recurrent cholestasis of pregnancy were referred while pregnant. In each, cholestasis developed with severe pruritus, gross increase of serum bile acids, and deranged liver tests. Each was treated with the choleretic agent ursodeoxycholic acid, with rapid clinical improvement and resolution of deranged biochemistry. In conclusion, cholestasis of pregnancy continues to be treated expectantly despite its association with increased morbidity and mortality and evidence suggesting improved prognosis with active treatment and the potential of reducing the associated perinatal mortality. In an uncontrolled series of three patients with cholestasis of pregnancy, ursodeoxycholic acid seemed to provide safe and effective therapy.

Adult↗
PubMed1994

Recovery despite impaired cerebral perfusion in fulminant hepatic failure.

We report 4 patients with fulminant hepatic failure who developed prolonged intracranial hypertension (> 35 mm Hg for 24-38 h) that was refractory to standard therapy and associated with impaired cerebral perfusion pressure (< 50 mm Hg for 2-72 h). All survived with complete neurological recovery. Refractory elevation of intracranial pressure and reduced cerebral perfusion pressure are generally thought to contra-indicate liver transplantation in hepatic failure and are indications to withdraw support. Our observations challenge this concept.

Adult↗
PubMed1994

Antibiotic-associated acute vanishing bile duct syndrome: a pattern associated with severe, prolonged, intrahepatic cholestasis.

We report cases of amoxycillin- and flucloxacillin-induced liver damage associated with an acute vanishing bile duct syndrome. Ductopenia was present at the time of first liver biopsy, 3 weeks and 3 months after administration of the two drugs, respectively. Ductopenia apparently occurred as the primary lesion, with no evidence of accompanying portal tract inflammation. Subsequent biopsies showed a persistent paucity of ducts, accompanied by increasing features of chronic cholestasis. Biochemical dysfunction persists at 2 year's follow-up and late prognosis remains guarded.

Abscess↗
PubMed1994

The adverse influence of pregnancy upon sulphation: a clue to the pathogenesis of intrahepatic cholestasis of pregnancy?

Sulphation of oestrogens and monohydroxy bile acids is important in attenuating their cholestatic potential. Thus, impairment of sulphation could lead to retention of cholestatic compounds and precipitate intrahepatic cholestasis in susceptible individuals. We tested the hypothesis that such a mechanism may be involved in the pathogenesis of intrahepatic cholestasis of pregnancy. In vivo and in vitro assessment of sulphation capacity was performed in patients with cholestasis of pregnancy, compared with control females on and off the oestrogen-containing oral contraceptive pill and control individuals during normal pregnancy and post partum, to assess the influence of high oestrogen states upon this metabolic pathway. During in vivo studies utilising paracetamol as a metabolic probe, the proportion of paracetamol sulphate and sulphate: glucuronide ratio were decreased in those with elevated oestrogens, whether the rise in oestrogens was endogenous, in pregnancy (paracetamol sulphate p < 0.05; paracetamol sulphate:glucuronide ratio p < 0.01), or exogenous, with the contraceptive pill (paracetamol sulphate p = 0.2; paracetamol sulphate:glucuronide ratio p < 0.001). In vitro, platelet sulphotransferase activity was measured, utilising phenol as substrate. Sulphotransferase activity decreased during pregnancy compared with repeat measurements post partum (p < 0.005) and compared with non-pregnant individuals (p < 0.05). In conclusion, we have shown that elevated oestrogens are associated with significant impairment in sulphation capacity. An imbalance of sulphation with glucuronidation provoked by high circulating oestrogen levels may be contributory in the pathogenesis of cholestasis of pregnancy.

Acetaminophen↗
PubMed1994

Plasma cysteine and sulphate levels in patients with cirrhosis of the liver.

1. Fasting levels of plasma cysteine, plasma sulphate and the plasma cysteine/sulphate ratio were measured in patients with primary biliary cirrhosis and compared with those in patients with other liver disease, general intensive therapy unit patients and healthy subjects. 2. Plasma cysteine was significantly elevated in patients with primary biliary cirrhosis (median 0.364 nmol/mg of protein, P < 0.0001) and patients with other liver disease (median 0.445 nmol/mg of protein, P < 0.0001), compared with healthy control subjects (median 0.125 nmol/mg of protein) and increased progressively with the severity of liver disease. Plasma cysteine was also elevated in intensive therapy unit patients (median 1.564 nmol/mg of protein) compared with healthy control subjects (P < 0.0001) and patients with other liver disease (P < 0.0001). 3. Plasma sulphate was reduced significantly only in patients with primary biliary cirrhosis (median 0.822 nmol/mg of protein) compared with healthy control subjects (median 1.37 nmol/mg of protein, P < 0.05). There was no significant difference in plasma sulphate between disease groups. 4. The plasma cysteine/sulphate ratio was significantly elevated in patients with primary biliary cirrhosis (median 0.448, P < 0.0001) and patients with other liver diseases (median 0.394, P < 0.0001) compared with healthy control subjects (median 0.095). The ratio was also elevated in intensive therapy unit patients (median 1.650, P < 0.0001) compared with healthy control subjects and liver disease groups (P < 0.0001). 5. In conclusion, cysteine rises in primary biliary cirrhosis and other forms of liver disease. This effect is not specific to liver disease, since cysteine is elevated in an heterogeneous group receiving intense care.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗