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Biomedical subjects

E Levin

Publications and source records attributed to E Levin.

At least 55 records · Page 3Linked to original sources
PubMed1994

Use of ampicillin/sulbactam versus imipenem/cilastatin in the treatment of limb-threatening foot infections in diabetic patients.

In a double-blind randomized trial, imipenem/cilastatin (I/C; 500 mg every 6 hours) and ampicillin/sulbactam (A/S; 3 g every 6 hours) were compared in regard to their efficacy for initial empirical and definitive parenteral treatment of limb-threatening pedal infection in diabetic patients. The major endpoints of treatment were cure (resolution of soft-tissue infection), failure (inadequate improvement, necessitating a change in antibiotic therapy), and eradication (clearance of all pathogens from the wound and any bone cultures). Patients in the two treatment groups were similar in regard to the severity of diabetes; presence of neuropathy and peripheral vascular disease; site and severity of infection; pathogen isolated; and frequency of osteomyelitis (associated with 68% of the 48 A/S-treated infections and 56% of the 48 I/C-treated infections). After 5 days of empirical treatment, improvement was noted in 94% of the A/S and 98% of the I/C recipients. At the end of definitive treatment (days' duration [mean +/- SD]: 13 +/- 6.5 [A/S], 14.8 +/- 8.6 [I/C]), outcomes were similar: cure, 81% (A/S) vs. 85% (I/C); failure, 17% (A/S) vs. 13% (I/C); and eradication, 67% (A/S) vs. 75% (I/C). Treatment failures were associated with the presence of antibiotic-resistant pathogens and possible nosocomial acquisition of infections. The number of adverse events among patients in the two treatment groups was similar: 7 in the A/S group (4 had diarrhea and 3 had rash) and 9 in the I/C group (5 had diarrhea, 2 had severe nausea, 1 had rash, and 1 had seizure). Efficacy of A/S and I/C is similar for initial empirical and definitive treatment of limb-threatening pedal infection in patients with diabetes.

Adult↗
PubMed1994

[Transcription factors and proliferative diversity of neoplastic cells].

Cancer is a multistage process with sequential steps: initiation, promotion, progression. However, the distinction between the agents that can trigger any of these processes is less clear, depending on doses, biological stage of the tissue, molecular interactions, genomic and somatic mutation, etc. Thus, steroid receptors, classically considered as promoters, could be acting as initiators under different alterations. On the other hand, chemical carcinogens that can produce DNA damage leading to cellular transformation, in lower dosage are able to alter nuclear proteins which in turn favor the action of other agents triggering the initiation process. Transcription factors (TF) are nuclear proteins with particular structural configurations for their interaction with DNA. There are families of TF with specificity for certain nucleotide sequences called "response elements". The association TF-DNA response elements modulate the genomic transcription and synthesis of proteins, many of which are related to cellular proliferation. The transcriptional message can also be influenced by TF protein-protein interactions, besides their association with the response elements. This "cross-talk" or "side regulation" becomes an important genomic regulatory mechanism. Certain biochemical signals acting on particular proteins (receptors, enzymes) can then trigger biological effects attributable to other proteins. Another transcriptional regulatory mechanism is the cytoplasm-nucleus shuttling of TF according to the cellular replication rhythm and other metabolic cellular requirements. These recent advances open new vistas for the pharmacological attack to the proliferative diversity of neoplastic cells.

Animals↗
PubMed1993

A shared pathway in atrioventricular nodal reentrant tachycardia and atrial flutter: implications for pathophysiology and therapy.

Atrioventricular (AV) nodal reentrant tachycardia and atrial flutter are considered 2 distinct supraventricular tachycardias. Recent clinical and experimental data suggest that both these tachycardias include an area in the lower right atrial septum in their reentrant pathways. This study was designed to test the hypothesis that there is an association between the mechanisms of AV nodal reentrant tachycardia and atrial flutter because of a shared pathway of reentry. Consecutive patients referred for evaluation and management of supraventricular tachycardia, thought to be due to AV nodal reentry, underwent electrophysiologic testing protocols designed to induce both AV nodal reentrant tachycardia and atrial flutter, if present. Fifteen of 29 patients (52%) had both AV nodal reentrant tachycardia and atrial flutter induced during electrophysiologic testing. Seven of these 15 patients (47%) underwent transcatheter radiofrequency current application (mean power 34 +/- 4 W) against the tricuspid annulus above the coronary sinus. In each patient, neither AV nodal reentrant tachycardia nor atrial flutter could be induced after the procedure. Repeat study after successful ablation (mean 6 days) showed no inducible supraventricular arrhythmia of either type at baseline study or during isoproterenol infusion. Atrial flutter occurs frequently (15 of 29 patients; 52%) in patients with AV nodal reentrant tachycardia, because of a shared pathway in their reentry circuits. Because of this shared pathway, both arrhythmias can be ablated at the same site. These observations promote new insights into the mechanism and therapeutics of supraventricular tachycardias.

Adult↗
PubMed1993

Anticoagulant activity of Hirulog, a direct thrombin inhibitor, in humans.

Hirulog (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095-101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers. In a randomized, placebo-controlled study (n = .54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 l kg-1 h-1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p < 0.001) and subcutaneous administration (r = 0.7, p = 0.002). To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide's activity. At the administered dose of 0.6 mg kg-1 h-1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Characterization of rat uterine estrogen receptors in vivo.

In vivo binding of [3H]estradiol ([3H]E2) in the rat uterus was performed by an intraluminal perfusion of the ligand for different time periods. In this way the binding takes place in the intact organ before processing the tissue. In 10 min, with 10 nM [3H]E2 apparent saturation or steady state incorporation of the [3H]E2 was achieved with a similar distribution of the label between cytosol and nuclear fractions. In vitro, the subcellular localization of the estrogen receptor (ER) is influenced by the extent of tissue damage. With the intact organ the ER subcellular distribution approaches that of the in vivo perfusion. With increasing [3H]E2 in the perfusate it was possible to obtain a "saturation" curve and to derive the kinetic parameters. For cytosol: Kd 16 nM; Bmax 235 fmol/mg prot. For nucleus: Kd 2.7 nM; Bmax 103 fmol/mg prot. To follow the time course of the ER movement in vivo, "pulse and wait" experiments were designed. Both uterine horns were perfused for 1 min. One of the horns was immediately processed (0 time) and the other was left in place after the perfusion for different periods. At 0 time 90% of the bound label appeared in the cytosol. At 5, 15 and 30 min, the label in the cytosol decreased and that of the nucleus increased approx. to 50%. Thus, translocation of the bound label from cytosol to nucleus was apparent. The role of the cytoplasm-nucleus ER traffic in the regulation of gene transcription by estrogens is discussed.

Animals↗
PubMed1991

The Norwegian, Danish and Dutch version of the Appraisal of Self-care Agency Scale; comparing reliability aspects.

This study was designed to test reliability aspects of a scale that was developed to measure the theoretical concept of self-care agency (Orem 1985). Equivalence and internal consistency of the scale were studied with populations of elderly patients and their nurses in The Netherlands, Norway and Denmark. Data was provided by 120 patients and 233 nurses. Not all criteria for reliability could be met for the Danish and the Norwegian versions of the scale. Nevertheless it is concluded that the results are indications for the reliability of the Dutch, as well as the Danish and Norwegian versions of the scale.

Denmark↗
PubMed1991

Brain and atrial natriuretic peptides bind to common receptors in brain capillary endothelial cells.

The recent discovery of brain natriuretic peptides (BNP) that stimulates natriuresis, diuresis, and vascular smooth muscle relaxation in a manner similar to that of atrial natriuretic peptide (ANP) suggests the possibility that these endocrine hormones function via some common mechanism. Indirect evidence from several laboratories suggests that BNP and ANP may bind to the same receptors. We examined whether ANP and BNP bind to a common set of receptors in cultured bovine brain capillary endothelial cells and in bovine aortic endothelial cells. Scatchard plot analysis of binding data shows a similar dissociation constant (KD) of approximately 0.3 nM and a maximal binding capacity (Bmax) of 50 fmol/mg protein for both natriuretic peptides in brain capillary cells and 0.6 nM and 80 fmol/mg protein, respectively, in the aortic endothelial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the affinity cross-linked receptor-ligand complex shows a strongly labeled 65-kDa receptor and a 125-kDa band that is likely to be a receptor of the guanylate cyclase type. ANP and BNP cross compete equally for binding to the two receptors identified on the gels. ANP and BNP also stimulate guanosine 3', 5'-cyclic monophosphate production in these cells, consistent with the presence of a functional guanylate cyclase-linked B receptor. We conclude that ANP and BNP share common receptors in brain capillary and aortic endothelial cells.

Animals↗
PubMed1990

Displacement by tamoxifen of the estradiol-estrogen receptor binding: a functional assay for breast cancer studies.

Displacement curves with estradiol (E2) and Tamoxifen (Tam) of the [3H]E2-ER binding in 49 ER+ mammary neoplasia showed a great heterogeneity suggesting the existence of more than one population of ER+ tumors when the relative binding affinity of both ligands for the ER was considered. The (D50E2/D50Tam) x 100 ratio was called Displacement Index (DI) with values asymmetrically distributed from 0.05 to 2.90. The range from 0.18 to 0.54 was adopted as central interval given by the median +/- SE (median: 0.36; SE: 0.09). DI values below 0.18 (24% of the tumors in our series) were considered as "lower", indicating that higher Tam doses would be necessary to displace the E2-ER binding. The potency of Tam as displacer is dependent not only of its own affinity for the ER, but also of that of E2 for the same receptor. The DI expresses their relative binding "strength". DI values were not correlated with ER and progesterone receptor content nor with the D50 Tam and D50E2 taken separately. Antiestrogen binding sites (AEBS) were determined in the cytosol (AEBSc) and in the microsomal fraction of 10 ER+ tumors from our series. The AEBSc/ER ratio was inversely correlated with the DI, that is, displacement of 3HE2 from the E2-ER complex by Tam would be lower in tumors with higher AEBSc/ER ratio. The DI is another parameter to be considered in the study of the sensitivity of breast neoplasias to antiestrogen treatments.

Breast Neoplasms↗
PubMed1989

Effect of antineoplastic drugs and estradiol on leucine uptake and proliferation of Ehrlich tumor cells.

Antineoplastic drugs (methotrexate, 5-fluorouracil, adriamycin) arrest the proliferation of Ehrlich ascites tumor cells in mice but have no influence on L-leucine uptake in vitro. Tamoxifen does not influence either process. Estradiol increases both the cellular proliferation and the amino acid uptake. The absence of estrogen receptors in the cells indicates that the hormone acts on cellular proliferation through mechanisms other than activation of DNA replication, such as stimulation of amino acid transport.

Animals↗
PubMed1988

Hydrolysis of 3H-bambuterol, a carbamate prodrug of terbutaline, in blood from humans and laboratory animals in vitro.

Tritiated bambuterol, a bis-dimethylcarbamate prodrug of terbutaline, was incubated in vitro with blood from both sexes of the following species: man, guinea pig, rat, mouse, dog and rabbit. The rates of hydrolysis of bambuterol to its monocarbamate derivative and further to terbutaline were measured. Large species variations were observed, e.g. blood from two of the human subjects was 15-fold more active than blood from the male rats. The rate of terbutaline formation as a function of initial bambuterol concentration was investigated in human plasma, and was found to describe a bell-shaped curve. Several pieces of evidence indicated that butyrylcholinesterase (EC 3.1.1.8) is the blood enzyme predominantly responsible for hydrolysis of bambuterol, although minor contributions from other esterases cannot be excluded. An exception may be blood from the rabbit, where the kinetics of the hydrolysis was different than in blood from the other species. The kinetics of bambuterol hydrolysis is discussed on basis of the established mechanism of carbamate interactions with cholinesterases, and the high affinity of bambuterol for butyrylcholinesterase.

Adult↗
PubMed1988

Chronic neuroleptics alter the effects of the D1 agonist SK&F 38393 and the D2 agonist LY171555 on oral movements in rats.

Vacuous oral movements (OMs) in rats chronically administered haloperidol (HAL), fluphenazine (FLU), or no drug were studied following injections of one of three doses of either a D1 agonist (SK&F 38393) or a D2 agonist (LY171555). Oral movements were observed via closed-circuit television and simultaneously recorded using a computerized video analysis system which measured the distance between two fluorescent dots painted above and below the rat's mouth. SK&F 38393 induced a dose-dependent increase in tremorous oral movements and repetitive chewing movements in the controls; this effect was more pronounced in rats treated with chronic HAL or FLU, both during chronic neuroleptic treatment and even more so when they were tested after drug withdrawal following 5 or 14 months of chronic neuroleptic administration. Conversely, LY171555 produced an inhibition of oral activity at all dose levels in controls. This inhibition was attenuated during chronic administration of HAL or FLU, but returned to control levels (without any signs of supersensitivity) when the animals were retested shortly after discontinuation of neuroleptics. These results indicate that heightened oral movements in rodents following chronic neuroleptic administration can be more clearly induced by D1 than by D2 receptor activation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Opposite effects of a D1 and a D2 agonist on oral movements in rats.

Oral movements in rats administered one of three doses of either a D1 agonist (SK&F 38393) or a D2 agonist (LY171555) were observed via closed-circuit television and simultaneously recorded using a computerized video analysis system which measured the distance between two fluorescent dots painted above and below the rat's mouth. The D1 agonist SK&F 38393 induced a dose-dependent increase in tremorous oral movements, tongue protrusions, and, at the highest dose, increased repetitive chewing movements. Conversely, the D2 agonist LY171555 produced an inhibition or oral activity at all dose levels. At the lowest dose tested this appeared to reflect a non-specific decrease in activity, for there was an inhibition of all categories of behavior measured, as well as of all amplitudes of computer-scored movements and slow, sluggish movements were recorded. But higher doses of LY171555 induced hyperactivity and stereotyped, repetitive head movements whereas chewing movements, tremorous oral movements, and tongue protrusions were still decreased. D1 and D2 dopamine receptors appear to have opposite effects on oral movements.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Tremorous mouth movements in rats administered chronic neuroleptics.

Oral movements (OMs) in rats administered chronic haloperidol (HAL) were quantified simultaneously by a human observer and via a computerized video analysis system which monitored the distance between the upper and low lips using TV images. The human observer data indicated that during HAL administration the total duration of OMs was initially decreased, gradually returned to levels slightly above controls, and then increased substantially upon drug withdrawal. The computer records confirmed these findings and further indicated that after prolonged HAL administration a syndrome developed in which large-amplitude OMs remained suppressed but OMs of the smallest detectable amplitudes increased. Upon drug withdrawal, these small OMs increased in amplitude and rhythmicity, developing into repetitive tremors.

Animals↗