Herniography: comparison of morbidity and image quality after use of high and low osmolality contrast media

The morbidity and image quality after administration of three different contrast media were compared in 229 patients referred for herniography. Sixty patients received metrizoate 150 mg I/ml, 92 received metrizoate 200 mg I/ml, and 77 patients, ioxaglate 200 mg I/ml. Patient discomfort was single-blindedly assessed based on an arbitrary verbal rating scale. The number of patients with pain increased with the osmolality of the contrast media. Metrizoate 200 induced pain in 57% of the patients, metrizoate caused pain in 39%, and ioxaglate 200 in 18%. Hernia patients who received metrizoate 200 had pain significantly more often (72%) than patients without hernia (45%). Seven patients, predominantly young men, had a vasovagal reaction associated with the administration of contrast media. The image quality was sufficient after all injections of 200 mg I/ml. The results indicate that low osmolality contrast media with an iodine concentration of about 200 mg I/ml are well suited for herniography.     

Atherosclerosis-related measures in digitized femoral arteriograms

Atherosclerosis is reflected in the arteriogram as narrowing of the arterial lumen and irregularity of the arterial wall. We have quantified these changes in digitized femoral arteriograms from 107 hypercholesterolaemic patients and defined 10 different measures concerning arterial diameter, cross-sectional area, stenosis and edge irregularity. We examined the precision of these measures and the correlations between them. Lumen volume and mean diameter for defined arterial segments had the highest precision and may be useful for follow-up studies. The linear correlation between the mean diameter and the square root of the lumen volume was greater than 0.99, so these two measures seem to be equivalent for all practical purposes. The measured variables could be separated into 2 groups: the measures concerning arterial diameter and lumen volume and those concerning edge irregularity and localized stenosis. The measures within each group showed strong positive mutual correlations, while the correlations between measures from different groups were negative and small. It was concluded that if the results of one measure from each group, suitably those of lumen volume and edge roughness, are known, the other described measures will add no further information about the atherosclerotic process.     

Paroxetine and amitriptyline in the treatment of depression in general practice

Christiansen PE, Behnke K, Black CH, Öhrström JK, Bork-Rasmussen H, Nilsson J. Paroxetine and amitriptyline in the treatment of depression in general practice. Acta Psychiatr Scand 1996: 93: 158–163. © Munksgaard 1996. A total of 144 outpatients in general practice in Denmark, aged 18–65 years and diagnosed as suffering from depression with a HAMD-17 score of 15 or more, were included in this 8-week double-blind, randomised, multicentre, controlled, parallel group comparison of paroxetine versus amitriptyline. The purpose of the study was primarily to evaluate efficacy and tolerance of treatment. In addition, focus was added on weight change and subjective well-being. The efficacy results showed equal effect of both drugs. However, paroxetine was tolerated better than amitriptyline, and this difference reached the level of significance when four non-evaluable patients were taken out of the analysis. Moreover, there was a significant weight increase in the amitriptyline group and no significant weight change in the paroxetine group. There was no difference between the groups as regards subjective well-being as measured by the VAS. In conclusion, paroxetine is an effective and well-tolerated antidepressant, and well-suited for the treatment of depression in general practice.     

99MTc-Dextran-Antibody Conjugates : Labelling procedures

Dextran forms stable chelates with ^99mTc, a radionuclide with ideal properties for planar scintigraphic and tomographic imaging. This study investigates some of the factors of importance to the formation of ^99mTc-dextran. The complex was used for the technetium labelling of a monoclonal antibody. Two radiolabelling methods were studied: direct dextran labelling with the reductant dissolved in HCl and labelling via a weak 'transfer' chelator (tartaric acid) with the reductant dissolved in ethanol. Different conditions during the labelling reaction were studied. Finally, dextran was coupled to a monoclonal anticytokeratin antibody and the conjugate was subsequently radiolabeled with ^99mTc. Gel filtration (GFR) and thin layer chromatography (TLC) were compared as methods for estimation of the labelling efficiency. When using 10-500μM of Ugand, 5-100μM SnCl₂ with 10-500 MBq of technetium at pH7 incubated for 10-15 min, the radiolabelling seemed optimal (70-75% labelling efficiency). It was found that 100 μM tartaric acid used as a weak intermediate chelator with SnCl₂ dissolved in ethanol improved the reproducibility of the labelling. The labelling efficiency was not affected by either the presence of oxygen or the addition of an oxygen scavenger during the labelling incubation. In general, TLC showed higher labelling efficiencies than GFR, indicating inadequate separation of the different moieties.     

Interactions between methylsulfonyl PCBs and the glucocorticoid receptor.

Persistent polychlorinated biphenyl (PCB) metabolites were studied with respect to their interaction with the human glucocorticoid receptor (GR). 3-Methylsulphonyl-2,5,6,2',4',5'-hexachlorobiphenyl (3-MeSO2-CB149) was shown to compete with 3H-dexamethasone for binding to the GR, with an IC50 (concentration that inhibits 50%) of approximately 1 microM. Using GRAF cells expressing human GR, glucocorticoid responsive element, and a reporter enzyme, we demonstrated that 3-MeSO2-CB149 functionally acts as an antagonist at the GR (IC50 = 2.7 microM). In accordance with the receptor binding, the antagonism mainly appeared to be of a competitive nature. When studying the competitive binding of 24 methylsulfonyl PCBs (relative to dexamethasone) to GR from mouse liver cytosol, seven compounds had a higher affinity to GR than 3-MeSO2-CB149. Structure-activity relationship studies indicated that the presence of three chlorine atoms in the ortho-position and chlorine and methyl sulfone groups on either end of the molecule (4 and 4'-position) increased the affinity to GR. The relevance of this finding for human health is not known, but PCB methyl sulfones are ubiquitous pollutants present in mother's milk. The results stress the need for studying endocrine disruptors that affect hormonal systems other than sex and thyroidogenic hormones.     

An ELISA technique for quantitation of human xenoantibodies binding to pig cells: Application in patients with pig kidneys extracorporeally connected to the circulation

ABSTRACT: A quantitative ELISA technique for determination of human anti-pig xenoantibody number in serum samples has been established using pig lymphocytes and pig/rabbit erythrocytes as target cells and a pool of serum from human blood group AB donors. The number of low affinity antibodies binding to the cells was determined by quantitation following the use of aqueous washing of the cells and separation of bound and unbound antibodies with the phthalate oil method. The efficiency of different soluble Galal-3Gal-terminating di- and tri-saccharides to inhibit antibody binding was tested and found to vary between 70–90% at a saccharide concentration of 10 mg/ml. The assay was used to evaluate the antibody changes in two patients who, after plasmapheresis treatments, had pig kidneys extracorporeally connected to their blood circulation. The number of anti-pig IgM/IgG antibodies bound to each pig lymphocyte were reduced from 5,600/13,200 to 1,300/3,100 in patient 1 and from 1,200/6,500 to 500/2,100 in patient 2 by three consecutive daily plasmapheresis treatments. Although the lymphocytotoxic titers were reduced to very low levels, the antibody numbers still present in the blood of patient 1 caused a hyperacute rejection of the pig kidney. However, the antibody levels in patient 2 did not cause rejection of this kidney during 15 min perfusion time. A strong anti-pig antibody response 3 weeks after the perfusion experiment was found in patient 1 as shown by 27,600/245,300 IgM/IgG molecules bound to pig lymphocytes corresponding to an increase of lymphocytotoxic titer from 8 to 512. The second patient showed a much weaker immune response with 1,400/19,800 IgM/IgG antibodies corresponding to a lymphocytotoxic titer increase from 8 to 32. The use of this quantitation technique enables more accurate investigation of antibody bindine to xenoeenic tareet cells than conventional titration techniaues.     

Total hip replacement in patients with hemophilia: 13 hips in 11 patients followed for 1-16 years

During 1973-88, we performed 13 total hip replacements in 11 hemophilia patients, mean age 46 (25-65) years. During the operation, blood loss averaged 920 mL, and a mean of 120, 000 units of factor VIII/IX were used. the mean duration of follow-up was 7 (1-16) years. 5 hips became loose within 6 years, and a further one after 13 years. 4 hips were revised, 2 of them due to infection in patients who were also seropositive for HIV. At the latest follow-up, 10 patients were alive. 6 had no hip pain and 7 could walk at least 1, 000 meters at a time. Although these results are inferior to those obtained in arthrosis, total hip replacement should be considered in hemophiliac patients.     

Factors predicting healing complications in femoral neck fractures: 138 patients followed for 2 years

We have previously studied the radiographic outcome of femoral neck fracture osteosynthesis with either two hook-pins or a four-flanged nail performed by a small group of surgeons with special interest in the methods. In 138 femoral neck fractures a backwards stepwise logistic regression analysis was used to study the significance of preoperative fracture-related factors, intraoperative factors and the osteosynthesis. The development of non-union/re displacement and segmental collapse of the femoral head was influenced by fracture displacement (P 0.001) and method of osteosynthesis (P 0.007). The postoperative scintimetric ratio was influenced by the method of osteosynthesis (P 0.0003), fracture displacement (P 0.004) and by the presence of a posterior fragment (P 0.03).

Reduction of the fracture and positioning of the osteosynthesis were to a large extent within the accepted limits. This may explain why the previously well documented negative effects of malpositioning of the osteosynthesis and inferior reduction were not demonstrated to influence the rate of healing-complications. We conclude that neither patient age, sex nor preoperative fracture variables, with the exception of the extent of fracture displacement, can be used to predict radiographic healing-complications in femoral neck fractures.     

A metabolic route of omeprazole involving conjugation with glutathione identified in the rat.

A metabolic route of omeprazole involving glutathione has been established through identification of endproducts excreted in the urine of rats after oral administration of 400 mumol/kg of a mixture of [3H]- and [14C]omeprazole. The labeled positions enabled facile tracing of metabolites that were formed through fission of omeprazole, producing [3H]pyridine and [14C]benzimidazole metabolites. The structures of the metabolites were established by HPLC thermospray MS and MS/MS. Two of the metabolites were isolated and characterized by 1H NMR studies. The fact that the N-acetylcysteine derivative of the benzimidazole was one of the endproducts indicated that the initial reaction involved glutathione. Three metabolites reflecting the fate of the pyridine moiety were identified. Their proposed formation route is via initial reduction to the pyridylmethylthiol compound followed by S-methylation and S-oxidation to the corresponding sulfoxide or sulfone. The quantity of metabolites formed via the glutathione route identified in urine was about 10% of the dose given, both in male and female rats. The male and female rats excreted the same cleaved metabolites and approximately equal quantities thereof.     

Effects of ethanol on the chemotactic peptide-induced second messenger generation and superoxide production in polymorphonuclear leukocytes.

The generation of oxygen radicals by polymorphonuclear leukocytes (PMNL) plays a pivotal role for host defense. Since ethanol reduced FMLP- but not PMA-induced superoxide ion (O2-) formation by PMNL, the effects of ethanol on second messenger systems in PMNL were studied. FMLP induced a biphasic rise in cytosolic calcium concentrations, [Ca2+]i. Ethanol treatment abolished the second phase (believed to reflect Ca2+ influx), an effect also observed in PMNL treated with La3+ or suspended in Ca(2+)-free buffer. The FMLP-induced inositol trisphosphate generation was unaffected by ethanol, whereas diacylglycerol formation was, as expected, markedly reduced. Propranolol, an inhibitor of diacylglycerol formation from phosphatidic acid, caused a prolonged transmembrane influx of Ca2+ and partially reversed the inhibitory effect of ethanol on FMLP-induced O2- production. Thus, the ability of ethanol to inhibit FMLP-induced O2- generation in neutrophils seems to be due to both impaired influx of Ca2+ across the plasma membrane and reduced phospholipase D-mediated generation of phosphatidic acid.