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Biomedical subjects

N Hahn

Publications and source records attributed to N Hahn.

At least 19 recordsLinked to original sources

[Properties and degradation of a new bioresorbable bone glue].

In trauma surgery gluing is an attractive method of bonding fractured bone, which is rapid and does not require the use of screws and plates. The purpose of this study was to analyze in vitro the properties of a new bioresorbable bone glue, and in vivo its structure and degradation. The newly developed bone glue is based on alkylenbis(oligolactoyl)methacrylates and employs a two-component initiator system. Starting components for synthesis are ethylene glycol, lactic acid and methacrylic acid. In vitro the solidified glue is degraded via hydrolysis of ester bonds. Degradation products are ethylene glycol, lactic acid and oligomeres of methacrylic acid. After the first week polymer pellets (MMA, HEMALA, ELAMA) showed a weight loss of 12%. From week 2-20 a linear weight loss of 1.5% per week, that is 40% after 20 weeks, was observed. The in vivo investigations of the ultrastructure of the glue revealed a transparent and homogeneous mass with large electron-tight vacuoles. Differences in structure and degradation were not observed. Degradation of glue by hydrolysis and phagocytosis, with good biocompatibility was demonstrated.

Absorbable Implants↗

[In Process Citation]

Cardiac excitation, conduction, and refractory parameters of the heart were investigated in 36 pigs (German country breed) to obtain basic values under influence of the following 10 anaesthetic regimes using HIS bundle electrography and programmed stimulation: 1. azaperone/metomidate/chloralose, 2. ditto + nitrous oxide, 3. azaperone/pentobarbital, 4. ditto + nitrous oxide, 5. ketamine/fentanyl/midazolam/pancuronium, 6. ditto + nitrous oxide, 7. ketamine/pentobarbital, 8. ditto + nitrous oxide, 9. ketamine/propofol, 10. ditto + nitrous oxide. Only the effects in the groups 5 and 6 just as 9 and 10 could be compared to former results in dogs under equal anaesthetic conditions. It could be shown that in almost all observed parameters there were differences between both species. This should be considered in experiments with other substances or in cardiovascular results.

Journal Article↗

Non-invasive transgenic mouse genotyping using stool analysis.

Commonly applied genotyping of transgenic mice involves using tail or ear biopsies which may cause discomfort to the animal. We tested the possibility of polymerase chain reaction (PCR)-based mouse genotyping using stool specimens from three transgenic mouse lines that overexpress 10-18 transgene copies of human keratin polypeptide 18, as compared to genotyping using tail biopsies. Stool specimens were obtained with ease and provided easy detection of the human transgene product. The method was also able to detect endogenous mouse actin and keratin genes which presumably are present at two copies each. Nested PCR was not necessary for genotyping using stool-derived genomic material but did increase the relative magnitude of the signal obtained. The non-invasive genotyping method described herein offers a reproducible, sensitive and effective modality that could replace invasive tissue sampling procedures currently used to test thousands of genetically altered mice.

Animals↗

The pharmacist's role in the optimal delivery of primary care in a managed care world.

For managed care to continue positive growth, pharmacists will have to offer support measures for primary care physicians, even as efforts are made to increase the supply of these physicians. The pharmacy practice at Medical University of South Carolina Family Medicine Center has gained national recognition for providing an expansive role model for pharmacists who are committed to providing pharmaceutical care and related services in primary care surroundings. This article discusses managed care in the primary care arena and pharmacists' role in providing pharmaceutical care and teaching future pharmacists their role in a managed primary care world.

Family Practice↗

[Basic values of blood coagulation parameters in pigs (Sus scrofa domesticus)].

On 23 clinical healthy pigs (2-4 months of age, body weight 13-42 kg) under ketamin-pentobarbital anaesthesia blood plasma coagulation parameters have been investigated. To obtain basic values 26 parameters were measured: number of thrombocytes, parameters of thrombelastogram and resonance-thrombogram, prothrombin time, activated partial thromboplastin time, thrombin time, reptilase time, factors I, II, V, VII, VIII, X, antithrombin III, plasminogen, alpha 1-antitrypsin, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrin degradation products D and E and euglobulin lysis-time. Parameters calculated in percent should be measured against a pig plasma pool. Measurement against a human plasma pool are hardly valid in values higher than 100%. In comparison to man the results indicate modifications of fibrinogenesis and fibrinolysis in pigs.

Animals↗

[Effects of anesthesia with inhalation anesthetics on excitation, conduction and refractory parameters of the heart. Experiments in dogs].

Cardiac excitation, conduction, and refractory parameters of the heart were investigated in 40 beagle dogs to obtain basic values under the influence of the following 9 inhalation anaesthetic regimes using HIS-bundle electrography and programmed stimulation: 1. halothane; 2. enflurane; 3. isoflurane; 4. halothane+nitrous oxide; 4. enflurane+nitrous oxide; 6. isoflurane+nitrous oxide; 7. alfentanil/midazolam/succinylcholine+nitrous oxide; 8. fentanyl/midazolam/pancuronium bromide+nitrous oxide; 9. propofol+nitrous oxide. It could be shown that inhalation anaesthetics under laboratory conditions exert some influences on the observed cardiac parameters, although they are not as strong as those of intravenous anaesthetics. Therefore their effects should be considered in experiments with other substances or in cardiovascular results.

Anesthesia, Inhalation↗

[Effects of intravenous anaesthetics on excitation, conduction, and refractory parameters of the heart. Experimental study in the dog].

Cardiac excitation, conduction, and refractory parameters of the heart were investigated in 59 beagle dogs to obtain basic values under the influence of the following 11 intravenous anaesthetic regimes using HIS-bundle electrography and programmed stimulation: 1. Alfentanil/midazolam/succinylcholine; 2. alfentanil/midazolam/succinylcholine/atropine; 3. fentanyl/midazolam/pancuronium bromide; 4. fentanyl-droperidol/chloralose/urethane; 5. ketamine/xylazine; 6. ketamine/xylazine/atropine; 7. propionylpromazine/pentobarbital; 8. propionylpromazine/levomethadon; 9. propofol; 10. propofol/alfentanil; 11. Tiletamine-zolazepam. It could be shown, that some intravenous anaesthetics under laboratory conditions have a strong influence on the observed cardiac parameters that must be considered in experiments with other substances or in cardiovascular results.

Anesthesia, Intravenous↗

[Acquired disorders of peritoneal cavity muscles. Abdominal wall denervation in pregnancy, denervation incontinence, and continent and incontinent constipation].

The peritoneal cavity has a fascial skeleton that is kept under tension by permanent variable resting tone maintained by the abdominal muscles. The lateral abdominal muscles, the diaphragm and the pelvic floor are all components of this fasciomuscular support system. Voluntary and reflective changes in muscle tension allow the entry and exit of matter into and out of the spherical abdominal cavity by opening and closing of specialized wall segments called sphincters. We have previously demonstrated the existence of a resting tone in the tail muscles of mammals from which the human pelvic floor muscles are derived. The pelvic floor and its integrated sphincters form the anorectal organ of continence. This organ is much weaker in females than in males. The spinal centers that govern continence, contain in the female significantly fewer ganglion cells than the corresponding centers in the male. Childbirth and a commonly found tendency to develop constipation are additional stressors for the congenitally weaker female organ of continence. We explain in this paper why the abdominal wall and the pelvic floor may suffer stretch-induced denervation injuries during pregnancy and delivery. Such damage may persist in later life and can give rise to incontinence and "flabby abdomen". Based on our work in this field, we found a new differentiation between continent and incontinent constipation. Continent constipation is caused by spasticity of the pelvic floor characterized by abnormally high sphincter activity. This spastic pelvic floor syndrome can be treated successfully by psychotherapeutic techniques. Incontinent constipation, in contrast, is always associated with subnormal activity of the sphincters and may be a cause of rectal prolapse. It can be treated successfully by anterior rectosigmoid resection. Incontinent constipation will also require operative approximation of the levators in many cases. Improvement cannot be expected to result from this procedure, however, unless the pelvic floor shows some residual resting activity.

Abdominal Muscles↗

[The cardiotoxicity of bupivacaine during pacemaker stimulation is dependent on the stimulation frequency. Results of an experimental study].

The cardiotoxic effects of bupivacaine are related to the temporal dispersion of effective refractory periods in different parts of the cardiac conduction system. This effect facilitates the occurrence of re-entry arrhythmias under burst stimulation [4, 8]. In this study physiological increments in heart rate were simulated by cardiac pacing, and the electrophysiological and haemodynamic effects under the influence of cardiotoxic concentrations of bupivacaine were measured. METHODS. After institutional approval we generated cardiotoxic arterial plasma concentrations of bupivacaine (6.9 +/- 1.6 micrograms/ml) in pigs (n = 8; 15-22 kg) by i.v. injection of 4 mg bupivacaine/kg, followed by a constant rate infusion of 0.2 mg/kg per min [8]. The pigs were anaesthetized with midazolam, fentanyl and pancuronium and normoventilated with a FiO2 of 0.4. Internal right atrial and right ventricular pacing was performed with increasing frequencies of 20, 40, 60, 80 and 100 stimulations/min above individual spontaneous heart rates (AL) before (control) and after the administration of bupivacaine. ECG, MAP, LVSP, dp/dtmax and stimulation thresholds were recorded. Student's t-test, and the U-test of Wilcoxon, Mann and Whitney were used for statistical testing with a significance level of 0.05. RESULTS. By inducing a frequency-dependent increase in stimulation threshold, bupivacaine prevented regular atrial pacing with frequencies higher than AL + 60. Ventricular pacing with a frequency of AL+40 induced a lethal arrhythmia in 1 animal. In the remaining 7 pigs ventricular pacing showed a frequency-dependent increase in stimulation thresholds (Fig. 1) and stimulus-QRS intervals (Fig. 5). MAP (Fig. 2), LVSP (Fig. 3) and cardiac inotropy (Fig. 4) showed frequency-dependent decreases under ventricular pacing. CONCLUSIONS. The toxic effects of bupivacaine on pacing thresholds, av conduction, intraventricular conduction, cardiac inotropy, and blood pressure are modulated by the stimulation frequency of a cardiac pacemaker. The cardiotoxic effects of bupivacaine seem to be use dependent. Even minor increments in heart rate can induce malignant arrhythmias. Cardiac pacing can be difficult in the presence of toxic bupivacaine concentrations, and high-frequency pacing should be avoided. It has to be verified whether higher heart rates generated by the physiological pacemakers of the heart do also increase the cardio-circulatory toxicity of bupivacaine. If that holds true, drugs that can induce tachycardias should be avoided in the treatment of bupivacaine toxicity.

Animals↗

Regional metabolic rate of exogenous glucose in the isoprenaline and dobutamine stimulated canine myocardium as estimated by the 2-deoxy-D[1-14C]glucose method.

The effect of beta-adrenoceptor stimulation by isoprenaline and dobutamine on the transmural distribution pattern of regional myocardial metabolic rate of exogenous glucose (RMMRGlc) was studied in the anesthetized closed chest dog using the 2-deoxy-D[1-14C]glucose method. In a previous series a lumped constant (LC) value of 0.93 +/- 0.47 (1 SD) was measured for [14C]2-deoxyglucose in the canine myocardium. In the control group (N = 12) RMMRGlc was significantly higher in the subendocardial layer of the left ventricular free wall than in both the middle and subepicardial layer, where it was quite evenly distributed (P less than or equal to 0.05). With i.v. dobutamine (N = 8) RMMRGlc was significantly lower in the midportion of left ventricular free wall than in the subepicardial layer (P less than or equal to 0.05), but it was not different from the inner wall section. Significant differences between the subepicardial and subendocardial portions of the left ventricular free wall could not be found, either. In the isoprenaline group (N = 9) no transmural gradients of RMMRGlc were observed in the left ventricular myocardium. In all groups, both the interventricular septum and the right ventricular free wall exhibited homogeneous distribution patterns of RMMRGlc. It is concluded that transmural distribution patterns of exogenous glucose utilization probably reflect corresponding gradients in energy demands of the left ventricular wall. Redistribution of RMMRGlc in the isoprenaline and dobutamine groups may result from altered working conditions, a change in local inotropic state of the left ventricular myocardium, or from regional differences in the proportions of substrate utilization, and from regional differences in adrenoceptor density.

Animals↗

Contribution of the gastrointestinal tract to lorazepam conjugation and clonazepam nitroreduction.

Domestic pigs received single intravenous and oral doses of lorazepam or clonazepam (1 mg/kg), benzodiazepine derivatives biotransformed by glucuronide conjugation and nitroreduction, respectively. Blood samples were simultaneously drawn from portal venous and systemic venous sampling sites during 8 h after dosage. After intravenous dosage with either drug, the area under the serum concentration curve (AUC) for the intact drug, as well as for the principal metabolites (lorazepam glucuronide and 7-aminoclonazepam, respectively), was nearly identical between portal and systemic serum. After oral dosage, absolute systemic availability (relative to intravenous administration) of both lorazepam and clonazepam was incomplete (mean values: 29 and 49%, respectively); however, metabolite levels were also correspondingly lower between oral and intravenous dosages. First-pass hepatic extraction also occurred for both drugs, with mean systemic/portal AUC ratios of 0.60 for lorazepam and 0.74 for clonazepam. Pretreatment with neomycin (1.0 g) had a minimal effect on portal or systemic AUC for intact clonazepam after oral dosage, but 7-aminoclonazepam concentrations were reduced by neomycin pretreatment. Thus incomplete absorption, together with first-pass hepatic biotransformation, appears to explain the incomplete systemic availability of orally administered lorazepam or clonazepam. Biotransformation within the gastrointestinal tract or during absorption through the gastrointestinal mucosa contributes minimally.

Administration, Oral↗

The effects of microsphere injections into the left atrium on the myocardial blood supply measured by thermal conductance probes.

Former experiments with thermal conduction probes showed signs of reductions or increases of myocardial perfusion shortly after injection of microspheres into the left atrium. Because of this, 210 measurements made during experiments on 66 dogs under propionyl-promazine/pentobarbital narcosis were newly analysed to verify a possible influence of microspheres (9 microns phi) injected into the left atrium on microcirculation. Using 20 additional dogs in identically performed experiments, the myocardial perfusion was measured using thermal conductance probes, following injections of isotonic NaCl solution (8 ml each), Ringer's solution, 5% glucose, the subject's blood, and isotonic NaCl solution mixed with the surface-active substance Tween 80. These suspension media were injected both with and without unlabelled microspheres (8.6 microns phi). The results led to the following conclusions: An obligatory decrease in the blood supply as the result of a mechanical blocking of capillaries by microspheres can be ruled out. The particles, the suspension media, and a suspension temperature not sufficiently adjusted to the body temperature induce reactive negative or positive changes in the microcirculation of the myocardium. This was found in approx. 45%-75% of cases. Solutions containing particles cause, in the majority of cases, a decrease. The suspension medium with the smallest effect proved to be isotonic NaCl solution. From the results one can conclude that artefacts may arise from the application of the heat conductance probe method when the temperatures are not perfectly matched. However, the injected solution itself can often lead to various reactions in microcirculation which may last up to 5 min. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pharmacokinetics and CSF entry of flurazepam in dogs.

Anesthetized dogs received a single 1.0-mg/kg intravenous dose of flurazepam hydrochloride, following which multiple blood and cerebrospinal fluid (CSF) samples were taken over the next 8 h. Concentrations of flurazepam and its metabolite, desalkylflurazepam, were determined by gas chromatography with electron-capture detection. Mean kinetic variables for flurazepam were: volume of distribution 7.9 l/kg, elimination half-life 2.3 h, clearance 37 ml/min/kg, serum free fraction 25% unbound. The metabolic product desalkylflurazepam appeared in serum in low concentrations, and was eliminated with a half-life of 4.9 h. Flurazepam rapidly entered CSF, then was eliminated in parallel with flurazepam in serum. However, the extent of entry into CSF was limited, with the mean ratio of area under the curve for CSF versus serum (0.24) nearly identical to the serum free fraction. Thus, intravenous flurazepam in dogs is characterized by extensive distribution, high clearance, and short half-life. Entry into CSF is rapid, and appears governed by passive diffusion. The extent of CSF entry is limited by protein binding in serum.

Animals↗

[Effect of forced respiration on the stress on puncture channels of sutures in transverse laparotomies of the upper abdomen; experimental studies in the anesthesized dog].

In 11 mongrel dogs in propiophenylpromazine-pentobarbital-anaesthesia the influence of forced respiration on the load of puncture channels of a suture was investigated. For this horizontal suture in the upper abdominal wall, threads No. 3 USP and round needles No. ECT-4 were used. The experiments were carried out in supine position with stretched hindlegs, in supine position with relaxed hindlegs, in lateral position, and in hanging abdominal position. Measurements were performed with a selfconstructed resistance strain gauge element. Rising forced respiration pressure increased the inspiratory load of puncture channels, but there were no significant differences between spontaneous breathing and forced respiration with pressure of 10 cm H2O. In contrary to this there were highly significant differences between spontaneous breathing and forced respiration with pressure of 20 and 30 cm H2O (multiple variance analysis). For instance the load during forced respiration with a pressure of 30 cm H2O in supine position with relaxed hindlegs rose about 67% above pressure values of spontaneous breathing. It could be shown that the expiratory load in the puncture channels was not influenced by forced respiration pressure, but depended on the body position; in dogs it was minimal in side position (45-48 g), higher in supine position with relaxed hindlegs (67-71 g), even higher in supine position with stretched hindlegs (88-92 g), and maximal in hanging abdominal position (109-113 g). By this investigation the increase of load in the puncture channels during forced respiration with pressures of 20 and 30 cm H2O was quantified.

Abdomen↗

[Endobronchial administration of adrenaline in cardiopulmonary resuscitation: pharmacokinetic and dynamic studies in the dog].

The present animal study was designed to investigate the pharmacokinetic behavior of epinephrine after endobronchial (e.b.) and intravenous (i.v.) administration and its correlation to pharmacodynamic measurements. We found the effectiveness of e.b.-epinephrine (100 micrograms/kg BW) to be in the same magnitude as i.v.-epinephrine (100 micrograms/kg BW) with only a slight delay in the pharmacodynamic onset of a few seconds. The bioavailability of e.b.-administration of epinephrine was in the range of 80-85%. The therapeutic effect of e.b.-epinephrine (100 micrograms/kg BW) lasted much longer (30 min) when compared to i.v.-epinephrine (10 micrograms/kg BW) where the pharmacodynamic effect was terminated after 3 to 5 min. For the clinical situation of cardiopulmonary resuscitation a dose of 2-3 mg epinephrine in 5-10 ml of physiological saline instilled deeply into the bronchial system should be considered as alternative administration technique with fast onset and good effectiveness.

Animals↗

Endobronchial instillation of epinephrine during cardiopulmonary resuscitation.

We used a standard animal CPR model to study the effectiveness and hemodynamic response of 100 micrograms/kg epinephrine administered endobronchially and to compare the findings after conventional iv administration. Results showed that the endobronchial and iv epinephrine medication improved the survival rate by 100% compared to that of a control group receiving no medication. Although the hemodynamic conditions during cardiac compression were not significantly different after both routes of drug administration, endobronchial instillation produced a prolonged drug action during the first hour of restored spontaneous circulation. A more extensive use of this type of drug administration, especially in out-of-hospital resuscitation, is suggested.

Animals↗

Hepatic vs. gastrointestinal presystemic extraction of oral midazolam and flurazepam.

An experimental model was developed to elucidate the site of presystemic extraction of drugs with incomplete bioavailability due to high extraction after p.o. dosage. Domestic pigs received single i.v. or p.o. doses of midazolam (1 mg/kg) or flurazepam (2 mg/kg), two benzodiazepine derivatives with high presystemic extraction after p.o. dosage. Multiple blood samples were simultaneously drawn from the portal vein and from a systemic vein during 8 hr after dosage. After i.v. administration, both drugs had high systemic serum clearance, averaging 24 ml/min/kg. Area under the serum concentration curve (AUC) for systemic vs. portal sites was nearly identical for midazolam (769 vs. 737 ng/ml x hr); for flurazepam, systemic AUC exceeded portal AUC (1035 vs. 778 ng/ml x hr, P less than .01). After p.o. dosage, the systemic/portal AUC ratio averaged 0.15 for midazolam and 0.11 for flurazepam; for both drugs, portal AUC after p.o. dosage did not differ significantly from systemic AUC after i.v. administration. Thus, the extensive presystemic extraction of orally administered midazolam and flurazepam are mainly attributable to hepatic biotransformation rather than metabolism either within the gastrointestinal tract or during absorption into the portal circulation.

Administration, Oral↗