Coexistence of ankylosing spondylitis and rheumatoid arthritis.

Ankylosing spondylitis and rheumatoid arthritis share many common features. However the presence of rheumatoid factor, histologically classic rheumatoid nodules, and the histocompatibility cell wall antigen (HLA-B27) helps distinguish one from the other. Two cases are reported in which these features established the coexisting diagnoses of ankylosing spondylitis and rheumatoid arthritis.     

Analysis of the apo(a) size polymorphism in Asian Indian populations: association with Lp(a) concentration and coronary heart disease

Most studies aiming to detect associations of genetic variation with common complex diseases, e.g. coronary heart disease (CHD) have been performed in populations with a western lifestyle but it is unclear whether associations detected in one geographic group exist also in others. We here have determined lipoprotein(a) levels and apo(a) K-IV-2 repeat genotypes in CHD patients (N=254) and controls (N=480) from two Asian Indian populations (Tamil Nadu and New Delhi). In both populations and also in the pooled dataset median Lp(a) levels were significantly elevated in the patients (27.4 mg/dl) compared with the controls (17.6 mg/dl). Apo(a) K-IV-2 allele frequencies were not different between the CHD patients and controls and thus did not explain the increased Lp(a) levels in CHD patients. Contrary to what has recently been observed in Black and White men short (K-IVor=30) apo(a) alleles were all associated with higher Lp(a) levels in the patients. Accordingly relative risk (estimated as odds ratio) for CHD rose continuously with increasing Lp(a) but was independent of apo(a) allele length. Together with previous studies our results indicate that the relation between apo(a) genotypes, Lp(a) levels, and CHD may be heterogeneous across ethnic groups and that it depends on the genetic architecture of the Lp(a) trait in a given population whether an association of K-IV-2 repeat length with CHD exists or not.     

Prognostic impact of RAS mutations in patients with myelodysplastic syndrome

RAS is an oncogene frequently mutated in human cancer. RAS mutations have been reported in 10–15% of cases of acute myeloid leukemia (AML) but they appear to be less frequent among patients with myelodysplastic syndrome (MDS). The impact of RAS mutations in patients with MDS is unclear. We conducted a retrospective study in 1,067 patients with newly diagnosed MDS for whom RAS mutational analysis was available. Overall, 4% of patients carried mutant RAS alleles. Notably, FLT3 mutations, which were found in 2% of patients, were mutually exclusive with RAS mutations. Patients with RAS mutations had a higher white blood cell count as well as bone marrow blasts compared with patients carrying wild‐type RAS. However, no differences were observed between both groups regarding the risk of AML transformation (9% vs. 7%) and overall survival (395 days vs. 500 days, P = 0.057). In summary, RAS mutations are infrequent in patients with MDS and do not appear to negatively impact their outcome. Am. J. Hematol. 88:365–369, 2013. © 2013 Wiley Periodicals, Inc.     

Assessment at 6 months may be warranted for patients with chronic myeloid leukemia with no major cytogenetic response at 3 months

Response to tyrosine kinase inhibitors at three months is a predictor for long-term outcome in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. We analyzed 456 newly diagnosed chronic myeloid leukemia patients treated with tyrosine kinase inhibitors to determine their outcome based on their response at six months. Forty-four (10%) patients did not achieve major cytogenetic response at three months: 18 of 67 (27%) patients treated with imatinib 400; 18 of 196 (9%) with imatinib 800; and 8 of 193 (4%) with 2nd generation tyrosine kinase inhibitors. Among them, 19 (43%) achieved major cytogenetic response at six months and subsequently had an overall outcome similar to the patients who achieved a major cytogenetic response at three months. In conclusion, the response to tyrosine kinase inhibitors at three months is a static, one-time measure. Assessing the response at six months of patients with poor response at three months may provide a better predictor for long-term outcome.     

Acetohydroxyacid synthase from Claviceps purpurea: Partial purification and characterization

An acetohydroxyacid synthase (EC 4.1.3.18) which synthesizes α-acetolactate from pyruvate has been isolated from two different Claviceps purpurea strains. A purification of about 142-fold was achieved by ammonium sulfate fractionation and the use of Sepharose 6B and DEAE-Sepharose CL-6B columns. The purified enzyme requires thiamine pyrophosphate and a divalent metal ion (Mn² + or Mg² +) for maximum activity but no FAD. The optimum pH is about 6.0 and the optimum temperature is 40 °C. The enzyme is not inhibited by branched-chain amino acids neither singly nor in combination. AHAS is strongly inhibited by p-chloromercuribenzoate and N-ethylmaleimide. The apparent K_m values for pyruvate and TPP are 1.7 × 10^?2 M and 1.2 × 10^?6 M , respectively.     

Acute Presentation in Adult in Bland‐White‐Garland Syndrome: Double‐Conduit,Two‐Coronary Repair

Abstract Adult presentation with myocardial infarction in anomalous origin of the left main coronary artery from the pulmonary artery is rare. We describe the different coronary flow physiology in the adult form. A double‐conduit repair with a separate feeder vessel to each limb of the left coronary circulation may be necessary to balance the myocardial demand and supply in large systemic collateral coronary beds. The report describes the use of the left internal mammary and radial artery for repair.     

Rheumatoid arthritis: can the long-term outcome be altered?

Although several agents (for example, intramuscularly administered gold, auranofin, D-penicillamine, hydroxychloroquine, and methotrexate) are of clinical benefit in the management of rheumatoid arthritis (RA), their effect on the long-term outcome of the disease is controversial. Assessment of the influence of therapeutic interventions in RA is difficult because the natural history of the disease remains poorly defined and unpredictable, and neither the traditional clinical and laboratory measurements of inflammation nor radiographic analyses of progression of joint destruction provide an accurate estimate of the long-term outcome of RA. Furthermore, there is little evidence that second-line agents yield benefits beyond 3 years. Therefore, adequately tested comprehensive measures should be used in large, long-term, multicenter controlled clinical trials to determine whether the long-term outcome of RA can be altered.