Do schizophrenia and bipolar disorders share a common disease susceptibility variant at the MMP3 gene?

There is growing evidence of partial etiological overlap between schizophrenia (SZ) and bipolar I disorder (BD-I) from linkage analysis, genetic epidemiology and molecular genetics studies. SZ and BD-I are neurodevelopmental disorders with genetic and environmental etiologies. Recent studies have demonstrated that matrix metalloproteinase 3 (MMP3) is a key event in associative memory formation, learning and synaptic plasticity, which are important in psychiatric disorders. In the light of these findings, we analyzed the genetic variations in the MMP3-1171 5A/6A in patients with SZ, patients with BD-I and healthy controls. To the best of our knowledge, this is the first study to report an association of variation in gene encoding MMP3 with SZ. Our study group consisted of 111 unrelated patients with SZ, 141 unrelated patients with BD-I, and 121 unrelated healthy controls. The frequencies of 6A6A genotype and 6A allele distributions of MMP3 in patients with SZ were significantly decreased when compared with controls. In contrast, in patients with SZ, the distributions of 5A5A genotype and 5A allele of MMP3 gene were significantly increased as compared with healthy controls. When the frequencies of genotypes or alleles in schizophrenic patients and bipolar patients were compared, 6A6A genotype and 6A allele in patients with BD-I were significantly higher than patients with SZ. In contrast, 5A5A genotype and 5A allele distributions of MMP3 gene were significantly frequent in patients with SZ. On the other hand, no significant differences were found in the allele or genotype distribution in patients with BD-I compared with controls. In conclusion, our data have supported the hypothesis that there is a possible relationship between − 1171 5A/6A polymorphism of MMP3 gene and SZ. A larger sample group is needed to confirm the potential role of this gene in the pathophysiology of psychiatric disorders.     

The effect of risedronate treatment on serum cytokines in postmenopausal osteoporosis: a 6-month randomized and controlled study

There is much evidence suggesting that the decline in ovarian function after menopause is associated with spontaneous increases in proinflammatory cytokines. Treatment with risedronate is accompanied by significant changes in bone turnover and bone mineral density. The objective of this study was to determine the effects of risedronate treatment on the level of serum cytokines including receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin among postmenopausal women with osteoporosis. The study group consisted of 61 postmenopausal women with osteoporosis. Patients were randomly divided in two groups: In group 1 (n = 41) postmenopausal women received oral risedronate (35 mg/week), calcium (1,000 mg/day), and vitamin D (400 IU/day) for 12 months. In group 2 (control group; n = 20) patients received only oral calcium (1,000 mg/day) and vitamin D (400 IU/day). Bone mineral density (BMD) of lumbar spine (L1–L4) and proximal femur were determined using dual X-ray absorptiometry at baseline and after one year. Venous blood samples were obtained for determination of serum cytokines including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), RANKL, osteoprotegerin, and markers of bone formation and resorption. Levels of serum cytokines were measured before therapy and after three and 6 months. Markers of bone metabolism were studied before therapy and after 6 months. In group 1 (risedronate plus calcium/vitamin D-treated patients), serum levels of RANKL and IL-1β significantly decreased and the level of osteoprotegerin significantly increased after three and 6 months, but no significant difference was found in TNF-α level. In group 2, however, the level of serum cytokines did not change after three and 6 months. In cases of bone turnover, both markers of bone resorption and formation significantly decreased after 6 months in group 1. In conclusion risedronate could improve osteoporosis by increasing osteoprotegerin and reducing RANKL and IL-1β.     

Theory of mind and unawareness of illness in schizophrenia

This study investigates the impact of theory of mind (ToM) deficits on poor insight in schizophrenia. The scale for unawareness of mental disorder (SUMD) was administered to 58 stable outpatients with schizophrenia. First and second order false belief tasks, the Eyes test and a battery of nonToM cognitive measures were administered. The Second order false belief task was the best predictor of each global insight and symptom attribution scores of the SUMD. ToM tasks explained the substantial amount of the variance (ranging from 22.5% to 29.9%) for the insight scores and classified the significant amount of the patients who were aware of the illness correctly. WCST perseveration scores did not contribute to insight scores beyond that contributed by second order false belief tasks. The Second order ToM tasks seems to have critical importance for the awareness of the disorder. Beyond more direct self-evaluation, the awareness of the disorder and its consequences may also require the ability to evaluate the self from the perspective of others. "Understanding the others' belief about another person" may be conceptually very similar to "understanding the others' belief about self" (instead of another person).     

Pneumocystis carinii pneumonia in a rheumatoid arthritis patient treated with adalimumab

Patients with rheumatoid arthritis (RA) have an increased risk of infection as a result of alterations in immune regulation, debility, and comorbid illnesses. TNF-alpha is of central importance in the pathophysiological responses to infection and inflammation, and plays a crucial role in host defence. Pneumocystis carinii is an opportunistic pathogen that commonly affects individuals with inadequate T-cell mediated immune response. Patients with acquired immune deficiency, as well as those receiving immunosuppressive drugs for various conditions have an increased risk of P. carinii pneumonia (PCP). We report the development of PCP in a woman with RA shortly after the initiation of anti-TNF-alpha treatment with adalimumab.     

Novel cardiovascular risk factors and cardiac event predictors in female inactive systemic lupus erythematosus patients

Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which cannot be explained by traditional risk factors alone. This study aims to investigate novel cardiovascular risk factors and cardiac event predictors in inactive SLE female patients who do not have any major cardiovascular risk factors. Twenty-five inactive (SLE disease activity index score <4) SLE female patients and 22 healthy control women were studied. SLE patients with a history of diabetes mellitus, hypertension, hyperlipidemia, smoking, or coronary artery disease (CAD) were excluded. Venous blood samples were analyzed for lipid subfractions and novel cardiovascular risk factors such as lipoprotein (a), homocysteine, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and serum amyloid A (SAA) levels. Endothelial dysfunction was assessed by flow-mediated dilatation (FMD) from the brachial artery at baseline and during reactive hyperemia. SLE patients and controls were similar in terms of age (40±10 years vs 38±10 years, p = NS). No significant difference was found between the groups regarding family history of premature CAD, blood pressure, body mass index, lipoprotein (a), homocysteine, fibrinogen, SAA, apoprotein A-1 and B levels. Compared with the controls, SLE patients had higher levels of hs-CRP [median (range): 1.82 (0.02–0.98) vs 0.68 (0.02–0.35), p=0.04]. FMD was lower in SLE patients than controls (7.1±2.1 vs 11.4±1.2%, p<0.001). Increased levels of hs-CRP and decreased FMD were found in inactive SLE patients. Increased hs-CRP levels may reflect ongoing low-grade inflammation that could be a cause of impaired FMD in SLE patients. These findings suggest that SLE patients without traditional major cardiovascular risk factors may have increased risk of cardiovascular disease and future cardiac events.     

Accurate diagnosis of acute abdomen in FMF and acute appendicitis patients: how can we use procalcitonin?

This study was conducted to define the value of procalcitonin (PCT) levels in the differential diagnosis of abdominal familial Mediterranean fever (FMF) attacks from acute appendicitis. From October 2006 to January 2007, 28 FMF (12 males, 16 females) patients with acute abdominal attacks and 34 patients (18 males) with acute abdomen who underwent operation with the clinical diagnosis of acute appendicitis were consecutively enrolled in this study. FMF patients with concurrent infectious diseases were excluded. PCT values were measured by an immunofluorescent method using the B.R.A.H.M.S. PCT kit (B.R.A.H.M.S. Diagnostica, Berlin, Germany). Erythrocyte sedimentation rate (ESR), C-reactive proteins (CRP) and leucocyte levels were also noted. Mean disease duration in FMF patients was 9.6 ± 8.1 years (range 2–33 years) and all were on colchicine therapy with a mean colchicine dosage of 1.2 ± 0.4 mg/day. Among the operated patients, 5 were excluded: 3 patients had normal findings and 2 had intestinal perforation (PCT levels were 2.69 and 4.93 ng/ml, respectively) at operative and pathologic evaluation. There were no significant differences between the two groups with respect to gender and age (p was not significant (NS) for all). Acute phase reactants and PCT levels were increased in patients with FMF compared to patients with acute appendicitis (0.529[0.12 ± 0.96] vs 0.095 [0.01–0.80] p < 0.001, respectively). PCT levels higher than 0.5 ng/ml were found in 11% (3/28) of FMF patients compared to 62% (18/29) of acute appendicitis patients (p < 0.001). Our results suggest that PCT could be a useful test in the differentiation of abdominal FMF attacks from acute appendicitis, though it should not supplant more conventional investigations.     

Cell type accuracy of transthoracic fine needle aspiration in primary lung cancer

In this study, we aimed to evaluate the diagnostic accuracy of transthoracic fine needle aspiration (TFNA) specimens in establishing the specific cell type in primary lung cancer and to study the influence of several factors on this accuracy. Forty-six patients with lung cancer diagnosed by TFNA specimens who subsequently underwent thoracotomy between April 2003 and December 2005 were included. Fourty-one patients were men and five were women with a mean age of 59.8 +/- 10 years (34-68 years). TFNA was performed by 22-Gauge Chiba needle with computed tomography guided in all patients. There was cell agreement in 38 of 46 cases (82.6%, Kappa= 0.73). The concordance was 70.8% (Kappa= 0.65) in cases with squamous cell carcinoma and 100% (Kappa= 0.74) in cases with adenocarcinoma (p= 0.01). Stage of the tumor, the diameter and location of the lesion had no effect on cell type agreement (p> 0.05). The concordance was 63.6% in poor differentiated tumors and 92.9% in well differentiated tumors (p> 0.05). Our results pointed out that tumor cell type was the only factor effecting tumor cell type agreement between TFNA and thoracotomy.