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Biomedical subjects

P J Schechter

Publications and source records attributed to P J Schechter.

100 records · Page 6Linked to original sources
PubMedDate not supplied

Effects of single doses of vigabatrin on CSF concentrations of GABA, homocarnosine, homovanillic acid and 5-hydroxyindoleacetic acid in patients with complex partial epilepsy.

Vigabatrin, as a single oral dose of 50 mg/kg, was administered to 11 patients with drug-refractory complex partial epilepsy. Serial lumbar punctures were performed prior to and 5 times within the first week following treatment. Cerebrospinal fluid (CSF) concentrations of total GABA, free GABA, homocarnosine, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and vigabatrin were determined as well as blood vigabatrin levels. CSF GABA, homocarnosine, HVA and 5-HIAA concentrations increased by 6 h after the single dose and remained elevated for up to 5-7 days. In contrast, CSF and blood vigabatrin levels were maximal within the first 24 h and were no longer detectable thereafter. Hence, these results are consistent with vigabatrin acting as an irreversible inhibitor of GABA-transaminase and suggest that it may also increase biogenic amine turnover.

Administration, Oral↗
PubMedDate not supplied

Hemodynamic effects of MDL 17,043, a new cardiotonic agent, in patients with congestive heart failure: comparison with sodium nitroprusside.

MDL 17,043 (MDL), a new cardiotonic agent, was given intravenously at a single dose of 0.5 mg/kg to 14 patients with congestive heart failure (stages II-III). The mean half-life of plasma elimination of the parent compound determined in eight subjects was 81 min. MDL is rapidly metabolized to the sulfoxide with a maximum plasma metabolite concentration reached at 15 min after parent drug infusion and a metabolite half-life of 164 min. In eight patients, the hemodynamic effects of MDL were compared with those of sodium nitroprusside (SN) given at a dose lowering mean blood pressure by 20 mm Hg. Both agents increased cardiac output (p less than 0.001 for MDL, p = 0.06 for SN) and decreased total peripheral resistance values (p less than 0.001 for both) and left ventricular end-diastolic pressure (wedge pressure) (p less than 0.001 for MDL, p less than 0.01 for SN). However, MDL was able to increase left ventricular stroke work, whereas SN failed. As both agents induced comparable changes in loading conditions, it can be assumed that MDL not only acts by peripheral vasodilation but also has a direct positive inotropic action on the heart muscle. Myocardial oxygen uptake, assessed indirectly by tension-time index, was not affected by MDL (p greater than 0.2) despite the improvement in myocardial contractile state, thus making this new agent suitable for the treatment of congestive heart failure secondary to ischemic heart disease.

Adult↗
PubMedDate not supplied

Acute hemodynamic effects of piroximone (MDL 19,205) in patients with moderate congestive heart failure: comparison with sodium nitroprusside.

Piroximone (MDL 19,205), a new imidazolone derivative, was given intravenously to 14 patients with congestive heart failure (NYHA class II-III), while under constant daily doses of digitalis and diuretics. In the first 3 patients, we determined the dose safely eliciting a favorable hemodynamic response. The subsequent 11 patients received 1 mg/kg of piroximone intravenously, and the hemodynamic effects were compared with those of sodium nitroprusside (SN) at a dose-lowering mean blood pressure by 10-20 mm Hg. Piroximone increased heart rate (13.2 +/- 2.0 beats/min, mean +/- SEM) and lowered mean arterial pressure (9 +/- 2.3 mm Hg). Both agents reduced similarly wedge pressure (6.5 +/- 2.9 and 9 +/- 2.9 mm Hg, respectively, for SN and piroximone) and total peripheral resistance. Cardiac index was increased less by SN (15%) than piroximone (48%) (p less than 0.001), and stroke work index significantly enhanced only by piroximone (p less than 0.001). The changes in loading conditions induced by the two agents being similar, it is likely that piroximone not only acts by peripheral vasodilation, but also possesses positive inotropic properties. Myocardial oxygen demand, assessed indirectly by tension-time index, was not affected by piroximone. Thus, piroximone appears to combine well-balanced vasodilator and inotropic properties which make this new agent potentially very useful for the management of congestive heart failure.

Adult↗
PubMedDate not supplied

Unusual effect of some alpha-mercaptoacrylic acids on metabolism of zinc in the rat.

1. Gavage of rats with beta-aryl derivatives of alpha-mercaptoacrylic acid resulted in pronounced and sustained elevation of serum zinc concentration. Greater than ten-fold increases above normal zinc levels were attained 2-8 h after doses of 50 mg/kg of the phenyl and furan derivatives. 2. These compounds were rapidly absorbed from the rat gastrointestinal tract and could be detected in serum for several days after a single dose. The return of serum zinc concentration to the normal level paralleled clearance of the mercaptoacrylic acid from plasma. 3. Close to 100% of the zinc and of the alpha-mercapto-beta-(2-furan)acrylic acid (MFA) in serum 4 h after administration of the compound were bound to serum macromolecules. 4. MFA decreased excretion of endogenous zinc; it altered neither the gastrointestinal absorption of zinc nor serum concentrations of copper, albumin and total protein. 5. These compounds appear to mobilize zinc from tissue stores and retard zinc clearance from plasma.

Acrylates↗
PubMedDate not supplied

Formation of a ternary complex with serum albumin: an explanation for the effect of alpha-mercapto-beta-(2-furan) acrylic acid on rat plasma zinc clearance.

1. Four, six and eight hours after gavage of rats with alpha-mercapto-beta-(2-furan)acrylic acid (MFA) (25 mg/kg) serum zinc concentration was increased ten-fold over control levels and a mean molar ratio of 1 albumin:0-4 zinc:0-8 MFA was found for seventeen sera. 2. At pH 7-5 a maximum of 1 mole of MFA could be bound per mole of metal-free bovine serum albumin. 3. In the presence of zinc ion, albumin-zinc-MFA complexes formed, since for each mole of albumin-zinc complex an additional mole of MFA could be bound to albumin. Complexes up to a molar stoichiometry of 1 albumin:2 zinc:3 MFA were prepared. 4. MFA stabilized the albumin-zinc complex against dissociation. 5. Formation of similar complexes in vivo may account for the markedly delayed clearance of plasma zinc rats administered beta-aryl derivatives of alpha-mercapto-acrylic acid.

Acrylates↗
PubMedDate not supplied

Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.

Adolescent↗
PubMedDate not supplied

[The use of difluoromethylornithine in congenital trypanosomiasis due to Trypanosoma brucei-gambiense].

The authors describe their experience with two cases of congenital Trypanosoma brucei-gambiense trypanosomiasis treated with orally administered difluoromethylornithine. The first case tolerated well his treatment (35 days of DFMO) and has probably been definitively cured. The second case, already in a desperate condition upon admission, died after only 4 days of difluoromethylornithine (DFMO). The authors hypothesize that difluoromethylornithine (DFMO) may be the drug of choice for congenital trypanosomiasis because of its good absorption by the oral route, its ability to penetrate the cerebrospinal fluid especially in presence of meningeal inflammation and its activity against Trypanosoma brucei-gambiense.

Animals↗
PubMedDate not supplied

[A trial treatment with eflornithine of trypanosomiasis caused by Trypanosoma brucei gambiense in the Peoples Republic of the Congo].

In a multiclinic trial in Brazzaville, Congo, 14 patients with late-stage Trypanosoma brucei gambiense trypanosomiasis were treated with eflornithine. All cases had previously been treated with one or several courses of melarsoprol. Eflornithine treatment consisted of 400 mg/kg/day intravenously for 14 days followed by 300 mg/kg/day orally for 21 days. After treatment all patients had a disappearance of trypanosomes from cerebrospinal fluid (CSF), a normalization of CSF WBC count, and, where present prior to study, a clear, rapid and lasting amelioration of neurological signs. Neither clinical nor biological adverse effects necessitated modifying or discontinuing treatment. These encouraging results in melarsoprol-refractory cases demonstrate, despite certain logistical problems, the interest of eflornithine in the treatment of human African trypanosomiasis.

Administration, Oral↗
PubMedDate not supplied

Treatment of mild and moderate hypertension with medroxalol, an alpha- and beta-adrenergic antagonist.

Medroxalol, a new antihypertensive agent with alpha- and beta-adrenoreceptor blocking properties in both animals and humans, was administered in a single-blind study for 12 weeks to 29 patients with mild and moderate hypertension (standing blood pressure: 188-130/130-100 mm Hg). After 4 weeks of placebo administration, treatment with oral medroxalol was begun. Six weeks later, half the subjects added hydrochlorothiazide, 12.5 mg twice daily, to medroxalol for an additional 6 weeks, and the other half added placebo. During the final 4-week period medroxalol, but not hydrochlorothiazide, was discontinued and placebo substituted. Oral medroxalol doses of 100-400 mg twice daily reduced standing diastolic pressure to less than 100 mm Hg in 21 of the 26 subjects who completed the study. Compared to the last values on placebo, mean standing blood pressure was decreased by 15.6/12.0 mm Hg during the first 6 weeks of medroxalol at mean daily doses of 388-407 mg. Addition of hydrochlorothiazide permitted some decrease in medroxalol dosage. Upon medroxalol withdrawal, blood pressure and heart rate returned toward pretreatment values, with subjects continuing on diuretic showing lower blood pressures than the untreated individuals. Tolerance to medroxalol, with or without hydrochlorothiazide, was good. Mild orthostatic dizziness was the most frequent complaint associated with therapy, but postural hypotension was not found on physical examination. Medroxalol appears to be effective and well tolerated for reducing the blood pressure of most patients with mild to moderate hypertension and may be useful for chronic oral therapy of this disease.

Adrenergic alpha-Antagonists↗