Prevalence of spondyloarthritis and its subtypes in southern Sweden.

OBJECTIVE: To estimate the prevalence of spondyloarthritis and its subtypes. METHODS: The Swedish healthcare organisation comprises a system where all inpatient and outpatient care is registered by a personal identifier. For the calendar years 2003-7, all residents aged ≥ 15 years in the southernmost county of Sweden (1.2 million inhabitants) diagnosed by a physician with spondyloarthritis (ankylosing spondylitis (AS), psoriatic arthritis (PsA), inflammatory arthritis associated with inflammatory bowel disease (Aa-IBD) or undifferentiated spondylarthritis (USpA)) were identified. To obtain valid point estimates of prevalence by the end of 2007, identification numbers were cross-referenced with the population register to exclude patients who had died or relocated. RESULTS: The authors estimated the prevalence of spondyloarthritis (not including chronic reactive arthritis) as 0.45% (95% CI 0.44% to 0.47%). The mean (SD) age of patients with prevalent spondyloarthritis by the end of 2007 was 53 (15) years. Among the component subtypes, PsA accounted for 54% of cases, AS 21.4%, USpA 17.8% and Aa-IBD 2.3% with a prevalence of 0.25%, 0.12%, 0.10% and 0.015%, respectively. The remaining 6.4% had some form of combination of spondyloarthritis diagnoses. The prevalence of spondyloarthritis at large was about the same in men and women. However, the subtype PsA was more prevalent in women and AS was more prevalent in men. CONCLUSION: In Sweden the prevalence of spondyloarthritis leading to a doctor consultation is not much lower than rheumatoid arthritis. PsA was the most frequent subtype followed by AS and USpA, and the two most frequent subtypes PsA and AS also display some distinct sex patterns.

Tiling resolution array CGH of dic(7;9)(p11 approximately 13;p11 approximately 13) in B-cell precursor acute lymphoblastic leukemia reveals clustered breakpoints at 7p11.2 approximately 12.1 and 9p13.1.

The dic(7;9)(p11 approximately 13;p11 approximately 13) is a recurrent chromosomal abnormality in acute lymphoblastic leukemia (ALL), mainly of B-lineage. Although more than 20 dic(7;9)-positive ALLs have been reported to date, the molecular genetic consequences of this aberration are unknown. We performed tiling resolution (32K) genome-wide array-based comparative genomic hybridization (array CGH) analysis of three cases with dic(7;9) in order to characterize the breakpoints on 7p and 9p. The analysis showed a clustering of breakpoints within 9p13.1 in all three cases and within 7p11.2 in two cases; the array CGH revealed two different breakpoints - 7p12.1 and 7p14.1 - in the remaining case. Based on these findings the abnormality should hence be designated dic(7;9)(p11.2 approximately 12.1;p13.1). Locus-specific fluorescence in situhybridization analysis of one of the cases narrowed down the 7p11.2 breakpoint to a <500-kb segment in this sub-band, a region containing three known genes. Unfortunately, lack of material precluded further molecular genetic studies, and it thus remains unknown whether the pathogenetically important outcome of the dic(7;9) is formation of a chimeric gene or loss of 7p and/or 9p material.

Effects of exercise on aerobic capacity and fatigue in women with primary Sjogren's syndrome.

OBJECTIVE: To investigate the effect of a moderate to high intensive exercise program on two primary outcomes (aerobic capacity, fatigue), and three secondary outcomes [anxiety, depression and health-related quality of life (HRQoL)] in women with primary Sjögren's syndrome (primary SS). METHODS: Twenty-one women with primary SS were ranked according to degree of fatigue and allocated to an exercise group (TG; n = 11) or a control group (CG; n = 10). The exercise method was Nordic walking for 45 min three times a week for 12 weeks. Outcome measures assessed at baseline and after 12 weeks were aerobic capacity, fatigue, ratings of perceived exertion (RPE), anxiety, depression and HRQoL. RESULTS: Nine women in the TG and 10 women in the CG completed the study. Analysis showed significant differences between the groups regarding aerobic capacity (P = 0.03), fatigue (P = 0.03), RPE (P = 0.03), and depression (P = 0.02) with the better values for the TG. There were no differences in anxiety or HRQoL. CONCLUSION: Our findings support the use of appropriate aerobic exercise in the treatment of primary SS.

FISH mapping of i(7q) in acute leukemias and myxoid liposarcoma reveals clustered breakpoints in 7p11.2: implications for formation and pathogenetic outcome of the idic(7)(p11.2).

Isochromosome 7q - i(7q) - is seen in a wide variety of hematologic malignancies and solid tumors, often as a secondary change to a characteristic primary translocation. Despite its high frequency, nothing is known about the formation and the pathogenetic outcome of this abnormality. To address these issues, we performed a detailed fluorescence in situ hybridization (FISH) investigation of four acute lymphoblastic leukemias, one acute myeloid leukemia, and two myxoid liposarcomas with i(7q). Using FISH with bacterial artificial chromosomes (BACs) mapping between 7p12.2 and 7q11.2, the breakpoints (BPs) in all seven cases were shown to cluster to an approximately 340 kb segment at 7p11.2, covered by the overlapping BAC probes RP11-760D2 and RP11-10F11. Thus, the i(7q) should formally be designated idic(7) (p11.2). In one of the cases, FISH with fosmids could narrow down the BP further to an 80-kb sequence delineated by G248P81983A10 and G248P8793H7. No known genes are located in the 340-kb BP cluster region, indicating that the idic(7)(p11.2) does not result in a fusion or deregulation of genes in this segment. The pathogenetically important outcome is thus likely to be an altered gene expression because of copy number changes. The clustering of breakpoints might be due to frequent intrachromosomal duplicons in the BP region.

High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration.

Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic--possibly primary--genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing >98% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8 Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.

Assessment of fatigue in primary Sjögren's syndrome: the Swedish version of the Profile of Fatigue.

OBJECTIVE: To translate the disease-specific Profile of Fatigue (ProF) into Swedish and to evaluate the reliability and validity of the Swedish version. METHODS: Forward and back translations were performed. Seventy patients with primary Sjögren's syndrome (PSS), 48 control persons, and two rheumatologists participated. Test-retest reliability, internal consistency, content, construct and discriminant validity were investigated. RESULTS: The translation was accepted without modifications. The test-retest reliability varied between moderate and good (weighted Kappa = 0.51-0.63). Internal consistency was high (Cronbach's alpha = 0.97). Construct validity was proved by significant correlations of the questionnaire items with the Visual Analogue Scale (VAS) for fatigue (r(s) = 0.55-0.70), and the Physical Function (PF) (r(s) = -0.20 to -0.41) and Vitality (VT) scales (r(s) = -0.60 to -0.77) of the MOS 36-Item Short-Form Health Survey (SF-36). Content validity was mainly judged as good. A significant difference between the scorings of the patients and the scorings of the control group was seen (mean difference 1.6, p<0.005). CONCLUSION: The Swedish version of the ProF is a relatively reliable and valid instrument for the measurement of fatigue in patients with PSS.

Fusion of the BCR and the fibroblast growth factor receptor-1 (FGFR1) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: the first fusion gene involving BCR but not ABL.

Constitutive activation of tyrosine kinases as a consequence of chromosomal translocations, forming fusion genes, plays an important role in the development of hematologic malignancies, in particular, myeloproliferative syndromes (MPSs). In this respect, the t(9;22)(q34;q11) that results in the BCR/ABL fusion gene in chronic myeloid leukemia is one of the best-studied examples. The fibroblast growth factor receptor 1 (FGFR1) gene at 8p11 encodes a transmembrane receptor tyrosine kinase and is similarly activated by chromosomal translocations, in which three alternative genes-ZNF198 at 13q12, CEP110 at 9q34, and FOP at 6q27-become fused to the tyrosine kinase domain of FGFR1. These 8p11-translocations are associated with characteristic morphologic and clinical features, referred to as "8p11 MPS." In this study, we report the isolation and characterization of a novel fusion gene in a hematologic malignancy with a t(8;22)(p11;q11) and features suggestive of 8p11 MPS. We show that the breakpoints in the t(8;22) occur within introns 4 and 8 of the BCR and FGFR1 genes, respectively. On the mRNA level, the t(8;22) results in the fusion of BCR exons 1-4 in-frame with the tyrosine kinase domain of FGFR1 as well as in the expression of a reciprocal FGFR1/BCR chimeric transcript. By analogy with data obtained from previously characterized fusion genes involving FGFR1 and BCR/ABL, it is likely that the oligomerization domain contributed by BCR is critical and that its dimerizing properties lead to aberrant FGFR1 signaling and neoplastic transformation.

Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors.

Although mechanisms for chromosomal instability in tumors have been described in animal and in vitro models, little is known about these processes in man. To explore cytogenetic evolution in human tumors, chromosomal breakpoint profiles were constructed for 102 pancreatic carcinomas and 140 osteosarcomas, two tumor types characterized by extensive genomic instability. Cases with few chromosomal alterations showed a preferential clustering of breakpoints to the terminal bands, whereas tumors with many changes showed primarily interstitial and centromeric breakpoints. The terminal breakpoint frequency was negatively correlated to telomeric TTAGGG repeat length, and fluorescence in situ hybridization with telomeric TTAGGG probes consistently indicated shortened telomeres and >10% of chromosome ends lacking telomeric signals. Because telomeric dysfunction may lead to formation of unstable ring and dicentric chromosomes, mitotic figures were also evaluated. Anaphase bridges were found in all cases, and fluorescence in situ hybridization demonstrated extensive structural rearrangements of chromosomes, with terminal transferase detection showing fragmented DNA in 5-20% of interphase cells. Less than 2% of cells showed evidence of necrosis or apoptosis, and telomerase was expressed in the majority of cases. Telomeric dysfunction may thus trigger chromosomal fragmentation through persistent bridge-breakage events in pancreatic carcinomas and osteosarcomas, leading to a continuous reorganization of the tumor genome. Telomerase expression is not sufficient for completely stabilizing the chromosome complement but may be crucial for preventing complete genomic deterioration and maintaining cellular survival.

Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10;16)(q22;p13).

The CBP gene at 16p13 fuses to MOZ and MLL as a result of the t(8;16)(p11;p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11;16)(q23;p13) in treatment-related AML, respectively. We show here that a novel t(10;16)(q22;p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated.

Isodicentric 7p, idic(7)(q11.2), in acute myeloid leukemia associated with older age and favorable response to induction chemotherapy: a new clinical entity?

Three adult de novo acute myeloid leukemias (AML M1, M2, and M4) with an isochromosome 7p are presented. No additional abnormalities were detected by G-band and multicolor, using combined binary ratio labeling, fluorescence in situ hybridization (FISH) analyses, indicating that the i(7p) was the sole, i.e., the primary, chromosomal aberration. Although the patients were elderly--68, 72, and 78 years old--they all responded very well to chemotherapy, achieving complete remission lasting more than a year. Further FISH analyses, using painting, centromeric, as well as 7q11.2-specific YAC probes, revealed that the i(7p) contained two centromeres and that the breakpoints were located in 7q11.2. Thus, the abnormality should formally be designated idic(7)(q11.2). The detailed mapping disclosed a breakpoint heterogeneity, with the breaks in 7q11.2 varying among the cases, being at least 1,310 kb apart. Furthermore, the breakpoints also differed within one of the cases, being located on both the proximal and the distal side of the most centromeric probe used. Based on our three patients, as well as on a previously reported 82-year-old patient with AML M2 and idic(7)(q11) as the only chromosomal change, we suggest that this abnormality, as the sole anomaly, is associated with AML in elderly patients who display a good response to induction chemotherapy and, hence, have a favorable prognosis. Furthermore, the heterogeneous breakpoints in 7q11.2 suggest that the important functional outcome of the idic(7)(q11.2) is the genomic imbalance incurred, i.e., gain of 7p and loss of 7q material, rather than a rearrangement of a specific gene.

Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH.

Fluorescence in situ hybridization (FISH), including COBRA-FISH, was used to characterize 11 salivary gland tumors that had been investigated by banding analysis. Five cases were pleomorphic adenoma (PA), three were adenoid cystic carcinoma, and one case each was mucoepidermoid carcinoma, carcinoma ex-pleomorphic adenoma (CaPA), and adenocarcinoma. All 11 cases were selected on the basis that they had shown rearrangement of 6q or 9p or had unresolved aberrations after karyotyping. The COBRA-FISH and FISH analyses led to a revised karyotype in all informative cases and made it possible to clarify almost all chromosomal rearrangements occurring in the tumors. Of particular note were the confirmation of the existence of 6q deletions, a common change in salivary gland carcinomas, and the demonstration that a seemingly balanced t(6;9) resulted in del(6q). Other rearrangements that were revealed by FISH included amplification of 12q sequences (MDM2 and CDK4) in one PA. We also investigated the status of the PLAG1 gene in four cases (one PA, one CaPA, one adenoid cystic carcinoma, and one mucoepidermoid carcinoma) with 8q12 rearrangements. Only in the former two cases were the FISH results compatible with intragenic rearrangements. Overall, the results of the study show that, even with good banding quality and in karyotypes of modest complexity, much new information will be gained by supplementing the banding analysis with a multicolor FISH approach, such as COBRA-FISH.

Health-related quality of life in primary Sjögren's syndrome, rheumatoid arthritis and fibromyalgia compared to normal population data using SF-36.

OBJECTIVE: To investigate the health-related quality of life in women with primary Sjogren's syndrome (prim SS) and compare with normative data and the health-related quality of life in women with rheumatoid arthritis (RA) and women with fibromyalgia. METHODS: A questionnaire including the MOS Short-Form 36 (SF-36) was completed by 42 prim SS women, 59 RA women, and 44 women with fibromyalgia. RESULTS: All three patient groups experienced a decreased quality of life level ranging from 5 to 65 % in all SF-36 scales compared to normative data. Differences between groups were seen in 7 of the 8 scales (p< or = 0.004). The prim SS patients experienced a higher quality of life level with regard to physical function than the women with RA and fibromyalgia, whereas in the psychological dimensions the quality of life level was comparable to that of the two other groups. CONCLUSION: The health-related quality of life was significantly decreased as compared to norms in prim SS women and comparable to the levels of women with RA and fibromyalgia.

Isochromosome 17q in blast crisis of chronic myeloid leukemia and in other hematologic malignancies is the result of clustered breakpoints in 17p11 and is not associated with coding TP53 mutations.

An isochromosome of the long arm of chromosome 17, i(17q), is the most frequent genetic abnormality observed during the disease progression of Philadelphia chromosome-positive chronic myeloid leukemia (CML), and has been described as the sole anomaly in various other hematologic malignancies. The i(17q) hence plays a presumably important pathogenetic role both in leukemia development and progression. This notwithstanding, the molecular consequences of this abnormality have not been investigated in detail. We have analyzed 21 hematologic malignancies (8 CML in blast crisis, 8 myelodysplastic syndromes [MDS], 2 acute myeloid leukemias, 2 chronic lymphocytic leukemias, and 1 acute lymphoblastic leukemia) with i(17q) by fluorescence in situ hybridization (FISH). Using a yeast artificial chromosome (YAC) contig, derived from the short arm of chromosome 17, all cases were shown to have a breakpoint in 17p. In 12 cases, the breaks occurred within the Smith-Magenis Syndrome (SMS) common deletion region in 17p11, a gene-rich region which is genetically unstable. In 10 of these 12 cases, we were able to further map the breakpoints to specific markers localized within a single YAC clone. Six other cases showed breakpoints located proximally to the SMS common deletion region, but still within 17p11, and yet another case had a breakpoint distal to this region. Furthermore, using chromosome 17 centromere-specific probes, it could be shown that the majority of the i(17q) chromosomes (11 of 15 investigated cases) were dicentric, ie, they contained two centromeres, strongly suggesting that i(17q) is formed through an intrachromosomal recombination event, and also implicating that the i(17q), in a formal sense, should be designated idic(17)(p11). Because i(17q) formation results in loss of 17p material, potentially uncovering the effect of a tumor suppressor on the remaining 17p, the occurrence of TP53 mutations was studied in 17 cases by sequencing the entire coding region. In 16 cases, no TP53 mutations were found, whereas one MDS displayed a homozygous deletion of TP53. Thus, our data suggest that there is no association between i(17q) and coding TP53 mutations, and that another tumor suppressor gene(s), located in proximity of the SMS common deletion region, or in a more distal location, is of pathogenetic importance in i(17q)-associated leukemia.

Evaluation of a structured multidisciplinary day care program in rheumatoid arthritis. A similar effect in newly diagnosed and long-standing disease.

The present study evaluated a multidisciplinary structured day-care programme in patients with rheumatoid arthritis of less than 2 years (n = 41) and more than 2 years disease duration (n = 46). During the 3 week intervention, outcome measures reflecting disability (HAQ, SOFI), the patient's perception of disease and pain (VAS for patient's global assessment and pain), Ritchie articular index (RAI), a 44 swollen joint count, and overall disease activity (DAS) improved significantly in the group as a whole. The improvements remained significant after 15 weeks and were of a similar magnitude in the patient groups with short and long disease duration. At week 3 and 15, the ACR and the EULAR criteria for individual response, for the total study group was fulfilled by 28% and 26%, and 36% and 52% respectively. Evaluation of a subgroup 6 weeks prior to admission indicated that the outcome measures were stable at the time of the intervention. Furthermore, administration of intraarticular glucocorticosteroids (GC) could only partly explain the observed improvement. This uncontrolled observational study supports that a multidisciplinary day-care rehabilitation program is beneficial and feasible for patients with rheumatoid arthritis of both short and long duration.

A problem-based education program for patients with rheumatoid arthritis: evaluation after three and twelve months.

OBJECTIVE: To develop and evaluate the effect of a new arthritis education program based on a previous study. METHODS: One hundred individuals with established rheumatoid arthritis randomized to an intervention group or a control group completed self-report questionnaires. RESULTS: Three months after the education program the patients in the intervention group had increased their knowledge about their disease. They reported increased practice of exercise and joint protection and reduction of disability and pain. After 12 months, increased knowledge and practice of joint protection was maintained. However, there was no longer any difference between the intervention group and the control group regarding reported pain, disability, and practice of exercise. At both intervals the individuals in the intervention group reported an increased ability to handle their pain and a reduction of problems with their disease. The control group remained stable except for a slight increase in pain. CONCLUSION: A structured patient education program had positive impact for 3 months, and some improvements were maintained for 12 months. We suggest that patient education should become an integrated part of the total management of rheumatoid arthritis.

Childhood acute lymphoblastic leukaemia with ider(21)(q10)t(12;21)(p12;q22): a new recurrent abnormality showing ETV6/CBFA2 fusion.

The cytogenetically unidentifiable t(12;21)(p12:q22), resulting in ETV6/CBFA2 fusion, is the most frequent chromosomal aberration in childhood acute lymphoblastic leukaemia ALL). We report a variant, ider(21)(q10)t(12:21)(p12;q22), which was shown to contain double ETV6/CBFA2 fusions by fluorescence in situ hybridization. This is the second case of such an ider(21) in childhood ALL, suggesting that it is a new recurrent abnormality. Since the ider(21) is cytogenetically indistinguishable from i(21)(q10) and idic(21)(p11), changes associated with similar clinical features as the t(12;21), i.e. pre-B-cell ALL and age 1-10 years, we suggest that all ALL displaying these changes should be tested for ETV6/CBFA2 fusion transcript.

Clonal CD5-positive B lymphocytes in myelodysplastic syndrome with systemic vasculitis and trisomy 8.

Bone marrow and peripheral blood from a myelodysplastic syndrome (MDS) patient with trisomy 8 and associated systemic vasculitis was investigated for clonal lymphoid lineage involvement using simultaneous metaphase and interphase fluorescence in situ hybridization (FISH) and immunocytochemistry with antibodies against CD13 (granulocytic), glycophorin A (GPA, erythroid), and the lymphocytic antigens CD3. CD5, CD20, and CD22. Trisomy 8 was detected in 55% of CD13+, 40% of GPA+, 6% of CD5+, and 5% of CD20/22+, but not in CD3+ cells. In a complementary experiment using interphase FISH on bone marrow cells sorted by flow cytometry, 13% of CD5/CD19 double-positive cells (76% purity) were found to be trisomic. The results indicate the existence of a small CD5-positive B-lymphoid clone as part of the MDS process in this patient. Since CD5/19-positive cells have been proposed to be autoantibody producing, this finding might be a clue to the pathogenesis underlying the propensity for MDS patients to develop immune-mediated complications.

Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2.

We previously reported the molecular cloning of a mouse guanosine-nucleotide-binding-protein-coupled receptor similar to the thrombin receptor. Since the physiological agonist was unknown, the receptor was named proteinase-activated receptor 2. We describe here the cloning and functional expression of the gene encoding the corresponding human receptor. The gene is divided into two exons separated by about 14 kb intronic DNA. The deduced protein sequence is 397 amino acids long and 83% identical to the mouse receptor sequence. Within the extracellular amino terminus, the residues predicted to form the tethered agonist ligand differ between the two receptors; of the first six residues only four are conserved. At positions five and six, a lysine residue and a valine residue, respectively, have replaced arginine and leucine residues found in the mouse sequence. When the human receptor is expressed in Chinese hamster ovary cells, it can be activated by low nanomolar concentrations of the serine proteinase trypsin and by peptides made from the receptor sequence. Northern-blot analysis of receptor expression showed that the receptor transcript is widely expressed in human tissues with especially high levels in pancreas, liver, kidney, small intestine and colon. Moderate expression was detected in many organs but none in brain or skeletal muscle. By fluorescence in situ hybridization, the human proteinase-activated receptor 2 gene was mapped to chromosomal region 5q13, where, previously, the related thrombin receptor gene has been located.

Learned helplessness and its correlation to impairment, pain, anxiety and depression in rheumatoid arthritis.

A Swedish version of the self-report instrument Arthritis Helplessness Index (AHI) is presented. Validity and reliability of the translation has been analyzed. 100 consecutive patients with rheumatoid arthritis (RA) were studied, 78 of which completed 2 self-administered questionnaires with AHI, impairment, pain, anxiety and depression. Furthermore 20 of the patients were interviewed with regard to AHI. Forty-two other patients with RA were analyzed for correlation between AHI and biochemical activity and Signals of Functional Impairment (SOFI). We conclude that the Swedish version of AHI has satisfactory validity and reliability. It correlates with age, physical impairment, pain, anxiety and depression but not with sex or disease activity. Five of the original 15 items could for various reasons be omitted, leaving a 10 statement instrument. AHI is promising as a variable in future outcome studies of RA.

Independent origin of uterine leiomyomas with karyotypically identical alterations.

Cytogenetic investigation of multiple uterine leiomyomas from the same patient revealed karyotypes containing cytogenetically indistinguishable del(7)(q21.2q31.2) in two of the tumors. Since this finding seemed to contradict the conclusion from previous glucose-6-phosphate dehydrogenase studies of multiple uterine leiomyomas in which an independent origin of these tumors was found, we assessed clonal tumor origin by DNA-recombinant X-chromosome inactivation analysis. The two leiomyomas with del(7)(q21.2q31.2) had different inactivated X-chromosomes. This proves that they originated independently and indicates that their cytogenetic similarity was coincidental.