Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Lysophosphatidylcholine potentiates the mitogenic effect of various vasoactive compounds on rabbit aortic smooth muscle cells

We examined the mechanism of action of lysophosphatidylcholine (lyso-PC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflamatory disorders, and its interaction with well-known vasoactive compounds such as hydrogen peroxide (H2O2), thromboxane A2 (TX-A2), serotonin (5-HT), angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) on VSMC proliferation. Growth-arrested rabbit VSMCs were incubated with given concentrations of lyso-PC with H202, TX-A2, 5-HT, Ang-II, ET-1, or U-II. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. Lyso-PC induced a maximal effect on [3H]thymidine incorporation at a concentration of 15 microM (156%), and its effect was significantly inhibited by the phospholipase C inhibitor U73122 (10 microM), the intracellular antioxidant NAC (400 microM), and the NADPH oxidase inhibitor diphenylene iodonium (1 microM), but not by the MAPK kinase inhibitor (10 microM). H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II also stimulated [3H]thymidine incorporation in a dose-dependent manner. A non-mitogenic concentration of lyso-PC (5 microM) significantly potentiated the effect of low concentrations of H2O2 (0.1 microM, 110 to 222%), TX-A2 (5 microM, 120 to 202%), 5-HT (5 microM, 182 to 259%), Ang-II (0.5 microM, 167 to 304%), ET-1 (0.01 microM, 139 to 297%), or U-II (0.025 microM, 120 to 332%) on [3H]thymidine incorporation. The results suggest that lyso-PC acts synergistically with the vasoactive compounds H2O2, TX-A2, 5-HT, Ang-II, ET-1, or U-II in inducing VSMC proliferation, which may play an important role in the progression of atherosclerosis.     

Rapamycin attenuates atherosclerotic plaque progression in apolipoprotein E knockout mice: inhibitory effect on monocyte chemotaxis

Rapamycin has been shown to reduce neointimal thickening in the setting of balloon angioplasty and chronic graft vessel disease. This study was designed to test the effect of oral rapamycin on atherosclerotic plaque progression and the possible mechanism involved. Apolipoprotein E (apoE) knockout mice were fed either a diet supplemented with cholesterol or with cholesterol and rapamycin. At 4 and 8 weeks, quantitative analyses of plaque area and macrophage numbers were determined. Plasma cholesterol, triglyceride, and whole-blood rapamycin levels were measured. Rapamycin could be detected in the blood of mice (117+/-7 pg/mL). In mice fed with rapamycin, atherosclerotic lesions covered 22% of the aortic arch as compared with 41% in cholesterol-fed mice. The macrophage count was significantly lower in the rapamycin-fed mice as compared with cholesterol-fed mice. Rapamycin, in a dose-dependent manner, inhibited monocyte chemotaxis elicited by stromal cell-derived factor-1. Lesions in the cholesterol-fed mice had complex atherosclerotic plaque with acellular core, cholesterol clefts, and an abundant collection of monocytes/macrophages. Lesions in the rapamycin-fed mice were mainly composed of monocytes/macrophages. Oral rapamycin is effective in slowing the progression of atherosclerosis. Along with its multitude actions, attenuation of monocyte chemotaxis may be one more way by which rapamycin attenuates plaque progression.     

Impact of continued hospitalization in patients pre-treated with clopidogrel prior to coronary angiography and undergoing coronary artery bypass grafting

Pre-treatment of patients with clopidogrel prior to coronary angiography (CAG) and possible percutaneous coronary intervention (PCI) is a standard practice. Candidates for coronary artery bypass surgery (CABG) are discharged or remain in the hospital until CABG after clopidogrel is discontinued. We investigated whether any differences exist in the rates of surgical complications and outcomes between these two groups of patients. We conclude that continued hospitalization of clopidogrel pre-treated patients does not confer any safety benefit with regard to post-operative complications and 30-day mortality. Discharging these patients after CAG may reduce hospitalization costs.     

Laparoscopic adrenalectomy - a cure for male pattern baldness

A 64-year-old woman presented to a dermatologist with male pattern hair loss and was found to have grossly elevated testosterone levels at 22.3 nmol/l (normal range, 0.0-2.9 nmol/l). The diagnosis of an androgen-secreting adrenal tumour was made and she underwent a laparoscopic retroperitoneal right adrenalectomy with an uneventful speedy recovery, being discharged in less than 48 h, underlining the clear advantage of this approach.     

Diagnosis and management of malignant spinal cord compression: part 1

Malignant spinal cord compression (MSCC) is a particularly challenging area of cancer care where early diagnosis and expert multidisciplinary care and rehabilitation are paramount in optimising quality of life for the affected individual. The effects of MSCC can range from minor sensory, motor and autonomic changes to severe pain and complete paralysis that significantly affects the remainder of a patient's quality of life. When caught early, the symptoms of MSCC can be prevented, minimised or possibly reversed. However, failure to recognise the condition and its serious nature, together with limited awareness of the importance of early referral for treatment, can result in irreversible paralysis. Therefore, it is essential that nurses providing clinical care for these at-risk patients are able to identify early symptoms, and undertake a thorough patient history and examination, educating the patient and their family about the signs and symptoms, which should be reported as soon as they occur.     

Bivalirudin versus heparin as an antithrombotic agent in patients who undergo percutaneous saphenous vein graft intervention with a distal protection device

Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a variety of percutaneous coronary interventions, and data on its usage in saphenous vein graft interventions are limited. This retrospective, observational study evaluated the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients who underwent saphenous vein graft intervention with distal protection devices. We found that bivalirudin use is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin.     

Laparoscopic partial nephrectomy with saline-irrigated KTP laser in a porcine model

PURPOSE: To evaluate the feasibility of using the potassium titanyl phosphate (KTP) laser to perform laparoscopic partial nephrectomy in a porcine model, with saline irrigation to reduce intraoperative smoke formation. MATERIALS AND METHODS: A high-power (80 W) KTP laser was used without hilar occlusion in 14 laparoscopic partial nephrectomies in four pigs. During laser discharge, the cutting plane was irrigated continuously with saline. RESULTS: Thirteen partial nephrectomies were completed. Hemostasis was obtained without the need for any non-laser techniques. Only minimal smoke was produced, not affecting visibility or the progress of surgery. Histologic examination of the resection margin showed only minimal tissue destruction. One procedure failed because the laser fiber broke and occluded the suction during the operation. The mean partial nephrectomy time was 13.14 minutes (range 7-19 minutes) with a mean estimated blood lost of 28.57 mL (range 5-80 mL). The mean saline irrigation used for each operation was 2600 mL (range 1500-3400 mL), and the amount of saline drained out was 1700 mL (range 900-3200 mL). CONCLUSION: Laparoscopic partial nephrectomy using the 80 W KTP laser is feasible and effective in the porcine model. Saline irrigation dramatically reduces smoke formation. The technique is deserving of clinical studies after the laser-application device and suction irrigation are refined.     

Preliminary evidence that the allogeneic response might trigger antitumour immunity in patients with advanced prostate cancer

OBJECTIVE: To explore the possibility that allogeneic responses might, by chance, encompass cross-reactive T cell clones specific for neo-antigenic tumour determinants, and thereby activate antitumour immunity; such cross-reactions are well documented for antiviral immunity, and genetic instability in developing cancers generates many neo-antigenic determinants as potential targets for immune responses, but the biology inevitably favours tumour progression. PATIENTS AND METHODS: Fourteen patients with hormone-refractory prostate cancer received full-thickness skin allografts from different, unrelated donors (fellow patients) until each had received six grafts. Serum prostate-specific antigen (PSA) level was used as a surrogate for tumour mass. RESULTS: One patient had a remarkable decline in PSA level, with levels at 1 year lower than before grafting. A second patient had stable PSA levels for almost 2 years. A third patient had stable PSA levels for 10-12 months before they resumed an exponential rise. Of four patients with PSA levels of > 10 ng/mL, three required surgery or radiotherapy for obstructive symptoms during or shortly after grafting. CONCLUSION: Transplant rejection involves mechanistically atypical T cell recognition of allogeneic major histocompatibility complex antigens, with massive polyclonal T cell activation. This unique aspect of T cell biology might represent a novel approach for initiating cross-reactive antitumour responses.     

GreenLight laser prostatectomy: a safe and effective treatment for bladder outlet obstruction by prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Although looked on as standard of care there is little published data on the use of “channel TURP” . Those case series that have been published show significant morbidity (in particular stress incontinence) and relatively long hospitalization compared to standard TURP. The use of vaprorising lasers in this patient group has not been addressed. GreenLight laser is a safe and efficacious treatment for bladder outflow obstruction in men with prostate cancer. Hospitalization is minimal (most were day cases) which we feel is important in men who are often in their last few months. We had no serious complications apart from a few patients with stress incontinence. The stress incontinence rate was dramatically lower than that reported in previous reported series of channel TURP – we are not however able to offer any obvious explanation for that finding.

OBJECTIVE

• ? To present our experience on photoselective vaporization of the prostate (PVP) in a cohort of men with bladder outlet obstruction (BOO) by prostate cancer.

PATIENTS AND METHODS

• ? From 2003 to 2008 we identified 43 patients with prostate cancer treated with PVP.
• ? The patients’ hospital records were comprehensively reviewed to obtain preoperative, intra‐operative and postoperative data.
• ? Inclusion criteria were patients with BOO or urinary retention with a diagnosis of prostate cancer.

RESULTS

• ? Mean operating time was 42 min, mean post‐operative hospital stay was 9.6 h. 32 out of 43 patients were discharged home within 24 h. Twelve patients (28%) did not need post‐operative catheter. Mean and median catheter times were 22 and 21.5 h respectively.
• ? Complications were mild: 1 patient needed bladder irrigation, 3 failed initial TWOC, 1 had early stress incontinence. Three had clot retention.
• ? At 3 months post‐operatively, 41 of 42 evaluable patients were voiding without a catheter. The mean peak flow rate had increased by 80% and a mean residual volume decreased of 49%.
• ? Four patients underwent a second laser treatment. Three had developed further retention between 7 and 23 months post‐operatively and did not want further surgery. The local failure rate at a mean follow up of 22 months was 7 of 39 patients (18%).

CONCLUSION

• ? The present study is the first on PVP applied to patients with prostate cancer.
• ? It is shown that, for patients with CaP bothered by LUTS or retention, GreenLight laser prostatectomy is very safe and gives excellent relief from symptoms, with a good improvement in peak flow rate.