Elevated hepatic SULT1E1 activity in mouse models of cystic fibrosis alters the regulation of estrogen responsive proteins.

BACKGROUND: Previous studies with cystic fibrosis transmembrane conductance regulator (CFTR) DeltaF508 mice indicate that estrogen levels may play a role in the occurrence or severity of CF-associated liver disease. However, the underlying mechanisms of liver disease in CF are poorly understood. METHODS: The levels of SULT1E1 (estrogen sulfotransferase) were measured in livers of control and CFTR-knockout (KO) mice. The impact of increased SULT1E1 activity on hepatic protein expression was assessed by immunoblot and MALDI mass spectrometric analysis. RESULTS: SULT1E1 expression was significantly elevated in livers of several CFTR-KO mice. SULT1E1 and CFTR were specifically detected in hepatocytes and cholangiocytes, respectively. Elevated SULT1E1 activity may result in lower levels of free beta-estradiol thereby altering estrogen-responsive hepatic protein expression. Estrogen receptors (ER)-alpha and beta were differentially regulated in CFTR-KO and CFTR-DeltaF508 mice. ERalpha expression was reduced in mice with high SULT1E1 activity. Glutathione S-transferase-P1 and carbonic anhydrase III were significantly decreased in CFTR (-/-) mice with high SULT1E1 activity. Furthermore, cytochrome P450 2B9, also estrogen regulated, was significantly induced in the livers of CFTR (-/-) mice with high SULT1E1 activity. CONCLUSIONS: Elevated SULT1E1 levels and associated alterations in estrogen-regulated hepatic protein expression may play an important role in CF liver disease.     

Diagnosis of diffuse and localized arrhythmogenic right ventricular dysplasia by gated blood-pool SPECT.

This study aimed to assess the ability of global and local systolic parameters measured with gated blood-pool SPECT (GBPS) to diagnose and characterize the severity of diffuse or localized arrhythmogenic right ventricular dysplasia (ARVD). METHODS: Fifty-nine subjects with symptomatic ventricular arrhythmias were prospectively included in the study. With the International Society and Federation of Cardiology criteria for ARVD as a gold standard, these subjects were classified as subjects without ARVD (21 control subjects) and patients with localized ARVD (16 patients) or diffuse ARVD (22 patients). Right ventricular volumes, right ventricular ejection fractions (EF), the SD of local EF (sigma-EF), and the SD of the local times of end systole (sigma-TES) were computed from GBPS data and compared among the groups in the study population. RESULTS: sigma-EF did not differ between control subjects and patients with diffuse or localized ARVD. Right ventricular EF and volumes differed between patients with diffuse ARVD and control subjects, with similar areas under the receiver-operating-characteristic curves, but right ventricular EF and volumes failed to differentiate patients with localized ARVD. In contrast, sigma-TES differed between patients with diffuse or localized ARVD and control subjects. Regression analysis showed that the systolic parameter most strongly associated with the diagnosis of ARVD was sigma-TES. The probabilities of a randomly chosen patient in the diffuse ARVD group and of a randomly chosen patient in the localized ARVD group having sigma-TES values greater than that of a randomly chosen control subject were 98.5% and 96.7%, respectively. For the diagnosis of localized ARVD, a threshold of 80 ms for sigma-TES corresponded to sensitivity, specificity, and positive and negative predictive values of 100%, 81%, 80%, and 100%, respectively. CONCLUSION: With GBPS, both diffuse ARVD and localized ARVD can be accurately diagnosed by computing sigma-TES for all of the pixels on the surface of the right ventricle.     

Reactive arthritis and internal derangement of the temporomandibular joint.

OBJECTIVE: The objective of this study was to determine if temporomandibular joint (TMJ) samples positive for Chlamydia trachomatis have a greater presence of tumor necrosis factor-alpha (TNFalpha) or interleukin-6 (IL-6) when compared with Chlamydia-negative samples. STUDY DESIGN: Posterior bilaminar tissue samples removed during TMJ surgery from 70 patients were evaluated. Cryosections were stained using monoclonal antibody that identifies C. trachomatis. The presence of IL-6 and TNFalpha were evaluated by immunostaining in 15 samples positive and in 25 samples negative for the presence of C. trachomatis. RESULTS: Of the 70 TMJ samples, 32 (46%) were positive for C. trachomatis. In 15 samples positive for C. trachomatis, 10 (67%) were positive for TNFalpha and 7 (47%) for IL-6. In 25 samples negative for C. trachomatis, only 4 (16%) were positive for TNFalpha and only 2 (8%) for IL-6. Differences in C. trachomatis-positive samples versus negative were significant for both TNFalpha (P < .002) and IL-6 (P < .008). CONCLUSION: The presence of C. trachomatis in the TMJ is associated with a significantly increased presence of TNFalpha and IL-6.     

The role of medical comorbidity in outcome of major depression in primary care: the PROSPECT study.

OBJECTIVE: The authors described the influence of specific medical conditions on clinical remission and response of major depression (MDD) in a clinical trial evaluating a care-management intervention among older primary-care patients. METHODS: Adults age 60 years and older were randomly selected and screened for depression. Participants were randomly assigned to Usual Care or to an Intervention with a depression care-manager offering algorithm-based care for MDD. In all, 324 adults meeting criteria for MDD were included in these analyses. Remission and response was defined by a score on the Hamilton Rating Scale for Depression <10 and by a decrease from baseline of > or =50%, respectively. Medical comorbidity was ascertained through self-report. Cognitive impairment was defined by a score <24 on the Mini-Mental State Exam (MMSE). RESULTS: In Usual Care, rates of remission were faster in persons who reported atrial fibrillation (AF) than in persons who did not report AF and slower in persons who reported chronic pulmonary disease than in persons who did not report chronic pulmonary disease; rates of response were less stable in persons with MMSE <24 than in those with MMSE > or =24. In the Intervention condition, none of the specific chronic medical conditions were significantly associated with outcomes for MDD. CONCLUSIONS: Because disease-specific findings were observed in persons who received Usual Care but not in persons who received more intensive treatment in the Intervention condition, our results suggest that the association of medical comorbidity and treatment outcomes for MDD may be determined by the intensity of treatment for depression.