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.     

颅内肿瘤影像学诊断及进展

颅内肿瘤是中枢神经系统常见病,它包括起源于颅内各种组织的原发性肿瘤及其他部位转移到颅内的继发性肿瘤。颅内肿瘤的诊断主要依靠影像学检查,伴随现代高科技的发展,常规影像学技术也正在发生着日新月异的进步,颅内肿瘤的诊断准确度越来越高。本文主要介绍颅内常见肿瘤的普通X线、CT、MRI图像特点及影像学进展。     

Methodological issues associated with using different cut-off points to categorize outcome variables.

Knowledge of the factors that contribute to delay in seeking medical treatment for acute myocardial infarction (AMI) provides the basis for interventions that are intended to facilitate prompt care-seeking behaviour. However, operational definitions of delay time vary across research studies. The use of inconsistent cut-off times to distinguish between delayers and non-delayers is likely to compromise comparability and generalizability of the findings across studies. The purpose of this paper is to examine the impact of inconsistent operationalization of delay, in terms of cut-off times, on the validity of research findings pertaining to identifying its predictors. Secondary data analysis was performed using a sample of 73 patients who had recently experienced out-of-hospital AMI and concluded that their symptoms were related to the heart. Several regression models were built to examine the influence of using different cut-off times (1, 2, 3, 6, and 12 hours, median delay) on the number and nature of predictors ofAMI care-seeking delay.The impact of varying cut-off times on the explained variance, sensitivity, specificity, and predictive values associated with each regression model was examined. The use of different cut-off times produced different sets of independent predictors, which varied in number and nature.The variance explained by the different regression models as well as their classification indices varied. Use of different cut-off times for the definition of delay time led to inconsistent results. Thus, it is recommended that criteria be established among clinicians and researchers with regard to operationally defining care-seeking delay for AMI.     

Effect of two preventive programs on oral health knowledge and habits among Brazilian schoolchildren

Abstract – The effect upon dental health knowledge and dental health behavior of a comprehensive and a less comprehensive preventive program was compared in a 3-yr follow up study. The comprehensive program included active participation of the students and parental involvement. The study group consisted of 186 Brazilian schoolchildren 13 yr of age at the start of the program. A reference group from another school of similar socioeconomic level was included in the analyses. The data were collected from questionnaires filled in by the children under surveillance after the completion of the program. Significant differences in knowledge as well as in reported behavior were observed. The children enrolled in the comprehensive program in general scored higher in dental health knowledge than did those in the less comprehensive program. However, the latter group of children seemed to have acquired more correct knowledge during the period than had the control and reference children. Similar results were obtained concerning reported dental health behavior.