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Biomedical subjects

P Hoffmann

Publications and source records attributed to P Hoffmann.

At least 163 records · Page 9Linked to original sources

[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↗

Carbon disulfide exposure attenuates adrenergic inotropic response in rats.

Catecholamine-induced myocardial necrosis is enhanced in carbon disulfide exposed rats. We investigated whether the reported morphological findings after carbon disulfide exposure are accompanied by functional disturbances of the adrenergic inotropic response as well as by biochemical alterations. The cardiac effects of epinephrine and norepinephrine were studied in urethane-anesthetized rats which had been subacutely exposed to carbon disulfide. Compared with not exposed control animals left ventricular inotropic response was diminished and the transient T-wave elevation of the ECG due to ischemic episodes was enhanced in carbon disulfide-exposed rats. Activity of LDH-isozymes in the myocardium was shifted toward LDH-M. Our results support the hypothesis that carbon disulfide causes disturbances of energy supply in the heart.

Animals↗

Adrenergic cardiovascular actions in rats as affected by dichloromethane exposure.

Dichloromethane sensitizes the myocardium to arrhythmia development in response to catecholamines. The effects of acute dichloromethane exposure (3.1, 6.2 or 12.4 mmol/kg) on cardiovascular actions of epinephrine (1 or 4 micrograms/kg iv) and norepinephrine (2 or 10 micrograms/kg iv) in the urethane-anaesthetized rat model was investigated. Hypertensive epinephrine effects as well as reflex bradycardia after epinephrine and norepinephrine injections were augmented in dichloromethane-exposed rats. Moreover we observed an enhanced negative dromotropic epinephrine action. The transient T-wave elevation after catecholamine injection was markedly increased in animals treated with 12.4 mmol/kg dichloromethane. The results show that dichloromethane exposure modifies cardiovascular actions after catecholamine administration. The release by dichloromethane of endogenous catecholamines could play a role in the manifestation of these effects.

Adrenergic Fibers↗

[B-image sonography in lymph node staging of the head and neck area. A comparison with palpation, computerized and magnetic resonance tomography].

The results of palpation, CT and MRI and high resolution ultrasound were compared in 100 patients with malignancy of the head and neck. Ultrasound detected far more lymph nodes than the other methods. These diagnostic findings were compared with the operative and histological results in 62 patients. Ultrasound proved superior to the other methods: a lymph node metastasis was missed in only 2 patients by sonography, whereas in 20 patients metastases were overlooked by CT and MRI scans, and in 27 patients by palpation. High resolution ultrasound is at present the most reliable method for the detection of lymph nodes in the head and neck.

Carcinoma, Squamous Cell↗

Cerebrospinal fluid immunoreactive beta-endorphin concentration is increased by voluntary exercise in the spontaneously hypertensive rat.

The effect of voluntary exercise on cerebrospinal fluid (CSF) levels of immunoreactive beta-endorphin has been studied in the spontaneously hypertensive rat (SHR). The exercise consisted of 5-6 weeks of spontaneous running in wheels and the average running distance was 3.5 +/- 0.4 km/24 h. CSF samples were obtained under anaesthesia from the cisterna magna. Five experimental groups were examined, four groups of runners and one group of sedentary controls. The runners were sampled either (a) shortly (0-3 h) after termination of exercise, or after the wheel had been locked for (b) 24, (c) 48 or (d) 96 h. The runners in group a had significantly higher immunoreactive beta-endorphin levels than the controls. The levels remained increased as compared with controls after 24 and 48 h of enforced abstinence but had returned to control after 96 h. The data indicate that voluntary exercise induces adaptive changes in central beta-endorphin systems.

Animals↗