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Biomedical subjects

J H Wilson

Publications and source records attributed to J H Wilson.

At least 109 records · Page 6Linked to original sources

Therapeutic partnership. A model for clinical practice.

The illness of a relative disturbs family equilibrium and creates a stressor of significant magnitude. Thus, interpretations of individual or family functioning must be placed in this context. The Therapeutic Partnership model is adept at reinforcing shared responsibility, accountability, and decision making. It conveys a culture of hope and appears to achieve its desired goals. Therapeutic Partnership stands in direct contrast to the notion of lifetime advocacy and other more traditional treatment approaches. It is a highly intense, time-limited, goal-directed involvement.

Adult↗

The difference in liver pathology between sporadic and familial forms of porphyria cutanea tarda: the role of iron.

Porphyria cutanea tarda is a disorder of porphyrin metabolism, of which familial and sporadic forms have been described. Factors such as iron seem necessary for porphyria cutanea tarda to become clinically manifest. To study the relationship between iron and uroporphyrins in hepatocytes of patients with porphyria cutanea tarda, a morphological and morphometrical study was performed in 13 liver biopsies of patients with porphyria cutanea tarda (eight with sporadic porphyria cutanea tarda and five with familial porphyria cutanea tarda). In addition, possible differences in clinical and biochemical features and in histopathological findings between patients with sporadic porphyria cutanea tarda and familial porphyria cutanea tarda were investigated. Familial porphyria cutanea tarda patients presented at a younger age than sporadic porphyria cutanea tarda patients (42.4 +/- 5.3 vs. 57.3 +/- 8.6 years). Biochemical features were not different between sporadic porphyria cutanea tarda and familial porphyria cutanea tarda patients. Uroporphyrin crystals and a variable degree of liver siderosis were detected in the biopsies of all 13 patients. Uroporphyrin crystals were often found close to ferritin-like iron deposits. The morphometrical analysis showed that an increased mean area fraction of ferritin iron was associated with an increased mean area fraction of uroporphyrin crystals in hepatocytes of sporadic porphyria cutanea tarda and familial porphyria cutanea tarda patients. Moreover, the amount of uroporphyrin crystals was significantly higher in livers of familial porphyria cutanea tarda than sporadic porphyria cutanea tarda patients. These findings are consistent with the hypothesis that uroporphyria is precipitated by an iron-dependent process.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The frequency of gene targeting in yeast depends on the number of target copies.

We have compared the efficiency of transformation by linear DNA fragments in yeast strains carrying different numbers of homologous targets for recombination. In strains carrying dispersed copies of a target and in strains carrying tandem arrays, the frequency of transformation is proportional to the number of targets. This result is in contrast to previous studies of transformation in mammalian cells, where targeted integration was insensitive to the number of targets. We conclude that, in yeast, the search for a homologous partner is a rate-limiting step in the successful recombination of linearized DNA fragments. Furthermore, the fact that we obtain the same results with both dispersed and clustered targets argues against models of homology searching in which DNA becomes nonspecifically associated with a chromosome and then slides along the DNA until homology is encountered.

Chromosome Mapping↗

Production of inflammatory mediators by human macrophages obtained from ascites.

Ascites is a readily available source of human macrophages (M phi), which can be used to study M phi functions in vitro. We characterized the mediators of inflammation produced by human peritoneal M phi (hp-M phi) obtained from patients with portal hypertension and ascites. The production of the cytokines interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) was found to be lipopolysaccharide (LPS) concentration dependent (0-10 micrograms/ml) with a maximal production at 10 micrograms/ml and also dependent on the time of exposure to the stimulus (0-36 h). IL-1 beta, IL-6 and TNF-alpha production after LPS administration reached a plateau at 24 h. In vitro stimulation for 24 h with LPS does not influence the eicosanoid production from endogenous arachidonate. 13 min of exposure of the cells to the calcium ionophore A23187 gives a significant increase in eicosanoid production from both exogenous and endogenous arachidonate. The main eicosanoids produced are the 5-lipoxgenase products LTB4 and 5-hydroxyeicosatetraenoic acid (HETE). The increase in production of the other eicosanoids is not significant. The eicosanoid production depends on the stimulus concentration. The optimal A23187 concentration is 1 microM. Oxygen radical production was measured in the M phi by a flowcytometric method. The fluorescence intensity of phorbol 12-myristate 13-acetate stimulated and dihydro-rhodamine 123 loaded hp-M phi increases significantly after 15 min. We conclude that LPS stimulation of hp-M phi from liver disease results in similar production of IL-1 beta, IL-6 and TNF-alpha, but that the profile of the eicosanoid production of these M phi stimulated with LPS and A23187 differs from M phi of other origin and species.

Adult↗

Endoscopic papillotomy for common bile duct stones: factors influencing the complication rate.

In a prospective study, the complications observed in 242 consecutive patients after endoscopic sphincterotomy for common bile duct stones were recorded over a period of up to three months. Patients with previous gastric surgery, papillotomy, or additional pancreato-biliary disease other than gallbladder stones were excluded. The overall complication rate was 14%, 74% of these complications being moderate or severe. The complication rate due to cholangitis was higher in (1) the group with retained stones following complete papillotomy and without biliary drainage, and (2) the group with failed precut papillotomy and drainage after cholangiography, both compared to patients with successful drainage (75% vs. 2.6%: p < 0.001 and 40% vs. 2.6%: p = 0.001 respectively). Both pancreatitis and retroperitoneal air leakage occurred in 1.7% of cases. They were more frequently observed in patients with a smaller diameter (< 10 mm) in the distal common bile duct (5.6% vs. 0%: p = 0.007 for pancreatitis, and 2.8% vs. 1.2%; n.s. for perforation) and especially following precut papillotomy (13.0% for pancreatitis and 8.7% for perforation), which had to be performed more often in these patients. Bleeding following sphincterotomy was relatively frequent when the papilla was located at the lower rim of or inside a diverticulum, compared to patients without a diverticulum (16.2% vs. 2.7%: p = 0.004 and 26.7% vs. 2.7%: p < 0.001 respectively). When the papilla was located inside diverticula, both the rate of perforation and bleeding increased following precut papillotomy, compared with standard papillotomy only (33% vs. 0%, n.s., and 33% vs. 22%, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

The contents of free-text endoscopy reports: an inventory and evaluation by peers.

Insight into the current status of endoscopy reports is needed for a discussion on the desirability and feasibility of (more) standardized endoscopy reporting. We collected, from ten endoscopists, 181 reports in two diagnostic and two indication categories. An inventory was made of the subjects dealt with in the reports, such as: indication, premedication, therapy plan, and descriptive aspects of ventricular ulcers and lower tract polyps. To assess endoscopists' opinions on their reports, 16 randomly selected reports were reviewed by the ten endoscopists, using the Delphi method. The reports varied enormously in content and detail; 19 of the 28 subjects were not explicitly described in more than 50% of the studied reports. Such variation in the contents of reports may decrease the quality of care. The large number of topics that endoscopists indicate to be missing in their reports (on average 14 topics per report) suggests that more detail should be given in endoscopy reports. The current method of reporting causes endoscopists to omit information that they consider important. Due to the low overall consensus among endoscopists on which specific topics to include (eight or more endoscopists agreed on 15% of topics) we conclude that general criteria for the contents of reports cannot yet be formulated. However, the fact that the endoscopists agreed with more than one-third of the remarks made by colleagues opens a perspective towards identifying criteria for the formalization of certain report categories.

Delphi Technique↗

Osteoporosis and fracture complications in an amenorrhoeic athlete.

We present the case of a 30-yr-old runner with amenorrhoea. She developed skeletal problems including low bone density and stress fractures. She then developed a (presumed) osteoporotic fracture of the proximal humerus. This is the first case report of such a fracture in a woman with athletic amenorrhoea and demonstrates that this disorder should not be regarded as a benign condition.

Adult↗

Pacing system analyzers: different systems--different results.

When a pacemaker is implanted, several electrophysiological parameters are measured using pacing system analyzers (PSA). Different PSAs may use different filter settings and measuring techniques when compared to the implanted pacemaker. In order to determine if there were significant differences in measurements obtained with different PSAs, we obtained measurements in a group of 99 patients with three different PSAs and a manual method. The results show that with each of the three different PSAs tested, different amplitudes of intracardiac electrograms are obtained and that they are usually higher than those obtained by manual measurement of recorded electrograms. Despite significant differences, however, all methods correlate well with each other. Following common practice of pacemaker programming, the use of a PSA for the implantation of a pacemaker that uses different sensing technique does not lead to clinical complications.

Humans↗

Budd-Chiari syndrome in a young patient with anticardiolipin antibodies: need for prolonged anticoagulant treatment.

The case of a 20 year old woman is reported with Budd-Chiari syndrome in whom lupus anticoagulant and anticardiolipin antibodies were shown; treatment with oral anticoagulants induced a considerable improvement. This treatment was interrupted after one year; interruption was followed by redevelopment of ascites. Further treatment with anticoagulants was continued for five years with noticeable improvement. When treatment with oral anticoagulants was stopped because of pregnancy, the patient redeveloped ascites and had a spontaneous miscarriage. Subsequently, treatment with oral anticoagulants was reintroduced and again resulted in noticeable improvement. In conclusion patients with Budd-Chiari syndrome should be tested for lupus anticoagulants and anticardiolipin antibodies, Budd-Chiari syndrome resulting from this cause may have a good response to treatment with oral anticoagulants; this treatment should be maintained permanently, and pregnancy in such patients may initiate serious difficulties.

Abortion, Spontaneous↗

Current status of photodynamic therapy in oncology.

Photodynamic therapy (PDT) is a cancer treatment based on the accumulation in malignant tissue of a photosensitiser with low systemic toxicity. Subsequent illumination induces a type II photochemical reaction with singlet oxygen production that results in destruction of biomolecules and subcellular organelles. The first full clinical report of PDT dates from 1976. Haematoporphyrin derivative, a complex mixture of porphyrins, was initially used as a photosensitiser. An enriched fraction (porfimer sodium) is now the most commonly used clinical agent. After systemic administration porphyrins bind to albumin and lipoproteins. Accumulation occurs mainly in tumours and organs of the reticuloendothelial system. The light of an argon-dye laser can be tuned to the appropriate wavelength and delivered either superficially, interstitially or intraluminally. Light distribution can be assessed by using a radiation transport model and tissue optical properties, or direct measurement with light detectors. The effects of PDT depend in a complex way on: characteristics, tissue concentration and localisation of the photosensitiser; the target tissue optical properties and oxygenation; activation wavelength, power density and treatment regimen. Future research is directed towards: better photosensitisers (i.e. phthalocyanines, chlorins or protoporphyrin IX endogenously produced from 5-aminolevulinic acid); improved light generation and delivery; and combination with hyperthermia, chemotherapy, radiotherapy or surgery. Adjuvant intraoperative PDT is a promising approach to destroying residual tumour after surgery.

Animals↗

Increased platelet activating factor synthesis in experimental colitis after diclofenac and 5-amino-salicylic acid.

We examined the role of platelet activating factor in dextran induced colitis in mice. The release of pro-inflammatory platelet activating factor by colonic mucosa after the application of prednisolone was markedly decreased, unaffected after treatment with the platelet activating factor receptor antagonist BN52021 and significantly increased after treatment with 5-amino-salicylic acid and diclofenac. This increase of platelet activating factor could be responsible for the harmful effects often seen after treatment with specific cyclooxygenase inhibitors during inflammation.

Aminosalicylic Acid↗

The effect of desferrioxamine on iron metabolism and lipid peroxidation in hepatocytes of C57BL/10 mice in experimental uroporphyria.

The effects of the iron chelator desferrioxamine (DFx) on liver iron accumulation, malondialdehyde (MDA) production, porphyrin accumulation and uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37) activity were investigated over a period of 14 weeks in C57BL/10 mice, made porphyric by the administration of hexachlorobenzene (HCB) and iron-dextran (Imferon, IMF) or IMF alone. In addition, we measured the amount of low molecular weight (LMW) iron in liver tissue to determine a possible correlation with MDA production. These experiments showed that combined treatment with HCB + IMF, as well as IMF alone, resulted in porphyrin accumulation, increased MDA production and reduced URO-D activity, whereas HCB alone had no effect. DFx caused a reduction in hepatic porphyrins, this reduction being more distinct in the IMF group than in the HCB + IMF group. The effect of DFx on MDA production and URO-D activity was in agreement with the results on porphyrin accumulation. LMW iron pool measurements at 11 weeks correlated well with data on MDA production in all treated groups in that period (r2 = 0.84), suggesting both variables are interdependent. In conclusion, these results suggest an important role for iron in porphyrin accumulation, probably through its catalytic role in the generation of oxygen-related free radicals, resulting in direct damage to URO-D. The effectiveness of DFx in reducing porphyrin accumulation is probably the result of a reduction in LMW iron, thus diminishing the amount of iron available for a catalytic role in the generation of oxygen-related free radicals.

Animals↗

[Acute liver failure caused by methylenedioxymethamphetamine ('ecstasy')].

A female aged 18 years who had regularly taken 1-2 tablets of methylenedioxymethamphetamine ('ecstasy') every weekend developed acute liver failure. She recovered after two months hospitalization with conservative treatment. This is the 10th case of hepatotoxicity after use of ecstasy described in the literature. One patient died, another required liver transplantation. In young patients with jaundice and liver dysfunction a side effect of use of ecstasy should be considered as a possible cause.

3,4-Methylenedioxyamphetamine↗

Ferritin accumulation and uroporphyrin crystal formation in hepatocytes of C57BL/10 mice: a time-course study.

To establish the time-sequence relationship between ferritin accumulation and uroporphyrin crystal formation in livers of C57BL/10 mice, a biochemical, morphological and morphometrical study was performed. Uroporphyria was induced by the intraperitoneal administration of hexachlorobenzene plus iron dextran and of iron dextran alone. Uroporphyrin crystal formation started in hepatocytes of mice treated with hexachlorobenzene plus iron dextran at 2 weeks and in mice treated with iron dextran alone a 9 weeks. In the course of time, uroporphyrin crystals gradually increased in size. Uroporphyrin crystals were initially formed in hepatocytes in the periportal areas of the liver, in which also ferric iron staining was first detected. The amount and the distribution of the main storage form of iron in hepatocytes, ferritin, did not differ between the two treatment groups. Ferritin accumulation preceded the formation of uroporphyrin crystals in hepatocytes in both treatment groups. Moreover, uroporphyrin crystals were nearly always found close to ferritin iron. We conclude that uroporphyrin crystals are only formed in hepatocytes in which also iron (ferritin) accumulates. Hexachlorobenzene accelerates the effects of iron in porphyrin metabolism, but does not influence the accumulation of iron into the liver.

Animals↗

Targeting vector configuration and method of gene transfer influence targeted correction of the APRT gene in Chinese hamster ovary cells.

A 21-bp deletion in the third exon of the APRT gene in Chinese hamster ovary (CHO) cells was corrected by transfection with a plasmid containing hamster APRT sequences. Targeted correction frequencies in the range of 0.3-3.0 x 10(-6) were obtained with a vector containing 3.2 kb of APRT sequence homology. To examine the influence of vector configuration on targeted gene correction, a double-strand break was introduced at one of two positions in the vector prior to transfection by calcium phosphate-DNA coprecipitation or electroporation. A double-strand break in the region of APRT homology contained in the vector produced an insertion-type vector, while placement of the break just outside the region of homology produced a replacement-type vector. Gene targeting with both linear vector configurations yielded equivalent ratios of targeted recombinants to nontargeted vector integrants; however, targeting with the two different vector configurations resulted in different distributions of targeted recombination products. Analysis of 66 independent APRT+ recombinant clones by Southern hybridization showed that targeting with the vector in a replacement-type configuration yielded fewer targeted integrants and more target gene convertants than did the integration vector configuration. Targeted recombination was about fivefold more efficient with electroporation than with calcium phosphate-DNA coprecipitation; however, both gene transfer methods produced similar distributions of targeted recombinants, which depended only on targeting vector configuration. Our results demonstrate that insertion-type and replacement-type gene targeting vectors produce similar overall targeting frequencies in gene correction experiments, but that vector configuration can significantly influence the yield of particular recombinant types.

Adenine Phosphoribosyltransferase↗

Inflammatory mediators and activity of human peritoneal macrophages.

Human peritoneal macrophages (hp-M phi) are a source of inflammatory mediators. After stimulation in vitro for 24 h with LPS there was a significant increase in cytokine production (IL-1, IL-6 and TNF alpha), but not in the production of eicosanoids from endogenous arachidonate. Leukotrienes are the predominant eicosanoids formed after stimulation with calcium ionophore for 15 min, while prostaglandin formation is insignificant. The fluorescence intensity of TPA-stimulated and DHR123 loaded hp-M phi (a measure of the respiratory burst) increases significantly in a short period of time. Hp-M phi will be useful as a model for testing the effects of anti-inflammatory drugs on eicosanoid and cytokine production and respiratory burst activity in vitro.

Ascitic Fluid↗

15-Hydroxy-eicosatetraenoic acid has minor anti-inflammatory properties in colitis.

This study was performed to determine whether 15-HETE, which is the major metabolite of arachidonic acid (AA) in inflamed and normal human colonic tissue, has pro- or anti-inflammatory properties. To investigate these effects, 15-HETE (100 micrograms/kg/day) was administered rectally to mice with colitis induced by dextran sodium sulphate (DSS). Colons were removed and examined macroscopically and histologically and specimens were incubated with [14C]-AA and stimulated with A23187. Exogenous eicosanoids were separated by HPLC; the endogenously formed mediators were measured by radioimmunoassay. DSS produced a marked diffuse inflammatory response in the colon, associated with a raised inflammation score (mean 7.6 vs. < 0.5) and a significant increase in endogenously formed metabolites PGE2, LTB4 and 12-HETE. 15-HETE treatment resulted in a slight decrease in inflammation score (6.4 vs. 7.6) and a slight, but not significant, decrease in endogenous LTB4.

Animals↗

Eicosanoid production by the mucosa in inflammatory bowel disease after 5-ASA treatment.

Eicosanoids were measured in biopsies of colonic mucosa from five patients with active ulcerative colitis before and after a four weeks of treatment with 5-amino-salicylic acid (5-ASA). Eicosanoid formation was determined after the addition of 14C-arachidonic acid and stimulation with calcium ionophore A23187. 5-ASA given intra-rectally caused a non-selective suppression of prostanoids, leukotrienes and hydroxy-eicosatetraenoic acids. Changes in arachidonic acid metabolism after 5-ASA treatment were not always reflected in changes in inflammation score.

Aminosalicylic Acids↗