Chronic physical conditions and use of health services among persons with mental disorders: results from the Israel National Health Survey

OBJECTIVE: This study aimed to determine the association between common mental disorders and common chronic physical conditions and the contribution of mental disorders to the likelihood of being a higher user of health services. METHOD: A representative sample extracted from the National Population Register of noninstitutionalized residents of Israel aged 21 or older were interviewed at their homes between May 2003 and April 2004. Mental disorders were assessed using a revised version of the World Mental Health Composite International Diagnostic Interview. Chronic physical conditions were measured via a checklist of chronic physical disorders. RESULTS: Current mood or anxiety disorders were found to be associated with higher likelihood of chronic pain, cardiovascular conditions, diabetes and respiratory conditions beyond the sociodemographic characteristics and the risk factors (BMI or smoking). Current mood or anxiety disorders increased the likelihood of being a higher user of primary care beyond the effects of gender, population group, self-evaluation of general health, chronic pain or chronic conditions. CONCLUSION: The results regarding the prevalence of mental-physical comorbidity emphasize the need for integration in the physical and mental care of people with mental disorders.     

The Ras antagonist farnesylthiosalicylic acid ameliorates experimental myocarditis in the rat

BackgroundMyocarditis is an inflammatory disorder of the heart in which T lymphocytes have a central role. No effective treatment is currently at hand for management of the myocarditis. Lymphocyte function requires the active signal transducer Ras. We thus hypothesized that S-farnesylthiosalicylic acid (FTS), a synthetic small molecule that detaches Ras from the inner cell membrane and induces its rapid degradation, will attenuate experimental autoimmune myocarditis (EAM).Methods and resultsTwo groups of Lewis rats were induced to develop EAM by immunization with porcine cardiac myosin. Group A received 5 mg/kg of FTS, and group B received phosphate-buffered saline (PBS) according to two protocols: FTS or PBS was given 2 days before myosin immunization in protocol 1 and FTS or PBS was given 14 days after myosin immunization in protocol 2. FTS significantly suppressed myocarditis, and this effect was accompanied by a reduction in myosin-specific cellular and humoral immune responses. In the longer regimen, FTS treatment for 6 weeks was associated with preservation of myocardial function made evident by echocardiography. In vitro, FTS significantly attenuated the proliferation of lymphocytes from untreated myocarditic rats to myosin.ConclusionsFTS is effective in suppressing the progression of EAM and its consequent functional myocardial dysfunction. The effect may be mediated by suppression of the cellular and humoral responses to myosin.     

Intentional injuries among the young: presentation to emergency rooms, hospitalization, and death in Israel

Purpose: To study the incidence and outcome of intentional injuries requiring emergency room (ER) care among children and adolescents in a national sample.

Method: The population included 0- to 17-year-olds who presented to the ER for injuries in 23 hospitals over a 1-year period. A 6% to 9% random sample of days was selected in each hospital, and for each selected day the relevant ER record was reviewed for cause, nature, and outcome of injuries and sociodemographic information.

Results: The annual incidence for intentional injuries resulting in ER visits was 19.6 in 10,000 children and adolescents aged 0 to 17 [95% confidence interval (CI) 17.4–21.8 in 10,000]. Fights/assaults constituted 54.1% of the presentations, abuse and rape, 10.3%, and self-inflicted injuries, 10.8%. Overall rates were higher among 10- to 17 year olds than at younger ages. The rates were higher among boys than girls for fights/assaults and abuse, whereas attempted suicide and rape were three times higher among girls than boys. Nearly twice as many Jewish children and adolescents presented to the ER for intentional injuries than Arab children and adolescents, with the ratio becoming even greater for attempted suicide.

Of all the intentionally injured, 21.7% were hospitalized. The mortality rate was 1.1 in 100,000 (95% CI = .7–1.7/100,00) with no significant gender difference observed. No cases of suicide were reported for the Arab population.

Conclusions: Adolescents aged 10 years and older are at higher risk for intentional injuries than younger children. The ethnic differences evident in this study, especially for attempted and completed suicide, may be real or the result of differential disclosure of information owing to sociocultural norms or differential recording by health professionals.     

Chloroquine synergizes with FTS to enhance cell growth inhibition and cell death

The Ras family of small GTPases transmits extracellular signals that regulate cell growth, differentiation, motility and death. Ras signaling is constitutively active in a large number of human cancers. Ras can also regulate autophagy by affecting several signaling pathways including the mTOR pathway. Autophagy is a process that regulates the balance between protein synthesis and protein degradation. It is important for normal growth control, but may be defective in diseases. Previously, we have shown that Ras inhibition by FTS induces autophagy, which partially protects cancer cells and may limit the use of FTS as an anti-cancer drug. Since FTS is a non toxic drug we hypothesized that FTS and chloroquine (an autophagy inhibitor) will synergize in cell growth inhibition and cell death. Thus, in the present study, we explored the mechanism of each individual drug and their combined action. Our results demonstrate that in HCT-116 and in Panc-1 cells, FTS induces autophagy, which can be inhibited by chloroquine. Furthermore, the combined treatment synergistically decreased the number of viable cells. Interestingly, the combined treatment enhanced apoptotic cell death as indicated by increased sub-G1 cell population, increased Hoechst staining, activation of caspase 3, decrease in survivin expression and release of cytochrome c. Thus, chloroquine treatment may promote FTS-mediated inhibition of tumor cell growth and may stimulate apoptotic cell death.     

Inhibition of contact sensitivity by farnesylthiosalicylic acid-amide, a potential Rap1 inhibitor

We hypothesized that Ras proximate 1 (Rap1) functions as an additional target for farnesylthiosalicylic acid (FTS) or its derivatives, and that the inhibition of Rap1 in lymphocytes by these agents may represent a method for treating inflammatory disorders. Indeed, we found that FTS-amide (FTS-A) was able to inhibit the elicitation phase of delayed cutaneous hypersensitivity in vivo. This effect was associated with the inhibition of Rap1 more than with the inhibition of Harvey rat sarcoma viral oncogene (Ras). Moreover, FTS-A inhibited Rap1 and contact sensitivity far better than FTS. We suggest that FTS-A may serve as a possible therapeutic tool in contact sensitivity in particular and T-cell-mediated inflammation in general.     

Effect of interpregnancy interval on adverse perinatal outcomes — a national study

Background

The interpregnancy interval (IPI) has been reported to influence the outcome of pregnancy and birth. We performed a national study in Israel to determine the impact of IPI on multiple adverse perinatal outcomes.

Study Design

This longitudinal cohort study used birth certificates of siblings born to the same biological mother, with at least one previous birth and a subsequent singleton pregnancy. Adverse pregnancy outcomes included preterm delivery, very preterm birth, small for gestational age (SGA), very SGA (VSGA), early neonatal death and major congenital malformations. Multivariate logistic regression was performed for each outcome.

Results

The study included 440,838 of a total of 846,845 reported live births in Israel over 5 years; excluded were primiparas (32%), multifetal births (4.9%) and those with incomplete data (10.9%). For IPIs shorter than 6 months, there were significantly increased risks for preterm birth (OR=1.23), SGA (OR=1.14), VSGA (OR=1.15), early neonatal death (OR=1.62) and congenital malformations (OR=1.14). Intervals of 60 months or longer had higher risks for preterm birth (OR=1.39) and VSGA (OR=1.16).

Conclusion

Optimal IPI recommendation of >11 months is an accessible and low-cost means to improve multiple adverse perinatal outcomes.     

Custom-Designed Wells and Flow Chamber for Exposing Air–Liquid Interface Cultures to Wall Shear Stress

The effects of mechanical stimuli such as wall shear stresses (WSS) on cellular processes have been studied in vitro in numerous cell types. In order to study WSS effects on cells cultured under air–liquid interface (ALI) conditions, we developed a custom-designed well that can be disassembled into sub-units that allow installation of the cultured cells in a flow chamber, and then, re-assembled for further incubation or biological tests. Human nasal epithelial cells were cultured in the new wells under ALI conditions, and some of their biological characteristics were compared with those cultured in commercial Millicells. The cultured cells from both types of wells secreted the same amount of mucin and had similar cytoskeletal structures. Preliminary WSS experiments demonstrated the advantage of the new wells and provided initial indications that WSS affects the performance of ALI cultured respiratory epithelial cells.     

Clinical and screening implications of the I1307K adenomatous polyposis coli gene variant in Israeli Ashkenazi Jews with familial colorectal neoplasia. Evidence for a founder effect

BACKGROUND: The authors previously found the I1307K adenomatous polyposis coli (APC) gene variant in 5% of Ashkenazi control participants, in 15.4% of those who had familial colorectal neoplasia, but also in 1.6% of non-Ashkenazi control participants. In this study, they evaluated its use in a screening program for familial colorectal neoplasia and examined for a founder effect. METHODS: Consecutive Ashkenazim with a personal and/or family history of colorectal neoplasia had the DNA test. Markers flanking the APC gene were examined in Ashkenazi and non-Ashkenazi I1307K carriers and noncarriers. RESULTS: Among 718 persons, I1307K occurred in 6.2% of Ashkenazi participants, in 1.5% of non-Ashkenazi control participants (P = 0.02), and in 10.7% of Ashkenazim with familial neoplasia (relative risk, 1.73 [not significant compared with controls]; 95% confidence interval, 0.7-3.2). Colorectal neoplasia was detected in carriers at a younger age (P < 0.05) without excess risk for multiple colorectal neoplasia or noncolorectal neoplasia. I1307K attributable risk for colorectal neoplasia was 0.5-0.6%. Compared with noncarriers, both Ashkenazi and non-Ashkenazi I1307K carriers had similar flanking polymorphic alleles (P < 0.01). CONCLUSIONS: I1307K is a low-penetrance genetic variant that indicates a 1.7 relative risk for neoplasia in carriers who have familial carcinoma, clinically equivalent to obtaining a family history of sporadic colorectal neoplasia and promoting early screening. I1307K is a founder genetic variant in Jews of different ethnic origin, mainly Ashkenazim, but it explains only partially their higher incidence of colorectal carcinoma.