Immunohistochemical detection of methadone in the human brain.

To develop a method of detecting methadone in the human brain by immunohistochemistry, brain tissue of frontal cortex, cerebellum, hippocampus, basal ganglions and brain stem from victims of a lethal methadone overdose was examined. The staining was performed with a monoclonal anti-methadone antibody from the mouse, originally developed for immunochemichal purposes (ELISA). With the help of the DAKO((R)) Catalyzed Signal Amplification (CSA) System, a specific positive immunoreaction was obtained in the neurons of the frontal cortex and hippocampus, as compared with specimen from deaths without exposition to methadone. Thus, along with metamphetamine, phenobarbital, morphine and insulin, immunohistochemical detection is also possible for methadone and the intake of this medicament can now be proven morphologically.

Delimitation of the time of death by immunohistochemical detection of thyroglobulin.

To improve the possibilities to delimit the time of death after longer laytime it was examined if this is possible by immunohistochemical detection of thyroglobulin. The results show that in our examination material the colloid and the follicular cells of the thyroid glands of up to 5-day-old corpses produce a positive immunoreaction towards thyroglobulin in all cases whereas none of the corpses older than 13 days show such a reaction. This means that in case of a negative immunoreaction the time of death can be assumed to lie more than 6 days before the autopsy. The fact that a negative immunoreaction occurs consistently after 13 days leads to the conclusion that when thyroglobulin has been stained in a specimen, the death of the respective person must lie a maximum of 12 days earlier, whereby these time-limits may change in considerably different surrounding conditions.

Percentile charts to determine the duration of child abuse by chronic malnutrition.

Longstanding quantitative or qualitative under-supply of nutrition leads to weight loss and, in children, to stagnation of growth and thus to stunted growth. A comparison of the expected growth, according to percentile growth curves, with the actual body size, gives an indication as to the period of time in which malnutrition took place. The moment in which the growth curve bends off and leaves the norm is to be interpreted as the earliest begin, the moment in which the attained growth would have been achieved as the latest begin of the nutritional impairment.

Delimitation of the time of death by immunohistochemical detection of insulin in pancreatic beta-cells.

To improve the possibilities to delimitate the time of death after longer laytime, it was examined if this is possible by immunohistochemical insulin detection. The results show that in our examination material, the pancreatic beta-cells of up to 12-day-old corpses produce a positive immunoreaction towards insulin in all cases, whereas none of the corpses older than 30 days show such a reaction. This means that in case of a negative immunoreaction, the time of death can be assumed to lie more than 12 days before the autopsy. The fact that a negative immunoreaction occurs consistently after 30 days leads to the conclusion that when insulin has been stained in a specimen, the death of the respective person must lie a maximum of 29 days earlier, whereby these time-limits may change in considerably different surrounding conditions.

Insulin- or morphine-injection? Immunohistochemical contribution to the elucidation of a case.

Two autopsy cases of an elderly couple who died on the same day will be used to underline the importance of immunohistochemistry of forensic practice. At first unexplainable injection marks on the upper arms of the corpses and the possibility of a closely related physician injecting insulin and certifying a natural death made it important, considering suspect insulin concentrations in the blood, to exclude insulin injections in these marks. Further, the statement that morphine had been injected for the analgesia of tumour pains, was reinforced by immunohistochemistry.

Myocardial lactate extraction during repeated fibrillation/defibrillation episodes in defibrillator implantation testing.

Intraoperative testing with several fibrillation/defibrillation episodes (FDEs) is routinely performed during defibrillator implantation. Testing is considered safe even in patients with severe cardiac impairment, provided the recovery timespans and number of FDEs are adapted to the individual patient. Myocardial lactate extraction (MLE) was examined in two testing protocols. In 30 patients with coronary artery disease defibrillator implantations were performed under intravenous anesthesia. A percutaneous catheter was positioned into the coronary sinus (CS) underfluoroscopy. Two groups were randomly formed: group A (n = 20, mean number of FDEs: 4.2/patient) with 2 minutes waiting time between FDEs, and group B (n = 10, mean number of FDEs 4.1/patients) with 10 minutes between FDEs. Defibrillation pulses were released 15 seconds after T wave shock induced fibrillation. To estimate MLE, arterial and CS blood samples were collected before and after each FDE. After the last FDE, samples were obtained after 5, 10, and up to 20 minutes. In group A, MLE fell from a baseline value of 29.6% +/- 3.6% before the FDEs to 7.8% +/- 5.4% immediately after the episodes. MLE recovered to 27.2% +/- 6.5% within 1 minute and overshot to 35.6% +/- 5.8% within 5 minutes. In group B, MLE decreased from 37.6% +/- 7.5% to 15.1% +/- 8.1% immediately after each FDE and rose to its original value (33.6 +/- 7.8) within the 5-minute recovery period. MLE decreased immediately after each FDE, and recovered within 1 minute even in poor left ventricular function. For full MLE recovery a 2-minute wait between episodes is sufficient, if the total number of FDEs does not exceed four.

[Histamine plasma concentration and cardiovascular effects of non-depolarizing muscle relaxants: comparison of atracurium, vecuronium, pancuronium and pipecuronium in coronary surgical patients at risk]. / Histaminplasmakonzentration und kardiovaskuläre Effekte nicht-depolarisierender Muskelrelaxantien: Vergleich von Atracurium, Vecuronium, Pancuronium und Pipecuronium bei koronarchirurgischen Risikopatienten.

OBJECTIVE: Cardiovascular effects of four commonly used non-depolarising muscle relaxants and their ability to increase histamine plasma concentrations were studied in patients scheduled for coronary artery bypass grafting. METHODS: 40 patients were included in the study after informed consent. After premedication with Flunitrazepam (2 mg p.o.) on the evening before and 1 hour prior to surgery anaesthesia was induced with Flunitrazepam (4-6 micrograms kg-1). Fentanyl (3 micrograms kg-1) und Etomidate (150 micrograms kg-1) and the patients were ventilated via face mask with 50% N2O in oxygen. Patients were randomly allocated to one of four groups, and, 15 min after induction of anaesthesia, received equipotent doses of either Pancuronium (0.09 mg kg-1, n = 10). Pipecuronium (0.08 mg kg-1, n = 10), Atracurium (0.6 mg kg-1, n = 10), or Vecuronium (0.1 mg kg-1, n = 10) injected over 20 seconds via a central venous catheter. Cardiovascular variables were determined in the awake patient, 15 min after induction of anaesthesia and following administration of the respective muscle relaxant. In addition, plasma histamine concentrations were assessed before and after relaxation. Evoked muscular response to TOF simulation of the ulnar nerve (plethysmo-mechanogram) was continuously recorded to determine the onset of neuromuscular blockade. RESULTS: Heart rate, mean arterial pressure and cardiac index significantly decreased in all patients following induction of anaesthesia while systemic vascular resistance remained unchanged. Only Pancuronium caused a significant increase in heart rate (53 +/- 11 to 61 +/- 15 min-1) whereas cardiac index and mean arterial pressure did not change significantly. No other neuromuscular blocking agent caused any changes in the cardiovascular variables measured and histamine plasma concentrations remained within the reference range in all of the four groups with no differences detectable between groups. CONCLUSIONS: All investigated neuromuscular blocking agents exhibited marked cardiovascular stability which permits their use, being based exclusively on pharmacodynamic and pharmakokinetic considerations even in patients with coronary heart disease. If an increase in heart rate appears beneficial Pancuronium may be advantageous.

[Immunohistochemical insulin evidence at the injection site]. / Immunhistochemischer Insulinnachweis an der Injektionsstelle.

Under suspicion on an injection of high doses of insulin with suicidal or homicidal intention, the local detection of a vital injection of insulin is necessary for the critical examination. The submitted immunohistochemical method shows, that: the insulin-specific positive immunoreaction of the subcutaneous fatty tissue is assigned to an injection of insulin, although a missing staining does not exclude a premortal application of insulin, a widened immunopositive intercellular space between the subcutaneous lipocytes as expression of a local edema points to the intravitality of the injection of insulin.

[Concentration dependent ethanol metabolism in steady-state]. / Konzentrationsabhängigkeit der Ethanolumsatzraten im steady-state.

Ethanol infusion rates necessary to maintain steady-state ethanol concentrations are dependent on the actual ethanol concentration in a monotonous increasing manner.

[Does chronic oral treatment with beta-receptor blockers have an effect on positive inotropic therapy of coronary patients with adrenaline after extracorporeal circulation?]. / Hat die chronische orale Behandlung mit Betarezeptorenblockern Einfluss auf eine positiv inotrope Therapie koronarkranker Patienten mit Adrenalin nach extrakorporaler Zirkulation?

UNLABELLED: For the prebypass period various authors have shown that patients on oral or intravenous beta blocking therapy respond to catecholamine treatment with marked increase in afterload and no change in cardiac index. Since positive inotropic therapy is usually not necessary until, but after termination of cardiopulmonary bypass, the question arises as to whether beta-blocking agents administered orally on the morning of the operation, can still have negative effects during this phase of the procedure. PATIENTS AND METHODS: 20 patients (NYHA classification II to III) undergoing coronary artery bypass grafting, half of them having been on chronic beta-adrenoceptor blocking therapy, were treated with 0.1 micrograms/kg/min adrenaline as an infusion, when following cardiopulmonary bypass cardiac index was < 2.4 l/min/m2 with left and/or right ventricular filling pressures being normal or raised. Haemodynamic monitoring consisted of ECG, direct arterial pressure, a pulmonary artery catheter and of an additional thermodilution catheter placed directly into the coronary sinus. The parameters looked at were mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), coronary perfusion pressure (CPP), total peripheral resistance (TPR), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), pressure work index (PWI), myocardial blood flow (MBF) and myocardial oxygen consumption (MVO2). Arterial and myocardial lactate levels were measured and from that myocardial lactate extraction and production were calculated. Measurements were made immediately following termination of cardiopulmonary bypass and then after 15, 30, 45 and 60 minutes under continuous infusion of adrenaline. In addition left ventricular pressure was measured via transseptal needle for calculation of myocardial contractility dp/dtmax directly after termination of cardiopulmonary bypass and 15 minutes later with adrenaline therapy. Prior to induction of anaesthesia and following termination of cardiopulmonary bypass blood samples were taken to measure plasma levels of the beta blocking drug. RESULTS: All 10 patients on oral beta blocking therapy had plasma levels within the therapeutic range prior to induction of anaesthesia. Following cardiopulmonary bypass the plasma levels had fallen by 50% on average, but with 2 exceptions, they were still within the therapeutic range (Table 2). Irrespective of the fact whether preoperatively beta blockers had been taken, adrenaline caused a significant increase in contractility (Table 3), mean arterial pressure (Figure 1), heart rate (Table 3) and cardiac index (Figure 2). There was a comparable increase of pressure work index (Figure 5), myocardial blood flow (Figure 6) and myocardial oxygen consumption (Figure 7) in both groups. Effect on afterload was significantly different. In both groups MAP was increased but that was more marked in the presence of beta blockade (Figure 1). Total peripheral resistance fell in the group without preoperative beta blockade whereas in patients on preoperative beta blockade TPR increased by 100 dyn.s.cm-5 on average (Figure 4). As a consequence adrenaline infusion caused an increase in CPP only in the presence of beta blockade (Figure 3). In both groups adrenaline infusion caused an increase in arterial and myocardial lactate levels (Tables 6 and 7). Some patients without preoperative beta blockade showed myocardial lactate production whereas in the presence of beta blockade myocardial lactate extraction was found at all points of measurement (Figure 8). CONCLUSION: Our results show, that observations made by various groups in the prebypass period on patients treated with beta blocking agents, which demonstrate dramatic increases in afterload with no improvement in cardiac index following catecholamine administration do not hold true for the post-bypass period. The reason could be a wash out effect of the Bretschneider cardioplegia on cardiac beta receptors.

The efficacy of amrinone or adrenaline on low cardiac output following cardiopulmonary bypass in patients with coronary artery disease undergoing preoperative beta-blockade.

We examined 20 patients undergoing coronary bypass grafting for coronary artery disease with NYHA classifications of II and III who had been treated with beta-blocking agents. Patients were randomised for administration of either adrenaline (0.1 microgram/kg/min) or amrinone (bolus 1 mg/kg, continuous infusion of 5-10 micrograms/kg/min), if following cardiopulmonary bypass their cardiac index was < 2.4 L/min/m2 with normal peripheral resistance and normal or increased right- or left-ventricular filling pressures. Over a period of 1 hour, the hemodynamic parameters mean arterial pressure (MAP), cardiac index (CI), heart rate (HR), coronary perfusion pressure (CPP), total peripheral resistance (TPR), as well as the pressure-work index (PWI) were registered or calculated. By means of a coronary sinus catheter myocardial arterio-venous oxygen content difference (AVDO2cor), myocardial blood flow (MBF), using the thermodilution method, and myocardial oxygen consumption (MVO2) could be measured or calculated. Simultaneously, arterial and myocardial lactate concentrations and, using the arterio-venous lactate ratio, myocardial lactate extraction or production were quantified. Using a transseptal approach, the left-ventricular pressure curve was measured and used to differentiate for myocardial contractility (dp/dtmax). Following induction of anesthesia and after cardiopulmonary bypass, plasma levels of the used beta-blocking agent were determined. Both substances caused a significant increase in myocardial contractility, with adrenaline showing a more potent effect than amrinone. Both substances caused a significant increase in CI with a mild increase in HR. Amrinone caused a significant drop in TPR, while MAP remained practically constant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of dopexamine on the hemodynamics of coronary surgery patients with and without bisoprolol blockade]. / Der Einfluss von Dopexamin auf die Hämodynamik koronarchirurgischer Patienten mit und ohne Bisoprolol-Blockade.

Patients with coronary artery disease undergoing coronary artery bypass grafting can develop perioperative low cardiac output failure requiring positive inotropic support. Commonly, the sympathetic amines, dopamine, dobutamine or adrenaline are used in low-output state. However, patients on long-term cardioselective beta-blocking therapy may experience problems with such a treatment. Dopexamine, a new synthetic amine, possesses positive inotropic effects by indirect stimulation of the beta 1-receptors and direct stimulation of the beta 2-receptors. We therefore studied the hemodynamic efficacy of dopexamine in patients with and without beta-receptor blockade. In 12 patients with coronary artery disease classed as NYHA II or III, six without any beta-blocker medication, and six with beta 1-blocker medication (bisoprolol 5 mg), anesthesia was induced with high-dose fentanyl (0.05 mg/kg) and pancuronium (0.1 mg/kg). The patients were normoventilated with a mask (O2:air 1:1, tidal volume 10 ml/kg with a rate of 10/min) for 5 min and then intubated. Following intubation anesthesia was continued with 0.025 mg/kg/h fentanyl. In anesthesia steady state the patients of both groups were treated with 2 micrograms/kg/min dopexamine over a period of 15 min and then with 4 micrograms/kg/min dopexamine over a further period of 15 min. Measurements of cardiovascular dynamics included heart rate (HR), cardiac index (CI), stroke volume index (SVI), mean arterial blood pressure (MAP), coronary perfusion pressure (CPP), systemic vascular resistance (SVR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrium pressure (RAP), pressure work index (PWI) and arterial-mixed venous oxygen content difference (AVDO2), which were monitored or calculated by standard formulas.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-output syndrome after heart surgery: is a monotherapy with phosphodiesterase-III inhibitors feasible? A comparative study of amrinone and enoximone.

In order to determine whether the primary use of a phosphodiesterase-III (PDE) inhibitor as monotherapy for severe cardiac low-output states (LOS) is in fact practicable, we investigated the haemodynamic effects of amrinone and enoximone in a prospective randomized study. After elective CABG, AVR, or MVR, patients with cardiac LOS were given amrinone (n = 10) or enoximone (n = 9). Following bolus saturation (1.0-2.0 mg/kg [XA = 1.4] or 0.5-1 mg/kg [XE = 0.9] in total), a dose of 5-10 microgram/kg/min was given by infusion. The standard monitoring program included discontinuous haemodynamic measurements (Swan-Ganz) over a maximum time period of 48 hours, arterial and venous blood-gas analyses, and clinical chemistry. The preoperative clinical and haemodynamic status of the enoximone (E) group (55% CABG patients; MPAP 27 +/- 2.5 mmHg, PCWP 20 +/- 2.9 mmHg, PVR 201 +/- 35 dyn.s.cm-5) was considerably worse than that of the amrinone (A) group (70% CABG patients; MPAP 23 +/- 2.3 mmHg, PCWP 16 +/- 3.5 mmHg, PVR 153 +/- 28 dyn.s.cm-5). Both PDE inhibitor preparations led to a significant increase in cardiac index (from 1.9 +/- 0.1 to 2.5 +/- 0.12 L/min/m2 (A) and from 1.98 +/- 0.1 to 2.6 +/- 0.18 L/min/m2 (E) within 30 minutes, accompanied by a simultaneous decrease in filling pressures and vascular resistances. For up to 2 hours, 3/10 (A) and 2/9 (E) patients required additional positive inotropic support with adrenaline. There were no significant differences between the two groups at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

[Reference values of n-propanol elimination]. / Kenndaten der n-Propanolelimination.

Injections of increasing doses of n-propanol provoke blood concentration curves of exponential decays with dose dependent rate constants. The n-propanol-specific clearance is approximately 10 ml/min. It is determined by a Michaelis-Menten-metabolism (max. velocity of metabolizing: approximately 2.5 mg/l min; Michaelis-Menten-constant: approximately 10 mg/l) and is inhibited in the presence of ethanol.

[Elimination properties of the congener n-propanol]. / Eliminationseigenschaften des Begleitstoffes n-Propanol.

Intravenous injections of n-propanol (25 mg, 50 mg, 100 mg, 200 mg, 300 mg) provoke blood concentration curves having exponential shapes of dose dependent rate constants after a sufficiently long time (2 min). They have to be seen therefore as a result of a non-linear elimination process controlled by a Michaelis-Menten-kinetic. Using the Lineweaver-Burk-method the characteristic data of metabolism are determined, namely the maximal velocity of metabolizing beta PrOHmax as 2.5 mg/l min and the Michaelis-Menten-constant as 10 mg/l. An increase of the ethanol exposition causes a prolongation of the mean residence time of n-propanol in the body. This phenomenon is to be interpreted as the result of an inhibition of the n-propanol metabolism by ethanol. The inhibition constant KPrOHEtOH concerned with this process is determined experimentally and has a value of 0.1%.