[A new case of vomiting gallstones].
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Biomedical subjects
Publications and source records attributed to P Andersson.
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The effect of topical glucocorticosteroids on the allergen-induced nasal hyperresponsiveness, with special reference to treatment time, was studied in a double-blind, randomized, placebo-controlled crossover study. Ten patients who previously had shown allergen-induced nasal hyperresponsiveness participated. After pretreatment with either placebo or various periods with topical glucocorticosteroids, they were subjected to an initial challenge with three increasing doses of allergen and were rechallenged after 24 hours with the lowest allergen dose from the previous day. The nasal responses were monitored by means of symptom scores and measurements of N alpha-p-tosyl-L-arginine methyl esterase (TAME) activity in nasal lavages. Five different treatment schedules were used. In the active treatment alternatives, the glucocorticosteroid treatment was started 48, 12 or 2 hours before or 2 hours after the initial allergen challenge. All treatments were continued up to rechallenge on the second day. As the active treatment we used budesonide, 100 micrograms in each nasal cavity every 12 hours. After placebo pretreatment, as expected, there was an increase in nasal symptoms at rechallenge as compared with the initial allergen challenge with the same allergen dose. The mean (+/- SEM) number of sneezes increased from 5.1 +/- 1.7 to 9.5 +/- 2.0 (p less than 0.05), a composite nasal symptoms score increased from 3.3 +/- 0.66 to 4.4 +/- 0.7 (NS), and TAME activity increased from 14.9 +/- 2.83 to 25.3 +/- 0.5 cpm.10(3) (p less than 0.05). Topical glucocorticosteroid treatment abolished this increase in nasal symptoms and TAME activity (p less than 0.05 for all treatment alternatives).(ABSTRACT TRUNCATED AT 250 WORDS)
Sixty-one patients, 16 with classic and 45 with common migraine, were treated during three subsequent attacks with pirprofen, a new inhibitor of prostaglandin synthesis; an ergotamine tartrate compound; or placebo, in a randomized, double-blind multicentre study. Pain relief after a single dose and reduction of the attack intensity occurred most often with pirprofen in patients who needed more than one dose. Among them, however, the duration of attack was shortest with ergotamine. Working ability was well preserved with pirprofen, especially among patients with common migraine, and this treatment was ranked highest by the patients. However, no statistically significant differences were found between pirprofen and ergotamine. No serious side effects were observed with pirprofen. This study establishes the usefulness of pirprofen in the treatment of acute migraine.
The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.
The presence of hepatitis B virus and delta agent markers was investigated in 41 patients referred during the years 1970-1985 with fulminant hepatitis classified as type B or non-A non-B and compared to findings in patients with uncomplicated hepatitis B and chronic hepatitis B infection. 13 patients had no markers of hepatitis B and delta infection and were classified as non-A non-B hepatitis. The remaining 28 patients were all HBsAg and IgM anti-HBc positive and 14 (50%) had evidence of delta infection. In contrast, only 13/71 patients (18%) with acute benign hepatitis B had evidence of delta coinfection (p less than 0.005). This corresponds to an odds ratio of 4.5 for development of fulminant hepatitis among patients with hepatitis B and delta coinfection. In 100 chronic HBsAg carriers 29% were positive for delta markers. 12 of the delta infected patients with fulminant hepatitis were positive for total antibody to the delta antigen, and 2 were delta antigen positive. Three were HBeAg positive/anti-HBe negative. None had hepatitis B virus DNA. Among the 14 patients without delta infection, hepatitis B virus DNA was found in 2/4 HBeAg positive/anti-HBe negative patients and in 1/8 patients negative for both markers. The present data indicate that a high proportion of Danish patients with fulminant hepatitis B have hepatitis B and delta agent coinfection. Further, the findings suggest that hepatitis B and delta coinfection may be associated with an increased risk of development of fulminant hepatitis as compared to that of hepatitis B alone.
Extracellular levels of excitatory and inhibitory amino acids were measured in the cortex and striatum of asphyxiated fetal lambs. The fetus was exteriorized from the anesthetized ewe and dialysis probes were placed in the parietal cortex and caudate nucleus. Cerebral blood flow was measured with Xe-clearance. Cortical somatosensory-evoked potentials and electroencephalogram (EEG) were continuously recorded. Asphyxia was induced by clamping the umbilical cord or by graded compression of the maternal aorta. Asphyxia accompanied by elevated cerebral blood flow resulted in a moderate rise in extracellular amino acid levels. During extreme asphyxia, i.e. abolished evoked potentials and reduced cerebral blood flow, marked extracellular elevations of glutamate (3- to 11-fold), aspartate (3- to 7-fold), gamma-aminobutyric acid (GABA) (3- to 5-fold) and taurine (3- to 18-fold) occurred, the higher values representing striatum. Excessive levels of excitatory amino acids may exert injurious effects on immature neurons during such hypoxic-ischemic states.
Selenium level in plasma (P-Se) was slightly, but statistically significantly (2p = 0.02) lower in 25 lead-exposed secondary smelter workers (P-Se 1.09 +/- 0.02 mumol l-1, mean +/- SEM; blood lead level, B-Pb, 1.9 +/- 0.1 mumol l-1) than in 25 matched controls (P-Se 1.16 +/- 0.03 mumol l-1; B-Pb 0.2 +/- 0.01 mumol l-1). Further, there was a significant negative (2p = 0.02) correlation (r = -0.33) between B-Pb and P-Se. The data indicate a minor interaction, in humans, between occupational lead exposure and selenium status.
It has been previously demonstrated in nasal challenge studies that there is an increased sensitivity to allergen following an initial allergen challenge. A similar feature has been demonstrated following natural allergen exposure in patients with seasonal allergic rhinitis. To further explore the characteristics of this "priming" phenomenon and its relationship to other expressions of their allergic airway disease, 28 hay fever patients with strictly seasonal disease were studied. Skin tests with the relevant pollen allergen and histamine were performed and the size of the immediate and late phase allergic reaction was determined. An initial nasal allergen challenge was followed by a rechallenge of the nose with allergen 24 h later using a lavage technique. Determinations of TAME-esterase activity, as a biochemical marker of the allergic reaction, were made in the returned lavage fluid. The number of sneezes was counted and nasal symptoms were also assessed using a scoring technique. 19 of 28 patients (67%), displayed an increased responsiveness at rechallenge with similar findings in terms of symptom scores and TAME-esterase measurements. The increase was statistically significant for the symptoms of nasal blockage, which increased from 0.7 +/- 0.1 (mean +/- SEM) to 1.1 +/- 0.2 (P less than 0.05), and nasal secretion which rose from 1.1 +/- 0.2 to 1.7 +/- 0.2 (P less than 0.01). A composite nasal symptom score which also took account of the number of sneezes, increased from 2.9 +/- 0.4 to 4.0 +/- 0.3 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Extracellular (EC) adenosine, hypoxanthine, xanthine, and inosine concentrations were monitored in vivo in the striatum during steady state, 15 min of complete brain ischemia, and 4 h of reflow and compared with purine and nucleotide levels in the tissue. Ischemia was induced by three-vessel occlusion combined with hypotension (50 mm Hg) in male Sprague-Dawley rats. EC purines were sampled by microdialysis, and tissue adenine nucleotides and purine catabolites were extracted from the in situ frozen brain at the end of the experiment. ATP, ADP, and AMP were analyzed with enzymatic fluorometric techniques, and adenosine, hypoxanthine, xanthine, and inosine with a modified HPLC system. Ischemia depleted tissue ATP, whereas AMP, adenosine, hypoxanthine, and inosine accumulated. In parallel, adenosine, hypoxanthine, and inosine levels increased in the EC compartment. Adenosine reached an EC concentration of 40 microM after 15 min of ischemia. Levels of tissue nucleotides and purines normalized on reflow. However, xanthine levels increased transiently (sevenfold). In the EC compartment, adenosine, inosine, and hypoxanthine contents normalized slowly on reflow, whereas the xanthine content increased. The high EC levels of adenosine during ischemia may turn off spontaneous neuronal firing, counteract excitotoxicity, and inhibit ischemic calcium uptake, thereby exerting neuroprotective effects.
Fifty consecutive patients with different esophageal symptoms were investigated with esophageal endoscopy, transit scintigraphy, and gastroesophageal (GE) scintigraphy with extra-abdominal compression. Scintigraphic findings were abnormal in 27 of those 31 patients (87%) who were classified as abnormal at endoscopy. A prolonged transit time was the commonest finding, but hiatal hernia and GE reflux were also found. However, the scintigraphic procedure showed abnormalities in 6 of 19 (31%) who were classified as normal at endoscopy. Esophageal scintigraphy is recommended as a screening test before endoscopy is decided on.
The effect of structural alterations on the biotransformation rate of glucocorticosteroids (GCS) by rat- and human-liver 9000 g supernatant fraction was studied. Insertion of a 16 alpha-hydroxy group in the prednisolone molecule (16 alpha-hydroxyprednisolone) was found to decrease the rate of biotransformation. Substitution of the 16 alpha,17 alpha-hydroxy groups with a symmetric acetal (in, for example, desonide) or especially a non-symmetric acetal (in, for example, budesonide), enhanced the biotransformation rate several-fold, particularly in human liver. Differences in the rates of metabolism in rat and human liver were observed. Hydrogenation of the 1,2-double bond in prednisolone and budesonide (hydrocortisone and 1,2-dihydrobudesonide) enhanced the biotransformation rate nine-fold in rat liver but only two-fold in human liver. Fluorination of the steroid nucleus in 6 alpha- and 9 alpha-positions enhanced the biotransformation rate several-fold in human liver, but in rat liver fluorination marginally decreased the rate of biotransformation. These in vitro results correlate well with available data on the first-pass liver metabolism of the studied GCS. This indicates that in vitro data can be useful in predicting oral bioavailability of GCS.
The effect of blocking N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid (EAA) receptors during brain ischemia was studied in order to test a link between EAAs and neuronal energy metabolism. The receptors were blocked unilaterally in the rat striatum before, during and after an ischemic insult. The receptor blocker, D-2-amino-5-phosphonovalerate (D-APV) was administered by dialysis perfusion, which also allowed continuous sampling for analysis of adenosine triphosphate degradation products, i.e. purine catabolites, in control and D-APV-treated striata. Purine catabolites were analysed with reversed-phase liquid chromatography. Hypoxanthine, xanthine, inosine and adenosine increased dramatically in the striatum during ischemia and reached maximum levels during early reperfusion. D-APV reduced the extracellular accumulation of all measured purine catabolites during ischemia/reflow and improved to some extent the recovery of the striatal electroencephalographic activity in the majority of the animals. The results suggest that NMDA receptor blockade attenuates acute changes in energy metabolism during ischemia.
We report a patient with classical chronic lymphocytic leukemia of IgM kappa phenotype and a stable clinical course, in which repeated chromosome analyses of blood lymphocytes revealed the coexistence of t(14;18), a marker often associated with follicular low grade lymphocytic lymphomas, and t(2;8), a variant of the t(8;14) typically seen in Burkitt's lymphoma. Both these translocations involve immunoglobulin gene regions, the t(2;8) being almost always found in patients with kappa light chain restriction. However, in an EBV-immortalized cell line of this patient, most karyotypes contained t(14;18) alone, without the t(2;8). This suggests that t(14;18) was the primary cytogenetic event, and that t(2;8) evolved subsequently. As a secondary cytogenetic event, the t(2;8) may not share the grave clinical consequences of a primary t(2;8) as seen in Burkitt's lymphoma and related disorders.
The presence of hepatitis B virus (HBV) DNA was investigated in 26 hepatitis B surface antigen-positive blood donors. Three donors (12%) were concordantly positive for HBV DNA and hepatitis B e antigen (HBeAg) and had IgM antibody to hepatitis B core antigen (anti-HBc). Two donors (8%) had HBV DNA without HBeAg; both were positive for antibody to HBeAg and lacked IgM anti-HBc. Twenty-one HBV DNA-negative donors had antibody to HBeAg, and all were negative for HBeAg and IgM anti-HBc. Blood units from 16 donors were transfused. A sufficient serological and clinical follow-up was available for 10 HBV-susceptible recipients. Three recipients of HBV DNA-positive blood units were infected irrespective of HBeAg status or presence of IgM anti-HBc. Six (86%) of seven recipients of HBV DNA-negative blood units developed HBV infection. Thus all hepatitis B surface antigen-positive blood donors should still be considered infectious irrespective of status with regard to HBeAg, HBV DNA, and IgM anti-HBc.
One-hundred-and-thirteen patients with endocarditis and valvular insufficiency were studied retrospectively with special regard to indications for operation and the optimum time for cardiac valve surgery. Thirty patients (group I) had acute, 63 (group II) subacute and 20 (group III) prosthetic valve endocarditis. Group I: Eleven patients underwent surgery in the acute stage, 8 while bacteremic; 5 of the latter died perioperatively. Of the 19 patients treated medically, 16 died. Group II: All patients underwent operation in a bacteria-free state. The mortality was 5%. Group III: Eight patients had early (less than 60 days postoperatively) and 12 late endocarditis. Total mortality was 40% (71% early and 25% late mortality). Ten patients underwent reoperation, with a mortality of 20%, compared with 60% in the medically treated group. The results support the indication for early operation in acute endocarditis with progressive cardiac failure and renal failure and prosthetic valve endocarditis, even during bacteremia.
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The tissue distribution and pharmacokinetics of 3H-budesonide were studied in the mouse after intravenous administration. The drug was rapidly (t1/2 alpha = 0.062 hrs) and extensively distributed into tissues and organs (V beta = 20.3 l/kg and Vss = 9.4 l/kg). The short elimination half-life (t1/2 beta = 1.55 hrs) and high blood clearance (Cl = 9.04 l/hr/kg) demonstrated a rapid elimination of budesonide from the body. Whole-body autoradiography showed very high amounts of radioactivity in the excretory organs liver and kidney. Also in the lung and lymphatic tissues high amounts of radioactivity were noted. The adrenal cortex but not the medulla was heavily labelled. Radioactivity passed the blood-placenta barrier and to some extent the blood-brain barrier. The identity of the radioactivity in some organs was analysed by liquid chromatography. At all times after dosing (up to 4 hours), the dominating part of the lung, spleen and brain radioactivity was attributable to unchanged budesonide. After 60 min., the dominating part of the kidney radioactivity was identified as polar metabolites of budesonide. The liver radioactivity was at all observation times found to consist mainly of polar metabolites, reflecting the efficient liver biotransformation of budesonide.
The tracheobronchial mucosa of anaesthetized guinea-pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min-1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelled in vivo with 99Tcm, and analysing for FITC-dextran, MW = 70,000, that had been given i.v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC-dextran. Capsaicin 0.1 nmol extravasated 223 micrograms of FITC-dextran per g wet weight of airway tissue (P less than 0.001). Substance P 0.1 nmol, 41 micrograms g-1 (P greater than 0.05); substance P 0.3 nmol, 142 micrograms g-1 (P less than 0.001); eledoisine 0.1 nmol, 101 micrograms g-1 (P less than 0.01); ovalbumin 0.1 microgram, 179 micrograms g-1 (P less than 0.001); LTC4 0.2 pmol, 180 micrograms g-1 (P less than 0.001); LTD4 0.2 pmol 223 micrograms ml-1 (P less than 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion (0.02 ml min-1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extravasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vascular permeability to macromolecules is subject to physiological and pharmacological control.