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Biomedical subjects

A M Costa

Publications and source records attributed to A M Costa.

At least 37 records · Page 2Linked to original sources

Desensitization of kainate receptors by kainate, glutamate and diastereomers of 4-methylglutamate.

The potencies of kainate, glutamate and diastereomers of 4-methylglutamate were determined for activation and steady-state desensitization of GluR6 and dorsal root ganglion-type kainate receptors using whole-cell voltage clamp. In HEK293 cells expressing GluR6, all four diastereomers induced desensitizing inward currents at relatively high concentrations (> 50 microM), however, the 2S,4R diastereomer (2S,4R-4MG; SYM 2081) was approximately 100-fold more potent than the other three. The EC50 for receptor activation by 2S,4R-4MG (1.0 microM) was similar to that for kainic acid (1.8 microM), but 2S,4R-4MG was significantly more potent than kainate, glutamate or the other diastereomers of 4-methylglutamate at producing steady-state desensitization of GluR6 receptors. IC50s for desensitization quantified using a fixed concentration of kainate as a test agonist were 7.6, 31 and 667 nM for 2S,4R-4MG, kainate and glutamate, respectively. In addition, 2S,4R-4MG fully desensitized native kainate receptors (of the GluR5 subtype) in dorsal root ganglion neurons with an IC50 of 11 nM, compared to 3.4 microM for glutamate. For GluR6, recovery from desensitization displayed a similar time course for kainate and glutamate (tau = 3-4 s) but was roughly 20-fold slower for 2S,4R-4MG, which suggests that the rate of recovery is not entirely dependent on the affinity of ligand for the desensitized receptor. Following exposure to concanavalin A, application of kainate, glutamate and 2S,4R-4MG evoked very similar maximal currents that showed little or no desensitization. Lectin pretreatment produced a leftward shift in the concentration-response relationship for 2S,4R-4MG with an 11-fold reduction in the EC50; however, no significant change in the EC50 for kainate was observed. The characteristic of 2S,4R-4MG to potently and completely desensitize both recombinant GluR6 receptors and native receptors on dorsal root ganglion neurons suggests that this compound will be useful to study selective blockade of these receptors in the nervous system.

Animals↗

Association between polyclonal B cell activation and the presence of autoantibodies in mice infected with Yersinia enterocolitica O:3.

Eight-week old conventional female Swiss mice were inoculated intravenously with Yersinia enterocolitica O:3. A second group of normal mice was used as control. Five mice from each group were bled by heart puncture and their spleens were removed for spleen cell collection on the 3rd, 5th, 7th, 10th, 14th and 21st day after infection. Immunoglobulin-secreting spleen cells were detected by the isotype-specific protein A plaque assay. Total immunoglobulin levels were determined in mouse serum by single radial immunodiffusion and the presence of autoantibodies was determined by ELISA. We observed a marked increase in the total number of cells secreting immunoglobulins of all isotypes as early as on the 3rd day post-infection and the peak of secretion occurred on the 7th day. At the peak of the immunoglobulin response, the total number of secreting cells was 19 times higher than that of control mice and most immunoglobulin-secreting cells were of the IgG2a isotype. On the 10th day post-infection, total serum immunoglobulin values were 2 times higher in infected animals when compared to the control group, and continued at this level up to the 21st day post-infection. Serum absorption with viable Y. enterocolitica cells had little effect on antibody levels detected by single radial immunodiffusion. Analysis of serum autoantibody levels revealed that Y. enterocolitica infection induced an increase of anti-myosin and anti-myelin immunoglobulins. The sera did not react with collagen. The present study demonstrates that Y. enterocolitica O:3 infection induces polyclonal activation of murine B cells which is correlated with the activation of some autoreactive lymphocyte clones.

Animals↗

(2S,4R)-4-methylglutamic acid (SYM 2081): a selective, high-affinity ligand for kainate receptors.

Glutamic acid activates ionotropic glutamate receptors that mediate excitatory transmission in the central nervous system. The introduction of a methyl group at position 4 of glutamic acid imparts selectivity for kainate receptors, relative to other (N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) ionotropic glutamate receptors. Among the stereoisomers of 4-methylglutamic acid, the potency of the (2S,4R)-isomer (SYM 2081) to inhibit [3H]kainic acid binding to both wild-type (rat forebrain) and recombinant (GluR6) kainate receptors (IC50 values of approximately 32 and 19 nM, respectively) was comparable to that of kainic acid (IC50 values of approximately 13 and 28 nM, respectively). SYM 2081 was approximately 800- and 200-fold less potent as an inhibitor of radioligand binding to wild-type (rat forebrain) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors, respectively. Preexposure of human embryonic kidney 293 cells stably expressing GluR6 receptors to low concentrations of SYM 2081 (30-300 nM) resulted in a reversible blockade of the rapidly desensitizing currents produced by kainate application. At higher concentrations, SYM 2081 (EC50 of approximately 1 microM) elicited kainate-like, rapidly desensitizing, inward currents. Pretreatment of recombinant GluR6 receptors with concanavalin A both abolished the effect of SYM 2081 to block kainate-induced currents and revealed nondesensitizing currents induced by SYM 2081 alone. The latter observations provide strong support for the hypothesis that SYM 2081 blocks kainate-induced currents through a process of agonist-induced desensitization. SYM 2081 also activated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents in primary cultures of cerebral cortex and, consistent with data obtained by radioligand binding, was approximately 5-fold less potent than kainate (EC50 values of 325 and 70 microM, respectively) in this measure. SYM 2081 is a high-affinity, selective, kainate agonist that may prove useful both as a probe to examine the physiological functions of kainate receptors and as the prototype of a novel class of therapeutic agents.

Animals↗

Extracellular matrix deposition, lysyl oxidase expression, and myofibroblastic differentiation during the initial stages of cholestatic fibrosis in the rat.

Early studies showed that during hepatic fibrosis induced by bile duct ligation, fibroblasts within the portal tracts proliferate and express alpha-smooth muscle (SM) actin, suggesting that they may be involved in the deposition of extracellular matrix components in cholestatic fibrosis. Thus, we investigated the deposition of extracellular matrix components (laminin, fibronectin EIIIA, collagen I and IV, procollagen III, elastin, tenascin) as well as the expression of lysyl oxidase and of alpha-SM actin in the portal zone at 24, 48, and 72 hours and 7 days after ligation of the common bile duct. Rat liver tissues were processed for immunofluorescence, in situ hybridization, immunohistochemistry, and for electron and immunoelectron microscopy. At all times examined after bile duct ligation, laminin was observed essentially in the basal membrane of vessels and portal ductules. In sham-operated animals, the fibronectin EIIIA was present exclusively in vessels; at 24 hours postinjury, fibronectin EIIIA expression appeared in both the portal zone and along sinusoids. Two days after ligation, increased expressions of collagen I and IV, procollagen III, and elastin were observed within the portal zone, compared with sham-operated animals. The deposition of these components increased thereafter. Tenascin expression increased soon after bile duct ligation in stroma surrounding proliferating ductules, reaching a maximum at 48 hours; thereafter, expression was restricted to the periphery of proliferating ductules. By in situ hybridization, procollagen I and tissue inhibitor of metalloproteinase-1 mRNA expression was greatly increased in periductular areas at 24 hours postligation and remained elevated throughout the experiment. At 24 hours, a strong reactivity for lysyl oxidase appeared in the portal zone, and, as in controls, alpha-SM actin expression was restricted to vascular SM cells. In the stroma adjacent to proliferating ductules, alpha-SM actin appeared at 48 hours, and the number of alpha-SM actin-positive cells increased until the 7th day. Lysyl oxidase staining increased until 72 hours after bile duct ligation, when it was located in areas surrounding the myofibroblastic cells. At 7 days, lysyl oxidase expression was restricted around myofibroblastic cells present at the periphery of the reactive tissue and appeared to extend into the surrounding parenchyma. These results show that after bile duct ligation, extracellular matrix deposition, and lysyl oxidase expression occur very early in portal connective tissue surrounding proliferating ductules, and precede myofibroblastic differentiation, ie, alpha-SM actin expression. In addition, the data are compatible with the suggestion that in the bile duct ligation model, myofibroblastic differentiation represents an adaptive response to modification of the extracellular matrix environment.

Actins↗

Pyoderma gangrenosum in association with undifferentiated seronegative spondylarthropathy.

The cases of 2 women with pyoderma gangrenosum (PG) and undifferentiated seronegative spondylarthropathy (SpA) are described. These 2 cases, together with the recently reported case of PG and B27-positive psoriatic spondylarthropathy, suggest that PG may also occur in association with forms of seronegative SpA that are different from primary ankylosing spondylitis (AS) and AS associated with inflammatory bowel disease.

Adult↗

[Relationship between mitral valve prolapse and arrhythmogenic right ventricular disease].

PURPOSE: To evaluate some features of ventricular arrhythmias in patients with mitral valve prolapse. METHODS: We studied 25 patients (female: 19; mean age: 37 +/- 13 years) with ventricular arrhythmias, mitral valve prolapse and normal ventricular function. All patients underwent a 24h Holter and high resolution ECG (HRECG). The Qtc intervals were measured in lead II (normal < 0.44 s). In order to define the possible origin of the ventricular focus, the morphology of the ectopic beats were analysed in leads I, II, aVF, V1 using the following criteria: 1) LBBB morphology with left axis deviation in the frontal plane (FP): origin at the inflow tract of the right ventricle (RV); 2) LBBB morphology with right axis deviation in the FP: origin at the outflow tract of the RV; 3) RBBB morphology with left axis deviation in the FP: origin at the posterior region of the left ventricle (LV). RBBB morphology with right axis deviation in the FP: origin at the anterior region of the LV. RESULTS: Twenty three (92%) patients showed > 720 isolated ventricular ectopic beats/24 h. Paired ventricular response was detected in 18 (72%) patients and non-sustained VT in 15 (60%). HRECG was positive in six (24%) patients and Qtc interval was prolonged in 13 (52%). RV was the site of origin of the ventricular ectopic beats in 85% of the patients (outflow: 85%; inflow: 15%). Only five (20%) patients had arrhythmias from the LV. CONCLUSION: There was a high incidence of ventricular arrhythmias with a low incidence of positive HRECG tests, suggesting that the mechanisms of the arrhythmias do not correlate with slow intramyocardial conduction. It was noted a strong association between mitral valve prolapse, arrhythmogenic right ventricular disease and Qtc prolongation. It is possible that in some of this patients the finding could represent a global myocardial disease.

Adolescent↗

Residual Ca2+ channel current modulation by megestrol acetate via a G-protein alpha s-subunit in rat hypothalamic neurones.

1. The inhibition of voltage-activated Ca2+ channel currents by the orally active progesterone derivative, megestrol acetate (MA), was examined in freshly dissociated rat ventromedial hypothalamic nucleus (VMN) neurones using the whole-cell voltage-clamp technique with 10 mM Ba2+ as the charge carrier. 2. The steady-state inhibition of the peak high-threshold Ca2+ channel current evoked by depolarization from -80 to -10 mV by MA increased in a concentration-dependent fashion. MA inhibited a fraction of the whole-cell Ca2+ channel current while progesterone had no effect on the peak Ca2+ channel current (7% at 10 microM). The low-threshold Ca2+ (T-type) current, evoked from -100 to -30 mV, was unaffected by MA. 3. Intracellular dialysis with MA had no effect on the Ca2+ channel current. Concomitant extracellular perfusion of MA showed normal inhibitory activity, suggesting that the MA binding site can only be accessed extracellularly. 4. The high-threshold Ca2+ channel current in VMN neurones was found to consist of four pharmacologically distinguishable components: an N-type current, an L-type current, a P-type current, and a residual current. MA had no effect on the N-, L- and P-type Ca2+ channel currents, but inhibited the residual current. 5. In neurones isolated from cholera toxin-treated animals, the MA-induced inhibition of the Ca2+ channel current was significantly diminished, suggesting a G-protein alpha S-subunit involvement. 6. Treatment with antisense phosphothio-oligodeoxynucleotides to the G alpha S-subunit (antisense-G alpha S) significantly reduced the MA-induced inhibition of the Ca2+ channel current. Treatment with either sense-G alpha S or antisense-G alpha 11 had no effect, confirming a G alpha S-subunit involvement. 7. These results suggest that appetite enhancement induced by MA in cachectic patients may in part be due to a novel central nervous system action, that is, inhibition of a fraction of the whole-cell Ca2+ channel current to attenuate the firing of VMN neurones that may be involved in satiety mechanisms.

Animals↗

Withdrawal from the endogenous steroid progesterone results in GABAA currents insensitive to benzodiazepine modulation in rat CA1 hippocampus.

1. The withdrawal properties of the endogenous steroid progesterone (P) were tested in female rats as a function of benzodiazepine modulation of gamma-aminobutyric acid-A (GABAA)-gated current with the use of the whole cell patch-clamp technique on acutely dissociated CA1 hippocampal neurons. In a previous study, this steroid was shown to exhibit withdrawal properties, behaviorally. 2. One day withdrawal from in vivo administration of physiological doses of P (5 mg ip, 5 days/wk for 3 withdrawal cycles) or its metabolite, the GABAA modulator 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-THP or allopregnanolone, 20 mg/kg ip) prevented the normally potentiating effect of lorazepam (LZM; 10(-7)-10(-4) M) on GABAA-gated current. Withdrawal from 500 micrograms P administered concomitantly with 2 micrograms 17 beta-estradiol also markedly diminished LZM potentiation of GABAA current. This effect was seen only after three withdrawal cycles. 3. P withdrawal produced no inhibitory effect on either basal levels of GABAA-evoked current, the GABAA EC50, or barbiturate (+/-Pentobarbital, 10(-7)-10(-4) M) modulation of this parameter. 4. The effect of steroid withdrawal on LZM modulation of GABAA-evoked current was blocked by picrotoxin as well as by indomethacin, a drug that prevents conversion of P to its metabolite, the GABAA modulator 3 alpha,5 alpha-THP. These results suggest that the withdrawal properties of P may be due to changes in GABAA receptor function produced by 3 alpha,5 alpha-THP.

Animals↗

[Profile of the user population of the Emergency Unit of the Heart Institute--HCFMUSP].

PURPOSE: Characterization of the population using the emergency unit of the Instituto do Coração--HCFMUSP. METHODS: The investigation was carried out in a randomly selected population of 225 people between January and April/93. To determine demographic profile, involvement of the accompanying people with the patient, the nosologic profile and patient's level of knowledge about the Social Health Security (SHS), a questionnaire was applied to the accompanying people. RESULTS: Of the 225 patients, 52.4% were males; age ranged from 1 day to 93 years (45.5% over 60 years old); 61% were living in the state of São Paulo; 17% were professionally active; 52% were beneficiaries of Social Security; 92.4% were users of SHS; 47.3% were illiterate; 67% presented with acute cardiovascular diseases and 33% with a noncardiologic diagnosis. CONCLUSION: This is an old population with a low level of instruction, coming from all regions of the country. Because SHS medical services and hospitals does not work well, including cardiology services, this population asked for care in our emergency unit.

Adolescent↗

[Antiarrhythmic drug effectiveness. Proposal for a new approach based on pharmacological hourly effects].

PURPOSE: To use a new approach in order to assess the antiarrhythmic drugs, based in the hourly autonomic effects and antiarrhythmic efficacy of sotalol. METHODS: Sixteen patients were evaluated in a randomized double-blind placebo-controlled study. Patients were classified in group 1 (anti-arrhythmic efficacy) and group 2 (no antiarrhythmic efficacy). The following parameters were analyzed: 1) clinical variables as age, gender, cardiac disease and ventricular ectopies density; 2) drug effects on pNN50 in 24-hour and on mean hourly cardiac cycle length; 3) percentage of hourly ventricular ectopies distribution and its correlation with pNN50 and with mean hourly cardiac cycle length in all patients; 4) drug effects on mean hourly cardiac cycle length in groups 1 and 2; 5) correlation between hourly pNN50 and ventricular ectopies density after sotalol administration in groups 1 and 2; 6) hourly drug efficacy in groups 1 and 2 and correlation with pNN50. RESULTS: Efficacy of the drug was present in 8 (50%) patients. Sotalol significantly increased 24-hour pNN50 (placebo 5.01 +/- 2.02%; after drug, 11.70 +/- 5.59%-p < 0.001), also increasing mean hourly cardiac cycle length during the day and night, in all patients (placebo 758.25 +/- 75.68 ms; after drug 967.71 +/- 80.17 ms-p < 0.000). It was noted that patients under placebo had different autonomic tonus; group 1 showed higher sympathetic activity as compared to group 2. Hourly drug efficacy was seen in 23 of 24-hour recordings in group 1 while it was not seen at any time in group 2. CONCLUSION: Sotalol significantly increased parasympathetic cardiac activity. The anti-arrhythmic response was related to the autonomic tonus seen before and after drug administration.

Adult↗

Perianal streptococcal dermatitis associated with guttate psoriasis and/or balanoposthitis: a study of five cases.

Perianal streptococcal dermatitis (PSD) is a recently described cutaneous entity caused by group A beta-hemolytic streptococci. It is characterized by perianal erythema, sometimes associated with functional disturbances. We describe four children (2 boys, 2 girls) who had acute guttate psoriasis and also PSD. One of these patients also had balanoposthitis. A fifth patient experienced an association of PSD and balanoposthitis without psoriasis. To our knowledge, the association between guttate psoriasis and PSD has only been reported in five children, and the one with balanitis has not been previously reported.

Anal Canal↗

[The electrocardiogram of high resolution during ventricular tachycardia].

PURPOSE: To evaluate by the signal averaged-ECG (SAECG) the initial portion of the activation of the sustained ventricular tachycardia (SVT) and monomorphic repetitive ventricular tachycardia (MRVT), correlating the findings with those obtained during sinus rhythm (SR). METHODS: Ten patients was studied; five with SVT and five with MRVT. Patients with SVT presented a positive SAECG while patients with MRVT the test was negative, during SR. The findings of this two populations were compared with those obtained in a group of ten patients with advanced bundle branch block (ABBB: five RBBB and five LBBB). We analyzed in the vector-magnitude obtained during VT and ABBB, the root mean square of the initial 40 ms portion of the activation (RMS40) and the duration of the low amplitude signals < 40 microV from the beginning of the filtered QRS (LAS). To define the positiveness of the test in SR, we analyzed the final RMS40 (normal > 20 microV), the duration of the LAS < 40 microV at the end of the activation (normal < 38 ms) and the total QRS duration (QRSD-normal < 114 ms). RESULTS: (mean)-SVT in SR: RMS40 = 11.2 +/- 6.2 microV; LAS = 47.4 +/- 5.8 ms; QRSD = 131.2 +/- 8.7 ms. SVT during VT: RMS40 = 6.9 +/- 4.5 microV; LAS = 54.5 +/- 9.1 ms. RMVT in SR: RMS40 = 59.7 +/- 49.0 microV; LAS = 28.3 +/- 8.5 ms; QRSD = 93.1 +/- 13.0 ms. MRVT during VT: RMS = 25.2 +/- 8.8 microV; LAS = 28.9 +/- 11.1 ms. RBBB: RMS = 53.3 +/- 34.2 microV; LAS = 22.6 +/- 9.8 ms. LBBB: RMS = 54.7 +/- 37.3 microV; LAS = 11.4 +/- 4.6 ms. The comparison between the data from SVT and MRVT/ABBB showed p < 0.01. CONCLUSION: In the studied population, the SAECG was able to identify abnormal LAS initiating SVT, that were not present in MRVT and ABBB. This signals probably represents intra-myocardial slow conduction, as a portion of a re-entry circuit. There was an excellent correlation between the findings during SVT and MRVT with those obtained in SR.

Action Potentials↗

[Study of the autonomic behavior of escape rhythms in congenital atrioventricular block].

PURPOSE: To study the autonomic behavior of the escape rhythm in congenital complete heart block (CCHB), using heart rate variability (HRV). METHODS: A group of 10 asymptomatic patients with CCHB and narrow QRS was studied, 7 females; mean age = 14 +/- 9 years. The following time domain indexes were analyzed from a 24 hour Holter monitoring. The mean of all RR intervals (NN); the standard deviation of the mean (CLV5); the mean of all standard deviations (SDNN); the percent of successive differences longer than 50 ms (pNN50); the shortest cycle (CC) and the longest cycle (CL). The results were compared with a control group, using the Wilcox test for statistical analysis. RESULTS: The results were: NN = 1016 +/- 276 ms in CHB and 725 +/- 121 ms in control (p < 0.01); CLV5 = 184 +/- 97 ms in CHB and 125 +/- 38 ms in control (p = NS); SDNN = 102 +/- 32 ms in CHB and 88 +/- 29 ms in control (p = NS); rMSSD = 113 +/- 69 ms in CHB and 78 +/- 28 ms in control (p = NS); pNN50 = 43 +/- 26% in CHB and 33 +/- 12% in control (p = NS); CC = 582 +/- 129 ms in CHB and 333 +/- 49 ms in control (p = 0.05). CONCLUSION: No statistical difference was noted by comparing HRV indexes in CHB with control subjects, showing that the autonomic behavior of the escape rhythm in CCHB is similar to the sinus node in asymptomatic patients. The differences in NN, CC and CL are probably related to intrinsic properties of each command.

Adolescent↗

[Efficacy of sotalol in idiopathic ventricular arrhythmia originating in the right ventricular outflow tract].

PURPOSE: To evaluate the effects of sotalol in patients (pts) with idiopathic ventricular arrhythmias (VT) from right ventricular outflow tract. METHODS: Eighteen pts with VT were enrolled (five with monomorphic repetitive ventricular tachycardia - MRVT). Pts were submitted to a double-blind crossover randomized study (placebo vs. 320 mg/po/d/sotalol; four weeks each), after a wash-out control period. Holter recording were recorded in control and placebo and drug periods. Eligible pts have > 50/h isolated ventricular premature beats (VPB) in control, with or without paired VPB or nonsustained VT (NSVT- > 3 beats, > 100bpm). Drug efficacy criteria was: > 75% reduction in isolated VPB and > 90% of paired VPB or NSVT. The effects of the drug on uncorrected QT interval was evaluated and also on circadian rhythm of VT through the hourly pNN50/VPB ratios. Values are given as mean +/- SD. Three recordings were compared by using paired Student's "t" test. Statistical significance was assumed for p < 0.05. RESULTS: Differences between control and placebo were NS. Drug was effective in 61% of pts, reducing the 3 types of ET (VPB: placebo = 23.508 +/- 34.537; drug: 975 +/- 1357; paired placebo = 443 +/- 587; drug = 9 +/- 20). The drug was evaluated in 4 pts with MRVT, reducing all ectopic events, with efficacy of 60% over VPB and paired and 80% over NSVT (VPB: placebo = 52.639 +/- 42.207; drug: 1631 +/- 2062; paired: placebo = 796 +/- 754; drug: 20 +/- 30; NSVT: placebo = 4287 +/- 6343; drug: 9 +/- 11). Mean QT interval was 0.40 +/- 0.01s in control and 0.50 +/- 0.04s in the drug period, with no correlation between duration and efficacy. Sotalol modified the circadian rhythm of VPB in the non-responders group, mainly during the morning. CONCLUSION: Sotalol was effective in control of VT, mainly the MRVT. Its effect on VPB circadian rhythm may independently contribute to the overall efficacy profile and myocardial protective effect of this drug.

Adult↗

[Repetitive monomorphic ventricular tachycardia].

PURPOSE: To evaluate retrospectively clinical features of repetitive monomorphic ventricular tachycardia (RMVT). METHODS: Files of 11 patients with RMVT were analyzed (9 females, mean-age 37 +/- 17 years). All patients were submitted to clinical evaluation, ECG, Holter monitoring stress test, high-resolution ECG and echocardiogram; they were treated with antiarrhythmic drugs. RESULTS: Patients were in NYHA class I or II, 9 asymptomatics and 2 with palpitations. The ECG was normal in all of them. Cardiac memory was observed in 3. A left bundle branch block with inferior axis deviation in the frontal plane was present during RMVT in all patients (right ventricular outflow tract focus). Holter monitoring revealed mean of 12031 +/- 8345 isolated PVC/24h; 2892 +/- 234 ventricular couplets/24h and 1367 +/- 890 VTs/24h (mainly nonsustained). In 6 patients RMVT was suppressed during maximal exercise treadmill. High-resolution ECG was negative in all group. Five patients had a normal echocardiogram while 5 showed mitral valve prolapse. One patient developed tachycardiomyopathy. The arrhythmia was controlled with 320mg of oral sotalol in 3 of 4 that used this drug and with 120mg oral propranolol in one of 6 that used this drug. Drug resistance was present in the others. The mean follow-up period was 38 +/- 16 months. CONCLUSION: The results demonstrate that RMVT is a benign form of VT with no detectable anatomic substract by the currently used methods. It is probably induced by nonreentrant mechanism and frequently drug resistance is observed. Among the antiarrhythmic drugs commonly used, sotalol showed to be the most effective.

Adult↗

[Videolaparoscopic cholecystectomy. Experience, evolution, and comparison of techniques].

The paper broadly outlines the technique of laparoscopic cholecystectomy used by the authors to treat patients suffering from calculosis of the gallbladder. Basing their comments on the French school, the authors review the literature to identify those innovations introduced by individual operators in elation to the original technique which have enabled this method to be extended to those cases complicated by acute cholecystitis, VBP calculosis or sequelae from abdominal surgery. The most important innovations include the use of a laparoscope with oblique 30-degrees vision, which is extremely useful during the dissection of Calot's triangle since it allows VBP to be identified with greater ease and precision, above all in the event of phlogistic sequelae enclosing the peduncle. In addition, laparoscopic suture or ligation using Roeder's running-knot, used by the Dundee school to treat the cystic duct and artery, presents considerable advantages compared to the conventional use of metal clips. The authors also emphasise the growing return to intraoperative cholangiography which is routinely performed by some authors and is of value in identifying anatomic anomalies, iatrogenic lesions and VBP calculi unnoticed by preoperative tests. A second innovation which is highlighted consists of the treatment of choledocholithiasis during the course of laparoscopic cholecystectomy, in addition to pre- and postoperative endoscopic papillo-sphincterotomy.

Adult↗

Peri- and postnatal developmental toxicity of beta-myrcene in the rat.

beta-Myrcene (MYR) and essential oils containing this monoterpene have been widely used as scenting agents in cosmetics, detergents, soaps, and as flavouring additives in food and beverages. Recently, MYR was reported to be an analgesic substance and the active principle of lemongrass tea. Despite the importance of human exposure to MYR, its toxicological profile has not been comprehensively studied. The aim of this study was to provide data on the peri- and postnatal developmental toxicity of this terpene. MYR (0.25, 0.5, 1.0 and 1.5 g/kg) in corn oil was given by gavage to female Wistar rats from day 15 of pregnancy, parturition and throughout the period of lactation up to weaning (postnatal day 21). The progeny were examined at birth and subsequently to weaning. Mortality, weight gain and physical signs of postnatal development (ear unfolding, incisor eruption, fur development and eye opening) were evaluated. When the exposed offspring reached maturity (120 days) their reproductive capacity was assessed. No adverse effects on the offspring were seen with the lowest dose tested, but 0.5 g/kg and higher doses decreased birth weight, increased perinatal mortality and delayed the day of appearance of landmarks of postnatal development. Moreover, fertility was impaired in female offspring exposed to the two highest doses of MYR. From the data presented in this paper the no-observed-adverse-effect level for peri- and postnatal developmental toxicity could be set at 0.25 g beta-myrcene/kg body weight.

Acyclic Monoterpenes↗