Anomalous “High Take‐Off” of the right coronary artery evaluated by coronary CT angiography

Congenital coronary anomalies are uncommon but can cause sudden cardiac death or myocardial ischemia. Conventional coronary angiography is an invasive and expensive modality, sometimes unable to delineate the exact origin and course of an anomalous artery. In this case report, we describe an “extremely rare” anomaly of the right coronary artery where a 64‐slice multidetector computed tomography provided valuable information regarding its exact site of the aortocoronary take‐off and its spatial relationship with the great vessels. Knowledge of CT appearances and an understanding of the clinical significance of these anomalies are essential for making the correct diagnosis and planning patient treatment. © 2010 Wiley Periodicals, Inc.     

Second marrow transplants in patients with aplastic anemia rejecting the first graft: use of a conditioning regimen including cyclophosphamide and antithymocyte globulin

Sixteen (11%) of 146 consecutive patients with severe aplastic anemia prepared for engraftment with cyclophosphamide (200 mg/kg) rejected marrow grafts from their HLA-identical siblings. They were given a second marrow transplant from either the same (n = 13) or a second (n = 3) HLA-identical sibling between 23 and 743 (median 86) days after the first transplant. The preparation for the second transplant included cyclophosphamide, 50 mg/kg, on each of four successive days. Twelve hours after each of the first three doses of cyclophosphamide, antithymocyte globulin, 30 mg/kg/dose, was infused. One of the 16 patients died from infection too early after the second transplant to be evaluated, two had failure of engraftment and died with infection, one rejected the second graft and is surviving almost 5 years later with full autologous marrow recovery, and 12 had successful and sustained second grafts. Of these 12, six are surviving between 11 months and 7 3/4 years. Four of the six have no graft-v-host disease (GVHD), while two have chronic GVHD requiring treatment. Five have Karnofsky scores of 100% and one of 90%. Six of the 12 patients with sustained grafts died between 63 days and 38 months after transplantation, four with infections (related in two patients to chronic GVHD), one with acute GVHD, and one with hemorrhage. The average interval from first to second transplant was 308 days during the past five years, compared to 61 days in earlier patients. Five of seven recent patients are surviving, compared to two of nine earlier patients. In conclusion, successful second transplants after cyclophosphamide and antithymocyte globulin are possible in most patients with aplastic anemia who have rejected their first marrow grafts; however, mortality remains high, with only 40% of the patients becoming long-term survivors.     

Pluronic L-81 ameliorates diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein

AIM： To test whether oral L-81 treatment could improve the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein （MTP） activity in the liver.
METHODS： Genetically diabetic （db/db） mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mechanism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B （apoB） secretion and mRNA level of the MTP gene were assessed.
RESULTS： Treatment of db/db mice with L-81 significantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also significantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter.
CONCLUSION： L-81 represents a promising candidate in the development of a selective insulin-mimetic molecule and an anti-diabetic agent.     

CD40 ligand triggered interleukin-6 secretion in multiple myeloma

Previous studies have suggested that interleukin-6 (IL-6) may mediate growth of multiple myeloma (MM) in either an autocrine or paracrine growth mechanism. However, those molecules which can trigger IL-6 secretion either by tumor cells or non-MM marrow cells are not well characterized. In the present study, we have examined the expression and functional significance of CD40 on MM and plasma cell leukemia (PCL) cells and derived cell lines, as well as long-term bone marrow stromal cells (BMSCs) and derived cell lines. CD40 was expressed on the majority of MM cells (> 90%) and BMSCs (> 70%). Triggering via CD40 using NIH3T3 CD40 ligand transfectant (CD40LT) cells increased (> 30%) cell surface CD80, CD18, CD11a, CD11b, and CD11c expression on MM cell lines. Culture with either fresh or paraformaldehyde fixed NIH3T3 CD40LT cells upregulates IL-6 secretion in MM cells and MM-derived cell lines, as well as normal and MM bone marrow mononuclear cells (BMMCs), BMSCs, and BMSC lines; this effect can be specifically blocked by anti- CD40 monoclonal antibody (MoAb). BMMCs and BMSCs from patients with MM secreted significantly more IL-6 than those from healthy donors (n = 3, P < .001); moreover, after stimulation using CD40L, IL-6 secretion was fourfold greater (n = 3, P < .001) from MM BMMCs and BMSCs than from normal BMMCs and BMSCs. Myeloma (CD38+CD45RA-) cells and non-MM (CD38+CD45RA+, CD38-CD45RA+, and CD38-CD45RA-) BMMCs were separated by dual fluorescence cell sorting. The latter secreted fourfold more IL-6 than the former (n = 2, P < .001). Increased IL-6 secretion (up to 28- fold) and proliferation (Stimulation index 10) by CD38+CD45RA-MM cells was triggered by culture with NIH3T3 CD40LT cells. Finally, anti- CD40MoAb partially (30%) blocked tumor cell to BMSC adhesion-induced IL- 6 secretion. These studies support the view that CD40L may trigger IL-6 secretion by both MM cells and BMSCs and that IL-6-mediated autocrine and paracrine growth mechanisms may be possible in MM.     

The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: a review

Bleeding and thrombosis are long recognized complications of myelofibrosis (MF) and contribute significantly to its morbidity and mortality. However, so far, few studies have evaluated the frequency of these events, their characteristics, and their prognostic impact. Based on these studies, thrombotic events in MF are about as common as in essential thrombocytemia (ET) but less common than in polycythemia vera (PV), while bleeding events are relatively more common in MF than in ET or PV. The emergence of the concept of prefibrotic primary MF (PMF), which is associated with a higher frequency of thrombohemorrhagic complications than ET, and the growing evidence that prefibrotic PMF may also have a different thrombotic and bleeding risk profiles than fibrotic (overt) PMF have emphasized the need for a reappraisal of the risk of thrombosis and hemorrhage in patients with MF. In this review, we discuss the frequency of thrombosis and bleeding in patients with MF, including prefibrotic PMF and their established and potential risk factors.     

Graded Pneumatic Dilation using Rigiflex Achalasia Dilators in Patients with Primary Esophageal Achalasia

Pneumatic dilation is the initial therapy for primary esophageal achalasia. Recently, polyethylene balloon (Rigiflex) dilators have been used with varying success and complication rate. We performed a total of 47 dilations in 29 consecutive patients with achalasia using the Rigiflex dilators. The 3.0-cm balloon was always used first. If there was no symptomatic response, a 3.5-cm balloon was used after 4–8 wk. If there was still no symptomatic response after 4-8 wk, a 4.0-cm dilator was used. Eighteen (62%) patients were successfully dilated with a 3.0-cm balloon only. Of 11 patients not responding to a 3.0-cm balloon, five were dilated successfully with a 3.5-cm balloon. Of six patients not responding to a 3.5-cm balloon, four were successfully dilated with a 4.0-cm balloon dilator. Two patients eventually required surgery. The overall success with Rigiflex balloon dilator was achieved in 27 of 29 (93%) patients. There were no complications. We conclude that pneumatic dilation for esophageal achalasia performed in a graded fashion starting with Rigiflex 3.0-cm balloon dilator has a high success rate without complications in patients with achalasia.     

Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital

A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics.     

Transient bone marrow oedema: A variant pattern of sacral insufficiency fractures

A 71-year-old woman presenting with severe low back pain was found to have a large oval area of increased sacral uptake on Tc-99m MDP scan, with corresponding T1-hypointense and T2-hyperintense areas on magnetic resonance (MR) images, highly suggestive of malignancy. Open biopsies showed only callus formation. The patient responded clinically to conservative measures, with twice-repeated follow-up Tc-99m MDP and MR scans documenting resolution of transient bone marrow oedema. We suggest that this form of marrow oedema represents a variant pattern of sacral insufficiency fractures.