The effect of cimetidine on anesthetic metabolism and toxicity

Because the H2-receptor antagonist cimetidine has been shown to inhibit drug metabolism, the effects of cimetidine on anesthetic metabolism and toxicity were investigated in a rat model. Cimetidine decreased inorganic plasma fluoride production after methoxyflurane administration both in 21% oxygen (P less than 0.001) and in 100% oxygen (P less than 0.001). Phenobarbital produces an increased fluoride formation after methoxyflurane anesthesia, and this fluoride formation is also reduced by cimetidine (P less than 0.005). There was no significant difference between the plasma fluoride levels in rats anesthetized with halothane or enflurane. Although cimetidine inhibited the in vivo defluorination of methoxyflurane, fluoride levels were still within the nephrotoxic range, and cimetidine is not likely to play a role as part of a preanesthetic regimen that would permit the increased clinical use of methoxyflurane. Cimetidine also inhibited the oxidative metabolism of halothane; cimetidine decreased (P less than 0.05) trifluoroacetic acid concentrations after halothane anesthesia in 21% oxygen and in 100% oxygen and decreased (P less than 0.05) bromide concentrations after halothane anesthesia in 100% oxygen. Trifluoroacetic acid levels were less (P less than 0.02) after halothane anesthesia in 14% oxygen as compared with 100% oxygen, indicating a reduction in oxidative metabolism under hypoxic conditions. However, bromide concentrations were maximal after halothane anesthesia in 21% oxygen, and significantly (P less than 0.001) less after halothane anesthesia in 14% and 100% oxygen. Bromide production, therefore, seems to be inhibited by both hypoxia and hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Onchocerca gutturosa and O. volvulus: studies on the viability and drug responses of cryopreserved adult worms in vitro

The viability and drug responses of cryopreserved adult Onchocerca have been examined in vitro. Male worms were cryopreserved in liquid nitrogen (-196 degrees C) using ethanediol as a cryoprotectant in a 2-step incubation procedure. After thawing, 85-90% of O. gutturosa males were normally motile. These motile worms were evaluated for viability using 4 measurements (long-term motility/survival in culture; [U-14C]adenine uptake and leakage; glucose utilization; MTT-formazan colorimetry) and were no different from unfrozen controls. Subsequent experiments demonstrated that the motility responses of cryopreserved worms exposed to the antifilarial drugs ivermectin, CGP 6140 and levamisole were virtually identical to unfrozen controls. Some success was also obtained with this technique in cryopreserving O. volvulus males, with 2 thawed specimens surviving in culture for 93 and 106 d respectively. Following collagenase isolation, female worms were cryopreserved in medium +10% serum without protectant at -79 degrees C. A batch of 8 female O. gutturosa were all motile when thawed 14 d later, with a mean survival time (based on 5 specimens) of 71 d (range 60-90). However, a batch of worms transferred from -79 degrees C to -196 degrees C were badly damaged when thawed. Female O. volvulus were cryopreserved at -79 degrees C in Guatemala and sent by air freight on solid CO2 to the UK. Most specimens were active when thawed. Survival of motile specimens ranged from 7 to 272 d in culture. It is concluded that these techniques are of practical value for the storage and transportation of adult Onchocerca.     

Transplantation for adults with congenital heart disease.

Heart transplantation is a recognised treatment for end-stage heart failure of any cause including congenital heart disease. Congenital heart disease has contributed relatively little to the adult heart transplant activities in the past two decades. However, this is likely to change as an increasing number of children with congenital heart disease reach adulthood because of the advances in paediatric cardiology and surgery. Some of these grown-ups with congenital heart disease (GUCH patients) will need transplantation for late myocardial dysfunction either secondary to uncorrected lesions, or despite previous repair or palliative surgery. These patients are managed along the same clinical principles as those with cardiac failure of other aetiologies, despite the lack of any evidence to support this approach. Nevertheless, they introduce new challenges. First, some may have pulmonary vascular disease and require heart-lung transplantation, or lung transplantation combined with repair of their cardiac defects. Second, those with failing Fontan circulation are usually much sicker than other transplant candidates, with protein-losing enteropathy along with renal and hepatic dysfunction. Third, a suitable donor organ may not be found due to elevated levels of antibodies in response to previous blood transfusions and possibly the previous implantation of homografts. Fourth, the operation may be technically difficult because of the presence of adhesions secondary to previous operations, collaterals, and unusual anatomy. Fifth, postoperative care may be complicated because of predisposition to bleeding, infection and pulmonary hypertension, and the presence of residual aortopulmonary collaterals resulting in a significant left-to-right shunt. Despite a higher early mortality, the overall results of heart transplantation so far have been encouraging with survivals similar to that of adults with acquired heart disease and that of the paediatric population. However, this may change as the proportion of high-risk patients (failing Fontans) increases. GUCH patients with Eisenmenger's syndrome may be offered lung transplantation with repair of the cardiac defect or heart-lung transplantation. However, because of the limited success of these approaches, and improved management of pulmonary hypertension, patient selection remains difficult.     

Persistent otitis media with effusion: A new experimental model

Objectives/Hypothesis: Numerous mechanical animal models for the creation of otitis media with effusion (OME) have been described since the 1920s. However, there are many problems associated with these models, including high infection rates, unreliability, and high resolution rates. The aim of the current study was to create a suitable mechanical animal model that would produce a sterile and long-lasting effusion. Study Design: A new technique using an external surgical approach on specific pathogen–free rats is described. Method: The eustachian tubes of 56 rats were obstructed in the mid portion along the skull base with gutta percha. Results: All animals developed an effusion within 1 week of the procedure. The resolution rate was 8%, with 80% maintaining sterile effusions for up to 1 year. Conclusions: This new procedure for an OME model has proved consistently reliable in creating a persistent and long-lasting effusion. It has a low infection rate and should benefit future studies on the prolonged effects of OME on the tympanic membrane and middle ear.     

Ziprasidone, Diazepam, or the Combination for Prevention of Cocaine Toxicity in a Mouse Model

Background Acute cocaine poisoning is a common problem in the United States. Sedation with benzodiazepines is the standard treatment, but animal studies have suggested that ziprasidone is also protective.
Objectives To assess whether the combination of these two medications would offer more protection than either treatment alone.
Methods This was a randomized, blinded, placebo-controlled trial in CF-1 mice. The authors administered intraperitoneal injections of 2 mg/kg diazepam (group D), 4 mg/kg ziprasidone (group Z), the same dose of both drugs (group DZ), or saline 15 minutes before intraperitoneal administration of 105 mg/kg cocaine (an estimated lethal dose to 70%). The number of animals with seizures and apparent lethality over the following 30 minutes was recorded.
Results All treatments increased survival relative to placebo (relative risk: D = 2.6, Z = 2.3, DZ = 2.9) and decreased seizures (relative risk: D = 0.5, Z = 0.3, DZ = 0.02).
Conclusions This study suggests that diazepam and ziprasidone have efficacy for preventing lethality from cocaine poisoning in an animal model but that the combination offers little addition to either therapy alone. However, the combination may be more effective for prevention of cocaine-induced seizures.     

Diffusion of oxygen and carbon dioxide through blood flowing in a channel

The numerical solutions of diffusion equations have been obtained for the cases of oxygen and carbon dioxide diffusing through blood flowing between two porous parallel planes. It is assumed that at the entrance to the channel the concentration profiles are uniform and the velocity profile is fully developed. The rheological characteristics of blood are described by the Casson equation. The computations have been made employing the explicit finite-difference forward-marching procedure. The results have been obtained for a wide range of yield numbers, inlet partial pressures, pH, membrane resistances and haemoglobin concentrations.