A first-in-human phase I trial of locally delivered human plasmin for hemodialysis graft occlusion.

BACKGROUND: Hemodialysis (HD) grafts often fail because of stenosis at the venous anastomosis and thrombotic occlusion. Percutaneous management relies on thrombolysis with plasminogen activators, mechanical removal of thrombus, and angioplasty of the stenotic lesion. OBJECTIVES: This report describes a phase I trial using Plasmin (Human) TAL 05-00018, a direct-acting fibrinolytic agent, to evaluate safety and, secondarily, to establish effective thrombolytic dosing. PATIENTS/METHODS: Six cohorts of five patients with acute HD graft occlusion documented by angiography were treated with escalating dosages of plasmin (1, 2, 4, 8, 12, and 24 mg) infused over 30 min via criss-crossed pulse-spray catheters within the graft. The primary efficacy endpoint was > or =50% thrombolysis, as determined by comparison of pre-plasmin and 30-min post-plasmin fistulograms. RESULTS: Of 31 subjects who received study drug (safety population), one withdrew and 30 completed the trial (evaluable for efficacy). There was no significant change in plasma alpha-2 antiplasmin or fibrinogen concentration, major bleeding did not occur, and there were no deaths. Serious adverse events in four patients were not related to the study drug. There was a dose-response relationship for the primary efficacy endpoint, all five subjects receiving 24 mg achieving >75% lysis. CONCLUSIONS: This first phase I study of Plasmin (Human) TAL 05-00018, infused into thrombosed HD grafts, documents safety at dosages of 1-24 mg and an effective thrombolytic dosage of 24 mg. The results establish a foundation for further clinical study of catheter-based plasmin administration in thrombotic disorders.

Endovascular stents for renal artery revascularization.

Revascularization cures or attenuates the clinical manifestations of renal artery stenosis (hypertension, ischemic nephropathy, pulmonary edema, angina, and congestive heart failure). Traditional approaches have been sub-optimal due to low rates of success and long-term patency after angioplasty, and to relatively high rates of perioperative morbidity and mortality. Endovascular stent placement is an alternative interventional method for renal artery revascularization. Technical success rates are excellent, and the impact on clinical outcomes (blood pressure, renal function, and cardiac complications) is promising.

Treatment of atherosclerotic ostial renal artery stenosis with the intravascular stent.

Traditional approaches to revascularization for atherosclerotic ostial renal artery stenosis (RAS) have been suboptimal because of the invasiveness and relatively high perioperative morbidity and mortality of surgery and the low rates of success and long-term patency with percutaneous renal angioplasty (PTRA). We report our 5-year (1991 to 1996) experience with the intravascular stent (Palmaz stent; Johnson & Johnson, Miami Lakes, FL) for the treatment of ostial RAS in 129 patients (63 men, 66 women) and 148 arteries. The mean age of the patients was 71+/-10 years; 98% were hypertensive and 57% had renal dysfunction. Angiographic characteristics of RAS were unilateral in 78%, bilateral in 15%, and single kidney in 7%. The technical success rates were 98% for stent versus 11% for PTRA in the ostial location. The stent restenosis rate (angiographic) was 14% at 8+/-5 months. Systolic and diastolic blood pressures were as follows: baseline, 158+/-3 and 84+/-2 mm Hg; 6 months, 149+/-3 and 81+/-2 mm Hg; 12 months, 149+/-3 and 79+/-2 mm Hg; and 24 months, 135+/-3 and 79+/-2 mm Hg. Follow-up values were significantly lower than baseline (P < 0.05). The number of medications for hypertension initially decreased from 2.2+/-0.1 at baseline to 1.6+/-0.1 and 1.8+/-0.1 at 1 and 3 months, respectively (P < 0.05). By 6 months, however, the number of medications had increased and was not significantly different from before stent placement. Renal function was stable in the group as a whole: Cockroft-Gault creatinine clearance (C-G CrCl) at baseline was 40+/-2 mL/min; at 6 months, 36+/-3 mL/min; at 12 months, 39+/-3 mL/min; and at 24 months, 39+/-4 mL/min. When stratified by degree of renal function, values were similarly stable. Patients with a baseline serum creatinine level of 2 mg/dL or less had C-G CrCl values as follows: baseline, 53+/-3 mg/dL; 6 months, 43+/-4 mg/dL; 12 months, 46+/-4 mg/dL; and 24 months, 52+/-5 mg/dL. Those with a baseline serum creatinine level greater than 2 mg/dL had C-G CrCl values as follows: baseline, 26+/-2 mg/dL; 6 months, 31+/-4 mg/dL; 12 months, 32+/-6 mg/dL; and 24 months, 23+/-3 mg/dL. Of eight patients who were dialysis dependent, four (50%) recovered renal function with a mean serum creatinine level of 2.3+/-0.5 mg/dL at 15+/-6 months (range, 9 to 24 months). Stent placement for the treatment of atherosclerotic ostial RAS has a high success rate and a low rate of restenosis. Control of hypertension improves in most patients. Renal function stabilizes or improves in the majority of patients, even those with severe renal failure. These favorable outcomes are maintained long term.

Errant percutaneous Greenfield filter placement into the retroperitoneum.

Percutaneous Greenfield filter placement through a femoral vein approach resulted in errant retroperitoneal placement in a patient with pulmonary emboli. A properly positioned filter was then placed surgically through the right internal jugular vein. The patient subsequently required removal of the errant retroperitoneal filter because of genitofemoral nerve irritation. Problems associated with percutaneous Greenfield filter placement and pertinent literature are discussed.

Meconium peritonitis: prenatal sonographic findings and their clinical significance.

Ultrasonographic (US) findings were correlated with clinical outcome in seven cases of meconium peritonitis detected with prenatal US during a 2-year period. Nineteen previously reported cases were also reviewed. US findings included intraabdominal calcifications (n = six cases), fetal ascites (n = 3), echogenic ascites without calcifications (n = 1), bowel dilatation (n = 2), and polyhydramnios (n = 5). Following delivery, six infants were still alive after a mean follow-up of 13 months (range, 6-26 months); the seventh died of hydrocephalus. Of the six, four required surgical correction of a small-bowel perforation and two did not. All six are thriving, and none has yet been found to have cystic fibrosis. In the 19 previously reported cases, there were only two cases of cystic fibrosis, neither with intraabdominal calcifications. The presence of calcifications was significantly associated with causes other than cystic fibrosis. Prenatally diagnosed cases of meconium peritonitis are associated with cystic fibrosis less frequently than previous studies suggest.

The incarcerated gravid uterus.

The case of a 28-year-old multiparous woman with an incarcerated gravid uterus is presented. This largely unknown entity invariably results in spontaneous abortion if untreated. Patients present with a characteristic and readily recognizable sign and symptom complex and ultrasonographic findings. Early diagnosis is emphasized and therapy is outlined.