Rapid metastasis to the scrotum and penis following laparoscopic radical cystoprostatectomy

We present a case of rapid metastasis to the scrotum and penis within 2 months following a laparoscopic radical cystoprostatectomy in a 61-year-old male. The aim of this case report is to highlight the potential risk of rapid metastasis to both urologist and urological oncologist in all patients undergoing a laparoscopic radical cystoprostatectomy.     

Tubular cell-Escherichia coli interaction products modulate migration of monocytes through generation of transforming growth factor-beta and macrophage-monocyte chemoattractant protein-1

BACKGROUND: Urinary tract infection is a common occurrence often associated with renal interstitial inflammation in the form of accumulation of mononuclear cells. We hypothesized that bacteria activate tubular cells to secrete cytokines, which may promote migration of mononuclear cells at the site of interaction. MATERIALS AND METHODS: We evaluated the migration of monocytes in response to tubular cell products (TC-S) and interaction products of E. coli with proximal tubular cells (TC-EC-S; concentrations of 5%, 10%, and 25%) using a modified Boyden chamber. To determine the molecular mechanism, we evaluated the effect of antibodies against macrophage-monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta (TGF-beta) on E. coli-tubular cell interaction product-induced migration of monocytes. In addition, we studied the effect of free-radical scavengers on activation of tubular cells. RESULTS: The TC-EC-S enhanced (p < 0.0001) migration of monocytes compared with TC-S. Both anti-TGF-beta and anti-MCP-1 antibodies partly inhibited (p < 0.0001) TC-EC-S-induced monocyte migration. The modified TC-EC-S (produced in the presence of superoxide dismutase [SOD], dimethyl thiourea [DMTU], or catalase, all scavengers of free radicals) induced lesser monocyte migration than did TC-EC-S alone. CONCLUSIONS: These results suggest that E. coli activates tubular cells to generate cytokines such as MCP-1 and TGF-beta that promote migration of monocytes. Free radicals such as superoxide and hydrogen peroxide may be acting as second messengers in E. coli-induced tubular cell activation.     

Morphine-induced macrophage apoptosis modulates migration of macrophages: use of in vitro model of urinary tract infection

BACKGROUND: Morphine has been reported to alter immune function. Morphine-induced macrophage apoptosis has been shown to contribute to altered immune status in an opiate milieu. We studied the effect of morphine-induced macrophage apoptosis on the migration of macrophages. Because urinary tract infection (UTI) is one of the commonest infections to evoke an inflammatory response; i.e., migration of neutrophils and monocytes to the site of infection, we used an in vitro model of UTI to test our hypothesis. MATERIALS AND METHODS: We carried out both in vivo and in vitro studies. Mice of the FVB/N strain were treated with morphine for short (three doses, 24 hours) and long (11 doses, 96 hours) durations, and their bone marrow cells were isolated. In addition, apoptotic macrophages were prepared by heat treatment. To simulate the in vitro model of UTI, E. coli-activated tubular cell (TC)-conditioned medium containing transforming growth factor-beta (TGF-beta) and macrophage-monocyte chemoattractant protein-1 (MCP-1) was used to test migration of macrophages across a filter in a modified Boyden chamber. In addition, migration of macrophages into the peritoneal cavity was evaluated in both control and morphine-treated states. The effect of morphine on apoptosis as well as migration was studied in murine macrophages and bone marrow cells. RESULTS: Morphine not only promoted apoptosis of bone marrow cells (20% apoptotic cells) but also inhibited their migration across the filter. Control cells showed minimal apoptosis but displayed greater migration. Similarly, heat-treated (apoptotic) cells showed minimal migration. In peritoneal macrophage studies, morphine treatment retarded migration. CONCLUSION: Morphine inhibits macrophage migration both in vivo and in vitro. This attenuated transmigration of macrophages seems to be secondary to the apoptotic effect of morphine.     

Laparoscopic renal-adrenal surgery in patients on oral anticoagulant therapy

PURPOSE: Patients requiring chronic anticoagulation are theoretically at increased risk for hemorrhage or thromboembolism perioperatively. Experience with laparoscopic renal/adrenal surgery in patients on chronic warfarin is limited. We assessed hemorrhagic/thromboembolic complications in this group of patients. MATERIALS AND METHODS: The records of 787 patients undergoing laparoscopic renal/adrenal surgery were retrospectively reviewed. A total of 25 patients on chronic oral anticoagulation with warfarin were identified. The indications for warfarin therapy as well as perioperative management were reviewed. Clinical parameters, including operative time, estimated blood loss, hemorrhagic/thromboembolic complications and transfusions, were documented and compared with those in patients not receiving chronic anticoagulation. RESULTS: Atrial fibrillation (56% of cases) and a prosthetic mitral valve (28%) were the most frequent indications for chronic anticoagulation. Bridging anticoagulation with unfractionated heparin was the most frequent management method (68% of cases). Patients with anticoagulation were older (p <0.001) and hospitalized longer (<0.001) than those without anticoagulation. Operative time, estimated blood loss and the conversion rate were not significantly different between the groups. However patients on chronic warfarin significantly more often required transfusion (24% vs 5.2%, p <0.005) and had more postoperative bleeding episodes (8% vs 0.9%, p <0.05) than patients not on chronic anticoagulation. No thromboembolic events occurred in the anticoagulated group, while 3 occurred in the nonanticoagulated group (p = 1). CONCLUSIONS: Laparoscopic renal/adrenal surgery in patients requiring chronic anticoagulation therapy can be performed safely. The risk of intraoperative bleeding is not increased, although the incidence of postoperative bleeding as well as transfusions is higher.     

Cerebrovascular events associated with infusion through arterially malpositioned triple-lumen catheter: report of three cases and review of literature

Analysis of 10 adult patients treated from January 1998 to November 2004 for arterial misplacement of triple-lumen catheter (TLC) during internal jugular vein cannulation was performed. Three cases that developed neurologic symptoms occurring in the context of infusion through a TLC that was arterially malpositioned are presented, along with the review of literature. In 7 patients, the diagnosis of arterial misplacement was suspected by the color or flow characteristics of blood and confirmed by a combination of blood gas analysis, connecting catheter to transducer, and/or chest film. In the remaining 3 patients, intraarterial misplacement was not suspected. In these patients, the initial review of chest films by qualified physicians prior to starting infusion failed to detect malposition of the catheter. Retrospectively, subtle clues suggestive of arterially placed TLCs were found. All 3 patients developed neurologic symptoms. Initiation of neurologic workup delayed a correct diagnosis by 6 to >48 hours. A volumetric pump was used for infusion in all patients. Of the 3 patients with neurologic symptoms, 1 recovered completely, 1 became comatose, and 1 partially improved.Based on our observations and review of literature, we conclude that cursory examination of chest films to verify proper positioning of central venous catheter attempted through the internal jugular vein may fail to detect arterial malposition. Infusion by volumetric pump precludes backflow of blood in the intravenous tubing as an indicator. Neurologic symptoms concurrent with the infusion of fluids and medication should raise suspicion of accidental arterial infusion.     

Experimental Chandipura virus infection in mice

Summary Chandipura virus was inoculated intraperitoneally into 9-day old mice. Rising viral titers were detected in blood, skeletal muscle and viscera, beginning 3 to 6 h post-inoculation. Significant quantities of virus were initially noted in the brain at 24 h, and titers in that region rose precipitously during the succeeding 72 h. Detectable clinical signs, including neurologic dysfunctions began 48 h post-inoculation. Death was common at 72 and 96 h. The most significant and consistently observed lesions were in the central nervous system and included necrosis of neurons and ependymal cells.Supported by U.S. Public Health Service Grants PHS-FR-05358-08 and PHS 2 PO 6 RR 00393.     

Aortic arch variation: a unique case with anomalous origin of both vertebral arteries as additional branches of the aortic arch distal to left subclavian artery

We present the case of bilateral anomalous origin of both vertebral arteries (VAs) in a 20-year-old male patient who presented for routine contrast-enhanced CT follow-up examination of the chest. Contrast-enhanced CT revealed abnormal origins of both the VAs from the aortic arch distal to the origin of the left subclavian artery. Following this, CT angiography was performed, which confirmed the findings. To our knowledge, this is the first report of anomalous origins of both VAs beyond the origin of the left subclavian artery. The possible embryonic mechanism and the clinical importance of this variant is also reviewed.     

Protease inhibitors modulate apoptosis in mesangial cells derived from a mouse model of HIVAN

BACKGROUND: Oxidative stress as well as opiate addiction has been shown to play a role in the development of complications associated with human immunodeficiency virus (HIV) infection. METHODS: We studied the occurrence of apoptosis in mesangial cells derived from control (NTrMC) mice and mice transgenic for HIV-1 genes (HTrMC) under basal and morphine-stimulated states (MSS). We evaluated the effect of free radical scavengers and antioxidants on HTrMC apoptosis and production of superoxide under basal and MSS. In addition, we examined the effect of protease inhibitors (PI) on apoptosis of NTrMCs/HTrMCs as well as morphine-induced superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase activation. RESULTS: HTrMCs showed greater apoptosis when compared with NTrMCs. Morphine triggered (P < 0.001) apoptosis of both NTrMCs and HTrMCs. Both antioxidants and free radical scavengers inhibited apoptosis of NTrMCs and HTrMCs under both basal and MSS. Morphine stimulated the production of superoxide by NTrMCs as well as by HTrMCs. Nevertheless, HTrMCs produced a greater (P < 0.001) amount of superoxide when compared with NTrMCs both under basal and MSS. PIs such as saquinavir and Indinavir inhibited HTrMC apoptosis in a dose-dependent manner. Saquinavir also protected HTrMCs against the proapoptotic effect of morphine. Moreover, saquinavir inhibited the production of superoxide by HTrMCs under both basal and MSS. Saquinavir also attenuated the morphine-induced expression of SOD and NADPH oxidase (Gp91phox) by HTrMCs. Interestingly, hemin exacerbated morphine-triggered HTrMC apoptosis. CONCLUSION: Oxidative stress seems to play a role in the accelerated rate of HTrMC apoptosis both under basal and MSS. Saquinavir may be inhibiting HTrMC apoptosis by mitigating oxidative stress.     

Syntheses and neuraminidase inhibitory activity of multisubstituted cyclopentane amide derivatives

In further studies aimed toward identifying effective and safe inhibitors of influenza neuraminidases, we synthesized a series of multisubstituted cyclopentane amide derivatives. Amides prepared were 14 examples of N-substituted alkyl or aralkyl types from primary amines, 13 examples of the N,N-disubstituted alkyl, aralkyl, or substituted-alkyl type from secondary amines, and 12 examples from cycloaliphatic or substituted cycloaliphatic secondary amines. These compounds bearing two chiral centers, at position-1 in the ring and position-1' in the side chain attached at position 3, were tested for their ability to inhibit A and B forms of influenza neuraminidase. The 1-ethylpropylamide, diethylamide, dipropylamide, and 4-morpholinylamide showed very good inhibitory activity (IC(50) = 0.015-0.080 microM) vs the neuraminidase A form, but modest activity (IC(50) = 3.0-9.2 microM) vs the neuraminidase B form. Since the parent amides bear two chiral centers (C-1 and C-1'), three of the better inhibitors were tested at higher levels of diastereomeric purity. The diastereomers corresponding to the active forms of the 1-(ethyl)propylamide, the diethylamide, and the dipropylamide (all of the same configuration at the C-1' chiral center), and the diastereomer of the diethylamide representing the active form at both C-1' and C-1 were isolated or synthesized from precursors that were isolated as diastereomers. These diastereomers showed some improvement in neuraminidase inhibition over the parent diastereomeric mixtures. 1-Carboxy-1-hydroxy derivatives of the best active compounds, the diethylamide and the dipropylamide, were also prepared. These compounds were not as active as the compounds without the 1-hydroxy group. In an in vivo study, the C-1' active isomer of the diethylamide from the 1-carboxy series was tested in influenza-infected mice by oral and intranasal administration and found to be very effective only intranasally in preventing weight loss at doses as low as 0.1 (mg/kg)/day.