[Physician administrator system in the time of DRGs].
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Diagnosis-Related Groups↗
Biomedical subjects
D Daub
Publications and source records attributed to D Daub.
A constitutional BWS-related t(11;16) chromosome translocation occurring in the same region of chromosome 16 implicated in Wilms' tumors.
Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder with a varying spectrum of clinical manifestations including macroglossia, omphalocele, hemihypertrophy, and a predisposition to a subset of embryonal tumors, most frequently Wilms' tumor (WT). A variety of cytogenetic, genetic linkage, and molecular mapping data implicate a gene or genes on chromosome band 11p15.5 in BWS and its related tumors. However, some families with BWS do not show linkage to 11p15, and other alterations have been found in Wilms' tumors as well. One such alteration is loss of heterozygosity (LOH) for chromosome arm 16q. Here we have analyzed a balanced t(11;16)(p15;q13) chromosomal translocation associated with the BWS phenotype and mapped the breakpoint positions for both chromosomes 11 and 16 by using somatic cell hybrids and polymorphic markers. The chromosome 11 breakpoint was found to lie distal to the D11S12 locus, but proximal to TH on 11p15.5, a region shown previously to contain other BWS-related chromosomal events. The chromosome 16 breakpoint was distal to D16S290 in 16q13, but proximal to loci D16S265, D16S267, and D16S164 in band 16q21. This area encompasses the region of LOH occurring through mitotic recombination in sporadic WT. This raises interesting possibilities for the genetic and epigenetic involvement of both chromosomal regions (11p15 and 16q13) in the pathogenesis of BWS and Wilms' tumor.
Adult↗
Molecular sublocalization and characterization of the 11;22 translocation breakpoint in a malignant rhabdoid tumor.
Malignant rhabdoid tumors are extremely aggressive soft-tissue sarcomas that tend to be widely metastatic at diagnosis. These tumors were first described as variants of the kidney neoplasm Wilms' tumor, although tumors of similar clinicopathologic features have been cited in a variety of extrarenal sites. Here, we have characterized the chromosomal translocation t(11;22)(p15.5;q11.23) from a retroperitoneal rhabdoid tumor. Somatic cell hybrids with segregated copies of the derivative 11 and derivative 22 chromosomes allowed sublocalization of the chromosome 11 breakpoint to a 1- to 2-Mb region between the proximal marker D11S12 and the distal locus tyrosine hydroxylase (TH). Translocation-associated aberrant fragments were identified by pulsed-field gel electrophoresis, with the smallest resulting from BssHII digestion as detected with a probe for TH. These data indicate that the locus or loci disrupted by this genetic abnormality might lie less than 60 kb proximal to this marker and place it in the chromosomal vicinity of genes involved in the etiologies of rhabdomyosarcoma, Wilms' tumor, and the congenital overgrowth disorder, Beckwith-Wiedemann syndrome. Analysis of two other tumor-associated loci, EWS1 and NF2, that have been mapped to the general region of 22q11.2 indicated that they were not involved in this translocation breakpoint. Isolation of the genes present at this translocation junction on both chromosomes 11 and 22 may yield important clinicopathologic and genetic markers for this enigmatic tumor as well as other pediatric diseases.
Animals↗
[Argon gas embolism in laparoscopic cholecystectomy with the Argon Beam One coagulator].
The report is about argon embolism in a 37-year-old female patient during laparoscopic cholecystectomy and coagulation of a liver bed bleeding with the "Argon Beam One". The presented case report is to show that in spite of technical perfection and correct use of the Argon Beam One coagulator unfavorable anatomical conditions can cause life threatening gas embolism.
Adult↗
[Reduction of preoperative anxiety. A study comparing music, Thalamonal and no premedication].
Ninety ASA I-II patients scheduled for a pre-planned surgical operation were randomly assigned to three groups: the first of these received no premedication, the second received 1-2 ml Thalamonal i.m., and the third were offered music from a walkman via earphones. Excluded from the study were patients under 15 and over 65 years of age, patients suffering from malignant diseases, those expecting operations of uncertain outcome, and patients whose mother tongue was not German. All 90 patients were cared for by the same investigator. She obtained informed consent on the eve of the scheduled operation and chose the music that was to be offered preceding the operation according to the patient's wishes. Each patient's history was evaluated, including the grade of anxiety and his or her attitude towards music. Of course, a physical examination was also conducted. Ninety minutes prior to the operation, psychometric tests (STAI-G-X2, STAI-G-X1, ESA-S, and BF-S) were performed. Thereafter, either music was offered or else 1-2 ml Thalamonal was injected, according to the random assignment: group 1 received neither. Fifteen minutes before entering the operating room, the tests expressing anxiety with regard to the situation were repeated as was the physical examination, and the investigator once again assessed the level of anxiety of the patients. On the evening of the day of surgery, all patients were asked to give an evaluation of the preoperative period. Trait-anxiety, as measured by the STAI-G-X2-Test, was comparable in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Opioid analgesia in extracorporeal shock wave lithotripsy: fentanyl versus alfentanil.
More than 1,600 patients have been treated by extracorporeal shock wave lithotripsy (ESWL) under fentanyl analgesia without any complications or severe side-effects. As secondary respiratory depression is still under discussion, we investigated the value of alfentanil--a short-term acting opioid--with special interest in its efficacy and side-effects. Neither fentanyl nor alfentanil significantly influenced blood pressure, respiratory rate and blood gases. With regard to minor side-effects and patient's acceptance, alfentanil analgesia should be preferred during ESWL treatment.
Alfentanil↗
[Comparative studies of the postoperative phase following opioid analgesia using fentanyl and alfentanil within the scope of extracorporeal shockwave lithotripsy].
30 patients (ASA Class I-III) received opioid analgesia with fentanyl and alfentanil for extracorporeal shock wave lithotripsy. Average doses were 0.41 mg for fentanyl and 4.14 mg for alfentanil. Blood pressure, respiratory frequency, and blood gases were investigated postoperatively until the 240th min under spontaneous breathing of room air. Blood pressure varied less than 10% from initial values in both groups. The respiratory rate decreased by 13% in the alfentanil group and by 20% in the fentanyl group until the 120th min. The blood gases (paCO2, paO2) showed a slow increase of about 10% in the paCO2 in both groups. The paO2 lay at 5.8% below the baseline after 240 min in the fentanyl group and there was roughly 3% below the baseline after 60 min in the alfentanil group.
Alfentanil↗
An anesthesia information system for monitoring and record keeping during surgical anesthesia.
We have developed an anesthesia information system (AIS) that supports the anesthesiologist in monitoring and recording during a surgical operation. In development of the system, emphasis was placed on providing an anesthesiologist-computer interface that can be adapted to typical situations during anesthesia and to individual user behavior. One main feature of this interface is the integration of the input and output of information. The only device for interaction between the anesthesiologist and the AIS is a touch-sensitive, high-resolution color display screen. The anesthesiologist enters information by touching virtual function keys displayed on the screen. A data window displays all data generated over time, such as automatically recorded vital signs, including blood pressure, heart rate, and rectal and esophageal temperatures, and manually entered variables, such as administered drugs, and ventilator settings. The information gathered by the AIS is presented on the cathode ray tube in several pages. A main distributor page gives an overall view of the content of every work page. A one-page record of the anesthesia is automatically plotted on a multicolor digital plotter during the operation. An example of the use of the AIS is presented from a field test of the system during which it was evaluated in the operating room without interfering with the ongoing operation. Medical staff who used the AIS imitated the anesthesiologist's recording and information search behavior but did not have responsibility for the conduct of the anesthetic.
Anesthesia Department, Hospital↗
[Anesthesiologic aspects of extracorporeal shockwave lithotripsy (ESWL)].
Anesthesiological considerations are discussed on the basis of the limited literature available and our own experience with more than 2000 ESWL treatments. Guidelines concerning anesthesia technique and ESWL treatment of renal and ureteral stones are outlined and compared to our own results and those in the literature. The following techniques are discussed: intubation anesthesia with halogenated carbohydrogens (Fluothane, Ethrane), intubation anesthesia with Fluothane/Ethrane plus opiates, neuroleptic anesthesia, catheter peridural anesthesia (lumbar/thoracic), opiate analgesia and high frequency jet ventilation.
Analgesics, Opioid↗
[Opioid analgesia--an alternative to general anesthesia].
The use of opioid analgesia in the awake, spontaneously breathing patient has not yet been published as an alternative to general anaesthesia or epidural analgesia. 297 patients were treated by injecting on demand up to 0.9 mg of fentanyl intravenously to abolish the considerable pain which is caused by extracorporal shock wave lithotripsy. In contrast to its alternatives, fentanyl analgesia had no effect on circulatory parameters when the patients were immersed in a bath at 37 degrees C. Arterial gas analysis showed only a slight increase in paCO2 values and a remarkably constant paO2 if oxygen was added to inhaled air. Breathing of pure air caused a dramatic decrease of paO2 6 to 15 minutes after the administration of the loading dose of fentanyl. The method is only practicable if the patient stays awake and is awakened whenever he is at the point of falling asleep.
Analgesia↗
[CO2-response curves as a measure of opiate-induced respiratory depression. Studies with fentanyl].
The ventilatory response to CO2 after fentanyl 4 micrograms/kg was studied in a group of 10 healthy volunteers of both sexes, aged 20 to 41 years. Following randomization intravenous premedication with either placebo, diazepam 5 mg, droperidol 5 mg or etomidate 10 mg, a total of four test series were performed with each individual in two-week intervals, in order to assess the additive effect of central depressants on opiate-induced respiratory depression. CO2-response curves were obtained during six-minute rebreathing periods up to 60 min after fentanyl. Respiratory frequency as well as slope and position of the curves were compared with pre-drug control values. After fentanyl, CO2-response curves usually showed combined decreases in slope and displacements to the right, which had not completely returned to control levels after one hour. Due to enormous inter- and intra-individual variations, no clearly significant differences could be observed between the premedication groups. Fentanyl plasma concentrations, determined by radioimmunoassay at 1, 3, 6, 10, 20, 30, 45, 60, 75 and 120 min after injection, showed only a poor correlation to the changes of the CO2-response curves. To assess the clinical relevance of results derived from CO2-stimulation studies, the literature is reviewed with respect to the respiratory control system and the interactions of various anaesthetics drugs (including opiate analgesics) with respiratory regulation. The activity of the reticular formation at lower brain stem level seems to be of decisive importance to guarantee adequate ventilation. Despite quite different action sites, most central depressant drugs reduce reticular activity, thus inhibiting compensatory mechanisms which usually help control respiration. CO2-response tests are therefore suggested to be unable to give sufficient clinical information about the respiratory regulation system.
Adult↗
[Disposition of fentanyl in human blood].
Plasma protein binding and uptake of fentanyl by erythrocytes was studied in a group of 30 healthy patients of both sexes (aged 4-84 years), undergoing orthopaedic or minor surgical operations. Using equilibrium dialysis (24 h, 37 degrees C, phosphate buffer pH 7.4 containing fentanyl 5 ng/ml) the protein bound fraction was found to be 72.4% +/- 7.9 (mean +/- standard deviation). Proteins in the plasma of children or elderly patients bound to a slightly higher degree as compared with the group of medium age, while no differences between sexes were observed. The addition of various intravenous anaesthetic drugs in a therapeutic concentration range did not alter plasma protein binding seriously. There seems to be a correlation between fentanyl plasma protein binding and the plasma content of acid alpha-1-glycoproteins. Human erythrocytes were found to equilibrate very rapidly with plasma fentanyl, the partition coefficient being almost unity. Distribution into the red cells was not influenced by adding intravenous anaesthetics or plasma expanders to the blood samples, nor was it altered by changes of pH or temperature. Storage of fentanyl did not modify erythrocyte morphology even at high concentrations, as indicated by normal MCV or MCHC. Fentanyl was found not to be metabolized in human whole blood, haemolysate or plasma. The activity of serum enzymes commonly used in routine diagnosis was not influenced by fentanyl concentrations in a range up to 1,000 ng/ml.
Adolescent↗
[Biotransformation of fentanyl. III. Effect of chronic drug exposure on the distribution, metabolism and excretion in the rat].
In male Wistar rats, tissue distribution and excretion of fentanyl and its metabolites were studied after intravenous of intramuscular injection. Oxidative desalkylation leading to phenylacetic acid and norfentanyl proved to be the main degradation pathway in-vivo, whereas other metabolites, including the pharmacologically still active p-hydroxy(phenethyl)fentanyl were formed only in minor quantities. All compounds could be detected in any tissue under study (brain, lung, liver, kidney, muscle and fat) as well as in the gastric contents, the amount of fentanyl in the latter cumulating to about 2% of the total dose 60 min after injection, compared with about 10% in the fat. In rats chronically treated with ethanol, nicotine, morphine, phenobarbital, promethazine or diazepam, major differences in in-vitro fentanyl metabolism by liver homogenates were observed including both inhibition and induction. Phenobarbital pretreatment also induced extrahepatic biotransformation in kidney, adrenals and intestinal mucosa. On the other hand, tissue concentrations of fentanyl and its metabolites did not clearly reflect the in-vitro changes in metabolic activity. Fentanyl brain levels were found to be lower in the treatment groups but seemed not to correlate with pharmacodynamics, less effects following injection being observed only after ethanol and morphine. The in-vitro metabolic drug interaction proved to be of less importance than changes in diuresis and/or urinary pH when excretion products were analysed. As a conclusion, it is suggested that altered sensitivity of brain tissue rather than changes in bioavailability must explain variations in dose-response relationship which are frequently believed to be seen when fentanyl is used in patients with chronic drug administration.
Animals↗
[A multifactorial study on the effect of diazepam].
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Adult↗
[Fentanyl pharmacokinetics and postoperative respiratory depression (author's transl)].
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Adult↗
[Biotransformation of fentanyl. II. Acute drug interactions in rats and men (author's transl)].
Rat tissue homogenates were used to study fentanyl biotransformation. The liver was shown to be the most important metabolizing organ, whereas extrahepatic metabolism occurred only to a minor degree in the kidneys. The products of oxidative desalkylation, phenylacetic acid and norfentanyl, could be identified as well as small amounts of p-hydroxy-(phenethyl)fentanyl, which is pharmacologically still active. Major sex differences were observed, male rats showing nearly twice as much activity as female animals. Several anaesthetic agents, often used in combination with fentanyl, were tested with respect to their influence on fentanyl metabolism. Most of them caused an inhibition of biotransformation and/or variations in product distribution, when they were added to in-vitro incubations or given to the animals prior to enzyme preparation. This experimental design proved to be useful as a screening method to predict metabolic drug interactions. Halothane and enflurane, which are strong inhibitors in rats, were demonstrated to delay fentanyl metabolism in man, too. Fentanyl plasma levels under halothane anaesthesia were found to be more than twice as high as during neuroleptanaesthesia. The importance of other agents, e.g. ketamine, promethazine or local anaesthetics, remains to be examined. Variations of biotransformation reactions among patients as well as the reported drug interactions might explain some differences in fentanyl blood concentrations reported in the past, but must also be taken into account when intensity and duration of effects or side-effects are discussed.
Adult↗
["Analgesic" fentanyl blood concentrations during neuroleptanalgesia].
In 72 patients (ASA I-III) undergoing all kinds of elective surgery under routine neuroleptanalgesia, fentanyl plasma concentrations were determined at the moment of diminishing analgesic effect. Minimum analgesic blood concentrations were found to be approximately log-normally distributed (mean 2.89 ng/ml, c.v. 77.56%). There was no significant difference between sex, age or type of surgery. The finding contradict the common opinion that analgesic threshold concentrations exist or that pharmacodynamic effects of the receptor specific drug fentanyl could easily be predicted by blood pharmacokinetics. It is suggested that individual dosing of fentanyl rather than continuous infusion should be preferred in routine neuroleptanalgesia.
Adult↗
[I. Metabolism by mouse tissue homogenates in vitro (author's transl)].
Mouse liver homogenates are shown to metabolize tritiated fentanyl intensively and in a nearly quantitative manner. The biotransformation activity is located in the microsomal fraction. NADH and NADPH are required as coenzymes for at least two enzymatic reactions leading to the products of oxidative desalkylation, phenylacetic acid and norfentanyl, and to four other metabolites, some of which are considered as products of aromatic hydroxylation, e.g. p-hydroxy(phenethyl)fentanyl. The degree of fentanyl biotransformation and the product distribution are demonstrated to be pH-dependent, the oxidative desalkylation reaction preferring higher pH. There is no information about the pharmacological activities of the unknown metabolites. Kidney and adrenal gland, too, are able to metabolize fentanyl, the oxidative desalkylation being of only minor importance. Other tissues and the serum prove to be inactive. The results of the present paper, in accordance with recently published work, may suggest a greater importance of fentanyl metabolism for the kinetics of effects and side effects than has been recognized before.
Animals↗