Long-Term Cholic Acid Treatment in a Patient with Zellweger Spectrum Disorder

Zellweger spectrum disorders (ZSDs) are a subgroup of peroxisomal biogenesis disorders with a generalized defect in peroxisome function. Liver disease in ZSDs has been associated with the lack of peroxisomal β-oxidation of C27-bile acid intermediates to form primary C24-bile acids, which prevents normal physiologic feedback and leads to accumulation of hepatotoxic bile acid intermediates. Primary bile acid therapy, oral cholic acid (CA), as adjunctive treatment for ZSDs, restores physiologic feedback inhibition on bile acid synthesis and inhibits formation of hepatotoxic bile acid intermediates. Our patient is a Caucasian male diagnosed with moderately severe ZSD at age 5 months, and he received long-term CA therapy from age 16 months through 19 years old. CA treatment was well tolerated, with no reports of adverse events. His liver biopsy prior to CA therapy showed cholestasis, periportal inflammation, and bridging fibrosis. Following 5 months of CA therapy, his liver biopsy showed improvement in inflammation and no change in fibrosis. Serum liver enzymes during CA therapy improved compared to pre-therapy levels but frequently were above the upper limit of normal. At age 19 years, following several years with clinical cirrhosis with severe portal hypertension, he presented with worsening jaundice, and he was diagnosed with hepatocellular cancer (HCC). Early-onset advanced liver disease associated with ZSD and natural disease progression that is not completely suppressed with CA treatment likely caused HCC in our patient. Greater awareness is needed of the possibility of development of HCC in patients with moderately severe ZSD who survive past childhood

Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans

BACKGROUND: Diets enriched with sphingolipids may improve blood lipid profiles. Studies in animals have shown reductions in cholesterol absorption and alterations in blood lipids after treatment with sphingomyelin (SM). However, minimal information exists on effect of SM on cholesterol absorption and metabolism in humans. The objective was to assess the effect of SM consumption on serum lipid concentrations and cholesterol metabolism in healthy humans. METHODS: Ten healthy adult males and females completed a randomized crossover study. Subjects consumed controlled diets with or without 1 g/day SM for 14 days separated by at least 4 week washout period. Serum lipid profile and markers of cholesterol metabolism including cholesterol absorption and synthesis were analyzed. RESULTS: Serum triglycerides, total, LDL- and VLDL- cholesterol were not affected while HDL cholesterol concentrations were increased (p = 0.043) by SM diet consumption. No change in cholesterol absorption and cholesterol fractional synthesis rate was observed with supplementation of SM compared to control. Intraluminal cholesterol solubilization was also not affected by consumption of SM enriched diet. CONCLUSIONS: In humans, 1 g/day of dietary SM does not alter the blood lipid profile except for an increased HDL-cholesterol concentration and has no effect on cholesterol absorption, synthesis and intraluminal solubilization compared to control. TRIAL REGISTRATION: Clinicaltrials.gov # NCT0032821

Reduction of the Body Burden of PCBs and DDE by Dietary Intervention in a Randomized Trial

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 noncoplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (−0.0829±0.0357 and −0.00864±0.0116 year−1, respectively; P=.04), but not during VO consumption (−0.0413±0.0408 and −0.0283±0.0096 year−1, respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes

Faster Discharge with Lactated Ringers than Normal Saline in First 72 H of Acute Pancreatitis: A Multicenter Randomized Trial

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS. STUDY DESIGN: A multi-site randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 hours. Primary outcomes were C-Reactive Protein (CRP) values on admission, 24 and 48 hours. Secondary outcomes were changes in CRP and other values, time to initiation of feeds, length of stay (LOS), Systemic Inflammatory Response Syndrome (SIRS) development, and progression to severe AP (SAP). RESULTS: We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02). CONCLUSION: The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs

Carbon outclasses wood in racket paddles: Ratings of expert and intermediate tennis players

Wooden racket paddles were modified with rubber and carbon fibre laminates and their differences tested in terms of flexural, damping, and coefficient of restitution properties. Four rackets types were designed: a wood reference, wood with rubber, carbon fibre 0°, and carbon fibre 90°. Seven expert and eight intermediate tennis players tested the rackets. To determine which of the four rackets suited the players best, we asked the players to compare the rackets two by two. After each pair tested, participants had to fill out a 4-item questionnaire in which different aspects of the rackets' performance were judged. The most preferred racket was the 0° carbon fibre racket, followed by the 90° carbon fibre racket, the wood racket and, finally, the 1-mm rubber racket. Thus, rackets with the highest stiffness, least damping, and highest coefficient of restitution were the most preferred. Interestingly, although experts and intermediate players overall judged the rackets in very similar ways according to force, vibration, and control, they were sensitive to quite different physical characteristics of the rackets

Carbon outclasses wood in racket paddles: Ratings of expert and intermediate tennis players

Wooden racket paddles were modified with rubber and carbon fibre laminates and their differences tested in terms of flexural, damping, and coefficient of restitution properties. Four rackets types were designed: a wood reference, wood with rubber, carbon fibre 0°, and carbon fibre 90°. Seven expert and eight intermediate tennis players tested the rackets. To determine which of the four rackets suited the players best, we asked the players to compare the rackets two by two. After each pair tested, participants had to fill out a 4-item questionnaire in which different aspects of the rackets' performance were judged. The most preferred racket was the 0° carbon fibre racket, followed by the 90° carbon fibre racket, the wood racket and, finally, the 1-mm rubber racket. Thus, rackets with the highest stiffness, least damping, and highest coefficient of restitution were the most preferred. Interestingly, although experts and intermediate players overall judged the rackets in very similar ways according to force, vibration, and control, they were sensitive to quite different physical characteristics of the rackets

Equal antipyretic effectiveness of oral and rectal acetaminophen: a randomized controlled trial [ISRCTN11886401]

BACKGROUND: The antipyretic effectiveness of rectal versus oral acetaminophen is not well established. This study is designed to compare the antipyretic effectiveness of two rectal acetaminophen doses (15 mg/kg) and (35 mg/kg), to the standard oral dose of 15 mg/kg. METHODS: This is a randomized, double-dummy, double-blind study of 51 febrile children, receiving one of three regimens of a single acetaminophen dose: 15 mg/kg orally, 15 mg/kg rectally, or 35 mg/kg rectally. Rectal temperature was monitored at baseline and hourly for a total of six hours. The primary outcome of the study, time to maximum antipyresis, and the secondary outcome of time to temperature reduction by at least 1°C were analyzed by one-way ANOVA. Two-way ANOVA with repeated measures over time was used to compare the secondary outcome: change in temperature from baseline at times1, 2, 3, 4, 5, and 6 hours among the three groups. Intent-to-treat analysis was planned. RESULTS: No significant differences were found among the three groups in the time to maximum antipyresis (overall mean = 3.6 hours; 95% CI: 3.2–4.0), time to fever reduction by 1°C or the mean hourly temperature from baseline to 6 hours following dose administration. Hypothermia (temperature < 36.5°C) occurred in 11(21.6%) subjects, with the highest proportion being in the rectal high-dose group. CONCLUSION: Standard (15 mg/kg) oral, (15 mg/kg) rectal, and high-dose (35 mg/kg) rectal acetaminophen have similar antipyretic effectiveness