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D Beales

Publications and source records attributed to D Beales.

17 recordsLinked to original sources
PubMed2003

Multimedia article. Laparoscopic Ladd's procedure in two adults: malrotation and the minimally invasive approach.

Malrotation is an intestinal rotation anomaly rarely diagnosed in adults. In the adult patient, obstructing peritoneal bands may lead to nausea and abdominal distention. Familiarity with this presentation as well as the aberrant anatomy associated with the unusual problem facilitates surgical treatment. While the minimally invasive approach requires meticulous dissection due to this abnormal anatomy, laparoscopic treatment does provide the advantages of short convalescence and low morbidity. This video briefly reviews embryologic intestinal development, rotational anomalies and two laparoscopic Ladd's procedures.

Digestive System Surgical Procedures↗
PubMed1996

Protection in the late stages of paracetamol-induced liver cell injury with fructose, cyslosporin A and trifluoperazine.

A fixed combination of the three components, fructose, cyclosporin A and trifluoperazine (FCAT), was found to protect in the late stage of paracetamol-induced liver cell injury both in vivo and in an in vivo/in vitro system. Rats pre-induced with phenobarbitone were given a paracetamol dose of 1 g/kg i.p. The combination of FCAT was given orally 3 h or 3 and 8 h after paracetamol and was able to afford protection as seen by measurements of plasma alanine transaminase (ALT) levels at 24 h. In the in vivo/in vitro system, rats pre-induced with phenobarbitone were dosed with paracetamol 1 g/kg i.p. to initiate injury and liver slices were then taken 3, 4 and 5 h later. The liver slices were then incubated for up to 18 h with the protective agents (FCAT) and the progression of injury followed. Injury was assessed by lactate dehydrogenase (LDH) leakage into the medium and potassium content of the slices. FCAT significantly reduced the injury even as assessed after 5 h in vivo initiation and 18 h progression in vitro. Mitochondrial membrane potential was also maintained in the FCAT-treated liver slices from paracetamol-treated rats as seen by the ability to maintain a gradient of triphenyl methyl phosphonium (TPMP+) between the cell and external medium. All three compounds are required for protection, indicating that more than one event is critical to the survival of the cell and each target point needs to be protected for effective long-term cell survival. The in vivo/in vitro system has been found to give a better comparability to the in vivo situation than injury models that take 6 h or less.

Acetaminophen↗
PubMed1996

Ethanol elimination by rats as a function of reproductive state, gender and nutritional status.

Alcohol elimination was studied in rats of different ages, reproductive states and nutritional deprivation, with the following results: 1) blood levels of ethanol 180 min after a single dose of 1.5 g/kg, ip were significantly higher in adult male (74 days old, N = 5) than in young male rats (34 days old, N = 5): 92.4 +/- 8.4 vs 6.8 +/- 3.4 mg/100 ml, means +/- SD, respectively; 2) when male rats were given a low protein diet for 48 h, blood ethanol levels after a single dose were significantly increased in young males (38.6 +/- 14.6 mg/100 ml) but no effect after a single dose was found in the same animals at an older age (93.2 +/- 5.0 mg/100 ml); 3) blood levels in female rats were higher than in young males both in the virgin and pregnant states, but during lactation a significant drop in blood levels of ethanol was observed. Blood levels of ethanol (mg/100 ml) 180 min after a single dose of 1.5 g/kg, ip, in females, were: virgin (N = 6): 44.9 +/- 16.1, pregnant (N = 5): 40.0 +/- 10.4, lactant (N = 5) 8.8 +/- 5.8. This difference between virgin and pregnant and lactant rats was not related to changes in ADH activity which did not differ between groups. The present study indicates that in male rats the effect of a short-term protein deprivation on ethanol elimination is dependent on the age of the animal. In females, reproductive state is an important factor in determining ethanol elimination.

Age Factors↗
PubMed1995

Cell injury and protection in long-term incubation of liver slices after in vivo initiation with paracetamol: cell injury after in vivo initiation with paracetamol.

Short-term in vitro methods (2-6 h) for study of cell injury by paracetamol are often used but, in vivo, injury is not apparent until 12 h or later. Many agents which protect in the short-term in vitro systems, such as fructose and glycerol which are effective, even in the late phase, after paracetamol has initiated injury, do not provide any protection in vivo. We have extended the in vitro liver slice system to a more realistic 18 h. Secondly, we have initiated injury with paracetamol in vivo, then followed the progression of injury in an in vitro system. Control liver slices incubated in a HEPES Ringer solution with antibiotics over 18 h show little sign of injury as demonstrated by leakage of lactate dehydrogenase (LDH) into the medium or loss of potassium. Liver slices exposed to 10 mM paracetamol for 2 h in vitro show extensive LDH leak at 6 h which is even more severe at 18 h. Liver slices from animals treated with paracetamol (1 g/kg i.p.) in vivo for 3 h show little LDH leakage at 6 h in vitro but by 18 h injury is very apparent. Fructose and glycerol which protect against paracetamol injury in the short-term (6-h) in vitro system, do not do so when observations are extended to 18 h. They also fail to provide any protection to the slice from animals pre-treated in vivo with paracetamol. Other agents show similar affects. There is no convincing evidence that these short-term protective agents afford any protection in vivo and we show that ibuprofen and dexamethasone do not protect in vivo. It is clear that short-term assays for cell protection have only a limited explanatory value.

Acetaminophen↗
PubMed1993

Induction of 5-oxoprolinuria in the rat following chronic feeding with N-acetyl 4-aminophenol (paracetamol).

The urine of rats fed on 1% paracetamol in the diet for up to 10 weeks was analysed using 500 MHz 1H NMR spectroscopy. After 3 weeks, paracetamol-dosed rats were found to excrete massive quantities of an unknown metabolite in the urine. Using a range of 1 and 2 dimensional 1H NMR spectroscopic techniques, solid phase extraction and mass spectrometry, the metabolite was identified at 5-oxoproline (5OXP, pyroglutamic acid). Rats fed paracetamol plus methionine, which prevents the depletion of sulphur-containing amino acids, did not develop 5OXP-uria during the study period. Quantitative 1H NMR spectroscopy of whole urine showed that no 5OXP appeared in the urine in the first 2 weeks of feeding paracetamol to the animals, but urinary concentrations then rose rapidly up to 1 M in some animals. This unusually high concentration of 5OXP in the urine and its prevention by methionine indicates that chronic high level paracetamol dosing leads to severe depletion of sulphur-containing amino acids including cysteine with consequent disruption of the glutathione cycle.

Acetaminophen↗
PubMed1992

Effect of dietary fat on the in vitro hepatotoxicity of paracetamol.

In the present study, we have examined the effect of dietary fat on paracetamol-induced liver injury in an in vitro rat liver slice model. Rats were fed, for 7-10 days, diets containing either butter or polyunsaturated vegetable margarine, two fat sources commonly consumed in the human diet. Liver slices were then exposed to paracetamol for 2 hr and further incubated for 4 hr without paracetamol. Cell damage in the slices was quantified at 6 hr by measuring leakage of lactate dehydrogenase, increase in water content and potassium loss. Covalent binding of radioactive paracetamol to liver and the membrane fatty acid composition of the liver were also measured. Liver slices from rats fed butter diets were significantly more sensitive to the toxic effects of paracetamol than those from margarine fed rats. The membrane lipid composition of the livers also reflected the differing fatty acid content of the two diets.

Acetaminophen↗
PubMed1991

Prevention of paracetamol-induced liver injury by fructose.

Hepatic cell injury was studied in an in vitro system using rat liver slices incubated in two stages. During the first 2 hr slices were exposed to 10 mM paracetamol, this was absent during the subsequent 4 hr of incubation. Cell damage was quantified at the end by measuring leakage of lactic dehydrogenase, increase in water content and potassium loss. Treatment of slices with 20 mM fructose in the second period of incubation prevented paracetamol-induced damage. The effect of fructose was not modified by the continued presence of paracetamol in the second incubation period. The inhibition of glycolysis either with 1 mM NaF or 10 microM iodoacetate blocked the effect of fructose. The protective effect afforded by fructose was not duplicated by the addition of lactate. All these findings strongly suggest an increase in intracellular ATP levels as the most probable explanation for the protective effect of fructose, and point to fructose as a potentially useful therapeutic tool for protection of the liver late in paracetamol intoxication.

Acetaminophen↗
PubMed1990

Electron transport and protection of liver slices in the late stage of paracetamol injury.

Cell injury by chemicals takes place in two stages, initial chemical interaction between the material and cell components, and subsequent stages of adaptation or failure of response to chemical modification of some parts of the cell apparatus. Paracetamol toxicity was studied in an in vitro system using liver slices incubated in two stages. During the first 2 hr slices were exposed to 10 mM paracetamol and this was absent during the following 4 hr of incubation. Damage was quantified at the end by measuring leakage of lactate dehydrogenase (LDH), increase in water content and potassium loss. Treatment of slices with 10 microM DCPIP or 2 mM ethanol in the second period of incubation prevented paracetamol-induced damage. The protective effect was not dependent on the activity of P450 since the second stage of incubation was insensitive to SKF-525A. The protective effect of ethanol was blocked by the presence of 1 mM pyrazole suggesting that ethanol needs to be metabolized to exert its effect. The addition of 20 mM pyruvate reversed the protection provided by ethanol. Nicotinamide did not alter toxicity or protection by ethanol. These findings suggest an increase of NADH and NADH/NAD ratio as the most probable explanation for the protective effect observed. The role of reducing equivalents in detoxification of quinones such as NAPQI by formation of hydroquinones, is discussed in relation to the mechanism of cell injury by paracetamol.

2,6-Dichloroindophenol↗
PubMed1989

Effect of D- or L-methionine and cysteine on the growth inhibitory effects of feeding 1% paracetamol to rats.

Rats fed 1% paracetamol in the diet failed to grow and a dose-dependent inhibition of growth was observed and found to be independent of hepatoxicity. Addition of 0.5% D- or L-methionine, or L-cysteine to a diet containing 1% paracetamol restored growth. Addition of L-methionine to the drinking water was equally effective. Feeding D-cysteine or sodium sulphate were ineffective. Acute paracetamol toxicity was also prevented by D- as well as by L-methionine. It is concluded that the inhibition of growth was due to depletion of sulphur amino acids in the course of paracetamol metabolism. This was sometimes followed by episodes of liver cell injury. Since the normal human dosage of paracetamol is up to 4 g/day, which is equivalent to 1% of the diet, the possibility of induction of amino acid deficiency by chronic use of paracetamol in normal dosage is raised.

Acetaminophen↗
PubMed1985

Lipid peroxidation, protein synthesis, and protection by calcium EDTA in paracetamol injury to isolated hepatocytes.

Hepatocytes from rats treated with phenobarbitone were exposed to 10 mM paracetamol for 1 hr and then incubated in buffered Ringer solution. Enzyme leakage and trypan blue entry became severe in the paracetamol treated cells some 2 hr after the end of exposure. These signs of cell injury could be blocked by 4 mM CaEDTA added during or after paracetamol exposure. CaEDTA did not alter covalent binding of [14C]paracetamol. Ca2+ free media did not prevent paracetamol injury. Lipid peroxidation was observed in cells but could be blocked without protecting the cells. Protein synthesis was depressed early on in cells previously exposed to paracetamol, CaEDTA did not protect against this inhibition. These observations suggest that an early cytoplasmic lesion develops into a later lethal lesion at the cell surface.

Acetaminophen↗
PubMed1977

Mechanism and specificity of increased amylase/creatinine clearance ratio in pancreatitis.

The amylase/creatinine clearance ratio (Cam/Ccr ratio) was determined in 239 subjects. In 87 hospitalised patients without pancreatic disease (controls) the Cam/Ccr ratio was 3.02 +/- 0.69 (mean +/- ISD). The ratio was above the normal range in all patients with acute pancreatitis but was normal in those with chronic pancreatitis and carcinoma of the pancreas. In 18 patients with choledocholithiasis a raised ratio distinguished those with pancreatitis as assessed independently by the surgeon at laparotomy from those with a macroscopically normal pancreas. Raised Cam/Ccr ratios were also found in diabetics with ketoacidosis and in three patients with fulminant alcoholic liver disease. Though a positive correlation was found between the Cam/Ccr ratio and serum creatinine concentration, abnormally high ratios did not occur in 30 patients with chronic renal failure. A significant increase in Cam/Ccr ratios was produced in six healthy volunteers by intravenous injection of glucagon. However, it is unlikely that hyperglucagonaemia alone accounts for the increased Cam/Ccr ratio seen in acute pancreatitis, as no correlation was found between the clearance ratio and the plasma glucagon concentration in a series of patients. In two other patients in whom excess circulating pancreatic polypeptide was detected the Cam/Ccr ratio was normal. It is concluded that, in view of the sensitivity and relative specificity of finding an increased Cam/Ccr ratio in acute pancreatitis, its determination should be valuable clinically, especially in those cases of hyperamylasaemia where the cause is in doubt. The mechanism whereby the ratio is increased is unknown, and it is unlikely that either glucagon or pancreatic polypeptide is a major factor in its production.

Adult↗