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Biomedical subjects

H Ochs

Publications and source records attributed to H Ochs.

At least 55 records · Page 3Linked to original sources

Effect of tumor promoting contraceptive steroids on growth and drug metabolizing enzymes in rat liver.

Liver tumor formation in rats treated with oral contraceptive steroids for long periods has been associated with the tumor promoting potential of these agents. As other known liver tumor promoters, e.g., phenobarbital and hexachlorocyclohexane, induce liver growth and hepatic monooxygenases, we investigated whether or not estrogens have similar effects. Female rats were treated with a wide range of doses of ethinylestradiol, including human contraceptive doses, which are approximately 1 microgram/kg. The physiological estrogen estradiol was studied for comparison. Also included were norethynodrel and norethisteron and its acetate and enanthate because these human progestins act predominantly estrogenic in rats. Daily s.c. doses of ethinylestradiol (0.5 mg/kg) produced a rapid increase of liver mass, DNA, RNA, and protein which was almost maximal after 7 days. The percentages of parenchymal cells involved in DNA synthesis and mitosis were enhanced up to 20-fold, suggesting parenchymal hyperplasia as the main cause of liver growth. Sinus wall cells showed a proportionate increase of number and DNA synthesis. Likewise, all other steroids tested produced significant increases of liver mass and DNA. For ethinylestradiol and estradiol extrapolated threshold doses were in the range of 1 microgram/kg. These doses are below those used in previous tumor promotion studies in rats. Using 5 different substrates to check monooxygenase activities of isolated liver microsomes, no induction or only very weak induction by estrogens was found. These studies suggest that induction of liver growth may be a property relevant for the tumor promoting activity of estrogens; in contrast, induction of hepatic monooxygenases does not appear to be necessary for liver tumor promotion in the rat.

Adipose Tissue↗

Necrotizing lymphoid vasculitis in X-linked lymphoproliferative syndrome.

An 8-year-old maternally related relative of three boys who had developed agammaglobulinemia associated with Epstein-Barr virus (EBV)-induced infectious mononucleosis was studied for X-linked lymphoproliferative syndrome (XLP) in 1979. At that time, he demonstrated no striking immunologic aberrations and was seronegative for EBV. Subsequently, immunologic abnormalities including failure to switch from IgM to IgG antibody synthesis after secondary immunization with bacteriophage phi X174 were detected. In 1983, he experienced episodic intracerebral hemorrhages, with the second being fatal. At autopsy, necrotizing vasculitis and aneurysms involving arteries of the central nervous system were observed. Studies of blood obtained immediately before and after death failed to show antibodies to EBV. However, EBV genome was demonstrated in tissues obtained at autopsy by DNA hybridization studies. Fatal lymphoid vasculitis in this patient is unique among boys with XLP in the registry. These findings probably extend the phenotypic expressions of XLP.

Antibodies, Viral↗

Studies of pyridine nucleotide oxidizing enzymes from human neutrophils.

An NADH cytochrome c reductase has been identified in plasma membrane fractions from neutrophils in addition to the superoxide producing NADPH oxidase which has been extensively studied by other investigators. Activation of neutrophils resulted in increased enzyme activities but to different degrees; the NADH cytochrome c reductase increased 2 fold in specific activity and the NADPH oxidase 30 fold. Treatment of the plasma membrane fraction with sonication and differential centrifugation yielded a particulate fraction (R2) with a 2 fold increase in specific activities of both enzymes and concentrations of cytochrome b and FAD. The cytochrome b in the preparation was not reduced under anaerobic conditions by either NADH or NADPH. Treatment of preparations of R2 with deoxycholate or potassium thiocyanate separated the two enzymes yielding particulate preparations with only NADPH oxidase or NADH cytochrome c reductase activity, respectively.

Cell Membrane↗

Epstein-Barr virus-induced lymphoblastoid cell lines derived from the peripheral blood of patients with X-linked agammaglobulinemia can secrete IgM.

We have established lymphoblastoid cell lines (LCL) from the peripheral blood of three individuals with X-linked agammaglobulinemia as well as three of their immunodeficient first-degree relatives. Lines could be induced with Epstein-Barr virus only when T lymphocytes were depleted from total mononuclear leukocytes. The LCLs derived from XLA patients expressed characteristics of IgM-secreting plasmacytes, including intense cytoplasmic fluorescence after staining with anti-mu, easily detectable amounts of IgM in culture supernatants, and radiolabeled IgM with both heavy and light chains in culture media and cell lysates. The cell lines induced from blood of the first-degree relatives of these patients were more varied. They often exhibited multiple isotypes for both heavy and light chains in different cells or expressed a B-lymphocyte phenotype (easily detectable surface Ig but no Ig secretion). These studies suggest that B-cell precursors are present in peripheral blood of individuals with classical XLA . Differentiation of such cells to mature cells of the B lineage can be accomplished using Epstein-Barr virus after removal of T cells.

Adult↗

Iron deficiency in the rat: effects on neutrophil activation and metabolism.

Studies were performed to determine the effects of iron deficiency in the rat on neutrophil activation and on levels of neutrophil myeloperoxidase and cytochrome b. The period of time required for neutrophil activation was not significantly affected by iron deficiency, but the maximum rates of respiration attained after activation were markedly lower (60% decrease) in iron-deficient neutrophils than in control cells. The myeloperoxidase activity of neutrophils from iron-deficient rats was also markedly decreased (approximately 75%) compared with the activity of control cells; however, the concentration of cytochrome b in the neutrophils was unaffected by iron deficiency.

Anemia, Hypochromic↗

Thymosin fraction 5 does not accelerate reconstitution of immunologic reactivity after human marrow grafting.

More than 1 year is required for immunologic function to recover following human marrow grafting. In an attempt to shorten the time required for immunologic reconstitution, 14 patients were treated with thymosin fraction 5 after transplantation. Two died before administration of thymosin could be completed. In the remaining 12 patients, immunologic studies were compared to those of patients who were transplanted but did not receive thymosin. While five patients had transient elevation of in vitro lymphocyte blastogenesis during thymosin treatment, results of other immunologic studies from patients treated with thymosin were similar to those from patients not treated. The subsequent development of graft-versus-host disease, major or minor infection, and leukaemic relapse was not different between the groups. Six patients are alive and five are well without problems; one has chronic graft-versus-host disease. We conclude that thymosin fraction 5 administered as described was not toxic. Although modifying some immunological parameters, thymosin did not appear to alter the incidence of graft-versus-host disease, infection or leukaemic relapse or to accelerate immunologic reconstitution.

Adolescent↗

[Pharmacokinetics of midazolam in man (author's transl)].

Plasma concentrations of midazolam (Ro 21-3981/001) were studied in six gynaecological patients following a 12.5 mg intravenous bolus injection of the drug for induction of anaesthesia. The plasma decay curves were found to be biphasic. Therefore the data were interpreted according to an open two compartment model. The fast distribution phase (alpha-phase) lasted about 30 to 45 min with a mean halflife of about 8-9 min. The half-life of the slow redistribution and elimination phase (beta-phase) amounted to a mean of about 150 min. The apparent volume of distribution of the cental compartment (V1) was calculated as 24.11 and the volume of distribution at steady state as 84.21 (Vd, ss). The volume of distribution in the beta-phase (Vd beta) ranged from 71.5 to 129.51 with a mean of 104.21. The total plasma clearance varied from 380 to 527 ml/min with a mean of 472 ml/min. It is suggested that the pharmacokinetic behavior is due to water-solubility and plasma protein binding of this new benzodiazepine.

Adult↗

25-hydroxy-vitamin D levels in a patient with hypervitaminosis D.

We measured the concentrations of serum calcium and 25-hydroxy-vitamin D in a patient with hypervitaminosis D during 3 months of therapy directed toward correcting the hypercalcemia. Serum calcium could not be maintained at normal concentration without specific therapy until 9 weeks after vitamin D was discontinued. Concentration of 25-hydroxy-vitamin D at the time was 285 ng/ml, approximately half of the value measured three weeks after withdrawal of vitamin D. Serial measurements of the concentration of 25-hydroxy-vitamin D seem to be a useful means of assessing the degree of intoxication in patients with hypervitaminosis D.

Aged↗

[Clinical study of the biological availability of lanatoside C and digoxin in long-term tests].

The bioavailability of digoxin and lanatoside C from tablets and dragees and from solutions of the two substances has been investigated intraindividually in patients on maintenance therapy. Plasma levels and urinary excretion were analyzed by radioimmunoassay. Both plasma concentrations and urinary excretion were significantly higher after digoxin tablets (1.5+/-0.17 ng/ml; 0.15 mg/24 h) than after lanatoside C dragees (0.98+/-0.15 ng/ml; 0.1 mg/24 h). When equimolar solutions of both drugs, corresponding to 0.5 mg digoxin, were given, plasma concentrations and urinary excretion after digoxin (1.6+/-0.08 ng/ml; 0.14 mg/24 h) were again significantly higher than after lanatoside C (1.18+/-0.09 ng/ml; 0.1 mg/24 h). These results suggest that while the absorption of lanatoside C is lower than that of digoxin, it is better than has been generally assummed. The variability in the absorption of lanatoside C between patients is no greater than with digoxin.

Adolescent↗

[Digoxin and beta-methyldigoxin concentrations in cerebrospinal fluid and plasma (author's transl)].

12 patients were treated for at least two days with digoxin or beta-methyldigoxin before a lumbar punction was done for diagnostic purposes. At the same time venous blood was drawn and both samples were radioimmunologically analysed for digoxin concentration. The relationship of concentrations from plasma to cerebrospinal fluid was 2 for beta-methyldigoxin and 8 for digoxin.

Central Nervous System↗

[Clinical and pharmacokinetic studies in patients with digitalis intoxication (author's transl)].

6 patients with severe digitalis intoxication were studied while hospitalised in a coronary care unit. 2 and 4 patients had ingested high doses of lanatosid C and digoxin, respectively. In three cases ventricular arrhythmias, in one of these and two further cases SA blocking and an additional A-V-block in one case were observed. Maximum blood levels of digoxin between 3.4 and 20 ng/ml were determined several hours after the ingestion. The maximal blood levels were achieved in one patient only 52 h after ingesting lanatosid C and in one patient taking digoxin after 12.5 h. Potassium concentrations in plasma were elevated in 4 patients. Antiarrhythmic and electrolyte therapy is discussed and the usefulness of a stomach lavage for diminishing the quantity of absorbed lanatosid C is shown in one patient who had a maximal blood level of 3.4 ng/ml after taking 23.7 mg of lanatosid C. Cumulative urinary excretion of this patient was 0.68 mg within 5.5 days. This result confirms the minimal enteral absorption under the therapy chosen.

Adult↗

Plasma 25-hydroxyvitamin D and urinary cyclic AMP in German patients with subtotal gastrectomy (Billroth II).

In an attempt to clarify the pathogenesis of the disturbed calcium metabolism which sometimes follows partial gastrectomy, we determined plasma 25-hydroxyvitamin D (25-OH-D) concentrations and urinary cyclic 3',5'-adenosine monophosphate (cAMP) excretion in patients who had previously undergone Billroth II gastrectomy and who were without clinical evidence of bone disease. In 17 Billroth II patients plasma 25-OH-D concentrations were reduced (12.6 +/- 4.6 ng/ml, mean +/- SD) compared to values in 17 control patients with diseases not affecting calcium metabolism (31.6 +/- 12.9 ng/ml, P less than 0.001). Urinary cAMP excretion, in part reflecting parathyroid function, was higher in 17 Billroth II patients (5.0 +/- 2.5 micronmol/day) than in the control patients (2.6 +/- 1.3 micronmol/day, P less than 0.001). These results suggest impaired nutrition of vitamin D and secondary hyperparathyroidism in Billroth II patients. While the cause of this phenomenon is unclear, it may contribute to the disturbance of calcium metabolism in patients who have had subtotal gastrectomy.

Adult↗

Effects of propranolol on regional myocardial function, electrograms, and blood flow in conscious dogs with myocardial ischemia.

The effects of coronary occlusion and of subsequent propranolol administration were examined in 18 conscious dogs. Overall left ventricular (LV) function was assessed by measurements of LV pressure and dP/dt, and regional myocardial function was assessed by measurements of segment length (SL), velocity of SL shortening and regional myocardial "work", i.e., pressure-length loops in normal, moderately, and severely ischemic zones. Regional intra-myocardial electrograms were measured from the same sites along with regional myocardial blood flow as determined by the radioactive microsphere technique. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reduction and graded elevation of the ST segment. Propranolol depressed overall LV function, function in the normal zone (work fell by 17+/-4%), and in the majority of moderately ischemic segments (work fell by 7+/-3%). In severely ischemic segments the extent of paradoxical motion and post-systolic shortening was reduced by propranolol. After propranolol regional myocardial blood flow fell in the normal zone (11+/-2%) and rose in the moderately (15+/-4%) and severely (63+/-10%) ischemic zones. Thus, in the conscious dog with regional myocardial ischemia, propranolol induces a redistribution of myocardial blood flow, with flow falling in normal zones and rising in moderately and severely ischemic zones. The improvement in perfusion of ischemic tissue was associated with slight but significant depression of shortening, velocity, and work in the moderately ischemic zones and of paradoxical bulging and post-systolic shortening in the severely ischemic zone.

Animals↗

[Aplastic anaemia and thymonal].

The combination of aplastic anaemia and thymona was observed in a 49-year old woman. Concomitant with severe normochromic anaemia and reticulocytopenia was a cell-rich bone marrow smear in which erythropoietic precursors were almost absent. Immunological phenomena could not be demonstrated. The erythropoietin level was maximally increased. Pathological anatomy typically revealed a predominantly spindle-cell thymonal with only minor capsular invasion.

Anemia, Aplastic↗