Background. We describe the emergence and spread of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing K. pneumoniae at a Greek University hospital. Methods. Isolates with a carbapenem minimum inhibitory concentration >1 mug/mL and a negative EDTA-imipenem disk synergy test result were submitted to boronic acid disk test and to polymerase chain reaction (PCR) for KPC gene and sequencing. Records from patients who had KPC-2-producing K. pneumoniae isolated were retrospectively reviewed. Clinical isolates were submitted to molecular typing using pulsed-field gel electrophoresis, and the beta-lactamase content was studied using isoelectric focusing and PCR. Results. From January 2007 through December 2008, 50 patients (34 in the intensive care unit [ICU]) were colonized ([Formula: see text]) or infected ([Formula: see text]) by KPC-2-producing K. pneumoniae. Increasing prevalence of KPC-2-producing K. pneumoniae coincided with decreasing prevalence of metallo-beta lactamase-producing isolates in our ICU. Multidrug resistance characterized the studied isolates, with colistin, gentamicin, and fosfomycin being the most active agents. Besides KPC-2, clinical isolates encoded TEM-1-like, SHV-11, SHV-12, CTX-M-15, and LEN-19 enzymes. Four different clonal types were detected; the predominant one comprised 41 single patient isolates (82%). Sporadic multiclonal cases of KPC-2-producing K. pneumoniae infection were identified from September 2007 through May 2008. The outbreak strain was introduced in February 2008 and disseminated rapidly by cross-transmission; 38 patients (76%) were identified after August 2008. Fourteen cases of bacteremia, 2 surgical site infections, 2 lower respiratory tract infections (1 bacteremic), and 1 urinary tract infection were identified. Most patients received a colistin-containing combination treatment. Crude mortality was 58.8% among ICU patients and 37.5% among non-ICU patients, but attributable mortality was 22.2% and 33.3%, respectively. Conclusions. The emergence of KPC-2-producing K. pneumoniae in Greek hospitals creates an important challenge for clinicians and hospital epidemiologists, because it is added to the already high burden of antimicrobial resistance. less...

Abstract Aim: The study aimed to assess long term function after total perineal reconstruction (TPR) with dynamic graciloplasty (DG) and systematic Malone appendicostomy (MA) adjunction after abdominoperineal resection (APER) for rectal cancer. Method: From 1999 to 2004, TPR using DG and MA was performed in 10 patients (7 females; mdian age 40 years (range, 28-55 years)) after APER for rectal cancer (1 cT2, 6 cT3, 3 cT4). We prospectively recorded early and late morbidity, mortality, oncological outcome, functional results (modified Working Party on Anal Sphincter Replacement "WPASR" scoring system) and quality of life (European Organisation for Research and Treatment of Cancer "EORTC" QLQ-C30 and QLQ-CR38 questionnaires). Results: There was no procedure-related mortality. One patient required intra-abdominal re-operation. Nine patients required local revision, one patient for coloperineal anastomosis (CPA) stenosis, five patients for CPA mucosal prolapse, three patients for stenosis related to graciloplasty, two patients MA stenosis and one patient for MA reflux. After a median follow-up of 78 months, there was no local recurrence and six patients were alive and disease-free. Regarding the functional results, the median modified WPASR score was good (score of 8) after a follow-up of 78 months. The overall Quality of Life (QoL) scores remained stable over time. Conclusion: In carefully selected patients who want to avoid definitive abdominal colostomy after APER for rectal cancer, reconstruction involving MA and DG after APER for low rectal cancer is followed by good long term function and quality of life. less...

A Case Series. BACKGROUND: There are few anecdotal reports of circulating antineutrophil cytoplasmic autoantibodies (ANCAs) in patients with immunoglobulin A (IgA) nephropathy. STUDY DESIGN: Retrospective case series. SETTING & PARTICIPANTS: We studied 8 patients with crescentic IgA nephropathy associated with ANCAs against myeloperoxidase (n = 5) and proteinase 3 (n = 3) followed up for 2.4 +/- 1.7 years. They were compared with 26 patients with IgA nephropathy with > 10% crescentic glomeruli, but negative for ANCAs. OUTCOMES: We analyzed clinical and histologic features of patients and their response to treatment. MEASUREMENTS: Screening for ANCAs was performed using indirect immunofluorescence, and positive results were verified using enzyme-linked immunosorbent assay. RESULTS: All patients with crescentic IgA nephropathy and positive for ANCAs, compared with only one-third of ANCA-negative patients, presented with the clinical syndrome of rapid progressive glomerulonephritis. ANCA-positive patients reached a higher peak serum creatinine level within the first 3 months (4.2 +/- 2.2 vs 2.5 +/- 1.9 mg/dL; estimated glomerular filtration rate, 19.3 +/- 10.2 vs 45.9 +/- 30.1 mL/min/1.73 m(2)). ANCA-positive patients with IgA nephropathy had a higher percentage of crescentic glomeruli (54.3% +/- 18%) compared with ANCA-negative patients with crescentic IgA nephropathy (34.5% +/- 26%). ANCA-positive patients were treated using cyclophosphamide and corticosteroids. Kidney function improved in all these patients: serum creatinine level decreased from the peak of 4.2 +/- 2.2 to 1.7 +/- 0.7 mg/dL at the end of follow up (estimated glomerular filtration rate, 19.3 +/- 10.2 to 44.6 +/- 11.1 mL/min/1.73 m(2)). In contrast, no significant improvement was achieved in ANCA-negative patients. CONCLUSION: Patients with IgA nephropathy, crescents, and positive for ANCAs represent a clinical entity with a diverse more exaggerated clinical and histologic picture. However, disease in these patients responded well to aggressive immunosuppressive therapy. less...

OBJECTIVES:: The aim of this study was to evaluate the efficacy and safety profile of 4 dose-dense cycles of docetaxel followed by 3 cycles of FEC100 neoadjuvant chemotherapy in patients with operable advanced breast cancer. METHODS:: Women were treated by 4 cycles of 100 mg/m docetaxel every 2 weeks, followed by 3 cycles of FEC100 given every 3 weeks. The primary end point was pathologic complete response. RESULTS:: Forty-five patients were treated. Ninety-three percent of the patients completed the planned 7 chemotherapy courses. The median relative dose intensity for docetaxel, 5-fluorouracil, epirubicin, and cyclophosphamide were 0.98, 0.97, 0.96, and 0.97, respectively. There were no therapy-related deaths. Two patients stopped chemotherapy because of cutaneous toxicity. During the docetaxel sequence, the most common grade 3-4 toxicities were (% pts): neutropenia (13.3), grade 3: cutaneous (24.4), myalgia and arthralgia (6.7). No clinical cardiac toxicity was observed. The pathologic complete response rate was 21.4% and 26.2% using Sataloff and Chevallier classifications, respectively. The conservative surgery rate was 62.2%. The median follow-up was 38.5 months. Two and 3-year disease-free survival rates were 79% and 64%, respectively. Two- and 3-year overall survival rate were 93% and 88%, respectively. CONCLUSIONS:: This trial confirms the feasibility and efficacy of this dose dense docetaxel neoadjuvant regimen. less...

Radiation-induced midbrain fibrosarcoma is a rare, highly aggressive tumor, which is associated with poor prognosis. We present the case of a 48-year old man with brainstem fibrosarcoma 20 years following radiation therapy received for a pituitary tumor. We discuss this case in the context of the diagnostic criteria for these tumors, and previous reports of secondary and primary sarcomas of the central nervous system. less...

AASV is an autoimmune disease with multiple-system involvement, which if untreated, carries a poor prognosis. The kidneys are the most common involved organ in these vasculitides. We present a case of AASV who presented with severe anemia and acute renal failure that was treated with steroids and cyclophosphamide. less...

The rare occurrence of T-cell lymphoblastic lymphoma as a primary tumor in the cavernous sinus is described. The patient, a 17-year-old girl, presented with right-sided ophthalmic and maxillary neuropathy and diplopia due to neuropathies of cranial nerves III and VI. An enhancing mass in the cavernous sinus was identified on MR imaging. Dexamethasone was prescribed but did not provide symptomatic relief. Rapid progression of symptoms led to open biopsy, and a diagnosis of T-cell lymphoblastic lymphoma was made. The patient promptly underwent aggressive chemotherapy in which a modified hyper-cyclophosphamide, vincristine, and dexamethasone without doxorubicin regimen with concurrent radiotherapy was used. The patient achieved complete remission and is currently completing the 2-year maintenance phase of chemotherapy. less...

Objective-To investigate the effects of exercise and osteochondral injury on concentrations of carboxy-terminal telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) and serum of Thoroughbred racehorses and to compare findings with radiographic and arthroscopic scores of joint injury severity. Animals-78 Thoroughbreds with (n = 38) and without (40) osteochondral injury. Procedures-Serum and metacarpophalangeal or carpal joint SF samples were collected from noninjured horses before and at the end of 5 to 6 months of race training (pre- and postexercise samples, respectively) and from horses with osteochondral injury (1 joint assessed/horse). Synovial fluid and serum CTX-II concentrations were determined by use of an ELISA. Radiographic and arthroscopic scores of joint injury severity were determined for the injured horses. Results-The CTX-II concentrations in SF and SF:serum CTX-II ratio were significantly higher for horses with joint injuries, compared with pre- and postexercise findings in noninjured horses. Serum CTX-II concentrations in postexercise and injured-horse samples were significantly lower than values in pre-exercise samples. On the basis of serum and SF CTX-II concentrations and SF:serum CTX-II ratio, 64% to 93% of serum and SF samples were correctly classified into their appropriate group (pre-exercise, postexercise, or injured-joint samples). In horses with joint injuries, arthroscopic scores were positively correlated with radiographic scores, but neither score correlated with SF or serum CTX-II concentration. Conclusions and Clinical Relevance-Results suggested that serum and SF CTX-II concentrations and SF:serum CTX-II ratio may be used to detect cartilage degradation in horses with joint injury. less...

Type 2 diabetes is associated with normal-to-higher bone mineral density (BMD) and increased rate of fracture. Hyperinsulinemia and hyperglycemia may affect bone mass and quality in the diabetic skeleton. In order to dissect the effect of hyperinsulinemia from the hyperglycemic impact on bone homeostasis, we have analyzed L-SACC1 mice, a murine model of impaired insulin clearance in liver causing hyperinsulinemia and insulin resistance without fasting hyperglycemia. Adult L-SACC1 mice exhibit significantly higher trabecular and cortical bone mass, attenuated bone formation as measured by dynamic histomorphometry, and reduced number of osteoclasts. Serum levels of bone formation (BALP) and bone resorption markers (TRAP5b and CTX) are decreased by approximately 50%. The L-SACC1 mutation in the liver affects myeloid cell lineage allocation in the bone marrow: the (CD3(-)CD11b(-)CD45R(-)) population of osteoclast progenitors is decreased by 40% and the number of (CD3(-)CD11b(-)CD45R(+)) B-cell progenitors is increased by 60%. L-SACC1 osteoclasts express lower levels of c-fos and RANK and their differentiation is impaired. In vitro analysis corroborated a negative effect of insulin on osteoclast recruitment, maturation and the expression levels of c-fos and RANK transcripts. Although bone formation is decreased in L-SACC1 mice, the differentiation potential and expression of the osteoblast-specific gene markers in L-SACC1-derived mesenchymal stem cells (MSC) remain unchanged as compared to the WT. Interestingly, however MSC from L-SACC1 mice exhibit increased PPARgamma2 and decreased IGF-1 transcript levels. These data suggest that high bone mass in L-SACC1 animals results, at least in part, from a negative regulatory effect of insulin on bone resorption and formation, which leads to decreased bone turnover Because low bone turnover contributes to decreased bone quality and an increased incidence of fractures, studies on L-SACC1 mice may advance our understanding of altered bone homeostasis in type 2 diabetes. less...

It has been shown in a previous study that brown coal-derived potassium humate is safe and effective in suppressing contact hypersensitivity in rats In this study the efficacy of potassium humate on other types of inflammation was determined. Preparative TLC followed by mass spectroscopy was used in an attempt to fingerprint the product. The effects of potassium humate, at an oral dose of 60 mg/kg bodyweight, on a delayed type hypersensitivity reaction, a carrageenan-induced inflammation model and an allogeneic graft-versus-host reaction (GVHR) in rats were investigated. Paw oedema was used as a measure of inflammation. It was found that potassium humate had no effect on the delayed type hypersensitivity reaction but significantly inhibited the increase in paw volume of the carrageenan-induced oedema in rats which compared favourably with indomethacin treatment. Furthermore, potassium humate inhibited the GVHR induced in normal and cyclophosphamide-treated immune-incompetent rats. The identification of a naturally occurring compound that is safe and effective in reducing different types of inflammation merits further evaluation in clinical trials. less...