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Biomedical subjects

Michael Darcy

Publications and source records attributed to Michael Darcy.

6 recordsLinked to original sources

Combined percutaneous and retrograde approach to staghorn calculi with application of the ureteral access sheath to facilitate percutaneous nephrolithotomy.

PURPOSE: We describe our technique and clinical experience with application of the ureteral access sheath for single access ablation of staghorn and partial staghorn calculi. MATERIALS AND METHODS: We retrospectively reviewed our experience with 9 patients who underwent percutaneous nephrolithotomy for staghorn (6) or partial staghorn (3) renal calculi using a combined antegrade and retrograde approach. Patient data, operative parameters, efficacy of stone ablation and convalescence parameters were reviewed. RESULTS: Mean operative time for the primary procedure was 3.1 hours with a mean estimated blood loss of 290 ml. Postoperatively, the mean analgesic requirement was 33.2 mg. MSO(4) equivalents. Hospital stay was 3.2 days. There were no major and 4 minor (44%) complications. No patient required transfusion. Complete stone clearance was achieved in 7 of the 9 cases (78%) using a single percutaneous nephrostomy tract. CONCLUSIONS: Our preliminary clinical experience using the ureteral access sheath during percutaneous nephrolithotomy for simultaneous antegrade and retrograde stone treatment has been favorable. A large renal stone burden can be successfully managed with a single percutaneous access and limited blood loss.

Humans↗

Treatment of lower gastrointestinal bleeding: vasopressin infusion versus embolization.

Traditionally, embolization has been reserved for treatment of upper gastrointestinal bleeding whereas lower gastrointestinal (LGI) bleeding has been controlled with vasopressin infusion. This is based on findings in older literature in which infarction frequently complicated LGI embolization. With modern embolization techniques, clinically significant bowel ischemia has become an uncommon complication. Although the efficacies of vasopressin and embolization are fairly comparable, embolotherapy has advantages in terms of quicker completion of therapy and decreased likelihood of systemic complications. Although vasopressin is still probably preferable for diffuse lesions and cases in which superselective catheterization is not technically possible, embolization should be considered a primary option for treating LGI bleeding.

Embolization, Therapeutic↗

Identification and biological characterization of heterocyclic inhibitors of the hepatitis C virus RNA-dependent RNA polymerase.

The hepatitis C virus (HCV) NS5B protein encodes an RNA-dependent RNA polymerase (RdRp), the primary catalytic enzyme of the HCV replicase complex. We established a biochemical RNA synthesis assay, using purified recombinant NS5B lacking the C-terminal 21 amino acid residues, to identify potential polymerase inhibitors from a high throughput screen of the GlaxoSmithKline proprietary compound collection. The benzo-1,2,4-thiadiazine compound 1 was found to be a potent, highly specific inhibitor of NS5B. This agent interacts directly with the viral polymerase and inhibits RNA synthesis in a manner noncompetitive with respect to GTP. Furthermore, in the absence of an in vitro-reconstituted HCV replicase assay employing viral and host proteins, the ability of compound 1 to inhibit NS5B-directed viral RNA replication was determined using the Huh7 cell-based HCV replicon system. Compound 1 reduced viral RNA in replicon cells with an IC(50) of approximately 0.5 microm, suggesting that the inhibitor was able to access the perinuclear membrane and inhibit the polymerase activity in the context of a replicase complex. Preliminary structure-activity studies on compound 1 led to the identification of a modified inhibitor, compound 4, showing an improvement in both biochemical and cell-based potency. Lastly, data are presented suggesting that these compounds interfere with the formation of negative and positive strand progeny RNA by a similar mode of action. Investigations are ongoing to assess the potential utility of such agents in the treatment of chronic HCV disease.

Cell Line↗

Lower extremity venous thrombolysis with adjunctive mechanical thrombectomy.

PURPOSE: To evaluate the use of adjunctive mechanical thrombectomy (MT) with pharmacologic catheter-directed lower extremity venous thrombolysis. MATERIALS AND METHODS: Catheter-directed thrombolysis with adjunctive MT was used to treat 28 symptomatic limbs in 20 patients (22 procedures) with lower extremity deep vein thrombosis (DVT) between August 1997 and July 2001. Procedural success, major bleeding, thrombolytic infusion time, and total thrombolytic agent dose were recorded. RESULTS: Procedural success was achieved in 23 of 28 limbs (82%). Fifteen patients (18 limbs) received iliac vein stents. Major bleeding was observed after three of 22 procedures (14%) and resulted in transfusion in two patients and endometrial ablation in the third patient. Mean per-limb infusion time was 16.8 hours +/- 12.8. Mean per-limb total doses were lower than those reported in published studies of DVT thrombolysis: 2.67 million U +/- 1.60 urokinase, 18.4 mg +/- 10.7 tissue plasminogen activator, and 13.8 U +/- 6.9 reteplase. Venographic analysis demonstrated minimal thrombus removal (26.0% +/- 24.1) when using MT alone, compared with substantial thrombus removal (62.0% +/- 24.9) when using MT after pharmacologic thrombolytic agents had been administered (P =.006). CONCLUSION: The use of adjunctive MT to augment pharmacologic catheter-directed DVT thrombolysis provides comparable procedural success and may reduce the required thrombolytic dose and infusion duration.

Aged↗