Postprocedural high-density lipoprotein cholesterol predicts carotid stent patency at 1 year.

The durability of carotid artery stenting (CAS) is affected by the occurrence of myointimal proliferation and in-stent restenosis (ISR). We aimed to identify clinical, angiographic, and laboratory predictors of ISR, paying special attention to postprocedural metabolic factors. A total of 102 consecutive patients with successful CAS for > or =70% atherosclerotic internal carotid artery stenosis were followed up with neurological assessment and duplex sonography 1 day, 1 month, and 1 year after CAS. Lipid profile and hemoglobin A(1c) were tested at the 1-month follow-up visit. Ten (10%) patients had ISR > or =50% after 1 year. Compared with patients without ISR (n = 92), patients with ISR were more often current smokers (33% vs. 70%, P = 0.034) and had significantly lower 1-month high-density lipoprotein (HDL) cholesterol: median (range) 47 (24-95) mg/dl vs. 39.5 (25-50) mg/dl, P = 0.031. Multivariate logistic regression analyses identified 1-month HDL cholesterol >45 mg/dl as the only independent predictor of carotid stent patency at 1 year (P = 0.033, OR = 0.09, 95% CI 0.01-0.83). Postprocedural HDL cholesterol levels predict carotid stent patency at 1 year. With the possibility of elevation of HDL cholesterol by lifestyle changes and medication, this finding may have implications for the future management of patients undergoing CAS.

Timing of stenting of symptomatic carotid stenosis is predictive of 30-day outcome.

For patients with symptomatic carotid stenosis, benefit from carotid artery stenting (CAS) highly depends on the 30-day stroke and death rates. Identification of predictors of unfavourable outcome would help guide the patient selection. We analysed the influence of clinical and angiographic factors on the 30-day outcomes of 77 consecutive patients who underwent CAS for > or = 60% symptomatic carotid stenosis within 180 days of transient ischaemic attack or moderate stroke (modified Rankin Scale score < or = 3). The 30-day composite end-point for stroke (7.8%) and death of any cause (1.3%) was 9.1%. Patients with complicated CAS were older than patients with uncomplicated CAS (mean age 75.1 +/- 8.2 vs. 65.9 +/- 9.5 years, P = 0.015) and underwent stenting significantly earlier after the qualifying event: median delay 1.5 weeks (range: 0.2-3.0) vs. 3.2 weeks (range: 0.5-26), P = 0.004. In multivariate logistic regression analyses, age [odds ratio (OR) = 1.148; 95% confidence interval (CI): 1.011-1.304 and P = 0.033] and delay of treatment < 2 weeks (OR = 22.399; 95% CI: 2.245-223.445 and P = 0.008) remained the only variables significantly associated with 30-day outcome. CAS carries a considerable risk in old patients and when performed early (< 2 weeks) after the qualifying event. Future reports should address the timing of CAS.

Acquired torticollis due to Grisel's syndrome: case report and follow-up of non-traumatic atlantoaxial rotatory subluxation.

Non-traumatic atlantoaxial rotatory subluxation is an uncommon entity, with inconsistent presentations. It is also known as Grisel's syndrome (GS), and most commonly follows infectious processes of the upper respiratory tract. A case is described of a non-traumatic rotatory atlantoaxial dislocation in a three-year-old boy. The patient presented with acute torticollis one week after mild upper respiratory infection. Neurological evaluation and lumbar punction were normal. After five days of intractable pain and non-reducible rotational tilt of the head to the left, CT and MR imaging were performed and showed atlantoaxial rotatory subluxation. In addition, MRI demonstrated middle ear and mastoid inflammation. Tilt reduction could be obtained through gentle skull traction under sedation and relaxation for 3 days. Antibiotic treatment was performed. The patient was then placed in a Minerva cast jacket. After seven weeks of immobilization, CT demonstrated regular atlantoaxial alignment. Follow-up after 5.5 years showed the boy neurologically intact and free of clinical complaints. Dynamic cervical radiographs confirmed that the atlantoaxial joints were stable.

Recurrent cryptic vascular malformation associated with a developmental venous anomaly.

Abnormal venous drainage patterns, such as developmental venous anomalies (DVAs), are frequent findings neighbouring cryptic vascular malformations (CVMs). Although the clinical relevance of DVAs remains controversial, increasing attention has been focused on the possible importance of venous outflow disturbance and venous hypertension in DVAs for the development of CVMs. We present the case of a 32-year-old man with dysphasic seizures symptomatic for recurrence and rebleeding of a CVM of the left angulare gyrus, which drained entirely into a large DVA. A cavernoma had been surgically removed 1 year before, while the associated DVA had been left in place. In the following second surgical procedure, the new malformation, which was histologically verified as arteriovenous angioma (AVM), was removed and the DVA was occluded for the length of the angioma. Postoperative course of the patient was unremarkable, the patient is seizure free and neurologically intact. This first report of such a sequence of events raises important questions regarding the association of various vascular malformations, regarding transitional and hybrid forms, as well as the role of anomalous venous drainage in their pathophysiology and probably in their development. Our case and selected cases in literature suggest that venous hypertension in a DVA might not be just a coincidential finding, but sometimes can induce or influence the development and recurrence of associated vascular lesions. The developmental interrelationship, the potential mechanisms for this association and the implications of similar cases reported in pertinent literature are discussed.

Apparent dose-dependent oral absorption of cyclosporin A in rats.

The oral absorption of cyclosporin A (CyA) was studied in rats after 6, 12, 18, and 23 mg kg-1 doses were given in an olive oil solution to determine if CyA absorption from the gastrointestinal tract was dose-dependent. Using serial blood samples obtained at various times after the respective doses, analysis of the resultant blood CyA concentration-time curves suggested that the rate of CyA absorption for all four doses was an apparent zero-order process. Moreover, the rate of CyA absorption appeared to be dose-dependent, increasing as the dose of CyA increased. Similarly, the extent of CyA absorption (F) also exhibited dose-dependent characteristics in this study. F increased from 0.13 after the 6 mg kg-1 dose to 0.22 with the 18 and 23 mg kg-1 doses (p less than 0.05). In the present investigation, the observed values for the duration of drug absorption (T), terminal first-order rate constant (beta) and corresponding elimination half-life (T 1/2 beta) of approximately 4-5 h, 0.030 h-1 and 21-28 h, respectively, were similar for all CyA doses. Moreover, no difference in beta was observed after oral or intravenous drug administration. Absorption lag times of 1-2 h were found. The results suggested that the dose-dependent absorption of CyA observed in the present study was possibly related to the effects of olive oil on gastric emptying and that CyA might be unstable in the gastric fluids and/or metabolized by the gastric mucosa.

Intravenous cyclosporine kinetics in renal failure.

Kinetics of the novel immunosuppressive cyclosporine were determined in four patients with terminal renal failure. After a short intravenous infusion (2.05 to 3.5 mg/kg in 4 hr), blood and plasma concentrations were measured (HPLC and radioimmunoassay [RIA] up to 36 hr. After infusion, concentration curves of the drug were characterized by a rapid initial fall (t 1/2 alpha 0.10 +/- 0.03 hr), followed by a biphasic elimination phase with corresponding t 1/2s of 1.08 +/- 0.25 hr (t 1/2 beta) and 15.8 +/- 8.4 hr (t 1/2 gamma). The volumes of distribution, calculated from whole blood concentrations (HPLC), were 0.140 +/- 0.48 l/kg (volume of the central compartment) and 3.49 +/- 2.65 l/kg (volume of distribution at steady state), whereas systemic clearances were 0.369 +/- 0.08 l/hr/kg. Blood levels measured by RIA exceeded the HPLC values after the fourth hour by up to 100%, indicating the production of cross-reacting cyclosporine metabolites. Plasma concentrations were considerably lower than in whole blood. Elimination of unchanged cyclosporine in patients with renal failure appears to be of the same order as in those with normal kidney function. Modification of the initial dosage regimens is therefore probably not required.

Intestinal lymphatic absorption of cyclosporin A following oral administration in an olive oil solution in rats.

The intestinal lymphatic absorption of cyclosporin A (CyA) following oral administration of 6.5 +/- 0.6 and 25.2 +/- 1.4 mg kg-1 doses of the drug dissolved in an olive oil solution was studied using a thoracic duct-cannulated rat model. Cumulative lymph samples were collected for up to 114 h post-dosing and assayed by liquid scintillation counting. In this study, the estimated amount of lymphatically absorbed CyA was 0.35 +/- 0.13 and 0.47 +/- 0.29 per cent of the respective doses. In terms of the overall oral bioavailability of CyA (Fpo) by all absorptive mechanisms, the intestinal lymphatics accounted for the absorption of approximately 2 per cent of the total amount of absorbed drug. Fpo was 21.3 +/- 2.5 per cent. The results of this study suggested that lipophilicity alone was not the only factor governing intestinal lymphatic drug absorption. An explanation for the low level of lymphatic CyA absorption is presented. In addition, some reasons for the low overall oral bioavailability of CyA are discussed.

Cyclosporin A: correlation between HPLC and RIA serum levels.

Serum levels of cyclosporin A were analysed in parallel with an HPLC and a RIA method for six patients who received repeated intramuscular and oral doses of this immunosuppressive drug after bone marrow transplantation. A good correlation was found between both methods with a similar time course of the serum curves. Due to cross-reacting metabolites, the values from the RIA assay were on average 30 to 100% higher than with the HPLC assay which is specific for the parent drug.