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PubMed1975

The efficiency of aquocobalamine as an antidote in cyanide poisoning when given alone or combined with sodium thiosulfate.

The antidotal activities of aquocobalamineacetates and sodium thiosulfate were tested in guinea pigs and cats. The animals were attached to artificial respirators throughout the experiment and were poisoned with a continuous infusion of sodium cyanide solution (4.1 muMol/kg.min NaCN). The rate of action of each antidote was determined from the time taken for the HCN exhalation to drop below the level of 100 nMol/kg.min in quinea pigs, and to values below 25 nMol/kg.min in cats; the detoxifying capacity of each antidote was determined from the time taken for the HCN exhalation to rise above the said values and the time interval for normal function of heart activity to be restored. Aquobalamine was characterized by its rapid rate of reaction in both the animal species; its detoxifying capacity showed, however, according to our expectations, variations corresponding to the applied doses. The combination of the antidotes aquocobalamine (100 mg/kg) and thiosulfate (500 mg/kg) proved to possess high rate of reaction and a large detoxifying capacity in guinea pigs. Similar results were obtained in cats with antidote doses of 200 mg/kg aquocobalamine combined with 500 mg/kg thiosulfate. The slow rate of reaction and large detoxifying capacity of thiosulfate were confirmed in our experiments. It combination with aquocobalamine showed no undesirable change in its antidotal action providing a time interval of 1 min was maintained between the 2 injections.

Animals↗
PubMed1976

Hypothalamic chemostimulation and autonomic changes in curarized rats.

Rats previously implanted with chronic double walled cannulae aimed at the lateral hypothalamic area (LHA) ate and drank reliably after minute injections of norepinephrine and carbachol respectively. Later on the rats were curarized and artificially respirated. After an habituation period during which rectal temperature, cardiac rate and peripheral vasomotor activity were continuously recorded, half of the subjects were injected with 1 mul of norepinephrine (40 x 10(-9) moles) and the other half with 1 mul of carbachol (2.4 x 10(-9)moles). Both drugs elicited hypothermia, bradycardia and vasodilatation. Bradycardia after carbachol was significantly greater than after norepinephrine and hypothermia and vasodilatation after norepinephrine were significantly greater than after carbachol. When the treatments were reversed essentially the same effects were observed.

Animals↗
PubMed1976

Neurotoxic and myotoxic effects of crotalus phospholipase A and its complex with crotapotin.

1. The acidic peptide crotapotin potentiated the toxicity of the basic crotalus phospholipase A in all species tested. The order of sensitivity to the lethal action of the phospholipase was: chick greater than mouse larger than or equal to rabbit greater than rat. After a latency period of a least 20 min the animals died of respiratory paralysis. Rabbits survived for more than 10 h, if they were artificially respired. The animals recovered very slowly from respiratory depression. 2. In rabbits even high doses of the basic crotalus phospholipase A or its complex with crotapotin did not affect the respiratory center nor its reactivity to asphyxia. Conduction of action potentials in the phrenic nerve was not changed. 3. Phospholipase-crotapotin complexes decreased the contractile response of isolated phrenic-hemidiaphragms of rats to direct and indirect stimulation in an irreversible manner. A latency period 20-100 min preceded the paralysis. 4. A similar block of neuromuscular transmission developed in vivo. After i. v. injection of PC-complexes the contractile response of isolated rat phrenic diaphragms to nerve stimulation was considerably lower than to direct stimulation. 5. Crotalus phospholipase A alone as well as its complex with crotapotin reduced the contractions of the isolated chick biventer cervicis muscle but did not cause a contracture, thus indicating that the phospholiphase PC-complexes act not as depolarizing blockers. 6. Blood pressure, heart rate and electrocardiogram were not substantially altered, when phospholipase A or PC-complex were injected slowly i.v. into rabbits or rats. No cardiotoxic effect was observed in the Langendorff preparation of rat hearts perfused with phospholipase A alone (6 x 10(-6) M) or together with crotapotin (10(-5) M). Rapid i.v. injection of the venom produced hypotension. The degree of haemolysis correlated with the enzymatic activity, and was low for the highly toxic PC-complexes.

Action Potentials↗
PubMed1993

Suspected maternal infanticide in a case of hydranencephaly.

A medico-legal autopsy case of hydranencephaly in a male infant which was first suspected of maternal infanticide is reported. The infant was 48 cm in height, weighed 2.86 kg and the circumference of the head, the chest and the abdomen was 32.2 cm, 31.0 cm and 30.4 cm, respectively, with no deformities of the head or body. Autopsy examination, however, revealed a severe defect in the central nervous system. The cranial cavity was filled with a cloudy dark red fluid (ca. 310 ml) instead of the cerebral hemispheres. The residual central nervous tissues were mostly subtentorial structures from the midbrain to the spinal cord namely, corpus mamillare, corpora quadrigemina, corpus pineale, crus cerebri, pons, cerebellum, medulla oblongata and spinal cord. The basal ganglia, thalamus, hypothalamus and chiasma opticum could not be found, although atrophic hypophysis, eyeballs and optic nerves were present. The usual distribution of cerebral blood vessels, especially the branches of the anterior and middle cerebral arteries and Willis' ring, was absent despite the presence of the internal and external carotid arteries. Other organs were, in general, congestive. The marked cortical atrophy of the adrenal glands (left 0.5 g, right 0.6 g), especially the zona fasciculata, was characteristic. The hydrostatic lung test gave partially positive results, but this was considered to be due to artificial respiration by an ambulance man because amniotic fluid components were microscopically noted and fully expanded alveoli were not found. In conclusion, the cause of the infant's death was diagnosed as stillbirth due to aspiration of amniotic fluid caused by the severe defect of vegetative hypothalamic function through hydranencephaly.

Brain↗
PubMed1989

Responses of nucleus ambiguus neurons to arterial pressure manipulations.

Nearly 69% of nucleus ambiguus neurons in the anesthetized, artificially respired dog responded to nonpharmacological manipulations of arterial pressure (AP). All were active at resting AP, most responded robustly to increased AP, and of these, about half showed activity modulated by the respiratory cycle. Other AP-sensitive neurons fired only during the inspiratory or expiratory phase of the pump-driven respiratory cycle, and were inhibited by increased AP and excited by decreased AP.

Action Potentials↗
PubMed1981

Electrophysiological study of evoked electrical activity in the pineal gland.

Experiments were carried out in rats, unanesthetized, paralyzed and artificially respirated. The electrical activity from the pineal gland was recorded with bipolar electrodes. Field potentials were evoked in the pineal after peripheral (photic and sciatic nerve) and central (septal area, habenular complex and optic tract) stimulations. In general these potentials were biphasic with the exception of that evoked by the sciatic nerve and optic tract, which exhibited a complex response and a triphasic field potential, respectively. Bilateral sympathectomy did not modify the pineal evoked responses, but when the pineal stalk was sectioned all the responses were immediately suppressed after the lesion. On the basis of the above experimental data one could conclude that the bulk of the inputs to the pineal gland come through its stalk. At the present, the physiological significance of these findings is not clear.

Animals↗
PubMed1983

[Relaparotomy, retrospective analysis and intensive care aspects].

A high mortality rate of the patients in the Surgical University Clinic Mainz in 2441 laparotomies from 1977 to 1979 with 92 relaparotomies in 66 patients (40% proving fatal) could be associated with the following factors: female sex, old age in males, malignant disease, esp. carcinoma of pancreas, colon and rectum, upper gastrointestinal bleeding, presence of concomitant affections, esp. three or more and particularly angiocardiopathy, liver diseases and after radiotherapy, long lasting primary operation, several operations in short intervals (about a week). Astonishingly we found a lower rate of mortality in cases of: Primary laparotomy in an emergency situation, postoperative complications within the first two days or after several weeks, multiple relaparotomies within intervals of at least two weeks. In cases of several severe postoperative complications, esp. renal insufficiency with dependence on dialysis and simultaneous respiratory insufficiency with dependence on artificial respiration a relaparotomy is indicated, if the intra-abdominal complication can be cured. In these cases the intensive care cannot cure the patient's conditions, but mechanical respiration and dialysis improve it. The existence of lethal trias of renal and respiratory insufficiency with a surely unremovable surgical problem forbids a relaparotomy.

Adolescent↗
PubMed1982

[Catheter epidural analgesia for treatment of postoperative and post-traumatic pain].

Postoperative epidural local anesthetics or opiates provide excellent analgesia but do not reduce the incidence of respiratory complications compared with systemic analgesics. Additional and sometimes lethal side effects reserve the routine use of epidural analgesia for highly selected patients. Thoracic epidural analgesia (TEA) may prevent ventilation in patients with serial rib fractures (SRF) without gross pulmonary parenchymal lesion. TEA results in fewer pulmonary complications, shorter hospital stay, and lower mortality than artificial respiration. Late global pulmonary tests after TEA for treatment of SRF show normal results within comparable groups without rib fractures.

Abdominal Injuries↗
PubMed1986

[Pancreatitis: conservative therapy].

The treatment of acute pancreatitis is primary conservative independent of the degree of severeness. The aim of our multimodal concept of therapy (stomach tube, catheterisation of urinary bladder, closed peritoneal dialysis, analgetics--peridural catheter-, substitution of volume-electrolytes, colloides, protein, plasma, blood-, antibiotics, heparin H2-receptor blocker, early artificial respiration, insulin, parenteral nutrition-glucose, amino acids, fat-, hemofiltration/-dialysis, percutaneous drainage of liquid formations) is to postpone or to avoid an operation. Only the erosion bleeding or a locally conditioned sepsis ask for an emergency operation. The lethality of the degrees II (n = 30) and III (n = 39) could be decreased to 20.3% in the last 7 years. The follow-up of 55 patients with severe pancreatitis was free of clinical symptoms in 80% with normal exocrine and endocrine function of pancreas. This confirms that the organ itself is mostly intact even in severe cases of pancreatitis, in hemorrhagic-necrotic pancreatitis.

Acute Disease↗
PubMed1987

Cooperative Group of Additional Immunoglobulin Therapy in Severe Bacterial Infections: results of a multicenter randomized controlled trial in cases of diffuse fibrinopurulent peritonitis.

A multicenter randomized controlled clinical trial, which was carried out in 10 hospitals in the Federal Republic of Germany between 1979 and 1983, studied the influence of i.v. immunoglobulin G on the mortality in patients with diffuse acute fibrinopurulent peritonitis. Altogether 288 patients were enrolled in the trial. There was no statistically significant difference in the mortality rates within the treated group (46%) vs the control group (41%). The power of the statistical test to detect a decrease of the mortality by 20% was calculated to be 0.93. This result did not change when we eliminated 50 patients not strictly obeying the entrance criteria of the analysis, or when we focused on a subgroup of patients with initial deficiency of immunoglobulin G. Factors influencing mortality were a preceding laparotomy, serum creatinine level above 2 mg/100 ml, and necessity for artificial respiration. These factors, reflecting the surgical situation and the severity of shock, essentially explain the mortality differences observed between the participating hospitals.

Bacterial Infections↗
PubMed1978

Significance of the ventricular fluid pressure wave form in the diagnosis of cerebral circulatory arrest and brain death.

The fluctuations in the absolute value of the ventricular fluid pressure (VFP) with simultaneous changes in the amplitude and frequency of the oscillations of the ventricular fluid wave form are described in seven patients who developed brain death following either a head injury or a cerebrovascular accident, and are compared with those observed in nineteen patients who survived similar brain pathology. The findings in the two groups were significantly different. It is suggested that VFP monitoring does provide reliable evidence of brain death even while the patient is on artificial respiration.

Adolescent↗
PubMedDate not supplied

Influence of the sympathomimetic activity of oxprenolol on haemodynamics in the anaesthetized dog.

In anaesthetized, artificially respirated mongrel dogs, the intravenous infusion of oxprenolol (0.3 mg and 1 mg/kg over 10 minutes) led to an increase in heart rate and cardiac output. Blood pressure in the pulmonary capillaries and right atrium, and vascular resistance were reduced. The pressure in the aorta was transiently decreased. Infusion of propranolol in the same doses was followed by a decrease in heart rate and cardiac output. The calculated peripheral resistances, pulmonary capillary pressure and right-atrial pressure increased slightly. Pressure in the aorta diminished slightly. In the light of the present results, it is evident that the intrinsic sympathomimetic activity of oxprenolol has a significant bearing on its haemodynamic effects in the anaesthetized dog.

Animals↗
PubMed1987

Antagonism of the in vivo and in vitro effects of leukotriene D4 by SC-39070 in guinea pigs.

Leukotriene D4 (LTD4) causes contractions of guinea pig isolated ilea, evokes pulmonary bronchoconstriction and induces lesions of the dermal vasculature. In the present study, we assessed the antagonism of these actions by SC-39070 compared to FPL-55712, a known LTD4 receptor antagonist. In guinea pig isolated ileum preparations, SC-39070 displayed selective antagonism of LTD4 with a pA2 = 8.20 +/- 0.06 (S.E.) and a Schild plot slope of -1.20. Administered intravenously to artificially-respired guinea pigs one minute prior to the agonist, SC-39070 antagonized (p less than 0.05) the bronchoconstrictive effect of LTD4 in a dose-dependent manner (0.5-10 mg/kg). At a dose of 2.0 mg/kg, i.v. this activity was retained through a 60 minute pretreatment interval. Similarly, after oral administration of SC-39070, there was a dose-dependent antagonism of the bronchoconstrictive activity of LTD4 (MED50 = 3.8 mg/kg). Antagonism of LTD4-induced bronchoconstriction was evidenced after oral administration of SC-39070 within one hour of treatment and efficacy was retained as long as 20 hours after treatment at a dose of 10 mg/kg. Finally, intravenously administered SC-39070 blocked LTD4-induced dermal permeability in guinea pigs with a minimum effective dose of 1.0 mg/kg. In each assay, the LTD4 antagonism evidenced after treatment with SC-39070 appeared to be equal to or greater than that observed after treatment with FPL-55712.

Animals↗
PubMed1993

Effect of pretreatment with CBDP on the toxicokinetics of soman stereoisomers in rats and guinea pigs.

Pretreatment of rats and guinea pigs with the specific carboxylesterase inhibitor 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) reduces the LD50 of the nerve agent C(+/-)P(+/-)-soman in these species to the same range as in primates. This suggests that such CBDP-pretreated animals can be used in investigations that are relevant for prophylaxis and therapy of intoxication with C(+/-)P(+/-)-soman in primates including humans. In order to test this hypothesis we have studied the toxicokinetics of the toxic C(+/-)P(-)-isomers of soman in artificially respirated and CBDP-pretreated rats and guinea pigs at intravenous doses corresponding to 6x LD50. A comparison of the areas under the curve (AUCs) of the blood levels of C(+/-)P(-)-soman in pretreated and non-pretreated animals at the same absolute dose shows extreme nonlinearity with dose, indicating that CBDP occupies highly reactive binding sites which are no longer available for sequestration of the soman isomers. The AUCs of C(+/-)P(-)-soman at equitoxic doses of 6x LD50 are reduced by pretreatment with CBDP from 1683 to 464 ng.min.ml-1 in rats and from 978 to 176 ng.min.ml-1 in guinea pigs, which is in the range of the AUC in non-pretreated marmosets at an equitoxic dose (419 ng.min.ml-1). The blood levels of the C(+/-)P(-)-isomers in marmosets and CBDP rats are rather similar during the first 7 min, but persist in CBDP rats for 2 h longer at toxicologically relevant levels than in marmosets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

CNS involvement in acute organophosphate poisoning: specific pattern of toxicity, clinical correlates and antidotal treatment.

The present review was designed to integrate both experimental and clinical data and to focus on the problems of management of severe cases of acute organophosphate poisoning, which always show CNS involvement. AChE activity, in discrete regions of the human brain, was studied by quantitative histochemistry of 40 mu thick sections. The regional effects of AChE inhibition by organophosphates was examined in a comparative study of the brains of two victims and two control brains, matched for age and sex. The pattern of AChE inhibition was regionally selective. The most significant decreases were observed in the neocerebellum, thalamic nuclei and the cortex. This specific distribution of AChE inhibition may be correlated with some of the clinical characteristics of acute organophosphate poisoning. The diagnostic value of blood AChE levels was examined in a personal series of 53 patients, who needed artificial ventilation, intensive care monitoring and antidotal treatment. The effects and side-effects of the antidotal treatment were reassessed. Recommended regimen of therapy was outlined, based upon experience in this series and in recent animal studies. The logical therapy would be and almost always in the co-administration of an anticholinergic drug (usually atropine) and an AChE reactivator (oximes) in order to rapidly obtain the most beneficial effect in the critically ill patient. Seizures that do not respond to the specific antidotal therapy, should be treated with I.V. benzodiazepines. Artificial respiration and supportive measures are essential for patient' survival. They enable the patient to gain the necessary time for sufficient recovery of AChE activity.

Acetylcholinesterase↗
PubMed1987

Favorable results of thymectomy combined with prednisolone alternate-day administration in myasthenia gravis.

Administration of anti-cholinesterase before operation and high doses of prednisolone after the operation are commonly prescribed in cases of thymectomy for the treatment of myasthenia gravis. Our policy is to carry out an extended thymectomy combined with pre- and post-operative administration of prednisolone on alternate days. Our method was used in the treatment of 50 patients with generalized myasthenia gravis, from January 1979 to December 1984. The results were examined in conjunction with the necessity for preoperative administration of an anti-cholinesterase preparation and also with factors influencing the follow-up result and postoperative process. This method made it feasible to perform surgery under conditions of stabilization of clinical symptoms and satisfactory postoperative management. A postoperative period of unstable symptoms could thus be avoided. The palliation rate at one year after the operation was 96 per cent, while the remission rate at 5 years after the operation was 70 per cent. The preoperative supplement of anti-cholinesterase and preoperative per cent forced vital capacity were considered to be predictive factors concerning the necessity of artificial respiration.

Adult↗
PubMed1984

[Principles of first aid to severely injured persons at the scene of the accident].

The therapy-free intervals after an accident have been considerably shortened by the introduction of an emergency system ensuring the treatment of the injured person by a physician on emergency duty already at the place of accident. Injuries threatening life have to be treated first in order to maintain the vital functions. Due to the lack of time and the insufficient equipment available at the place of accident, a precise diagnosis is possible only in exceptional cases. The most dangerous complications are respiratory deficiency, loss of blood, inconsciousness and lack of skeletal stability, and these are to be treated in this order. Intubation and artificial respiration are the most adequate methods to maintain the respiratory function. Exterior bleedings have to be staunched , losses of blood must be compensated by administration of colloidal solutions and electrolyte solutions. Urgent admission to a hospital is necessary in case of interior hemorrhages and in case of inconsciousness , especially if an intracranial hemorrhage is suspected. Fractures and luxations are not primarily threatening life, nevertheless the provisional reposition and immobilization of the injured extremities belong to the task of a physician on emergency duty. The reanimation of patients injured in an accident has a poor prognosis; if a cardiac arrest persists more than ten minutes, further reanimation measures are nearly never successful.

Accidents↗