Temporomandibular joint: surgically created disk displacement causes arthrosis in the rabbit.

To document a causal relationship between temporomandibular joint disk displacement and arthrosis, the disk was surgically displaced in one temporomandibular joint in each of three rabbits. The rabbits were sacrificed after 4 weeks and the mandibular condyles were studied radiographically and histologically. All three joints that underwent disk displacement had radiographic and histologic evidence of arthrosis, which included erosion of the bone, irregularity and fissure formation of the articular soft tissue cover, disruption of the subchondral layer of cartilage cells, and chondrocyte proliferation. No radiographic or histologic changes occurred in the joints that were untouched. The results suggest that surgically created disk displacement can cause arthrosis in the temporomandibular joint of the rabbit.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

The measurement of preoperative anxiety.

Preoperative anxiety was assessed using the hospital anxiety and depression (HAD) scale, multiple affect adjective check list (MAACL) and linear analogue anxiety scale (LAAS) in 100 consecutive day case patients undergoing termination of pregnancy. The HAD scale, a recently introduced self assessment scale comprising 7 multiple choice questions, was readily accepted and easily understood by patients. There was a high degree of correlation between the HAD scale and both the MAACL (correlation coefficient 0.74) and the LAAS (correlation coefficient 0.67). There was only a moderate degree of correlation between the HAD scale and the anaesthetist's assessment of anxiety (correlation coefficient 0.46). The HAD scale is a useful method of subjective measurement of preoperative anxiety.     

In-vitro teratogenicity of retinoids

Mid-gestation rat conceptuses were cultured for 48 h in serum containing the retinoids all-trans-retinoic acid (TRA), 13-cis-retinoic acid (13-CRA), etretinate (ETR), etretin or one of six retinamides at concentrations ranging from 0.5 to 400 micrograms/ml. TRA was toxic at a concentration of 0.5 microgram/ml. 13-CRA and etretin caused abnormal development at 1.0 microgram/ml. However, the six retinamides were less toxic and adverse developmental effects were only evident at concentrations of 50 or 100 micrograms/ml. ETR was without effect at 100 micrograms/ml, the highest dose level of this compound tested. In vivo, TRA, 13-CRA and ETR are highly teratogenic. In this culture system, TRA and 13-CRA caused abnormal development at very low concentrations but in contrast, ETR was non-toxic at 100 micrograms/ml. Therefore these findings indicate that in vivo, maternal pharmacokinetics, and bioactivation in particular, play a major role in inducing abnormal development. Cis/trans isomerization was not a major determinant of toxicity. However, there appeared to be a relationship between abnormal development and the actual or estimated pKa values of the 10 retinoids tested.     

AB or ABC: pre-hospital fluid management in major trauma.

Pre-hospital trauma care in the United Kingdom is a neglected field with little consideration being given to this phase. Of the 14,500 annual fatalities from road traffic accidents in this country, 60% die before reaching hospital and it has been estimated that one-third of these fatalities are due to hypovolaemia. The pre-hospital fluid resuscitation of trauma patients is a controversial area and although it would seem sensible to commence intravenous (i.v.) fluids at the roadside, several large studies have failed to show any benefit from this intervention. By delaying departure to hospital, initiation of i.v. fluid replacement may actually worsen outcome. This paper reviews recent studies and discusses current thought on pre-hospital fluid replacement in major trauma.     

Coronary artery bypass graft surgery in older women and men.

OBJECTIVE: To compare women and men younger than 70 years of age and 70 years or older undergoing coronary artery bypass surgery. DESIGN: Retrospective chart review, case-control series. SETTING: University medical center. PATIENTS: All women (n = 465) having first-time isolated coronary artery bypass surgery between 1983 and 1988, and 465 men matched for age and year of surgery. Predominantly white; 33% were 70 years or older. MEASURES: Medical record data: demographics, preoperative comorbidities, perioperative and postoperative complications, mortality, length of stay. RESULTS: Preoperatively, women 70 years of age or older had a higher incidence of congestive heart failure, renal disease and hypertension, and a lower incidence of smoking history compared with women less than 70 years old. Men 70 years or older had a higher incidence of congestive heart failure and renal disease, and a lower incidence of smoking history compared with men less than 70 years old. There was no difference in mortality between older and younger women, whereas the mortality rate for older men was higher than that for younger men. There were fewer differences between women younger than 70 and those 70 years or older in incidence of postoperative complications than between men of those same age groups. Among patients 70 years or older, incidence of postoperative congestive heart failure was greater in women than in men. There were no other differences between women and men younger than 70 and those 70 years or older in incidence of postoperative complications. Controlling for the influence of postoperative complications, age was related to length of stay for women and men. CONCLUSIONS: Older women were at no greater risk of mortality or the occurrence of postoperative complications compared with younger women or older men. A functional component influencing recovery and length of hospital stay needs to be considered to provide optimal nursing care after surgery.     

Interaction between Marihuana and Ethanol: Effects on Psychomotor Performance

This is a report of the results of a placebo-controlled study in which the effects of the interaction between ethanol and marihuana on drug plasma concentrations, subjective ratings of intoxication, heart rate acceleration, and psychomotor performance were investigated. Six healthy, male, paid volunteers, moderate users of ethanol and marihuana, participated in the study. Ethanol (0.42 g/kg, 0.85 g/kg, or placebo) was administered over a 30-min interval. Fifteen minutes later the subjects smoked, in their customary manner, NIDA cigarettes containing 2.4% or 0.0004% (placebo) delta-9-tetrahydrocannabinol (THC). Each subject was tested in a single-blind, latin-square crossover design with the following six conditions: placebo ethanol/placebo marihuana; low dose ethanol/placebo marihuana; high dose ethanol/placebo marihuana; placebo ethanol/marihuana; low dose ethanol/marihuana; and high dose ethanol/marihuana. The variables measured in the study were: (a) subjective rating of ethanol and/or marihuana intoxication; (b) heart rate; (c) accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI) task; (d) blood ethanol concentration by gas chromatography; and (e) plasma concentration of THC by radioimmunoassay. The results indicate that the decrements due to ethanol in performance of skills necessary to drive an automobile were significantly enhanced by marihuana in an additive and perhaps synergistic manner. The administration of ethanol prior to marihuana smoking did not produce significant effects on the subjective rating of "high," heart rate acceleration, or THC plasma concentration.     

Anaphylactic hypersensitivity in isolated smooth muscle preparations from adjuvant-treated guinea-pigs

Anaphylactic hypersensitivity of isolated guinea-pig ileum preparations has been evaluated by investigation of antigen-dose/response relationships, in vitro. The influence of Freund's adjuvants on active sensitization has been investigated. In contrast to the inhibitory influence previously observed in vivo, the degree of hypersensitivity of isolated tissues in vitro was potentiated by the adjuvants. It is thought that high circulating titres of antibody in vivo exerted a protective or neutralizing effect in relation to challenging doses of antigen. Isolated tissues were freed from this influence. Tissues sensitized with the aid of Freund's complete adjuvant (FCA) revealed the influence of other inhibitory mechanisms, due probably to interaction of various antibody types.     

Psychopathic personality traits: heritability and genetic overlap with internalizing and externalizing psychopathology

BACKGROUND: Little research has examined genetic and environmental contributions to psychopathic personality traits. Additionally, no studies have examined etiological connections between psychopathic traits and the broad psychopathological domains of internalizing (mood and anxiety) and externalizing (antisocial behavior, substance abuse). The current study was designed to fill these gaps in the literature. METHOD: Participants were 626 pairs of 17-year-old male and female twins from the community. Psychopathic traits were indexed using scores on the Multidimensional Personality Questionnaire (MPQ). Symptoms of internalizing and externalizing psychopathology were obtained via structured clinical interviews. Structural equation modeling was used to estimate genetic and environmental influences on psychopathic personality traits as well as the degree of genetic overlap between these traits and composites of internalizing and externalizing. RESULTS: Twin analyses revealed significant genetic influence on distinct psychopathic traits (Fearless Dominance and Impulsive Antisociality). Moreover, Fearless Dominance was associated with reduced genetic risk for internalizing psychopathology, and Impulsive Antisociality was associated with increased genetic risk for externalizing psychopathology. CONCLUSIONS: These results indicate that different psychopathic traits as measured by the MPQ show distinct genetically based relations with broad dimensions of DSM psychopathology.