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Biomedical subjects

H Hoff

Publications and source records attributed to H Hoff.

At least 19 recordsLinked to original sources

[Urapidil for treatment of postanesthetic shivering following general anesthesia. A placebo controlled pilot study].

OBJECTIVE: Postanaesthetic shivering is common during recovery from general anaesthesia. Therefore we studied whether urapidil suppresses postanaesthetic shivering. METHODS: With written informed consent and approval of the local ethics committee, patients (ASA I-II) recovering from general anaesthesia were monitored for 1 h. Patients with continuous shivering for a period of 5 min were randomly treated either with 5 ml placebo (isotonic saline) or 25 mg urapidil in a double-blind trial. This treatment procedure was repeated if shivering did not stop. A complete suppression of shivering was appraised as a sufficient treatment. RESULTS: Shivering occurred in 20 of the patients studied and urapidil stopped shivering in 7 out of the 10 treated patients, whereas the placebo stopped shivering in only 2 out of 10 patients (P < 0.05). CONCLUSION: In a placebo controlled trial, it was demonstrated that postanaesthetic shivering can be successfully treated by urapidil in 70% of the patients.

Adrenergic alpha-Antagonists↗

A comparison between meperidine, clonidine and urapidil in the treatment of postanesthetic shivering.

UNLABELLED: Postanesthetic shivering can be treated with many types of drugs. We compared the effects of meperidine, clonidine, and urapidil on postanesthetic shivering. Sixty patients shivering during recovery from general anesthesia were treated in a randomized, double-blinded fashion with 25 mg meperidine IV, 0.15 mg clonidine IV, or 25 mg urapidil IV in three separate groups of 20 patients each. If shivering did not stop within 5 min, the treatment was repeated once; clonidine was replaced with saline for the second dose. Rectal temperature, arterial blood pressure, heart rate, SaO(2) and vigilance were monitored. Clonidine stopped shivering in all 20 patients. A single dose of meperidine stopped the shivering in 18 of 20 patients, with the other 2 patients needing a second dose. Urapidil was less effective: the first dose stopped the shivering in only six patients; the second dose was effective in another six; the drug was ineffective in 8 of 20 patients. Meperidine and clonidine were both nearly 100% effective in treating postanesthetic shivering without negative side effects. By comparison, urapidil was only effective in 60% of patients treated (P <0.01). IMPLICATIONS: Patients shivering during recovery from general anesthesia were treated in a randomized double-blinded fashion with meperidine, clonidine, or urapidil. Meperidine and clonidine were both very effective, whereas urapidil was only effective in 60% of patients treated.

Adrenergic alpha-Agonists↗

Mitogen-independent phosphorylation of S6K1 and decreased ribosomal S6 phosphorylation in senescent human fibroblasts.

The p70 ribosomal S6 kinase (S6K1) is rapidly activated following growth factor stimulation of quiescent fibroblasts and inhibition of this enzyme results in a G(1) arrest. Phosphorylation of the ribosomal S6 protein by S6K1 regulates the translation of both ribosomal proteins and initiation factors, leading to an increase in protein synthesis. We have examined the activation of S6K1 in human fibroblasts following mitogen stimulation. In early passage fibroblasts S6K1 is activated following serum stimulation as evidenced by increased kinase activity and site-specific phosphorylation. In contrast, site-specific phosphorylation of S6K1 at Thr421/Ser424 is diminished in senescent fibroblast cultures. A second phosphorylation site within S6K1 (Ser411) is phosphorylated even in the absence of serum stimulation and the enzyme shows increased phosphorylation as judged by decreased electrophoretic mobility. Inhibitor studies indicate that this phosphorylation is dependent upon the mammalian target of rapamycin, PI 3-kinase, and the MAPK pathway. In order to understand the consequences of the altered phosphorylation of the S6K1, we examined the phosphorylation state of the ribosomal S6 protein. In early passage fibroblasts the ribosomal S6 protein is phosphorylated upon serum stimulation while the phosphorylation of the ribosomal S6 protein is drastically reduced in senescent fibroblasts. These results suggest that the intracellular regulators of S6K1 are altered during replicative senescence leading to a deregulation of the enzyme and a loss of ribosomal S6 phosphorylation.

Blood Proteins↗

Insulin-like growth factor I-mediated degradation of insulin receptor substrate-1 is inhibited by epidermal growth factor in prostate epithelial cells.

We have sought to determine whether insulin-like growth factor I (IGF-I) regulates the levels of insulin receptor substrate-1 (IRS-1) in prostate epithelial cells. Exposure of prostate epithelial cells to IGF-I in the absence of other growth factors leads to a reduction in IRS-1 levels. Ubiquitin content of IRS-1 is increased in the presence of IGF-I, and inhibitors of the proteasome prevented the reduction of IRS-1 levels seen following IGF-I exposure. These results imply that IRS-1 is targeted to the proteasome upon exposure to IGF-I. The addition of epidermal growth factor (EGF) maintained IRS-1 levels even in the presence of IGF-I and inhibits IGF-I-dependent ubiquitination of IRS-1. Thus, these two growth factors, IGF-I and EGF, had antagonistic effects on IRS-1 protein levels in prostate epithelial cells. This regulation of IRS-1 reveals a novel level of cross-talk between the IGF-I and EGF signal pathways, which may have implications in tumors that harbor activating mutations in the EGF receptor.

Cells, Cultured↗

Activation of the insulin-like growth factor type 1 receptor by deletion of amino acids 870-905.

We have created a deletion mutant of the insulin-like growth factor type 1 receptor (IGF-1 R) which lacks the 36 amino acids (aa) immediately N-terminal to the transmembrane domain (Delta870-905 IGF-1 R). This region has been reported to have a negative effect on the transforming potential of an avian sarcoma virus gag-IGF-1 R fusion protein. We have sought to determine whether this region plays a similar role in the intact IGF-1 R. Analysis of the tyrosine kinase activity of the Delta870-905 IGF-1 R shows that the mutant receptor is autophosphorylated without IGF-1 stimulation, indicating that the tyrosine kinase domain is constitutively active. In addition, processing of the receptor is decreased, resulting in accumulation of a high molecular weight proreceptor containing both alpha and beta-subunits. A well-characterized substrate of the IGF-1 R, IRS-1, is constitutively phosphorylated by the Delta870-905 IGF-1 R and phosphoinositide (PI) 3-kinase activity, which is normally activated by the phosphorylation of IRS-1 following IGF-1 stimulation, is increased even in the absence of IGF-1. A second intracellular signal pathway normally activated by IGF-1, the MAP kinase pathway, showed no increase in activity in the absence of IGF-1. The Delta870-905 IGF-1 R promoted cell proliferation only in the presence of IGF-1. We conclude that this deletion increases the basal activity of the IGF-1 receptor tyrosine kinase and activates PI 3-kinase, but is unable to stimulate MAP kinase in the absence of ligand. These results confirm those seen in the gag-IGF-1 R fusion protein and indicate that aa 870-905 exert a negative effect on the tyrosine kinase domain of the beta-subunit of the IGF-1 R.

Amino Acid Sequence↗

Lipopolysaccharide induces time-dependent increases in prostaglandin H synthase-2 and cytosolic phospholipase A2 mRNA in cultured human microvessel-derived endothelial cells.

The effect of lipopolysaccharide (LPS) upon the cellular content of mRNA for several enzymes associated with the arachidonic acid cascade was determined in human microvessel-derived endothelial cells. Cells were treated with either vehicle or 10 ng/mL LPS for up to 24 h. Reverse transcription followed by DNA amplification and Southern blotting were used to quantify mRNA for prostaglandin H synthase-1, prostaglandin H synthase-2, cytoplasmic PLA2, and a group II secretory PLA2. LPS treatment resulted in an increase in prostaglandin H synthase-2 mRNA after 4 h with a second peak occurring at 12 h of incubation. The expression of prostaglandin H synthase-1 mRNA was not altered by LPS treatment. An increase in cytoplasmic PLA2 mRNA but not group II PLA2 mRNA was seen after 12 h. These data demonstrate that LPS can increase mRNA production for the inducible form of prostaglandin H synthase and for cytoplasmic PLA2 in a time-dependent manner in human microvessel-derived endothelial cells. These multiple, specific increases in the prostaglandin H synthase-2 and phospholipase A2 mRNA values suggest a complex interaction between bacterial LPS and the endothelial cell eicosanoid system.

Base Sequence↗

The effect of major railway accidents on the psychological health of train drivers--I. Acute psychological responses to accident.

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8). Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.

Accidents, Occupational↗

The effect of major railway accidents on the psychological health of train drivers--II. A longitudinal study of the one-year outcome after the accident.

The psychological impact on 101 train drivers of accidents causing major injuries or death to persons was studied by means of clinical interviews and questionnaires (Impact of Event Scale, General Health Questionnaire and a questionnaire addressing stress symptoms plus past and pre accident expectancies of being involved in accidents). The drivers were examined within hours to a few days after the accident and later at 1 month and 1 year. One month after the accident the symptoms of distress were significantly reduced and most so among the drivers with no preaccident risk experience according to self reports during the acute phase. A minor further reduction of distress was found at 1 year. Drivers with two or more previous accident experiences and those who had worried about being involved in accidents showed highest symptoms of distress at follow-up. Eleven out of 101 drivers reported sick leave more of than 1 week after the accident and this was related to higher intrusion scores. The few drivers who report longterm psychological distress are best predicted by a combination of acute high IES scores, experience of previous accidents and risk expectancy prior to the current accident. The study suggests that premorbid and non-accident related variables are more important for the 1 year psychological outcome of healthy drivers after on-the-track accidents than the stress event itself.

Absenteeism↗

Metabolic products of microorganisms. 261. Obscurolides, a novel class of phosphodiesterase inhibitors from streptomyces. I. Production, isolation, structural elucidation and biological activity of obscurolides A1 to A4.

A novel class of butyrolactones, named obscurolides, was isolated from the culture filtrate of Streptomyces viridochromogenes by chemical screening methods. The structural elucidation of the obscurolides A1 to A4 (1 approximately 4) is described. The carboxy group of the 4-aminobenzoic acid moiety of obscurolide A1 (1) is reduced in the other compounds. The isolated natural products have been proved to be diastereomeric mixtures by a partial racemization at C-7 which belongs to an allylic alcohol system. The obscurolides showed a weak inhibitory activity against calcium/calmodulin-dependent and independent phosphodiesterases from bovine.

4-Butyrolactone↗

Mechanism of fusion of Sendai virus: role of hydrophobic interactions and mobility constraints of viral membrane proteins. Effects of polyethylene glycol.

The mechanism of Sendai virus fusion was investigated by studying the effect of the dehydrating agent polyethylene glycol (PEG) on the interaction of the virus with erythrocyte membranes. The initial rate of virus fusion, monitored continuously by a fluorescence membrane fusion assay, increases approximately 5-fold in the presence of small amounts (4%, w/v) of PEG. The polymer did not trigger a massive nonspecific fusion event, as the limited number of virus particles that fuse per erythrocyte ghost remains unaltered. A mass action kinetic analysis reveals that the binding rate constant increases approximately 1.5-fold; however, the fusion rate constant is enhanced by about an order of magnitude. The results demonstrate that hydrophobic interaction forces dominate the actual fusion step of the virus. Below about 22 degrees C, the viral membrane proteins appear to be clustered, as revealed by temperature-dependent fluorescence measurements of fluorescently tagged viral proteins. Clustering is not modulated by the presence of PEG, and fusion at those conditions is not observed. It is concluded that in addition to hydrophobic interactions, constraints in the mobility of the viral membrane proteins codetermine the fusogenic capacity of the virus. Such constraints have to be relieved in order to allow the occurrence of the hydrophobic interactions. PEG primarily affects the surface properties of the viral membrane, including the properties of the membrane glycoproteins. We hypothesize that during virus-target membrane interaction but prior to the actual fusion reaction, the fusion protein may undergo a conformational change, triggered by an enhancement in hydrophobic environment, which accounts for the need to establish close, i.e. fusion-susceptible intermembrane contact between virus and target membrane.

Cell-Free System↗

Contrasting effects on plasma lipoproteins of intravenous versus oral administration of a triglyceride-phospholipid emulsion.

The effect of fat on plasma lipoproteins was compared when administered by the oral and intravenous routes to healthy control subjects on a low fat diet for 5-6 weeks. During this time each subject underwent two 5 day periods of fat supplementation with a soya bean triglyceride-egg yolk phospholipid emulsion (Intralipid), once via intragastric tube, once intravenously. Changes in plasma lipoproteins were assessed by measurement of their lipid and protein content. Intragastric fat administration significantly decreased the level of very low density lipoprotein (VLDL), whereas intravenous fat administration caused a significant rise in low density lipoprotein (LDL). Morphological evidence of persistence of exogenous phospholipid in plasma following intravenous fat administration was confirmed by alterations in the fatty acid composition of lecithin in the d 1.006-1.063 fraction of plasma. In vitro studies showed that exchange readily occurred between Intralipid and LDL lecithin, causing the latter to assume a more saturated pattern. It is concluded that the occurrence of similar changes in vivo could explain the rise in low density lipoprotein following intravenous fat, possibly by influencing the catabolic rate of the apoprotein. Hydrolysis of ingested phospholipids during absorption presumably explains why none of these changes occurred after oral fat supplementation, and would seem to be an important regulatory function of the small intestine in relation to plasma lipoprotein metabolism.

Administration, Oral↗

[Disorders of lateralization caused by severe organic brain damage].

The decisive period of the development of dominance is in the fourth year. Aphasic disturbances in younger children therefore have as their prerequisite bilateral lesions, it being only after this period that aphasias may be observed to be associated with unilateral cerebral lesions. Up to the fourth year of life it is, therefore, possible for unilateral cerebral lesions to be relatively easily compensated by a "change of dominance".

Aphasia↗