Effect of acid suppressant medications on the laxative action of magnesium preparations in patients with opioid-induced constipation: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.

Objective: Magnesium oxide is widely used for treating opioid-induced constipation, a serious analgesic-associated problem. Opioid analgesic users are often prescribed non-steroidal anti-inflammatory drugs, which are sometimes combined with acid suppressants to prevent gastrointestinal adverse events. Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect. This study was aimed at evaluating the effect of magnesium preparations combined with acid suppressants on the incidence of opioid-induced constipation by using the Food and Drug Administration Adverse Event Reporting System. Methods: Adverse events were defined per the Medical Dictionary for Regulatory Activities; the term 'constipation (preferred term code: 10010774)' was used for analysis. After adjusting for patient background factors using propensity score matching, acid suppressants' effect on constipation incidence was evaluated in opioid users prescribed magnesium preparations alone as laxatives by using a test for independence. Key Findings: The Food and Drug Administration Adverse Event Reporting System contains 14,475,614 reports for January 2004 to December 2021. Significantly increased constipation incidence was related to magnesium preparations combined with acid suppressants, especially proton pump inhibitors (P < 0.0001, McNemar's test). Conclusion: Magnesium preparations combined with acid suppressants may diminish magnesium preparations' laxative effect; healthcare professionals should pay attention to this issue.

Differential diagnosis of hyperintense cerebrospinal fluid on fluid-attenuated inversion recovery images of the brain. Part II: non-pathological conditions.

The fluid-attenuated inversion recovery imaging sequence is a widely used MRI sequence of the brain. It is an inversion recovery pulse sequence, designed to suppress signals from the cerebrospinal fluid. It is highly sensitive for detection of lesions adjacent to or within the cerebrospinal fluid, associated with T(2) prolongation or T(1) shortening. The term "hyperintense cerebrospinal fluid" is used to describe failed suppression or hyperintensity of cerebrospinal fluid on fluid-attenuated inversion recovery imaging of the brain. It is often encountered in many important pathological conditions, including subarachnoid haemorrhage, meningitis and leptomeningeal metastasis. However, certain non-pathological states in which there is no definite cerebrospinal fluid abnormality can also present with hyperintense cerebrospinal fluid. Correct interpretation of abnormalities is important to arrive at an appropriate diagnosis. This pictorial review provides fluid-attenuated inversion recovery images of hyperintense cerebrospinal fluid of the brain and describes distinguishing features, focusing on non-pathological conditions.

Differential diagnosis of hyperintense cerebrospinal fluid on fluid-attenuated inversion recovery images of the brain. Part I: pathological conditions.

The fluid-attenuated inversion recovery imaging sequence is a widely used MRI sequence of the brain. It is an inversion recovery pulse sequence, designed to suppress signals from the cerebrospinal fluid. It is highly sensitive in detection of lesions adjacent to or within the cerebrospinal fluid associated with T(2) prolongation or T(1) shortening. The term "hyperintense cerebrospinal fluid" is used to describe failed suppression, or hyperintensity, of cerebrospinal fluid on fluid-attenuated inversion recovery imaging of the brain. It is often encountered in many important pathological conditions, including subarachnoid haemorrhage, meningitis and leptomeningeal metastasis. However, certain non-pathological states in which there is no definite cerebrospinal fluid abnormality can also present with hyperintense cerebrospinal fluid. Correct interpretation of abnormalities is important to arrive at an appropriate diagnosis. This pictorial review provides fluid-attenuated inversion recovery images of hyperintense cerebrospinal fluid of the brain and describes distinguishing features. Part I features pathological conditions whereas Part II focuses on non-pathological conditions.

Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.

Eating disorders (EDs) have a highly heterogeneous etiology and multiple genetic factors might contribute to their pathogenesis. Ghrelin, a novel growth hormone-releasing peptide, enhances appetite and increases food intake, and human ghrelin plasma levels are inversely correlated with body mass index. In the present study, we examined the 171T/C polymorphism of the ghrelin receptor (growth hormone secretagogue receptor, GHSR) gene in patients diagnosed with EDs, because the subjects having ghrelin gene polymorphism (Leu72Met) was not detected in a Japanese population, previously. In addition, beta3 adrenergic receptor gene polymorphism (Try64Arg) and cholecystokinin (CCK)-A receptor (R) gene polymorphism (-81A/G, -128G/T), which are both associated with obesity, were investigated. The subjects consisted of 228 Japanese patients with EDs [96 anorexia nervosa (AN), 116 bulimia nervosa (BN) and 16 not otherwise specified (NOS)]. The age- and gender-matched control group consisted of 284 unrelated Japanese subjects. The frequency of the CC type of the GHSR gene was significantly higher in BN subjects than in control subjects (chi(2) = 4.47, p = 0.035, odds ratio = 2.05, Bonferroni correction: p = 0.070), while the frequency in AN subjects was not different from that in controls. The distribution of neither beta3 adrenergic receptor gene nor CCK-AR polymorphism differed between EDs and control subjects. Therefore, the CC type of GHSR gene polymorphism (171T/C) is a risk factor for BN, but not for AN.

Dose-dependency of life span prolongation of F344/DuCrj rats injected with (-)deprenyl.

The effect of (-)deprenyl (D) on prolonging survival has previously been reported in different species of animals. In rats, three studies reported a positive effect, while one study reported a shortening of life spans. In the present study, we attempted to clarify past discrepancies in the results based on the speculation that there exists a certain effective dose range for this effect of the drug. F344/DuCrj rats of both sexes began to receive subcutaneous (s.c.) injections of D at the age of 18 months at a dose of 0.25 mg/kg/injection (inj.), 3 times a week. Control animals were given a vehicle (a saline solution). Average life spans of animals (days) were significantly increased in both male (895 +/- 109.7, n=30; 967.8 +/- 88.6, n=30, control vs. D treated, P<0.01, t-test) and female (924.7 +/- 132.2, n=38; 987.1 +/- 133.4, n=39, P<0.05) rats by 8.1% and 6.7%, respectively. We have previously reported that a dose of 0.5mg/kg/inj. (s.c.) significantly increased the life span of male F344 rats, while a dose of 1.0 mg/kg/inj. somewhat shortened the life span, although the difference was not statistically significant. The results of the present study coupled with our previous reports clearly indicate that a proper dose of D within a certain dose range can significantly increase the life span of animals of both sexes, but that a greater dose becomes less effective and may actually adversely affect the life span of rats. The presence of this effective dose range of D may explain discrepancies in the effect of D on life spans of animals previously reported.

Recent trends in pediatric fluid therapy.

Virtually all hospitalized pediatric patients require some form of intravenous fluid administration. The foundation of current pediatric fluid therapy practice was formulated in the 1950s when pediatricians were dealing with relatively simple dehydration and normal homeostasis could largely be assumed. Recent advances in pediatric medicine have resulted in increased severity of illness and normal physiology can no longer be assumed. The traditional approach to pediatric fluid therapy has been recently challenged by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), cerebral salt wasting syndrome (CSWS), diabetic ketoacidosis (DKA) and hyponatremia caused by the inappropriate use of hypotonic solutions, all of which involve unusual sodium and serum osmolarity dynamics causing life threatening central nervous system (CNS) pathophysiology. In this review, we give an overview of the recent understanding of pediatric fluid therapy. The widespread use of acetate in place of lactate as a bicarbonate precursor and the expanding role of nonalbumin plasma expanders in pediatrics are also discussed as they will play a clinical role in the near future.

Role of 5-HT1B receptors in entrainment disorder of Otsuka Long Evans Tokushima fatty (OLETF) rats.

The role of 5-HT1A and 5-HT1B receptors in entrainment function was studied in Otsuka Long Evans Tokushima fatty (OLETF) rats and control Long Evans Tokushima Otsuka (LETO) rats. Light-induced (100 lux, 30 min) Fos expression in the suprachiasmatic nucleus was studied. Light-induced Fos expression was significantly decreased in OLETF rats compared to that in LETO rats. The decrease of light-induced Fos expression in OLETF rats was significantly reversed by pretreatment with the 5-HT1B receptor antagonist, isamoltan (3 mg/kg, i.p.). Simultaneous administration of CGS12066B (5 mg/kg, i.p.), a 5-HT1B agonist, blocked the reversal effect of isamoltan on Fos expression. Fos expression was not changed in LETO rats by pretreatment with isamoltan (3 mg/kg, i.p.). The Fos expression in LETO and OLETF rats was significantly decreased by pretreatment with the 5-HT1A antagonist, WAY-100,635. Phase shifts in locomotor activity paralleled the Fos expression. Light-induced phase shifts of locomotor activity in OLETF rats were significantly smaller than those in LETO rats. The phase shifts were significantly increased by isamoltan (3 mg/kg, i.p.) in OLETF rats. These results suggest that 5-HT1B receptors are involved in the reduced entrainment function of OLETF rats.

MRI in methotrexate-related leukoencephalopathy: Disseminated necrotising leukoencephalopathy in comparison with mild leukoencephalopathy.

We report two fatal cases of methotrexate (MTX)-induced disseminated necrotising leukoencephalopathy (DNL) in which MRI was repeated from the onset. Initial T2-weighted images showed multiple areas of high signal, mainly in deep cerebral white matter, which on follow-up, spread and coalesced to involve the entire white matter. Small irregular low-signal foci on T2-weighted images were seen within the high-signal lesions. Multiple areas of contrast enhancement corresponded to these low-signal foci. The condition of both patients deteriorated and they died. We compared their MRI findings with those of seven patients with mild MTX-related leukoencephalopathy, six of whom were asymptomatic; one had transient neurological symptoms. They showed no contrast enhancement, but rather mild-to-moderate diffuse high signal in deep white matter, which later disappeared. These findings suggest that multiple low-signal foci on T2-weighted images with contrast enhancement may be characteristic of DNL, and that contrast-enhanced imaging is useful to differentiate this condition from mild leukoencephalopathy.

Hepatic artery embolization for postoperative hemorrhage in upper abdominal surgery.

BACKGROUND: The purpose of this study was to evaluate angiographic findings and radiologic and clinical results of transcatheter arterial embolization (TAE) of the hepatic artery for hemorrhage after upper abdominal surgery. METHODS: Ten patients (nine male, one female, mean age = 63.5 years) with postoperative hemorrhage underwent emergency hepatic artery embolization. We retrospectively analyzed the angiographic findings and the effectiveness of TAE. RESULTS: Angiography demonstrated pseudoaneurysms (n = 6) and extravasation (n = 5). Portal veins were not compromised in any patient. The bleeding points were at the gastroduodenal artery (n = 3), proper hepatic artery (n = 3), right hepatic artery (n = 2), left hepatic artery (n = 1), and intrahepatic artery (n = 2). Embolization was performed at the extrahepatic site (n = 6) and intrahepatic site (n = 4). TAE was successful in eight patients. Hemostasis was achieved in eight patients. Two patients in whom TAE was not successful died of bleeding after TAE. In six patients whose collateral arteries were visualized at TAE, hypoxic hepatic failure was avoided and the patients had a favorable clinical course. CONCLUSION: TAE is a useful treatment for postoperative hemorrhage, but the presence of collateral arteries at the time of TAE can affect the patients' prognoses.

Diffusion-weighted magnetic resonance imaging in early stage of 5-fluorouracil-induced leukoencephalopathy.

We report a case of 5-fluorouracil (5-FU)-induced leukoencephalopathy in which magnetic resonance imaging (MRI) of the brain, including diffusion-weighted imaging (DWI), was performed serially. The initial T2-weighted and FLAIR images showed diffuse mild hyperintensity in bilateral deep cerebral white matter and corpus callosum, which on T1WI appeared as non-enhanced faint hypointensity. Isotropic DWI disclosed the abnormality as well-conspicuous diffuse hyperintensity with decreased ADC. Serial studies revealed that majority of the abnormal signal intensity on these sequences resolved, and the decreased ADC values approached normal. Some hyperintensity remained in the deep cerebral white matter and the splenium, but no further significant ADC change after normalization was noted. Measurement of ADC along the three orthogonal directions showed the presence of directional dependence of diffusion throughout the length of study. These findings suggest that early stage of 5-FU-induced leukoencephalopathy is associated with reversible restricted diffusion and preservation of anisotropy. Diffusion-weighted imaging may be useful for the diagnosis.

Effect of intravenous infusion of NIK-716 in anesthetized pediatric patients.

NIK-716 is a maintenance fluid based on the new concept of containing acetate as a base source and 5% glucose as an energy source. It was administered to pediatric patients under general anesthesia for less invasive surgical operations, and its efficacy was investigated by performing blood chemistry examination and urinalysis before and after administration. For efficacy assessment, the three items selected as efficacy parameters, i) the replacement and maintenance of water (assessment of hydration and urine output); ii) the maintenance of serum electrolytes (Na and K); and iii) the utilization of glucose (blood glucose and urinary glucose), were evaluated based on the results of laboratory examination (hematology, blood chemistry and urinalysis), and overall improvement was rated on the basis of total scores of these assessment items. No adverse events or abnormal laboratory values attributable to the maintenance fluid were observed in any of the 25 children administered NIK-716. In an overall improvement rating, NIK-716 proved markedly effective or effective in 79.2% of the 24 children evaluated. The overall safety rating was judged as 'no problem' in all 25 children. These findings suggest that NIK-716 is a useful and safe maintenance fluid that can be administered to pediatric patients during the course of surgery.

Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion: a study in CCK-A receptor knockout mice.

Bile and pancreatic secretions were determined in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. Under the urethane anesthesia, the common bile duct was cannulated, and the mixture of bile-pancreatic juice was collected every 30 min. After the 1 h basal secretion, CCK-8 (0.5 and 1.0 nmol/kg), acetylcholine (500 nmol/kg), and neuromedin C (1.0 micromol/kg) were injected subcutaneously, and the secretions were collected following 1 h. Amylase and bile acid outputs were determined as parameters of pancreatic secretion and gallbladder contraction, respectively. In some CCK-A receptor (+/-) animals, LacZ staining was performed. CCK-8 significantly increased amylase and bile acid outputs in CCK-A receptor (+/+) and (+/-) mice, whereas no response was observed in (-/-) mice. Neuromedin C and acetylcholine increased amylase secretion in CCK-A receptor (-/-) mice similar to (+/-) and (+/+) mice. The same doses of neuromedin C and acetylcholine could not increase bile acid secretion. The gallbladder smooth muscles, pancreatic acinar cells, duct cells, and islets were stained by LacZ. CCK and CCK-A receptor are important for pancreatic secretion and gallbladder contraction. Neuromedin C and acetylcholine may compensate pancreatic function, but not gallbladder contraction.

Analysis of portal venous waveform after living-related liver transplantation with pulsed Doppler ultrasound.

We evaluate the portal venous waveform (PVW) with pulsed Doppler ultrasound (US) after living-related liver transplantation (LRLT) and correlate it with subsequent abnormalities. In the first 2 wk after LRLT, pulsed Doppler US demonstrated three types of PV waveform (PVW) in 33 recipients: non-phasic PVW in 19 patients, pulsatile in 10, and turbulent in 4. In the pulsatile PVW group, arterio-portal (A-P) shunt was confirmed in three grafts by either arteriograhy or computed tomography during hepatic arteriography. A severe stenosis in the grafted vein was confirmed in one case by both US and venography. The pulsatile PVW in the remaining six cases spontaneously disappeared and turned to the non-phasic PVW without treatment. The graft volume/liver standard volume (GV/SV) ratio was significantly smaller in the pulsatile PV waveform group than in the non-phasic PVW group (p<0.01). In the turbulent PVW group, aneurysmal-like dilatation of the portal vein at the umbilical portion was formed in 3 of the 4 patients. The pulsatile waveform in the PV is frequently observed with pulsed Doppler after LRLT, especially in patients that received small grafts. We should keep in mind that they often disappear without any treatment, although some examples of pulsatile waveforms represent vascular complications.

Clinical efficacy of telemedicine in emergency radiotherapy for malignant spinal cord compression.

The authors developed a Telecommunication-HElped Radiotherapy Planning and Information SysTem (THERAPIST), then estimated its clinical benefit in radiotherapy in district hospitals where consultation with the university hospital was required. The system consists of a personal computer with an image scanner and a digital camera, set up in district hospitals and directly connected via ISDN to an image server, and a treatment planning device set up in a university hospital. Image data and consultative reports are sent to the server. Radiation oncologists at the university hospital determine a treatment schedule and verify actual treatment fields. From 1998 to 1999, 12 patients with malignant spinal cord compression (MSCC) were treated by emergency radiotherapy with the help of this system. Image quality, transmission time, and cost benefit also were satisfactory for clinical use. The mean time between the onset of symptoms and the start of radiotherapy was reduced significantly from 7.1 days to 0.8 days (P < .05) by the introduction of the system. Five of 6 nonambulant patients became ambulant after the introduction of THERAPIST compared with 2 of 8 before the introduction of THERAPIST. The treatment outcome was significantly better after the introduction of the system (P < .05), and suggested to be beyond the international standard. The telecommunication-helped radiotherapy and information system was useful in emergency radiotherapy in district hospitals for patients with MSCC for whom consultation with experienced radiation oncologists at a university hospital was required.

Inhibitory effect of somatostatin on cholecystokinin release is independent of luminal cholecystokinin-releasing factor content in conscious rats.

INTRODUCTION: Exclusion of bile-pancreatic juice from the intestine increases pancreatic secretion via cholecystokinin (CCK) release in conscious rats. Luminal CCK-releasing factor (LCRF), purified from rat intestinal secretions, is an intraluminal regulator of CCK secretion during bile-pancreatic juice diversion. AIMS: Because somatostatin is a potent inhibitor of CCK release and pancreatic secretion, the inhibitory effect of somatostatin on LCRF was examined. METHODOLOGY: Rats were prepared with bile and pancreatic cannulae and two duodenal cannulae and with an external jugular vein cannula. The experiments were conducted without anesthesia. After 1.5-hour basal collection of pancreatic juice with bile-pancreatic juice return, bile-pancreatic juice was diverted for 2 hours, during which time somatostatin (2, 10 nmol/kg/h) was infused intravenously. The rats were killed before and 1 and 2 hours after bile-pancreatic juice diversion. To examine the effect of luminal somatostatin, 50 or 200 nmol/kg/h of somatostatin was infused into the duodenum. The plasma CCK and luminal content of LCRF were measured by specific radioimmunoassays. RESULTS: Bile-pancreatic juice diversion significantly increased pancreatic secretion, plasma CCK, and LCRF levels. Intravenous infusion of somatostatin inhibited CCK release and pancreatic secretion, but not LCRF content. Luminal administration of somatostatin did not show any effect. CONCLUSION: Inhibitory effect of circulating somatostatin on CCK release and pancreatic secretion is independent of LCRF content.

Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation.

This study compared pathophysiological and biochemical indexes of acute lung injury in a saline-lavaged rabbit model with different ventilatory strategies: a control group consisting of moderate tidal volume (V(T)) (10-12 ml/kg) and low positive end-expiratory pressure (PEEP) (4-5 cmH(2)O); and three protective groups: 1) low V(T) (5-6 ml/kg) high PEEP, 2-3 cmH(2)O greater than the lower inflection point; 2) low V(T) (5-6 ml/kg), high PEEP (8-10 cmH(2)O); and 3) high-frequency oscillatory ventilation (HFOV). The strategy using PEEP > inflection point resulted in hypotension and barotrauma. HFOV attenuated the decrease in pulmonary compliance, the lung inflammation assessed by polymorphonuclear leukocyte infiltration and tumor necrosis factor-alpha concentration in the alveolar space, and pathological changes of the small airways and alveoli. Conventional mechanical ventilation using lung protection strategies (low V(T) high PEEP) only attenuated the decrease in oxygenation and pulmonary compliance. Therefore, HFOV may be a preferable option as a lung protection strategy.

Diffusion-weighted MR findings in a reversible case of acute Wernicke encephalopathy.

We report a case of acute Wernicke encephalopathy (WE) in which apparent diffusion coefficient maps showed areas of increased diffusion in the bilateral medial thalami that corresponded to the hyperintense lesions on T2-weighted imaging. The hyperintense lesions on T2-weighted imaging disappeared with full recovery from symptoms. These findings suggest that the hyperintense lesions of the acute changes of WE include reversible vasogenic edema and are not caused by acute ischemia.

MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging.

We assessed the utility of fluid-attenuated inversion-recovery (FLAIR) and diffusion-weighted (DWI) images in investigation of tacrolimus (FK-506) encephalopathy, and to see whether we could predict its cause from clinical and imaging data. In seven patients with presumed FK-506 toxicity the areas involved on MRI were similar to those in cyclosporin A (CsA) toxicity. The abnormal signal was most evident on FLAIR in all cases. In three of four patients who underwent DWI, no diffusion abnormalities were detected; in the remaining patient, increased diffusion was seen in the deep white matter bilaterally on the apparent diffusion coefficient map, consistent with the findings on T2-weighted spin-echo and FLAIR images. Five of the six patients for whom we had clinical data showed sudden changes in electrolyte or fluid equilibrium due to diarrhoea, a polyuria or oliguria one day before or on the day of onset of the central nervous system disturbances. We speculate that FK-506 encephalopathy is triggered by the disturbance of the electrolyte and/or fluid equilibrium, given a certain serum level of FK-506.

Effect of Phenyl-P/HEMA acetone primer on wet bonding to EDTA-conditioned dentin.

OBJECTIVES: The purpose of this study was to examine the effect of 2-methacryloyloxyethyl phenyl phosphoric acid (Phenyl-P)/2-hydroxyethyl methacrylate (HEMA) acetone-based primer on moist dentin surfaces that were preconditioned with ethylenediaminetetraacetate (EDTA) to remove the smear layer. METHODS: Bovine dentin were prepared with 180-grit paper, conditioned with 0.5M EDTA (pH 7.4) for 60s followed by water rinsing and then blot drying. Each surface was then primed with Phenyl-P/30 wt% HEMA in acetone for 10s followed by blot drying. A light-cured bonding agent was then applied, cured and trimmed to give dumbbell-shaped specimens. The Phenyl-P concentration ranged from 1 to 20 wt%. During the bonding procedure, no compressed air was used. After storage in water at 37 degrees C for one day, tensile bond strengths were measured and analyzed using one-way ANOVA. Dentin discs treated under the same conditions were observed under a scanning electron microscope (SEM). RESULTS: When the concentration of Phenyl-P was 12 wt%, the highest mean tensile bond strength was obtained (27 MPa). It was significantly higher than that of the 3, 5, 15 or 20 wt% groups (9-11 MPa) (p<0.05). The samples of 1 wt% group were all broken during trimming the dumbbell-shaped specimens. SEM observations showed a 1 microm-thick layer of hybridized dentin after polished cross-sections were chemically challenged with 6N HCl for 30s and then 1% NaOCl for 60 min. SIGNIFICANCE: The experimental Phenyl-P/HEMA acetone primer is effective in bonding resin to EDTA-conditioned dentin. Acetone as a solvent for Phenyl-P/HEMA primer has the clinical advantage of not requiring an air-stream to evaporate the solvent. The experimental bonding procedure can minimize the skin irritation by HEMA.