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Biomedical subjects

N Friedmann

Publications and source records attributed to N Friedmann.

At least 19 recordsLinked to original sources
PubMed2001

Agrammatism and the psychological reality of the syntactic tree.

Syntactic trees, or phrase markers, have originally been suggested as a representation of syntax in the mind based on purely linguistic grounds. In this paper, the psychological reality of syntactic trees and hierarchical ordering is explored from another perspective--that of the neuropsychology of language breakdown. The study reported here examined several syntactic domains that rely on different nodes in the tree--tense and agreement verb inflection, subordinations, interrogatives, and verb movement, through a study of 14 Hebrew- and Palestinian Arabic-speaking agrammatic aphasics and perusal of the cross-linguistic literature. The results show that the impairment in agrammatic production is highly selective and lends itself to characterization in terms of a deficit in the syntactic tree. The complex pattern of dissociations follows from one underlying deficit--the inaccessibility of high nodes of the syntactic tree to agrammatic speakers. Structures that relate to high nodes of the tree are impaired, while "lower" structures are spared.

Aphasia, Broca↗
PubMed1997

Tense and agreement in agrammatic production: pruning the syntactic tree.

This paper discusses the description of agrammatic production focusing on the verbal inflectional morphology. Agrammatism in Hebrew is investigated through an experiment with a patient who displays a highly selective impairment: agreement inflection is completely intact, but tense inflection, use of copula, and embedded structures are severely impaired. A retrospective examination of the literature shows that our findings are corroborated by others. A selective account of the agrammatic production deficiency is proposed, according to which only a subclass of the functional syntactic categories is impaired in this syndrome. The consequence of this deficit is the pruning of the syntactic phrase marker of agrammatic patients, which impairs performance from the impaired node and higher. These findings also bear upon central issues in linguistic theories, particularly that of Pollock (1989), regarding split inflection.

Aged↗
PubMed1996

Evaluation of a CD5-specific immunotoxin for treatment of acute graft-versus-host disease after allogeneic marrow transplantation.

Acute graft-versus-host disease (GVHD) is most often treated with high dose glucocorticoids, but less than half of patients have durable overall improvement. Previous phase I and phase II studies suggested that treatment with a CD5-specific immunotoxin (XomaZyme-CD5 Plus) could ameliorate symptoms of GVHD. In a randomized, double-blind trial, we compared XomaZyme-CD5 Plus and glucocorticoids versus placebo and glucocorticoids as initial therapy for 243 patients who developed acute GVHD after allogeneic marrow transplantation. The study drug (XomaZyme. CD5-Plus or an identical appearing placebo) was administered at a dose of 0.1 mg/kg body weight on each of 14 consecutive days. All patients were treated concomitantly with a standard regimen of methylprednisolone. At the time of entry on study, 94% of patients had a rash, 56% had hyperbilirubinemia, 61% had diarrhea, and 84% had nausea and vomiting. At 3, 4, and 5 weeks after starting treatment, symptom severity was less in the CD5 group than in the placebo group. At 4 weeks, 40% of patients assigned to the CD5 group had complete response compared with 25% of those assigned to the control group (P = .019). At 6 weeks, 44% of patients assigned to the CD5 group had complete response as compared with 38% in the placebo group (P = .36). Clinical extensive chronic GVHD developed in 65% of patients in the CD5 group compared with 72% in the control group (P = .35). Survival at 1 year after treatment was 49% in the CD5 group and 45% in the control group (P = .68). Side effects required close monitoring and appropriate adjustment of treatment. The combined administration of a CD5-specific immunotoxin and glucocorticoids controls GVHD manifestations more effectively than treatment with glucocorticoids alone during the first 5 weeks after starting treatment. Use of this immunotoxin does not result in any long-term clinical benefit for patients with acute GVHD.

Acute Disease↗
PubMed1996

A phase I safety and pharmacokinetic study of a recombinant amino terminal fragment of bactericidal/permeability-increasing protein in healthy male volunteers.

A phase I pharmacokinetic and safety clinical trial of rBPI23, a recombinant amino terminal fragment of bactericidal/permeability-increasing protein, was conducted in healthy male volunteers. rBPI23 was administered as a 5 or 30 min infusion at doses of .1 to 1 mg/kg. The pharmacokinetics of rBPI23 in human subjects were described by a bi-exponential disposition function with evidence of concentration-dependent kinetics. The alpha half-life increased significantly with increasing dose, from 4-5 min at .1 mg/kg to 7-8 min at 1 mg/kg. The beta half-life varied between 18 and 29 min regardless of dose and the clearance varied from 5 to 10 mL/min/kg. Very little, if any, of the administered rBPI23 was excreted intact in the urine. Electrocardiograms, ionized calcium concentration, prothrombin and partial prothrombin times, hematologic parameters, and blood chemistries remained normal. Furthermore, no antibody response to rBPI23 was observed in any of the subjects.

Adolescent↗
PubMed1995

Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23).

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo-controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.

Anticoagulants↗
PubMed1995

Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein.

To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature. The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1-antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23. The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans.

Antimicrobial Cationic Peptides↗
PubMed1995

Recombinant endotoxin-binding protein (rBPI23) attenuates endotoxin-induced circulatory changes in humans.

In the present study the protective effect of a recombinant endotoxin-binding protein rBPI23 on the circulatory changes in experimental endotoxemia in humans was investigated. In a controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg body weight), and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). Hemodynamic parameters were obtained non-invasively by means of M-mode, two-dimensional, and Doppler echocardiography. rBPI23 significantly reduced indices of the endotoxin-induced hyperdynamic circulation. rBPI23 treatment significantly reduced increase in cardiac index (P = 0.0156). rBPI23 treatment diminished the endotoxin-induced decrease in systemic vascular resistance index (P = 0.0304). rBPI23 did not prevent the endotoxin-induced rise in body temperature and systolic, diastolic and mean arterial pressure were not significantly different in the rBPI23- and placebo-treatment arm. Both treatment periods showed a small reduction in end diastolic and end systolic volumes. rBPI23 treatment slightly reduced the increase in M-mode ejection fraction and fractional shortening. These results indicate that rBPI23 is capable of attenuating the potentially deleterious circulatory effects of endotoxin in humans.

Adult↗
PubMed1985

Thymopentin: safety overview.

This paper reviews all available data on thymopentin derived from the extensive preclinical safety program; most of those studies have been concluded, only the carcinogenicity studies are nearing completion. The overview also compiles the safety parameters generated from patients treated with thymopentin for different clinical conditions; in some cases treatment lasted for 12-24 months (56 patients). Different doses and modes of administration were used. The percentage of patients with side effects was comparable to the incidences in the placebo groups. Thymopentin was also well tolerated when administered concomitantly with a long list of drugs given for other reasons. The overall conclusion in that thymopentin is a safe compound.

Animals↗
PubMed1981

Effect on growth in pemoline-treated children with attention deficit disorder.

The growth of 22 children with attention deficit disorder (ADD) was monitored longitudinally for up to four years. Each child received at least one year of continuous, successful pemoline (Cylert) therapy, after which drug "vacations" were allowed. The effective dosage of pemoline ranged from 56 to 150 mg/day during the first year of treatment. Stature and weight measurements at six-month intervals were matched to those of paired "normal" children from the Fels Longitudinal Study. Significant deficits were observed for mean weight change at six and 12 months after baseline, and for mean stature change at 12 and 18 months after baseline. However, all subsequent six-month results up to four years did not differ significantly between the two groups. These results show a temporary retardation in the rate of growth in weight and stature with later catch-up growth in children treated wih pemoline.

Adolescent↗
PubMed1980

Characterization of the hormone-sensitive Ca2+ uptake activity of the hepatic endoplasmic reticulum.

The characteristics and kinetics of calcium uptake activity were studied in isolated hepatic microsomes. The sustained accumulation of calcium was ATP- and oxalate-dependent. Glucagon increased microsomal Ca2+ uptake upon either in vivo injection, or in vitro perfusion of the hormone in the liver. In contrast, the effect of insulin depended on the route of administration. Calcium accumulation by subsequently isolated hepatic microsomes increased when insulin was injected intraperitoneally whereas it decreased when the hormone was perfused directly into the liver. These effects of glucagon and insulin were dose dependent. When insulin was added to the perfusate prior to the addition of glucagon, insulin blocked the glucagon-stimulated increase in microsomal Ca2+ uptake. Cyclic AMP mimicked the effect of glucagon on microsomal Ca2+ accumulation when the cyclic nucleotide was perfused into the liver. The effects of glucagon and insulin on the kinetics of hepatic microsomal Ca2+ uptake were investigated. In microsomes isolated from perfused rat livers treated with glucagon the V of the uptake was significantly increased over the control values (12.2 vs. 8.6 nmol Ca2+ per min per mg protein, P less than 0.02). In contrast, the addition of insulin to the perfusate significantly decreased the V of Ca2+ uptake by subsequently isolated microsomes (6.8 vs. 8.3 nmol Ca2+ per min per mg protein, P less than 0.05). However, neither hormone had an effect on the apparent Km for Ca2+ (4.1 +/- 0.5 microM) of the reaction. The effect of these hormones on the activity of Ca2+-stimulated ATPase was also studied. No significant changes in either V or Km for Ca2+ of the enzymatic reaction were detected.

Adenosine Triphosphatases↗
PubMed1980

Antagonistic effect of insulin on glucagon-evoked hyperpolarization. A correlation between changes in membrane potential and gluconeogenesis.

In the perfused rat liver, administration of glucagon causes a hyperpolarization of the liver cell membrane and increases gluconeogenesis. Insulin, a hormone which is known to antagonize the effect of glucagon on gluconeogenesis also blocks the hyperpolarizing effect of glucagon. Because of this inhibitory effect of insulin of the glucagon-evoked hyperpolarization, a systematic study of possible correlation between changes in membrane potential and gluconeogenesis was undertaken. The membrane potential was changed by valinomycin, tetracaine, or by varying the ionic composition of the perfusate. A highly significant correlation between changes in membrane potential and the rate of gluconeogenesis was noticed. The possibility was raised that changes in membrane potential might exert an influence on metabolic process by a yet unknown mechanism.

Animals↗
PubMed1980

Bioavailability of valproic acid under fasting/nonfasting regimens.

Valporic acid absorption was faster from a syrup than from a capsule form. Peak serum levels occurred with an hour with the syrup formulation. The drug was absorbed more rapidly when administered fasting and immediately before meal compared with immediately after meal. The extent of absorption from each formulation and for each meal regimen was similar. Pharmacokinetic evaluation of the data indicate a serum half-life of 12 hours.

Adult↗