Diseases of the intracranial meninges: MR imaging features

Although the meninges are often thought of simplistically as a connective tissue sac that contains the CSF and the contents of the CNS, they are far more complex. Anatomically, they comprise several layers. Pathologically, numerous disease processes may affect the meninges; different processes may even involve different areas of the meninges. These factors all influence the MR imaging characteristics of meningeal lesions. This review briefly discusses the anatomy of the meninges, the MR imaging technique when meningeal disease is suspected, and the appearance of the normal meninges. It then focuses on tumors, infections, cysts, and other lesions that primarily involve the meninges, excluding lesions that secondarily involve the meninges.     

Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis

BACKGROUND: There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS: Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.     

Molecular basis of resistance to HIV-1 protease inhibition: a plausible hypothesis

The binding thermodynamics of the HIV-1 protease inhibitor acetyl pepstatin and the substrate Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln, corresponding to one of the cleavage sites in the gag, gag-pol polyproteins, have been measured by direct microcalorimetric analysis. The results indicate that the binding of the peptide substrate or peptide inhibitor is entropically driven; i.e., it is characterized by an unfavorable enthalpy and a favorable entropy change, in agreement with a structure-based thermodynamic analysis based upon an empirical parameterization of the energetics. Dissection of the binding enthalpy indicates that the intrinsic interactions are favorable and that the unfavorable enthalpy originates from the energy cost of rearranging the flap region in the protease molecule. In addition, the binding is coupled to a negative heat capacity change. The dominant binding force is the increase in solvent entropy that accompanies the burial of a significant hydrophobic surface. Comparison of the binding energetics obtained for the substrate with that obtained for synthetic nonpeptide inhibitors indicates that the major difference is in the magnitude of the conformational entropy change. In solution, the peptide substrate has a higher flexibility than the synthetic inhibitors and therefore suffers a higher conformational entropy loss upon binding. This higher entropy loss accounts for the lower binding affinity of the substrate. On the other hand, due to its higher flexibility, the peptide substrate is more amenable to adapt to backbone rearrangements or subtle conformational changes induced by mutations in the protease. The synthetic inhibitors are less flexible, and their capacity to adapt is more restricted. The expected result is a more pronounced effect of mutations on the binding affinity of the synthetic inhibitors. On the basis of the thermodynamic differences in the mode of binding of substrate and synthetic inhibitors, it appears that a key factor to understanding resistance is given by the relative balance of the different forces that contribute to the binding free energy and, in particular, the balance between conformational and solvation entropy.     

Efficacy and pharmacokinetics of gallopamil in patients with coronary artery disease

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.     

Fluconazole versus itraconazole for candida esophagitis in acquired immunodeficiency syndrome. Candida Esophagitis

BACKGROUNDS & AIMS: Contrasting opinions exist about the pharmacological treatment of esophageal candidiasis in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to assess the long-term efficacy of fluconazole and itraconazole treatment. METHODS: This study evaluated 2213 human immunodeficiency virus-positive patients at first episode of esophageal candidiasis diagnosed by endoscopy; 1105 received fluconazole and 1108 received itraconazole. The endoscopic and clinical response to treatment was assessed periodically until the end of the follow-up period (1 year). RESULTS: At week 2, endoscopic cure occurred in 81.2% of patients treated with fluconazole and in 65.6% of patients treated with itraconazole (P < 0.001). Clinical cure was observed in 81.5% of patients treated with fluconazole and in 75.2% of patients treated with itraconazole (P < 0.001). At the end of the follow-up period, endoscopic and clinical cure were observed in 96% of patients treated with fluconazole and in 95.6% of patients treated with itraconazole (P = 0.788), with similar differences by intention-to-treat analysis (93.6% vs. 93.3%; P = 0.853). Treatment failure was observed in 22.3% of fluconazole-treated patients and in 26.6% of itraconazole-treated patients (P = 0.022). CONCLUSIONS: Fluconazole and itraconazole are provided with good long-term therapeutic efficacy in the treatment of Candida esophagitis in patients with AIDS. Fluconazole is associated with a higher rate of cure than itraconazole in short-term treatment.