Succinylcholine infusion associated with hyperthermia in ponies anesthetized with halothane.

Succinylcholine was administered by infusion to halothane-anesthetized ponies to determine dosage requirements for surgical relaxation up to 3 hours' duration. This was not possible to do, since 4 of 6 ponies studied developed severe reactions characterized by prolonged muscle fasciculations after the initial succinylcholine dose, muscle rigidity, hyperthermia, hypercapnia, tachycardia, increasing pulse pressure, and metabolic acidosis. The reactions resembled those associated with malignant hyperthermia, a disease recognized in persons and swine. Two ponies showed signs of the phase II or desensitization block of succinylcholine. All ponies recovered from anesthesia without signs of muscle injury.

Antagonism of pancuronium neuromuscular blockade in halothane-anesthetized ponies using neostigmine and edrophonium.

Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked after neostigmine. Blood pressure increased within 1 to 2 minutes of antagonist administration. Heart rate decreased after edrophonium injection, but this occurred after blood pressure increase. Heart rate increased or did not change after neostigmine administration.

Dosage requirement of pancuronium in halothane-anesthetized ponies: a comparison of cumulative and single-dose administration.

Cumulative vs single-bolus administration of pancuronium was studied in halothane-anesthetized ponies. Dosage levels were determined by giving small increments (0.01 to 0.04 mg/kg of body weight) until the desired relaxation occurred (0.125 +/- 0.038 mg/kg for 90% to 99% reduction of prerelaxant twitch height), then an additional 0.037 +/- 0.024 mg/kg for obliteration of twitch response. The dosage level defined by cumulative administration was then administered as a single bolus 2 more times, once on each of 2 days. Dosage requirements for the 2 methods correlated well. The difference in duration of paralysis caused by doses of different magnitude was compared, 1 dose to produce discernible surgical relaxation (90% to 99% reduction of twitch height) and a larger dose that obliterated discernible twitch height. The larger dose produced a significantly (P less than 0.05) longer duration of paralysis until a 10% recovery of prerelaxant twitch height was attained. The recovery phase, defined as the duration from 10% to 75% recovery of prerelaxant twitch tension, was not significantly different in ponies given either dose. Seemingly, after relaxant recovery began, the larger dose did not slow recovery. Duration of maximum paralysis until 10% recovery took 41 +/- 16 minutes for the larger dose and 10 +/- 5 minutes for the smaller dose. The recovery phase (10% to 75%) took 12 +/- 3.2 minutes and 11 +/- 4 minutes for the large and smaller doses, respectively.

Neuromuscular and cardiovascular effects of pancuronium bromide in calves anesthetized with halothane.

Pancuronium bromide was administered to calves to define the dosage level necessary to produce surgical relaxation (90% to 99% reduction of base-line evoked, hindlimb digital-extensor muscle twitch tension). Initial dosage level requirement was 43 +/- 9 micrograms/kg of body weight. Calves with this degree of relaxation required 26 +/- 14 minutes to achieve 50% recovery and 43 +/- 19 minutes to achieve complete return of base-line muscle twitch. Calves given a repeat injection of pancuronium at base-line muscle twitch required 27 +/- 9 micrograms/kg to achieve relaxation similar to that of the 1st dose. The 2nd dose did not last as long as the 1st, with complete recovery occurring in 37 +/- 12 minutes. Maximum evoked tension occurred at 200- to 400-g resting tension on the hoof. There was an absence of heart rate or blood pressure changes after injection of relaxant and a variable and inconsistent fade response to train-of-four and tetanic stimulus of the facial muscles. Acid-base values were alkalemic (pHa 7.5 +/- 0.08) when ventilation was controlled at eucapnia (PaCO2, 25 to 45 mm of Hg).

Neuromuscular and cardiovascular effects of atracurium in ponies anesthetized with halothane.

Atracurium besylate, a recently developed, intermediate-duration acting, neuromuscular-blocking agent, was given to 15 halothane-anesthetized ponies to produce surgical relaxation (95% to 99% reduction of hoof twitch). All 15 ponies were given 3 injections; 8 of the 15 ponies were given 2 additional injections. Initial dosage of 0.11 +/- 0.01 mg/kg (mean +/- SD) and all subsequent injections of 0.052 mg/kg produced desired relaxation. Paralysis phase (maximum twitch reduction to 10% twitch recovery) lasted 24 +/- 5 minutes for the initial injection. Paralysis from subsequent injections lasted for a slightly shorter time. Recovery phase (10% to 75% twitch recovery) was similar for all injections (initial and repeated) and lasted approximately 11 minutes. Cardiovascular side effects were not seen. Reversal of effects of atracurium with administration of 0.5 mg of edrophonium/kg was achieved when the evoked digital extensor tension (twitch height) had returned to 95% of base line after the last atracurium injection. Edrophonium caused systolic blood pressure to increase 121% +/- 7% of base-line pressure, which was 133 +/- 18 mm of Hg. Heart rate changed to 93% +/- 9% of base line after edrophonium was given, which was 49 +/- 7 beat/min, but this change did not occur until after the blood pressure increased. Recovery to standing was smooth and strong. Five ponies stood on their first attempt to rise, 5 on the 2nd attempt, 2 on the 3rd, and 1 on the 4th. Seven ponies stood within 30 minutes after transportation to the recovery stall, 7 within an hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Clostridium difficile toxin A stimulates enzyme secretion from isolated rat pancreatic acini.

Although Cl difficile bacteremia and the presence of antibodies to toxin A (TxA) have been reported, little information is available at present on TxA effect on the functional properties of various visceral organs. We have, therefore, examined the in vitro effects of TxA on amylase and trypsin secretion from rat isolated pancreatic acini. Dispersed rat pancreatic acini were exposed for 60 min to different concentrations of highly purified TxA and the rate of amylase, trypsin and LDH release were monitored. Free cytosolic calcium release in pancreatic acini after toxin A (10(-10)M to 10(-8)M) treatment was measured with Fura-2/AM, Ca-indicator dye. TxA (10(-10) to 10(-8)M) increased significantly the rate of both the amylase and trypsin secretion without any membrane damage, with toxin A exerting its action via calcium dependent pathway as suggested by intracellular calcium release measured with Fura-2/AM.

Chronic Q fever.

Sixteen cases of chronic Q fever are described. In eight there was a history of exposure to infection from farms or farm products. All had valvular heart disease, involving the mitral valve in nine and the aortic valve in seven. Infection occurred on a prosthetic valve in two patients. Arterial embolism was common. Venous thrombosis occured in three patients, and pulmonary embolism occurred in three other patients. Complement fixing antibodies to phase 1 antigen were found in a titre of 1:200 or greater in all except two patients. In one of these post-mortem examination revealed rickettsial bodies in mitral valve vegetations, and in the other Coxiella burneti was isolated from heart valve tissue. The majority presented with infective endocarditis but two presented primarily with liver disease. All patients had evidence of liver involvement and in one this led to death from cirrhosis. Abnormal tests of liver function, particularly hyperglobulinaemia, raised alkaline phsophatase and abnormal bromsulphthalein retention were found in all patients. Hepatic histology was abnormal in all eight patients in whom it was studied. The commonest features were mononuclear cell infiltration of the portal tracts and prominence of the sinusoidal Kupffer cells. Patchy focal necrosis of parenchymal cells, granulomata, fatty change, and eosinophilia of the sinusoidal walls were also noted in several patients and cirrhosis developed in one. Six patients had a purpuric rash, and in 12 there was thrombocytopenia. It is suggested that the presence of hepatomegaly and liver involvement and thrombocytopenia may help to differentiate Q fever endocarditis from bacterial endocarditis. Raised serum IgM and IgA levels occured frequently, but with only a moderate dominance of IgM. Sheep cell agglutination and latex fixation tests for rheumatoid factor were occasionally positive. Several features of the disease suggest the possibility that immune-complex mechanisms may play a role in chronic Q fever. Treatment was with prolonged courses of tetracycline usually combined with lincomycin. Seven patients underwent valve replacement surgery for haemodynamic reasons. Five patients died; two from heart failure, one from cirrhosis, one seven days after valve replacement and one from intraperitoneal haemorrhage following percutaneous liver biopsy. Three patients have survived for more than five years, and another six for more than three and a half years after diagnosis. Of these nine patients, three received medical therapy alone and six required valve replacement as well. Antibiotics have been discontinued in four patients who have had valve surgery and three others. Six patients had received antibiotics for continuous periods varying from 29-62 months. In the period after stopping therapy varying from 15-21 months, no relapse has occured. A seventh patient, who had received antibiotics for four months prior to valve replacement, has survived 43 months after the withdrawal of antibiotics...

Multicentre post-infarction trial of propranolol in 49 hospitals in the United Kingdom, Italy, and Yugoslavia.

A multicentre study of survivors of an anterior myocardial infarction is reported. The trial consisted of 720 patients and was a double-blind, placebo-controlled study with propranolol 40 mg three times a day. Trial entry was at two to 14 days (mean 8.5 days) and follow-up at one, three, and in most centres, six and nine months. The trial was designed to detect a 50 per cent reduction in mortality and this was not shown. The non-fatal reinfarction rate was similar in both groups. Subgroup analysis identified several prognostic risk factors for death, none of which interacted with treatment.

Streptokinase in acute myocardial infarction: a controlled multicentre study in the United Kingdom.

In a multicentre trial of streptokinase in acute myocardial infarction 302 patients received an intravenous infusion of 2 500 000 IU of streptokinase over 24 hours, while 293 patients served as controls. Neither group received anticoagulants unless indicated by thromboembolic complications. No significant difference in mortality was evident during inpatient treatment nor at six-week or six-month follow-up. The inpatient death rate was 12-6% in the streptokinase group and 13-7% among controls. There was no significant difference in the peak levels or pattern of enzyme increase. The incidence of cardiac failure and reinfarction was similar in the two groups, but major arrhythmias were less common in those on streptokinase (P less than 0-05). In the streptokinase group there were 36 minor and six more serious haemorrhagic complications. Gastrointestinal haemorrhage may have contributed to the death of one patient in each group. There were 18 thromboembolic complications in the streptokinase group and 38 among the controls. Pathological examination of the hearts of 25 patients who had taken streptokinase and 24 controls showed no striking differences between the groups, but haemorrhagic infarcts were found in three patients who had received streptokinase. An infusion of streptokinase within 24 hours of the onset of acute myocardial infarction does not significantly affect the mortality or course of the illness up to six months.