Improvement of Pulmonary Function by Oral Treatment with a VLA-4 Antagonist in a Mouse Asthmatic Model

We investigated in vivo efficacies of the newly synthesized VLA-4 antagonist Compound A {trans-4-[1-[[2,5-Dichloro-4-(1-methyl-3-indolylcarboxamido)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid} on Ascaris antigen–induced airway inflammation and hyperresponsiveness in a murine asthmatic model. Oral administration of Compound A significantly inhibited eosinophil infiltration into BALF and airway hyperresponsiveness 48 h after the antigen challenge. Histologic analysis of the lung sections confirmed the BALF result and revealed suppression of edema and mucus hyperplasia at 8 and 48 h after the challenge, respectively. These findings clearly show that orally active Compound A has therapeutic potential for treatment of asthma.     

Dysfunctional family functioning in high socioeconomic status families as a risk factor for the development of psychiatric disorders in adoptees: the Finnish Adoptive Family Study of Schizophrenia

Purpose

Earlier findings indicate that socioeconomic status (SES) of family associates with family functioning. This study examined the impacts of family functioning and genetic risk for schizophrenia on psychiatric morbidity of adoptees in families of high SES (HSES) and low SES (LSES).

Methods

The study population is a subgroup of the Finnish Adoptive Family Study of Schizophrenia. Of the adoptees, 152 had high genetic risk for schizophrenia spectrum disorders (HR) and 151 adoptees had low risk (LR). Of the adoptees, 185 (HR = 94, LR = 91) were raised in high-SES (HSES) families and 118 (HR = 58, LR = 60) in low-SES (LSES) families. The family SES was determined by the occupational status of the main provider of the family. The functioning of adoptive families was assessed based on Global Family Ratings (GFRs) and psychiatric disorders on DSM-III-R criteria.

Results

In the HSES families, the psychiatric morbidity of the adoptees was emphasized by HR (OR = 4.28, CI 2.14–8.56) and dysfunctional family processes (OR = 6.44, CI 2.75–15.04). In the LSES families, the adoptees´ psychiatric morbidity was almost significantly increased by HR (OR = 2.10, CI 0.99–4.45), but not by dysfunctional family processes (OR = 1.33, CI 0.53–3.34).

Conclusions

This study showed that in HSES families, dysfunctional family processes and HR for schizophrenia increased the likelihoods for the development of psychiatric disorders in adoptees. The results can be utilized in identifying risk factors in the development of psychiatric disorders and focusing preventative strategies on risk groups with acknowledging the importance of family functioning.

     

Employment status, mental disorders and service use in the working age population

OBJECTIVES: This study examined the association between employment status and specific DSM-IV (Diagnostic and Statistical Manual for Mental Disorders, IVth edition) depressive, anxiety and alcohol use disorders and the association between employment status and service use for these disorders. METHODS: As part of the representative population-based "Health 2000 Study" of Finns aged 30 years or over, 3440 employed, 429 unemployed, and 820 economically inactive persons of working age (30-64 years) participated in a comprehensive health examination, including the standardized Composite International Diagnostic Interview. RESULTS: The risk of mental disorders was generally higher among the unemployed and the economically inactive than among the employed. The respective odds ratios were 1.79 [95% confidence interval (95% CI) 1.26-2.54] and 1.54 (95% CI 1.06-2.25) for depressive disorders, 2.68 (95% CI 1.85-3.89) and 2.53 (95% CI 1.76-3.65) for anxiety disorders, and 2.58 (95% CI 1.82-3.65) and 1.43 (95% CI 0.91-2.22) for alcohol use disorders. Similar results were obtained for most of the specific categories of these disorders. Among the persons with anxiety disorders, the odds for treatment contact were 2.35 (95% CI 1.06-5.23) times higher for the unemployed than for the employed after control for disorder severity. For those with an alcohol use disorder, the corresponding odds ratio was 3.51 (95% CI 1.23-9.98). CONCLUSIONS: Common mental disorders are less prevalent among the employed than among unemployed and economically inactive people. Among those with anxiety or alcohol use disorders, service use is less common among the employed than among the unemployed. This difference is not explained by the severity of the clinical state.     

Pulse pressure responses to psychological tasks improve the prediction of left ventricular mass: 10 years of follow-up

OBJECTIVES: To examine the role of casual blood pressure measurements and blood pressure responses to psychological tasks in the prediction of future left ventricular mass index (LVMI), and to determine the importance of different components of blood pressure, and the predictive value of an individual's personal characteristics and antihypertensive medication on future LVMI. METHODS: At baseline, blood pressure was recorded by casual measurements; during tests it was recorded by intra-arterial monitoring. The participants were healthy, untreated 35-45-year old men. Echocardiography data both at baseline and after 10 years of follow-up were available from 65 individuals, of whom 49 (75%) were not taking antihypertensive medication at follow-up. Those not taking antihypertensive medication were included in the prediction of LVMI (g/m2). RESULTS: Baseline LVMI correlated significantly with future LVMI only among the 49 unmedicated individuals (r = 0.52, P < 0.0001). The predictive value of baseline LVMI on future LVMI among them (adjusted coefficient of determination = 0.26) was not improved by the inclusion of casual blood pressure. In contrast, blood pressure responses to the psychological tasks improved the prediction of future LVMI by 4-13%. Pulse pressure was the blood pressure variable that entered the final prediction models; the correlations with future LVMI were best for pulse pressure response to habituation task (r = 0.43, P < 0.05) and to relaxation (r = 0.37, P < 0.05). CONCLUSIONS: To our knowledge, this is the longest prospective follow-up to show that blood pressure responses to psychological tasks improve the prediction of LVMI compared with casual blood pressure measurements. The pulse pressure, which reflects the properties of the arterial wall, is the most significant blood pressure variable in predicting future LVMI.     

3D-visualization of the temporomandibular joint with focus on the articular disc based on clinical T1-, T2-, and proton density weighted MR images

Objective An approach of 3D-visualization of the temporomandibular joint (TMJ) with special focus on the articular disc based on magnetic resonance imaging (MRI) was developed for the purpose of diagnosis support. Materials and methods Mandibular condyle and fossa were reconstructed as 3D-surfaces. Articular disc, retrocondylar tissue, and the lateral pterygoid muscle were visualized by means of direct volume rendering. By simultaneous visualization of both, the bony surfaces and the soft tissue, anterior disc displacement could be recognized in 3D-context. Additional superposition of the 3D-visualization with the original 2D-MRI slices allowed for a combination with conventional diagnostics. The method was tested for clinical T1-, T2-, and proton density weighted MRI data from four independent medical institutions. Results For all cases, the skeletal anatomy could be reproduced. Applied validation approaches showed good results. Anterior disc displacement could be clearly depicted as well as the incidence of reduction of the disc. By several experienced observers, the approach was rated as significant. Conclusion Although partially non-standard in the clinical routine the new method provided promising results for efficient diagnosis support. Its validity in the medical practice, namely, its impact for dislocation/deformity of the mandibular disc will be further analyzed. This paper has been written on behalf of a publication request following Cars 2006 conference held in June 2006 in Osaka, Japan. The title of the talk at Cars 2006 conference was “An approach for three-dimensional rendering of the mandibular disc based on high-resolution MR images” authored by Kober C, Hayakawa Y, Kinzinger G, Yamamoto M, Sano T, Sader R, see Int J Comput Assist Radiol Surg 2006 1(Suppl 1): 405–406. I apologize for the delay which was caused by very dense time schedule. In return, the article is a considerable extension of the work presented at Cars 2006.