Two pathways of signal transduction are activated in the same cell by different cytokines.

NFS60, a murine leukemia cell line, responds to both interleukin 3 and 6 by proliferating, apparently by different signal transduction pathways. Although stimulation by both cytokines increases the uptake of 3H-arachidonic acid, the response to IL-6 was much faster. Furthermore, the effect of various arachidonic acid metabolites on the response to cytokine was different. PGE2 inhibited IL-6-induced proliferation and potentiated the response to IL-3. Additionally the G proteins which coupled the IL-3 and IL-6 receptor to the proliferative response are probably different, based on the ability of cholera toxin to inhibit the IL-3 but not the IL-6 response. These data are evidence of two pathways of signal transduction.     

Intracanalicular arachnoid cyst mimicking acoustic neuroma: CT and MRI.

A patient with a surgically proven intracanalicular arachnoid cyst was studied using computed tomography, magnetic resonance imaging, and air CT cisternography. The lesion had a similar radiographic appearance to acoustic neuroma and therefore, although rare, must be considered in the differential diagnosis of intracanalicular mass lesions. We report a case in which examination was performed, in evaluating the lesion, utilizing high-resolution air CT cisternography and magnetic resonance imaging (MRI).     

Is a learning curve for arterial switch operation in small countries still acceptable? Model for cooperation in Europe.

OBJECTIVES: To assess the results of a cooperative arrangement between Slovakia and Slovenia for neonatal cardiac surgery. The aim of the study was to analyze the performance of this approach for complete transposition of the great arteries (D-TGA). METHODS: Due to the overall small number of new patients with D-TGA in Slovenia a decision was made to avoid a prolonged learning curve by centralizing the experience of two countries at one center. Since 1995 the center in Slovakia has become the only referral center for Slovenia. Between February 1993 and June 2002 in this center, 147 patients with D-TGA underwent arterial switch operation (ASO). The median age at operation was 11 days, with 110 patients from Slovakia and 37 patients from Slovenia. RESULTS: Overall hospital mortality was 4.8% (seven patients). The 1, 2, 3, 4 and 5 year survival rate was 95% with the mean follow-up of 4 years. Operation before 1997 (P=0.0001) was identified as a risk predictor for death by multivariate analysis. There are no deaths among the 90 patients operated on after 1996. All patients are without medication with normal left ventricular function. Stenosis (gradient >30 mmHg) was noted in the pulmonary artery reconstruction in seven patients (5%). More than mild aortic regurgitation was noted in five patients (4%). The incidence of redo or reintervention was 5% at 5 years of follow-up. CONCLUSIONS: In the current era a prolonged learning curve for ASO is not acceptable to most European countries and their patients. The risk of surgery can be minimized by concentrating surgical experience as part of the quality control of congenital heart programs. If the number of new patients is small due to the birth rate and size of the population, institutions should merge activity. Such centralization amplifies the experience to the benefit of the patient.     

Acuity of amblyopic children for small field gratings and recognition stimuli

Tests of grating acuity often underestimate amblyopia and underrefer esotropic infants with a fixation preference. To evaluate the effect of the large grating field used in preferential looking (PL) procedures, an eight-alternative, small field (about 1 degrees) grating acuity test was devised. Gratings contained at least eight cycles. Thirty-seven strabismic and/or anisometropic amblyopes, ages 3-13 yr, were tested. In most amblyopic eyes, grating acuities were better than recognition acuities; the difference was reduced, however, in the small field test compared to the large field (6 degrees test (means, 1 oct vs. 1.6 oct; paired-t = 5.5, P less than .001). Nevertheless, the same relation between grating and recognition acuities occurred for small as for large fields: an increased discrepancy between grating and recognition acuities accompanied poorer acuity. This larger discrepancy is attributed to increased probability summation of amblyopic eyes for low spatial frequencies. For preschool children who can be tested by both procedures, the eight-alternative grating acuity test may be preferable to operant PL because it is more easily administered and materials are simpler.     

Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS)

1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.

2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.

3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.     

Intracerebral hemorrhage: natural history and rationale of ultra-early hemostatic therapy

Stroke is a major health problem worldwide, causing high morbidity and mortality. Intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. It is less treatable than other forms of stroke and causes higher morbidity and disability. Data suggest that early hematomy growth is the principal cause of early neurological deterioration after ICH. Prospective and retrospective studies indicate that early hematoma growth occurs in 18–38% of patients scanned within 3 h of ICH onset, and that hematoma volume is an important predictor of 30-day mortality. As hematoma growth in acute ICH is a dynamic process, intervention with ultra-early hemostatic therapy could lead to minimization and even prevention of early hematomy growth. Recombinant activated factor VII (rFVIIa, ‘NovoSeven’), a powerful initiator of hemostasis, is approved for the treatment of bleeding in patients with hemophilia and inhibitors and may also promote hemostasis in patients with normal coagulation. rFVa acts locally at the bleeding site without activating systemic coagulation and may be a valuable therapy during the hyperacute stage of ICH. A randomized, double-blind, placebo-controlled, dose-ranging trial is currently in progress to investigate the potential of rFVIIa as an ultra-early hemostatic therapy to prevent or minimize hematoma growth in ICH patients without coagulopathy.     

Is substance P a primary afferent neurotransmitter for nociceptive input? III. Valproic acid and chlordiazepoxide decrease behaviors elicited by intrathecal injection of substance P and excitatory compounds

Intrathecal (i.t.) injections of substance P (SP) and kainic acid in rats produced rostrally directed scratches with the hindlimbs and caudally directed bites or licks. These behaviors, together with myoclonic twitches and vocalization, were also produced by I.T. morphine and strychnine. Intrathecal valproic acid (VA) significantly reduced all behaviors when these occurred spontaneously, and VA and chlordiazepoxide both reduced these behaviors when they were evoked by a light cotton swab tap to the lumbosacral region, in rats treated with the excitatory compounds. Since neither anticonvulsant affected the thermal or mechanical pain threshold at these doses, these results suggest that (a) the behaviors elicited by i.t. injection of the excitatory compounds are not responses to perceived pain, but rather the expression of a spinal convulsive-like state, and (b), since scratching and biting were the only behaviors produced by SP, this peptide is neither necessary nor sufficient for the elicitation of pain at the spinal level. Although our experiments do not rule out other roles for SP in pain processes such as that of a neuromodulator, it is unlikely that this compound is a traditional primary afferent neurotransmitter of pain.