Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss.

OBJECTIVES: Orlistat, an intestinal lipase inhibitor, has recently been approved by the US Food and Drug Administration for treatment of obesity. The effects of orlistat on hepatobiliary function have not been previously defined. A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet. METHODS: A total of 23 obese (BMI 30-41 kg/m2) subjects were randomized to a double blind t.i.d. treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet (1200-1500 kcal/day). The study was designed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat. Cholesterol saturation, bile composition, and gallbladder motility were measured. RESULTS: At the end of the treatment period, mean weight loss of 3.8 kg was achieved in the orlistat group (vs 2.3 kg with placebo, p = NS). Total bile acid concentration decreased significantly with placebo (-18.57 +/- 6.99 mmol/L; 95% CI = -32.26 to -4.87), but not with orlistat. Biliary phospholipid concentration decreased significantly with placebo (-4.38 +/- 1.91 mmol/L; 95% CI = -8.13 to -0.64) but not with orlistat. Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups. Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group. CONCLUSIONS: Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids. Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function. We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat.

Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease.

BACKGROUND: Localized Lyme disease, manifested by erythema migrans, is usually treated with oral doxycycline or amoxicillin. Whether acute disseminated Borrelia burgdorferi infection should be treated differently from localized infection is unknown. METHODS: We conducted a prospective, open-label, randomized, multicenter study comparing parenteral ceftriaxone (2 g once daily for 14 days) with oral doxycycline (100 mg twice daily for 21 days) in patients with acute disseminated B. burgdorferi infection but without meningitis. The erythema migrans skin lesion was required for study entry, and disseminated disease had to be indicated by either multiple erythema migrans lesions or objective evidence of organ involvement. RESULTS: Of 140 patients enrolled, 133 had multiple erythema migrans lesions. Both treatments were highly effective. Rates of clinical cure at the last evaluation were similar among the patients treated with ceftriaxone (85 percent) and those treated with doxycycline (88 percent); treatment was considered to have failed in only one patient in each group. Among patients whose infections were cured, 18 of 67 patients in the ceftriaxone group (27 percent) reported one or more residual symptoms at the last follow-up visit, as did 10 of 71 patients in the doxycycline group (14 percent, P > or = 0.05). Mild arthralgia was the most common persistent symptom. Both regimens were well tolerated; only four patients (6 percent) in each group withdrew because of adverse events. CONCLUSIONS: In patients with acute disseminated Lyme disease but without meningitis, oral doxycycline and parenterally administered ceftriaxone were equally effective in preventing the late manifestations of disease.