Frequency-dependent effects of amitriptyline and maprotiline on conduction in the guinea pig His-Purkinje-system in vivo

In the Cardiac Arrhythmia Suppression Trial antiarrhythmic drug therapy with slow kinetic sodium channel blockers (class Ic antiarrhythmic drugs) was associated with excess mortality, presumably due to drug induced proarrhythmia. It has been suggested that the degree of rate-dependent conduction slowing produced by agents that have sodium channel blocking properties may be related to the proarrhythmic propensity of these agents.In the present study, rate-dependent conduction slowing by the antidepressants amitriptyline and maprotiline was investigated in anesthetized guinea pigs. After electrical ablation of the sinus node the left atrium was stimulated at cycle lengths between 200 ms and 500 ms. His bundle electrograms were registered by means of an epicardial electrode. Drugs were administered by i.v. infusion of 0.2 mg kg^–1 min^–1 for 30 min followed by 0.1 mg kg^–1 min^–1 for up to 30 min. Both drugs produced substantial rate-dependent conduction slowing within the His-Purkinje-system. The relationship between pacing rate and conduction slowing was well fitted by linear regression. The steepness of the regression line was significantly greater for amitriptyline than for maprotiline (slope factors: 9.10×10^–4±7.85 × 10^–5, n = 6, vs. 6.29×10^–4±2.97×10^–5, n=6, P<0.001), indicating that conduction slowing by amitriptyline exhibits a greater degree of rate-dependence than conduction slowing by maprotiline. On abruptly changing the driving cycle length from 500 ms to 300 ms, conduction slowing reached a new steady state with rate constants of 0.83±0.093 beat^–1 (amitriptyline) and 0.14±0.05 beat^–1 (maprotiline, P<0.001). Following interruption of rapid pacing at a cycle length of 250 ms, conduction slowing recovered with time constants of 332.4±52.8 ms (amitriptyline) and 1088.1 ± 143.5 ms (maprotiline, P = 0.001). Thus, amitriptyline exhibited fast kinetic properties similar to class Ib antiarrhythmic action while the slower kinetic properties of maprotiline resembled those of class Ia agents.Deceased Correspondence to: H. Todt at the above address     

Recurrent intussusception due to a primary colloid carcinoma of the large bowel in a child

A case of recurrent colo-colic intussusception due to a primary colloid carcinoma of descending colon with widespread lymphatic involvement in a child, is reported. The unusual mode of presentation and lack of awareness were responsible for a delay of 6 months before the final diagnosis was made. Two years after the operation the patient is well and there is no evidence of clinically detectable secondaries.     

The effect of enamel de- and remineralization on permeability to iodide and urea

Blocks of bovine enamel subjected to de- and remineralization were measured for changes in permeability to iodide and urea. Results were similar, indicating that the diffusion pathways for the two species were comparable, and that sites for iodide binding did not appear to exit.     

A microcomputer oxygen control system for ventilatory therapy

A computer-based feedback system has been developed to adjust the concentration of oxygen in the inspired gas of a patient under artificial respiration. The system uses a proportional plus integral controller and feedback of arterial oxygen saturation to adjust the inspired oxygen fraction. The effectiveness of the controller has been tested using a dynamic, mathematical model of the human respiratory system. This relatively sophisticated model has been developed and examined in the past, and it has been shown that it can realistically describe the human respiratory system for a wide variety of test conditions. The performance of the oxygen control system has been evaluated using the simulation model. The response of the controller to different disturbances is always stable, with arterial pressure of oxygen returning to normal in less than 12 minutes. Some of the simulation results are presented to illustrate the dynamic behavior and robustness of the controller.     

Clathrin-coated vesicles from bovine brain contain uncoupled GABAA receptors

Clathrin-coated vesicles are thought to be a vehicle for the sequestration of GABA_A receptors. For coated vesicles from bovine cerebrum, we examined the binding properties of [³H]muscimol, a GABA_A-specific agonist, [³H]flunitrazepam, a benzodiazepine agonist, and [³⁵S]t-butylbiocyclophosphorthionate (TBPS), a ligand for GABA_A receptor channels. Under standard conditions, the binding level of [³H]muscimol, [³H]flunitrazepam, and [³⁵S]TBPS to coated vesicles represented 12.3±1.8%, 7.9±1%, and 10.2±1.8%, respectively, of that in crude synaptic membranes. Coated vesicles showed a single [³H]flunitrazepam binding site with a K_D value (12 nM) which was 9-fold that for synaptic membranes. The allosteric coupling between binding sites was measured by the addition of GABA to [³H]flunitrazepam and [³⁵S]TBPS binding assays. For [³H]flunitrazepam binding to synaptic membranes, GABA gave an EC₅₀=2.0 μM and at saturation (100 μM) an enhancement of 122%. This stimulation was completely blocked by the GABA antagonist SR95531. In contrast, neither GABA nor SR95531 had a significant effect on [³H]flunitrazepam binding to CCVs, indicating that the allosteric interaction between GABA and benzodiazepine binding sites is abolished. Likewise, GABA displaced nearly all of the [³⁵S]TBPS binding to synaptic membranes but had no effect on binding to coated vesicles, indicating that coupling between the GABA binding sites and chloride channel is also impaired. Thus GABA_A receptors appear to be uncoupled during normal intracellular trafficking via coated vesicles. The presence of major GABA_A receptor subunits on these particles was verified by quantitative immunoblotting. Relative to the levels in synaptic membranes, CCVs contained 110±14% and 29.5±3.8%, respectively, of the immunoreactivity for GABA_A receptor β2 and α1 subunits. Thus, in comparison to GABA_A receptors on synaptic membranes, those on CCVs have a reduced α1/β2-subunit ratio. It may be suggested that a selective decline in the content of α1 subunits in coated vesicles could in part account for GABA_A receptor uncoupling.     

Demineralization potential of different concentrations of gelatinized wheat starch

Six subjects wore intraoral devices carrying bovine enamel blocks covered with a layer of Streptococcus mutans. They swished solutions of 5% glucose or maltose, or sols or gels of 3, 5, 10, 15, or 20% gelatinized wheat starch in the mouth for 3 X 1 min. Demineralization was measured after 45 min by determining the change in iodide permeability (delta Ip) of the enamel. Spittings of the administered materials and samples of saliva, taken at intervals during the test, were analyzed for maltose, and the time of clearance was calculated. Demineralization was greatest for glucose followed by maltose, the starch gels, and the sols. The latter gave close to zero scores. The salivary clearance time increased with increase in concentration of the starch. Although the starch was hydrolyzed rapidly in the mouth, its oral retentiveness was greater than that of the maltose rinse. Demineralization was closely correlated with the final pH of the S. mutans cell layer. The data indicate that the starch in baked or cooked foods may have a significant demineralization potential and that it enhances oral retentiveness.     

Scheimpflug biometry of the anterior segment after implantation of foldable iris-fixated lenses

PURPOSE: To evaluate intraocular dimensions of the anterior segment of myopic phakic eyes after implantation of foldable iris-fixated lenses. METHODS: Seventeen myopic eyes that received a foldable iris-fixated phakic intraocular lens (PIOL) were assessed. Distances between the cornea and the IOL-optic edge and between the IOL optic and the crystalline lens were evaluated using Scheimpflug photography 3 months postoperatively. RESULTS: The average postoperative distance between the central corneal endothelium and the anterior surface of the IOL was 2.01 +/- 0.26 mm. The distance between the corneal endothelium and the peripheral edge of the IOL averaged 1.32 +/- 0.18 mm at the 12 o'clock position and 1.34 +/- 0.21 mm at the 6 o'clock position. The distance between the crystalline lens and the posterior surface of the IOL averaged 0.73 +/- 0.09 mm. CONCLUSIONS: The high quality of the three-dimensional Scheimpflug images allowed measurements of intraocular distances in PIOL implanted eyes. Distances between the foldable iris-fixated IOL and crucial surrounding tissues could be determined 3 months postoperatively.     

Epidemiological aspects of rotavirus infection in Ahwaz, Iran

Rotavirus is the major cause of diarrhoea in children worldwide. In this study, conducted in the city of Ahwaz, Iran, during November 2001-March 2002, stool samples from 200 inpatient (n=63) and outpatient (n=137) children aged 1-24 month(s) were analyzed. Polyacrylamide gel electrophoresis was used for isolating rotavirus. Rotavirus was isolated from 36 (26.3%) of the 137 stool samples of outpatients and from 23 (36.5%) of the 63 stool samples of inpatients. The overall frequency of rotavirus in this population was 29.5%. The highest detection of rotavirus was made in children aged 7-12 months, which demonstrated that the relationship between age and rate of rotaviral infection was statistically significant (p < 0.05). The predominant electrophoretic pattern detected was the long (L) electrophoretype (46 of 59; 78%), followed by the short (S) electrophoretype (12 of 59; 20.3%). One strain had a mixed pattern. Such analysis throughout Iran would assist in developing sound guidelines for the prevention of rotavirus infections.     

Artifactual changes in hematological variables in equine blood samples stored at different temperatures and various anticoagulants

The objective of this study was to determine the effect of storage time, temperature, and anticoagulant on hematologic parameters in equine blood samples. Blood samples were obtained from 50 clinically healthy warm-blooded horses at two major equestrian complexes in Tehran, Iran. The samples were collected in three different tubes containing EDTA, sodium citrate, or heparin and were analyzed within 4?h of collection. Blood samples collected into EDTA-containing tubes were stored at 4°C or 24°C. Each sample was analyzed again at 24, 48, and 72?h after collection. The statistically significant (P?<?0.05) alterations included decreased RBC count and increased hemoglobin concentration [Hgb] in blood samples stored at 24°C after 48 and 72?h; increased hematocrit in blood samples stored at 24°C after 24?h; decreased hematocrit in blood samples stored at 4°C after 72?h; decreased MCHC in blood samples stored at 4°C after 72?h; and decreased total WBC count in blood samples stored at 24°C after 48?h. Although there was no significant difference in hematologic analytes between heparinized and EDTA-anticoagulated blood samples, most of the hematologic analytes were decreased significantly (P?<?0.05) in sodium citrate-containing blood samples, compared with blood samples stored in EDTA. The results of this study suggest that within certain limitations for some hematologic analytes, equine blood samples stored in EDTA at 4°C for up to 72?h may be suitable for hematologic testing.