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Familial dysautonomia is a hereditary sensory neuropathy that involves sensory, motor, and central components of the nervous system. Orofacial features include a tendency toward facial concavity in the child, and convexity in the adult. There is increased salivation, and crowded teeth and malocclusion are characteristic. This patient is not Jewish; this makes his case an extremely rare one.
Intestinal handling of water and electrolytes and motility were monitored in conscious dogs with chronic 25-cm Thiry-Vella loops of proximal jejunum. Absorption/secretion was quantitated using a neutral isosmotic perfusate containing [14C]polyethylene glycol as a recovery marker. Under basal conditions the animals absorbed water, Na+ and Cl-, while there was no net action on K+. Intravenous serotonin infusion (30 micrograms/kg/min) increased circulating levels of serotonin to a mean of 1556 +/- 191 ng/ml within 15 min of the commencement of the infusion. The infusion induced a significant secretion of water (mean -73 +/- 7 microliters/min) and electrolytes (sodium -10.4 +/- 0.7 muEq/min; potassium -0.8 +/- 0.05 muEq/min; chloride -12.4 +/- 1.0 muEq/min) in the dogs and all showed signs of hyperserotoninemia (salivation, loose bowel movements, tachypnea). After administration of ketanserin (33 micrograms/kg/min), a significant reduction in secretion was demonstrated (water +20.8 +/- 16.1 microliters/min; sodium 7.2 +/- 3.0 muEq/min; potassium -0.02 +/- 0.1 muEq/min; and chloride -1.9 +/- 2.8 muEq/min) as well as reduced motor activity. A similar antisecretory effect was demonstrated with atropine infusion (20 micrograms/kg/min), although this drug had a far more significant effect on the gastrointestinal motility recorded in the loop. Infusion of methysergide (33 micrograms/kg/min) did not significantly affect secretion (water -111.4 +/- 59.0 microliter/min; sodium -17.4 +/- 9 muEq/min; potassium -0.9 +/- 0.4 muEq/min; chloride -20.3 +/- 7.0 muEq/min). These results suggest possible actions which may make ketanserin useful in the treatment of symptoms of the carcinoid syndrome.
The acute and subactue toxicity of 2,3-dihydro-9H-isoxazolo[3,2-b]quinazolin-9-one (W-2429), a non-narcotic analgesic agent, was investigated in mice, rats and dogs. The subacute toxicity study was conducted by repeated oral administration of the compound for 30 days. Treatment with W-2429 was well tolerated by rats as well as dogs. In the dog, the only signs of toxicity observed were decreased appetite and salivation at 100 mg/kg/day. No other significant evidence of physical, chemical, gross or histopathologic change was observed.
Clinical and immunologic responses of sheep to vaccination and subsequent bluetongue virus (BTV) challenge exposure were studied and compared with those of non-vaccinated sheep. Sheep were vaccinated with inactivated BTV administered with aluminum hydroxide and cimetidine or levamisole. After sheep were vaccinated, precipitating group-specific antibodies to BTV were detected, but serotype-specific neutralizing antibodies were not detected. Cellular immune responses (lymphocyte blastogenesis) to BTV were not detected. After virulent BTV challenge exposure, vaccinated and nonvaccinated sheep developed acute clinical disease of similar severity. Clinical signs included hyperemia and petechiae of oral mucosa and coronary bands of the feet, excess salivation, nasal discharge with crusting, ulceration of the muzzle, and edema of lips and intermandibular space. Marked increases in serum creatine kinase activity were associated with stiff gait, reluctance to move, and vomiting. Fever and leukopenia were detected in most of the challenge-exposed sheep. Viremia and neutralizing antibodies were detected in vaccinated and nonvaccinated sheep after challenge exposure. Bluetongue virus-specific reaginic antibodies were not detected in sera from any of the sheep when the passive cutaneous anaphylaxis test was used.
Effects of thyrotropin-releasing hormone (TRH) on serum concentrations of thyroid hormones were studied in 36 mixed-bred dogs. Dogs were randomly assigned to 7 groups. Significant increases (P less than 0.05) of serum thyroxine (T4) values occurred as early as 2 hours and reached a peak at 6 to 8 hours after IV injection of 300 to 1,100 micrograms of TRH. Thyroxine concentrations in response to a TRH dose greater than 500 micrograms were similar to those observed with the 300-micrograms dose. Transient coughing, vomiting, salivation, and defecation after large doses (900 and 1,100 micrograms) were observed. Mean serum T4 concentration decreased from 2.1 micrograms/dl to 0.9 micrograms/dl within 1 day of thyroidectomy. Clinical signs of hypothyroidism, including lethargy, dry coats, and diffuse alopecia, were present in 2 dogs at a month after surgical operation. Thyroxine concentrations were detectable for greater than 2 months. Injection (IV) of 700 micrograms of TRH 6 weeks after surgical operation had no effect on serum concentration of T4 in thyroidectomized dogs. In 5 T4-treated dogs, TRH (700 micrograms, IV) significantly increased the serum T4 value, indicating that pituitary thyrotropes were responsive to TRH, in spite of daily medication of 0.8 mg of T4. Four dogs were treated orally with 200 mg of propylthiouracil/day for 5 weeks. Intravenous injection of 700 micrograms of TRH in propylthiouracil-treated dogs had no effect on the serum T4 concentration, indicating that TRH had no effect on serum T4 values in these dogs during the experimental period. These results indicate that TRH can replace bovine thyrotropin for the canine thyroid function test.(ABSTRACT TRUNCATED AT 250 WORDS)
The cardiopulmonary consequences of diazepam (0.5 mg/kg, IV) followed by ketamine (10 mg/kg, IV) were evaluated in 11 dogs. Diazepam did not exhibit a tranquilizing effect and was frequently associated with excessive excitement. It produced minimal cardiopulmonary effects, except for a significant increase in heart rate. Ketamine administration was associated with less cardiovascular stimulation when administered after diazepam than it did when administered alone; the respiratory depression was greater. Compared with ketamine alone, the diazepam-ketamine combination was associated with more vomition, less muscle hypertonus, less seizure activity, and less salivation.
The main medication is Madopar and Sinemet; various additives are able to reduce the Dopa dose in order to avoid various side effects. Additives: Deprenil (Jumex), Amantadin derivatives) Symmetrell, PK Merz, Hofkomant). Furthermore Dopamin agonists (Umprel, Dopergin). Delpral for dyskinesias. Driving antidepressive in the morning (Noveril, Dixeran, Tofranil). In the evening tranquillizing antidepressive like Tryptizol, Saroten, Sinequan, Ludiomil, Tolvon. Anticholinergica for Salivation, L-Tryptophan in hot environment.
Cyanobacteria (blue-green algae) implicated in the deaths of 9 dogs at Richmond Lake, SD, on Aug 26, 1985, were analyzed. The dominant cyanobacterial species from the water sample was Anabaena flos-aquae. The lyophilized bloom material or the high-performance liquid chromatography purified toxin peak, when administered to mice IP, induced clinical signs of salivation, lacrimation, urinary incontinence, defecation, convulsion, fasciculation, and respiratory arrest. Further comparison of the semipurified bloom toxin with an irreversible anticholinesterase anatoxin-a(s), produced by A flos-aquae strain NRC-525-17, revealed the bloom toxin and anatoxin-a(s) had similar properties on high-performance liquid chromatography and on the inhibition of electric eel acetylcholinesterase (EC 3.1.1.7).
Boiled cytosols prepared from a wide variety of sources contain a low Mr factor that inhibits glucocorticoid receptor transformation to the DNA-binding state (Leach, K.L., Grippo, J.F., Housley, P.R., Dahmer, M.K., Salive, M.E., and Pratt, W.B. (1982) J. Biol. Chem. 257, 381-388). In this work, we show that this endogenous factor, which is partially purified from rat liver, produces all of the effects of the group VI-A transition metal oxyanions molybdate and vanadate on the structure and function of glucocorticoid receptors in cytosol preparations. Like molybdate, the endogenous factor behaves as a strong anion with an apparent Mr of 340 on Bio-Gel P-2, and it binds to both hydroxylapatite and Chelex 100 resins. The receptor stabilizing activity of the factor is completely stable to heating at 320 degrees C for 1 h. The small size, profound heat stability, and absorption by a metal chelating resin strongly suggest that the factor is an endogenous metal anion. As reduction of the concentration of the factor in cytosol promotes generation of the DNA-binding form of the receptor, we suggest that this endogenous metal anion interacts with the receptor to stabilize the 9 S complex and maintain the receptor in its untransformed, non-DNA-binding state. We propose that molybdate and vanadate may exert their effects on the untransformed receptor by interacting with the binding site for the endogenous metal anion.
The clinical, biochemical and pathological effects of the fresh shoots of Chrozophora plicata on Nubian goats and Desert sheep were investigated. The animals were given single or repeated daily doses of 10, 5, 1 and 0.5 g/kg of chrozophora shoots by stomach tube and died at various times post dosing. The main signs of Chrozophora poisoning in both species of ruminants were salivation, dyspnea, bloat, inappetence, dullness, diarrhea, paresis of the hind limbs, recumbency and lateral deviation of the head and neck. The main lesions were hemorrhage in the lungs, heart and kidneys, pulmonary cyanosis and edema, hepatic fatty change and depletion of glycogen, catarrhal enteritis, ascites, hydropericardium and serous atrophy of the cardiac fat and renal pelvis. An increase in the concentration of urea, ammonia and bilirubin and in the activity of GOT and a decrease in total protein were detected in the serum. Hematological changes indicated the development of anemia.
Levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526), a new antitussive drug, was submitted to toxicological studies. Acute toxicity, both oral and intraperitoneal, in rats and mice and oral toxicity in guinea-pigs was low. Subchronic and chronic toxicity studies were performed in rats and dogs. For both species the maximum tolerated oral dosage was 24 mg/kg/d. Dose-related clinical signs were observed, consisting mainly in salivation in rats and sedation, peripheral vasodilatation and increased heart rate in dogs. Liver toxicity was found in both species at higher dosages. In rats, food intake and body weight gain were reduced. There were no effects on fertility, nor any teratogenic effects. Foetal and peri- and post-natal toxic effects were observed in rats only at 150 mg/kg/d. A set of mutagenicity tests yielded negative results. Therefore, levodropropizine is safe up to dosages 10 times greater than the one intended for clinical use and only slight adverse reactions were recorded at a dosage 30 times greater.
Electrocardiograms were recorded from 25 clinically normal male ferrets anesthetized with ketamine and xylazine and from 7 ferrets anesthetized with ketamine alone. Ferrets anesthetized with ketamine alone had excessive salivation, open eyes, muscle tremors, muscle twitching, paddling motions, attempts to stand, and an unstable ECG baseline. Because ketamine/xylazine combination resulted in induction and good muscle relaxation, the ECG had little interference resulting from muscular movement.
The administration of propofol by infusion for maintenance of anesthesia has attracted much attention recently. We investigated the necessary infusion rate of propofol to maintain anesthesia for short surgical procedures without loss of the evident advantages of this substance. Forty unpremedicated female patients aged 18-59, scheduled for minor gynecological procedures, were randomly assigned to four groups. Anesthesia was induced with 2.0 mg/kg propofol i.v. and simultaneously an infusion of 0.05, 0.10, 0.15, or 0.20 mg propofol/kg per minute was started. The patients were breathing N2O/O2 with FIO2 33%. Additional propofol was administered as a bolus of 10 to 20 mg when the patients moved. With 0.05 mg propofol/kg per minute all patients required additional bolus injections of propofol; with 0.10 mg 8 patients, with 0.15 mg 5 patients, and with 0.20 mg 1 patient required bolus injection. Therefore, 0.15 mg/kg per minute can be considered as an approximate ED50 value. The total propofol consumption (infusion + bolus) increased from 0.102 +/- 0.028 (+/- SD) with the lowest infusion rate to 0.202 +/- 0.006 mg/kg per minute with the highest infusion rate and recovery time from 5.2 +/- 1.4 to 9.9 +/- 2.6 min. There was a significant correlation between propofol consumption and recovery time. After induction, arterial blood pressure decreased by systolic/diastolic 20/10-15 mmHg. With the low infusion rate, arterial pressure increased to its control value during operation; it remained at the postinduction value with high infusion rates. Side-effects: 10 patients had salivation that in some instances lead to coughing, 9 reported pain at the injection site during induction, and 9 reported dreams of a pleasant nature.(ABSTRACT TRUNCATED AT 250 WORDS)
The clinical and laboratory features of moderate to severe organophosphate and carbamate toxicity in 37 infants and children are presented. Ingestion of an improperly stored liquid pesticide was the most common route of intoxication (76% of patients); five (14%) children became intoxicated after playing on carpets and floors of homes that had been sprayed or fogged by unlicensed exterminators. The transfer diagnoses were incorrect for 16 or 20 patients who were transferred to our center from another institution. Miosis (73%), excessive salivation (70%), muscle weakness (68%), and lethargy (54%) were the most common abnormal signs; 49% and 22% of patients had tachycardia and seizures, respectively, and 38% of children had respiratory insufficiency that required endotracheal intubation and mechanical ventilation. The results of erythrocyte and serum cholinesterase activity assays were concordant in 83% of patients. Thirty-four (92%) patients were treated with atropine and/or pralidoxime; three patients required only supportive care. Most patients had a prompt response to therapy; however, two patients with organophosphate toxicity required multiple doses of atropine during a 24-hour period; in both instances, the doses of atropine were subtherapeutic. There were no deaths. Pneumonitis and/or atelectasis developed in ten patients, including six who had ingested a petroleum distillate-containing insecticide.
Pirmenol hydrochloride (CI-845), a new orally effective antiarrhythmic agent, has undergone a comprehensive preclinical safety evaluation program. Repeated dose studies to evaluate chronic toxicity in rodents revealed few drug-related findings. A dose-related body weight gain suppression occurred in mice receiving up to 160 mg/kg for thirteen weeks. Rats also exhibited decreased body weight in a fifty-two-week study. Depressed fasting glucose levels were seen in rats at 50 mg/kg after thirteen weeks, but this effect was less prominent following fifty-two weeks of dosing. No other drug-related signs of toxicity were seen in rodents. Four-week repeated-dose intravenous studies in rats were uneventful. Occasional emesis and salivation, together with dryness of the oral mucosa, occurred in dogs given 10 mg/kg intravenously for four weeks. Drug-related increased heart rates, increased QRS duration, and reduced ST interval were seen thirty minutes postdose in dogs receiving 5 mg/kg or more intravenously. When dogs received pirmenol orally for fifty-two weeks, electrocardiographic and heart rate changes were variable and less pronounced than seen in the intravenous study. Clinical signs consisted of exaggerated pharmacologic responses similar to those found after intravenous dosing. Reproduction studies in rats and rabbits showed that pirmenol is not teratogenic. Reduced food intake and a 50% decrease in body weight gain were seen in rats at the top dose level of 150 mg/kg. Significantly reduced mean fetal weight and increased postimplantation loss indicated that 150 mg/kg was embryotoxic to rats. A top dose of 50 mg/kg in rabbits did not produce any signs of maternal or fetotoxicity, aside from a moderate suppression of maternal weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)
6 beta,7 beta-Epoxy-3a(1aH,5aH)-tropanyl-(S)-tropate (scopolamine) has proved to be a very effective drug in the prevention of motion sickness, however, the drug has a small therapeutic window, a low bioavailability and a short half-life. A transdermal drug delivery system (Scopoderm TTS) was developed to circumvent these problems as well as the variability in gastric absorption. In order to study the pharmacokinetics of the drug and its glucuronide, a highly sensitive radioreceptor assay with an absolute detection limit of 15 pg scopolamine was developed. In children undergoing minor surgery, a Scopoderm TTS patch of different sizes (according to the age of the children) was applied to the retro-auricular skin. Urine samples were collected and assayed for free and conjugated scopolamine. Furthermore possible anticholinergic effects on the pupil reaction, salivation, blood pressure and heart rate were monitored. The urine excretion of free and glucuronidated scopolamine showed large intra- and interindividual variations. However, in all age groups relatively high percentages of free scopolamine were found, namely 47.5% (3-6 years), 48.3% (7-12 years) and 36.0% (13-18 years) of the sum of free plus glucuronidated scopolamine. During the application of the patch, a prolonged plateau of scopolamine excretion could be found. Although in general the patches were well tolerated, both locally and systematically, moderate anticholinergic effects were observed in patients.
Two fatal cases of Japanese pieris poisoning in goats are reported. The clinical symptoms of the two animals consisted in vomiting, salivation, excitation and depression. Despite rumenotomy and symptomatic treatment, the goats died within four days after the onset of the symptoms. Pulmonary oedema accompanied by lobular aspiration pneumonia was found to be present in one goat at autopsy. Hyperaemia, pulmonary oedema and acute tubular nephrosis were observed in the other animal.
Dermal application of endosulfan to male (18.75, 37.50 and 62.50 mg/kg/day) and female (9.83, 19.66 and 32.0 mg/kg/d) rats for 30 days produced hyperexcitability, tremor, dyspnea and salivation. There were no deaths. The signs of toxicity subsided after a week. Endosulfan produced no significant changes in the organ:body weight ratio. No significant changes were seen in the histological and hematological indices. However, a significant decrease in liver GOT and GPT and serum GPT activities and a significant rise in serum alkaline phosphatase and total protein were recorded in the endosulfan-treated animals. There were no changes in LDH. Residue analysis revealed higher levels of total endosulfan in fatty tissues of rats receiving the highest dose of endosulfan.