Plasma neutrophil gelatinase-associated lipocalin levels are positively associated with diabetic retinopathy in patients with Type 2 diabetes.

AIM: To assess the relationship between plasma neutrophil gelatinase-associated lipocalin (NGAL) levels and diabetic retinopathy in patients with Type 2 diabetes. METHODS: In total, 204 patients with Type 2 diabetes were investigated in this cross-sectional study. They were classified as having no diabetic retinopathy, non-proliferative diabetic retinopathy (NPDR) or proliferative retinopathy (PDR), according to the degree of diabetic retinopathy. Thus, diabetic retinopathy in the patients in this study was either NPDR or PDR. RESULTS: Plasma NGAL concentrations were significantly higher in patients with diabetic retinopathy than in those without. The mean plasma NGAL levels differed significantly according to the severity of diabetic retinopathy (no diabetic retinopathy, 120.8 ng/ml; NPDR, 217.8 ng/ml; PDR, 372.4 ng/ml; P for trend = 0.002) after adjustment for other covariates. In multivariable analysis, plasma NGAL levels were significantly associated with diabetic retinopathy (odds ratio for each standard deviation increase in the logarithmic value, 7.75; 95% confidence interval, 2.04-29.41, P = 0.003). CONCLUSION: Plasma NGAL levels were positively associated with diabetic retinopathy in patients with Type 2 diabetes.

Upfront plerixafor plus G-CSF versus cyclophosphamide plus G-CSF for stem cell mobilization in multiple myeloma: efficacy and cost analysis study.

Cyclophosphamide plus G-CSF (C+G-CSF) is one of the most widely used stem cell (SC) mobilization regimens for patients with multiple myeloma (MM). Plerixafor plus G-CSF (P+G-CSF) has demonstrated superior SC mobilization efficacy when compared with G-CSF alone and has been shown to rescue patients who fail mobilization with G-CSF or C+G-CSF. Despite the proven efficacy of P+G-CSF in upfront SC mobilization, its use has been limited, mostly due to concerns of high price of the drug. However, a comprehensive comparison of the efficacy and cost effectiveness of SC mobilization using C+G-CSF versus P+G-CSF is not available. In this study, we compared 111 patients receiving C+G-CSF to 112 patients receiving P+G-CSF. The use of P+G-CSF was associated with a higher success rate of SC collection defined as ⩾5 × 10(6) CD34+ cells/kg (94 versus 83%, P=0.013) and less toxicities. Thirteen patients in the C+G-CSF arm were hospitalized owing to complications while none in the P+G-CSF group. C+G-CSF was associated with higher financial burden as assessed using institutional-specific costs and charges (P<0.001) as well as using Medicare reimbursement rates (P=0.27). Higher rate of hospitalization, increased need for salvage mobilization, and increased G-CSF use account for these differences.

Serum Cystatin C Levels are Positively Associated with Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes.

AIMS: Previous studies have reported that cystatin C is associated with degenerative disorder in the nervous system. However, the relationship between serum cystatin C concentrations and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes is currently unknown. The aim of this study was to assess the relationships between serum cystatin C levels and CAN in patients with type 2 diabetes. METHODS: A total of 357 patients with type 2 diabetes were studied in this cross-sectional study. CAN was diagnosed by a cardiovascular autonomic reflex test. According to the American Diabetes Association criteria, the degree of cardiovascular autonomic dysfunction was graded as normal, early, definite, or severe. CAN was either definite or severe in the subjects of the present study. RESULTS: Serum cystatin C concentrations were significantly higher in patients with CAN than in those without CAN. The mean cystatin C levels differed significantly according to the degree of cardiovascular autonomic dysfunction (normal, 0.78 mg/l; early, 0.79 mg/l; definite, 0.87 mg/l; severe, 0.90 mg/l; P for trend=0.021) after adjustment for other covariates. In multivariate analysis, serum cystatin C levels were significantly associated with CAN (odds ratio [OR] of each standard deviation increase in the logarithmic value, 5.25; 95% confidence interval [CI], 1.17-23.70, P=0.025). CONCLUSIONS: Serum cystatin C levels are positively associated with CAN in patients with type 2 diabetes.

Effect of hypoxia on generation of neurospheres from adipose tissue-derived canine mesenchymal stromal cells.

Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are good candidates for cell therapy due to the accessibility of fat tissue and the abundance of AT-MSCs therein. Neurospheres are free-floating spherical condensations of cells with neural stem/progenitor cell (NSPC) characteristics that can be derived from AT-MSCs. The aims of this study were to examine the influence of oxygen (O2) tension on generation of neurospheres from canine AT-MSCs (AT-cMSCs) and to develop a hypoxic cell culture system to enhance the survival and therapeutic benefit of generated neurospheres. AT-cMSCs were cultured under varying oxygen tensions (1%, 5% and 21%) in a neurosphere culture system. Neurosphere number and area were evaluated and NSPC markers were quantified using real-time quantitative PCR (qPCR). Effects of oxygen on neurosphere expression of hypoxia inducible factor 1, α subunit (HIF1A) and its target genes, erythropoietin receptor (EPOR), chemokine (C-X-C motif) receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF), were quantified by qPCR. Neural differentiation potential was evaluated in 21% O2 by cell morphology and qPCR. Neurospheres were successfully generated from AT-cMSCs at all O2 tensions. Expression of nestin mRNA (NES) was significantly increased after neurosphere culture and was significantly higher in 1% O2 compared to 5% and 21% O2. Neurospheres cultured in 1% O2 had significantly increased levels of VEGF and EPOR. There was a significant increase in CXCR4 expression in neurospheres generated at all O2 tensions. Neurosphere culture under hypoxia had no negative effect on subsequent neural differentiation. This study suggests that generation of neurospheres under hypoxia could be beneficial when considering these cells for neurological cell therapies.

Factors impacting stem cell mobilization failure rate and efficiency in multiple myeloma in the era of novel therapies: experience at Memorial Sloan Kettering Cancer Center.

Thalidomide, lenalidomide and bortezomib have increasingly been incorporated in first-line induction therapies for multiple myeloma. Concerns regarding the impact of these agents, especially lenalidomide, on stem cell mobilization prompted us to re-evaluate the risk factors that impact mobilization, including exposure to novel induction regimens. Among 317 patients who proceeded to stem cell collection after induction therapy between 2000 and 2009, the rate of mobilization failure, defined as the inability to collect 5 × 10(6) CD34+ cells/kg following the first collection attempt, was 13%. By multivariate analysis, independent risk factors associated with mobilization failure included older age (P=0.04), lower platelet count (P=0.002) and use of single-agent G-CSF for mobilization (P<0.0001). When considering for outcome measurement stem cell collection efficiency measured by the number of CD34+ cells yielded per pheresis performed during first collection attempt, lower platelet count, use of single-agent G-CSF and older age were also associated with lower efficiency. In this population mobilized mostly with cyclophosphamide and G-CSF, the use of lenalidomide during induction was not associated with a lower stem cell collection efficiency by multivariate analysis. The data support the current International Multiple Myeloma Working Group guidelines recommending the use of cyclophosphamide and G-CSF based mobilization for patients previously exposed to lenalidomide.

A laminin-2-derived peptide promotes early-stage peripheral nerve regeneration in a dual-component artificial nerve graft.

The DLTIDDSYWYRI motif (Ln2-P3) of human laminin-2 has been reported to promote PC12 cell attachment through syndecan-1; however, the in vivo effects of Ln2-P3 have not been studied. In Schwann cells differentiated from skin-derived precursors, the peptide was effective in promoting cell attachment and spreading in vitro. To examine the effects of Ln2-P3 in peripheral nerve regeneration in vivo, we developed a dual-component poly(p-dioxanone) (PPD)/poly(lactic-co-glycolic acid) (PLGA) artificial nerve graft. The novel graft was coated with scrambled peptide or Ln2-P3 and used to bridge a 10 mm defect in rat sciatic nerves. The dual-component nerve grafts provided tensile strength comparable to that of a real rat nerve trunk. The Ln2-P3-treated grafts promoted early-stage peripheral nerve regeneration by enhancing the nerve regeneration rate and significantly increased the myelinated fibre density compared with scrambled peptide-treated controls. These findings indicate that Ln2-P3, combined with tissue-engineering scaffolds, has potential biomedical applications in peripheral nerve injury repair.

Therapeutic effect of high-intensity focused ultrasound combined with transarterial chemoembolisation for hepatocellular carcinoma <5 cm: comparison with transarterial chemoembolisation monotherapy--preliminary observations.

OBJECTIVE: To retrospectively compare the therapeutic effects of combined high-intensity focused ultrasound (HIFU) and transarterial chemoembolisation (TACE) with TACE alone for the treatment of non-advanced hepatocellular carcinomas (HCCs) <5 cm. METHODS: We retrospectively reviewed the tumour responses of 32 HCCs of 25 patients who underwent combined HIFU and TACE, and 46 HCCs of 32 patients who underwent TACE only. The mean follow-up observation of the TACE+HIFU group was on average 31 months and that of the TACE group was 33 months. Those patients who had undergone any other treatment modality (including systemic chemotherapy) during the follow-up observation period were excluded. The therapeutic effects were classified according to the modified Response Evaluation Criteria In Solid Tumors (mRECIST): complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Additionally, we defined CR', PR', SD' and PD' as the therapeutic effects "per tumour". RESULTS: The disease control rate calculated using the RECIST criteria (CR+PR+SD/All) was 48% in the HIFU+TACE group and 47% in the TACE group (p=0.78, Fisher's exact test). The disease control rate "per tumour" (CR'+PR'+SD'/All) was 78% in the HIFU+TACE group and 54% in the TACE group (p=0.035, Fisher's exact test). In the HIFU+TACE group, no HIFU-related complications requiring treatment were observed. The median survival time was 57 months in TACE+HIFU group and 36 months in the TACE group (p=0.048). CONCLUSION: This preliminary study shows that the combination therapy of HIFU and TACE is more effective than TACE monotherapy for treating HCCs <5 cm.

Metastatic acinar cell carcinoma of the liver from a benign-appearing pancreatic lesion: a mimic of hepatocellular carcinoma.

Acinar cell carcinoma (ACC) is a rare pancreatic tumour with a favourable prognosis compared with the more common ductal adenocarcinoma. The radiological findings of this tumour have been described in the literature; however, only limited data are available regarding the metastatic features of ACC of the liver, the most common metastatic site. We report a case of ACC of the pancreas with a hepatic metastasis from a benign-appearing malignant pancreatic lesion.

Surgical repair of anterior wall vaginal defects.

OBJECTIVE: To compare the clinical efficacy of 3 surgical procedures for central types of anterior vaginal wall defect. METHODS: A total of 138 patients diagnosed with central types of anterior vaginal wall defect who underwent classic transvaginal repair (n=72), transvaginal repair with polypropylene mesh (n=28), and internal repair (n=38) were followed up for at least 1 year. RESULTS: There were no differences in development of fever, vaginal erosion, detrusor overactivity, and voiding difficulty among the 3 groups, but the incidence of postoperative urinary tract infections was significantly higher in the polypropylene mesh repair group. The difference in preoperative and postoperative hemoglobin levels and wound infection incidence were significantly higher in the internal repair group. Moreover, the recurrence rate of the anterior vaginal wall defect was significantly higher at 1 year in the internal repair group. CONCLUSION: Transvaginal surgical repair seems to be more efficacious than internal surgical repair for central types of anterior vaginal wall defects.

Risk factors for pelvic organ prolapse.

OBJECTIVES: To evaluate the risk factors for pelvic organ prolapse (POP) and to determine the relationship between these risk factors and stage or other components of POP. METHODS: 244 patients with primary POP and 314 women without POP were included. Age, parity, smoking, body mass index (BMI), menopause, and hormone replacement therapy (HRT) were investigated. RESULT: Independent risk factors for POP included age over 70, parity higher than 3, and menopause. Age, parity, menopause, and HRT were significantly associated with stage of POP. Genital hiatus (GH) and perineal body (PB) showed a significant positive and negative correlation with age and parity, respectively. Menopause and HRT were also associated with them. CONCLUSION: Age, parity and menopause are possible risk factors of POP and associated with the lengths of GH and PB in POP women. Further, these risk factors and HRT are significantly correlated with the severity of the disease.

Increased telomerase activity and human telomerase reverse transcriptase mRNA expression in the endometrium of patients with endometriosis.

BACKGROUND: Endometriosis is considered a frequent, benign disease with the ability to undergo neoplastic processes. The aim of this study was to evaluate the limitless replication potential of the endometrium in patients with endometriosis by examining human telomerase reverse transcriptase (hTERT) mRNA expression and telomerase activity. METHODS: Endometrium samples from 30 endometriosis patients and 30 patients without endometriosis were obtained via endometrial biopsy. The expression of hTERT mRNA was determined by real-time RT-PCR assay, and telomerase activity was measured by telomerase repeat amplification protocol (TRAP) assay. RESULTS: The mean normalized hTERT (N hTERT) mRNA level was significantly higher in the endometriosis than in the control group (P = 0.013). The mean hTERT mRNA levels during the proliferative phase and during the secretory phase were higher in the endometriosis group than in the control group, although the difference was only significant for the secretory phase (P = 0.036). We found a prominent difference in endometrial telomerase activity between moderate-to-severe endometriosis and the control group (P = 0.048). The levels of hTERT mRNA and telomerase activity increased as the disease became more severe (P = 0.038, P = 0.016). CONCLUSIONS: This study showed the overexpression of hTERT mRNA and telomerase activity in the endometrium of endometriosis patients. These finding suggest that replication potential of endometrial cells may have an important role in the pathogenesis of endometriosis.

Deciduoid peritoneal mesothelioma: CT findings with pathologic correlation.

We report a rare case of deciduoid peritoneal mesothelioma in a 47-year-old woman who had no history of asbestos exposure or previous surgery. Immunohistochemistry and electron microscopic findings showed that the tumor was a subtype of epithelioid mesothelioma. Awareness of this disease entity is helpful for the differential diagnosis of peritoneal masses.

Radiologic findings of Behçet syndrome involving the gastrointestinal tract.

Behçet syndrome is characterized by the histopathologic finding of nonspecific vasculitis in multiple organs. The diagnosis is usually made on the basis of the combination of clinical signs and symptoms. This disease involves the gastrointestinal tract in 10%-50% of patients, and the terminal ileum and cecum are chiefly affected. Barium study is useful in demonstrating the characteristic radiographic features of Behçet syndrome involving the gastrointestinal tract. The presence of deep, penetrating ulcers results in a high rate of complications, such as perforation, fistula, hemorrhage, and peritonitis. Furthermore, recurrence of disease adjacent to or at the surgical anastomosis is common. Computed tomography is useful in determining the extent of the lesions and in identifying cases in which complications are likely to occur. Familiarity with the various radiologic findings of Behçet syndrome involving the gastrointestinal tract helps in making an early diagnosis, as well as in establishing an appropriate treatment strategy.

Apoplexy of pituitary macroadenoma after combined test of anterior pituitary function.

Pituitary apoplexy has been reported as a very rare complication of combined tests of anterior pituitary function and of TRH or gonadotropin-releasing hormone (GnRH) administration in pituitary tumor. A 34-year-old man with a GH-secreting pituitary macroadenoma and diabetes mellitus received an injection of 400 microg TRH, 100 microg GnRH, and 0.15 U/Kg regular insulin. Twenty minutes later, he complained of a severe headache and vomited. Visual acuity and visual field did not change and his headache was persistent during the next 24 hours of conservative management. Magnetic resonance imaging (MRI) of the sella turcica done the day after the event showed definitive elevation of the optic chiasm and slight enlargement of tumor and focal areas of mixed high signal and low signal intensities in the macroadenoma on noncontrast T1-weighted images. Headache subsided markedly within a day of octreotide therapy. Transsphenoidal removal of the pituitary tumor was performed 9 days after the hormone study. Ischemic necrosis and hemorrhage were confirmed in the acidophilic adenoma with positive immunostaining for GH. Postoperative course was uneventful and his serum insulin-like growth factor-1 (IGF-1) level and blood glucose levels were normalized. Three months after the surgery the dynamic test was repeated without adverse effects. To our knowledge, this is a very rare case of apoplexy of GH-secreting pituitary adenoma after a combined stimulation test of anterior pituitary function.

Non-Hodgkin's lymphoma of the thyroid and adrenal glands.

We report a case of non-Hodgkin's lymphoma(NHL) with simultaneous involvement of both thyroid and bilateral adrenal glands. Literature review on a computerized search showed that this is an extremely rare condition. The final diagnosis of diffuse large B cell lymphoma was confirmed by biopsies of thyroid gland, enlarged cervical lymph node, and adrenal gland. The significant endocrine dysfunction of the thyroid, adrenal or other endocrine glands was absent in our case. The patient responded dramatically to three cycles of chemotherapy with no complication or endocrine dysfunction and continues to be followed.

Tuberculous aneurysm of the abdominal aorta: endovascular repair using stent grafts in two cases.

Tuberculous aneurysm of the aorta is exceedingly rare. To date, the standard therapy for mycotic aneurysm of the abdominal aorta has been surgery involving in-situ graft placement or extra-anatomic bypass surgery followed by effective anti-tuberculous medication. Only recently has the use of a stent graft in the treatment of tuberculous aortic aneurysm been described in the literature. We report two cases in which a tuberculous aneurysm of the abdominal aorta was successfully repaired using endovascular stent grafts. One case involved is a 42-year-old woman with a large suprarenal abdominal aortic aneurysm and a right psoas abscess, and the other, a 41-year-old man in whom an abdominal aortic aneurysm ruptured during surgical drainage of a psoas abscess.

Effect of petroleum ether extract of Panax ginseng roots on proliferation and cell cycle progression of human renal cell carcinoma cells.

Panax ginseng roots have long been used as a medicinal herb in oriental countries. We have investigated anti-proliferative effects of lipid soluble Panax ginseng components on human renal cancer cell lines. Petroleum ether extract of Panax ginseng roots (GX-PE) or its partially purified preparation (7:3 GX) was added to cultures of three human renal cell carcinoma (RCC) cell lines, A498, Caki-1, and CURC II. Proliferation of RCC cells was estimated by a [3H]thymidine incorporation assay and cell cycle distribution was analyzed by flow cytometry. GX-PE, 7:3 GX, panaxydol and panaxynol inhibited proliferation of all three RCC cell lines in a dose dependent manner in vitro with an order of potency, 7:3 GX > panaxydol > panaxynol = GX-PE. Additive effect of interleukin 4 was also demonstrated, most prominently in Caki-1 which responded poorly to GX-PE alone. Analysis of cell cycle in CURC II and Caki-1 treated with GX-PE demonstrated increase in G1 phase population and corresponding decrease in S phase population. The present study demonstrated that proliferation of human RCC cell lines were inhibited by lipid soluble components of Panax ginseng roots by blocking cell cycle progression at G1 to S phase transition.

Inhibitory effects of interleukin-4 on human renal cell carcinoma cells in vitro: in combination with interferon-alpha, tumor necrosis factor-alpha or interleukin-2.

BACKGROUND: Immune cytokines have been shown to play important roles in regulating the growth of neoplastic cells, as well as the function of immune cells. The present study assessed the effects of interleukin (IL)-4 alone, and in combination with recombinant interferon (IFN)-alpha 2b, or with IL-2, or with tumor necrosis factor (TNF)-alpha on the in vitro proliferation of human renal cell carcinoma (RCC) cell-lines. METHODS: Growth-inhibitory effects of IL-4 alone, and in combination with other cytokines, on three human RCC cell-lines, Caki-1, CURC-II, and A-498, were measured by the [3H]thymidine incorporation assay. RESULTS: IL-4 inhibited proliferation of all three human RCC cell-lines (P < 0.001). The maximum growth inhibition of RCC cell-lines by IL-4 alone was observed at the concentration of 1 to 3 ng/mL, depending on the cell-line. Antihuman IL-4 antisera was able to reverse the growth-inhibitory effects of IL-4 on Caki-1 in a dose-dependent manner, proving that the growth inhibition was mediated by IL-4 itself. When other cytokines were added in combination with IL-4, only IFN-alpha 2b resulted in significant additional growth inhibition (P < 0.005). However, when the proliferation was compared to that of RCC cells that were not treated with any cytokine, all combinations produced marked growth inhibition. CONCLUSION: Our data suggest that IL-4 alone, or in combination with IFN-alpha 2b, can be used to develop new strategies for treatment of human RCC.