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Biomedical subjects

S Farkas

Publications and source records attributed to S Farkas.

At least 37 records · Page 2Linked to original sources

Randomized, double-blind study of ciprofloxacin and cefuroxime axetil for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In a prospective, multicenter, double-blind study, the interval to clinical relapse in patients with acute bacterial exacerbations of chronic bronchitis from whom a pretherapy pathogen was isolated was compared following treatment with ciprofloxacin or cefuroxime axetil. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Outpatients randomly received either ciprofloxacin or cefuroxime axetil (500 mg twice a day for 14 days). Three hundred seven patients with acute exacerbations of chronic bronchitis were enrolled, of whom 208 had an exacerbation due to a bacterial pathogen. Clinical resolution at the end of ciprofloxacin and cefuroxime axetil therapy for patients for whom efficacy could be evaluated was 93% and 90%, respectively. Bacteriologic eradication rates were statistically higher for ciprofloxacin recipients (96% [89 of 93]) than for cefuroxime axetil recipients (82% [80 of 97]) (P < .01). The median infection-free interval was 146 days for ciprofloxacin recipients vs. 178 days for cefuroxime axetil recipients (P = .37). In conclusion, ciprofloxacin was associated with an infection-free interval and clinical response that were similar to those associated with cefuroxime axetil, but the bacteriologic eradication rate associated with ciprofloxacin was statistically significantly higher than that associated with cefuroxime axetil.

Acute Disease↗

A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group.

Because of the critical role of neutrophils in host defenses, it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia. To test this hypothesis, a randomized, placebo-controlled, multicenter trial of Filgrastim (300 micrograms/day up to 10 days) as an adjunct to antibiotics was conducted for these patients. Outcome measures included time to resolution of morbidity (TRM, a composite measure of temperature, respiratory rate, blood oxygenation, and chest radiograph), 28-day mortality, length of stay, and adverse events. Filgrastim increased blood neutrophils 3-fold, but TRM, mortality, and length of hospitalization were not affected. Treatment, however, accelerated radiologic improvement and appeared to reduce serious complications (e.g., empyema, adult respiratory distress syndrome, and disseminated intravascular coagulation). Filgrastim administration was safe and well tolerated in these patients. Additional trials are needed to establish the value of this approach to treatment of infectious diseases.

APACHE↗

Effect of methionine enrichment on the biological activities of food proteins.

A special enzymatic technique, the enzymatic peptide modification (EPM) reactions have been worked out in our laboratory, by which proteins can be modified with respect to their biological activities. Enzymatic modification methods provide several advantages in producing proteins of desired nutritional properties. Proteolytic modification, particularly when combined with methionine enrichment, significantly altered the biological activities and leads to increased nutritional value.

Blotting, Western↗

Angiotensin-converting enzyme inhibition by enalapril: a novel approach to reduce ischemia/reperfusion damage after experimental liver transplantation.

Angiotensin-converting enzyme (ACE) inhibitors have proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. Whether this favorable effect can be related to other models of ischemia and reperfusion has not yet been investigated. Therefore, we studied in a model of syngeneic liver transplantation in the rat the effect of recipient enalapril treatment on postischemic liver injury. Untreated animals served as the control group. Treatment with enalapril was started 5 minutes before reperfusion by intravenous infusion of enalapril at a dosage of 5 mg/kg/h. By means of in vivo microscopy, the sinusoidal perfusion rate and leukocyte adherence in sinusoids and postsinusoidal venules were analyzed during 45 to 60 minutes of reperfusion. Liver function was monitored by measuring bile output over a period of 60 minutes. Analysis of coagulation factors (prothrombin time, factor V, fibrinogen) and liver enzymes (alanine transaminase [ALT], aspartate transaminase [AST]) served for the evaluation of organ dysfunction and damage secondary to ischemia/reperfusion injury. The sinusoidal perfusion rate was significantly improved by enalapril treatment (94.7% [1.0] vs. 75.3% [3.8]; mean [SEM]; P = .005). In addition, leukocyte-sticking in both liver sinusoids and postsinusoidal venules was remarkably reduced in enalapril-treated animals as compared with controls (stickers/lobule: 21.0 [3.3] vs. 59.2 [2.1]; P = .0004; stickers/mm2 venular surface: 20.5 [4.7] vs. 110.3 [18.1]; P = .0004). Moreover, bile output was increased (1.13 [0.35] vs. 0.43 [0.18] g bile/60 min x 100 g liver; P = .06). Values for PT (22.5% [2.1] vs. 9.7% [1.8]; P = .005), factor V 99.4% [9.5] vs. 49.5% [8.5]; P = .007), and fibrinogen (64.1% [7.7] vs. 12.8% [3.2]; P = .001) were significantly improved, paralleled by a remarkable reduction in serum ALT (1,428 U/L [190] vs. 2,315 [248]; P = .02). Our data show for the first time that ACE inhibition in the liver recipient by enalapril attenuates hepatic ischemia/reperfusion damage after experimental liver transplantation. Our results may offer a novel approach to reduce ischemia/reperfusion injury in clinical liver transplantation.

Angiotensin-Converting Enzyme Inhibitors↗

Prenatal diagnosis and management of neonatal alloimmune thrombocytopenia.

Neonatal alloimmune thrombocytopenia (NAIT) is an uncommon (1 in 2,000 livebirths) but serious disorder characterized by marked thrombocytopenia in the fetus and neonate. Platelet destruction is caused by a maternal antibody directed against a fetal platelet antigen inherited from the father and lacking in the mother's platelets. Intracranial hemorrhage (ICH) is the most devastating complication of NAIT, affecting approximately 20% of all proven cases, up to 50% of which occur antenatally. Because close to 100% of subsequent pregnancies will be equally or more severely affected, antenatal management directed at preventing ICH in utero has assumed great clinical importance. In recent years, considerable progress has been made in this regard, and although clinical uncertainties still exist, the natural history of this disease and its response to various antenatal interventions have become reasonably well understood. This review will focus on the diagnosis and current management of NAIT, including controversies surrounding current treatment modalities and future prospects for treatment and prevention.

Blood Platelets↗

Conditioning of liver grafts by donor bolus pretreatment with epoprostenol.

Despite improved preservation methods, graft dysfunction after liver transplantation continues to contribute considerably to postoperative morbidity and mortality. In clinical and experimental studies prostaglandin (PG)I2 analogs proved effective in the treatment of liver damage of different origin. Using in vivo fluorescence microscopy in a rat liver transplantation model, we studied the effect of donor bolus pretreatment with the PGI2 analog epoprostenol on hepatic graft revascularization. After epoprostenol bolus pretreatment (group 1: liver transplantation/PGI2), perfusion of liver sinusoids after reperfusion was significantly improved as compared with untreated donor livers (group 2: liver transplantation (95.2+/-0.6% vs. 75.3+/-3.8%, mean +/- SEM; P=0.001) and epoprostenol was found almost in the range of that in normal nontransplanted livers (99.4+/-0.2%). In addition, leukocyte adherence in liver lobules (21.0+/-3.5 vs. 115+/-11.5 n/lobule; P=0.001) and postsinusoidal venules (23.0+/-3.8 vs. 113+/-11.3 n/mm2 endothelial surface; P=0.002) was significantly reduced in the pretreated grafts. Bile production in the recipient was significantly increased by epoprostenol pretreatment of the donor (1.88+/-0.4 vs. 0.63+/-0.13 g/100 g liver*1 hr; P=0.015), indicating restored liver function. These results suggest that the prostacyclin analog epoprostenol is effective in preconditioning the graft prior to transplantation, i.e., improving preservation and increasing graft resistance to ischemia/reperfusion injury. Thus, favorable effects on early graft function after clinical liver transplantation may be achieved by introducing epoprostenol pretreatment into the harvesting procedure.

Animals↗

Impact of enalapril on microvascular perfusion and leukocyte adherence in a model of rat liver transplantation assessed by in vivo microscopy.

ACE inhibitors have been proven to be effective in the reduction of ischemia/reperfusion damage after myocardial ischemia. In an attempt to investigate this effect in a model of syngeneic liver transplantation in the rat, we compared a control group with an ACE inhibitor treatment group, in which enalapril was given i.v. before and during reperfusion. By means of in vivo microscopy, sinusoidal perfusion rate, permanent leukocyte sticking in sinusoids and postsinusoidal venules, and leukocyte rolling in postsinusoidal venules were assessed. Liver function was evaluated by measuring bile output. The sinusoidal perfusion rate was significantly improved by enalapril treatment. Leukocyte sticking in both sinusoids and postsinusoidal venules was found to be remarkably reduced in enalapril-treated animals; the fraction of rolling leukocytes remained unchanged. Bile output was increased in enalapril-treated animals. These results demonstrated, in a model of rat liver transplantation, that ACE inhibition by enalapril is effective in reducing hepatic ischemia/reperfusion damage as assessed by the leukocyte-endothelium interaction using in vivo microscopy and postreperfusion bile production.

Angiotensin-Converting Enzyme Inhibitors↗

Participation of NMDA and non-NMDA excitatory amino acid receptors in the mediation of spinal reflex potentials in rats: an in vivo study.

1. The effect of various intravenously administered excitatory amino acid (EAA) antagonists on the dorsal root stimulation-evoked, short latency (up to 10 ms) spinal root reflex potentials of chloralose-urethane anaesthetized C1 spinal rats was studied, in order to gain information on the involvement of non-NMDA (AMPA/kainate; AMPA = alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) and NMDA (N-methyl-D-aspartate) receptors in their mediation. The competitive non-NMDA antagonist, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX; 1-32 mg kg-1), the non-competitive non-NMDA antagonist, 1-(amino)phenyl-4-methyl-7,8-methylendioxy-5H-2,3-benzodiazepine (GYKI 52466; 0.5-8 mg kg-1), the competitive NMDA antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP, 2-8 mg kg-1) and two non-competitive NMDA antagonists: MK-801 (0.5-2 mg kg-1) and ketamine (2-32 mg kg-1) were used as pharmacological tools. 2. Validating the applied pharmacological tools regarding selectivity at the applied doses, their effects were tested on direct (electrical) as well as on synaptic excitability of motoneurones evoked by intraspinal stimulation. Furthermore, their effect was investigated on the responses elicited by microiontophoretic application of EAA agonists (AMPA, kainate and NMDA) into the motoneurone pool, where the extracellular field potential evoked by antidromic stimulation of the ventral root was recorded to detect the effects of EAA agonists. 3. NBQX and GYKI 52466 were able to abolish completely the mono-, di- and polysynaptic ventral root reflexes (MSR, DSR, PSR) and the synaptic excitability of motoneurones, while hardly influencing direct excitability of motoneurones. They markedly attenuated AMPA and kainate responses whilst having little or no effect on NMDA responses. 4. Apparently 'supramaximal' doses of CPP and MK-801 slightly inhibited MSR (by about 10%) moderately reduced DSR and PSR (by about 20-30%) and did not influence excitability of motoneurones. They selectively blocked responses to NMDA. 5. Ketamine dose-dependently inhibited MSR, DSR and PSR. Nevertheless, diminution of none of the responses exceeded 50%. It reduced both direct and synaptic excitability of motoneurones, thus displaying a local anaesthetic-like effect, which may contribute to its reflex inhibitory action. It depressed responses to NMDA whilst having negligible effects on responses to AMPA and kainate. 6. We conclude that non-NMDA receptors play a substantial role in the mediation of MSR, DSR and PSR, while NMDA receptors contribute little to this. Neither MSR nor PSR is mediated exclusively by non-NMDA or NMDA receptors, respectively. 7. The drugs investigated in this study, with the exception of ketamine, proved to be useful tools for elucidation of the involvement of EAA receptors in various processes in vivo Keywords: Glutamate receptors; AMPA; kainate; NMDA; NBQX; GYKI 52466; CPP; MK-801; spinal reflex; spinal cord

Animals↗

White cell depletion of red cell and pooled random-donor platelet concentrates by filtration and residual lymphocyte subset analysis.

This study comparing the relative white cell (WBC)-depleting efficiency of single and double filtration used two filters and new, sensitive, and reliable methods for performing WBC counts on WBC-depleted blood products. A single filtration of red cell (RBC) concentrates with a cotton-wool filter reduced WBC content by 98.64 percent, but the range of residual WBCs was wide, and many filtered units still contained more than the theoretical immunizing dose of 5 to 10 x 10(6) WBCs. A second filtration, however, always produced RBC units that had less than 5 x 10(6) WBCs. Although the degree of WBC depletion observed after a single filtration of a 6-unit pool of random-donor platelet concentrates was greater with a polyester filter than with the cotton-wool filter (98.92 vs. 98.14% reduction, respectively, when mean prefiltration WBC count was less than 600 x 10(6], in both cases, 25 percent of filtered products still contained greater than 5 x 10(6) WBCs; a second filtration (with the cotton-wool filter), however, produced units that were always below the immunizing dose. All double-filtered platelet concentrates had less than 10(6), and one-half had less than 10(4) residual WBCs. Platelet loss was similar with both filters (+/- 16% loss with one filtration). The effectiveness of the filters in producing products that were WBC-depleted below the immunizing dose was dependent on the prefiltration WBC content (but not on the age of the units), and it may be worthwhile to employ methods to ensure that total prefiltration WBC count of the product is less than 400 x 10(6).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Electrophysiological studies with a 2,3-benzodiazepine muscle relaxant: GYKI 52466.

The effects of GYKI 52466, a new 2,3-benzodiazepine with muscle relaxant and anticonvulsant properties, were investigated and compared to those of midazolam in electrophysiological experiments. The effects of the drugs on the reflex potentials evoked by afferent nerve stimulation and recorded from the spinal roots in unanesthetized spinal cats were studied. GYKI 52466 exerted a strong inhibitory effect on the monosynaptic as well as the polysynaptic ventral root reflexes, while the dorsal root responses decreased slightly. In contrast, midazolam markedly enhanced the dorsal root responses, did not modify the monosynaptic reflex and partially inhibited the polysynaptic reflex. The spontaneous firing of cerebellar Purkinje cells was depressed by midazolam, but not by GYKI 52466. These results suggest strongly that, contrary to the classical 1,4-benzodiazepines, potentiation of the GABA-A receptor-mediated inhibition does not play a significant role in the pharmacological actions of GYKI 52466.

Animals↗

Effects of some centrally acting muscle relaxants on spinal root potentials: a comparative study.

The effects of intravenously administered mephenesin, tolperisone, baclofen, diazepam and midazolam on reflex activity were studied in unanesthetized spinal cats. Monosynaptic, as well as polysynaptic ventral root reflexes, the dorsal root potential and the dorsal root reflex were recorded simultaneously from L6-S1 segments. An analogue integrating method was developed for quantitative monitoring and recording ipsilateral spinal root potentials evoked by stimulation of the tibial nerve. Mephenesin (12.5-50 mg/kg) caused a significant and dose-dependent reduction in the polysynaptic and the dorsal root reflexes, slightly decreased the dorsal root potential but minimally affected the monosynaptic ventral root reflex. Tolperisone (2.5-10 mg/kg) dose-dependently inhibited both ventral root reflexes and the dorsal root reflex. It slightly prolonged the dorsal root potential without affecting the amplitude. Baclofen (0.5 mg/kg) abolished the monosynaptic reflex, partially inhibited the polysynaptic reflex, while dorsal root responses were less attenuated. Both benzodiazepines exerted similar actions, both qualitatively as well as quantitatively: the polysynaptic reflex was partially reduced while the monosynaptic reflex was not modified by diazepam or midazolam. Dorsal root responses were enhanced and the half-time of decay of the dorsal root potential was prolonged. Different patterns of action of muscle relaxants studied here are discussed in terms of their possible mechanisms of action. Profound depressant effects of mephenesin and tolperisone on the dorsal root reflex are in contrast to the small effect of both drugs on the dorsal root potential and might reflect their inhibition of spike-generating mechanisms. For a yet unknown reason, various spinal pathways are affected differentially by baclofen. In spinal cats, the reduction by benzodiazepines of the polysynaptic reflex may be related to the potentiation of some unidentified GABA-ergic inhibitory processes. The use of water-soluble midazolam, as a model compound instead of diazepam, is suggested because the usual organic solvents for diazepam may affect its action.

Animals↗