Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse: A Noninferiority Randomized Controlled Trial

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Pharmacokinetics and brain penetration study of chlorogenic acid in rats

1. The present study is designed to investigate the brain distribution and plasma pharmacokinetics profiles of chlorogenic acid (CGA) after intranasal administration in Charles–Foster rats to evaluate whether the CGA molecules are transported directly via the nose-to-brain path.

2. The CGA is administered intravenously (IV) and intranasally (IN) at the dose of 10?mg/kg. Further, its concentration in the plasma, cerebrospinal fluid (CSF) and the whole brain is analyzed by HPLC-UV method.

3. The study observes that CGA is rapidly absorbed in plasma with t_max of 1?min similar to IV route after IN administration. The peak plasma concentration and AUC_0–24 are higher by 3.5 and 4.0 times respectively in IV administration, compared to IN delivery that represents the significant less systemic exposure of CGA in IN route.

4. However, the concentration of CGA in the brain is 4, 6.5, 5.3, 5.2 and 4.5 times higher at 30, 60, 120, 240 and 360?min, respectively in IN administration compared to IV administration. The exposure of CGA in the brain after IN administration (AUC_{brain, IN}) was significantly greater (4 times) as compared to the exposure of CGA in the brain (AUC_{brain, IV}) after IV administration reflecting significant brain uptake of CGA through nasal route. Therefore, IN delivery of CGA can be a promising approach for the treatment of stroke and neurodegenerative disorders.     

Effect of sequential administration of an opioid and cholecystokinin on gallbladder ejection fraction: brief communication.

This study was undertaken to test the effect of sequential administration of an opioid and intravenous cholecystokinin (CCK) on gallbladder ejection fraction. METHODS: Forty-nine patients who had received an opioid underwent quantitative cholescintigraphy with octapeptide of CCK (CCK-8). Gallbladder ejection fraction and CCK-8-induced paradoxical filling were calculated. RESULTS: In the basal state, more of the hepatic bile entered the gallbladder (67%) than the small intestine (33%). After CCK-8 infusion, gallbladder ejection fraction was low in 37 (76%) of 49 patients and normal in 12 (24%). All 5 types of opioids lowered ejection fraction. CCK-induced paradoxical filling of the gallbladder was noted in 7 patients, but only one showed paradoxical filling of greater than 20% and none had a normal gallbladder ejection fraction. The lowering effect of opioids on gallbladder ejection fraction may last as long as 18 h after intake. CONCLUSION: CCK-8 produced a normal gallbladder ejection fraction in 24% of patients who had received an opioid and thus could exclude both acute and chronic cholecystitis during a single hepatobiliary study.     

Patient experience with, and use of, an electronic monitoring system to assess vaccination responses

OBJECTIVE: To evaluate the user experience and acceptability of an electronic patient monitoring system. SETTING AND PARTICIPANTS: 822 Military and civilian personnel at a health clinic at a major US military headquarters used an Internet and telephone-based electronic monitoring system to report vaccination-site responses and symptoms after receiving the smallpox vaccination. Focus groups of vaccinees were conducted to help develop a survey about the experience that was distributed to 379 vaccinees (96% completion rate). RESULTS: Users of the electronic monitoring system reported that it was fast and easy to use and reported they would use a system like this again and recommend an electronic monitoring system to a friend or relative. Most users (84%) were comfortable with a physician tracking their vaccine reaction using their electronic reports, but only half (51%) were comfortable with eliminating the post-vaccination follow-up visit with their health-care provider based on their electronic reports. CONCLUSIONS: This electronic monitoring system was well received by vaccinees and allowed health-care providers to track the status of vaccinees. However, vaccinees were not comfortable replacing a physician visit with electronic monitoring, at least for the smallpox vaccination. A monitoring system like this may be useful in public health settings, such as mass vaccination or prophylaxis during a bioterrorism event, a pandemic influenza outbreak, or another public health emergency.     

Constancy and variability of gallbladder ejection fraction: impact on diagnosis and therapy.

The main objective of this study was to test the constancy and variability of gallbladder (GB) ejection fraction (EF) in long-term studies to (a) determine whether EF ever becomes normal once it is low, (b) determine how long it takes for the EF to become abnormal once it is found to be normal, (c) explore the cause of low EF, and (d) define objective parameters for biliary and nonbiliary abdominal pain. METHODS: Fifty-two patients (42 women, 10 men) who underwent quantitative cholescintigraphy twice (total studies, 104), over a mean period of 38.54 mo between studies, were chosen for retrospective analysis. They were divided into the following groups: control (n = 13; nonbiliary abdominal pain), chronic acalculous cholecystitis (CAC) (n = 27; biliary abdominal pain), chronic calculous cholecystitis (CCC) (n = 6; biliary abdominal pain), and opioid (n = 6; nonbiliary abdominal pain). The last group had received an opioid before cholecystokinin-8 (CCK-8) infusion in one study but not in the other study. A GBEF value of > or =35% was considered normal with a 3-min infusion and > or =50% as normal with a 10-min infusion of CCK-8. RESULTS: The mean GBEF value was reproducible between the 2 sequential studies in the control group (66.0% +/- 20.5% vs. 73.9% +/- 17.7%), CAC group (24.4% +/- 22.3% vs. 16.9% +/- 10.9%), and CCC group (20.8% +/- 20.9% vs. 27.5% +/- 34.5%) but not in the opioid group (14.8% +/- 14.6% vs. 56.5% +/- 31.7%). The severity of GBEF reduction in CAC increased with time: 7.2% +/- 8.1% within 12 mo, 16.1% +/- 14.9% in 13-47 mo, and 23.5% +/- 21.3% in 48-168 mo. None of the 27 patients with CAC developed a gallstone as detected by ultrasound during the study period. In 5 patients with CAC, a mean period of 52.6 +/- 28.9 mo was required for conversion from normal to a low EF. CCK-induced cystic duct spasm is the etiology for low EF in both CAC and CCC. CONCLUSION: Normal and low GBEF values are reproducible in long-term studies. Once the EF reaches a low value, it does not return to normal, and a normal value requires many years to become abnormal. CCK-induced cystic duct spasm is the cause of low GBEF in CAC and CCC, and the severity of EF reduction is similar for both. Exclusion of opioid intake immediately before the study is critical before attributing a low GBEF value to an irreversible GB motor dysfunction.     

Immunological changes in normal pregnancy.

During pregnancy the mother must tolerate intra-uterine allogenic fetal tissue. Failure of this tolerance may cause spontaneous abortion. The immunological changes occurring in normal pregnancy are poorly understood. The aim of this study was to investigate the immunological changes occurring in pregnancy. Thirty women in the first trimester; 10 in the second and 10 in the third trimester of pregnancy were studied and compared to age matched non-pregnant controls. In normal pregnancy there was an increase in the total white cell count with no change in the lymphocyte count. There was a fall in total T cell numbers and activated T cell numbers, with no change in helper/inducer or suppressor/cytotoxic T cell numbers. [3H]Thymidine uptake in response to three different mitogens was increased. This implies an increase in potential for the cells to respond to mitogens. There was no change in interleukin-2 receptor levels, suggesting that despite this increased potential there was no general activation of the immune system. A rise in IgM and IgG was found after mitogen stimulation of peripheral blood lymphocytes, suggesting an increase in potential antibody production. These results demonstrate that lymphocytes from pregnant women have an increased potential rather than an increased activity.     

Sensitivity-encoded (SENSE) proton echo-planar spectroscopic imaging (PEPSI) in the human brain.

Magnetic resonance spectroscopic imaging (MRSI) provides spatially resolved metabolite information that is invaluable for both neuroscience studies and clinical applications. However, lengthy data acquisition times, which are a result of time-consuming phase encoding, represent a major challenge for MRSI. Fast MRSI pulse sequences that use echo-planar readout gradients, such as proton echo-planar spectroscopic imaging (PEPSI), are capable of fast spectral-spatial encoding and thus enable acceleration of image acquisition times. Combining PEPSI with recent advances in parallel MRI utilizing RF coil arrays can further accelerate MRSI data acquisition. Here we investigate the feasibility of ultrafast spectroscopic imaging at high field (3T and 4T) by combining PEPSI with sensitivity-encoded (SENSE) MRI using eight-channel head coil arrays. We show that the acquisition of single-average SENSE-PEPSI data at a short TE (15 ms) can be accelerated to 32 s or less, depending on the field strength, to obtain metabolic images of choline (Cho), creatine (Cre), N-acetyl-aspartate (NAA), and J-coupled metabolites (e.g., glutamate (Glu) and inositol (Ino)) with acceptable spectral quality and localization. The experimentally measured reductions in signal-to-noise ratio (SNR) and Cramer-Rao lower bounds (CRLBs) of metabolite resonances were well explained by both the g-factor and reduced measurement times. Thus, this technology is a promising means of reducing the scan times of 3D acquisitions and time-resolved 2D measurements.