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Biomedical subjects

P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 19 recordsLinked to original sources

Decrease of epinephrine-induced arrhythmia threshold in ethanol exposed rats.

An association between cardiac arrhythmias and ethanol use has been observed for some time. The sympathetic nervous system presumably plays an important role in the manifestation of cardiovascular ethanol responses. Therefore, we investigated the effects of ethanol treatment on epinephrine-induced arrhythmias. Female Wistar rats received 10 vol% ethanol or 2.5% glucose (control group) in their drinking water for 45 days. In ether anesthetized animals of both groups epinephrine (10 micrograms/kg.min) was infused via a lateral tail vein. The threshold dose for arrhythmias after epinephrine infusion (mainly 2nd and 3rd degree AV-blocks) was reduced beginning 2 days after the start of the ethanol treatment and the incidence of AV-blocks during epinephrine infusion was increased. During the ethanol treatment the prohypertensive epinephrine effect was slightly increased. The reflex bradycardia was not changed after repeated epinephrine infusion by ethanol treatment, whereas it was nearly abolished in the control group. No blood ethanol could be detected during the time of epinephrine infusion (9-12 a.m.), but determinations at 11 p.m. yielded a concentration of 0.13 +/- 0.02 mg/g. The results show that the epinephrine-induced bradyarrhythmia threshold is reduced and the frequency of arrhythmic events is augmented in rats exposed to ethanol in the drinking fluid.

Animals

Calcium transients in isolated cardiac myocytes are altered by 1,1,1-trichloroethane.

1,1,1-Trichloroethane is a widely used solvent that is annually linked to several cases of sudden death following accidental exposure or abuse. Sudden death is believed to be due to ventricular fibrillation or myocardial depression. The purpose of this study was to investigate the mechanism of myocardial depression by assessing the influence of 1,1,1-trichloroethane on intracellular Ca transients in single neonatal rat ventricular myocytes using spectrofluorometric analysis of fura-2-Ca binding. Cells were exposed to 1,1,1-trichloroethane in Hanks' balanced salt solution aliquoted as a 0.2% DMSO solution by a single pass suffusion in an environmentally controlled chamber. 1,1,1-Trichloroethane (0.25 mM-8 mM) reduced the height of electrically (1 Hz, 60 V, 10 ms) induced Ca transients concentration dependently and reversibly to a maximum of about 50% with no effect on diastolic Ca concentration. Video motion analysis revealed an inhibition of contractility in the same concentration range. 1,1,1-Trichloroethane inhibited cytosolic Ca increase in response to KCl-induced (90 mM) depolarizations and further decreased the limited Ca transients in ryanodine (1 microM) pretreated myocytes. Increased external Ca (5 mM) antagonized the effect of 0.5 mM 1,1,1-trichloroethane on the Ca transients. 1,1,1-Trichloroethane reduced the caffeine (10 mM) releasable Ca pool in myocytes. These results show that 1,1,1-trichloroethane inhibits Ca mobilization during excitation-contraction coupling in ventricular myocytes. An inhibitory action on the influx of extracellular Ca as well as on sarcoplasmic reticulum Ca release and sequestration is likely to be responsible for this action.

Animals

Effect of chronic ethanol consumption upon cardiovascular reactivity, heart rate and blood pressure in spontaneously hypertensive and Wistar-Kyoto rats.

OBJECTIVE: Clarification of the effect of chronic ethanol consumption upon cardiovascular reactivity in rats. DESIGN: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats were randomly allocated in groups of 10 to ethanol in tap water [20% (v:v) after the first week or tap water for 7-12 weeks]. METHODS: Intra-arterial blood pressure and heart rate were measured at rest and in response to vibration and noise stress. Vascular reactivity was assessed in isolated paired perfused hindquarters and in mesenteric arterioles in a Mulvany-Halpern myograph. RESULTS: Resting intra-arterial blood pressure but not heart rate was lower in both ethanol-treated groups. The ethanol treatment increased the SHR heart rate response to sudden noise but the WKY response did not increase. Pressor responses to noise were initially greater in the ethanol-treated SHR. The ethanol had no effect upon isolated perfused hindquarter resistance at maximal dilation, dose-response curves in response to noradrenaline or vasopressin, or maximal contractile strength. Isolated mesenteric arterioles showed that ethanol had no effect upon responses to nerve stimulation or upon the 50% effective dose required for a response to noradrenaline or vasopressin. CONCLUSIONS: Ethanol treatment heightened the heart rate reactivity to stress without substantially affecting vascular neuro-effector characteristics in SHR. This is likely to be a central effect, caused by suppression of the central nervous inhibitory systems that influence the heart rate and baroreflex activity in a strain of rat already showing evidence of an impaired ability to modulate the heart rate and blood pressure in response to stress. The small reduction in resting blood pressure may be a consequence of the lower weight in the ethanol-treated rats, and/or may reflect a direct depressing action by the alcohol on vascular and cardiac muscle. These findings are discussed in the context of ethanol-induced hypertension in humans and possible genetic variations in central nervous, cardiac and vascular effects.

Alcoholism

In vitro and in vivo evaluation of BMY 45243, a new 5-amino-naphthyridone derivative.

BMY 45243 is the first representative of 5-amino naphthyridone derivatives prepared following a new methodology developed by the authors. BMY 45243 is a highly lipophilic compound, very active in vitro and in vivo on S. aureus and was found to be as potent as ciprofloxacin on Gram-negative organisms with identical in vivo activity against Pseudomonas aeruginosa. Pharmacokinetics in mice showed better AUC and Cmax and longer t1/2 for BMY 45243 than for sparfloxacin and ciprofloxacin.

Animals

[Oncocytic tumors of the kidney apropos of 2 cases. Actualities in the preoperative diagnosis and therapeutic attitude].

The authors report two cases of renal oncocytoma treated by radical nephrectomy. There is still a controversy because the term oncocytoma is used for all tumors containing oncocytes, either true oncocytoma or adenocarcinoma with oncocytoma cells. The main problem is to distinguish, prior to surgery, between renal oncocytoma, a tumor with benign evolution, and renal adenocarcinoma with oncocytes, to offer conservative surgery for renal oncocytoma.

Adenoma

[Therapy of acute lung failure with nifedipine. A study with interventional analysis].

In 24 patients with severe ARDS after major gastro-intestinal surgery the effect of the calcium antagonist nifedipine on pulmonary function was investigated. Besides descriptive statistics and comparison between group means, intervention analysis was employed to assess the treatment effect for the individual patient. The treatment effect could always be assessed after 12 hours. 14 out of 15 patients with initially high PVR showed a significant decrease of PVR followed by an improvement of AaDO2. 8 out of 9 patients with initially normal PVR did not improve in pulmonary function as no significant changes in PVR occurred. No unwanted side-effects on cardio-vascular function (MAP, CI, LVSWI, RVSWI) could be observed. 9 out of 24 patients decreased. Lethality among patients who showed a significant decrease of PVR under nifedipine infusion was 3 out of 15, whereas 5 out of 9 patients died without changes in PVR. Thus nifedipine can improve pulmonary function in ARDS. Especially in the early stages of ARDS with elevated PVR the administration of nifedipine p.i. appears advantageous.

Aged

[Ketamine racemate or S-(+)-ketamine and midazolam. The effect on vigilance, efficacy and subjective findings].

Ketamine is a racemic mixture containing equal amounts of optical isomers that have almost identical pharmacokinetic properties but different pharmacodynamic effects. The S-(+)-isomer of ketamine has about twice the anaesthetic and analgesic potency of the racemic ketamine preparation and is judged to induce less psychic emergence reactions and to be followed by a more rapid recovery of vigilance. The present study was designed to assess whether the S-(+)-isomer of ketamine is superior to the racemic mixture in cardiovascular characteristics, emergence reactions and cognitive functions, and whether side effects may be reduced or prevented by administration of midazolam prior to injection of S-(+)-ketamine. METHODS. Following ethics committee approval and informed consent, 30 volunteers were randomly allocated in this double-blind study to three groups of 10 each. Group 1 received 2 mg/kg bw racemic ketamine, group 2, 1 mg/kg bw S-(+)-ketamine and group 3, 1 mg/kg bw S-(+)-ketamine after premedication with 0.1 mg/kg midazolam i.v. Cardiovascular changes, state of vigilance, cognitive performance, subjective mood and acceptance of anaesthesia were assessed by means of haemodynamic routine monitoring, electroencephalography (EEG), psychometric tests and interview. RESULTS. The increases in mean arterial pressure and heart rate following the injection of racemic ketamine and S-(+)-ketamine were identical and the differences from baseline values significant after both. Premedication with midazolam ensured stable haemodynamics after injection of S-(+)-ketamine. EEG analysis displayed the characteristic changes well known from ketamine anaesthesia for both racemic and S-(+)-ketamine. The vigilosomnoscript showed an identical profile of vigilance up to 30 min after injection of both drugs. The vigilance status after 125 min was less impaired by S-(+)-ketamine than by racemic ketamine. Psychological assessment showed a prompter recovery of visual attentiveness and sensorimotor performance in the S-(+)-ketamine group. Subjective mood was judged by the volunteers to be significantly better after S-(+)-ketamine, and volunteers found S-(+)-ketamine to be more acceptable than racemic ketamine. The frequency of dreams was the same after both drugs. No unpleasant dreams were reported after S-(+)-ketamine, but one of the volunteers who received racemic ketamine had uncomfortable dreams. Midazolam prevented any unpleasant emergence sequelae. On the other hand, the cognitive performance could not be restored to the baseline values until at least 240 min after injection of S-(+)-ketamine, because of the sedative effects of midazolam. DISCUSSION. These results suggest that S-(+)-ketamine offers the advantages of faster recovery of cognitive performance, greater acceptance by the volunteers and identical depth of anaesthesia after injection of half the dose compared with racemic ketamine. The clinical use of S-(+)-ketamine therefore seems to be justified. Premedication with benzodiazepines, e.g. midazolam, is essential. The dose to be administered, however, should be carefully selected in order not to abolish the positive effect of S-(+)-ketamine on vigilance by the sedative effects of the benzodiazepine.

Adult

[Expert assessment for long-term care--starting point for comprehensive help in medical and social rehabilitation].

Based on the various definitions of people in need of constant care the authors describe the needs and chances of professional assessment in the process of financing care at home and in nursing homes. They stress the often neglected point of rehabilitation and plead for participation of social workers and nurses in the assessment process. The precarious situation for many relatives of people in need of care is pointed out. The authors come to the conclusion that public health offices in Germany should--as an important task in the future--concentrate more intensively on the actual problems of people in need of care and participate in local strategies to improve their living conditions.

Comprehensive Health Care

Effect of isoniazid or phenobarbital pretreatment on the metabolism of dihalomethanes to carbon monoxide.

An oral dose of 6.2 mmoles of diachloromethane (DCM), bromochloromethane (BCM) or dibromomethane (DBM) per kg body mass yielded a maximum carboxyhemoglobin (COHb) level of about 9% (at 6 hr), 11% (at 8 hr) and 22% (at 12 hr), respectively. Pretreatment of rats with isoniazid, 4 x 0.36 mmol/kg i.p., produced significant enhancements of the COHb formation; the values were 18.0 +/- 0.8% COHb after DCM, 24.1 +/- 0.8% COHb after BCM, and 39.0 +/- 1.3% COHb after DBM. Prior administration of phenobarbital, 4 x 0.31 mmol/kg i.p., caused no appreciable alterations in the COHb levels after DCM and slight but significant increases after BCM as well as after DBM. The data indicate that the oxidative metabolism of dihalomethanes to carbon monoxide is mainly catalyzed by cytochrome P-450 IIE1 and that the DCM-evoked COHb formation seems to be a method of testing whether a chemical is an inducer of this form of cytochrome P-450 in vivo.

Animals

Percutaneous absorption of mercury vapor by rats.

With respect to occupational exposure situations, more information is needed to assess the importance of the skin absorption route for elemental mercury. The purpose of the experiments reported here is to prove the suitability of the rat tail as a model of Hg skin uptake. A vapor generation system used with a tail-only exposure system is described and first results are reported. An Hg uptake via the rat tail skin could be confirmed. The Hg uptake rate cannot be estimated quantitatively by these experiments.

Animals

Lipopeptides containing 2-(palmitoylamino)-6,7-bis(palmitoyloxy) heptanoic acid: synthesis, stereospecific stimulation of B-lymphocytes and macrophages, and adjuvanticity in vivo and in vitro.

Lipopeptides, carrying the N-terminal lipoamino acid 2-(palmitoylamino)-6,7-bis(palmitoyloxy) heptanoic acid (Pam3Adh-OH, 1), were obtained by solid-phase synthesis and by synthesis in solution. 2-Amino-6,7-dihydroxyheptanoic acid (Adh) can be regarded as a methylene analogue of S-glycerylcysteine, the N-terminal amino acid of lipoprotein from the outer cell membrane of Escherichia coli (a methylene group substitutes for the sulfur atom). The lipopeptides Pam3Adh-Ser-Ser-Asn-Ala 2a-d, in which the four possible stereoisomers of Pam3Adh-OH (2S,6S)-1 (1a), (2S,6R)-1 (1b), (2R,6S)-1 (1c), and (2R,6R)-1 (1d) are linked to the naturally occurring sequence Ser-Ser-Asn-Ala of the N-terminus of lipoprotein, and also Pam3Adh-Ser-(Lys)4 [2S,6S)-3), with a peptide part rendering the molecule water soluble, were capable of stimulating murine splenocytes polyclonally in vitro, as determined in a proliferation assay and in a hemolytic plaque assay against trinitrophenylated sheep erythrocytes. The diastereomers (2S,6S)-2 and (2R,6S)-2 with S-configurated C-6 were more active than the diastereomers (2S,6R)-2 and (2R,6R)-2 with R-configurated C-6; a change of the configuration at C-2 had less effect on the stimulatory activity. (2S,6S)-2 and (2S,6S)-3 are potent immunoadjuvants. A significantly enhanced primary immune response against trinitrophenylated sheep erythrocytes was obtained in vitro at lipopeptide concentrations of about 5 micrograms/mL and an immunization dose of 10(7) sheep erythrocytes/mL. Balb/c mice, which were immunized with a mixture of ovalbumin and (2S,6S)-2 or (2S,6S)-3, respectively, had a substantially higher antiovalbumin titer 28 days after immunization than mice which had received ovalbumin, (2S,6S)-2 or (2S,6S)-3 alone. Finally, the novel lipopeptides constitute potent macrophage activators: (2S,6S)-3 was able to induce tumor cytotoxicity against the tumor cell line L929 in bone marrow derived macrophages.

Adjuvants, Immunologic

[Analgosedation of the ventilated intensive care patient].

Seven different schemes for analgesic anaesthesia were investigated for their clinical applicability, potential side effects, and impacts on circulation parameters of the systemic and pulmonary (peripheral) circulation as well as on the intracranial pressure. In all, so patients per group were treated. The results revealed different reactions of patients, such as a higher incidence of disturbances of the autonomic nervous system and excitation after medication withdrawal. Favourable effects not only on clinical reactions but also on circulation parameters were seen during fentanyl/midazolam or alfentanil/midazolam therapy. In several instances, a clear increase in the right atrial and the pulmonary arterial mean pressure as well as the intracranial pressure was observed during ketamine/flunitrazepam therapy. The combinations pethidine/promethazine or pethidine/flunitrazepam also showed clear side effects on the circulation and evoked an increase in the intracranial pressure. Fentanyl/midazolam or alfentanil/midazolam treatments were the most favourable combinations for most of the patients who were artificially respirated.

Adolescent

[Arousal in various analgosedation schedules].

The patterns of recovery of patients who received seven different analgesic and sedative treatments were investigated with regard to the time at which the subjects awoke. For observations of the neurologic status, we developed a special score. The analgesic and sedative therapies were given at three various doses. The combination of fentanyl/midazolam, alfentanil/midazolam and ketamine/flunitrazepam showed the best results. Piritramid/promethazine, pethidine/flunitrazepam, pethidine/promethazine and tramadol/methohexital required more time for awakening. On the basis of these results, we prefer to use the combination of fentanyl/midazolam, alfentanil/midazolam and ketamine/flunitrazepam to judge all patients' neurologic scores.

Analgesia

[Social psychiatric service as a cornerstone of psychiatric community care].

Psychiatric care has gradually been shifting in Germany from its original inpatient basis to outpatient and complementary treatment. This shift of emphasis resulted in a transfer of psychiatry-political responsibility to communal bodies and hence also to communal public health services. Sociopsychiatric service ranks high in communal psychiatric care setups, since it promotes cooperation and helps to coordinate efforts in individual cases in respect of focal points on which such care is centered. For the future, an expert commission has suggested that the various institutions actively engaged in community psychiatric care should team up in each region. This applies in particular to mobile services visiting the patients in their homes, and to the offices providing contracts to sociopsychiatric services of public health offices. Despite positive outlooks there are also quite a few negative aspects of present-day practice. One of them is poor definition of tasks and functions of communal sociopsychiatric services, whereas another one are the unsatisfactory quantitative and qualitative means at their disposal. It is also too often overlooked that psychiatric patients and disabled persons are entitled to compensation insurance payments to promote their rehabilitation, as provided for by individual legislation in the various German laender. To tap these sources sufficiently well, sociopsychiatric services must be better equipped in every respect. The professional competence of social workers and physicians, as well as of the relevant staff, must be safeguarded by continuing education and specialist training measures.

Community Mental Health Services

Biological activity of bacterial surface components. Immunogenicity and immunomodulatory properties of a bacterial extract from Escherichia coli.

The immunogenic and immunomodulatory properties of a lysed fraction from selected E. coli strains (OM-89, Uro-Vaxom) were determined in vivo and in vitro. It could be demonstrated that OM-89 constitutes an active immunogen in mice. Maximum OM-89-specific antibody titers were obtained after 4-5 i.p. immunizations; the titers could be further enhanced by the simultaneous injection of lipopeptide adjuvants. It was shown by ELISA that the antibodies obtained bound to the bacterial strains used for the preparation of the OM-89 extract. Immunogenicity was observed both after intraperitoneal and oral application of the extract. Besides being active as an immunogen. OM-89 was able to act in vitro as a polyclonal lymphocyte activator, as determined in splenocyte cultures of different inbred murine strains, and in cultures of human peripheral blood lymphocytes. Our results show that the B lymphocyte stimulating activity of the bacterial extract OM-89 was comparable to that of lipopeptide adjuvants. In conclusion, the bacterial extract both an active immunogen in vivo, and a polyclonal B cell activator in vitro. These findings may be of importance for the understanding of the therapeutic effect of OM-89.

Adjuvants, Immunologic