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Biomedical subjects

J Neumann

Publications and source records attributed to J Neumann.

At least 181 records · Page 10Linked to original sources

[Inflammation of the thyroid gland from the aspect of surgical treatment].

The authors submit surgeons' and endocrinologists' views on treatment of thyroiditis. In the course of a 16-year period an acute spell of thyroiditis was treated by surgery only twice, once a case of subacute thyroiditis, and in all other 348 instances chronic thyroiditis was involved. In the latter group Hashimoto's thyroiditis predominated. Among various controversial reports concerning its treatment the authors maintain that surgery is suitable after failure of short-term conservative therapy. The extent of the operation usually corresponds to total thyroidectomy.

Humans↗

[Comments on Wang's method of preparation of the recurrent laryngeal nerve in total thyroidectomy].

The authors focus their attention on the problem of preparation of the recurrent laryngeal nerve in total thyroidectomy. Similarly as the majority of authors, the present authors use as the main guide during preparation of the recurrent nerve its relationship to the lower thyroid artery. As an alternative procedure they mention Wang's method which they tested in several tens of total thyroidectomies. In the submitted paper they discuss the advantages and disadvantages of this method.

Humans↗

Tissue-specific regulation of the alpha-myosin heavy chain gene promoter in transgenic mice.

The intergenic region between the mouse alpha-myosin heavy chain (MHC) and beta-MHC genes was analyzed in terms of its ability to drive gene expression in transgenic mice. Earlier, we reported that the entire intergenic region was sufficient to direct expression of the bacterial chloramphenicol acetyl transferase reporter gene in a tissue-specific and developmental stage-specific manner. Additional transgenic lines have been generated which include two deletions. The first deletion, alpha-3, which lacks the distal 2.5 kilobase pairs of the upstream region, is competent to direct tissue- and developmental-specific expression of the transgene. A larger deletion, in which only 138 base pairs upstream of the transcriptional start site remain, shows no chloramphenicol acetyltransferase activity in either muscle or non-muscle tissue. Tissue surveys of transgene expression indicated low levels of activity in the lung, and analyses via the polymerase chain reaction confirmed the presence of the endogenous alpha-MHC gene transcripts in this tissue. Subsequently, an alpha-MHC gene-specific riboprobe was used to detect the cognate transcripts in lung sections by in situ hybridization. The data show that, in the lung, the transcripts are localized to the thick intimal wall of the veins and venules.

Animals↗

Isolation and characterization of the mouse cardiac myosin heavy chain genes.

Two mouse genomic libraries were probed in order to isolate the murine cardiac myosin heavy chain (MHC) genes. Two overlapping cosmid clones that encode the cardiac genes were isolated. One of them encompasses the entire alpha-cardiac MHC gene, its 5'-flanking region and approximately 10 kilobase pairs (kb) of the 3'-end of the beta-cardiac MHC gene which we determined is located approximately 4 kb upstream of the alpha-cardiac MHC gene. Four clones isolated from a bacteriophage library were found to overlap with the 5'-region of the cosmid clones, and sequence analysis confirmed that the 5'-end of the beta-cardiac MHC gene was contained within one of the clones. Primer extension and polymerase chain reaction (PCR) analyses were used to define the transcriptional start site and the 5'-organization of the alpha-cardiac MHC gene. This region exhibits greater than 90% homology to the corresponding nucleotides of the rat alpha-cardiac MHC gene. To assess the importance of the intergenic region in directing expression of the alpha-cardiac MHC gene, a fragment containing the 3'-end of the beta-cardiac gene and the 5'-end of the alpha-cardiac gene was linked to a chloramphenicol acetyltransferase gene and used to generate transgenic mice. Analyses of the chloramphenicol acetyltransferase (CAT) activity in two lines indicate that the intergenic region is sufficient to properly direct expression in a tissue-specific manner.

Animals↗

Mechanism underlying the reduced positive inotropic effects of the phosphodiesterase III inhibitors pimobendan, adibendan and saterinone in failing as compared to nonfailing human cardiac muscle preparations.

The present study was performed to compare the effects of the new positive inotropic phosphodiesterase III inhibitors pimobendan, adibendan, and saterinone on the isometric force of contraction in electrically driven ventricular trabeculae carneae isolated from explanted failing (end-stage myocardial failure) with those from nonfailing (prospective organ donors) human hearts. In preparations from nonfailing hearts the phosphodiesterase inhibitors, as well as the beta-adrenoceptor agonist isoprenaline, the cardiac glycoside dihydro-ouabain, and calcium, which were studied for comparison, revealed pronounced positive inotropic effects. The maximal effects of pimobendan, adibendan, and saterinone amounted to 56%, 36% and 45%, respectively, of the maximal effect of calcium. In contrast, in preparations from failing hearts the phosphodiesterase III inhibitors failed to significantly increase the force of contraction and the effect of isoprenaline was markedly reduced. The effects of dihydroouabain and calcium were almost unaltered. The diminished effects of isoprenaline were restored by the concomitant application of phosphodiesterase inhibitors. To elucidate the underlying mechanism of the lack of effect of the phosphodiesterase III inhibitors in the failing heart we also investigated the inhibitory effects of these compounds on the activities of the phosphodiesterase isoenzymes I-III separated by DEAE-cellulose chromatography from both kinds of myocardial tissue. Furthermore, the effects of pimobendan and isoprenaline on the content of cyclic adenosine monophosphate (determined by radioimmunoassays) of intact contracting trabeculae were studied. The lack of effect of the phosphodiesterase inhibitors in failing human hearts could not be explained by an altered phosphodiesterase inhibition, since the properties of the phosphodiesterase isoenzymes I-III and also the inhibitory effects of the phosphodiesterase inhibitors on these isoenzymes did not differ between failing and nonfailing human myocardial tissue. Instead, it may be due to a diminished formation of cyclic adenosine monophosphate in failing hearts, presumably caused mainly by a defect in receptor-adenylate cyclase coupling at least in idiopathic dilated cardiomyopathy. Both the basal and the pimobendan-stimulated or isoprenaline-stimulated contents of cyclic adenosine monophosphate of intact contracting trabeculae from failing hearts were decreased compared with the levels in nonfailing hearts. However, under the combined action of isoprenaline and pimobendan the cyclic adenosine monophosphate level reached values as high as with each compound alone in nonfailing preparations, and in addition the positive inotropic effect of isoprenaline was restored. These findings may have important clinical implications. Along with the elevated levels of circulating catecholamines the positive inotropic effects of the phosphodiesterase inhibitors may be maintained in patients with heart failure.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-3-isobutylxanthine↗

Effects of isomazole on force of contraction and phosphodiesterase isoenzymes I-IV in nonfailing and failing human hearts.

The phosphodiesterase (PDE) inhibitor isomazole increased the force of contraction to 278.3 +/- 89.1% (n = 7) of the predrug value in ventricular trabeculae carneae isolated from nonfailing human hearts. This effect can be attributed mainly to a PDE III or a combined PDE III/IV inhibition since at the concentration of the maximal positive inotropic effect of isomazole, PDE III and PDE IV were completely inhibited. In explanted failing human hearts (end-stage myocardial failure, NYHA IV), isomazole increased the force of contraction only marginally to 110.1 +/- 10.7% of the predrug value. The lack of a distinct positive inotropic efficacy of isomazole in failing human hearts could not be explained by an impairment of PDE inhibition since the properties of the PDE I-IV isoenzymes separated by DEAE-Sepharose chromatography and the inhibitory effects of isomazole did not differ in both preparations. The positive inotropic effect of the beta-adrenoceptor agonist isoprenaline was also reduced in failing hearts. However, in the presence of isomazole, the diminished positive inotropic effect of isoprenaline was restored to values obtained with isoprenaline alone in nonfailing hearts. Thus, the decreased effect of inotropic drugs like isoprenaline or isomazole in preparations from failing human heart might be explained mainly by a diminished cAMP formation due to a defect in receptor-adenylate cyclase coupling.

Adult↗

Evidence for isoproterenol-induced phosphorylation of phosphatase inhibitor-1 in the intact heart.

The positive inotropic effect of the beta-adrenoceptor agonist isoproterenol is accompanied by inhibition of phosphatase type 1 activity in myocardium. Indirect assays suggest that this effect is due to activation of protein phosphatase inhibitor-1, which inhibits phosphatase activity only when phosphorylated. To test this hypothesis directly, electrically stimulated (3 Hz) guinea pig ventricular preparations were perfused according to the Langendorff method with physiological buffers with or without 5 mCi 32P/heart, and then various concentrations of isoproterenol were applied. Contractility was recorded. Hearts were freeze-clamped and cAMP and inhibitor-1 activities were measured. In 32P-labeled hearts a protein at about 26 kd on autoradiograms of 12% sodium dodecyl sulfate gels was detected. Isoproterenol (1 microM) increased rate of tension development to 238% of the predrug value, cAMP concentrations 1.5-fold, and inhibitor-1 activity threefold. Concomitantly, there was an increase in a 32P-labeled band at about 26 kd from 380 to 540 pmol 32P/mg protein. This protein at about 26 kd, after transfer to nitrocellulose, was recognized by an antiserum prepared against rabbit skeletal muscle inhibitor-1. More radioactive protein of about 26 kd could be immunoprecipitated by the antiserum from isoproterenol-treated than from untreated hearts. It is concluded that a protein, probably identical to phosphatase inhibitor-1, is phosphorylated in vivo in the heart in the presence of isoproterenol. Phosphorylation of inhibitor-1 with consequent modification of type 1 phosphatase activity may contribute to the effects of isoproterenol in the heart.

Animals↗

Psychiatry in eastern Europe today: mental health status, policies, and practices.

The author describes the impact of the recent social and political changes in Eastern Europe on psychiatrists and psychiatry. The observations contained in this paper are drawn from his personal experiences as a practicing psychiatrist in East Germany who also served as a member of the Executive Committee of the World Psychiatric Association from 1984 to 1989. The practice of psychiatry in Eastern Europe before the recent social and political changes was highly variable depending on the country, the locale of practice, and the social and political positions of the involved psychiatrists. Adapting to the recent changes will be very difficult, and it will be a long time before the modernization of psychiatric practice in Eastern Europe takes place. Psychiatrists in the Western world can play an important part in the future development of psychiatry in Eastern Europe. Their understanding of the current situation and the historical forces that shaped it is extremely important to the psychiatrists of Eastern Europe.

Communism↗

Effect of gallopamil on myocardial ischaemia during percutaneous transluminal coronary angioplasty.

This report summarises selected preliminary results from an ongoing study designed to investigate the effect of the calcium antagonist gallopamil on myocardial ischaemia during percutaneous transluminal coronary angioplasty (PTCA). To date, 12 adult males with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) have been randomly assigned to gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralisation of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease or renal failure were excluded from the study. PTCA was performed using at least 2 balloon inflations, each of 2 minutes' duration. Gallopamil 0.4 mg or placebo (normal saline) were administered during the 10-minute interval between the 2 inflations. Blood samples were taken simultaneously from the coronary sinus and the femoral artery before and immediately after each inflation. Lactate concentration and the relative amount of activated neutrophils were selected for trend analysis. Furthermore, ECG changes were analysed by calculating the sum of the absolute ST-segment deviations (80 msec after J point, maximal T deviation) of leads I, II, III, V2, V4 and V6. In the presence of gallopamil, the degree of ST-segment/T-wave changes induced by balloon inflation was reduced. Additionally, gallopamil attenuated myocardial lactate release and appeared to prevent the increase in activated neutrophils observed during control inflations. These preliminary results suggest a beneficial effect from intracoronary administration of gallopamil during PTCA, achieved by attenuation of the ischaemic reaction during coronary occlusion.

Adult↗

Cigarette smoking, gastric acidity and peptic ulceration. What are the relationships?

The influence of cigarette smoking on intragastric acidity was assessed in duodenal ulcer patients in symptomatic remission and in healthy volunteers in a retrospective study. Continuous 24-hr pH recordings in 150 nonsmokers and 174 smokers receiving placebo treatment were compared. Daytime intragastric acidity was higher in smokers with a median pH (interquartile range) of 1.56 (1.34-1.80) than in nonsmokers, who had a median pH of 1.70 (1.45-1.97) (P less than 0.001). There was no difference in 24-hr and nighttime median pH between the two groups. The small difference in daytime intragastric acidity in smokers and nonsmokers is unlikely to account for the increased prevalence of peptic ulcer disease in smokers. The analysis of smoking status in duodenal ulcer patients and healthy controls and males and females supports the general trend towards higher daytime acidity in smokers. Again, no differences in pH during the 24-hr or night period were found between the groups. The epidemiological and clinical correlation between smoking and duodenal ulcer disease is not adequately explained by increased intragastric acidity.

Circadian Rhythm↗

Effect of external beam radiation therapy on serum prostate-specific antigen.

The effect of external beam radiation on serum prostate-specific antigen (PSA) was determined in 20 patients with nonmetastatic carcinoma of the prostate. An abnormal PSA was measured in 91 percent and 93 percent, respectively, of the samples collected prior to or during radiation therapy. By seven months, 8/15 men still had an abnormal PSA level. Four of 5 men with an elevated PSA at least twenty-three months after radiation therapy had a positive prostatic biopsy, and 3/3 patients with a normal PSA had a negative ultrasonically guided biopsy. The rate of decline of serum PSA after radiation therapy is variable. These preliminary data suggest that serum PSA may be useful for assessing the local response of prostate cancer to radiation therapy.

Adenocarcinoma↗

Immunological tolerance in human transplantation. The possible existence of a maternal effect.

We analyzed data from 93 patients who received a kidney graft from their parents; 55 were transplanted with a kidney from their mothers (Mat.) and thirty-eight from their fathers (Pat.) The Pat. group has shown a better graft and patient survival as well as long-term renal function when compared with the Mat. group. This pattern was more evident with time. Long-term graft function assessed by creatinine levels also showed differences between the groups, favoring the Pat. group. The results are interesting since recent reports have claimed a tolerance developed by the individual to noninherited HLA antigens of their mother.

Adolescent↗

[Assessment of health status and current life style of patients with malignant neoplasms].

A review is given on the results of a study investigating the state of health and the psycho-social situation of 211 patients who underwent follow-up for malign neoplasm in the oncological Health Center of Magdeburg. In the course of a conversation the patients were questioned about social and other factors specific for their disease. For evaluating the psychic situation the questionnaire of Höck and Hess was used. The results of the study allowed to conclude that more than 50% of the patients showed psychoreactive disorders. Depending from age and sex as well as the diagnosis marked differences concerning the frequences of psychic peculiarities and the evaluation of the state of health were revealed. The results demonstrate that in addition to specific oncological knowledge the consideration of social and psychic factors is necessary for an optimum follow-up in order to recognize and prevent disorders in this field.

Adaptation, Psychological↗

Differential antagonism by 1,3-dipropylxanthine-8-cyclopentylxanthine and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo(1,5-c)quinazolin-5-im ine of the effects of adenosine derivatives in the presence of isoprenaline on contractile response and cyclic AMP content in cardiomyocytes. Evidence for the coexistence of A1- and A2-adenosine receptors on cardiomyocytes.

The antagonism by the A1-adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and the A2-adenosine receptor antagonist [9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo (1,5-c)quinazolin-5-imine] (CGS 15943A) of the effects of the A1-adenosine receptor agonist (-)-N6-phenylisopropyladenosine (R-PIA) and the A2-adenosine receptor agonist 5'-N-ethyl-carboxamideadenosine (NECA) in the presence of isoprenaline on contractile response and cyclic AMP (cAMP) content in cardiomyocytes from guinea pig cardiac ventricles were studied. In electrically driven (1 Hz) guinea pig ventricular cardiomyocytes R-PIA concentration-dependently (0.0001-100 microM) reduced the stimulatory effects of isoprenaline (0.01 microM) on contractile response and on cAMP content. The A1-adenosine receptor antagonist DPCPX (0.3 microM) antagonized the effects of R-PIA on contractile reponse and on cAMP content, whereas the A2-adenosine receptor antagonist CGS 15943A (0.01 microM) was ineffective. NECA (0.0001-100 microM) reduced the effects of isoprenaline (0.01 microM) on contractile response to about the same extent as R-PIA. However, NECA did not change cAMP content. DPCPX (0.3 microM) antagonized the effects of NECA on contractile response and evoked a cAMP-increasing effect of NECA, which was 38% of the isoprenaline value at most. In contrast, CGS 15943A did not affect the reduction of contractile response induced by NECA, whereas CGS 15943A revealed a cAMP-decreasing effect of NECA (0.1-10 microM). This study provides functional evidence that both, cAMP-decreasing A1- and cAMP-increasing A2-adenosine receptors are present on ventricular cardiomyocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

[Pancytopenia during low-dose oral methotrexate therapy of psoriatic arthritis].

Pancytopenia and interstitial pneumonia occurred in a 70-year-old woman with psoriatic arthritis and compensated renal insufficiency while she was being treated with low doses of the folic-acid antagonist methotrexate (5 mg weekly). Despite the administration of platelets, red blood cells, antibiotics, acyclovir and folinic acid (100 mg daily), the pneumonia progressed, and the patient died of global respiratory failure.

Administration, Oral↗

Effects of adenosine analogues on force and cAMP in the heart. Influence of adenosine deaminase.

The effects of the adenosine receptor agonists (-)-N6-phenylisopropyladenosine (PIA) and 5'-N-ethylcarboxamideadenosine (NECA) on the force of contraction, adenylate cyclase activity and cAMP content in the presence of isoprenaline (Iso) were studied in ventricular preparations of the guinea-pig heart. Only in the presence of adenosine deaminase (ADA) and 50 mM sodium chloride, i.e. under 'optimal' conditions, did PIA and NECA reduce the Iso-stimulated adenylate cyclase activity in broken cell preparations, with a maximal effect of about 25%. In electrically driven (1 Hz) papillary muscles from guinea-pigs, both compounds concentration dependently reduced the Iso-stimulated force of contraction maximally by about 50% in the presence of ADA (1 microgram/ml). cAMP was measured in the same preparations. Low concentrations (0.1-1 microM) of PIA reduced the cyclic AMP content while higher concentrations increased the cyclic AMP content. The negative inotropic effect of NECA was accompanied by a concentration-dependent increase in the cyclic AMP content. We conclude that the negative inotropic effect of PIA in the presence of Iso is only in part due to a decrease in the cyclic AMP content resulting from inhibition of adenylate cyclase activity. Such an effect was only detected in the presence of ADA so that endogenous adenosine can obviously mask small effects of PIA on adenylate cyclase activity or the cyclic AMP content. In addition, the negative inotropic effect of NECA in the presence of isoprenaline was not accompanied by a reduction but an increase in the cyclic AMP content.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Effects of adenosine analogues on contractile response and cAMP content in guinea-pig isolated ventricular myocytes.

In the present study the effects of adenosine analogues were investigated on cAMP content and contractile response in guinea-pig ventricular myocytes. The adenosine analogues (-)-N6-phenylisopropyladenosine (R-PIA), 5'-N-ethylcarboxamideadenosine (NECA) and (+)-N6-phenylisopropyladenosine (S-PIA) in the presence of 0.01 mumol/l isoprenaline reduced contractile response concentration-dependently. R-PIA and NECA were about equipotent (IC25: 0.01 mumol/l and 0.039 mumol/l respectively), while S-PIA was less potent (IC25: 0.6 mumol/l). Isoprenaline stimulated cAMP content was reduced by R-PIA (IC25: 0.004 mumol/l) and with lower potency by S-PIA (IC25: 0.15 mumol/l), but the extent of reduction of cAMP by R-PIA and S-PIA (to 55% and 64% respectively) was less than the reduction of contractile response (to 26% and 55% respectively). This suggests that the effects of R- and S-PIA on contractile response are only in part due to a reduction in cAMP content. In addition, NECA did not decrease cAMP content but decreased contractile response to the same extent as R-PIA. Similar results were obtained in the presence of the phosphodiesterase inhibitor Ro 20-1724. Time course studies revealed that the effects of R-PIA (1 mumol/l) on cAMP content and contractile response coincided reaching steady state after 5 min and remained stable thereafter. The effects of NECA (1 mumol/l) on contractility also reached steady state within 5 min, whereas it did not change cAMP content. It is concluded that the reduction of contractility by adenosine analogues in the presence of isoprenaline can only in part be explained by a reduction of cAMP content.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗