Neuromuscular interaction between cisatracurium and mivacurium, atracurium, vecuronium or rocuronium administered in combination

We compared the dose-response relationships of cisatracurium, mivacurium, atracurium, vecuronium and rocuronium and examined the interactions of cisatracurium with mivacurium, atracurium, vecuronium and rocuronium in humans by isobolographic and fractional analyses. We studied 180 adult patients during nitrous oxide-fentanyl-propofol anaesthesia. Neuromuscular block was monitored using mechanomyography to detect the twitch response of the ulnar nerve at the wrist. The dose-response curves were determined by probit analysis. The calculated ED50 values and their 95% confidence intervals were 40.9 (38.1-43.7), 49.8 (47.0-52.6), 187.2 (175.1-199.3), 36.6 (34.7-38.5) and 136.4 (129.2-143.6) micrograms.kg-1 for cisatracurium, mivacurium, atracurium, vecuronium and rocuronium, respectively. Corresponding ED95 values were 57.6 (53.5-61.7), 91.8 (88.1-95.5), 253.1 (238.9-267.3), 52.9 (49.1-56.7) and 288.7 (276.2-301.2) micrograms.kg-1, respectively. The interaction between cisatracurium and mivacurium, vecuronium or rocuronium was found to be synergistic, but the interaction between cisatracurium and atracurium was found to be additive. Synergy between cisatracurium and vecuronium or rocuronium was greater than between cisatracurium and mivacurium.     

Interactions between lonidamine and beta- or hydroxypropyl-beta-cyclodextrin

Equilibrium dialysis and Scatchard plots were used to establish that human and rabbit paraoxonases both have two calcium binding sites. Independent-site and stepwise constant analyses were used to calculate a higher affinity site (Kd1) of 3.6 +/- 0.9 x 10(-7) M for human A paraoxonase, and 1.4 +/- 0.5 x 10(-8) M for rabbit paraoxonase, and a lower affinity site (Kd2) of 6.6 +/- 1.2 x 10(-6) M for human A paraoxonase, and 5.3 +/- 0.94 x 10(-6) M for rabbit paraoxonase. In both species, the higher affinity sites were found to be essential to maintain hydrolytic activity; complete removal of calcium led to irreversible inactivation. The lower affinity sites were required for catalytic activity, and their binding of calcium was reversible. Experimentally estimated values of Kd2 based on the concentration of calcium required to obtain half the maximum enzymatic activity were 3 microM for human A and B paraoxonases, and also in the order of 3 microM for rabbit paraoxonase, using three different substrates. Calcium was the only metal found that protects against denaturation and also confers hydrolytic activity with these two mammalian paraoxonases.     

Evaluation of succinylcholine-induced fasciculations and myalgias with or without atracurium pretreatment

Pretreatment regimens that decrease the incidence of fasciculations and postoperative myalgias have been the focus of many research studies. The subject of pretreatment remains controversial. An experimental double blind study was conducted of 50 patients, men and women, aged 18 to 65 years who were having elective minor orthopedic surgery. Group A participants (n = 24) received normal saline, and group B participants (n = 26) received atracurium 0.05 mg/kg, followed by succinylcholine 1.5 mg/kg. Data that were collected included age, ASA physical status, weight, height, anesthesia and postanesthesia recovery times, type of procedure, medications administered, and allergies. Phase I of the study consisted of evaluation for the presence of fasciculations. In phase II, the intubation conditions (e.g., character of the vocal cords, presence of coughing, and degree of ease with laryngoscopy) were evaluated. Phase III included evaluation of postoperative myalgias at 24 and 72 hours. Data were analyzed using measures of central tendency, chi square, Pearson's r and the Student's t test. The incidence of fasciculations was less in the atracurium pretreatment group (group B) than in the group treated with normal saline (group A). Intubation conditions were not compromised by atracurium pretreatment. There was no statistically significant difference between group B and group A in postoperative myalgias. Thus, no recommendations for pretreatment can be made on the basis of this study.     

Interactions between genetics and environment]

In 1986, a 26% seroprevalence of IgG- anti-Borrelia burgdorferi antibodies was observed among 950 orienteers and the incidence of new clinical infections was 0.8%. In 1993, a total of 305 seropositive orienteers were reexamined. During that time, 15 cases (4.9%) of definite/probable Lyme disease occurred in this seropositive group (12 skin manifestations and 3 monoarticular joint manifestations). Among the 12 definite cases, 9 showed new clinical infections (7 EM, 1 acrodermatitis chronica atrophicans, 1 arthritis), and 3 were recurrent (2 EM, 1 arthritis). The annual incidence (0.8%) in this seropositive group was identical to the incidence observed among the whole population in 1986. The individual antibody titer decreased slightly but the seroreversion rate was low (7%). Serology was not very helpful in identifying clinical cases and evolutions, and it can be stated, that a positive serology is much more frequent in this risk group than clinical disease.     

Interactions between anticoagulants and cardiovascular drugs

Brain membrane lipid in rats were analyzed after being fed either 30 or 100 ppm fluoride for 3, 5, and 7 months. The protein content of brain with fluorosis decreased, whereas the DNA content remained stable during the entire period of investigation. After 7 months of fluoride treatment, the total brain phospholipid content decreased by 10% and 20% in the 30 and 100 ppm fluoride groups, respectively. The main species of phospholipid influenced by fluorosis were phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine. The fatty acid and aldehyde compositions of individual phospholipid classes were unchanged. No modifications could be detected in the amounts of cholesterol and dolichol. After 3 months of fluoride treatment, ubiquinone contents in brain were lower; however, at 7 months they were obviously increased in both groups of fluoride treatment. The results demonstrate that the contents of phospholipid and ubiquinone are modified in brains affected by chronic fluorosis and these changes of membrane lipids could be involved in the pathogenesis of this disease.     

Interactions between pacemakers and security systems

BACKGROUND: Hot flashes are often a troublesome symptom in breast carcinoma survivors and men with prostate carcinoma who have undergone androgen deprivation therapy. A previous clinical study demonstrated that, on a short term basis, low dose megestrol acetate markedly reduced hot flashes and was well tolerated. Little information has been available regarding the long term use of low dose megestrol acetate for hot flashes. METHODS: Patients previously enrolled on a randomized placebo-controlled trial that evaluated the short term use of megestrol acetate for hot flashes were contacted and interviewed by telephone. RESULTS: A total of 132 persons were contacted. Nine percent of the patients discontinued megestrol acetate after resolution of their hot flashes. Forty-five percent of the patients contacted were continuing to utilize megestrol acetate approximately 3 years beyond the conclusion of the 1992 study. Three-quarters of these patients were utilizing < or =20 mg of megestrol acetate per day. Potential toxicities attributed to megestrol acetate included episodes of chills, appetite stimulation/weight gain, vaginal bleeding, and carpal tunnel syndrome symptoms. CONCLUSIONS: A substantial proportion of patients continue to use megestrol acetate for periods of up to 3 years or longer with continued control of hot flashes. This treatment appears to be relatively well tolerated.     

The effects of midazolam or propofol followed by suxamethonium on the QT interval in humans

Atretic encephaloceles or myelomeningoceles are frequently solid due to hamartomatous proliferation of fibrous tissue and blood vessels. Because of the fibrous nature of the tumor with no cystic cavity and unusual location with no connection to CNS, they are frequently regarded as insignificant hamartomas. Apart from this terminology, they are also described as cutaneous meningiomas or hamartomas with ectopic meningothelial elements by the presence of meningothelial cells. We report a case of atretic encephalocele in the parietal scalp of an 8 year-old boy and a case of myelomeningocele in the posterior mediastinum of a 31 year-old woman. The terms atretic encephalocele and myelomeningocele are more appropriate for these cases because they include their pathogenesis and the non-neoplastic nature of the lesion.     

Increase in serum creatine phosphokinase concentrations after suxamethonium during sevoflurane or isoflurane anaesthesia in children

We have studied whether sevoflurane or isoflurane anaesthesia modulates the effect of suxamethonium on serum concentrations of enzyme markers of skeletal muscle function in paediatric patients. Eighty patients undergoing bilateral tonsillectomy, aged 5-12 yr, were allocated randomly to receive anaesthesia with either sevoflurane and nitrous oxide or isoflurane and nitrous oxide. Serum creatine phosphokinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) concentrations were measured before, and at 30 min and 20 h after induction of anaesthesia. Mean CK concentrations increased from 97.0 (SD 17.3) to 478 (170) iu litre-1 in the sevoflurane group and from 86.9 (22.4) to 628 (223) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum CK concentration in the sevoflurane group (478 (170) iu litre-1) was significantly less (P < 0.05) than that in the isoflurane group (628 (223) iu litre-1). Mean serum AST concentration increased from 17.5 (4.9) to 31.7 (3.5) iu litre-1 in the sevoflurane group and from 17.3 (2.4) to 34.8 (5.7) iu litre-1 in the isoflurane group, 20 h after induction of anaesthesia. Mean peak serum AST concentrations in the sevoflurane group were significantly lower (P < 0.05) than those in the isoflurane group. There were no significant differences in serum ALT or LDH concentrations between the groups either before or after anaesthesia. We conclude that administration of suxamethonium during either sevoflurane or isoflurane anaesthesia caused a marked increase in serum CK concentrations in paediatric patients. The clinical significance of this finding is uncertain.     

Interactions between cyclosporine and newer antidepressant medications

We measured adenosine 2a receptors in basal ganglia of 13 schizophrenics and 10 controls, using [3H] CGS21680 as a ligand for the receptor binding assay. There was a significant increase in the specific [3H] CGS21680 binding in the putamen and caudate, but not in the globus pallidus of externa, of the schizophrenic patients, compared to those of controls. These results provide evidence suggesting that adenosine 2a receptors play a role in the pathophysiology of schizophrenia.     

Interactions between bacterial toxins and intestinal cells

Bacterial toxins which act on intestinal cells display a great diversity of size, structure and mode of action. Some toxins interact with the cell by transducing a signal across the membrane leading to stimulation of intracellular second messenger (E. coli heat stable enterotoxin), others form pores (C. perfringens enterotoxin, ...) permitting the leakage of cellular components and cell lysis. The most sophisticated toxins comprise at least two functional domains or components, one being a binding domain permitting the internalization into the cell of an enzymatic domain which modifies an intracellular target. The enzymatic modification (ADP-ribosylation, UDP-glucosylation, glycohydrolysis, proteolysis, ...) of a specific target (heterotrimeric G-protein, small G-protein, monomeric actin, ribosomal RNA, ...) alters the cell physiology (increase of ions and water secretion, cytoskeleton rearrangement, protein synthesis inhibition, apoptosis, ...) and tissue organization (modification of barrier permeability, necrosis, ...). The study of bacterial toxins leads to the understanding of the interactions between pathogenic bacteria and their hosts and constitutes also a new approach in cell biology, by facilitating the exploration of certain regulatory pathways such as that controlling actin polymerization.     

Interactions between the jaw-opening reflex and mastication

Electrical stimulation of the anterior hard palate or upper lip was used to evoke the jaw-opening reflex in rabbits lightly anesthetized with urethane. The amplitude of each excitatory response recorded in the digastric electromyogram during mastication was compared with the mean amplitude of 10 prior control responses. When weak stimuli were used, the mean amplitude of the reflex dropped markedly during mastication and was smallest when the digastric muscle was inactive (closing and occlusal phases of the masticatory cycle). As the stimulus strength was increased, the size of the response during closing rose progressively until it exceeded values obtained during the control period or the jaw-opening phase. In addition, strong stimuli altered the total cycle length and the duration and amplitude of muscle activity in a phase-dependent manner. Stimuli given during closing were particularly effective in causing inhibition of jaw-closing muscle activity and in reducing the velocity and amplitude of closure. It is concluded that the cyclical gain changes of the reflex response to noxious stimuli are controlled to a large extent by premotoneuronal mechanisms and that the overall effect on the masticatory cycle structure is phase dependent.     

Interactions between nurses and patients on ventilators

Image cytometric analysis of DNA ploidy status of 40 fresh primary breast carcinomas was performed in a comparative study on cytologic preparations stained directly by the Feulgen method and smears from the same tumors Feulgen-stained after Papanicolaou staining. There was a 0.82 overall concordance in diploid and aneuploid tumor classification and a good correlation (r = 0.736, P < 0.001) between the DNA indices determined by the two methods. Discordances are probably due to tumor heterogeneity. This study demonstrates that image cytometric DNA analysis on previously routine-stained cytologic preparations is feasible and reliable for pretreatment DNA analysis and suggests potential applications in retrospective studies with cytologic material from archives.     

Interactions between PVC Geomembranes and Compacted Clays

The interactions between plastic soils and polyvinyl chloride (PVC) geomembranes were studied using a direct shear device under as-compacted conditions. The PVC geomembranes had smooth or textured surfaces, and the soils were of plasticity index (PI) ranging from 35 to 100%. The peak and residual failure envelopes were expressed using Coulomb failure criteria. The adhesion and angle of friction increased for PIs up to 70% and subsequently recorded a decrease. The adhesion is larger for the peak strength compared to the residual strength, but it was the reverse for the angle of friction. The efficiency in terms of adhesion appeared more relevant than that of the angle of friction in expressing the interactions between geomembrane and cohesive soils. The smooth and textured geomembranes showed little difference in results at the residual state.     

Prolonged mivacurium infusion in young and elderly adults

PURPOSE: This study was designed to evaluate pharmacodynamically and pharmacokinetically if the cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients. METHODS: The mechanomyogramic neuromuscular response of the adductor pollicis was recorded in 32 adults 18-59 yr. and 19 elderly (> 60 yr.) patients during N2O:O2:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 +/- 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response. RESULTS: The mean mivacurium infusion requirement to maintain 97 +/- 1 (mean +/- SD)% depression of the twitch response was 6.0 +/- 0.4 micrograms.kg-1.min-1 in young adults, and 4.3 +/- 0.3 micrograms.kg-1.min-1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 +/- 1.2 micrograms.kg-1.min-1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with low cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients. CONCLUSION: When the mivacurium infusion was titrated to maintain 95 +/- 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.