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Biomedical subjects

D Kessel

Publications and source records attributed to D Kessel.

At least 19 recordsLinked to original sources
PubMed2005

Ruthenium red-mediated suppression of Bcl-2 loss and Ca(2+) release initiated by photodamage to the endoplasmic reticulum: scavenging of reactive oxygen species.

The photosensitizer 9-capronyloxytetrakis (methoxyethyl) porphycene localizes predominantly in the endoplasmic reticulum (ER) and, to a lesser extent, in mitochondria of murine leukemia L1210 cells. Subsequent irradiation results in the loss of ER > mitochondrial Bcl-2 and an apoptotic response. Although an increase in cytosolic Ca(2+) was observed after irradiation, apoptosis was not inhibited by either the presence of the calcium chelator BAPTA or by the mitochondrial uniporter inhibitor ruthenium amino binuclear complex (Ru360). Moreover, neither reagent prevented the loss of Bcl-2. Ruthenium red (RR) devoid of Ru360 prevented Bcl-2 loss, release of Ca(2+) from the ER and the initiation of apoptosis. Since RR was significantly more sensitive than Ru360 to oxidation by singlet oxygen, we attribute the protective effect of RR to the quenching of reactive oxygen species. Although cytosolic and (to a lesser extent) mitochondrial Ca(2+) levels were elevated after photodynamic therapy, these changes were apparently insufficient to contribute to the development of apoptosis.

Animals↗
PubMed2004

A mechanism for the proapoptotic activity of ursodeoxycholic acid: effects on Bcl-2 conformation.

Ursodeoxycholic acid (UDCA), a relatively nontoxic bile acid, enhanced the apoptotic response of tumor cells to both photosensitizers that cause photodamage to Bcl-2 and to the nonpeptidic Bcl-2/Bcl-x(L) antagonist HA14-1. The latter agent binds to the surface pocket formed by the BH1, BH2 and BH3 domains of Bcl-2 and Bcl-x(L). Fluorescence polarization studies indicated that affinity of HA14-1 for Bcl-2 was enhanced in the presence of UDCA. Moreover, Bcl-2 photodamage was promoted by UDCA using a photosensitizing agent with affinity for the endoplasmic reticulum, a site of Bcl-2 localization. Fluorescence resonance energy transfer (FRET) studies revealed that the proximity of Bcl-2 to a hydrophobic photosensitizing agent embedded in liposomes was enhanced by UDCA. Since photodamage will occur only if a protein is in close contact with a photosensitizing agent, we propose that these findings support the hypothesis that UDCA causes a conformational change in Bcl-2, promoting HA14-1 binding and enhancing affinity for certain membrane-bound photosensitizers.

Animals↗
PubMed2003

An audit of out of hours interventional vascular radiology.

BACKGROUND: in 1996 the Royal College of Radiologists established a set of guidelines for out of hours radiology. Part of the recommendations determined that all units should regularly assess their own out of hours workload. In light of these guidelines we have audited our units interventional radiology activity. METHODS: this was a retrospective study looking at the number of emergency angiograms and procedures performed over a 1-year period. Patients were identified from a vascular radiology database and case notes reviewed. RESULTS: a total of 1902 patients had angiograms with 686 having further procedures. Of these, 1093 patients (57%) having 380 procedures (55%) were under the care of a consultant vascular surgeon. Of the vascular surgical patients only 17 patients (1.6%) were actually investigated out of hours (1700-0800 weekdays and at weekends). 5/17 (29%) patients received thrombolysis and 7/17 (41%) had either an angioplasty or stent. Despite being a major vascular unit only 2/17 (12%) were patients referred from outside the units own trust. Following diagnostic angiography, 13/17 (76%) of patients had an intervention performed within the first 24h. CONCLUSION: in a unit performing a large number of angiograms only a small number of patients require out of hours emergency angiography and interventional vascular procedures. Our impression is that this is the result of a flexible and responsive in hour's service. At the present time extra-hospital referrals do not appear to generate large amounts of out of hours work. This level of out of hours activity has implications in the provision of vascular radiological services in the future.

Adult↗
PubMed2003

Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding.

UNLABELLED: The management of bleeding gastric varices has not been standardized. Although transjugular intrahepatic portosystemic shunt (TIPS) is used in most centers, endoscopic treatment with N-butyl-2-cyanoacrylate (cyanoacrylate) glue has recently been shown to be effective. Cost-effectiveness analyses of these methods are lacking. METHODS: We performed a retrospective review of patients with bleeding gastric varices treated either by TIPS or cyanoacrylate glue injection. Economic analysis was based on direct costs for a fixed financial year. The two groups were compared for a period of 6 months follow-up, to liver transplantation, or death for each patient. RESULTS: Between January, 1995 and December, 1999, 20 patients with bleeding gastric varices had TIPS; 23 patients had cyanoacrylate glue injection from January, 2000 to October, 2001. There were no significant differences between the two groups in patient characteristics, transfusion requirement, and gastric variceal anatomy. In the TIPS group, 15/20 patients had the procedure performed within 24 h of hemorrhage, and 90% of stent insertions were successful. Complications consisted of two cases of pulmonary edema, two cases of severe encephalopathy, and a 15% stenosis rate at 6 months. In the glue group, there were 3 +/- 1.5 endoscopies and 2 +/- 1 injections per patient, with a 96% initial hemostasis. There was one case of (glue) pulmonary embolism and one blocked front endoscope lens, which required repair. The initial rebleed rate was significantly lower in patients who had TIPS (15% vs 30%, p = 0.005). The inpatient stay was shorter in the glue group (13 +/- 1 vs 18 +/- 2 days, p = 0.05), but there was no difference in the overall mortality rate. The median cost within 6 months of initial gastric variceal bleeding was $4,138 US dollars ($3,009-$8,290 US dollars) for glue versus $11,906 US dollars ($8,200-$16,770 US dollars) for TIPS (p < 0.0001). CONCLUSION: In this comparable group of patients, cyanoacrylate glue injection was more cost effective than TIPS in the management of acute gastric variceal bleeding. A prospective, randomized trial would be required to confirm our analysis.

Acute Disease↗
PubMed2002

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves Bid cleavage.

Photodynamic therapy (PDT) protocols employing lysosomal sensitizers induce apoptosis via a mechanism that causes cytochrome c release prior to loss of mitochondrial membrane potential (DeltaPsi(m)). The current study was designed to determine how lysosomal photodamage initiates mitochondrial-mediated apoptosis in murine hepatoma 1c1c7 cells. Fluorescence microscopy demonstrated that the photosensitizer N-aspartyl chlorin e6 (NPe6) localized to the lysosomes. Irradiation of cultures preloaded with NPe6 induced the rapid destruction of lysosomes, and subsequent cleavage/activation of Bid, pro-caspases-9 and -3. Pro-caspase-8 was not activated. Release of cytochrome c occurred at about the time of Bid cleavage and preceded the loss of DeltaPsi(m). Extracts of purified lysosomes catalyzed the in vitro cleavage of cytosolic Bid, but not pro-caspase-3 activation. Pharmacological inhibition of cathepsin B, L and D activities did not suppress Bid cleavage or pro-caspases-9 and -3 activation. These studies demonstrate that photodamaged lysosomes trigger the mitochondrial apoptotic pathway by releasing proteases that activate Bid.

Animals↗
PubMed2002

Pharmacological salvage of a combined distal bypass and free flap with catheter-directed thrombolysis.

With recent improvements in microvascular techniques, the use of combined distal bypass and free-flap transfer has been advocated for salvaging the critically ischaemic limb in extreme conditions. Distal bypass, however, carries an inherent risk of graft failure due to thrombosis, and this may threaten the viability of the free flap and, indeed, the lower limb. We present the case of a 66-year-old man with acute-on-chronic ischaemia of his left leg and rectus abdominis free flap. Despite a prolonged ischaemic time of 72 h, both were successfully salvaged using catheter-directed recombinant tissue plasminogen activator. This is previously unreported in the literature.

Aged↗
PubMed2002

Flexible tubular replicas of abdominal aortic aneurysms.

The aim of this study was to manufacture life-size, flexible, tubular replicas of human abdominal aortic aneurysms and the associated vasculature, suitable for use in a training simulator for endovascular procedures. Selective laser sintering was used to create a geometrically correct master model for each of ten anatomical variations. The masters were used to generate flexible latex replicas. The use of the replicas in the training simulator was demonstrated. In total ten silicone rubber models were produced. When connected into the training simulator and perfused at arterial pressure it was possible to deploy an endovascular stent under fluoroscopic control and to perform angiography. The study has shown that conventional rapid prototyping technology can be used to manufacture flexible, radiolucent replicas which provide a realistic training environment for endovascular procedures.

Angiography, Digital Subtraction↗
PubMed2002

False aneurysm of the peroneal artery: an unusual complication of femoro-peroneal bypass grafting.

Non-traumatic false aneurysm formation involving the native crural vessels is rare. We present the case of a false aneurysm of the native peroneal artery, which complicated femoro-peroneal bypass grafting. It seemed most likely to be of an infective aetiology, arising as a consequence of contiguous methicillin resistant Staphylococcus aureus wound infection. This was previously unreported in the literature. Successful management was achieved by primary suture, local wound debridement, excision of the distal graft and replacement with an interposition vein graft through uninfected tissue planes.

Aged↗
PubMed2001

Pro-apoptotic interactions between XK469 and the peripheral benzodiazepine receptor.

XK469 (2-[4-(7-chloro-2-quinoxalinyloxy) phenoxy]propionic acid) is a new anti-tumor agent with substantial activity against several drug-resistant cell lines. Using murine leukemia L1210 cells in culture, we found the chiral R(+) form of XK469 to be substantially more cytotoxic than the S(-) form, while the herbicide analog 'Assure' was essentially inactive. The cytotoxic response to these agents was accompanied by apoptosis, and was found to be correlated with drug binding to the peripheral benzodiazepine receptor in cell culture, suggesting that receptor binding may be a factor in drug-induced cytotoxicity.

Animals↗
PubMed2001

Endovascular repair of an inflammatory abdominal aortic aneurysm complicated by aortoduodenal fistulation with an unusual presentation.

Aortoenteric fistulation (AEF) is a well-documented late complication of open abdominal aortic aneurysm (AAA) repair, occurring in between 0.4% and 4% of cases. In the absence of an anastomosis, AEF is likely to be rare after endovascular aneurysm repair (EVAR) and has only recently been described in the literature as a result of mechanical stent failure or migration. We present the case of a 61-year-old man who underwent EVAR for an AAA with a "nonspecific" periaortic inflammatory mass. Six months postoperatively, an AEF developed, presenting with metastatic sepsis followed by septic infective thromboembolization to his right leg, and amputation was necessary. His stent was well positioned and mechanically intact. We emphasize the need for vigilance about the risk of AEF when adopting an endovascular approach to repair the AAA with a nonspecific periaortic inflammatory mass and highlight the need for awareness about the unusual septic manifestations of AEF.

Aortic Aneurysm, Abdominal↗
PubMed2001

Cyclist's iliac syndrome: temporary relief by balloon angioplasty.

External iliac stenosis due to endofibrosis is a rare condition that predominantly affects top level cyclists. Short term symptomatic relief is reported in an Olympian after percutaneous transluminal angioplasty, which was performed to allow the patient to return to training without delay.

Adult↗
PubMed2001

Evidence that bcl-2 is the target of three photosensitizers that induce a rapid apoptotic response.

We originally proposed that the subcellular target for one class of photosensitizing agents was the mitochondrion. This classification was based on effects that occur within minutes of irradiation of photosensitized cells: rapid loss of the mitochondrial membrane potential (delta psi m), release of cytochrome c into the cytosol and activation of caspase-3. These effects were followed by the appearance of an apoptotic morphology within 30-90 min. Fluorescence localization studies on three sensitizers initially classified as 'mitochondrial' revealed that these agents bind to a variety of intracellular membranes. The earliest detectable effect of photodamage is the selective loss of the antiapoptotic protein bcl-2 leaving the proapoptotic protein bax undamaged. Bcl-2 photodamage can be detected directly after irradiation of cells at 10 degrees C. Subsequent warming of cultures to 37 degrees C results in loss of delta psi m, release of cytochrome c and activation of caspase-3. The latter appears to amplify the other two effects. Based on results reported here we propose that the apoptotic response to these photosensitizers is derived from selective photodamage to the antiapoptotic protein bcl-2 while leaving the proapoptotic protein bax unaffected.

Animals↗