Thyroid Hormone in the Treatment of Post-transplant Acute Tubular Necrosis (ATN)

Delayed graft function (DGF) in cadaver kidney transplants is a common problem and is often due to acute tubular necrosis (ATN). DGF in transplants may have a deleterious effect on long-term graft survival. Since thyroid hormone has been shown to hasten recovery from ATN in experimental models, we designed a trial to determine if a defined course of triiodothyronine (T3) would improve the short- or long-term outcome of patients with DGF in cadaveric transplants. A prospective, randomized, placebo controlled, double blind trial of T3 was carried out in patients with DGF in cadaveric renal transplants. End-points were percentage requiring dialysis, percentage recovering function, time to recovery and length of hospital stay. Long-term outcomes were percentage grafts functioning at 1 year and mean serum creatinine at 1 year. Forty-four patients were randomized to receive either T3 or placebo. Three patients were dropped from each group when early biopsies disclosed that DGF was due to rejection. The groups were well matched by age, cold ischemia time of the graft, and percentage reactivity to a random panel of antigens. Baseline thyroid function studies, including T3, reverse T3 (rT3), and thyroid stimulating hormone (TSH) levels, were similar between the two groups and typical of 'euthyroid-sick syndrome'. T3 had no effect on percentage requiring dialysis, time to recovery, percentage recovering function, or length of stay. At 1 year follow-up, graft function was similar in both groups and significantly lower than that seen in patients with good initial function. Thyroid hormone, given early in the course of DGF in cadaver kidney recipients, had no effect on the course of DGF. Long-term graft function is impaired in patients who experience post-transplant DGF compared to those who have good initial function.     

Vasculature-targeted tumor necrosis factor-alpha increases the therapeutic index of doxorubicin against prostate cancer

BACKGROUND: Poor penetration and uneven distribution of doxorubicin in tumors limits the efficacy of this drug in patients with prostate cancer (PC). Aim of the study was to investigate whether pre-treatment with NGR-TNF, a tumor necrosis factor-alpha derivative able to target tumor vessels and alter vessel permeability, increases the penetration and the efficacy of doxorubicin in pre-clinical models of PC. METHODS: Wild type C57BL/6 mice bearing androgen-independent TRAMP-C1 PC and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which spontaneously develop PC and metastasis, were treated with repeated cycles of doxorubicin, administered either alone or following NGR-TNF. Tumor growth and drug uptake by cancer cells was evaluated. RESULTS: Doxorubicin as a single agent blocked the growth of TRAMP-C1 cells in vitro but not in vivo. Pre-treatment of mice bearing subcutaneous TRAMP-C1 tumors with NGR-TNF favored doxorubicin penetration into the tumor mass, and in both TRAMP-C1 and TRAMP models significantly delayed tumor growth without increasing drug-related toxicity. CONCLUSIONS: Pre-treatment with NGR-TNF significantly expanded the therapeutic index of doxorubicin in mouse models of hormone-dependent and -independent PC.     

High incidence of complications encountered in chronic otitis media surgery in a U.S. metropolitan public hospital

OBJECTIVES: To examine the incidence and nature of complicating factors in surgery for chronic otitis media (COM) in a metropolitan public hospital in the United States. METHODS: A retrospective review was performed over 2 years in a metropolitan public hospital to identify cases of surgery for chronic ear disease with the following complicating factors: intracranial or extracranial abscess, labyrinthine fistula, dural dehiscence with or without associated encephalocele or meningocele, or extensive involvement of the facial nerve by cholesteatoma with or without paralysis. RESULTS: Thirty-three of 90 consecutive operations for COM (37%) met criteria for complicated chronic otitis media (CCOM). The majority (85%) of patients had cholesteatoma involvement. Most patients (73%) were managed by an extended modified radical mastoidectomy. An additional 31 procedures were required in these 33 patients for control of complications. There was no iatrogenic sensorineural hearing loss or facial paralysis. CONCLUSIONS: The incidence of CCOM in this large, U.S. metropolitan public hospital is similar to that observed in developing nations. CCOM significantly complicates chronic ear surgery and substantially increases the use of resources. Maintaining functional hearing is possible, but difficult, and should be considered secondary to prevention of further complications and eradication of disease. Access to health care and proper follow-up are crucial in prevention of CCOM.     

The endovascular management of visceral artery aneurysms and pseudoaneurysms

OBJECTIVE: Visceral artery aneurysms may be treated by aneurysm exclusion, excision, revascularization, and endovascular techniques. The purpose of this study was to review the outcomes of the management of visceral artery aneurysms with catheter-based techniques. METHODS: Between 1997 and 2005, 90 patients were identified with a diagnosis of visceral artery aneurysm. This was inclusive of aneurysmal disease of the celiac axis, superior mesenteric artery (SMA), inferior mesenteric artery, and their branches. Surveillance without intervention occurred in 23 patients, and 19 patients underwent open aneurysm repair (4 ruptures). The endovascular treatment of 48 consecutive patients (mean age 58, 60% men) with 20 visceral artery aneurysms (VAA) and 28 visceral artery pseudoaneurysms (VAPA) was the basis for this study. Electronic and hardcopy medical records were reviewed for demographic data and clinical variables. Original computed tomography (CT) scans and fluoroscopic imaging were evaluated. RESULTS: The endovascular treatment of visceral artery aneurysms was technically successful in 98% of 48 procedures, consisting of 3 celiac axis repairs, 2 left gastric arteries, 1 SMA, 12 hepatic arteries, 20 splenic arteries, 7 gastroduodenal arteries, 1 middle colic artery, and 2 pancreaticoduodenal arteries. Of these, 29 (60%) were performed for symptomatic disease (5 ruptured aneurysms). Procedures were performed in the endovascular suite under local anesthesia with conscious sedation (94%). The femoral artery was used as the preferential access site (90%). Coil embolization was used for aneurysm exclusion in 96%. N-butyl-2-cyanoacrylate (glue) was used selectively (19%) using a triaxial system with a 3F microcatheter for persistent flow or multiple branches. The 30-day mortality was 8.3% (n = 4). One patient died from recurrent gastrointestinal bleeding after gastroduodenal embolization, and the remaining died of unrelated causes. All perioperative deaths occurred in patients requiring urgent or emergent intervention in the setting of hemodynamic instability. No patients undergoing elective intervention died in the periprocedural period. Postprocedural imaging was performed after 77% of interventions at a mean of 16 months. Complete exclusion of flow within the aneurysm sac occurred in 97% interventions with follow-up imaging, but coil and glue artifact complicated CT evaluation. Postembolization syndrome developed in three patients (6%) after splenic artery embolization. There was no evidence of hepatic insufficiency or bowel ischemia after either hepatic or mesenteric artery aneurysm treatment. Three patients required secondary interventions for persistent flow (n = 1) and recurrent bleeding from previously embolized aneurysms (n = 2). CONCLUSION: Visceral artery aneurysms and pseudoaneurysms can be successfully treated with endovascular means with low periprocedural morbidity; however, the urgent repair of these lesions is still associated with elevated mortality rates. Aneurysm exclusion can be accomplished with coil embolization and the selective use of N-butyl-2-cyanoacrylate. Current catheter-based techniques extend our ability to exclude visceral artery aneurysms, but imaging artifact hampers postoperative CT surveillance.