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Biomedical subjects

R Wenzel

Publications and source records attributed to R Wenzel.

At least 37 records · Page 2Linked to original sources

The beta-adrenoceptor subtype(s) mediating adrenaline- and dobutamine-induced blood pressure and heart rate changes in healthy volunteers.

In order to characterize the beta-adrenoceptor subtype(s) mediating blood pressure and heart rate changes induced by adrenaline and dobutamine, we compared the effects in healthy male volunteers of propranolol (5 mg i.v.) and of the beta 1-adrenoceptor selective antagonist bisoprolol (15 mg p.o.) on adrenaline- and dobutamine-infusion induced changes in systolic (P(syst)) and diastolic blood pressure (P(diast)) and heart rate with those on blood pressure and heart rate (HR) changes induced by "pure" alpha- or beta-adrenoceptor agonists (phenylephrine, selective alpha, terbutaline, selective beta 2, isoprenaline, non-selective beta 1 and beta 2). Both beta-adrenoceptor antagonists did not affect phenylephrine (0.25 -1.0 microgram/kg/min for 10 min) infusion induced P(syst)- and P(diast)-increases and HR-decreases. On the other hand, propranolol completely suppressed terbutaline (25-150 ng/kg/min for 15 min) and isoprenaline (3.5-35 ng/kg/min for 8 min) infusion induced P(syst)- and HR-increases and P(diast)-decreases while bisoprolol significantly attenuated only isoprenaline-effects but had nearly no effect on terbutaline effects. Thus, in these doses bisoprolol antagonized only beta 1-adrenoceptor mediated effects, propranolol both beta 1- and beta 2-adrenoceptor mediated effects, but both antagonists had no alpha-adrenoceptor antagonistic effects. Dobutamine (1.0-6.0 micrograms/kg/min for 15 min) infusion significantly increased P(syst), but did not significantly affect P(diast) and HR; bisoprolol markedly reduced dobutamine-induced P(syst)-increase. In the presence of propranolol, however, dobutamine caused P(syst)- and P(diast)-increases and HR-decreases. Adrenaline (20-120 ng/kg/min for 15 min) infusion increased P(syst) and HR and decreased P(diast). Bisoprolol did not affect P(syst)- and HR-increases, but significantly attenuated P(diast)-decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Codon reading scheme in Mycoplasma pneumoniae revealed by the analysis of the complete set of tRNA genes.

The 33 genes encoding the complete set of tRNA species in Mycoplasma pneumoniae have been cloned and sequenced. They are organized into 5 clusters in addition to 9 single genes. No redundant gene was found, indicating that 33 tRNAs correspond to 32 different anticodons and decode all 62 codons used in this organism. There is only one single tRNA for each of the Ala, Leu, Pro, and Val family boxes. Therefore, a simplified decoding system resembling that recently described for Mycoplasma capricolum (1) has to also exist in M.pneumoniae. However, analysis of the anticodon set and codon usage revealed features characteristic of the latter: (i) there is no obvious preference toward AT rich synonymous codons, (ii) CGG codons are assigned for arginine and are translated by tRNA Arg(UCG), and (iii) CNN or GNN anticodons are encountered in the Ser, Thr, Arg, and Gly family boxes. We thus propose that this codon-anticodon recognition pattern has emerged in the 'M.pneumoniae cluster' under a genomic economization strategy but without the influence of AT pressure.

Amino Acid Sequence

Studies on oral contraceptive-induced changes in blood coagulation and fibrinolysis and the estrogen effect on endothelial cells.

Blood coagulation (fibrinogen, thrombin-antithrombin III complexes, TAT, and prothrombin fragment F1 + 2) and fibrinolytic parameters [fibrin split-product D-dimer, tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor-1 activity (PAI-1), and plasmin-antiplasmin-complexes (PAP)] were evaluated in 16 women on low estrogen (EE) oral contraceptive (OC) therapy. Blood samples were taken before and between days 18 and 22 of the first, third, and sixth treatment cycle. Fibrinogen levels were found significantly elevated during OC treatment compared with pretreatment values, while TAT and also F1 + 2 levels remained unchanged. Treatment-induced activation of fibrinolysis was documented by elevated D-dimer [pretreatment (pt): 172 ng/ml (range: 65-640 ng/ml), cycle 6 (c.6): 351 ng/ml (range: 93-960 ng/ml), p < 0.05)] and PAP [(pt: 46.6 ng/ml (13-220 ng/ml), c.6: 66.4 ng/ml (21-200 ng/ml), p < 0.05] plasma levels. Among the fibrinolytic components a decrease in PAI-1 [pt: 10.8 ng/ml (2-56 ng/ml), c.6: 5.3 ng/ml (2.2-14.4 ng/ml), p < 0.05] and an increase in t-PA activity [pt: 0.23 U/ml (0.17-0.45 U/ml), c.6: 0.33 U/ml (0.2-0.9 U/ml), p < 0.05] were detected. Experiments with cultured human endothelial cells (EC) showed that EE influenced neither EC hemostatic regulatory activities (tissue factor, thrombomodulin) nor the secretion of the fibrinolytic components t-PA and PAI-1.

Adult

Impact of the changing epidemiology of fungal infections in the 1990s.

The increase in fungal infections over the past decade is striking. This is particularly true for hospitalized patients where the rate of candidal bloodstream infection has increased by as much as 487% over the decade of the 1980s. This increase in fungal infections is accompanied by a significant excess mortality and excess length of stay in hospital. The emergence of "new" fungal pathogens such as Candida krusei, Torulopsis glabrata, Fusarium and Trichosporon beigelii is now recognized as a significant problem in many patient populations. The documentation of nosocomial transmission of fungal pathogens and the recognition of resistance to both new and established anti-fungal agents poses a significant problem entering the 1990s. Continued effort is needed to develop new and better therapeutic agents and more effective strategies for prophylaxis of endogenous infections and prevention of transmission within the hospital setting.

Candidiasis

The use of dopexamine after cardiac surgery: acute and long-term effects in patients with impaired cardiac function.

The haemodynamic efficacy of dopexamine, a beta 2-adrenergic agonist with dopaminergic activity, was evaluated during dosetitration and longterm infusion in 20 cardiosurgical patients with low cardiac output following coronary artery bypass grafting and/or valve replacement or repair. After infusion of four doses (1, 2, 4, and 6 micrograms/kg/min), the dose producing the optimal response was administered for up to 36 h. Dopexamine infusion resulted in a dose-dependent significant increase in cardiac index (CI: 2.2-->3.3 L/min/m2) associated with a marked reduction of systemic vascular resistance (SVR: 1820-->1144 dyn.sec.cm-5). Heart rate increased significantly (HR: 89-->117 beats/min), while mean arterial blood pressure remained unchanged (MAP: 94-->89 mmHg). Unwanted effects (tachycardia and hypotension) were chiefly seen at higher doses (-->4 micrograms/kg/min). The beneficial haemodynamic effects were well maintained during the extended infusion period up to 36 hours at a mean dopexamine dose of 2.8 micrograms/kg/min. At these low doses, the positive chronotropic response to the drug remained within the limits of clinical acceptability. During long-term infusion up to 36 hours there was no indication of tolerance or an effect attenuation. It can be concluded that dopexamine acting as "inodilator" with dopaminergic properties is an useful adjunct to the pharmacological spectrum in the management of low-output states following cardiac surgery.

Adrenergic Agonists

Haemodynamic effects of different doses of dopexamine hydrochloride in low cardiac output states following cardiac surgery.

We studied the haemodynamic effects of dopexamine hydrochloride, a beta 2-adrenergic agonist with dopaminergic (DA1) activity, in 20 patients with low cardiac output following surgery for coronary artery bypass grafting and/or valve replacement or repair. Following titration of four doses (1, 2, 4 and 6 micrograms.kg-1.min-1), the dose producing the optimal response was infused for up to 48 h (five patients). During the infusion, significant increases in cardiac index and stroke volume were accompanied by significant decreases in systemic vascular resistance. Heart rate increased significantly up to 6 h and thereafter returned to control levels. Mean blood pressure was reduced but did not fall below 60 mmHg. However, in five patients treated for 48 h mean blood pressure had returned to control levels. Unwanted effects (tachycardia and hypotension) were seen chiefly at higher doses, leading us to conclude that infusion rates of 4 micrograms.kg-1.min-1 or less will be useful in the treatment of low cardiac output following cardiac surgery.

Adrenergic Agonists

Construction of an EcoRI restriction map of Mycoplasma pneumoniae and localization of selected genes.

A restriction map of the genome of Mycoplasma pneumoniae, a small human pathogenic bacterium, was constructed by means of an ordered cosmid library which spans the complete bacterial chromosome. The positions of 143 endonuclease EcoRI restriction fragments were determined and aligned with the physical map. In addition, restriction sites for the rare-cutting enzymes XhoI (25 sites), ApaI (13 sites), NotI (2 sites), and SfiI (2 sites) were included. The resulting map consists of 185 restriction sites, has a mean resolution of 4.4 kbp, and predicts a genome size of 809 kbp. In addition, several genes were identified and mapped to their respective genomic EcoRI restriction fragments.

Amino Acid Sequence

Resurgence of tuberculosis.

Since 1985 there has been an 18% increase in the number of cases of tuberculosis nationally. Even more alarming is the increasing incidence of multidrug-resistant tuberculosis which presents a serious public health problem, particularly for HIV-infected patients.

Anti-Bacterial Agents

Prolonged myocardial stunning after thrombolysis: can left ventricular function be assessed definitely at hospital discharge?

To assess whether myocardial dysfunction after acute reperfusion ('stunning') may show delayed recovery, 33 patients of the European Cooperative Study (rtPA vs placebo) had radionuclide angiocardiography on day 9 and after 3-6 months. Sixteen patients (13 inferior, three anterior infarcts) had a normal left ventricular ejection fraction (LVEF) which remained unchanged (55.4 vs 53.9%). In contrast, LVEF of 17 patients (10 inferior, seven anterior infarcts) with depressed values on day 9 improved during follow-up from 38.8 to 45.2% (P less than 0.01). Improvement was only observed in patients with early reperfusion defined a priori as peak creatine kinase value less than or equal to 15 h of pain onset (from 40.9 to 49.3%; P less than 0.05) in contrast to patients without reperfusion (from 34.0 to 35.2%; ns). Accordingly, LVEF increased in patients with open infarct-related arteries at hospital discharge (n = 8; P = 0.053) but not with persistent occlusion (n = 7; P = 0.11). Thus, a depressed LVEF observed 9 days after reperfusion may show delayed recovery due to prolonged stunning. Therefore, after thrombolysis, left ventricular function may not be evaluated definitively at hospital discharge; results of such studies should be interpreted with caution.

Adult

Analysis of three different repeated DNA elements present in the P1 operon of Mycoplasma pneumoniae: size, number and distribution on the genome.

Mycoplasma pneumoniae, a bacterium pathogenic for humans, has a relatively small genome size of 840 kbp. Even though, several repeated DNA elements have been identified in the genome of this prokaryote, particularly within the P1 gene which codes for a major adhesin protein of M. pneumoniae. These elements were characterized in detail with respect to size, number and distribution on the genome, represented by an ordered cloned library covering the complete chromosome. Three different repetitive elements were detected in and around the P1 gene designated as RepMP2/3, RepMP4 and RepMP5. The length of these elements varies between 1.1-1.5 kbp (RepMP4), 1.8 kbp (RepMP2/3) and 1.9-2.2 kpb (RepMP5). They occur at least 8 to 10 times on the chromosome. Possible functions are discussed and a uniform nomenclature for these repeats is proposed.

Blotting, Southern

[10 years' comparison of inpatient treated affective diseases].

A comparison was carried out between 237 hospitalised patients with emotional disorders during the years 1972-1975, and 316 patients between 1982 and 1985. The number of admissions as a percentage of all psychiatric admissions rose from 18.21% to 26.49%. There was a significant rise in the number of readmissions, notably from the third admission upwards, but a considerable reduction in the length of stay in hospital. During the period the number of admissions to general hospitals within the catchment area was reduced by about one half, with the result that there was no appreciable overall increase in the number of admissions for in-patient treatment of emotional disorders in the ten-year period.

Bipolar Disorder

Cloning of the complete Mycoplasma pneumoniae genome.

The complete genome of Mycoplasma pneumoniae was cloned in an ordered library consisting of 34 overlapping or adjacent cosmids, one plasmid and two lambda phages. The genome size was determined by adding up the sizes of either the individual unique EcoRI restriction fragments of the gene bank or of the XhoI fragments of genomic M. pneumoniae DNA. The values from these calculations, 835 and 849 kbp, are in good agreement. An XhoI restriction map was constructed by identifying adjacent DNA fragments by probing with selected cosmid clones.

Cloning, Molecular

Fungicidal activity of cilofungin (LY121019) alone and in combination with anticapsin or other antifungal agents.

Cilofungin (LY121019) was shown to have potent fungicidal activity against clinical isolates of Candida albicans and Candida tropicalis but not Candida parapsilosis. Fungicidal activity was evident against both replicating and non-replicating Candida albicans and was progressive over the first 12 h of incubation. The combination of cilofungin (LY121019) with anticapsin but not with amphotericin B, ketoconazole or 5-fluorocytosine resulted in synergistic fungicidal activity. This compound warrants further investigation of its safety and efficacy in the treatment of Candida infections.

Alanine

Value of the Cand-Tec Candida antigen assay in the diagnosis and therapy of systemic candidiasis in high-risk patients.

A total of 911 sera from 171 patients at risk for systemic candidiasis and 24 sera from 24 non-hospitalized control subjects were analyzed for the presence of candida antigen using a commercially available latex agglutination test (Cand-Tec). Thirty-seven (22%) patients had systemic candidiasis documented by positive blood cultures, deep biopsy culture and histopathology or autopsy. Six patients had transient candidemia, 20 patients had candiduria, 53 patients had mucous membrane colonization, 21 patients were not colonized but received empiric amphotericin B, and 34 patients were not colonized and not treated with amphotericin B. The intraobserver reproducibility was 90% for the exact titer and 100% for a deviation of one dilution. The sensitivity and specificity of the candida antigen test in detection of systemic candidiasis was 95% and 50% (greater than or equal to 1:2), 73% and 72% (greater than or equal to 1:4), and 46% and 80% (greater than or equal to 1:8) respectively. Despite the poor specificity, serial antigen determinations in patients with documented systemic candidiasis demonstrated both an early diagnostic and prognostic role for the candida antigen test. Seventy-one percent of patients whose antigen titer increased during the course of amphotericin B therapy of documented infection died versus only 13% of those whose titer decreased while on therapy (p = 0.01). The candida antigen test has a limited yet potentially useful role in the diagnosis and management of systemic candidiasis in high-risk patients.

Amphotericin B

[Seasonally-related inpatient admission of affective patients].

Over a period of four years, 316 emotionally disordered patients were inspected for the frequency of seasonally conditioned hospitalisation, considering however solely the most recent prior hospitalisation within the four-year period. A cautious interpretation of the results would suggest significant differences in the seasonal frequency of emotional disorders that have resulted in hospitalisation. Manic depressive disorders, endogenous depression, and involutional depressions treated in hospital occur with the greatest frequency in autumn. These results suggest the possibility of employing thymoleptic treatment, notably to effect an influence on biorhythms, for instance, lithium, deprivation of sleep, and bright-light therapy.

Depressive Disorder