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.     

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.     

Robotic urological surgery in patients with prior abdominal operations is not associated with increased complications

BACKGROUND: The da Vinci Surgical Robotic System is being increasingly used to perform complex urological operations by minimally invasive techniques. Prior abdominal surgery associated with intra-abdominal adhesions may complicate robotic surgery. METHODS: We used a cohort of consecutive 49 patients undergoing a variety of robotic urological procedures at our institution to study the impact of prior abdominal operations on early perioperative complications. RESULTS: A total of 21/49 (43%) patients (Group A) had no history of prior abdominal surgery and the rest 28/49 (57%; Group B) had undergone prior abdominal surgery. The incidence of peritoneal adhesions was significantly higher in patients with prior abdominal surgery compared to the rest of the cohort, 54% versus 10% (P=0.002). The median operative time, estimated blood loss, postoperative drop in hemoglobin, time to hospital discharge, postoperative narcotic analgesic use and postoperative complication rate between group A and group B were not statistically different. The overall perioperative complication rate for the entire cohort was 14.3%, with 6-8% of complications occurring in each of the two groups (P=1.0). Comparative subset analysis of 28 patients in Group B, 15 (54%) and 13 (46%) with or without intra-abdominal adhesions did not reveal a significant difference in perioperative complication rates either. However, operative time was longer in patients with intra-abdominal adhesions compared to patients without, median of 590 (281-922) and 434 (153-723) min respectively, although not statistically significant (P=0.059). CONCLUSION: Our study demonstrates that robotic urological surgery can be performed in patients with prior abdominal surgery without increased perioperative complications.     

Vertical reduction mammaplasty utilizing the superomedial pedicle: is it really for everyone?

Background: Classically, the vertical-style reduction mammaplasty utilizing a superomedial pedicle has been limited to smaller reductions secondary to concerns for poor wound healing and nipple necrosis. Objectives: The authors reviewed a large cohort of patients who underwent a vertical-style superomedial pedicle reduction mammaplasty in an attempt to demonstrate its safety and efficacy in treating symptomatic macromastia. Methods: A retrospective review was performed of 290 patients (558 breasts) who underwent a vertical-style superomedial pedicle reduction mammaplasty. All procedures were conducted by one of 4 plastic surgeons over 6 years (JDR, MAA, DLV, DRA). Results: The average resection weight was 551.7 g (range, 176-1827 g), with 4.6% of resections greater than 1000 g. A majority of patients (55.2%) concomitantly underwent liposuction of the breast. The total complication rate was 22.7%, with superficial dehiscence (8.8%) and hypertrophic scarring (8.8%) comprising the majority. Nipple sensory changes occurred in 1.6% of breasts, with no episodes of nipple necrosis. The revision rate was 2.2%. Patients with complications had significantly higher resection volumes and nipple-to-fold distances (P = .014 and .010, respectively). Conclusions: The vertical-style superomedial pedicle reduction mammaplasty is safe and effective for a wide range of symptomatic macromastia. The nipple-areola complex can be safely transposed, even in patients with larger degrees of macromastia, with no episodes of nipple necrosis. The adjunctive use of liposuction should be considered safe. Last, revision rates were low, correlating with a high level of patient satisfaction.     

Evaluation of a rapid stoolantigen test for the diagnosis of Helicobacter pylori infection in Chinese patients

OBJECTIVE: To evaluate the accuracy of a rapid assay that wasdeveloped to detect Helicobacter pylori antigen in the stool,using the principle of immunochromatography, in the Chinese population. METHODS: Eligible patients without prior treatment of H.pylori were recruited. An in‐house rapid urease test (RUT) andhistology were used as the gold standard. The results of the rapidstool antigen test were compared with the gold standard. RESULTS: Valid rapid stool antigen test results for interpretationwere obtained from 94 consecutive patients (mean age: 52.5, range:22?82 years). Sensitivity, specificity, positive predictivevalue, negative predictive value and accuracy were, respectively, 77.5%,87.0%, 81.6%, 83.9% and 83.0%.The test was easy to perform and results were available within 15 min. CONCLUSION: The rapid stool antigen test using immunochromatography accuratelydiagnoses H. pylori infection in Chinese patients.