Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage

A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.     

Incidence of Finding Residual Disease for Incidental Gallbladder Carcinoma: Implications for Re-resection

Re-resection for gallbladder carcinoma incidentally discovered after cholecystectomy is routinely advocated. However, the incidence of finding additional disease at the time of re-resection remains poorly defined. Between 1984 and 2006, 115 patients underwent re-resection at six major hepatobiliary centers for gallbladder carcinoma incidentally discovered during cholecystectomy. Data on clinicopathologic factors, operative details, TNM tumor stage, and outcome were collected and analyzed. Data on the incidence and location of residual/additional carcinoma discovered at the time of re-resection were also recorded. On pathologic analysis, T stage was T1 7.8%, T2 67.0%, and T3 25.2%. The median time from cholecystectomy to re-resection was 52 days. At the time of re-resection, hepatic surgery most often consisted of formal segmentectomy (64.9%). Patients underwent lymphadenectomy (LND) (50.5%) or LND + common bile duct resection (43.3%). The median number of lymph nodes harvested was 3 and did not differ between LND alone (n = 3) vs LND + common duct resection (n = 3) (P = 0.35). Pathology from the re-resection specimen noted residual/additional disease in 46.4% of patients. Of those patients staged as T1, T2, or T3, 0, 10.4, and 36.4%, respectively, had residual disease within the liver (P = 0.01). T stage was also associated with the risk of metastasis to locoregional lymph nodes (lymph node metastasis: T1 12.5%; T2 31.3%, T3 45.5%; P = 0.04). Cystic duct margin status predicted residual disease in the common bile duct (negative cystic duct, 4.3% vs positive cystic duct, 42.1%) (P = 0.01). Aggressive re-resection for incidental gallbladder carcinoma is warranted as the majority of patients have residual disease. Although common duct resection does not yield a greater lymph node count, it should be performed at the time of re-resection for patients with positive cystic duct margins because over one-third will have residual disease in the common bile duct. Presented at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract at Digestive Week 2007, Plenary Session, Washington, DC, March 23, 2007.     

Diagnosing osteoporosis by using dental panoramic radiographs: the OSTEODENT project.

OBJECTIVES: Measurement of cortical thickness and subjective assessment of cortical porosity on panoramic radiographs are methods previously reported for diagnosing osteoporosis. The aims of this study were to determine the relative efficacy of the mandibular cortical index and cortical width in detecting osteoporosis, both alone and in combination, and to determine the optimal cortical width threshold for referral for additional osteoporosis investigation. STUDY DESIGN: Six hundred seventy-one postmenopausal women 45 to 70 years of age were recruited for this study. They received dual energy x-ray absorptiometry (DXA) scans of the left hip and lumbar spine (L1 to L4), and dental panoramic radiographic examinations of the teeth and jaws. Three observers separately assessed the mandibular cortical width and porosity in the mental foramen region of the mandible. Cortical width was corrected for magnification errors. Chi-squared automatic interaction detection analysis (CHAID) software was used (SPSS AnswerTree, version 3.1, SPSS Inc., Chicago, IL). RESULTS: Chi-squared automatic interaction detection analysis showed that the cortical porosity was a poorer predictor of osteoporosis than mandibular cortical width. For the 3 observers, a mandibular cortical width of <3 mm provided diagnostic odds ratios of 6.51, 6.09, and 8.04. The test is therefore only recommended in triage screening of individuals by using radiographs made for purposes other than osteoporosis. CONCLUSION: When evaluating panoramic radiographs, only those patients with the thinnest mandibular cortices (i.e., <3 mm) should be referred for further osteoporosis investigation.     

Pyruvate-modified perfadex improves lung function after long-term hypothermic storage.

BACKGROUND: Lungs harvested for transplantation are stored while inflated with oxygen, which can serve to support oxidative metabolism. However, strategies aimed at increasing graft metabolism during storage have received little attention. In this study, we added pyruvate to the preservation solution Perfadex and measured the effects on oxidative metabolism and reperfusion lung function. METHODS: Rat lungs were stored for 6 and 24 hours in low-potassium dextran solution at 10 degrees C containing either 5 mmol/liter uniformly carbon-13 (U-(13)C) labeled glucose (Perfadex), 32 mmol/liter 3-(13)C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of (13)C into tricarboxylic acid cycle intermediates by magnetic resonance spectroscopy. Additional groups of lungs with each substrate modification were preserved for 6 or 24 hours and then reperfused. RESULTS: Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast, enrichment was significantly increased in both the pyruvate group (50% and 59%, respectively) and combined group (39% and 54%, respectively) compared with the Perfadex group (p<0.01). Graft function was excellent after 6-hour storage in all groups. All lungs stored for 24 hours exhibited inferior lung function, but oxygenation, pulmonary artery pressures, and airway pressures in the combined group were significantly improved compared with the Perfadex group (p<0.05). CONCLUSIONS: Preservation solution substrate composition influences graft metabolism during storage. The addition of pyruvate to Perfadex increases metabolism during storage and improves reperfusion lung function.