Biomedical subjects

R Greco

Publications and source records attributed to R Greco.

At least 37 records · Page 2Linked to original sources

PubMed2000

Relation of left ventricular diastolic properties to systolic function in arterial hypertension.

BACKGROUND: It is unclear whether impairment of left ventricular (LV) diastolic characteristics is independent of systolic dysfunction. METHODS AND RESULTS: To address this issue, 159 consecutive hypertensive patients (44+/-11 years, 78 obese, 96 women) and 165 normotensive subjects (32+/-11 years, 84 obese, 110 women) were studied with the use of Doppler echocardiography. After adjustment for age, body mass index (BMI), and sex, we found that ejection fraction (EF; M-mode, z-derived) was higher in hypertensive (66. 6+/-5.2%) than in normotensive (63.9+/-4.4%, P<0.0001) subjects, whereas midwall shortening (MS) was lower (hypertensive patients 16. 9+/-2.0%, normotensive subjects 17.8+/-2.2%, P<0.02), even after correction for end-systolic wall stress (P<0.05). Isovolumic relaxation time (IVRT) was greater in hypertensive patients (103+/-14 ms) than in normotensive subjects (78+/-19 ms), as was deceleration time of E velocity and peak A velocity (all P<0.0001). In multivariate analysis, IVRT was unrelated to EF, but a negative relation was found with MS (P<0.001), independent of age, BMI, presence of arterial hypertension, LV geometry, and load (multiple R(2)=0.58). For comparable age, sex distribution, BMI, and blood pressure values, hypertensive patients with lower afterload-adjusted MS exhibited longer IVRT than patients with normal MS (P<0.005). However, IVRT remained higher than in normotensive control subjects after control for LV geometry and load. CONCLUSIONS: Doppler indices of delayed LV relaxation can be detected in the presence of normal or supranormal EF but are independently related to impaired MS. A less severely abnormal relaxation, however, can be also detected in the presence of normal midwall function, independent of LV geometry and load. Thus, diastolic abnormalities may occur before systolic dysfunction even when it is measured at the midwall.

Adult↗

PubMed2000

Synthesis and beta-blocking activity of (R,S)-(E)-oximeethers of 2, 3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2, 3-b]pyridine:potential antihypertensive agents - part IX.

The synthesis of oximeethers of 2,3-dihydro-1,8-naphthyridine and 2, 3-dihydrothiopyrano[2,3-b]pyridine is described. These compounds exhibit a selective beta-blocking activity, with a selectivity towards beta(2)-receptors. Groups in the N(1) position giving rise to a considerable steric hindrance led to a higher beta(2)-blocking selectivity, whereas groups creating a moderate hindrance caused a weak but significant decrease in beta(2)-antagonist potency. Substitution of the N(1)-R group with a sulfur atom led to compounds possessing beta(1)-, beta(2)- and beta(3)-blocking properties. Compounds 9c(1) and 10a(1) showed a beta(3)-antagonist activity slightly lower than that of propranolol.

Adipose Tissue↗

PubMed2000

Renal tubular function in patients receiving anticonvulsant therapy: a long-term study.

PURPOSE: The goal of the study was to evaluate the tubular renal function in children and adolescents who are undergoing monotherapy with sodium valproate (VPA), carbamazepine (CBZ), and phenobarbital (PB). METHODS: The urinary excretion of N-acetyl-beta-glucosaminidase (NAG), beta-galactosidase (beta-Gal), alanine-amino-peptidase (AAP), and alpha1-microglobulin (alpha1M) was measured in 58 epileptic patients (29 girls and 29 boys), aged 12.6 +/- 3.9 years, who were subdivided into three groups according to their therapy. Fifty healthy sex-and age-matched children served as controls. The measurements were taken before the beginning of therapy and after 6 months, 1 year, and 2 years of therapy. RESULTS: Before the beginning of therapy, there were no significant differences in NAG, beta-Gal, AAP, and alpha1M values between the control group and the three groups of epileptic children. After 6 months of therapy, patients treated with VPA and CBZ showed a significant increase in the urinary excretion of NAG and beta-Gal compared with baseline data and control values. After 1 and 2 years, these patients showed a persistence of the changes found after 6 months of therapy. In patients treated with PB, we did not find any significant variation in NAG, beta-Gal, AAP, and alpha1M urinary excretion. CONCLUSIONS: Our study demonstrates that in patients treated with VPA and CBZ, an impairment of tubular function can be present, whereas PB does not cause any significant change.

Adolescent↗

PubMed2000

Increased expression of periplasmic Cu,Zn superoxide dismutase enhances survival of Escherichia coli invasive strains within nonphagocytic cells.

We have studied the influence of periplasmic Cu,Zn superoxide dismutase on the intracellular survival of Escherichia coli strains able to invade epithelial cells by the expression of the inv gene from Yersinia pseudotuberculosis but unable to multiply intracellularly. Intracellular viability assays, confirmed by electron microscopy observations, showed that invasive strains of E. coli engineered to increase Cu,Zn superoxide dismutase production are much more resistant to intracellular killing than strains containing only the chromosomal sodC copy. However, we have found only a slight difference in survival within HeLa cells between a sodC-null mutant and its isogenic wild-type strain. Such a small difference in survival correlates with the very low expression of this enzyme in the wild-type strain. We have also observed that acid- and oxidative stress-sensitive E. coli HB101(pRI203) is more rapidly killed in epithelial cells than E. coli GC4468(pRI203). The high mortality of E. coli HB101(pRI203), independent of the acidification of the endosome, is abolished by the overexpression of sodC. Our data suggest that oxyradicals are involved in the mechanisms of bacterial killing within epithelial cells and that high-level production of periplasmic Cu,Zn superoxide dismutase provides bacteria with an effective protection against oxidative damage. We propose that Cu,Zn superoxide dismutase could offer an important selective advantage in survival within host cells to bacteria expressing high levels of this enzyme.

Base Sequence↗

PubMed2000

Celiac disease diagnosis in misdiagnosed children.

Antiendomysial antibodies (EMA) are today considered the most sensitive and specific serological marker of celiac disease (CD). The aim of the present study was to assess the occurrence of EMA of IgG isotype in EMA IgA negative children with clinical suspicion of malabsorption and their relationship with CD. Serum EMA IgG1 determination was performed on 30 EMA IgA negative children with clinical suspicion of CD. Total serum IgA levels were further investigated. Sixty children with gastroenterological diseases other than CD were used as control disease patients and 63 healthy children were evaluated as the control group. Eighteen out of 30 children in the study showed EMA IgG1 positivity in sera and a villous height/crypt depth ratio <3:1 as index of intestinal atrophy. It is noticeable that a selective IgA deficiency was present in only 9 of 18 EMA IgG1 positive children. In addition, clinical symptoms, EMA IgG1, and mucosal atrophy disappeared after 8-10 mo on a gluten-free diet. Neither EMA IgA nor EMA IgG1 were detected in the children in the control groups. The other 12 children in study group showed no histologic abnormalities and were EMA IgG1 negative. In this study, we reveal a group of EMA IgG1 CD children without IgA deficiency. The diagnosis was based on the presence of gluten-dependent typical serological and histologic features of CD. Our data suggest that EMA IgG1 determination could be a new tool in the diagnostic workup of CD, useful in avoiding possible misdiagnosis.

Adolescent↗

PubMed2000

[Percutaneous closure of atrial septal defects: midterm results of a new therapeutic strategy].

OBJECTIVE: To evaluate the midterm results of percutaneous closure of the atrial septal defect using two new devices. PATIENTS AND METHODS: Nine children (weight 19.7 +/- 7 kg, age 5.1 +/- 1.9 years) underwent percutaneous type II atrial septal defect closure through the antegrade pathway under general anaesthesia, and monitored by transesophageal echocardiography. The closing devices used were DAS-Angel Wings and Ampaltzer. RESULTS: The hemodynamic results were: mean diameter of the defects was 11.4 +/- 2 mm by TEE measurement and 12.3 +/- 2.6 mm using balloon occlusion reference. Mean pulmonary artery pressure was 12.7 +/- 2 mmHg and mean pulmonary vascular resistance 1.5 +/- 0.5 U/m2. A total of 13 devices were used: 9 Amplatzer and 4 DAS-Angel Wings. Four Amplatzer through the introducer were retrieved without complications. Two of which because of lack of sufficient stability in the atrial septum because they were too small inappropriate and the other two because of inappropriate expansion of distal disk of the device. Finally in all patients the device was a successfully deployed. The angiographic evaluation immediate post-procedure showed a minimal shunt in five patients that was no longer present by color Doppler echocardiography 24 hours later. The children were discharged 38 +/- 12 hours after the procedure and at a mean follow up of 9.6 +/- 2.2 months they remain asymptomatic without any clinical or technical problems. CONCLUSION: With the right selection of patients percutaneous closure of atrial septal defects can obtain a very high success rate without complications.

Cardiac Catheterization↗

PubMed2000

Increased bone turnover in epileptic patients treated with carbamazepine.

Bone turnover has been investigated in 12 epileptic patients before and after treatment with carbamazepine and in 15 sex- and age-matched control subjects. We found higher values of markers of bone formation (serum bone alkaline phosphatase, osteocalcin, and propeptides of types I and III procollagen) and of bone resorption (serum telopeptide of type I collagen and urine N-telopeptides of type I collagen) in patients than in controls. Our study demonstrates that carbamazepine induces an increase of bone turnover.

Adolescent↗

PubMed2000

Pulmonary venous flow and mitral inflow velocity pattern in uncomplicated obesity: evidence for late diastolic dysfunction.

BACKGROUND: Active left ventricular relaxation, assessed by Doppler isovolumic relaxation time, is impaired in obesity. There is little information on left ventricular passive properties during filling. METHODS: To evaluate left ventricular late diastolic stiffness in obesity, Doppler echocardiographic interrogation of mitral inflow tract and pulmonary vein flow velocities were obtained from 47 normotensive, young obese subjects (11 males, 36 females) and 43 normotensive, young normal-weight volunteers (13 males, 30 females) of comparable age. RESULTS: After controlling the effect of blood pressure and left ventricular mass, isovolumic relaxation time was prolonged in obese subjects (p < 0.0001 vs normal-weight controls). No difference was found in transmitral peak early and late flow velocities. Obese subjects exhibited prolonged pulmonary vein reverse flow velocity during atrial contraction (p < 0.004), and a higher difference or ratio between duration of pulmonary reverse flow and duration of transmitral forward late flow (6 +/- 31 vs -20 +/- 39 ms or 1.06 +/- 0.3 vs 0.84 +/- 0.3, p < 0.002 and p < 0.001, respectively). These differences were also confirmed after controlling blood pressure and left ventricular mass. Non-invasively estimated left ventricular end-diastolic pressure was higher in obese subjects than in controls (p < 0.002). At multivariate analysis a higher body mass index was the sole predictor of prolonged difference between duration of pulmonary reverse flow and duration of transmitral forward late flow (beta = 0.38, p < 0.001). CONCLUSIONS: Obesity is associated with prolonged left ventricular active relaxation and abnormalities of filling pressure not detectable by the sole mitral inflow velocity pattern. These latter abnormalities are consistent with the presence of early increased left ventricular passive stiffness.

Adult↗

PubMed2000

Cardiac abnormalities in type 1 diabetes.

BACKGROUND: Left ventricular (LV) structural and hemodynamic consequences of type 1 diabetes mellitus are not fully understood. METHODS: To evaluate LV geometry, systolic and diastolic function in type 1 diabetes, Doppler echocardiograms were performed in 40 normotensive, type 1 diabetic patients without coronary heart disease or valvular lesions (22 men, 18 women, mean age 43 +/- 6 years, body mass index 24.7 +/- 2.8 kg/m2) and in 40 age and sex-matched non-diabetic normotensive controls (22 men, 18 women, mean age 43 +/- 5 years, body mass index 23.2 +/- 2.8 kg/m2), in a case-control design. RESULTS: Patients had higher systolic blood pressure than controls (p < 0.03) and comparable diastolic blood pressure and heart rate. LV dimension and mass were higher in patients than in controls (both p < 0.0001) whereas relative wall thickness did not differ. For comparable levels of end-systolic stress, patients exhibited a higher ejection fraction than controls (p < 0.01) and normal midwall shortening. Cardiac output was also higher (p < 0.001), whereas total peripheral resistance was lower in patients than in controls (p < 0.0001). Isovolumic relaxation time and E deceleration were prolonged in patients and peak A velocity was greater than in controls (all p < 0.01), whereas the difference in duration between A and pulmonary vein peak reverse flow at atrial contraction was comparable. In subgroup analyses, all reported features were independent of a) presence of target organ damage; b) duration of disease; c) levels of glycosylated hemoglobin. CONCLUSIONS: In normotensive patients with type 1 diabetes: 1) there was a moderate increase in LV mass; 2) LV chamber function was supernormal and wall mechanics was normal; 3) LV active relaxation was impaired but chamber stiffness was normal.

Adult↗

PubMed1999

Apoptosis of Caco-2 intestinal cells invaded by Listeria monocytogenes: protective effect of lactoferrin.

The apoptosis of infected hepatocytes is a critical step in nonspecific defense against Listeria monocytogenes infection. We have observed that infection by L. monocytogenes in enterocyte-like cells (Caco-2) results in apoptosis. However, a large fraction of infected intestinal epithelial cells escape from cellular condensation and fragmentation, typical of programmed cell death, and become necrotic. The balance between apoptosis and necrosis seems to be influenced by the number of internalized bacteria. The presence of 1 mg/ml of bovine lactoferrin, an iron-binding protein, added to monolayers before the bacterial infection, decreases the number of internalized bacteria and therefore the overall number of dead cells, and, more importantly, all dead cells are killed by apoptosis and not necrosis.

Animals↗

PubMed1999

Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs.

Plasma ammonia and total and free carnitine were measured in 84 children requiring anticonvulsant drugs: 32 patients (group A) on valproic acid alone, 28 children (group B) on polytherapy including valproic acid, and 24 patients (group C) on polytherapy without valproic acid. The other anticonvulsant drugs used in groups B and C were carbamazepine and phenobarbital. Plasma ammonia concentrations were elevated in both group A and B compared with controls. Group B patients showed significantly higher hyperammonemia than group A (59.9 +/- 16.3 micrograms/dl vs. 36.7 +/- 12.4 micrograms/dl; P < 0.05). Group C patients had plasma ammonia levels similar to those of controls (31.1 +/- 14.7 micrograms/dl vs. 29.7 +/- 12.1 micrograms/dl; NS). In both group A and group B patients, plasma ammonia levels were correlated with the valproic acid dosage (r = 0.32, P < 0.01) and with serum concentrations of valproic acid (r = 0.41, P < 0.001). Moreover, a significant correlation between plasma ammonia and duration of valproic acid therapy was found in the patients as a whole (r = 0.31, P < 0.01). Plasma total and free carnitine concentrations were significantly reduced in groups A and B (total carnitine 36.9 +/- 6.9 mumol/l vs. 32.9 +/- 9.7 mumol/l; free carnitine 28.9 +/- 5.1 mumol/l vs. 25.7 +/- 4.3 mumol/l, respectively) compared with group C patients who did not receive valproic acid and in whom values were similar to controls (total carnitine 46.1 +/- 9.0 mumol/l vs. 47.7 +/- 10.1 mumol/l; free carnitine 40.1 +/- 7.1 mumol/l vs. 42.9 +/- 8.0 mumol/l, respectively). Twenty-eight patients (18 of group A and 10 of group B) were re-evaluated and showed a complete normalization of plasma ammonia, and total and free carnitine levels which were similar to controls. Our data suggest that hyperammonemia is an important problem in patients receiving valproic acid, particularly in association with other anticonvulsant drugs. This increase of plasma ammonia and the concomitant reduction of carnitine seem to be transient and completely reversible.

Adolescent↗

PubMed1999

Lung transplantation from ventilated non-heart-beating donors: experimental study in a neonatal swine model.

BACKGROUND/PURPOSE: A shortage of transplantable lungs is a constant and frustrating reality. The use of organs retrieved from ventilated non-heart-beating donors (VNHBD) may alleviate this problem. The purpose of this work was to assess lung function of donor grafts subjected to different time lengths of in situ warm ischemia (WIT). METHODS: Twenty piglets weighing between 6 and 8 kg were allocated randomly to the following study groups: Sham (n = 5), heart-beating donors, non warm ischemia; I-30 (n = 5), I-60 (n = 5) and I-90 (n = 5), VNHBD-WIT of 30, 60, and 90 minutes, respectively. Recipients were rendered dependent on the single left transplanted lung by clamping right pulmonary artery and bronchus 1 hour after transplantation. Assessment of pulmonary function was monitored hourly by hemodynamic, oxygenation, and pulmonary mechanic measurements during a period of 6 hours after reperfusion. Lung grafts were weighed pre- and posttransplantation. RESULTS: Final mean lung weight was significantly greater in VNHBD (92.5+/-3.1 v Sham values 75.6 g+/-2.4; P < .01). Cold ischemic time averaged 80.1+/-2.7 minutes. After right lung exclusion, hemodynamic changes consisted of a sustained increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated with a gradual rise in airway resistance and a fall in compliance. CONCLUSIONS: These data suggest that posttransplantation lung graft function from VNHBD with up to 90 minutes of WIT, is preserved and equivalent to those achieved by grafts harvested after heart-beating donation.

Analysis of Variance↗

PubMed1999

Platelet count and function in children receiving sodium valproate.

To evaluate whether valproic acid (VPA) can cause thrombocytopenia and impaired platelet function, the authors prospectively studied 20 children (12 female and eight male; age range 4.9-9.2 years) before and after 6 months of VPA monotherapy. Fifteen healthy sex- and age-matched children served as control subjects. VPA was prescribed at normal dosages (19.7 +/- 9.9 mg/kg), and plasma levels were within the therapeutic range (60.1 +/- 16.5 microg/mL). At the first evaluation, no significant difference between patients and control subjects was observed for platelet count and function. At the second evaluation the platelet counts were significantly lower in the patients (194,200 +/- 37,800/microL; range 157,700-222,400) than in the control subjects (291,100 +/- 41,300/microL; range 261,000-332,500; P < 0.01). Significant differences occurred between patients and control subjects in the release of adenosine triphosphate (ATP) after collagen and adenosine diphosphate (ADP) stimuli and in aggregation after stimulation with collagen, ADP, and arachidonic acid. Significant correlations between platelet count, aggregation, and ATP release and VPA dosage and plasma concentration were also observed. VPA can cause a decreased platelet count and aggregation and ATP release impairment. These side effects can appear after a few months of therapy and with plasma valproate levels within the normal range. They do not seem to be associated with clinical symptoms, and drug discontinuation is not necessary.

Adenosine Triphosphate↗

PubMed1999

Porins and lipopolysaccharide (LPS) from Salmonella typhimurium induce leucocyte transmigration through human endothelial cells in vitro.

Bacteria or bacterial products may constitute important inducers of surface molecule expression on endothelial cells and leucocytes. This study was undertaken to determine the effects of the Salmonella typhimurium porins, LPS-S and LPS-R on the transendothelial migration of leucocytes through human umbilical vein endothelial cells (HUVEC). Treatment of the HUVEC with either porins or LPS-S or LPS-R increased the transmigration of different leucocyte populations, in particular that of neutrophils. The maximal increase occurred using LPS-S treatment, whereas porin stimulation fell between LPS-S and LPS-R. The transmigration increase was dose-dependent and reached its maximum at about 100-1000 ng/ml of stimulus. Optimal endothelial activation occurred after 2-4 h and 4-6 h using LPS and porin, respectively. Stimulation of leucocytes with either porins or LPS slightly increased their transmigration through non-activated endothelial cells. Transmigration increased remarkably during the simultaneous stimulation of endothelial cells by IL-1ss together with either porins or LPS. To assess participation of E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and leucocyte adhesion complex (CD11/18) in porin- or LPS-mediated leucocyte migration, blocking MoAbs were used. Each blocking MoAb partially and selectively decreased leucocyte transmigration. The obtained results contribute to clarify some aspects of the inflammatory process at sites of infection.

Antibodies, Monoclonal↗

PubMed1999

Centro-temporal spikes in non-epileptic children: a long-term follow up.

OBJECTIVE: This study was undertaken in order to determine the natural evolution of centro-temporal spikes (CTS) in a healthy paediatric population. METHODOLOGY: Forty children and adolescents (mean age +/- SD: 9.9 +/- 4.1 years) with non-epileptic disturbances (tics, headache, pavor nocturnus, vertigo, etc), who showed CTS during routine EEG recordings were studied. No patient suffered from seizures. A clinical and electroencephalographic follow-up of at least 5.5 years was carried out in all subjects. RESULTS: At the follow-up examination, 33 of the 40 cases (82.5%) had no CTS or other epileptic discharges in awake and sleep EEGs, while six subjects continued to show CTS discharges in sleep EEG. Among those subjects who showed persistence of CTS in sleep EEG, rolandic epilepsy developed in two cases, while all other subjects continued to be seizure free. CONCLUSIONS: This study demonstrates that CTS can be present in non-epileptic children and adolescents; in the majority of subjects this EEG abnormality disappears spontaneously and only a small percentage of subjects who have persistence of this pattern develops rolandic epilepsy.

Action Potentials↗

PubMed1999

31-43 amino acid sequence of the alpha-gliadin induces anti-endomysial antibody production during in vitro challenge.

BACKGROUND: Wheat gliadin is the culprit antigen of coeliac disease (CD). Two short sequences of NH2-terminal portion of gliadin seem to be responsible for CD. Antiendomysial antibodies (EMA), highly sensitive and specific for CD, are detectable in the culture media from treated CD patients, after in vitro challenge with peptic-tryptic (PT) digest of gliadin. In this study we detected EMA production after in vitro challenge with 31-43 peptide. We used 56-68 peptide, lacking toxic sequences, as a negative control. METHODS: Duodenal samples from 11 treated CD patients and 9 control patients were cultured with 31-43 and 56-68 peptides and PT gliadin. Indirect immunofluorescence analysis was used for EMA detection. RESULTS: EMA were detected in culture media of 10 of 11 specimens challenged with PT-gliadin and in the media of all specimens challenged with 31-43 peptide. No EMA were detectable in any treated patients cultured with 56-68 peptide or with medium alone. No EMA were observed in cultures of control specimens. DISCUSSION: The ability of the 31-43 sequence of the alpha-gliadin to induce EMA production suggests its involvement in the pathogenesis of CD. Furthermore, it may be a more useful antigenic substance than PT gliadin for both in vitro and in vivo studies of CD.

Adult↗

PubMed1999

Function search in a large transcription factor gene family in Arabidopsis: assessing the potential of reverse genetics to identify insertional mutations in R2R3 MYB genes.

More than 92 genes encoding MYB transcription factors of the R2R3 class have been described in Arabidopsis. The functions of a few members of this large gene family have been described, indicating important roles for R2R3 MYB transcription factors in the regulation of secondary metabolism, cell shape, and disease resistance, and in responses to growth regulators and stresses. For the majority of the genes in this family, however, little functional information is available. As the first step to characterizing these genes functionally, the sequences of >90 family members, and the map positions and expression profiles of >60 members, have been determined previously. An important second step in the functional analysis of the MYB family, through a process of reverse genetics that entails the isolation of insertion mutants, is described here. For this purpose, a variety of gene disruption resources has been used, including T-DNA-insertion populations and three distinct populations that harbor transposon insertions. We report the isolation of 47 insertions into 36 distinct MYB genes by screening a total of 73 genes. These defined insertion lines will provide the foundation for subsequent detailed functional analyses for the assignment of specific functions to individual members of the R2R3 MYB gene family.

Arabidopsis↗

PubMed1999

Epilepsy with myoclonic absences with early onset: a follow-up study.

We studied six children (four girls and two boys) suffering from cryptogenic myoclonic absence seizures with early onset. The age at onset of the seizures ranged between 6 and 27.8 months (mean age +/- SD: 18.5+/-12.4 months). The neurologic evaluation was normal in all patients at the first hospital admission. After the diagnosis, we followed up all children for at least 5 years. At the end of follow-up, two of these patients (a girl and a boy) showed severe mental retardation, a high number (from one to three per day) of seizures, and persistent pathologic electroencephalograms. The other patients showed normal electroencephalograms: all of them were seizure free and without mental retardation. The two patients with mental retardation have been treated with polytherapy. In all other children we used valproate alone successfully. Our data suggest that myoclonic absence seizures with early onset can have a good long-term prognosis. Valproate is a useful anticonvulsant drug in these patients. Mental retardation is present only in patients with poor seizure control.

Anticonvulsants↗