The CC genotype of the C825T polymorphism of the G protein beta3 gene (GNB3) is associated with a high relapse rate in patients with chronic lymphocytic leukaemia

A C825T polymorphism has been described in the GNB3 gene which encodes the Gbeta3 subunit of heterotrimeric G proteins. The GNB3 825T allele is predictive of enhanced Gi protein activation. This study was performed to correlate genotypes of the C825T polymorphism with various clinical aspects of chronic lymphocytic leukaemia (B-CLL). The GNB3 genotype distribution in B-CLL patients was similar to that in other Caucasian populations, arguing against a role of the polymorphism in the susceptibility to develop B-CLL. No statistically significant differences were observed at diagnosis between patients with the CC genotype and homozygous or heterozygous T allele carriers with respect to age at disease onset, sex distribution, proportion of patients with CD38+ leukaemia or patients in Binet stage A, blood cell counts, degree of bone marrow infiltration or serum levels of lactate dehydrogenase, thymidine kinase or beta2-microglobulin. In a subgroup of 44 patients requiring chemotherapy, the median interval between diagnosis and first treatment and the response to treatment were similar in patients with CC or CT/TT genotypes. A statistically significant difference, however, was found in the proportion of patients relapsing and requiring second line chemotherapy (CC: 95%; CT/TT: 52%; p = 0.0043). The GNB3 genotype (p = 0.024) and age (p = 0.042) were identified as independent prognostic factors for a second therapy. Thus, the long-term success of the treatment appears to be correlated with the GNB3 genotype.     

Quantitative determination of piroxicam in a new formulation (piroxicam-beta-cyclodextrin) by derivative UV spectrophotometric method and HPLC

A derivative ultraviolet (UV) spectrophotometric method for the determination of piroxicam in piroxicam--beta-cyclodextrin tablets was developed. Phosphate buffer (pH 7.8, 0.1 M) and ethanol were used as a solvent system throughout the study. In this study, determination of piroxicam was conducted by using first order derivative amplitudes at 261.4 nm (n=4). Standards for the calibration graph ranging from 2.40 to 20.0 microg/ml were prepared from working standard. The proposed method is accurate with 99.70%+/-0.50 recovery value and precise with coefficient of variation (CV) of 1.29. The results were compared with those obtained using a high-performance liquid chromatography (HPLC) procedure. A reversed-phase C(18) column with aqueous phosphate buffer:methanol, 60:40, v/v, mobile phase was used. UV detector was set at 254 nm. Calibration solutions used in HPLC were ranging from 5 to 20 microg/ml. Results obtained in HPLC were comparable to those obtained by derivative UV spectrophotometric method.     

Left main coronary artery aneurysm associated with extensive coronary arterial calcification: case report and review

We present a 68-year-old male with left main coronary artery aneurysm and extensive coronary calcification involving the entire coronary arterial tree detected by coronary angiography and electron beam computerized tomography. With this article we also discussed the relationships between the pathogenesis of coronary atherosclerosis, coronary calcification, and coronary aneurysm formation.     

Pathophysiology underlying drooling in Parkinson’s disease: oropharyngeal bradykinesia

We aimed to investigate the association between drooling and possible etiological factors in Parkinson’s disease (PD) and to determine its effect on the quality of life. Demographic data of the 63 patients with idiopathic PD were recorded. Radboud Oral Motor Inventory for Parkinson’s disease (ROMP) test was administered to all patients to evaluate speech, swallowing functions, and saliva control. The freezing of gait questionnaire (FOGQ) was used to evaluate gait and freezing of gait. Dynamic Parkinson gait scale (DYPAGS) was administered for the objective quantification of PD gait features. Disease severity was assessed by UPDRS and modified Hoehn & Yahr Scale. PD specific health-related quality was evaluated by PDQ-39 questionnaire. Drooling was only significantly correlated to UPDRS score; a stronger association was found between drooling and UPDRS 3 motor score; and a more significant association was determined between drooling and the bradykinesia questions of the motor part of UPDRS 3. Interestingly, no significant association was found between sialorrhea score and PDQ-39 score. Based on the results of this study, we concluded that oropharyngeal bradykinesia may be responsible for drooling in PD. In contrast to a general expectation, we did not find any adverse impact of drooling on the quality of life.     

Co-existence of chronic renal failure, renal clear cell carcinoma, and Blau syndrome

Blau syndrome is a rare, multisystem, autosomal-dominant, and granulomatous disorder caused by susceptibility variants in the NOD2 gene. We describe here a 14-year-old girl with Blau syndrome with incidentally diagnosed renal carcinoma. The index case presented with growth retardation and recurrent symmetric arthritis. Her clinical symptoms included bilateral cataract due to recurrent uveitis, camptodactyly, and persistent erythematous rash with ichthyosis. Her two sisters and her mother were affected with combinations of these conditions—symmetric polyarthritis, uveitis, and skin involvement—suggesting an autosomal dominant trait. The index case developed a chronic renal insufficiency, and an abdominal computerized tomography scan revealed a 2.5-cm mass in the left kidney. The histopathological examination showed renal clear cell carcinoma, chronic tubulointerstitial nephritis, and giant cell granulomas in both the tumor and non-neoplastic renal tissue. Granulomatous inflammation was observed in the skin biopsy specimen. The patient was diagnosed with Blau syndrome based on her family history, uveitis, granulomatous inflammation proved by skin biopsy, and polyarthritis. Sequencing of the NOD2 gene showed a heterozygous p.R334Q mutation in all affected family members. To the best of our knowledge, this is the first reported case of a patient with Blau syndrome accompanied by chronic renal failure and renal carcinoma.     

Xanthogranulomatous salpingitis as a rare pathologic aspect of chronic active pelvic inflammatory disease

Xanthogranulomatous salpingitis (XGS) is a rare form of chronic inflammation of the fallopian tubes. A 41-year old woman with a history of secondary infertility for 2 years is presented. The patient underwent bilateral salpingooopherectomy with presumptive diagnosis of adnexal mass with cystic component. Intraoperative pathology consultation was done. The diagnosis of bilateral XGS associated with chronic active follicular salpingitis was made. XGS is reported to be caused by an unsuccesfully treated pelvic inflammatory disease. Its association with chronic active follicular salpingitis has not been previously reported. Chronic active follicular salpingitis with xanthogranulomatous inflammation might give the impression of a cystic adnexal mass with septations on preoperative pelvic computed tomography. Frozen sections are necessary to rule out malignancy as done in our case.     

Rosiglitazone Attenuates Liver Inflammation in a Rat Model of Nonalcoholic Steatohepatitis

Rosiglitazone is an insulin-sensitizing agent. We aimed to assess the effects of rosiglitazone on a methionine- and choline-deficient diet (MCDD) model of nonalcoholic steatohepatitis (NASH) in rats. Wistar rats were fed either MCDD or a control diet in the 4-week induction study; they were given saline or 4 mg/kg/day rosiglitazone. After the induction study period, the rats were divided into four groups and fed MCDD or given a control diet for an additional 8 weeks and received saline or rosiglitazone. Serum and tissue samples were obtained. Rosiglitazone improved inflammation in NASH and improved ALT, alkaline phosphatase, and interleukin-6 levels in the induction study and interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in the treatment study. Our preliminary study is the first to show the anti-inflammatory effects of rosiglitazone in NASH. Rosiglitazone’s effect on cytokines may be a key mechanism of its anti-inflammatory effect in NASH.