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Biomedical subjects

S Weber

Publications and source records attributed to S Weber.

At least 397 records · Page 22Linked to original sources
PubMedDate not supplied

Systemic genotoxic effects of tobacco-related nitrosamines following oral and inhalational administration to Sprague-Dawley rats.

An ex vivo model to detect nonspecific DNA damage in different rat tissues has been developed and employed to study systemic properties of tobacco-specific N-nitrosamines. One hour after treatment of rats with the carcinogens, primary, intact cells were isolated from various organs. Viability of the cells was monitored by trypan blue exclusion. Genotoxicity was determined by alkaline elution, in situ nick translation or microgel electrophoresis. We found that oral application of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces genotoxic effects in the liver (3.125-50 mg/kg), whereas N-nitrosonornicotine (NNN) is only moderately active (50-100 mg/kg). Furthermore, oral administration of NNK, NNN, and of N-nitrosodimethylamine (NDMA), induces DNA damage in the nasal cavity. In peripheral blood lymphocytes genotoxicity of NDMA (less than 2 mg/kg), but not of NNK (50 mg/kg), was observed. NDMA and NNK are just as genotoxic in the liver when administered by inhalation as orally (effective doses: 0.1-1 and 50 mg/kg, respectively). For human cancer, these results indicate that in addition to the susceptibilities in local organs (oral cavity after snuff dipping and lung after tobacco smoke inhalation), these nitrosamines also pose a risk systemically for more remote organs.

Administration, Inhalation↗
PubMedDate not supplied

Evaluation of first pass effect and biliary excretion of diperdipine in the dog.

Intravenous, oral and intraportal doses of diperdipine were given to bile duct cannulated dogs in order to assess the impact of first pass effect on the pharmacokinetics of this compound. After intravenous and oral doses, absolute bioavailability was calculated to be 18.7%. Biliary excretion accounted for about 0.1% of the total clearance of diperdipine and did not contribute to the overall elimination of the drug. After intraportal administration, the bioavailable fraction of diperdipine was increasing up to 44.3% suggesting a prehepatic site of loss of the drug. This was also substantiated by the fact that after oral administration a lesser fraction was excreted in the bile, than after the intraportal dose. The drug was highly bound to plasma proteins (greater than 96%) and was largely distributed in the blood cells for which a concentration dependent process was observed.

Administration, Oral↗
PubMedDate not supplied

Mivacurium infusion during nitrous oxide-isoflurane anesthesia: a comparison with nitrous oxide-opioid anesthesia.

STUDY OBJECTIVE: To determine the potentiation of the neuromuscular blockade induced by a titrated infusion of mivacurium in the presence of isoflurane versus a nitrous oxide (N2O)-opioid anesthesia. DESIGN: An open-label, controlled study. SETTING: The inpatient anesthesia service of two university medical centers. PATIENTS: Thirty adults divided into two groups. INTERVENTION: An intravenous infusion of mivacurium during anesthesia with N2O-opioid or N2O-isoflurane. MEASUREMENTS AND MAIN RESULTS: A neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. The mivacurium infusion rate was significantly less in the presence of isoflurane [4.0 +/- 0.8 micrograms/kg/min (mean +/- SEM)] than during N2O-opioid anesthesia (6.4 +/- 0.6 micrograms/kg/min). The recovery rates did not differ between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 of at least 0.75 occurred in an average of 17.9 +/- 1.5 minutes, with a mean recovery index (T25-75) of 6.0 +/- 0.7 minutes. CONCLUSION: Isoflurane anesthesia reduces the infusion rate of mivacurium required to produce about 95% depression of neuromuscular function.

Adult↗
PubMedDate not supplied

[Molsidomine in the treatment of coronary insufficiency].

Molsidomine, a predominantly venous vasodilator, has been coronary disease. The basic mechanism of its anti-anginal effect is a reduction in myocardial oxygen consumption due to a fall in left ventricular end-diastolic pressure resulting from the vasodilator action of the drug. To this may be added direct dilatation of the main coronary vessels on the surface of the heart, which may account for part in its therapeutic effects in unstable and vasospastic angina. The effectiveness of molsidomine has been evaluated by controlled drug versus placebo or drug versus reference anti-anginal drug studies in 3 types of angina pectoris: exertion, unstable and vasospastic. The usefulness of the drug has also been established in acute and chronic left ventricular failure of ischaemic origin. Because of its high bioavailability when administered orally, molsidomine shows little inter-individual variations in its pharmacodynamic effects. Unlike nitrates, it can be administered for long period without gradual loss of activity with time. Finally, on several experimental models molsidomine has been shown to exert an antiplatelet effect, but the therapeutic implications of this finding have yet to be evaluated.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[Stenosis of the main trunk of the left coronary artery. Apropos of 54 cases].

In the 54 patients studied coronary arteriography alone showed stenosis of the left main coronary artery (a lesion observed in 5.2 p. 100 of pathological coronary arteriographies), associated with other coronary lesions, 72.2 p. 100 of which involved all three major vessels. Ventriculography was abnormal in 53 p. 100 of the cases, with a less than 45 p. 100 left ventricular ejection fraction in 37.4 p. 100 of them. Nine patients were considered inoperable; 4 of these died during a 40-month follow-up period under medical treatment. Forty-five patients underwent coronary bypass; there were 4 peri-operative deaths (8.9 p. 100), 8 post-operative myocardial infarctions (17.8 p. 100) and one late death (2.2 p. 100). These patients were followed up for a mean period of 26.4 months. All authors who have studied the subject agree that surgery is beneficial: not only does it improve cardiac function, but it also prolongs survival. In spite of the peri-operative risks, surgery must be contemplated in patients with a more than 50 p. 100 stenosis of the left main coronary artery, provided the cardiac vascular bed is accessible to revascularization.

Arteriosclerosis↗
PubMedDate not supplied

Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by cDNA-transfected tumor cells induces a more potent antitumor response than exogenous GM-CSF.

Clinical cancer gene therapy trials have generally focused on the transfer of cytokine cDNA to tumor cells ex vivo and with the subsequent vaccination of the patient with these genetically altered tumor cells. This approach results in high local cytokine concentrations that may account for the efficacy of this technique in animal models. We hypothesized that the expression of certain cytokines by tumor cells would be a superior immune stimulant when compared with local delivery of exogenous cytokines. Granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA in a nonviral expression vector was inserted into MDA-MB-231 (human breast cancer), M21 (human melanoma), B16 (murine melanoma), and P815 (mastocytoma) cells by particle-mediated gene transfer. The ability of transfected tumor cells to generate a tumor-specific immune response was evaluated in an in vitro mixed lymphocyte-tumor cell assay and in an in vivo murine tumor protection model. Peripheral blood lymphocytes cocultured with human GM-CSF-transfected tumor cells were 3- to 5-fold more effective at lysis of the parental tumor cells than were peripheral blood lymphocytes incubated with irradiated tumor cells and exogenous human GM-CSF. Mice immunized with murine GM-CSF-transfected irradiated B16 murine melanoma cells or P815 mastocytoma cells were protected from subsequent tumor challenge, whereas mice immunized with the nontransfected tumors and cutaneous transfection of murine GM-CSF cDNA at the vaccination site developed tumors more frequently. The results indicate that GM-CSF protein expressed in human and murine tumor cells is a superior antitumor immune stimulant compared with exogenous GM-CSF in the tumor microenvironment.

Animals↗
PubMedDate not supplied

Effect of botulinum toxin A injections in the treatment of chronic tension-type headache: a double-blind, placebo-controlled trial.

In addition to vascular and supraspinal influences, contraction of craniofacial muscles or central sensitization processes following continuous nociceptive input of craniofacial muscles may play an important role in the pathogenesis of tension-type headache. Chemodenervation induced by botulinum toxin injection is successfully used to decrease muscle tension. If muscle tension is important in this type of headache, then botulinum toxin could be helpful in its treatment. We conducted a randomized, placebo-controlled study to examine the effect of 20 U botulinum toxin injected into frontal and temporal muscles in patients with chronic tension-type headache. During a baseline of 4 weeks and a posttreatment period of 8 weeks, the effect was evaluated with daily records and the West Haven-Yale Multidimensional Pain Inventory. Some improvement in affective variables were demonstrated in the botulinum group, but important outcome variables, such as pain intensity, the number of pain-free days, and consumption of analgesics, were not statistically different between the groups. Reasons for these moderate effects may include the injection sites, dose of botulinum toxin, and duration of treatment.

Adult↗
PubMedDate not supplied

[Indication for exercise therapy in infancy in the prevention of childhood cerebral palsy].

As in physiotherapy of cerebral palsy early therapy is desired, if possible even in early infancy, a period, when a safe diagnosis does not yet exist, infants at risk have to be identified. The resulting difficulties in early diagnosis and inevitability of treating a considerable number of not affected infants are discussed. The most common methods of physiotherapy are briefly described and evaluated critically concerning possible side effects as well. Superiority in effectivity improving motor efficiency of one method over another cannot be proven. It is shown, however, that in the Vojta method adverse psychological side effects cannot be excluded. Therefore, physiotherapy being a purely prophylactic and not a therapeutic procedure in the multitude of cases should be considered in ordering and selecting a particular method and the one according to Bobath should be favoured.

Cerebral Palsy↗