Schizophrenics show a failure in the decoding of violations of conversational implicatures

OBJECTIVES: Recent approaches to the 'theory of mind' and pragmatics support that, if we did not have any idea about what other people know, we could hardly use language effectively. Successful communication (the pragmatic aspect of language) depends on inferring the beliefs and intentions of the partner in the conversation. Such successful communication is linguistically realized in part by cohesion and in part by abiding by the maxims derived from the cooperative principle. However, the violations of the Gricean implicatures are generally used in everyday language, mainly to point at a hidden, most commonly negative opinion on others. We hypothesize that schizophrenics have difficulties in the decoding of these violations, as the core deficit in this disorder is around social cognition, theory of mind and pragmatic language use. MATERIAL AND METHOD: We have examined 26 paranoid schizophrenic patients and 26 normal control subjects by using 4 'question and answer' vignettes, where the Gricean maxim of relevance was violated to express a hidden, negative opinion by one partner during the communicative act. The subjects were asked to judge these opinions and were evaluated by the investigators on a score from 0 to 2 points. In a pilot study, interrater reliability was judged to be satisfactory. The data were analysed statistically by parametric and non-parametric tests. RESULTS: Statistical analyses of our data have shown that schizophrenics made significantly more mistakes during the decoding of the violated maxim as compared with controls (p < 0.0001), reflecting on the difficulties during the correct exploration of the social context, i.e. recognition of the speaker's hidden opinion. CONCLUSION: We conclude that patients with schizophrenia fail to decode intentional violations of conversational implicatures. These results point at a dysfunctional pragmatic language use among schizophrenic patients.     

Opposing cartilages in the patellofemoral joint adapt differently to long-term cruciate deficiency: chondrocyte deformation and reorientation with compression

OBJECTIVE: The purposes of this study were to quantify patellofemoral histology in the feline knee 67 months post-anterior cruciate ligament transection (ACL-T) and to apply an in situ static load of physiological magnitude to the articular cartilage and evaluate the resulting cartilage and chondrocyte deformation. DESIGN: Six cats were sacrificed 67+/-6 months post-unilateral ACL-T. Static compression was applied to the cartilage surfaces of the patellofemoral joint using a cylindrical metal indentor. After fixation, full thickness osteochondral blocks were harvested and sections cut from not-indented and indented areas. Chondrocyte shape, orientation and volumetric fraction as well as cartilage thickness were evaluated. RESULTS: Experimental and contralateral patellae were histologically different compared to normal with thickened cartilage, rounded superficial chondrocytes, and uneven proteoglycan staining throughout. In contrast, no differences were apparent in 10 of the 12 femoral groove samples. The structural reorganisation of the experimental patellae cartilage that occurred with load was also different compared to normal. Specifically, the indentation shape was deeper and had steeper sides and the realignment of deep zone cells at angles of 45 degrees and 135 degrees observed in normal cartilage was no longer apparent in the experimental tissue. CONCLUSIONS: Two directly articulating cartilage surfaces of the feline patellofemoral joint have completely contrasting responses to long-term ACL-T. We speculate that this could be a result of the different nature of the loads experienced by the two surfaces (intermittent vs constant) and/or the differences in the histology and material properties of the two tissues in their normal state, and/or an inherent difference in the biological response capabilities of the articular cartilages.     

Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents

OBJECT: Clinical application of the convection-enhanced delivery (CED) technique is currently limited by low infusion speed and reflux of the delivered agent. The authors developed and evaluated a new step-design cannula to overcome present limitations and to introduce a rapid, reflux-free CED method for future clinical trials. METHODS: The CED of 0.4% trypan blue dye was performed in agarose gel to test cannula needles for distribution and reflux. Infusion rates ranging from 0.5 to 50 microl/minute were used. Agarose gel findings were translated into a study in rats and then in cynomolgus monkeys (Macacafascicularis) by using trypan blue and liposomes to confirm the efficacy of the reflux-free step-design cannula in vivo. Results of agarose gel studies showed reflux-free infusion with high flow rates using the step-design cannula. Data from the study in rats confirmed the agarose gel findings and also revealed increasing tissue damage at a flow rate above 5-microl/minute. Robust reflux-free delivery and distribution of liposomes was achieved using the step-design cannula in brains in both rats and nonhuman primates. CONCLUSIONS: The authors developed a new step-design cannula for CED that effectively prevents reflux in vivo and maximizes the distribution of agents delivered in the brain. Data in the present study show reflux-free infusion with a constant volume of distribution in the rat brain over a broad range of flow rates. Reflux-free delivery of liposomes into nonhuman primate brain was also established using the cannula. This step-design cannula may allow reflux-free distribution and shorten the duration of infusion in future clinical applications of CED in humans.     

Static compressive loading reduces the mRNA expression of type II and X collagen in rat growth-plate chondrocytes during postnatal growth

The mechanisms by which chondrocytes modulate longitudinal bone growth are not well understood. This in vitro study investigated the effects of loading on the mRNA expression pattern of key molecular components of the growth-plate related to the extracellular matrix (type II and type X collagen) and the PTH-PTHrP feedback loop. Short-term static compressive loading was applied to rat proximal tibial growth-plate explants. Four age groups at specific developmental stages were investigated. The spatial variation in the mRNA expression was compared among loaded explants, their contralateral sham controls, and uncultured growth plates from normal animals. Basic cell metabolism (18S rRNA) was unaffected by load. Results indicated a narrower spatial distribution of mRNA expression of type II collagen throughout the growth plate; similarly, a narrowed distribution of expression of type X collagen was noted in the lower hypertrophic zone of the growth-plate. This suggests that mechanical compression influences chondrocytes of the hypertrophic zone to alter their expression of specific genes encoding proteins of the extracellular matrix, while PTH-PTHrP receptor mRNA, a regulatory protein, remained unaffected by loading. The effects of compression were similar at the different stages of growth, suggesting that additional factors may be involved in the clinical progression of skeletal deformities observed during growth spurts. Although this study was done in vitro and limited to static loading, it furthers our understanding of growth-plate mechanobiology as a first step toward providing a scientific rationale for treating progressive musculoskeletal deformities.     

Minor physical anomalies in non-familial unipolar recurrent major depression

BACKGROUND: The prevalence of minor physical anomalies (MPAs) was evaluated in patients with unipolar recurrent major depression to get indirect data on the possible role of aberrant neurodevelopment in the aetiology of major depression. One published study [Lohr et al., Am. J. Geriatr. Psychiatry 5 (1997) 318] on the MPA prevalence in unipolar depression, evaluated by the recently widely criticized Waldrop-scale, reports on a significantly higher MPA rate among patients. METHODS: A scale developed by Méhes [Prog. Clin. Biol. Res. 163 (1985) 45] was used to detect the presence or absence of 57 MPAs in 30 patients with major depression and in 30 matched controls. RESULTS: The depressive sample did not differ significantly from the control group (P=0.200). By comparing each MPA individually we could not find any significant differences between the depressive and the control sample. LIMITATIONS: Patients and control subjects had a negative family history in connection with affective disorders; a high-risk population should give significant positive results. CONCLUSIONS: The results do not support the role of an 'early neurodevelopmental origin' in unipolar depression.     

Indirect injury stimulates scar formation-adaptation or pathology?

In several animal models of osteoarthritis induced by cruciate ligament transection, a dense, scar-like tissue mass forms rapidly on the medial side of the knee joint. This mass mimics clinical fibrosis that sometimes occurs after joint surgery. It is unknown exactly why this medial tissue mass forms and what cells are involved in its formation. This study characterizes this medial mass by histology, biochemistry, and the expression of types I and III collagen mRNA. The medial mass is compared with the medial collateral ligament (MCL) and the MCL epiligament in anterior cruciate-transected and unoperated joints, and to normal skin and skin scar. The morphology of the medial mass resembled the epiligament and skin scar more than the MCL. The concentration of DNA and RNA and the RNA-DNA ratio were elevated dramatically in the medial mass compared with all other tissues including skin scar. However, the mRNA copy number and ratio of collagen types I and III mRNAs did not differ significantly among the medial mass, MCL, epiligament, and skin in either the control or the operated joints. The response of the medial mass, MCL, and MCL epiligament to cruciate transaction involves both hyperplasia and hypertrophy, but without a dramatic shift in cell phenotype. The medial mass may be a useful mimic or model of intraarticular adhesions, hypertrophic scars, ligament sprains, and arthrofibrosis.     

Tularemia on Martha's Vineyard: seroprevalence and occupational risk

We conducted a serosurvey of landscapers to determine if they were at increased risk for exposure to Francisella tularensis and to determine risk factors for infection. In Martha's Vineyard, Massachusetts, landscapers (n=132) were tested for anti-F. tularensis antibody and completed a questionnaire. For comparison, serum samples from three groups of nonlandscaper Martha's Vineyard residents (n=103, 99, and 108) were tested. Twelve landscapers (9.1%) were seropositive, compared with one person total from the comparison groups (prevalence ratio 9.0; 95% confidence interval 1.2 to 68.1; p=0.02). Of landscapers who used a power blower, 15% were seropositive, compared to 2% who did not use a power blower (prevalence ratio 9.2; 95% confidence interval 1.2 to 69.0; p=0.02). Seropositive landscapers worked more hours per week mowing and weed-whacking and mowed more lawns per week than their seronegative counterparts. Health-care workers in tularemia-endemic areas should consider tularemia as a diagnosis for landscapers with a febrile illness.     

Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia

BACKGROUND: Tumor necrosis factor alpha (TNFalpha), a cytokine involved in inflammatory processes, has been implicated in the pathophysiology of schizophrenia. The chromosomal location in the major histocompatibility complex (MHC) region on 6p21.1-21.3, a region with evidence for linkage, suggests a role in susceptibility to schizophrenia. Association of the minor (A) allele of the -G308A TNFalpha gene polymorphism with schizophrenia has been reported [Mol. Psychiatry 6 (2001) 79]. METHODS: Association of the -G308A TNFalpha gene and the lymphotoxin alpha (LTalpha)+A252G gene polymorphisms with schizophrenia was studied in 79 sib pair families with linkage in the MHC region and in 128 trio families using the transmission disequilibrium test (TDT). RESULTS: Weak association of the common G allele was detected for TNFalpha -G308A in both samples independently with borderline significance in the sib pair families (0.064) and with a nominally significant value of P=0.022 in the trio families. Combining both samples produced P=0.003, while LTalpha+A252G, located approximately 2-3 kb distally, revealed P=0.03 and the two locus haplotype yielded a P value of 0.001. CONCLUSION: Our data suggests association of the common G allele of the -G308A TNFalpha gene polymorphism with schizophrenia in a sample of 207 families. However, linkage disequilibrium with a different allele of the TNFalpha gene or another gene in the MHC region cannot be excluded.     

Coexistence of delusions of pregnancy and infestation in a male

The coexistent appearance of delusions of pregnancy and infestation is reported in a male patient with posttraumatic epilepsy. While published organic cases of delusions of pregnancy have involved patients with severe or mild mental retardation, our reported patient had a higher than average IQ. The interpretative role of these delusions in a probable perceptual symptomatology cannot be excluded, as both delusions can be based on sensations in the abdomen or on the skin.