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)     

Dendrotoxin-sensitive K+ currents contribute to accommodation in murine spiral ganglion neurons

We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation ( Mo & Davis, 1997 a ). In order to understand the underlying ionic basis of these characteristic firing patterns, we used α-dendrotoxin (α-DTX) to eliminate the contribution of a class of voltage-gated K⁺ channels and assessed its effects on a variety of electrophysiological properties by using the whole-cell configuration of the patch-clamp technique. Exposure to α-DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range. We found a non-monotonic relationship between number of action potentials fired and membrane potential in the presence of α-DTX that peaked at voltages between –40 to –10 mV and declined at more depolarized and hyperpolarized test potentials. The α-DTX-sensitive current had two components that activated in different voltage ranges. Analysis of recordings made from acutely isolated neurons gave estimated half-maximal activation voltages of –63 and 12 mV for the two components. Because α-DTX blocks the Kv1.1, Kv1.2 and Kv1.6 subunits, we examined the action of the Kv1.1-selective blocker dendrotoxin K (DTX-K). We found that this antagonist reproduced the effects of α-DTX on neuronal firing, and that the DTX-K-sensitive current also had two separate components. These data suggest that the transformation from a rapidly adapting to a slowly adapting firing pattern was mediated by the low voltage-activated component of DTX-sensitive current with a potential contribution from the high voltage-activated component at more depolarized potentials. In addition, the effects of DTX-K indicate that Kv1.1 subunits are important constituents of the underlying voltage-gated potassium channels.     

Randomized, double-blind, controlled trial of long-term diuretic therapy for bronchopulmonary dysplasia

The effects of continuous therapy with hydrochlorothiazide and spironolactone on pulmonary function in 34 premature infants with severe bronchopulmonary dysplasia were assessed in a randomized double-blind controlled trial. Subjects were greater than or equal to 30 days old, were supported by mechanical ventilation in greater than or equal to 30% oxygen, and had radiographic evidence of bronchopulmonary dysplasia. The treatment group (n = 19) and the placebo group (n = 15) were similar in all respects except for distribution of gender. Anthropometrics, ventilatory measurements, and the results of pulmonary function tests were evaluated at study entry and at 1, 4, and 8 weeks into therapy. Poststudy chest radiographs were compared with those obtained before the study. The proportion of infants alive at discharge was significantly increased (84%) in the treatment group compared with the placebo group (47%) (p = 0.05). There were no statistically significant differences in total hospital days or in total ventilator days. Total respiratory system compliance at 4 weeks was higher in the treatment group (0.61 +/- 0.18) than in the placebo group (0.45 +/- 0.13) (p = 0.016). No difference in outcome was detected between male and female infants in the treatment group. These results suggest that long-term diuretic therapy improves outcome in infants with bronchopulmonary dysplasia.     

In vitro and in vivo evaluation of seven 50 mg and 100 mg nitrofurantoin tablets

Four 50 mg and three 100 mg marketed nitrofurantoin tablets were studied in 14 healthy male subjects. Urine was collected 1, 2, 3, 4, 6, 8, 12, and 23 h after each dose, and nitrofurantoin was assayed by HPLC. The in vitro dissolution of the tablets was determined using USP Apparatus 1 and 2, with 0.1 N hydrochloric acid and pH 7.2 buffer as the dissolution fluids. One of the 50 mg tablets was more rapidly and completely absorbed than the other six products. The incidence of side-effects for this product was as low or lower than the other products. It was determined that the use of the USP Apparatus 1, at 100 rev min-1, with sampling of the pH 7.2 fluid at 30 min, provided for the best overall relationship between the urinary excretion and in vitro dissolution.     

Free vascularized bone transfers for nonunions, segmental gaps, and following tumor resection

Free vascularized bone transfer is recognized as a valuable technique for skeletal reconstruction and salvage with certain nonunions, skeletal defects, and following tumor resection. This procedure is most often indicated for reconstruction of lengthy skeletal defects or under circumstances where conventional bone grafting techniques are unlikely to succeed. Factors affecting selection of donor bone and technical peculiarities relative to the recipient sites are discussed. The results of 49 cases at the Mayo Clinic for management of nonunion, segmental gaps or following tumor resection suggest a union rate of 82%. The most consistent rate of success was found for reconstruction of defects affecting the tibia, mandible or forearm bones.     

In vivo effects of anti-idiotype on Plasmodium chabaudi infection in mice.

A polyclonal anti-idiotype was raised in rabbits following immunization with a murine monoclonal antibody which recognized a 250,000 MW antigen of Plasmodium chabaudi-infected erythrocytes. The monoclonal antibody, NIMP M23 (clone 3,) has been shown to protect mice against homologous parasite challenge. Following purification, the anti-idiotype was shown to bind only the immunizing idiotype and to recognize antigen-binding site-associated anti-idiotype. Mice primed with anti-idiotype and challenged with live parasites had an altered course of infection, with significant reduction in their peak parasitaemia levels. Anti-idiotype priming did not induce an antigen-reactive antibody response in vivo but a population of T cells capable of proliferating in vitro to P. chaubaudi-infected red cells was stimulated. These data are discussed in the context of possible idiotypic interaction in murine malaria.     

International primary care classifications: the effect of fifteen years of evolution.

To better understand the development of primary care classifications over the past 15 years, 10 primary care databases have been retrospectively analysed using the structure of the International Classification of Primary Care (ICPC) as the basis. All datasets were based on routine data collection using different classification systems by several family physicians during all encounters with their patients over considerable periods of time, in most cases one year. The prevalences or the rates of the available diagnostic--and reason for encounter--classes were distributed over four frequencies. With a few exceptions the distribution of diagnostic labels referring to common diseases is surprisingly similar. The use of ICPC however results in a quantum leap in the use of symptom and complaint diagnoses. Because of this shift primary care physicians now have available a classification with 400 diagnostic classes used with a prevalence of > or = 1/1000 patient-years or per 1000 visiting patients per year. The classification of reasons for encounter allows the physician to identify over 300 reasons for encounter used > or = 1/1000 patient years or per 1000 visiting patients per year. Family physicians have been successful in the development of new primary care classifications. Rag bag rubrics which are the result of the structure of ICPC are used relatively often and deserve more attention from primary care taxonomers.     

Strength, endurance, and stability of the tongue and hand in Parkinson disease.

Weakness and fatigue in the orofacial system often are presumed to contribute to the dysarthria associated with neuromotor disorders, although previous research findings are equivocal. In this study, tongue strength, endurance, and stability during a sustained submaximal effort were assessed in 16 persons with mild to severe Parkinson disease (PD) and a perceptible speech disorder. The same measures were taken from one hand for comparison. Only tongue endurance was found to be significantly lower in these participants than in neurologically normal control participants matched for sex, age, weight, and height. Analyses of data from a larger sample comprising the present and retrospective data revealed lower-than-normal tongue strength and endurance in participants with PD. No significant correlations were found between tongue strength and endurance, interpause speech rate, articulatory precision, and overall speech defectiveness for the present and previously studied participants with PD, bringing into question the influence of modest degrees of tongue weakness and fatigue on perceptible speech deficits.     

Can we predict the outcome of a partial rupture of the anterior cruciate ligament? A prospective study of 43 cases

The concept of partial rupture of the anterior cruciate ligament (ACL) has been confirmed by arthroscopic examination and palpation. We present a prospective study of 43 patients who were diagnosed arthroscopically as suffering from a partial rupture of the ACL by the same surgeon. The patients followed a rehabilitation protocol and were examined by an independant observer after 5 years. Twenty-five patients had a stable knee, whereas 18 eventually suffered a complete ACL rupture. ACL partial rupture is easily recognizable with arthroscopy, but the quantity and state of the still intact fibres is difficult to assess. Received: 20 April 1996 Accepted: 17 December 1996