International spondyloarthritis interobserver reliability exercise--the INSPIRE study: II. Assessment of peripheral joints, enthesitis, and dactylitis

OBJECTIVE: To determine whether the assessments of peripheral joints and enthesitis were reproducible for both AS and PsA with axial disease, and whether dactylitis assessment is reproducible in patients with PsA. METHODS: A group of 20 rheumatologists from 11 countries with expertise in spondyloarthritis (SpA) met for a combined physical examination exercise to assess 10 patients with PsA with axial involvement (9 men, 1 woman, mean age 52 yrs, disease duration 17 yrs) and 9 patients with AS (7 men, 2 women, mean age 38 yrs, disease duration 16 yrs). A modified Latin-square design that enabled assessment of patient, assessor, and order effect was used. Measures included were number of tender and swollen joints, presence of enthesitis using 6 different indices, and dactylitis score. Data were analyzed using intraclass correlation (ICC) adjusted for order of measurements. RESULTS: The majority of the variance was contributed by the patients. There was no order effect. The assessment of tender joints (ICC 0.69) was more reliable than the assessment of swollen joints (ICC 0.54). Moreover, there was better agreement in patients with PsA (ICC 0.78) than in patients with AS (ICC 0.62). There was excellent agreement on the number of active enthesitis sites (ICC 0.86). All the enthesitis indices provided substantial to excellent agreement among observers. Agreement for the dactylitis score was substantial (ICC 0.70). CONCLUSION: The assessment of peripheral joints is more reliable in patients with PsA. Enthesitis instruments can be used reliably in patients with AS and patients with PsA with spinal involvement. The Leeds dactylitis instrument functions well in PsA.     

Cytokine gene polymorphisms in acquired bone marrow failure

Some acquired aplastic anemia (AA) results from immune-mediated destruction of hematopoietic stem cells. Cytokine gene polymorphisms are implicated in controlling cytokine production and increasing the susceptibility to some autoimmune diseases. We characterized the IL-6/-174, TNF-alpha/-308, IL-10/-1082, IFN-gamma/+874, TGFbeta1/-509 single nucleotide polymorphisms (SNP's) and the IL1-RA second intron variable number tandem repeat (VNTR) alleles in 73 patients with AA and compared the frequency of genotypes to established control populations. We found that some patients with acquired AA have polymorphisms which are linked to high production of proinflammatory cytokines, particularly TNF-alpha and IFN-gamma.     

Live/real time three-dimensional transthoracic echocardiographic assessment of tricuspid valve pathology: incremental value over the two-dimensional technique

Twenty-nine patients with different tricuspid valve (TV) pathologies were studied by both two-dimensional transthoracic (2DTTE) and live/real time three-dimensional transthoracic echocardiography (3DTTE). A major contribution of 3DTTE over 2DTTE was the en face visualization of all three leaflets of the TV in all patients. This allowed accurate assessment of TV orifice area in patients with TV stenosis and carcinoid disease. Loss of TV leaflet tissue, defects in TV leaflets and size of TV systolic non-coaptation could also be delineated and resulted in identifying the mechanism of tricuspid regurgitation (TR) in patients with Ebstein's anomaly and rheumatic heart disease. Prolapse of TV leaflets could also be well visualized and enabled us to develop a schema for systematic assessment of individual segment prolapse which could help in surgical planning. The exact sites of chordae rupture in patients with flail TV as well as right ventricular papillary muscle rupture could be well seen by 3DTTE. 3DTTE also permitted sectioning of various TV masses for more specific diagnosis of their nature. In addition, color Doppler 3DTTE provided an estimate of quantitative evaluation of TR severity, since the exact shape and size of the vena contracta could be accurately assessed. In conclusion, our preliminary experience with 3DTTE has demonstrated substantial incremental value over 2DTTE in the assessment of various TV pathologies.     

Inoperable hepatocellular carcinoma: transarterial 188Re HDD-labeled iodized oil for treatment--prospective multicenter clinical trial

PURPOSE: To prospectively evaluate, in a multicenter clinical trial, dosimetry-guided transarterial radionuclide therapy (TART) with rhenium 188 ((188)Re) 4-hexadecyl 1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)-labeled iodized oil in inoperable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ninety-three patients were recruited from 2000 to 2005 for this ethics committee-approved study. Informed written consent was obtained. After complete clinical evaluation (including assessment of liver status, serum alpha-fetoprotein [AFP] level, tumor size, portal vein status, Child-Pugh classification, Okuda staging), radiation absorbed dose (RAD) to various organs, including tumor, was calculated after injecting 185 MBq of (188)Re HDD iodized oil via the hepatic artery. From this value, the maximum tolerable activity of (188)Re, defined as the amount of radioactivity delivering no more than 12 Gy of RAD to lungs, 30 Gy to normal liver, or 1.5 Gy to bone marrow, was calculated and injected. RESULTS: Mean patient age was 53 years (80 men and 13 women). Sixty-eight percent of patients had serologic evidence of hepatitis B and/or C; 40% had clinicoradiologic evidence of cirrhosis. Mean tumor diameter was 10.3 cm +/- 4.4, with 40% of patients having more than three lesions; in 50% of patients, tumor was either unilateral, occupying 50% or more of the liver, or bilateral. AFP was elevated in 68% of patients and was elevated to more than 300 ng/mL in 44% of patients. There was portal vein thrombosis in 38% of patients, Child-Pugh status B disease in 37% of patients, and Okuda stage II or III disease in 50% of patients. Mean first administered activity was 5.3 GBq +/- 1.6, which delivered 88 Gy of RAD to the tumor. Treatment was tolerated well. Of 66 patients in whom complete tumor response occurred, five (8%) had complete tumor mass ablation, 17 (26%) had a partial response (>50% tumor reduction), and 23 (35%) had stable disease. Only RAD to the tumors was found to be significantly (P = .001) associated with tumor and/or AFP response. Survival rates at 6, 9, 12, 24, and 36 months among patients with objective tumor response were 100%, 95%, 90%, 58%, and 30%, respectively, with a median survival of 980 days. CONCLUSION: TART appears to be a safe, effective, and promising therapeutic option in patients with inoperable HCC.     

Best practices: surveillance and management of diabetes in a CMHC population

To improve detection and management of diabetes at a community mental health center, a cross-sectional study of the prevalence and management of type 2 diabetes mellitus was conducted among patients receiving maintenance antipsychotic medication (N=494). Diabetes was more than two-and-a-half times as prevalent among participants (17.4%) as in the general population. Fourteen percent of patients classified as diabetic had previously undiagnosed disease, compared with national sample rates of over 30%. Impaired fasting glucose was found for 26% of the sample. Glucose dysregulation was common. The known poor cardiovascular profile of persons with serious mental illness, reflected in the high rates of tobacco use and obesity in the sample, requires contextualizing efforts to screen and monitor for diabetes within overall efforts to monitor cardiovascular health.     

Relaxation and susceptibility MRI characteristics in Hallervorden-Spatz syndrome

PURPOSE: To evaluate the imaging characteristics of the brain with respect to relaxation and susceptibility in Hallervorden-Spatz syndrome (HSS), a rare inherited neurodegenerative disorder (also referred to as neurodegeneration with brain iron accumulation). MATERIALS AND METHODS: We reviewed 13 affected individuals who satisfied the inclusion criteria for HSS. Clinically, the patients were divided into two groups: early-childhood onset (age of onset before 10 years) and late-childhood onset (age of onset after 10 years). MRI was performed on 1.5T MR equipment. The imaging protocol included spin-echo (SE) T1-weighted (T1W), turbo spin-echo (TSE) T2W, and fluid attenuated inversion recovery (FLAIR) sequences in all patients. Susceptibility-weighted imaging (SWI) included a fast low-angle shot (FLASH) sequence in 10 patients and a blood oxygen level-dependent (BOLD) sequence in two patients. RESULTS: All of the patients showed hyperintensity on T1WI and hypointensity on T2WI in the globus pallidi (GPs) bilaterally. Central or anteromedial hyperintensity was found in all but one patient. FLASH showed augmented hypointensity in 10 patients, and BOLD showed bilateral striatonigral abnormal pigmentation in two patients. MR spectroscopy (MRS) showed normal spectra in four patients, and a reduced NAA/Cho ratio in two. CONCLUSION: MRI showed prominent signal abnormalities in the GP bilaterally in HSS. T1WI showed hyperintensity in all cases of HSS in addition to the "eye-of-the-tiger" sign on T2WI. SWI, FLASH, and BOLD demonstrated mineral deposition in the GP better than conventional imaging. Involvement of the striatonigral pathways was demonstrated for the first time on BOLD SWI.     

Genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) and upper aerodigestive tract cancer risk among smokers, tobacco chewers and alcoholics in an Indian population

The glutathione-S-transferase (GST) genes are involved in the detoxification of various carcinogens that increase the risk to upper aerodigestive tract (UADT) cancers. In the present study, 408 unrelated histopathologically confirmed cases and 220 population based controls, matched by age and gender, which belonged to the Tamilian population of south India were genotyped for polymorphisms in GSTM1, GSTT1 and GSTP1 using polymerase chain reaction (PCR) based methods. The multivariate logistic regression analyses demonstrated that GSTT1 null genotype was significantly associated with increased risk for UADT cancers (odds ratio (OR) 2.5; 95% confidence intervals (CIs) 1.3–4.7). The combined effects of GST genes have shown that concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR 4.6; 95% CI 1.3–15.6), while GSTT1 null genotype along with GSTP1 polymorphic variants further increased the cancer risk (OR 5.3; 95% CI 2.0–13.6). The most remarkable risk was seen among individuals carrying GSTM1 null, GSTT1 null genotypes and GSTP1 polymorphic variants (OR 7.8; 95% CI 1.0–61.0). Tobacco chewers carrying GSTM1 null genotype had an enhanced risk for UADT cancers. An enhanced risk among tobacco chewers and alcoholics (regular) was noted in individuals with GSTT1 null genotype. Similarly, a significant interaction was observed among smokers (>40 pack-year (PY)) and tobacco chewers carrying GSTP1 mutant genotypes. Although the null genotype of GSTT1 is a strong predisposing risk factor for UADT cancers, we conclude that the significant gene–gene and gene–environment interactions of GST genes may confer a substantial risk to UADT cancers in the Tamilian population of south India.     

Distress overlaps with anxiety and depression in patients with head and neck cancer

Psychological problems in cancer patients often go unrecognized until they are specifically sought. This is more in patients with depression as they are reluctant to complain about their symptoms. The present study was carried out to evaluate the relation of distress with anxiety and depression in 123 patients with head and neck cancers using Distress Inventory for Cancer version 2 (DIC2) and the Hospital Anxiety and Depression scale (HADS). The mean DIC 2 scores were 24.6 while that of subscales ranged from 2.6 to 11.0. Fifteen patients were found to have clinical caseness for anxiety while 12 (10%) were caseness for depression. Total distress, emotional and social distress subscales were found to have positive correlation with anxiety and depression suggesting a possible overlap of two constructs. In multivariate analysis only belief in god was found to significantly affect the distress. Results of present study suggest significant psychological morbidity in head neck cancer patients undergoing curative treatment. This is the first study reporting on the psychometric properties of distress inventory on cancer version 2 since its validation, the results suggest a possible overlap of two constructs similar to that seen with other tools on distress and this may have major implications for clinical practice.