Identification of a novel common genetic risk factor for lumbar disk disease

CONTEXT: Lumbar disk disease (LDD) is one of the most common musculoskeletal diseases, with a prevalence of about 5%. A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD. OBJECTIVE: To determine if other collagen IX gene sequence variations play a role in the pathogenesis of LDD. DESIGN AND SETTING: Case-control study conducted from February 1997 to May 1998 at university hospitals in Finland. PARTICIPANTS: A total of 171 individuals with LDD (evaluated clinically and by magnetic resonance imaging or computed tomography) and 321 controls without LDD (186 healthy individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid arthritis, and 21 with chondrodysplasias). MAIN OUTCOME MEASURES: Frequencies of sequence variations covering the entire coding sequences and exon boundaries of the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the alpha1, alpha2, and alpha3 chains of the protein, detected by conformation-sensitive gel electrophoresis and confirmed by sequencing, compared between individuals with and without LDD. RESULTS: Mutation analysis of all 3 collagen IX genes resulted in identification of an Arg103-->Trp (arginine-->tryptophan) substitution in the alpha3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identified Gln326-->Trp (glutamine-->tryptophan) substitution in the alpha2 chain (Trp2 allele), and was 4.7% among controls. The difference in the frequency was statistically significant (P =.000013). Presence of at least 1 Trp3 allele increases risk of LDD about 3-fold. CONCLUSION: This study led to the identification of a novel common genetic risk factor for LDD, confirming that genetic risk factors likely play a significant role in LDD.     

Sertraline-induced panic attacks

Sertraline is a selective serotonin reuptake inhibitor that is approved by the U.S. Food and Drug Administration for the treatment of major depression, obsessive-compulsive disorder (in adults and children), and panic disorder. Although numerous studies have found sertraline to be very effective in the treatment of anxiety, there have been few case reports of panic attacks actually being induced by treatment with sertraline. In this article, we present the cases of two patients without any personal or family history of anxiety disorders who developed panic attacks shortly after the initiation of sertraline therapy. We will also review the literature in regard to the development of anxiety symptoms during treatment with the newer antidepressants and discuss the neurochemical basis of these antidepressant-induced panic attacks.     

Intra‐arterial embolization of lumbar artery pseudoaneurysm following percutaneous nephrolithotomy

The management of a patient with haematuria following percutaneous nephrolithotomy is described. The patient underwent renal angiography to assess the cause of bleeding. A pseudoaneurysm arising from first left lumbar artery was incidentally discovered, which was then successfully embolized using an indigenously fabricated metallic coil and gel foam particles in the same sitting.     

Sonography and MRI in the evaluation of painful arthritic shoulder

We evaluated 31 painful shoulders of 30 patients with chronic arthritis by ultrasonography (US) and compared the results with those of magnetic resonance imaging (MRI). Both US and MRI revealed effusion in the subacromial-subdeltoid (SA-SD) bursa, biceps tendon sheath (BTS) and glenohumeral (GH) joint, but MRI was more accurate in depicting joint inflammation because of its ability to visualize synovial hypertrophy. US visualized biceps tendon ruptures equally well as MRI. MRI was better able to reveal full-thickness tear of the supraspinatus tendon, whereas US showed better other changes of the supraspinatus tendon (degeneration or partial-thickness tear). Both of the imaging methods were able to depict erosions of the humeral head, but the locations occasionally differed. Inexpensive and easily available US can be recommended as the first imaging method for the detection of soft- tissue changes in the arthritic shoulder, but in rotator cuff problems both methods may be needed.      

Cytokine balance and lipid antigen presentation in the NOD mouse pancreas during development of insulitis

The role of cytokine balance and lipid antigen presentation in the development of diabetes was studied using immunohistochemistry of cytokines in the pancreas of non-obese diabetic mice (NOD) and BALB/c mice at various ages. In both the NOD and BALB/c mice, interleukin 10 (IL-10) was expressed in the islets. IL-10 was also present in the epithelial cells of the exocrine tissue in both strains. In the NOD mice, IL-10 disappeared from both the islets and the exocrine tissue at 16 weeks of age. At this age, IL-10 was still present in the islets and exocrine tissue of the BALB/c pancreata. IL-10 was not present in the pancreata of diabetic NOD mice. IL-6 first appeared in the pancreas at 10 weeks of age and disappeared at the age of 16 weeks in both NOD and BALB/c mice. It was present in the endothelial cells. Neither the pancreata of normal BALB/c mice nor NOD mice at 2-16 weeks of age contained tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), IL-4, or IL-12. At 8 weeks of age, a few IL-2+ cells were found in the pancreas of one of three NOD mice. CD1d was already present in both strains at 2 weeks of age but disappeared from the NOD mice at 16 weeks of age. CD1d localized to walls of tubular structures probably representing collecting tubules. These results suggest that in the NOD mice the disappearance of the T(H0), T(H1), and T(H2) responses inhibiting IL-10 from the islets at the age of 16 weeks may trigger the final stage of the immune response leading to overt diabetes. The simultaneous disappearance of CD1d suggests that activation of immune responses against lipid antigens does not play a role in this stage of the disease.     

How aggressive should initial therapy for rheumatoid arthritis be? The Finnish experience

SIR, We read with interest the report of Matteson et al. [1]concerning 2-yr results of hydroxychloroquine (HCQ) treatmentin 111 patients with early rheumatoid arthritis (RA). After2 yr of follow-up, inflammatory activity decreased statistically     

Evaluation of cardiovascular risk for renal transplantation in diabetic patients

Cardiovascular disease contributes in a major way to morbidity and mortality in diabetic patients with end-stage renal disease. Sixty patients with type I diabetes were evaluated prior to renal transplantation to determine the risk of cardiovascular complications. On the basis of results of thallium stress testing and/or cardiac catheterization, each patient was assigned to one of five categories. There were no cardiovascular events in the seven patients who had negative results on stress testing. Of the remaining 53 patients, all of whom underwent cardiac catheterization, 30 had normal coronary arteries. None of these 30 patients had any cardiac morbidity, and the two deaths that occurred in this group were not attributable to cardiac causes. Significant coronary artery disease was present in 38 percent of the patients. The overall mortality rate was 5.4 percent in those patients without coronary artery disease and 43.5 percent in those with the disease. In addition, the mortality rate in patients with coronary disease classified as severe was 62 percent, whereas it was 20 percent in those categorized as having moderate disease. The data indicate that patients with diabetes and end-stage renal disease who are at highest risk for cardiovascular events can be identified, and these patients probably should not undergo renal transplantation.     

Contrast-enhanced dynamic and static MRI correlates with quantitative 99Tcm-labelled nanocolloid scintigraphy. Study of early rheumatoid arthritis patients

OBJECTIVE: The aim of this study was to evaluate the roles of contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative 99Tcm-labelled nanocolloid (NC) scintigraphy in detecting wrist joint inflammation in early rheumatoid arthritis (RA) patients. METHODS: Twenty-eight early RA patients (median symptom duration 5 months, range 1-12 months) underwent MRI, NC scintigraphy, laboratory and clinical examinations. Static wrist MRI scans were retrospectively scored for synovitis, bone oedema and erosions by two independent readers using the recently published rheumatoid arthritis MRI scoring system (RAMRIS). Twenty NC scans were analysed quantitatively by measuring maximum 99Tcm-NC uptake in three small areas of each wrist. From the same locations on the wrists, dynamic MRI gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement rates (E-rate) were measured. The average 99Tcm-NC uptake of the whole wrist region was also measured and average E-rates were calculated. Correlations between MRI and NC scintigraphy measurements were calculated. Correlations between imaging methods of the wrist and the global measures of inflammation (laboratory and clinical examinations) were also assessed. RESULTS: Strong correlations emerged between maximal 99Tcm-NC uptake and MRI E-rates, reflecting similar performance of the methods in detecting local synovial inflammation. 99Tcm-NC uptake and MRI E-rate correlated with semiquantitative scoring of synovitis and bone oedema from static MRI scans. The erythrocyte sedimentation rate (ESR) correlated with MRI scores, E-rate and 99Tcm-NC uptake. No correlation between the clinical parameters and the imaging methods was detected. Inter-observer reliability for scoring synovial hypertrophy, bone oedema and bone erosions from static MR images were high (single-measure fixed-effects intra-class correlations 0.87, 0.93 and 0.91 respectively). Intra-observer reliability for E-rate and 99Tcm-NC measurements of 10 randomly picked scans was found to be high, with an intra-class correlation of 0.92; 95% confidence interval (CI) 0.84-0.96 and 0.99; 95% CI 0.98-1.00, respectively. CONCLUSIONS: Objective information about wrist joint inflammation can be obtained with contrast-enhanced dynamic MRI and quantitative 99Tcm-labelled NC scintigraphy. MRI also allows visualization and semiquantitative scoring of bone oedema and erosions of the wrist. Dynamic MRI and NC scintigraphy are safe and easy to perform, and they can be used in a long-term follow-up of rheumatoid patients.