Advances in the Development of Multimodal Imaging Agents for Nuclear/Near-infrared Fluorescence Imaging.

Multimodal imaging agents were first introduced a decade ago and consist of a targeting moiety that is dual-labeled with radioactive and fluorescent contrast. These compounds allow whole-body and intraoperative imaging to be performed through administration of a single agent and provide complementary diagnostic information that can be used to guide tumor resection. Since their initial evaluation, interest in dual-labeled agents has continued to grow and their design has subsequently evolved alongside the development of novel chelating agents, improved fluorophores, and highly selective coupling techniques for bioconjugate formation. In this review, will discuss how changes in the labeling components and schemes for multimodal agent development have impacted imaging performance and will focus on antibody- and peptide-based agents as models for dual labeling. We will also describe the growing role of modular dual labeling strategies as well as direct labeling methods using radiohalogens.

A concealed small bowel perforation in an adult secondary to bicycle handlebar trauma.

Traumatic abdominal wall hernia (TAWH) secondary to bicycle handlebar is a rare injury. The majority of the literature describes abdominal wall herniation in children. We present a rare case of TAWH in an adult with a concealed small bowel perforation. Although clinical examination in conjunction with computed tomography can exclude the majority of solid organ injuries, small bowel injuries can often be missed. Our case initially revealed a serosal tear in the small bowel but, on close inspection, a separate 3mm perforation was identified, hidden in the small bowel mesentery. We strongly support a low threshold for operative intervention if there is any suspicion. Moreover, we stress the importance of meticulous examination during laparotomy as this injury could have been easily missed, resulting in potential morbidity or mortality in a patient sustaining such an injury.

The effect of GaAs(100) surface preparation on the growth of nanowires.

The influence of GaAs(100) substrate surface preparation on Au-catalysed GaAs nanowires was studied. Elongated pits of varying dimensions and orientation were formed on GaAs(100) substrates depending on the interaction with Au and surface oxides. The resulting surface topography is shown to influence the density and orientation of nanowires. [111] B-oriented nanowires nucleated from Au particles lying on the sidewall facets of the pits, while [011]-oriented nanowires nucleated from Au particles lying outside the pits.

MRP- and BCL-2-mediated drug resistance in human SCLC: effects of apoptotic sphingolipids in vitro.

Multidrug-resistance-associated protein (MRP) and BCL-2 contribute to drug resistance expressed in SCLC. To establish whether MRP-mediated drug resistance affects sphingolipid (SL)-induced apoptosis in SCLC, we first examined the human SCLC cell line, UMCC-1, and its MRP over-expressing, drug-resistant subline, UMCC-1/VP. Despite significantly decreased sensitivity to doxorubicin (Dox) and to the etoposide, VP-16, the drug-selected line was essentially equally as sensitive to treatment with exogenous ceramide (Cer), sphingosine (Sp) or dimethyl-sphingosine (DMSP) as the parental line. Next, we observed that high BCL-2-expressing human H69 SCLC cells, that were approximately 160-fold more sensitive to Dox than their combined BCL-2 and MRP-over-expressing (H69AR) counterparts, were only approximately 5-fold more resistant to DMSP. Time-lapse fluorescence microscopy of either UMCC cell line treated with DMSP-Coumarin revealed comparable extents and kinetics of SL uptake, further ruling out MRP-mediated effects on drug uptake. DMSP potentiated the cytotoxic activity of VP-16 and Taxol, but not Dox, in drug-resistant UMCC-1/VP cells. However, this sensitization did not appear to involve DMSP-mediated effects on the function of MRP in drug export; nor did DMSP strongly shift the balance of pro-apoptotic Sps and anti-apoptotic Sp-1-Ps in these cells. We conclude that SL-induced apoptosis markedly overcomes or bypasses MRP-mediated drug resistance relevant to SCLC and may suggest a novel therapeutic approach to chemotherapy for these tumors.

Sphingolipids and the sphingosine kinase inhibitor, SKI II, induce BCL-2-independent apoptosis in human prostatic adenocarcinoma cells.

BACKGROUND: Elevated BCL-2 is one mechanism of therapeutic resistance in prostate cancer (PC), and new approaches are needed to overcome such resistance. METHODS: We evaluated the effects of BCL-2 over-expression in human prostatic adenocarcinoma cells on their susceptibility to sphingolipids (SLs) and to the sphingosine kinase (SpK) inhibitor, SKI II. RESULTS: In survival assays, no significant differences were observed in the responses to sphingosine or ceramide among parental PC-3 cells lacking detectable BCL-2 and BCL-2 over-expressing PC-3 transfectants; similarly, the responses to dimethyl-sphingosine (DMSP) of parental LNCaP cells and a BCL-2 over-expressing LNCaP transfectant were equivalent. SKI II induced protracted, BCL-2-independent survival loss in both PC-3 and LNCaP parental/transfectant pairs; in contrast, DMSP induced rapid cell shrinkage, caspase activation and caspase-dependent DNA fragmentation. DMSP-induced DNA fragmentation and loss of mitochondrial membrane potential were equivalent in BCL-2 transfectants and parental PC-3 cells and were not associated with BCL-2 downregulation. DMSP-mediated cytotoxicity was not associated with the enhanced production of reactive oxygen intermediates. SL analyses of parental and transfectant PC-3 cells did not reveal increased levels of sphingosine-1-phosphate in the BCL-2 transfectants; further, there only a modest early shift, corresponding to apoptotic onset, in pro- versus anti-apoptotic SLs in response to DMSP treatment. CONCLUSIONS: Thus, in contrast to the inhibitory effects of BCL-2 on apoptosis induced by various agents in tumor cells, SKI II and selected pro-apoptotic SLs appear atypical in their independence from such inhibition, and may have merits as new candidates for treatment of AI PC.

Beneficial effects of cocarboxylase in the treatment of experimental myocardial infarction in dogs.

Cocarboxylase, or thiamine pyrophosphate, is an essential coenzyme in the catabolism of pyruvate. The authors evaluated the effects of a stable cocarboxylase solution in the treatment of an experimentally created acute myocardial infarction in 14 healthy mongrel dogs. The left anterior descending artery was ligated for 60 minutes and data were collected at the following points: A) prior to ligation, B) 15 minutes after ligation, C) 30 minutes after ligation, and D) 60 minutes after ligation. In one group (Group II), cocarboxylase (150 mgm/kg) was given systematically via a central line 15 minutes and 45 minutes after ligation, while in Group I an equal amount of D5W was given. Hemodynamic data include heart rate, systolic and mean arterial pressure, pulmonary wedge pressure, right arterial pressure, and cardiac output. Myocardial O2 consumption was determined by the method of Rooke and Feigl. Electrocardiographic data were also monitored throughout the experiment. In both groups, preligation (point A) hemodynamic data were similar. In Group II, there were beneficial hemodynamic changes versus Group I (expressed as percentage recovery of hemodynamic performance from preligation) at points C and D, with significant (P less than 0.05) decreases in heart rate, increased stroke volume, decreased systemic vascular resistance, and decreased myocardial O2 consumption. EKG criteria also showed improvement in Group II versus Group I. In conclusion, this experiment suggests that cocarboxylase may be beneficial to ischemic canine myocardium by virtue of its favorable systemic hemodynamic effects.

Diagnosis and management of traumatic ventricular septal defect.

Four cases of ventricular septal defect secondary to stab wounds of the heart are presented. One of three patients arriving at the Emergency Department in shock and who were resuscitated required an emergency thoracotomy. These patients had immediate repair of their external cardiac wounds in the Operating Room. Cases 1 and 3 developed heart failure and loud systolic murmur postoperatively. Case 4 was treated with chest tube for a left hemothorax and developed heart failure after discharge. In Cases 1, 2, and 3, 2-D echocardiography detected and located a VSD. In Case 3 Doppler measurement showed elevated RV pressure (45 mm Hg) and decreased peak tricuspid to mitral flow ratio (0.36, normal = 0.6). All patients underwent cardiac catheterization. In Case 4 there was associated mitral regurgitation. Cases 1 and 3 had pulmonary to systemic flow ratios greater than 3:1. Cases 1, 3, and 4 underwent operative repair. In Case 1 the VSD was closed with a dacron patch, and in Cases 3 and 4 it was sutured with Teflon pledgets. In Case 4 a puncture wound of the mitral valve annulus was simultaneously repaired. All patients are alive but in Case 1 postoperative 2-D echocardiography demonstrated partial dehiscence of the patch which has not required reoperation and in Case 3 post-repair 2-D echocardiography and Doppler flow studies have shown an intact VSD repair. This series of post-traumatic VSD demonstrates its varying clinical presentation and the diagnostic and followup benefits offered by 2-D echocardiography, especially when combined with Doppler flow measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Transfemoral removal of a chronically implanted pacemaker lead: report of a case.

A transfemoral angiographic technique was used to remove a chronically implanted, infected pacemaker wire that could not be withdrawn by using direct traction. The case and a description of the technique are detailed, and the principles of nonsurgical extraction of chronically implanted pacemaker wires are discussed.

Clinical experience with subxyphoid pericardial decompression.

Between 1971 and 1981, 108 patients with pericardial effusion were treated by subxyphoid pericardial decompression. 68 patients (63%) had local anesthesia, while general anesthesia was used in 40 (37%). The total group included nonspecific (viral) pericarditis in 35 patients (32.4%), uremic pericarditis in 30 (27.8%); and 20 patients (18.5%) with a malignant etiology, traumatic in ten patients (9.3%), six patients (5.6%) following radiation for malignant disease, and seven patients (6.5%) due to other causes. Echocardiography was diagnostic in all cases. Acute cardiac tamponade necessitated pericardiocentesis as an initial procedure in seven patients (6.5%). Subxyphoid pericardial decompression included drainage of the pericardial fluid and performance of a 5 X 5 cm pericardial window and biopsy of all patients. There were two (1.8%) operative deaths in the general anesthesia group but none in the local anesthesia group. There were no major complication in the local anesthesia group, but one patient in the general anesthesia group, who was severely hypertensive preoperatively, developed hemiplegia on the left side. There were five recurrences (4.6%) requiring total pericardiectomy at a later date. Subxyphoid pericardial decompression under local anesthesia was seen to be a safe and effective procedure for primary decompression and diagnosis of acute or chronic pericardial effusion.

Spontaneous disruption of Ionescu-Shiley bovine pericardial xenograft in the mitral position.

We report a case of spontaneous disruption of the Ionescu-Shiley pericardial xenograft in the mitral position at 3 years and its successful management.

Use of a ringed intraluminal graft in the surgical treatment of dissecting aneurysms of the thoracic aorta. A new technique.

An intraluminal graft made of woven tubular Dacron with cloth-covered grooved rings at both ends is used to repair dissecting aneurysms of the thoracic aorta. Six consecutive white male patients ranging in age from 31 to 69 years with an average age of 55 years were operated upon with the use of this graft. Three patients had a dissecting aneurysm of the ascending aorta and three others had a dissecting aneurysm of the descending aorta. Total cardiopulmonary bypass was utilized in repairing dissecting aneurysms of the ascending aorta and left heart bypass was used in patients with dissecting aneurymsms of the descending aorta. The basic technique consists in inserting the whole ringed graft into the true lumen of the dissected aorta and circumferentially ligating the aorta against the groove in the rings. The proximal ring of the graft effectively stabilized the flail aortic valve in two patients with aortic regurgitation associated with dissection of the ascending aorta. There were no hospital deaths. All patients are doing well 1 year, 1 month to 2 years, 8 months after the operation.