Gallstone pancreatitis: combined endoscopic and laparoscopic approaches.

Of 11 patients with gallstone pancreatitis, 10 underwent preoperative ERCP. Calculi were removed from the common duct in two patients. All patients underwent laparoscopic cholecystectomy, with normal rapid convalescence. The eleventh patient is recovering from pancreatitis with the bile duct accessed percutaneously. A combined endoscopic and laparoscopic approach to gallstone pancreatitis is safe and was associated with minimal risk in this small series.     

Evaluation of the developmental toxicity of crocetin on Xenopus.

Crocetin, a carotenoid isolated from the spice saffron, has been found to be effective in treating certain types of cancer treatable with all-trans retinoic acid (ATRA). ATRA, however, is a potent teratogen, and the possibility that crocetin may also be a teratogen becomes an important medical issue. The teratogenic potential of crocetin and ATRA were evaluated in frog (Xenopus) embryos. The data show that crocetin is a teratogen, but far less potent than ATRA. This suggests that crocetin may be a safer alternative to treat ATRA-sensitive cancers in women of childbearing age.     

A hybrid approach for quantification of aortic valve stenosis using cardiac magnetic resonance imaging and echocardiography.

BACKGROUND: Doppler-derived calculation of aortic valve area (AVA) using the continuity equation can be difficult at times, e.g. due to poor acoustic windows, heavy calcification of the aortic valve, or significant flow acceleration in the left ventricular outflow tract. The aim of this study was to compare AVA as assessed by means of transthoracic echocardiography (TTE) with a hybrid approach, where the Doppler-derived numerator in the continuity equation was replaced by cardiovascular magnetic resonance (CMR) determination of stroke volume. METHODS: Twenty consecutive patients admitted for evaluation of aortic stenosis underwent transthoracic echocardiography and CMR determination of stroke volume within a time period of 3 weeks. Additionally, continuous-wave Doppler spectra of the aortic valve were acquired immediately after the CMR examination. RESULTS: There was no statistically significant difference for mean AVA between the two methods (0.88 +/- 0.23 cm2 by the standard continuity equation versus 0.86 +/- 0.23 cm2 by the hybrid approach, p = 0.55; r = 0.73, p < 0.01). The mean difference was 0.02 cm2 and the limits of agreement were -0.32 to 0.36. Only 2 patients were classified differently by the two methods. Intraobserver and interobserver variability and reproducibility were superior for the hybrid approach. CONCLUSION: The hybrid method for determination of AVA is an excellent alternative to the standard approach by TTE.     

Pharmacological characterization of rat retinal dopamine receptors

The dopamine (DA) D-1 and D-2 receptors coupled to adenylate cyclase in the rat retina were characterized pharmacologically. In confirmation of reports using other neural tissues, activation of D-1 receptors with DA, apomorphine or SKF 38393 resulted in activation of adenylate cyclase and enhanced accumulation of cyclic AMP (cAMP). The response to DA was blocked by SCH 23390, a D-1 receptor antagonist. D-2 receptors negatively coupled to adenylate cyclase were demonstrated by preincubating retina with SCH 23390 and then with DA or apomorphine. D-2 receptor responses were also elicited with quinpirole or bromocriptine, D-2 receptor agonists, in the absence of SCH 23390. (+)-Butaclamol, but not (-)-butaclamol, blocked the D-2 receptor-induced decrease of cAMP. Moreover, I-sulpiride was more active than d-sulpiride in reversing the DA-induced inhibition of cAMP accumulation. D-1 and D-2 receptor responses were also evident in forskolin-activated retina. The intraocular injection of pertussis toxin prevented the fall of cAMP and enhanced the rise of cAMP by DA, indirectly implicating the need for a guanine nucleotide regulatory protein in the process. Our results demonstrate that retinal tissue contains DA receptors that are similar to those found in brain and they imply that therapeutic agents that interact with the receptors in brain might interact with the receptors in retina.     

Sirolimus-associated hepatotoxicity in liver transplantation

BACKGROUND: Sirolimus is an immunosuppressant that exerts anti-rejection activity by inhibiting T-cell activity and is used to treat chronic rejection and calcineurin-related nephrotoxicity. Unlike tacrolimus and cyclosporine, it has no effect on calcineurin activity in liver transplant recipients. OBJECTIVE: To report correlates of survival outcomes in a series of patients with putative sirolimus-related hepatotoxicity after liver transplant. METHODS: We retrospectively reviewed the medical records of patients who underwent a liver transplant for chronic hepatitis C virus (HCV) and who received sirolimus immunosuppressive therapy between November 2000 and November 2003. Extracted data included sirolimus serum concentrations, frequency of sirolimus-related adverse effects, drug-related clinical hepatitis, and survival outcomes. RESULTS: Ten patients were found to have been treated with sirolimus for either renal insufficiency (n = 6) or chronic rejection (n = 4). Six patients had liver biopsies, while the remaining 4 patients were clinically diagnosed with rejection. Two of the 6 patients demonstrated changes consistent with sinusoidal congestion and one with eosinophilia, consistent with an allergic drug reaction. HCV viral load increased slightly, from 600 000 to 700 000 IU/mL. Mean baseline transaminase levels were 45 IU/L for aspartate aminotransferase and 50 IU/L for alanine aminotransferase, with peak levels of 210 and 180 IU/L, respectively. The time to transaminase increase was a mean of 21 days when sirolimus was added, with resolution within 27 days (mean) after its discontinuation. No changes were evident in antiviral therapy. Combination sirolimus and tacrolimus concentrations were maintained at >10 ng/mL; average monotherapy with sirolimus was 12 ng/mL, and average time on therapy was 25 weeks. CONCLUSIONS: Sirolimus-related hepatotoxicity is an important complication after liver transplant. Immediate recognition is critical to avoid confusion with other causes of abnormal serum aminotransferases after liver transplant, and discontinuation of the drug may be required.