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Biomedical subjects

S Fischer

Publications and source records attributed to S Fischer.

At least 325 records · Page 18Linked to original sources
PubMed1990

[Clinical management of persistent primary hyperparathyroidism].

Persistent hypercalcemia following operation for hyperparathyroidism presents a challenge to both the patient and the surgeon. Between 1/79 and 3/90 a total of 351 patients with parathyroid disease were operated and 34 (10%) patients had persistent hyperparathyroidism. Average age was 62 years. 1/3 of pat. was asymptomatic and 1/3 had renal calculi. Preoperative studies were successful in diagnosing the affected side in 34% using CT, in 44% using sonography and in 63% when selective venous catheterization was used. A total of 44 operations were performed in 34 pat. Up to three operations were performed in 24% of patients. Eight of 34 pat. have refused additional surgery. Repeated surgery was successful in 24 pat. In eight pat. ectopic glands were identified and six of these were located in the mediastinum.

Adult↗
PubMed1990

Home self-administration of intravenous immunoglobulin therapy in children.

Twelve children with primary immunodeficiency, aged 2 to 17 years (mean +/- 1 SD = 9.8 +/- 5.3), were enrolled in a 9-month study to evaluate the feasibility and safety of home self-infusion of intravenous immunoglobulin (IVIg). An initial 2-month training and supervisory period was followed by a 6- to 7-month period during which the children or their parents infused IVIg in a home setting. Eight children received an average dose of 204 +/- 12 mg/kg every 2 weeks, two children received a dose of 400 mg/kg every month, and an additional two children received 240 to 250 mg/kg every 10 days. Peak and trough levels varied from 946 +/- 20 mg/dL and 627 +/- 16 mg/dL, respectively, in children receiving IVIg every 2 weeks. The peak-trough values for the children receiving IVIg every month were 1105 +/- 94 mg/dL and 457 +/- 78 mg/dL, while those of children receiving IVIg every 10 days were 840 +/- 24 mg/dL and 553 +/- 109 mg/dL. A total of 224 infusions were administered, with only two minor reactions occurring (reaction rate of 0.9%). There was no difference in the frequency of infections and antibiotic use during the study compared with the previous phase. The results demonstrate that home self-infusion of IVIg in children is safe and feasible.

Adolescent↗
PubMed1990

Platelet-neutrophil interactions. 12S,20- and 5S,12S-dihydroxyeicosapentaenoic acids: two novel neutrophil metabolites from platelet-derived 12S-hydroxyeicosapentaenoic acid.

Dietary marine n-3 polyunsaturated fatty acids have demonstrated an antiinflammatory potential in epidemiologic and intervention studies in humans. Proposed mechanisms, involving only leukocytes, fall short of explaining this potential completely. Enriched by dietary means with eicosapentaenoic acid (EPA), stimulated human platelets release substantial amounts of eicosapentaenoic acid and 12S-hydroxyeicosapentaenoic acid (12S-HEPE) in addition to 12S-hydroxyeicosatetraenoic acid (12S-HETE) derived from arachidonic acid. Human neutrophils metabolize 12S-HETE to 5S,12S-DiHETE when stimulated, whereas unstimulated neutrophils produce 12S,20-DiHETE. This study was undertaken to characterize metabolism of 12S-HEPE in human neutrophils. We demonstrate herein for the first time that 12S-HEPE is metabolized by human neutrophils. In unstimulated neutrophils 20-hydroxylation to 12S,20-DiHEPE occurs, whereas in stimulated neurtrophils 5-lipoxygenation to 5S,12S-DiHEPE takes place. The structures of these metabolites were characterized by their relative retention times on reversed-phase high pressure liquid chromatography, by their UV absorbance spectra, and by gas-liquid chromatography-mass spectrometry. With increasing amounts of 12S-HEPE, stimulated neutrophils produced increasing amounts of 5S,12S-DiHEPE, which is virtually inactive biologically. Concomitantly, production of the potent chemokinetic and chemoattractant arachidonic acid derivative leukotriene B4 decreased. Thus, 12S-HEPE can compete with endogenous arachidonic acid for 5-lipoxygenation in stimulated human neutrophils. 12,20-DiHEPE, LTB5, and 5S,12S-DiHEPE were detectable after coincubating EPA-enriched platelets with unenriched neutrophils, and arachidonic acid-derived 5-lipoxygenase products were decreased. We conclude that 12S-HEPE can participate in platelet-neutrophil interactions in a manner similar to 12S-HETE. By providing competing substrates for neutrophil 5-lipoxygenase, platelets might contribute to the antiinflammatory potential of dietary n-3 fatty acids through platelet-neutrophil interaction.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Properties of a novel plasminogen activator (BM 06.022) produced in Escherichia coli.

Since currently available thrombolytics still show disadvantages, such as administration by infusion, occurrence of intracranial hemorrhage, major hemorrhagic complications, allergic reactions, and high price, a novel tissue plasminogen activator has been developed. BM 06.022 is a t-PA mutant produced in Escherichia coli by DNA technology. It has no oligosaccharide side-chains and comprises the kringle 2- and protease domains of t-PA. Like t-PA, the enzymatic activity of BM 06.022 can be stimulated by fibrin. However, BM 06.022 binds to neither endothelial cells nor fibrin. Despite this, BM 06.022 demonstrates the same fibrin selectivity in vivo as t-PA. Investigation of the pharmacokinetic properties in rats, rabbits, dogs, and primates reveals, depending on species, a 4.5- - 10.4-fold longer dominant half-life and 3- - 8.4-fold slower plasma clearance than t-PA (alteplase). In spite of its lower specific activity in vitro, BM 06.022 has a thrombolytic potency which is 4.6 - 11.5 times higher in vivo than that of alteplase in the rabbit model of venous thrombosis and the canine model of coronary artery thrombosis. BM 06.022 achieves reperfusion significantly more rapid than long-acting anistreplase. Therefore, because of its improved pharmacokinetic properties, BM 06.022 might be administered to infarct patients by i.v. injection in the pre-hospital phase to achieve rapid lysis. Due to its lack of fibrin- and endothelial-cell-binding, combined with retained fibrin selectivity, BM 06.022 further promises to induce fewer hemorrhagic complications than either t-PA or streptokinase.

Animals↗
PubMed1990

[Quantification of changes in the skeletal muscle blood circulation following revascularization using a 99m technetium-labeled tracer].

A new 99mTc-labelled tracer (99mTc-Sestamibi) was used for the first time to demonstrate the perfusion of the skeletal muscle. In 16 patients with obstructive atherosclerosis of the lower limbs the change of perfusion of thigh and lower leg was studied with SPECT before and after vascular surgery (n = 11) or percutaneous transluminal angioplasty (n = 5). Comparative results of scintigraphic measurements and clinical observations (ankle-arm pressure, treadmill test) in 10 surgical patients (14 operated legs) showed correct positive or negative results in 86% (12/14).

Aged↗
PubMed1990

Glomus tumours. An immunohistochemical study.

The histological and immunohistochemical features of 20 glomus tumours (glomangiomas) were studied retrospectively in routinely processed material. The tumours came from 18 patients (9 women and 9 men, aged 25 to 80 years); two were recurring lesions. Twelve were classified as solid glomus tumours, eight as glomangiomas. Small nerve fibres were present in all except one. A variable number of mast cells were found in the stroma. The glomus tumour cells were negative when stained for Neuron-Specific Enolase, Glial Fibrillic Acidic Protein, S-100 Protein, Chromogranin, or with the Ulex Europaeus Lectin type 1. Conversely, all were found to be positive for Actin, Myosin, and Vimentin. Four exhibited an equivocal reaction for Desmin, the rest were negative. This immunohistochemical profile is in accordance with the findings of other investigators and can be helpful in differential diagnosis. It also shows the glomus cell to be related to smooth muscle cells and pericytes. The majority of these lesions are probably hamartomas, but a few may be true neoplasms.

Adult↗
PubMed1990

[The protective effect of adsorbents against ochratoxin A in swine].

Adsorption of the mycotoxin ochratoxin A by activated charcoal, various bentonites (acid, alkaline, neutral), and hydrated sodium calcium aluminosilicate was tested in vitro as well as in feeding experiments with pigs. In vitro tests showed that the 1% addition of activated charcoal leads to complete adsorption of ochratoxin A from aqueous solutions. This effect was not influenced by pH-values ranging from 3-8. In contrast, adsorption by bentonite and hydrated sodium calcium aluminosilicate occurred primarily in the acid range (pH 3-4). Dietary addition of hydrated sodium calcium aluminosilicate (1%) and acid bentonite (1%, 10%) to ochratoxin A-contaminated feed (1.0 mg/kg) had no effect on the blood or tissue levels of the toxin in pigs. The addition of 1% activated charcoal caused a slight decrease of ochratoxin A in the blood, whereas a tenfold dosage resulted in a 50% to 80% reduction of ochratoxin A levels in both blood and tissue. Reduction of ochratoxin A absorption via the dietary administration of activated charcoal (5%) was confirmed in a 16 week feeding experiment. However, this experiment also showed the serum level of vitamin E to be lower than in the controls receiving adsorbent-free feed.

Absorption↗
PubMed1990

Efficacy of a combined bezafibrate retard-colestyramine treatment in patients with hypercholesterolemia.

In a placebo-controlled randomized study the effect of combined bezafibrate-colestyramine therapy in comparison with monotherapy with both drugs was investigated. 47 patients with primary hypercholesterolemia received 400 mg bezafibrate (Cedur) retard/d, subsequently bezafibrate retard plus colestyramine (24 g/d) or colestyramine plus placebo in a double-blind fashion. The combination therapy was most effective (LDL decrease 36%, HDL-C increase 31%, apoprotein B decrease 28%), bezafibrate and colestyramine were equally effective with regard to LDL-C and apoprotein B, but only bezafibrate decreased triglycerides (-37%) and increased HDL-C (+24%). Bezafibrate was well-tolerated, but gastro-intestinal side-effects were frequent during therapy with colestyramine, and 16 patients tolerated only a reduced dosage of this drug. From the results presented it can be concluded that combined therapy with bezafibrate retard plus colestyramine is highly effective in the treatment of severe hypercholesterolemia.

Bezafibrate↗
PubMed1990

[Application of fluoride varnish Duraphat with a cotton carrier respectively a syringe for cartridges--a comparison study].

A study for comparing two methods of Duraphat application in children of the 1st and 6st grade was carried out to examine material allowed, expenditure of time, handling of the instruments and hygienic aspects. There was established, that application with syringe for cartridges and bended tubule was better than the application with cotton carrier, concerning both the duration of application and economical aspects of the material allowed. Therefor the use of syringe for cartridges for the application of Duraphat in collective and individual caries prevention is recommended.

Child↗
PubMed1990

[Preventing the recurrence of common bile duct calculi following endoscopic papillotomy with ursodeoxycholic acid].

The effect of ursodeoxycholic acid on recurrence prevention of choledochal calculi after endoscopic sphincterotomy (EPT) was evaluated in 46 patients, whose bile duct stones had been removed endoscopically. 22 patients received 500 mg of ursodeoxycholic acid once a day, 24 patients received placebo. 1 recurrent stone could be detected in the ursodeoxycholic acid treated group 19 months after EPT, whereas 4 recurrent stones occurred in the placebo group about 16 months after EPT. Cholesterol saturation index decreased significantly by the ursodeoxycholic acid treatment 12 and 24 months after EPT (0.93 +/- 0.17 vs. 0.69 +/- 0.12 vs. 0.72 +/- 0.07). The nucleation time increased statistically significant from 9.0 days to 20.4 (12 months) and 17.7 (24 months) days, respectively. Obviously, pharmacological effects of ursodeoxycholic acid exist which modify important processes in the gallstone's pathogenesis.

Aged↗
PubMed1990

Tobacco-specific nitrosamines in European and USA cigarettes.

More than 170 types of commercial cigarettes from several European countries and the USA were analyzed for tobacco-specific nitrosamines (TSNA) in tobacco and mainstream smoke as well as for nitrate in tobacco. The cigarettes included filter and nonfilter cigarettes with different tar and nicotine yields. The observed range for N'-nitrosonornicotine (NNN) was from 4 to 1353 ng/cigarette in mainstream smoke and from 45 to 12454 ng/cigarette in tobacco. For 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) the values were between not detected (less than 4 ng/cigarette) and 1749 ng/cigarette in mainstream smoke and between not detected (less than 50 ng/cigarette) and 10745 ng/cigarette in tobacco. Nitrate levels ranged from 0.6 to 19.4 mg/cigarette. The TSNA levels for the cigarettes from the different countries investigated were in a similar range with the exception of few individual brands. The results demonstrated that there is no correlation between TSNA and tar deliveries in mainstream smoke. The TSNA deliveries in mainstream smoke depend on the amount or preformed TSNA in the actual tobacco composition, which is influenced by the nitrate level of the tobacco and the tobacco type. According to these results the tar delivery, although crucial, is not a sufficient index for the biological activity and the carcinogenic potential of cigarette smoke. Reduction of TSNA exposure can be achieved by selecting tobaccos with low levels of preformed TSNA in tobacco, which means a low nitrate content and reduction of the amount of Burley tobaccos and stems in blended cigarettes.

Chromatography, Gas↗
PubMed1989

A critical evaluation of urinary immunoreactive thromboxane: feasibility of its determination as a potential vascular risk indicator.

Urinary immunoreactive thromboxane (irTXB2) has been found helpful in acute settings with altered renal, but also extrarenal thromboxane formation. As only trace amounts of systemically formed thromboxane are excreted unmetabolized, the nature of urinary irTXB2 was explored. The two most abundant metabolites of systemic thromboxane, 2,3-dinor-TXB2 and 11-dehydro-TXB2, crossreacted about 70% and less than 1%, respectively, with a widely used thromboxane antiserum. After solid-phase extraction of urine samples and separation on reversed-phase HPLC, the bulk of immunoreactivity always eluted as one peak shown to correspond to 2,3-dinor-TXB2. Much less was found in fractions where TXB2 eluted. Therefore, urines were read against calibration curves constructed with 2,3-dinor-TXB2. This direct estimation gave good recoveries for standard 2,3-dinor-TXB2 and correlated well, both in healthy controls and in patients at increased risk or with overt vascular disease, to values obtained after solid phase extraction, purification on reversed-phase HPLC and quantitation by either gas-chromatography mass-spectrometry or radioimmunoassay. Patients with multiple cardiovascular risk factors but free from detectable vascular disease excreted significantly more irTXB2 than age-matched controls with non-vascular conditions or normals. Therefore, urinary irTXB2 measured with this antiserum represents 2,3-dinor-TXB2, reflecting the systemic formation of TXB2. This simple approach is feasible for screening thromboxane formation in large series of patients. Its acumen in detecting the early development of vascular disease and its relation to established risk factors deserves large-scale prospective testing.

Chromatography, High Pressure Liquid↗
PubMed1989

Structure of the human lck gene: differences in genomic organisation within src-related genes affect only N-terminal exons.

Although cDNA sequences coding for several Rous sarcoma virus Src-related protein tyrosine kinases (PTKs) have been reported for several years, knowledge of the structure and organisation of genes of the src family is still limited. In this work, a detailed structure and organisation of the human lck gene is reported. A 17-kb genomic clone encoding human p56 Lck, a lymphocyte-specific PTK of the Src-related subfamily, has been isolated. The human lck gene is organized in 13 exons, one more than in the human cellular (c)-src gene. The twelve coding exons are located in this clone, whereas the putative 5'-noncoding exon is probably located very far upstream from the second exon. Splicing sites for exons 4 to 12, which encode both conserved phospholipase-C-like and catalytic domains of the Src-like PTKs, arise exactly at the same position for the human lck, human c-src and c-fgr genes. The only differences concern the splice sites of exons 1' and 2, which encode the unique N-terminal domain of human Lck. These results give further evidence that the different PTKs of the Src-like family have probably evolved through the mechanism of exon shuffling.

Amino Acid Sequence↗
PubMed1989

[Congenital methemoglobinemia with cytochrome-b5-reductase deficiency: 4th Swiss family].

In a female newborn presenting with pronounced cyanosis in the absence of cardiopulmonary disease, the cyanosis was due to methemoglobinemia of 33% at birth and 17% at 24 hours (upper limit 0.5%) which was found to be secondary to deficiency of red blood cell cytochrome b5 reductase (EC 1.6.2.2.). Only residual activity of this enzyme was measurable, thus indicating homozygosity. Both parents were found to be heterozygous for this inherited disease. Of the six sisters and brothers of the newborn's father, five were investigated and all found to be heterozygous for the defective allele. Measurement of cytochrome b5 reductase showed both soluble and membrane bound fractions to be affected equally in the red cells of the baby's heterozygous parents.

Adult↗
PubMed1989

Phosphorylation of p56lck by external ATP in intact cells.

Recent studies have suggested a role for extracellular ATP. In this report we show that extracellular labelled ATP crosses the plasma membrane of intact lymphoma cells and peripheral blood lymphocytes and phosphorylates p56lck a tyrosine protein kinase specific of lymphoid cells. Two other phosphoproteins of 92Kd and 35Kd become detectable on alkali treated gels. Phosphorylation occurs within minutes following addition of ATP. ATP, GTP, ADP and an ATP analog prevent phosphorylation but not AMP nor Pi; trypsinization of cells abolishes labelling. The possible involvement of P2 purinergic receptors is discussed.

Adenosine Triphosphate↗
PubMed1989

[Drug cholelitholysis and the nucleation time].

Nucleation time (time elapsed until first appearance of cholesterol crystals in incubated bile fluid) and the lithogenic index were measured on 25 patients (aged 45.1 +/- 16.8 years; Broca index 106.7 +/- 4.2%) with radiolucent gallstones, before receiving daily 500 mg chenodeoxycholic acid and ursodeoxycholic acid orally. The nucleation time in the group of nine patients in whom complete lysis was achieved was 4.7 +/- 0.8 days, compared with 15.0 +/- 2.2 days in those with only incomplete lysis (P less than 0.001). There was no statistically significant difference between the two groups as to age, Broca index, lithogenic index and biochemical values. Thus the determination of nucleation time can contribute to distinguishing between responders and nonresponders to oral treatment for dissolving gallstones and may improve the success rate of the method.

Adult↗
PubMed1989

In vivo formation of metabolites of prostaglandins I2 and I3 in the marmoset monkey (Callithrix jacchus) following dietary supplementation with tuna fish oil.

Recent studies have shown that ingestion of eicosapentaenoic acid (EPA) in man results in the formation of 'trienoic' prostanoids which amy partly explain the potent antithrombotic/antiatherogenic properties of long-chain polyunsaturated n-3 fatty acids (PUFAs). However, endogenous formation of cyclooxygenase metabolites of EPA has not been demonstrated in an animal model, and in vitro studies indicate a clear species difference in the conversion of EPA to PGI3. Thus, in the present study, the in vivo formation of PGI3 following long-term dietary tuna fish oil supplementation was investigated in a small non-human primate - the marmoset monkey (Callithrix jacchus). The excretion of major urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and delta 17-2,3-dinor-6-keto-PGF1 alpha (PGI3-M) was estimated as an index of total body synthesis of PGI2 and PGI3, respectively. Following extraction, dinor prostanoid metabolites were separated by capillary gas chromatography and identified by negative ion chemical ionization mass spectrometry. Supplementation of the standard (reference) diet with either sheep fat or sunflower seed oil did not alter the body production of PGI2-M. However, following the tuna fish oil-enriched diet, there occurred not only an increase in urinary PGI2-M (reference 70.7 +/- 9.0; tuna fish oil 115.5 +/- 12.1 ng/g creatinine, P less than 0.05), but also a considerable formation of PGI3-M (62.9 +/- 5.3 ng/g creatinine), which was not seen in any other dietary group; in addition, the urinary level of immmunoreactive 2,3-dinor-thromboxane B2/3 was reduced after ingestion of tuna fish oil. These urinary changes were accompanied by a rise in plasma phospholipid-bound EPA and docosahexaenoic acid (DHA). In addition, tuna fish oil supplementation resulted in a significant reduction in plasma cholesterol (53%) and triacylglycerols (44%). The present study provides for the first time experimental evidence for the in vivo formation of PGI3 in an animal model and also confirms the earlier observations in man following dietary fish oil supplementation.

Animals↗