Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.

ASSOCIATION BETWEEN SADDLE NOSE DEFORMITY AND RETRO-ORBITAL MASS IN WEGENER`S GRANULOMATOSIS

Objectives: The relationship between saddle nose deformity (SND) in Wegener`s granulomatosis (WG) and other clinical features, including retro-orbital mass formation (ROM), has been poor described. Therefore, this relationship was analyzed retrospectively from 2000 to 2010. Patients and Methods: Eighteen consecutive WG patients with SND diagnosed by computed tomography were matched to 36 WG patients without SND (control group) for gender, age at WG diagnosis and disease duration. Results: No difference was found between the two groups in relation to WG type (limited and systemic forms), ethnicity, laboratory features, constitutional symptoms or clinical manifestations, including upper respiratory tract, and treatment, except for ROM (33.3 vs. 2.8% in SND(+) and SND(-) groups, respectively; p=0.004) and subglottic stenosis (22.2 vs. 2.8%; p=0.038). However, on multivariate analysis, only ROM (OR 17.15; 95% CI 1.11-265.52) was statistically associated to SND. In addition, in more than half of the cases, SND manifested prior to ROM. Conclusions: Results of this prospective analysis showed that SND was strongly associated to ROM in WG. Since early diagnosis and aggressive treatment of orbital involvement could lead to better prognosis, the presence of SND warrants additional vigilance.

Diffuse systemic sclerosis and autoimmune hepatitis: a unique association

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology characterized by continuing hepatocellular necrosis and inflammation that afflicts 100,000 to 200,000 persons in the United States. It is a rare manifestation of systemic sclerosis. Only about nine reports of this association have been previously reported in the literature. Importantly, all cases had the limited clinical form of systemic. The authors describe herein the first report of a patient with diffuse systemic sclerosis who was diagnosed with AIH with positive antimitochondrial antibody and had an excellent response to immunosuppressive drugs. We also briefly review the literature regarding this issue.

Prevalence of Alcohol-Related Problems in an Elderly Population and Their Association With Cognitive Impairment and Dementia

Background: Studies investigating the association between alcohol use and cognitive disorders in the elderly population have produced divergent results. Moreover, the role of alcohol in cognitive dysfunction is not clear. The aims of this study were to estimate the prevalence of alcohol-related problems in an elderly population from Brazil and to investigate their association with cognitive and functional impairment (CFI) and dementia. Methods: A community-based cross-sectional study was performed. A sample of 1,145 elderly people was examined in 2 phases. Several instruments were utilized in the first phase: the CAGE questionnaire was used to identify potential cases of alcohol-related problems, and a screening test for dementia was used to estimate CFI. The CAMDEX interview (Cambridge Examination) and DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria were used for the clinical diagnosis of dementia in the second phase. Results: ""Heavy alcohol use"" (CAGE >= 2) was found in 92 subjects (prevalence: 8.2%). It was associated with gender (males, p < 0.001), low education (only in females, p = 0.002), and low socioeconomic level (p = 0.001, in females; p = 0.002, in males). The Mini Mental State Examination exhibited a nonlinear relationship with alcohol-related problems in females; ""mild-moderate alcohol use"" (CAGE < 2) presented the highest score. A significant association between alcohol-related problems and cognitive dysfunction was found only in females. ""Heavy alcohol use"" was associated with higher CFI and dementia rates compared to ""mild-moderate alcohol use"" (p = 0.003 and p < 0.001, respectively). ""Mild-moderate alcohol use"" had a tendency of association with lower CFI and dementia rates when compared to ""no alcohol use"" (p = 0.063 and 0.050, respectively). Conclusion: Our findings suggest that alcohol use does not have a linear relationship with cognitive decline.

Behcet`s disease associated with celiac disease: a very rare association

There are common findings between Beh double dagger et`s disease (BD) and celiac disease (CD); however, association in the same patient is a rarity. We relate the third case in the literature of this overlap in a 40-year-old woman with history of obstipation since her childhood. She also presented asymmetric polyarthralgia, loss of weight, anemia, oral recurrent aphthas (> 3/year) and genital ulcerations, inflammatory lower back pain, bowel bleeding and abdominal colic. Afterwards, she presented episodes of erythema nodosum, superficial thrombophlebitis, pseudofolliculitis and aseptic meningitis, thus fulfilling criteria for BD. Due to persistence of the digestive complaints, a gastrointestinal endoscopy was performed. The biopsy showed chronic duodenitis with intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. Endomysial antibody was positive. She fulfilled the diagnosis criteria for CD; a gluten-free diet was applied with clinical improvement. Ascertaining whether pathogenic mechanisms are common in these two conditions requires further investigation.

Hyaluronan in vaginal secretions: association with recurrent vulvovaginal candidiasis

OBJECTIVE: We evaluated whether vaginal concentrations of hyaluronan were altered in women with recurrent vulvovaginal candidiasis (RVVC). STUDY DESIGN: Lavage samples from 17 women with acute RVVC, 27 women who were receiving a maintenance antifungal regimen, and 24 control women were tested for hyaluronan and interleukin (IL)-6, IL-12, and IL-23 by enzyme-linked immunosorbent assay. RESULTS: Median vaginal hyaluronan concentrations were 33.8 ng/mL (range, 21.6-66.3 ng/mL) in women with acute RVVC, 15.0 ng/mL (range, 11.2-50.6 ng/mL) in women who were receiving maintenance therapy, and 4.2 ng/mL (range, 3.6-12.0 ng/mL) in control subjects (P <= .02). The vaginal hyaluronan concentration was 27.4 ng/mL (range, 15.4-37.7 ng/mL) when Candida was detected by microscopy and 9.5 ng/mL (range, 7.7-14.6 ng/mL) in microscopy-negative cases (P = .0354). Elevated hyaluronan levels were associated with itching plus burning (40.7 ng/mL) or itching plus discharge (42.1 ng/mL), as opposed to itching only (6.2 ng/mL; P = .0152). Hyaluronan and IL-6 levels were correlated (P = .0009). CONCLUSION: Hyaluronan release is a component of the host response to a candidal infection and may contribute to symptoms.

Primary antiphospholipid syndrome with thrombotic thrombocytopenic purpura: a very unusual association

This report considers the rare situation in which primary antiphospholipid syndrome (PAPS) is linked with thrombotic thrombocytopenic purpura (TTP). It describes the case of a young lady with PAPS, characterized by recurring cerebro-vascular abnormalities and marked livedo reticularis, combined with circulating anticardiolipin and lupus anticoagulant antibodies. On follow-up, while on oral anticoagulation, she developed severe thrombocytopenia associated with hematuria, microangiophatic anaemia and neurological manifestations consistent with a diagnosis of TTP. The patient was treated with pulses of methylprednisolone and plasmapheresis with plasma exchange. The result was a favourable outcome. To our knowledge, this is the seventh report on this rare association in the English-language literature of this field. Lupus (2009) 18, 841-844.

Juvenile dermatomyositis and toxoplasmosis: a rare association

Dermatomyositis is an unknown cause`s disease that in general is characterized by muscular inflammation with weakness and typical skin rash (heliotrope and Gottron`s papules). In this article we describe a 13-year-old girl with juvenile dermatomyositis associated with toxoplasmosis. Myositis was treated with corticosteroids and immunosuppressive drugs, but she had good response only after anti-parasitary drug was started.-

Association Between Increased Platelet P-Selectin Expression and Obesity in Patients With Type 2 Diabetes A BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) substudy

OBJECTIVE- To determine whether obesity increases platelet reactivity and thrombin activity in patients with type 2 diabetes plus stable coronary artery disease. RESEARCH DESIGN AND METHODS- We assessed platelet reactivity and markers of thrombin generation and activity in 193 patients from nine clinical sites of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D). Blood taken at the time of enrollment was used for assay of the concentration of prothrombin fragment 1.2 (PT1.2, released when prothrombin is activated) and fibrinopeptide A (FPA, released when fibrinogen is cleaved). Platelet activation was identified with the use of flow cytometry in response to 0, 0.2, and 1 mu mol/l adenosine diphosphate (ADP). RESULTS- Concentrations of FPA, PT1.2, and platelet activation in the absence of agonist were low. Greater BMI was associated with higher platelet reactivity in response to 1 mu m ADP as assessed by surface expression of P-selectin (r = 0.29, P < 0.0001) but not reflected by the binding of fibrinogen to activated glycoprotein IIb-IIIa. BMI was not associated with concentrations of FPA or PT1.2. Platelet reactivity correlated negatively with A1C (P < 0.04), was not related to the concentration Of triglycerides in blood, and did not correlate with the concentration of C-reactive peptide. CONCLUSIONS- Among patients enrolled in this substudy of BARI 2D, a greater BMI was associated with higher platelet reactivity at the time of enrollment. Our results suggest that obesity and insulin resistance that accompanies obesity may influence platelet reactivity in patients with type 2 diabetes.

Can a N-2-fixing Gluconacetobacter diazotrophicus association with sugarcane be achieved?

Several published studies claim that high rates of N-2 fixation occur in sugarcane and sorghum, and have ascribed this result to infection by the bacterium Gluconacetobacter diazotrophicus, abetted by arbuscular mycorrhizal infection ( Glomus clarum). These results have not been confirmed within Australia. In this study, G. diazotrophicus was detected in stalks of field-grown sugarcane in Australia ( based on phenotypic tests, and a PCR test using species-specific primers developed to amplify a fragment of the G. diazotrophicus 16S rRNA gene). Isolates were nitrogenase positive ( acetylene reduction assay) in vitro. However, in glasshouse trials involving inoculation of sugarcane setts with G. diazotrophicus, co-inoculation with mycorrhizae, and plant growth under low N status, recovery of bacteria from maturing plants was variable. At 165 days from planting, no appreciable N-2-fixation, as assessed by dry weight increment, N budget, or N-15 ratio, of either an Australian or a Brazilian cultivar of sugarcane, or a sorghum cultivar, was achieved. We conclude that a N-2-fixing sugarcane - G. diazotrophicus association is not easily achievable, being primarily limited by a lack of infection.

Association of Changes in Bone Remodeling and Coronary Calcification in Hemodialysis Patients: A Prospective Study

Background: Vascular calcification is common and constitutes a prognostic marker of mortality in the hemodialysis population. Derangements of mineral metabolism may influence its development. The aim of this study is to prospectively evaluate the association between bone remodeling disorders and progression of coronary artery calcification (CAC) in hemodialysis patients. Study Design: Cohort study nested within a randomized controlled trial. Setting & Participants: 64 stable hemodialysis patients. Predictor: Bone-related laboratory parameters and bone histomorphometric characteristics at baseline and after 1 year of follow-up. Outcomes: Progression of CAC assessed by means of coronary multislice tomography at baseline and after 1 year of follow-up. Baseline calcification score of 30 Agatston units or greater was defined as calcification. Change in calcification score of 15% or greater was defined as progression. Results: Of 64 patients, 26 (40%) had CAC at baseline and 38 (60%) did not. Participants without CAC at baseline were younger (P < 0.001), mainly men (P = 0.03) and nonwhite (P = 0.003), and had lower serum osteoprotegerin levels (P = 0.003) and higher trabecular bone volume (P = 0.001). Age (P 0.003; beta coefficient = 1.107; 95% confidence interval [Cl], 1.036 to 1.183) and trabecular bone volume (P = 0.006; beta coefficient = 0.828; 95% Cl, 0.723 to 0.948) were predictors for CAC development. Of 38 participants who had calcification at baseline, 26 (68%) had CAC progression in 1 year. Progressors had lower bone-specific alkaline phosphatase (P = 0.03) and deoxypyridinoline levels (P = 0.02) on follow-up, and low turnover was mainly diagnosed at the 12-month bone biopsy (P = 0.04). Low-turnover bone status at the 12-month bone biopsy was the only independent predictor for CAC progression (P = 0.04; beta coefficient = 4.5; 95% Cl, 1.04 to 19.39). According to bone histological examination, nonprogressors with initially high turnover (n = 5) subsequently had decreased bone formation rate (P = 0.03), and those initially with low turnover (n = 7) subsequently had increased bone formation rate (P = 0.003) and osteoid volume (P = 0.001). Limitations: Relatively small population, absence of patients with severe hyperparathyroidism, short observational period. Conclusions: Lower trabecular bone volume was associated with CAC development, whereas improvement in bone turnover was associated with lower CAC progression in patients with high- and low-turnover bone disorders. Because CAC is implicated in cardiovascular mortality, bone derangements may constitute a modifiable mortality risk factor in hemodialysis patients.

Anxiety Disorders and Rheumatic Fever: Is There an Association?

Introduction: Findings suggest that obsessive-compulsi e disorder (OCD) and related disorders, referred to as obsessive-compulsive spectrum disorders (OCSDs), are more common in patients with rheumatic fever (RF). Objectives: To determine whether RF or Sydenham`s chorea increases the probability of anxiety disorders in the relatives of individuals with RF with and without SC. Methods: This was a case-Control family study in which 98 probands and 389 first-degree relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson regression model was used to determine whether the presence of any disorder in one family member influences the rate of disorders in the remaining family members. Results: Generalized anxiety disorder (GAD) occurred more frequently in the FDRs of RF probands than in those of control probands (P=.018). The presence of RF,GAD, or separation anxiety disorder in one family member significantly increased the chance of OCSDs in another member of the family.

Association of mannose-binding lectin gene polymorphism but not of mannose-binding serine protease 2 with chronic severe aortic regurgitation of rheumatic etiology

N-Acetylglucosamine (GlcNAc) is the major immunoepitope of group A streptococcal cell wall carbohydrates. Antistreptococcal antibodies cross-reactive with anti-GlcNAc and laminin are present in sera of patients with rheumatic fever. The cross-reactivity of these antibodies with human heart valvular endothelium and the underlying basement membrane has been suggested to be a possible cause of immune-mediated valve lesion. Mannose-binding lectin (MBL) encoded by the MBL2 gene, a soluble pathogen recognition receptor, has high affinity for GlcNAc. We postulated that mutations in exon 1 of the MBL2 gene associated with a deficient serum level of MBL may contribute to chronic severe aortic regurgitation (AR) of rheumatic etiology. We studied 90 patients with severe chronic AR of rheumatic etiology and 281 healthy controls (HC) for the variants of the MBL2 gene at codons 52, 54, and 57 by using a PCR-restriction fragment length polymorphism-based method. We observed a significant difference in the prevalence of defective MBL2 alleles between patients with chronic severe AR and HC. Sixteen percent of patients with chronic severe AR were homozygotes or compound heterozygotes for defective MBL alleles in contrast to 5% for HC (P = 0.0022; odds ratio, 3.5 [ 95% confidence interval, 1.6 to 7.7]). No association was detected with the variant of the MASP2 gene. Our study suggests that MBL deficiency may contribute to the development of chronic severe AR of rheumatic etiology.

Association between tumoral GH-releasing peptide receptor type 1a mRNA expression and in vivo response to GH-releasing peptide-6 in ACTH-dependent Cushing`s syndrome patients

Objective: GH secretagogues (GHS) produce exaggerated ACTH and cortisol responses in Cushing`s disease (CD) patients, attributable to their direct action on GH-releasing peptide receptor type la (GHSR-1a). However, there are no studies correlating the ill vivo response to GHS and GHSR-1a mRNA expression in ACTH-dependent Cushing`s syndrome (CS) patients. The aim of this study is to correlate the patterns of ACTH and cortisol response to GH-releasing peptide-6 (GHRP-6) to GHSR-1a expression in ACTH-dependent CS patients Design: Prospective study in a tertiary referral hospital center. Fifteen CD patients and two ectopic ACTH syndrome (EAS) patients were studied. Methods: Tumor fragments were submitted to RNA extraction, and GHSR-1a expression was studied through real-time qPCR and compared with normal tissue samples. The patients were also submitted to desmopressin test and vasopressin receptor type 1B (AVPR1B) mRNA analysis by qPCR. Results: GHSR-1a expression was similar in normal pituitary samples and in corticotrophic tumor samples. GHSR-1a expression was higher in patients (CD and EAS) presenting ill vivo response to GHRP-6. Higher expression of AVPR1B was observed in the EAS patients responsive to desmopressin, as well as in corticotrophic tumors, as compared with normal pituitary samples, but no correlation between AVPR1B expression and response to desmopressin was observed in the CD patients. Conclusions: Our results revealed a higher expression of GHSR-1a in the ACTH-dependent CS patients responsive to GHRP-6, suggesting an association between receptor gene expression and ill vivo response to the secretagogue in both the CD and the EAS patients.