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Biomedical subjects

J H Wilson

Publications and source records attributed to J H Wilson.

At least 145 records · Page 8Linked to original sources

Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence.

Thirty-eight patients with porphyria cutanea tarda (PCT) have been seen in the last 18 years. Five of these patients (13%) developed hepatocellular carcinoma (HCC) during follow-up. We analyzed the differences in clinical, laboratory and liver histology findings at presentation, between patients who developed HCC during follow-up (HCC-group, n = 5) and those who did not (PCT-group, n = 33). Of the clinical features the duration of skin-symptoms was longer in the HCC-group (mean: 10.4 +/- 1.1 years) than in the PCT-group (mean: 1.4 +/- 1 years) (p less than 0.001). No differences in routine laboratory findings were found. Although 11/38 (29%) patients had serologic evidence of a past hepatitis B virus infection and 7/38 (18%) patients had antibodies against hepatitis C virus, no differences in these parameters were found between the PCT-group and the HCC-group. In all 34 liver biopsies a variable degree of siderosis was found (PCT-group vs. HCC-group: NS). Only piecemeal necrosis (p less than 0.01) and advanced fibrosis or cirrhosis (p less than 0.001) were more common in liver biopsies in the HCC-group. In conclusion, factors related to an increased risk of HCC in PCT are: a) a long symptomatic period before start of treatment and b) the presence of chronic active hepatitis and/or advanced fibrosis or cirrhosis in liver biopsies.

Adult↗

Blood culture bottles are superior to lysis-centrifugation tubes for bacteriological diagnosis of spontaneous bacterial peritonitis.

The conventional method of ascitic fluid culturing was compared with the bedside inoculation of ascites into blood culture bottles and into lysis-centrifugation tubes. The conventional culture method was compared with the blood culture bottle method in 31 episodes of spontaneous bacterial peritonitis (SBP). Cultures were positive with the conventional culture method in 11 (35%) episodes and with the blood culture bottle method in 26 (84%) episodes (P less than 0.001). The lysis-centrifugation tube method was compared with the blood culture bottle method in 24 episodes of SBP. Cultures were positive with the lysis-centrifugation tube method in 11 (46%) episodes and with the blood culture bottle method in 19 (79%) episodes (P less than 0.05). Moreover, the blood culture bottle method also shortened the time needed for the detection of bacterial growth. In conclusion, bedside inoculation of ascites into blood culture bottles should be used routinely for patients with suspected SBP. Culturing of ascites in lysis-centrifugation tubes is more laborious than and inferior to that in blood culture bottles.

Ascites↗

Eicosanoid production by density-defined human peritoneal macrophages during inflammation.

Density-defined macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 (LTB4, 16%) and 5-hydroxy-eicosatetraenoic acid (5-HETE, 24%) and the cyclooxygenase products 12-hydroxyheptadecatrienoic acid (HHT, 22%) and thromboxane B2 (TXB2, 18%). The synthesis of eicosanoids was linear with the maturity of the macrophage subpopulations, suggesting that eicosanoid production is increased in in-vivo activated macrophages.

Eicosanoids↗

15-HETE is the main eicosanoid formed by human colonic mucosa.

Eicosanoids were measured in colonic biopsies from eleven patients with active ulcerative colitis and from thirteen controls. Eicosanoid formation was measured after the addition of arachidonic acid and stimulation with calcium ionophore A23187. The 15-lipoxygenase derivative 15-hydroxy-eicosatetraenoic acid (15-HETE) was the predominant product formed in all biopsies. The amount of 15-HETE formed was dependent on the site of biopsy and decreased in the controls in biopsies taken in an aboral direction in the colon. The formation of 15-HETE and that of prostaglandin E2 (PGE2) and PGF2 alpha was proportional to the histologically obtained inflammation score. The role of 15-H(P)ETE as a mediator in ulcerative colitis should, therefore, be considered in addition to the effects of known modulators such as leukotriene B4 (LTB4) and PGE2.

Adult↗

Species differences in the pattern of eicosanoids produced by inflamed and non-inflamed tissue.

The synthesis of 14C labelled arachidonic acid metabolites was measured in colonic tissues obtained from mice, rats, guinea pigs, rabbits, piglets and in colonic biopsies from humans during colonoscopy. The main eicosanoids formed after stimulation with calcium ionophore A23187 were: in humans, 15-hydroxy-eicosatetraenoic acid (15-HETE); in mice, 12-HETE; in rats, 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandin F1 alpha (6kPGF1 alpha); in guinea pigs, PGD2; in rabbits, 6kPGF1 alpha, PGE2 and 15-HETE; and in pigs PGE2 and 12-HETE. In inflamed 15-HETE production was increased in man, HHT and 12-HETE production in rats and overall eicosanoid production in mice.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Experimental colitis in mice: effects of olsalazine on eicosanoid production in colonic tissue.

In rodents colitis can be induced by adding 2% (w/v) carrageenan (CARR) for 4 weeks or 10% (w/v) dextran sulphate sodium (DSS) for 7 days to their drinking water. These models are suitable to test anti-inflammatory drugs used in inflammatory bowel disease in man. Mice were treated with olsalazine (400 mg/kg body wt) starting 7 days before the DSS or CARR administration. Colonic tissues were incubated with [1-14C]-arachidonic acid and stimulated with A23187 and, thereafter, the pattern of eicosanoids was determined by separation on HPLC. DSS and CARR produced a marked diffuse inflammatory response in the colon and a subsequent 5-fold increase of all eicosanoids after DSS, whereas after CARR only a 2-fold increase of PGs was observed. Olsalazine treatment decreased all cyclooxygenase and lipoxygenase products to baseline levels.

Aminosalicylic Acids↗

Test selection in jaundice: a comparison between physician behavior and a diagnostic model.

The results of an observational study aimed at a formal assessment of clinicians' test-selection behavior are presented. We first make a proposal for diagnostic test usage in the latter phases of jaundice diagnosis. Next we compute a probabilistic estimate of the patient diagnosis, based on the COMIK algorithm. From the proposal and the probabilistic estimate we can predict the "test-selection behavior" of clinicians. The assessment follows from a tabulation of the predicted behavior against the tests selected by clinicians. It is shown that for most tests, the predictions are consistent with the observed test-selection behavior at a statistically significant level. Discussions of discrepancies between prediction and observation, and reasons for deviations from general guidelines, provide new dimensions for medical education. The methodology applied is a useful tool to improve medical care for the jaundiced patient.

Algorithms↗

Gene targeting in Chinese hamster ovary cells is conservative.

Two fundamentally different pathways for homologous recombination have been identified in mammalian cells. For most chromosomal recombination events, two copies of a homologous sequence recombine to yield two copies in the products; such events are said to be conservative because the number of copies is preserved. By contrast, virtually all extrachromosomal recombination events are nonconservative; two copies recombine to give a product containing a single intact copy (the other copy is destroyed in the mechanism). Since gene targeting involves an introduced (extrachromosomal) plasmid and a chromosomal target, it was not clear which pathway would apply. We used a marked vector to determine whether targeted integrants were products of recombination events that involved two copies (the conservative pathway) or three copies (the nonconservative pathway) of the homologous sequence. Among 51 gene targeting events, we identified 17 homologous integrants and analyzed their structures. All match the predictions for a conservative pathway. We conclude that the principal pathway for gene targeting in mammalian cells is conservative.

Adenine Phosphoribosyltransferase↗

Fidelity of targeted recombination in human fibroblasts and murine embryonic stem cells.

Targeted recombination in murine embryonic stem cells promises to be a powerful tool for introducing specific mutations into target genes to study development in mice and to create animal models of human disease. Gene targeting also holds potential for correcting genetic defects as an approach to human gene therapy. To precisely modify target genes, homologous recombination must proceed with high fidelity. However, several results have suggested that targeted recombination may be highly mutagenic. To test the accuracy of gene targeting we analyzed 44 independent targeted recombinants at the hypoxanthine phosphoribosyltransferase (HPRT) locus in a human fibroblast cell line and in mouse embryonic stem cells. We surveyed 80 kilobases around the sites of recombination by using chemical cleavage of mismatches. Only two mutations were found: a T----G transversion and a thymidine deletion. Thus, gene targeting in mammalian cells can be extremely accurate. These results demonstrate the feasibility of generating precise modifications of mammalian genomes by gene targeting.

Animals↗

Porphyrin synthesis by human hepatocytes and HepG2 cells--effects of enzyme inducers and delta-aminolevulinic acid.

Experiments were carried out to investigate the possibility of inducing porphyria in human hepatocytes and HepG2 cells in culture. After treatment with hexachlorobenzene, 3-methylcholanthrene, phenobarbital or dimethyl sulfoxide, protoporphyrin was the predominating porphyrin accumulating in presence of delta-aminolevulinic acid. The typical uroporphyrin accumulation, as is seen in hexachlorobenzene-induced porphyria in vivo, was absent. In HepG2 cells, the activities of uroporphyrinogen decarboxylase and porphobilinogen deaminase were not influenced by cytochrome P-450 inducers, hexachlorobenzene or dimethyl sulfoxide during 48 h of culture. Therefore, the use of these cells in the study of porphyria cutanea tarda does not seem promising.

Aminolevulinic Acid↗

Prognostic implications of tumor diameter in carcinoma of the head of the pancreas.

Two hundred twenty patients with a carcinoma in the head of the pancreas were divided into three tumor diameter groups: group 1, 0.5 to 4.4 cm (n = 72); group 2, 4.5 to 6.0 cm (n = 77); and group 3, 6.1 to 15.0 cm (n = 71). For these tumor diameter groups a six-fold eliminatory curability analysis was performed. Of the patients with liver metastases in group 1 the last patient had died at 10 months and in groups 2 and 3 no patients were alive at 18 months after the start of complaints. Patients with extrahepatic metastases did not survive 12 months in group 1, 16 months in group 2, and 25 months in group 3. The 6% actuarial survival rate for inoperable patients was reached in group 1 after 17 months, in group 2 after 36 months, and in group 3 after 27 months after the start of complaints. For groups 1 through 3 in curable, but not curatively operated patients, the respective 0% actuarial survival rate was reached at 24 months, 23 months, and 14 months. The 0% actuarial survival rate in patients with irresectable vessel invasion was reached in group 1 at 33 months, in group 2 at 23 months, and in group 3 at 25 months. The 0% actuarial survival rate in patients with an irresectable tumor was reached at 33 months, 31 months, and 27 months after the start of complaints in groups 1, 2, and 3, respectively. The 0% actuarial survival rate in curatively operated patients was reached in group 3 after 26 months and in group 2 after 29 months. In group 1 25% of the patients were alive at 36 months after the start of complaints. Small tumors were associated with the greatest chance of curative operation and on average had the longest survival. However, small tumors with liver or other metastases carried a worse prognosis than large tumors with liver or other metastases. If tumors were found not to be resectable at the time of operation, the size of the tumor did not appear to affect survival.

Aged↗

Glafenine-associated anaphylaxis as a cause of hospital admission in The Netherlands.

In 1981 generalized anaphylaxis was registered on 166 occasions in Dutch general and academic hospitals. Clinical details of 120 of those patients revealed that in 107 anaphylaxis was either probable (n = 90) or possible (n = 17), whereas in 13 cases some other reaction than anaphylaxis had occurred. The series of confirmed cases contained 46 men and 61 women, with mean ages of 47 y and 48 y, respectively. There was a complete recovery in 102 patients and two patients died. Hypotension was present in 79 cases (74%), dyspnoea in 34 cases (32%) and a skin reaction, mainly urticaria, erythema or angioedema, was mentioned in 62 cases (58%). Most cases of anaphylaxis were drug-induced (76%), the main causes being the analgesic glafenine and contrast media. Glafenine was mentioned as the cause in 36% of all admissions for drug-induced anaphylaxis. Only 3.7% of cases had been reported to the voluntary reporting scheme of the Netherlands Centre for Monitoring of Adverse Reactions to Drugs. On the basis of reimbursement data, the risk of developing severe anaphylaxis to glafenine was estimated at 11.7-19.3-fold relative to indomethacin, and 13.4-20.2-fold relative to oral penicillins.

Adolescent↗

Electrocautery does not interfere with the function of the automatic implantable cardioverter defibrillator.

The automatic implantable cardioverter defibrillator (AICD) manufactured by Cardiac Pacemakers, Inc, contains an automatic sensitivity adjustment. We tested whether this feature would prevent sensing of signals generated by electrocautery by implanting three different models of the AICD in 4 mongrel dogs. Unipolar electrocautery was applied at maximum output to a site close to the rate-sensing leads. The devices were monitored with an AICD-check probe and by auditory monitoring of QRS synchronous tones. No sensing of the electrocautery by the device occurred. Three patients with two different AICD models (1550 and 1520) underwent five surgical procedures in which electrocautery was used. No sensing of electrocautery signals, device charging, or other device malfunction occurred.

Animals↗

A shift in balance between profibrinolytic and antifibrinolytic factors causes enhanced fibrinolysis in cirrhosis.

The aim of this study was to assess the cause of enhanced fibrinolysis in cirrhosis by studying the balance between profibrinolytic and antifibrinolytic proteins in 24 patients with mild or severe cirrhosis. Antigen levels of both tissue-type plasminogen activator and plasminogen-activator inhibitor 1 were increased in mild and severe cirrhosis. Activity levels showed a very wide variability, but median activity levels of both proteins were normal. In most patients, the increase in tissue-type plasminogen activator was counterbalanced by the increased levels of plasminogen-activator inhibitor 1, but in a subgroup of patients the change in balance resulted in extremely high tissue-type plasminogen-activator levels. The specific activity of both proteins (activity/antigen quotient) was reduced in either mild or severe cirrhosis. This finding indicates either that more enzyme-inhibitor complexes circulate in the blood of patients with cirrhosis than in normal individuals or that dysfunctional molecules circulate. Plasminogen and alpha 2-antiplasmin antigen and activity levels were decreased in both mild and severe cirrhosis. The binding of alpha 2-antiplasmin to fibrin was decreased in severe cirrhosis, making fibrin clots more susceptible to lysis. Clot lysis experiments were performed to see if equal decreases in plasminogen and alpha 2-antiplasmin levels, as found in cirrhosis, result in a change in the rate of fibrinolysis. It was found that the proportionate decreases led to enhancement of fibrinolysis, indicating that the inhibitor depletion is more important than the proenzyme depletion. The authors conclude that enhanced fibrinolysis frequently found in cirrhosis may be attributed to an increased tissue-type plasminogen-activator activity relative to plasminogen-activator-inhibitor activity and decreased levels of alpha 2-antiplasmin, resulting in a reduced binding of alpha 2-antiplasmin to fibrin.

Fibrin↗

Chronic administration of ethanol with high vitamin A supplementation in a liquid diet to rats does not cause liver fibrosis. 1. Morphological observations.

Rats of two strains (BN/BiRij and WAG/Rij) were fed the ethanol-containing Lieber-De Carli liquid diet supplemented with high amounts of vitamin A for 16 months. In contrast to Lieber and co-workers, who showed liver fibrosis developing within 9 months on the same diet in Sprague-Dawley rats, we were unable to demonstrate a histological and biochemical increase in liver collagen in either strain. Steatosis was present to a varying degree in both strains in ethanol-treated rats, but also in control animals. Considerable liver inflammation with focal necrosis accompanied by severe systemic inflammation was observed in 60% of the ethanol-treated WAG rats. This suggests that, at least in rats, the main effects of chronic ethanol consumption on the liver may be secondary to interference with host resistance to infections. The ethanol-high vitamin A Lieber-De Carli liquid diet does not necessarily elicit fibrosis or other characteristic histological abnormalities of human alcoholic liver disease.

Animals↗

Chronic administration of ethanol with high vitamin A supplementation in a liquid diet to rats does not cause liver fibrosis. 2. Biochemical observations.

The inability of the 'ethanol/high vitamin A Lieber-DeCarli diet' to induce liver fibrosis in two different rat strains was further evaluated by determining changes in parameters of liver cell damage and of retinoid and lipid metabolism. In the ethanol/vitamin A-treated group, slight but constant hepatic cell damage, as indicated by elevated alanine aminotransferase, aspartate aminotransferase and glutamate dehydrogenase activities in blood, was already observed at 6 months and maintained until the time of death at 16 months. Serum gamma-glutamyl transaminase activities were not raised. Moderate parenchymal liver cell damage was not accompanied by fibrosis. Hypertriglyceridemia or hypercholesterolemia were observed at 6-16 months of chronic alcohol administration. This response was strain dependent. In ethanol-treated rats of both strains, total liver retinoids and serum retinol concentrations were not altered. Therefore, the hypothesis that interaction between alcohol and retinoids is a major factor in the pathogenesis of alcoholic liver disease, needs to be reconsidered.

Animals↗

15-HETE is the main eicosanoid present in mucus of ulcerative proctocolitis.

Prostaglandins, leukotrienes and mono-hydroxy acid products of arachidonic acid were measured in mucus of freshly recovered morning stools of a patient with an exacerbation of ulcerative proctocolitis. Eicosanoids in ether extracts were separated by high performance liquid chromatography and amounts determined by radioimmunoassay. Four hydroxy-eicosatetraenoic acids were detected, of which the most important one was identified as 15-hydroxy eicosatetraenoic acid (530 ng/g mucus). Leukotriene B4 was also present (21 ng/g mucus) and small amounts of immunoreactive leukotriene C4 (less than 0.8 ng/g mucus). The prostaglandins 6-keto-PGF1 alpha and PGE2 and thromboxane B2 were found in amounts of 3.7, 2.0 and 9.2 ng/g mucus, respectively.

Adult↗

Bone strength of caged layers as affected by dietary calcium and phosphorus concentrations, reconditioning, and ash content.

1. The effects of preconditioning, dietary calcium and phosphorus concentrations, ash content, body weight, and bone geometry on the shear strength of the radius of caged layers were investigated. 2. Birds that did not lay for three or more weeks before the end of the production period had higher radius bone strengths than the birds producing eggs. 3. Shear breaking force increased with bone ash content. 4. The shear breaking force and stress of the radius were not affected by increasing dietary calcium and phosphorus during the last 8 weeks of production. 5. Freezing and thawing before testing had no effect on bone strength. 6. Body weight cannot be used to predict the breaking force of the radius of caged layers.

Animals↗