Biplane fluoroscopy-guided percutaneous spinal cord stimulation.

OBJECTIVE: Fluoroscopy is useful for spinal cord stimulation (SCS) lead placement. We employed biplane fluoroscopy for SCS lead placement. In this study, we sought to confirm the validity of using biplane fluoroscopy for SCS lead placement and to establish whether biplane fluoroscopy safely reduces the duration of surgery. METHODS: Clinical data were retrospectively collected from the medical records of patients who underwent SCS lead placement under local anesthesia from 2015 to 2022. The duration of the surgical phase and the total radiation exposure time per case were recorded. RESULTS: Forty-six patients underwent percutaneous SCS lead implantation. Recording was completed in 41 cases: one lead was placed in 13 cases and two leads were placed in 28 cases. Monoplane and biplane fluoroscopy was used in 15 and 26 patients, respectively. Although the type of fluoroscopy did not significantly affect the mean duration of the surgical phase in patients in which one lead was placed, biplane fluoroscopy was associated with a significant reduction in the mean duration of the surgical phase in patients that underwent placement of two leads (P=0.002). No significant differences in the total radiation exposure time were observed between patients in the monoplane and biplane fluoroscopy groups that were implanted with one (P=0.21) or two leads (P=0.62). CONCLUSIONS: The use of biplane fluoroscopy reduced the duration of surgery necessary for the placement of two SCS leads. Biplane fluoroscopy represents a practical and safe adjustment to the current practice of SCS lead implantation.

Protective effects of SM-20302, an orally active GPIIb/IIIa antagonist, in an ADP/epinephrine-induced guinea pig model of transient cerebral ischemia.

The potential benefits of SM-20302, (2S)-3-(3-(4-amidinobenzoylamino)propanoylamino)-2-(4-ethyl)benzensulfonylaminopropionic acid hydrochloride, a nonpeptide GPIIb/IIIa receptor antagonist, were compared with those of aspirin and ticlopidine in a transient cerebral ischemia model in guinea pigs. Transient cerebral ischemia was induced in guinea pigs by an infusion of ADP/epinephrine into the left internal carotid artery. Each compound was orally administered 1 h (SM-20302 and aspirin) or 3 h (ticlopidine) before the ADP/epinephrine infusion. The ischemic area in coronal brain slices was assessed 1 min after the cessation of ADP/epinephrine infusion by a carbon black perfusion method. In a separate experiment, neurological deficits and lactate contents of ipsilateral hemispheres were evaluated 60 min after the cessation of ADP/epinephrine infusion by neurological scores and the standard enzymatic method, respectively. SM-20302 (0.3 and 1 mg/kg p.o.) significantly reduced the ischemic area, neurological deficits and lactate contents in comparison with the vehicle control. Aspirin (100 mg/kg po) had no significant effect on either parameter. Ticlopidine (300 mg/kg p.o.) reduced the lactate content. Although a combination of aspirin (100 mg/kg p.o.) and ticlopidine (300 mg/kg po) also reduced the lactate content, no additive effect was observed. These results suggest that SM-20302 is of potential clinical benefit in the treatment of thromboembolic diseases.

SM-20302, a nonpeptide GPIIb/IIIa receptor antagonist, exhibits a wide therapeutic window in a newly developed hemorrhage model in mice.

We have developed a gastrointestinal hemorrhage model in mice and thereby assessed the potential risk of bleeding following administration of SM-20302, a nonpeptide GPIIb/IIIa receptor antagonist. First, SM-20302 selectively inhibited the interaction between human platelets and fibrinogen in vitro. Second, SM-20302 dose-dependently inhibited ADP-induced ex vivo platelet aggregation in mice and produced an ED50 value of 0.02 mg/kg. ED50 values of cyclo(RGDT)2, aspirin and ticlopidine were 0.48, 0.74 and 13.3 mg/kg, respectively. Finally, the bleeding risk of SM-20302 was examined in our newly developed hemorrhage model. Gastrointestinal hemorrhage was assessed 24 h later when the antiplatelet agents tested were administered to mice prior to the oral dosing of 0.1 N hydrochloric acid in 90% ethanol. The resulting hemorrhage was classified into three grades, major, minor or no bleeding, primarily based on the criteria used in the TIMI trial. All compounds tested induced gastrointestinal hemorrhage in a dose-dependent manner. Minimum hemorrhagic doses, MHDs, of SM-20302, cyclo (RGDT)2, aspirin and ticlopidine were 3, 3, 1 and 100 mg/kg, respectively. The potential risk of bleeding was assessed by the ratio of MHD to ED50 value. MHD/ED50 values of SM-20302, cyclo(RGDT)2, aspirin and ticlopidine were calculated to be 150, 6.3, 1.4 and 7.5, respectively. These results suggest that this experimental hemorrhage model may be useful for the evaluation of the bleeding complications of antiplatelet agents and that SM-20302 may have a wider therapeutic window than nonspecific integrin inhibitor and conventional antiplatelet agents.

Antithrombotic effect of SM-20302, a nonpeptide GPIIb/IIIa antagonist, in a photochemically induced thrombosis model in guinea pigs.

SM-20302, a synthetic inhibitor of the fibrinogen receptor of platelets, has been shown to inhibit the platelet aggregation induced by various stimuli. In the present study, we performed ex vivo platelet aggregation studies by using heparinized platelet-rich plasma (PRP) as well as citrated PRP and compared the antiaggregatory activity with the in vivo antithrombotic efficacy of SM-20302. The oral administration of SM-20302 (0.3-10 mg/kg) to guinea pigs completely inhibited the ADP-induced ex vivo platelet aggregation in citrated PRP. In heparinized PRP, SM-20302 (1-10 mg/kg) showed a dose-dependent inhibition of ex vivo platelet aggregation, and it exhibited complete inhibition at a dose of 3 and 10 mg/kg, respectively. The concentration of ionized calcium in the citrated samples was approximately 35 times lower than that in heparinized samples. Chelation of ionized calcium caused an enhancement of the antiaggregatory activity of SM-20302 in guinea pig heparinized PRP in vitro. And addition of CaCl2 to citrated PRP reversed the enhancement. Citrate therefore appeared to enhance the inhibitory activity of SM-20302 by lowering the ionized calcium levels. We also examined the in vivo efficacy of SM-20302 in a photochemically induced femoral artery thrombosis model in guinea pigs. The photochemical injury of the endothelium of femoral artery resulted in a progressive decline in the blood flow. The oral administration of SM-20302 (0.1-3 mg/kg) produced a dose-dependent maintenance of the femoral artery patency and significantly prolonged the time to occlusive thrombus formation at a dose of 1 and 3 mg/kg, respectively. These results suggest that SM-20302 may be an orally active antithrombotic agent, and its in vivo antithrombotic efficacy appeared to correlate well with the ex vivo platelet inhibition in PRP prepared from heparinized blood but not in PRP anticoagulated with citrate.

Hyperdibasicaminoaciduria and hyperammonemia in familial protein intolerance.

A 3-year-old boy with hyperdibasicaminoaciduria and hyperammonemia showed characteristics of familial protein intolerance (FPI). Oral loading tests of lysine and arginine disclosed a remarkably reduced capability for intestinal absorption of these amino acids. Because urinary excretion and renal clearance of dibasic amino acids were only moderately elevated in the patient, the conspicuously decreased serum concentration of lysine, arginine, and ornithine was attributed to the defect in internal absorption. A possible explanation for elevated blood ammonia levels in FPI is that it is due to a deficiency of arginine and ornithine in the urea cycle that in turn results from a severe impairment in absorption of the amino acids by the gut mucosa.