Biomedical subjects

D French

Publications and source records attributed to D French.

At least 37 records · Page 2Linked to original sources

PubMed1998

Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene.

To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 +/- 14.6 years, mean +/- SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine = 48.1 micrograms/24 hours). Thyroid tumors were follicular or Hürthle cell adenomas (no. = 3), follicular carcinomas (FC, no. = 4), papillary carcinomas (PC, no. = 2) and anaplastic carcinomas (no. = 2). Eleven patients (age 47.1 +/- 15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine = 95.2 micrograms/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76 +/- 0.33 vs 1.80 +/- 1.22 mU/l, p = 0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no. = 6), Hürthle cell carcinoma (no. = 1), FC (no. = 2), PC (no. = 2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70-80% of the tumor cells) than in the other two cancers (1+; < 5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.

Adult↗

PubMed1998

Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children.

Administration of GH-releasing peptide-2 (GHRP-2) represents a potential mode of therapy for children of short stature with inadequate secretion of GH. Requisite information to determine the dosing route and frequency for GHRP-2 consists of the pharmacokinetics (PK) and pharmacodynamics (PD) for this compound, neither of which have been previously evaluated in children. The purpose of this study was to characterize the PK and PD of GHRP-2 in children with short stature. Ten prepubertal children (nine boys and one girl; 7.7 +/- 2.4 yr old) received a single 1 microg/kg i.v. dose of GHRP-2 over 1 min, followed by repeated (n = 9) blood sampling over 2 h. GHRP-2 and GH were quantitated by specific RIA methods. PK parameters were calculated from curve fitting of GHRP-2 and GH vs. time data. Posttreatment plasma GH concentrations (normalized for pretreatment values) were used as the effect measurement. PD parameters were generated using the sigmoid Emax model. Disposition of GHRP-2 best fit a biexponential function. GHRP-2 PK parameters (mean +/- SD) were: alpha = 13.4 +/- 9.7 h(-1), beta = 1.3 +/- 0.3 h(-1), t(1/2beta) = 0.55 +/- 0.14 h, AUC(0-infinity) = 2.02 +/- 1.37 ng/mL x h, Cmax = 7.4 +/- 3.8 ng/mL, plasma clearance = 0.66 +/- 0.32 L/h x kg, and apparent volume of distribution = 0.32 +/- 0.14 L/kg. PK parameters for GH were: appearance rate constant = 5.9 +/- 3.1 h(-1), elimination t(1/2) = 0.37 +/- 0.15 h, lag time = 0.05 +/- 0.01 h, Cmax = 50.7 +/- 17.2 ng/mL, Tmax = 0.42 +/- 0.16 h, and AUC(0-infinity) = 47.9 +/- 26.1 ng/mL x h. PD parameters for GHRP-2 were: Ke0 = 1.13 +/- 0.94 h(-1), gamma = 13.15 +/- 9.44, E0 = 6.63 +/- 4.86 ng/mL (GH), Emax = 67.5 +/- 23.5 ng/mL (GH), and EC50 = 1.09 +/- 0.59 ng/mL. We concluded that 1) GHRP-2 produced a predictable and significant (i.e. compared to pretreatment values) increase in plasma GH concentrations; 2) the PK-PD link model enabled quantitative assessment of GHRP-2 modulation of serum GH levels; and 3) definition of the EC50 for GHRP-2 will enable PD and PK evaluations of extravascular dosing regimens for children.

Child↗

PubMed1998

Alterations in locomotor activity during chronic cocaine administration: effect on dopamine receptors and interaction with opioids.

Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist.

Adenylyl Cyclases↗

PubMed1998

Correlation of body mass index with thoracic and abdominal panniculus.

Obesity can play a significant role in chronic diseases, sudden unexpected death, and morbid obesity may be important as a cause of death for forensic pathologists. Our study attempted to determine if there is a correlation between panniculus measurements and body mass index (BMI) since BMI has been used in most studies to categorize obesity. Using data obtained from a review of 524 adult autopsies conducted at the University of Michigan from 1990 to 1992 we were able to show a correlation between both thoracic and abdominal panniculus and BMI (r2 = 0.335 and 0.296 respectively) which is statistically significant (p = 10(-47) and 10(-41) respectively). A prospective study confirmed the correlation (r2 = 0.552 for thoracic and 0.436 for abdominal panniculus) when the measurements were taken at the xyphoid process and 3 cm below the umbilicus. Using these data we calculated a panniculus index (PI) which is equal to the thoracic + abdominal panniculus in centimeters divided by the square of the height (in meters). The PI strongly correlated with BMI and was able to predict obesity. Using a BMI cutoff of 39 for morbid obesity, a PI value of 4.07 for females and 3.25 for males predicted morbid obesity with the probability of a false positive less than or equal to 2.5%. Mild and severe obesity could also be determined using the PI. Based on these data we've concluded that a concise mathematical relationship does exist between BMI and panniculus measurements. Therefore panniculus measurements can be used either as a surrogate measurement of morbid obesity or to support BMI calculations.

Abdomen↗

PubMed1997

A Study to Determine Susceptibility to Hepatitis A of Travelers from South Africa.

Hepatitis A is an important cause of acute hepatitis in travelers to developing countries. In 1991, 33 million persons living in industrialized countries traveled to developing countries where hepatitis A is highly endemic (World Tourism Organization, unpublished data, 1993). Reports indicate that 40-50% of cases of hepatitis A infection in the United Kingdom,1 Switzerland2 and Sweden3 are associated with recent international travel. The disease is usually benign, but the severity increases with age.4 Because the disease is enterically transmitted, occurrence is related to water quality and level of sanitation. In developing countries, with poor water quality and sanitation, especially in the tropics where hepatitis A is endemic, exposure is virtually universal before the age of 10 years.4 In developed countries with good food and water hygiene, the rate of exposure to hepatitis A in children is low. The rate of seropositivity increases slowly during early adulthood and reaches moderate levels during late adulthood.5 Studies have demonstrated the higher prevalence among people who live in poor, overcrowded conditions.6 Travelers going from low incidence countries to endemic areas are particularly at risk for acquiring hepatitis A, especially if they stay for extended periods.7 The risk that Danish travelers to North Africa would acquire hepatitis A was estimated to be 3.5 per 10,000, and this population accounted for at least 20% of all cases of hepatitis in Denmark. Similarly, Germans traveling or living in tropical countries have a 40 times higher risk of acquiring hepatitis than do groups living at home.8 The pattern in South Africans ranges from minimal exposure to hepatitis A in childhood in populations with good water quality and sanitation (mainly white), to high exposure in those exposed to poor water quality and sanitation in childhood (mainly black). Hepatitis A vaccine has been found to be effective in reducing the incidence of infection in travelers. After the introduction of hepatitis A vaccine into Switzerland in 1992, there has been a reduction by 15% in the cases of imported hepatitis A.9 Hepatitis A vaccine should be offered to South African travelers to high risk areas.10,11 However for the vaccine to be the most cost-effective, it would be important to identify groups of travelers who would benefit from empiric vaccination as opposed to other groups who should undergo screening prior to vaccination. This study was undertaken to establish the seroprevalence of hepatitis A in the South African traveler and to identify groups of travelers that should be vaccinated.

Journal Article↗

PubMed1996

Exposure versus cognitive restructuring in the treatment of panic disorder with agoraphobia.

The aim of this study was to assess the rate of change on clinical, behavioral and cognitive variables during exposure therapy and cognitive restructuring in the treatment of panic disorder with agoraphobia. A total of 28 Ss who received a diagnosis of panic disorder with agoraphobia were randomly assigned to either of two treatment conditions: exposure therapy or cognitive restructuring. Treatment conditions were kept as distinct as possible from each other. Subjects were assessed on five occasions: pretreatment, after 5, 10, and 15 (posttreatment) sessions of treatment and at a 6-month follow-up. Analyses of outcome data revealed strong and significant time effects on all measures. However, no group x time interaction reached statistical significance, suggesting that both strategies operate at the same pace. Furthermore, power analyses suggest that any difference that might exist in the rate of improvement between exposure and cognitive restructuring in the treatment of panic disorder with agoraphobia is marginal.

Adult↗

PubMed1995

High cell kinetics is associated with amplification of the int-2, bcl-1, myc and erbB-2 proto-oncogenes and loss of heterozygosity at the DF3 locus in primary breast cancers.

Cell kinetics is a predictive parameter of breast-cancer aggressiveness, and mutations occurring in mammary tumorigenesis may favor uncontrolled cell proliferation. In this study, cell kinetics, clinico-pathological characteristics and genetic alterations at the int-2, bcl-1, c-myc, c-erbB-2, and DF3 loci were analyzed and correlated in 54 primary breast carcinomas. The occurrence of mutations at more than one locus was also studied. Tumor-proliferative activity was evaluated by determination of the thymidine labeling index (TLI). Amplification (AMP) of int-2 was observed in 11.2%, of bcl-1 in 9.4%, of c-myc in 5.7% and of c-erbB-2 in 8.6% of the carcinomas. Loss of heterozygosity (LOH) at the DF3 locus was detected in 13.9% of the tumors. Genetic alterations demonstrated a significant association with patient's age and high TLI values. AMP and LOH+AMP did not appear to be statistically related to histotype, histological grade, tumor size or lymph-node status. Alone, allele loss at the DF-3 locus was not significantly associated with any of the clinico-pathological characteristics studied. Alterations at more than one locus, including int-2/bcl-1, int-2/c-myc, int-2/bcl-1/c-erbB-2, and c-myc/DF3, were detected in 11.1% of the tumors. Multiple mutations were found only in less differentiated tumors, which included the 2 cases from the youngest patients of the series.

Adult↗

PubMed1995

The mechanism of binding of exogenous DNA to sperm cells: factors controlling the DNA uptake.

Mature sperm cells have the spontaneous capability of taking up exogenous DNA. Potential substrates for the interaction of the DNA with the sperm heads are specific classes of DNA-binding proteins. In the present work three major classes of DNA-binding proteins were identified by Southwestern analysis of sperm head protein extracts: a first class of about 50 kDa in molecular weight, a second one of 30-35 kDa, and finally a third one below 20 kDa. The latter group most probably contains sperm protamines. Our attention was particularly focused on the 30- to 35-kDa proteins as a substrate for DNA binding, as they represented the only group whose electrophoretic mobility was conserved among mammalian species. In addition they were the only class of DNA-binding proteins accessible to exogenous DNA in intact sperm cells. The purified 30- to 35-kDa proteins interacted in vitro with exogenous DNA and generated discrete protein/DNA complexes as determined by band shift assay. A factor blocking the binding of exogenous DNA to sperm cells was also identified in the seminal fluid of mammals and in echinoid spermatoza. The factor also exerted a powerful inhibitory effect on DNA uptake in sperm cells of heterologous species. The 30- to 35-kDa DNA-binding proteins appeared to be the specific target through which the inhibition was mediated. In the presence of the inhibitory factor, the 30- to 35-kDa lost the ability to bind exogenous DNA. Thus, the interaction of exogenous DNA with sperm cells does not appear to be a casual event but, on the contrary, relies on a molecular mechanism based on the cooperation of specific protein factors.

Animals↗

PubMed1995

Pilgrim's progress: the effect of salmeterol in older children with chronic severe asthma.

Twenty-four children aged 12-17 years entered a randomized, double-blind placebo-controlled study investigating the use of salmeterol in chronic severe asthma. In addition to their usual medication, the children were given either placebo or 100 micrograms salmeterol b.d. by dry powder inhalation. Treatment was continued throughout one term at a residential school for asthma. Symptom scores, peak expiratory flow rates, spirometry and quality-of-life scores were compared between the two treatment groups. One child withdrew during the run-in period. Twelve pupils received placebo and 11 pupils received salmeterol. There were consistent improvements in favour of salmeterol, reaching statistical significance for morning and evening peak flow rates and spirometry when measured on four occasions during the study period. There were no medication-related adverse events recorded and no pulse rate changes. Salmeterol (100 micrograms b.d.) is well tolerated and efficacious in older children with chronic severe asthma.

Adolescent↗

PubMed1995

[Rapid detection of platelet glycoprotein IIb, IIIA gene variety by single strand conformation polymorphism analysis].

Glanzmann thrombasthenia (GT) is the most common inherited disorder of platelet defective function. Most of the molecular defects of GT identified in recent years have been caused by point mutation in the platelet glycoprotein (GP) IIb, IIIa genes. Trying to rapidly detect point mutation (or subtle variety) in GPIIb, IIIa genes, we have used single strand conformation polymorphism analysis (SSCPA) and studied the gene structure of platelet GPIIb. IIIa from normal controls and patients with Glanzmann thrombasthenia. After DNA preparation from peripheral blood, all the exons of GPI-Ib, IIIa were amplified by PCR. Denaturated PCR products were separated on mini polyacrylamide gel and stained by silver staining method in the Phast System. Only the PCR products with different migration on the gel were sequenced. 2 GT patients with point mutations and 1 GT patient with 16 bp deletion were found in our study. At the same time, we determined 3 polymorphisms in GPIIb gene. We conclude that SSCPA is a rapid, sensitive and effective method for detecting platelet IIb, IIIa gene variety.

DNA Mutational Analysis↗

PubMed1995

Papillon-Lefèvre syndrome associated early onset periodontitis: a review and case study.

A case of Papillon-Lefèvre syndrome that has been managed successfully for six years is reported. Papillon-Lefèvre syndrome is a rare form of early onset periodontitis that occurs at a rate of 1-3 per million. Diagnostic features include palmar-plantar hyperkeratosis and rapid periodontal destruction. Although the etiology of this syndrome is unknown, current theories on the nature of the underlying defect fall into three main categories: anatomical, bacterial and host response. Historically, Papillon-Lefèvre syndrome was thought to lead to the inevitable loss of both the primary and permanent dentitions. However, a recently proposed treatment involving antibiotic coverage, extraction of the primary dentition and a period of edentulism has been shown to be effective in maintaining the permanent dentition. Since treatment may begin prior to the eruption of the permanent dentition, early recognition of Papillon-Lefèvre syndrome is critical. Any young patient who exhibits palmar hyperkeratosis should be examined carefully for periodontal breakdown. Since the number of cases available for study is limited, referral of such individuals to University dental clinics may allow for a more specific analysis of immune or bacterial factors that may lead to a better understanding of this disease.

Aggregatibacter actinomycetemcomitans↗

PubMed1995

Discriminative stimulus effects of R-(+)-3-amino-1-hydroxypyrrolid-2-one, [(+)-HA-966], a partial agonist of the strychnine-insensitive modulatory site of the N-methyl-D-aspartate receptor.

The strychnine-insensitive glycine site on the N-methyl-D-aspartate (NMDA) receptor complex is a target for development of a host of therapeutic agents including anxiolytics, antidepressants, antiepileptics, anti-ischemics and cognitive enhancers. In the present experiments, the discriminative stimulus effects of (+)-HA-966 [R-(+)-3-amino-1-hydroxypyrrolid-2-one], a low-efficacy partial agonist of the glycine site, was explored. Male, Swiss-Webster mice were trained to discriminate (+)-HA-966 (170 mg/kg i.p.) from saline in a T-maze under which behavior was controlled by food. Other glycine partial agonists, 1-amino-1-cyclopropanecarboxilic acid and D-cycloserine, fully substituted for the discriminative stimulus effects of (+)-HA-966 despite known differences in other pharmacological effects of these compounds. The glycine site antagonist, 7-chlorkynurenic acid, did not substitute for (+)-HA-966. Likewise other functional NMDA antagonists acting at nonglycine sites of the NMDA receptor also did not substitute: neither the high (dizocilpine) or low affinity (ibogaine) ion-channel blocker, the competitive antagonist, NPC 17742 [2R,4R,5S-2-amino-4,5-(1, 2-cyclohexyl)-7-phosphonoheptanoic acid], nor the polyamine antagonist, ifenprodil, substituted for (+)-HA-966. Although the full agonist, glycine, did not substitute, this compound fully blocked the discriminative stimulus effects of (+)-HA-966. In a separate group of mice trained to discriminate 0.17 mg/kg of dizocilpine from saline, (+)-HA-966 produced a maximum of only 50% dizoclipine-appropriate responses. These data suggest that the discriminative stimulus effects of (+)-HA-966 are based upon its partial agonist actions at the strychnine-insensitive glycine site.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1994

p53 expression and genetic evidence for viral infection in intraepithelial neoplasia of the uterine cervix.

Infections with high-risk strains of human papillomaviruses (HPVs) and with herpes simplex virus type 2 (HSV 2), as well as inactivation of the p53 tumor suppressor gene, are important cofactors in cervical carcinogenesis. We analyzed 41 paraffin-embedded cervical intraepithelial lesions, including 25 cases of low-grade cervical intraepithelia neoplasia (CIN), and 16 cases of high-grade CIN for the presence of HPV 16/18 and HSV 2 genomic sequences and for the nuclear accumulation of the p53 protein. HPV 16 DNA was detected in 24.% of low-grade CINs and in 43.7% of high-grade CINs. HPV 18 was found only in 8.% of low-grade CINs. None of the cases tested scored positive for HSV 2 DNA. Nuclear accumulation of p53 was found in 4% of low-grade CINs, and in 31.2% of high-grade CINs, including 57.1% of the lesions that were positive for HPV 16. These results indicate that HPV 16 infection was over sixfold more common than HPV 18 infection and that p53 overexpression was significantly associated with high-grade lesions.

Adult↗

PubMed1994

The role of home practice in the thermal biofeedback treatment of migraine headache.

The present study examined the role of home practice of hand warming in the thermal biofeedback treatment of migraine headache. Seventeen female migraine sufferers were randomly assigned to one of the following conditions: thermal biofeedback with regular home practice (HP) or thermal biofeedback without home practice (NHP). Biofeedback treatment consisted of 12 training sessions over a 6-week period, and all subjects completed 5 weeks of headache monitoring before and after treatment. Results indicated that subjects in the HP condition experienced decreases in headache activity and medication intake that were both statistically and clinically significant compared with the NHP condition. None of the outcome measures revealed significant improvement in the NHP condition. Thus, regular home practice appears to enhance the efficacy of biofeedback in the treatment of migraine.

Adult↗

PubMed1993

Evidence for nuclear internalization of exogenous DNA into mammalian sperm cells.

Mature sperm cells have the spontaneous capacity to take up exogenous DNA. Such DNA specifically interacts with the subacrosomal segment of the sperm head corresponding to the nuclear area. Part of the sperm-bound foreign DNA is further internalized into nuclei. Using end-labelled plasmid DNA we have found that 15-22% of the total sperm bound DNA is associated with nuclei as determined on isolated nuclei. On the basis of autoradiographic analysis, nuclear permeability to exogenous DNA seems to be a wide phenomenon involving the majority of the sperm nuclei. In fact, the foreign DNA, incubated with sperm cells for different lengths of time, is found in 45% (10 min) to 65% (2 hr) of the sperm nuclei. Ultrastructural autoradiography on thin sections of mammalian spermatozoa, preincubated with end-labelled plasmid DNA, shows that the exogenous DNA is internalized into the nucleus. This conclusion is further supported by ultrastructural autoradiographic analysis on thin sections of nuclei isolated from spermatozoa preincubated with end-labelled DNA.

Animals↗

PubMed1993

Integrin beta 4 expression in the neoplastic progression of cervical epithelium.

Integrin alpha 6 beta 4, a putative laminin receptor, is expressed in normal squamous epithelium and in squamous cell carcinomas. We evaluated by immunohistochemistry the topography of the beta 4 subunit in 35 biopsy samples representative of the sequence from normal exocervical epithelium to invasive squamous cell carcinoma. In normal and metaplastic squamous cervical epithelium, in condylomas, and in squamous epithelium with low-grade dysplasia (CIN 1), beta 4 was detected in basal and parabasal cells. In high-grade CIN (2-3) there was enhanced beta 4 expression and upward shift of beta 4 topography to the whole epithelial thickness. The beta 4 chain was diffusely expressed in most invasive squamous cell carcinomas. These observations suggest that profound alterations in the expression of the alpha 6 beta 4 adhesion glycoprotein occur in the intraepithelial phase of cervical carcinogenesis.

Antigens, Neoplasm↗

PubMed1993

Effects of the dopamine release inhibitor, CGS 10746B, on the locomotor stimulant and discriminative stimulus effects of cocaine and methamphetamine.

CGS 10746B or 5-(4-methyl-1 piperazinyl)-imadazo[2,1-b]1,3,5]benzothiadiazepine maleate is a clozapine analog that, unlike clozapine, produces decreases in neostriatal dopamine release without changing dopamine metabolism or occupying D2 receptors. CGS 10746B also blocks neuronal impulse flow. The ability of this atypical antipsychotic candidate to alter the discriminative stimulus effects induced by cocaine or methamphetamine in rats or the stimulation of locomotor activity in mice was evaluated. A range of doses of CGS 10746B was tested against maximally effective doses of the psychomotor stimulants. Although CGS 10746B completely blocked the locomotor stimulant effects of cocaine and methamphetamine, it also decreased spontaneous activity in mice over the same dose range. Rats were trained to discriminate 10 mg/kg cocaine or 1 mg/kg methamphetamine from saline. The discriminative stimulus effects of cocaine or methamphetamine were not blocked by CGS 10746B. Thus, in contrast to other potential atypical antipsychotic compounds (e.g., D1 receptor antagonists), CGS 10746B does not appear to produce selective blockade of these behavioral effects of psychomotor stimulant compounds.

Animals↗

PubMed1993

Behavioral correlates of individual differences in road-traffic crash risk: an examination method and findings.

This article considers methodological issues relevant to the study of differential crash involvement and reviews the findings of research in this area. Aspects of both driving skill and driving style appear to contribute to crash risk. Of the former, hazard-perception latency appears to play an important role, and this may be attributable to generalized abilities to identify visual targets in a complex background and to switch attention rapidly. Of the latter, faster driving speed and willingness to commit driving violations increase crash risk, and these factors may be explicable in terms of personality and antisocial motivation. The article concludes with an examination of the practical implications and of the ways in which research in this area might usefully proceed.

Accidents, Traffic↗