Development and preliminary validation of a systemic lupus erythematosus-specific quality-of-life instrument (SLEQOL)

OBJECTIVES: Systemic lupus erythematosus (SLE), a chronic illness with an unpredictable and variable course, profoundly affects the quality of life (QOL). General health questionnaires are used to assess QOL in SLE, but a disease-specific instrument could offer enhanced responsiveness and content validity. We detail the steps we took to develop and validate a new SLE-specific QOL instrument, SLEQOL. METHODS: Rheumatology professionals nominated items that they felt were important determinants of QOL of SLE patients. One hundred SLE patients were asked to assess the importance and frequency of occurrence of these items and to suggest those that had not been listed. Item reduction was performed using Rasch model and factor analyses to create a new questionnaire in English. This final questionnaire was administered to a cohort of 275 patients to study its psychometric properties. RESULTS: Fifty-one items covering a wide range of QOL concerns were identified. The patients' responses led to the elimination of 11. The new questionnaire of 40 items was found to have Cronbach's alpha of 0.95 and to consist of eight domains covering physical, mental and social QOL issues. It has good test-retest reliability, poor to fair cross-sectional correlation with the SF-36, with poor correlation with lupus activity or damage indices. The SLEQOL was more responsive to change than the SF-36. CONCLUSIONS: We have developed a new 40-item SLEQOL in English and showed that it is valid for use in SLE patients in Singapore. It offers better content validity and responsiveness to change than the SF-36.     

A novel T cell receptor transgenic animal model of seborrheic dermatitis-like skin disease

We have characterized a novel animal model of the common inflammatory skin disease seborrheic dermatitis (SD) that involves the expression of the self-specific 2C transgenic T cell receptor on the DBA/2 genetic background. Opportunistic fungal pathogens are present in the primary histological lesions and severe disease can be mitigated by the administration of fluconazole, demonstrating a role for infection in disease pathogenesis. Spontaneous disease convalescence occurs at 70-90 d of age and is preceded by an expansion of CD4+ T cells that partially restores the T cell lymphopenia that occurs in these animals. The adoptive transfer of syngeneic CD4+ T cells into pre-diseased DBA/2 2C mice completely abrogates the development of cutaneous disease. The pattern of disease inheritance in DBA/2 backcrosses suggests that one, or a closely linked group of genes, may control disease penetrance. Bone marrow reconstitution experiments demonstrated that the DBA/2 susceptibility factor(s) governing disease penetrance is likely non-hematopoietic since bone marrow from disease-resistant 2C mice can adoptively transfer the full disease phenotype to non-transgenic DBA/2 animals. This model implicates fungal organisms and CD4+ T cell lymphopenia in the development of a SD-like condition and, as such, may mimic the development of SD in acquired immunodeficiency syndrome.     

Genetic influences in the aetiology of tears of the rotator cuff. Sibling risk of a full-thickness tear

From a retrospective, cohort study of 205 patients diagnosed with full-thickness tears of the rotator cuff, we determined, using ultrasound, the prevalence of such tears in their 129 siblings. Using 150 spouses as controls, the relative risk of full-thickness tears in siblings versus controls was 2.42 (95% CI 1.77 to 3.31). The relative risk of symptomatic full-thickness tears in siblings versus controls was 4.65 (95% CI 2.42 to 8.63). The significantly increased risk for tears in siblings implies that genetic factors play a major role in the development of full-thickness tears of the rotator cuff.     

Gene expression profiling of renal medullary carcinoma: potential clinical relevance

BACKGROUND: Renal medullary carcinoma is a rare kidney tumor with highly aggressive behavior. This tumor occurs exclusively in young patients with sickle cell trait or disease. To the authors' knowledge, very little is known to date regarding the underlying molecular genetics of this tumor, and no effective therapy has been established. METHODS: The authors analyzed the gene expression profiles of 2 renal medullary carcinomas from patients with sickle cell trait using microarrays containing 21,632 cyclic DNA (cDNA) clones and compared them with the gene expression profiles of 64 renal tumors. RESULTS: Based on global gene clustering with 3583 selected cDNAs, the authors found a distinct molecular signature of renal medullary carcinoma, which clustered closely with urothelial (transitional cell) carcinoma of the renal pelvis, rather than renal cell carcinoma (RCC). This finding of a significant difference in the gene expression patterns of renal medullary carcinoma compared with RCC suggests that this tumor should not be treated as a conventional RCC but, rather, as a special malignancy. This study also identified genes/proteins that may serve as biomarkers for renal medullary carcinoma or as potential targets of novel therapies. In addition, comparative genomic microarray analysis allowed the authors to predict the lack of chromosomal imbalances in this tumor. CONCLUSIONS: To the authors' knowledge, the current study is the first molecular profiling of renal medullary carcinoma, a rare but highly aggressive kidney carcinoma. The genes that are expressed specifically in this tumor may lead to not only a better understanding of its molecular pathways and discoveries of novel diagnostic markers but also, more important, to effective therapeutic interventions.     

A meiotic recombination in a new isolated familial somatotropinoma kindred

We report here the genetic findings of a new isolated familial somatotropinoma (IFS) kindred in which the mother (subject I:2) and one daughter (subject II:2) are affected; their ages at diagnosis were 25 and 14 years respectively. Additionally, patient I:2 developed virilization due to an androgen-secreting adrenocortical mass, presenting clinical and molecular features of sporadic adrenal carcinoma. To genotype this family and to narrow down the candidate interval of the putative IFS gene at 11q13, we performed haplotyping on the DNA from all five members of the family and allelotyping of one available somatotropinoma using polymorphic microsatellite markers from chromosome region 11q12.1-11q13.5. Results indicated that the disease haplotype, between markers D11S956 and D11S527, was transmitted from subject I:2 only to subject II:2. A meiotic recombination event was detected in the fraternal twin sister of II:2 (subject II:1), but her disease status is unknown. Since she is only 18 years old this genetic event cannot yet narrow down the area involved in the pathogenesis of IFS. Allelotyping of the somatotropinoma from II:2 revealed loss of the chromosome carrying the wild-type copy of the putative IFS gene inherited from her father. These results support the involvement of a tumor suppressor gene at 11q13.1-q13.3 in the pathogenesis of IFS.     

Rare case of metastatic prostate adenocarcinoma to the pituitary

We report a rare case of metastatic prostate adenocarcinoma to the pituitary gland. The patient had lung and bone metastases when he presented with bitemporal hemianopsia. He was also receiving total androgen blockade at that time. Magnetic resonance imaging showed an intrasellar mass, and biopsy confirmed metastatic prostate cancer. Radiotherapy, in the form of intensity-modulated radiotherapy, was delivered to the intrasellar mass. The patient responded well to radiotherapy. The mechanisms of spread to the pituitary gland and treatment options, including intensity-modulated radiotherapy, are discussed.     

MR renography using a dynamic gradient-echo sequence and low-dose gadopentetate dimeglumine as an alternative to radionuclide renography

OBJECTIVE: Our aim was to evaluate the feasibility of acquiring an MR signal intensity-time renographic curve and dynamic serial images in a way similar to that of acquiring radionuclide renograms, with a dynamic gradient-echo sequence and a low-dose gadopentetate dimeglumine technique, using a commonly available 1.5-T MR scanner. SUBJECTS AND METHODS. Patients who underwent both radionuclide and MR renographic studies within a 3-month period were included in the analysis. This yielded 21 studies from 19 patients. Nineteen of the 21 studies were available for analysis. Two studies were excluded because of technical errors during MR renographic acquisition. Serial MR renograms were obtained using a dynamic two-dimensional spoiled gradient-echo fast low-angle shot T1-weighted sequence. Low-dose IV furosemide and gadopentetate dimeglumine (0.025 mmol/kg of body weight) were administered. Intensity-time curves were obtained from the manually selected regions of interest over the renal parenchyma and whole kidney for calculation of split renal function and assessment of urinary excretion, respectively. Results were compared with those obtained with radionuclide renography. RESULTS: Good correlation (Pearson's correlation coefficient, r = 0.97, p < 0.001) was observed when the volume-corrected split renal function acquired with MR renography was compared with that obtained with radionuclide renography. There was also good agreement in the excretory curve patterns (weighted kappa(observer 1) = 0.77 and kappa(observer 2) = 0.81) between the two techniques. CONCLUSION: Dynamic MR gradient-echo imaging with a low-dose gadopentetate dimeglumine technique can produce an intensity-time curve and serial dynamic images of the urinary system, in a way similar to that of radionuclide renography. This technique allows assessment of split renal function and urinary excretory status and is a feasible alternative to radionuclide renography.