Search PubMed⌕ Search

Biomedical subjects

K Jacob

Publications and source records attributed to K Jacob.

At least 73 records · Page 4Linked to original sources
PubMed1989

Different therapeutic efficacy of ketoconazole in patients with Cushing's syndrome.

The property of ketoconazole to inhibit adrenal biosynthesis of cortisol was used in a clinical study of 14 patients with Cushing's syndrome (pituitary-dependent Cushing's disease, n = 10; adrenocortical adenoma, n = 2; adrenocortical carcinoma, n = 1; ectopic ACTH syndrome, n = 1). Five patients were treated in a short-term manner (1000 mg over 24 h) and nine patients for a longer period (600 mg/die from 1 week up to 12 months). After short-term administration of ketoconazole, serum cortisol levels fell distinctly only in the patient with adrenocortical adenoma, but not at all or only slightly in the other patients, whereas serum levels of progesterone and 11-deoxy-compounds increased markedly in all patients, with the exception of the patient with adrenocortical carcinoma. Plasma ACTH levels increased in the patients with Cushing's disease but not in the patients with tumor. After long-term treatment of three patients with Cushing's disease over 3, 10, and 12 months, the clinical signs of hypercortisolism persisted or were only slightly ameliorated. In these three patients as well as in three other patients with Cushing's disease treated for a shorter period of 1 to 4 weeks, serum and urinary cortisol levels decreased, but were not normalized, whereas plasma ACTH levels increased variably. Only in one patient with Cushing's disease, in the second patient with adrenocortical adenoma, and in the patient with ectopic ACTH syndrome, serum and urinary cortisol levels returned to normal. We conclude from our data, that the antimycotic drug inhibits biosynthesis of cortisol by blocking adrenal 11 beta- and 17 alpha-hydroxylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

ACTH Syndrome, Ectopic↗
PubMed1989

Release of glutamate and of free fatty acids in vasogenic brain edema.

The pathophysiological potential of mediator substances in manifestations of secondary brain damage is attracting increased attention. This is particularly true of the excitatory transmitters glutamate and arachidonic acid. Noxious properties of these compounds in central nervous tissue have been demonstrated. The current study was performed to determine whether glutamate and arachidonate are released in brain tissue secondary to focal trauma. For this purpose, a cold injury of exposed cerebral cortex was induced in cats. Marked accumulation of glutamate was observed in interstitially drained edema fluid, reaching 10 to 15 times the level that was assessed in normal cerebrospinal fluid (CSF) prior to trauma. The extracellular release of glutamate was further dramatically enhanced by a critical decrease of the cerebral perfusion pressure due to a malignant increase of intracranial pressure. Under these conditions, glutamate concentrations 1000 to 1500 times normal levels accumulated in vasogenic edema fluid, demonstrating a relationship between the extent of the release of glutamate in damaged brain and the severity of the insult. Although under normal conditions glutamate concentrations in plasma were considerably higher than in the interstitial fluid, the pronounced increase of glutamate in this compartment due to trauma cannot be explained by transport of the compound together with the plasma-like edema from the intravascular space. Corresponding findings were obtained for free fatty acid concentrations in edema fluid. Almost all fatty acids that were studied had a significantly higher concentration in edema fluid than in normal CSF obtained as a control prior to trauma. However, contrary to the findings for glutamate, fatty acid concentrations in edema fluid were lower than in plasma. Accumulation of fatty acids in vasogenic edema fluid might, therefore, have resulted from uptake of the material together with edema fluid through the breached blood-brain barrier. Arachidonic acid was an exception. Its concentrations were significantly higher in edema fluid than in plasma, suggesting that it was released from cerebral parenchyma as the underlying mechanism of its extracellular accumulation. The current observations provide further support for a mediator function of glutamate and arachidonic acid in acute traumatic lesions of the brain. Quantitative assessment of the release of highly active mediator substances in brain tissue may facilitate analysis of the therapeutic efficiency of specific treatment aimed at interfering with the release or pathological function of mediators of secondary brain damage.

Animals↗
PubMed1989

Coproporphyrin isomers II and IV are normal constituents of human urine.

We describe for the first time the detection of small amounts of the atypical coproporphyrin isomers II and IV in urine from healthy subjects. Efficient sample preparation procedures together with a highly selective isocratic ion-pair high-performance liquid chromatographic method enabled the determination of these unexpected compounds. Formation of the atypical coproporphyrin isomers was shown to result mostly from non-enzymatic isomerization at the coproporphyrinogen level within the human body, whereas only traces were formed in vitro during collection and storage of the urine samples under the conditions applied.

Chemical Phenomena↗
PubMed1988

[Renal and enteral elimination of coproporphyrin isomers in Rotor's syndrome. A family study].

Urinary and fecal total, isomer I, and isomer III coproporphyrin excretion of a Rotor's syndrome patient and his family were determined. The propositus showed increased urinary total coproporphyrin excretion (248 micrograms/24 h) and a shift of the coproporphyrin isomer I/III relation (70%/30%). The propositus's father and two siblings also had elevated renal excretion of coproporphyrin I. Total coproporphyrin excretion was enhanced only in the propositus's father and one sibling, while being normal in another sibling. All family members that could be investigated showed considerably decreased fecal porphyrin excretion. In Rotor's syndrome porphyrin excretion is mainly renal. The coproporphyrin isomer I/III relation is shifted towards isomer I. Phenotypically normal relatives with normal bilirubin plasma levels may have alterations in both their renal and enteral coproporphyrin excretion.

Adult↗
PubMed1988

Detection of non-typical porphyrin isomers in human urines by ion-pair reversed-phase high-performance liquid chromatography.

An improved ion-pair reversed-phase high-performance liquid chromatographic system has been developed for the separation of uroporphyrin isomers I, II and III, whereas the isomers III and IV could not be resolved. Application of this method to the analysis of urines from porphyric patients indicated the presence of small amounts of the non-typical uroporphyrin isomer II. The questionable presence of the isomer IV was confirmed by acid-catalyzed decarboxylation to the corresponding coproporphyrin isomers, which were completely separated by a modified ion-pair method at elevated column temperatures. These procedures enabled the detection of small fractions of the atypical isomers II (1-3%) and IV (8-15%) besides the normal isomers I and III in urines of patients suffering from attacks of acute intermittent porphyria. Because such urines contain large amounts of porphobilinogen, the nonenzymatic self-condensation of porphobilinogen to uroporphyrinogens was studied under mild reaction conditions. In these experiments quite similar isomeric compositions were observed as compared to those in urines of patients with acute intermittent porphyria. Thus the non-typical uroporphyrin isomers II and IV present in human urines originate from a simple non-enzymatic condensation of porphobilinogen.

Chromatography, High Pressure Liquid↗
PubMed1987

Identification of clinical and environmental isolates of Legionella pneumophila by analysis of outer-membrane proteins, ubiquinones and fatty acids.

47 strains of L. pneumophila, 9 reference strains of eight serogroups, 15 clinical isolates and 23 water-derived strains from different cities were analysed with respect to three chemical constituents of the cell envelope: outer- membrane proteins (OMPs), ubiquinones and fatty acids. The OMPs were obtained by Sarkosyl-extraction of a total membrane preparation and analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The ubiquinone content was quantitated by high-performance liquid chromatography (HPLC) and the fatty acid composition was established by gas-liquid chromatography coupled with mass spectrometry (GLC-MS). In all strains the OMP yielded the known characteristic pattern with the major component of 29 kilodalton. The ubiquinone content was very consistent within different strains revealing Q-12 with 65% as the predominant feature. Q-11 and Q-13 were present in amounts of 11% and 23%, respectively. Q-14 was found in trace amounts of about 0.65%. Only a very few ubiquinones with side chains shorter than 11 residues were present. GLC-MS allowed an unequivocal identification of each fatty acid. The branched chain fatty acid i-16:0 was the predominant feature with 33% followed by the unsaturated straight-chain acid 16:1. In this respect earlier reports by other authors were confirmed but minor compounds not detected so far could be revealed as 15:1, the doublet 18:1 and i-18:0, 19:1 and 20:1. OMP profiles are easy to establish and to interpret. They are well suited for identification of the species L. pneumophila. Ubiquinone analysis permits rapid but preliminary species identification, whereas fatty acid analysis by GLC-MS is an intricate technique providing a valuable chemical marker for L. pneumophila. The biochemical analyses presented here can supplement immunological studies, clarify immunological findings and help to identify new serogroups of L. pneumophila.

Bacterial Outer Membrane Proteins↗
PubMed1984

Myopathic carnitine deficiency associated with lymphocytic malignant non-Hodgkin lymphoma and monoclonal immunoglobulin G-K.

A 47-year-old male patient suffered from recurrent myalgia, induced by fasting or physical exercise. Later, he developed progressive muscular weakness. Serum levels of creatine phosphokinase (CPK) were elevated to approx. 400 U/1. Muscle biopsies showed lipid storage myopathy and signs of acute fiber necrosis, muscle carnitine was decreased to below 20% of controls, carnitine palmitoyl transferase (CPT) activity was normal. Carnitine was also moderately decreased in a liver biopsy and in plasma. Urine excretion of carnitine was low, no elevation of short-chain dicarboxylic acids could be found. The patient was also found to suffer from a lymphocytic malignant non-Hodgkin lymphoma, a monoclonal immunoglobulin (Ig) G-k in plasma and lymphocytic infiltration of bone marrow were demonstrated. At that time no evidence had been obtained to indicate that these two diseases could be related to each other. Autoantibodies against skeletal muscle could not be demonstrated. Absorption of L-carnitine p.o. was normal, however, plasma levels of carnitine fell again rapidly. Administration of 3 X 2 g L-carnitine per day normalized the patient's plasma carnitine levels and led to an increase of plasma short-chain acylcarnitine and ketone bodies, particularly beta-hydroxybutyrate (B-HOB). However, no significant clinical improvement could be seen. Additional application of prednisone led to normalization of CPK serum levels.

Carnitine↗
PubMed1984

Improved separation and detection of free porphyrins by high-performance liquid chromatography.

Porphyrins were separated using ion-pair reversed-phase high-performance liquid chromatography. The eluents were aqueous potassium phosphate buffer and tetrabutylammonium phosphate in methanol. The influences of pH value and ionic strength of the phosphate buffer and molarity of the ion-pair reagent in methanol were investigated to improve separation and detection. A linear response curve was obtained from 0.38 to 7.64 pmol for coproporphyrin I. The detection limits were determined to be 0.12 pmol for coproporphyrin I and 0.22 pmol for uroporphyrin I.

Buffers↗
PubMed1984

Sensitive mass fragmentographic determination of acidic catecholamine metabolites in human body fluids.

A sensitive and simple method for the simultaneous quantitation of homovanillic acid and vanilmandelic acid in small samples (0.1-1.0 ml) of urine, serum, plasma and cerebrospinal fluid is described. The stable dimethylthiophosphinyl methyl ester derivatives are detected specifically by mass fragmentography using the respective deuterated compounds as internal standards. Gas chromatographic separation is performed on a fused-silica DB-1 capillary column combined with a cold injection system for large sample volumes. Linear response curves and a detection limit of 1 ng/ml are obtained. The method has been applied to the localization of pheochromocytoma by selective determination of venous vanilmandelic acid.

Adrenal Gland Neoplasms↗
PubMed1981

Analysis of free stool porphyrins by high-performance liquid chromatography.

The determination of stool porphyrins is necessary for the diagnosis of some porphyrias in clinical laboratories. Quantitative methods for the analysis of faeces for porphyrins are unpleasant and difficult to perform. An extraction and ion-pair reversed-phase high-performance liquid chromatographic procedure is described for the separation and determination of individual free stool porphyrins. The within-assay coefficients of variation range from 2 to 6%. A linear response curve is observed between 38 and 380 nmol/g for coproporphyrin I in dry stool The method can be applied to the routine analysis of free stool porphyrins in the clinical laboratory.

Chromatography, High Pressure Liquid↗
PubMed1981

Evaluation of a new valproic acid enzyme immunoassay and comparison with a capillary gas-chromatographic method.

A new homogeneous immunoassay (EMIT) for valproic acid was evaluated. Besides testing the manual version of this enzyme immunoassay, we also developed two mechanized procedures for centrifugal analyzers (the CentrifiChem and the COBAS system), which take less time and are more precise than the manual method. Within-assay precision (CV) was 4.5% with the manual technique and 2% with the analyzers. Between-assay precision (CV) ranged from 4 to 13% for all three techniques. Accuracy of th manual method was checked by dilution and analytical recovery experiments. Our comparison of the EMIT results with those obtained by a comparison method (capillary gas chromatography) showed no significant difference. No interference from hemolysis, hyperbilirubinemia, or aliphatic amino acids was observed. At high concentrations of bile acids and with lipemic sera the analytical recovery rates decreased slightly, to 87% and 92%, respectively.

Amino Acids↗
PubMed1980

Highly sensitive method for the quantitation of homovanillic acid in cerebrospinal fluid.

Homovanillic acid in minute samples (50-100 microliters) of cerebrospinal fluid can be quantitated as its O-dimethylthiophosphinate methyl ester. The derivative is determined after glass capillary gas chromatography (GC) with high sensitivity by using a phosphorus-specific thermionic detector or by mass fragmentography, combined with a large sample volume split-splitless injector. The dimethylthiophosphinic esters show excellent stability against moisture and air. The precision of the overall procedure is 5.4% (GC) and 3.8% (GC-mass spectrometry). The method shows good linearity (r = 0.9999) over three orders of magnitude, from 500 pg to 500 ng. The lowest detectable concentration of homovanillic acid is 2-5 ng/ml. Concentrations of homovanillic acid determined in cerebrospinal fluid were 9.9-63.1 ng/ml (n = 10, mean = 30.9 ng/ml).

Dopamine↗