A comparison of gastric emptying of soluble solid meals and clear fluids matched for volume and energy content: a pilot crossover study.

We previously demonstrated that the gastric emptying time of different liquids with the same volume mainly depended on their energy content, regardless of differences in composition. In this crossover study, we investigated whether the same applies when soluble solid foods are ingested with water. Ten healthy volunteers ingested one of five test diets consisting of two test meals (Calorie Mate® 100 and 200 kcal) and three test solutions (water and glucose solutions of 100 and 200 kcal), each given in a volume of 400 ml, and then underwent ultrasonography to measure the gastric antral cross-sectional area every 10 min for 120 min. The gastric emptying time was defined as the time for the antral cross-sectional area to revert to its initial value. When test diets with the same energy content were ingested, the gastric emptying curves were nearly identical, regardless of whether the original form was solid or liquid. The median (IQR[range]) gastric emptying times of Calorie Mate® of 100 kcal with water vs. isocaloric glucose solution were 65 (60-78 [50-80]) vs. 65 (60-70 [50-80]) min (p = 0.58), and for Calorie Mate® of 200 kcal with water vs. isocaloric glucose solution they were 100 (93-108 [90-120]) vs. 105 (90-110 [90-120]) min (p = 0.54). The median (IQR [range]) for water was 40 (30-40 [30-50]) min. Energy content may be a critical determinant of the gastric emptying time when ingesting soluble solid diets with water.

Characterization of SPATA5-related encephalopathy in early childhood.

Mutations in SPATA5 have recently been shown to result in a phenotype of microcephaly, intellectual disability, seizures, and hearing loss in childhood. Our aim in this report is to delineate the SPATA5 syndrome as a clinical entity, including the facial appearance, neurophysiological, and neuroimaging findings. Using whole-exome sequencing and Sanger sequencing, we identified three children with SPATA5 mutations from two families. Two siblings carried compound heterozygous mutations, c.989_991del (p.Thr330del) and c.2130_2133del (p.Glu711Profs*21), and the third child had c.967T>A (p.Phe323Ile) and c.2146G>C (p.Ala716Pro) mutations. The three patients manifested microcephaly, psychomotor retardation, hypotonus or hypertonus, and bilateral hearing loss from early infancy. Common facies were a depressed nasal bridge/ridge, broad eyebrows, and retrognathia. Epileptic spasms or tonic seizures emerged at 6-12 months of age. Interictal electroencephalography showed multifocal spikes and bursts of asynchronous diffuse spike-wave complexes. Augmented amplitudes of visually evoked potentials were detected in two patients. Magnetic resonance imaging revealed hypomyelination, thin corpus callosum, and progressive cerebral atrophy. Blood copper levels were also elevated or close to the upper normal levels in these children. Clinical delineation of the SPATA5-related encephalopathy should improve diagnosis, facilitating further clinical and molecular investigation.

Determinants of liquid gastric emptying: comparisons between milk and isocalorically adjusted clear fluids.

BACKGROUND: Although current preoperative fasting guidelines apply restrictions to drinks containing milk because of delayed gastric emptying, the safe volume of milk that can be consumed up to 2 h before surgery on a theoretical basis has not yet been defined. We aimed to determine whether delayed gastric emptying depended mainly on the total amount of calories irrespective of compositional differences between milk and clear fluids. METHODS: We prepared five beverages with a uniform volume (500 ml) and step-wise increments in calories (0, 220, and 330 kcal), comprised mainly of non-human milk, pulpless orange juice, water, and gum syrup. The gastric emptying rate of each beverage was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by eight healthy fasting volunteers. RESULTS: The emptying rates of 500 ml of orange juice and 330 ml of non-human milk with 170 ml of water (both were 220 kcal) from the stomach were similar. Furthermore, 450 ml of orange juice with 50 ml of gum syrup and 500 ml of non-human milk (both were 330 kcal) left the stomach at similar rates. The 220 kcal beverages emptied faster than the 330 kcal beverages. CONCLUSIONS: There were no significant differences in liquid gastric emptying after drinking equal volumes of either orange juice or milk as long as both had the same amount of calories. Liquid gastric emptying depends chiefly on the total caloric content. CLINICAL TRIAL REGISTRATION: UMIN000012537.

Computerized method for estimation of the location of a lung tumor on EPID cine images without implanted markers in stereotactic body radiotherapy.

The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 x 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s(-1) by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 +/- 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

Cytokine-related and sodium channel polymorphism as candidate predisposing factors for childhood encephalopathy FIRES/AERRPS.

Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B, IL6, IL10, TNFA, IL1RN, SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN, the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls (p=0.0067), and A allele at rs4251981 in 5' upstream of IL1RN with borderline significance (p=0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40-10.8, p=0.0057). For SCN1A, no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A, the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance (p=0.011). We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.

A point mutation within each of two ATP-binding motifs inactivates the functions of elongation factor 3.

We have investigated how point mutations in the two ATP-binding motifs (G(463)PNGCGK(469)ST and G(701)PNGAGK(707)ST) of elongation factor 3 (EF-3) affect ribosome-activated ATPase activity of EF-3, polyphenylalanine synthesis, and growth of Saccharomyces cerevisiae. The point mutation impaired the ribosome-activated ATPase activity of EF-3, when glycine(463 and 701) and lysine(469 and 707) were replaced with valine and arginine, respectively. Thus, each glycine and lysine residue in both ATP-binding motifs is indispensable for EF-3's binding with ATP and the ensuing generation of ribosome-activated ATPase activity. Additionally, the mutant EF-3s did not catalyze polyphenylalanine synthesis in vitro when each glycine(463 and 701) was replaced with valine. The mutant EF-3s did not support cell growth in TEF3-disrupted S. cerevisiae, when each lysine(469 and 707) and glycine(463) was replaced with arginine and valine, respectively. Thus, each of the two ATP-binding motifs of EF-3 is indispensable for the ribosome-activated ATPase activity of EF-3, which is required for protein synthesis and cell growth in S. cerevisiae.

Effect of aldose reductase inhibitor ONO 2235 on reduced sympathetic nervous system activity and peripheral nerve disorders in STZ-induced diabetic rats.

To test the hypothesis that inhibitors of aldose reductase, a key enzyme for polyol synthesis, prevent the decrease of sympathetic nervous system (SNS) activity and improve motor nerve conduction velocity (MNCV) through the reduction of sorbitol accumulation in streptozocin (STZ)-induced diabetic rats, norepinephrine (NE) turnover (reliable indicator of SNS activity in the interscapular brown adipose tissue (IBAT), heart, and pancreas), and MNCV were measured in untreated STZ-induced diabetic rats, STZ-induced diabetic rats treated with an aldose reductase inhibitor (ARI) (ONO 2235, 50 mg X kg-1 X day-1, orally), STZ-induced diabetic rats treated with insulin therapy, control rats, and control rats treated with ARI. As expected, results from studies with the inhibition of NE biosynthesis with alpha-methyl-p-tyrosine or radiolabeled NE to measure NE turnover demonstrated significant reductions in SNS activity in IBAT, heart, and pancreas of untreated STZ-induced diabetic rats, compared with those in control rats. MNCV determined with the tail nerve was significantly reduced in untreated STZ-induced diabetic rats, compared with that of the controls. Both daily ARI treatment and insulin therapy in STZ-induced diabetic rats prevented partially but significantly the decrease of NE turnover in IBAT, heart, and pancreas, ameliorated MNCV, and reduced sorbitol accumulation in the nerve tissue and red blood cells. ARI treatment in control rats had no effect on NE turnover, MNCV, or sorbitol content. These results suggest that STZ-induced diabetic rats had not only motor neuropathy but also sympathetic nervous dysfunction and that ARI treatment might prevent these as well as insulin therapy does through the reduction of sorbitol accumulation.

Expression of non-hepatic-type S-adenosylmethionine synthetase isozyme in rat hepatomas induced by 3'-methyl-4-dimethylaminoazobenzene.

It is known that a high incidence of hepatocellular carcinoma in rat liver can be induced by such azo dye carcinogens as 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). Mammalian S-adenosylmethionine (AdoMet) synthetase exists as two isozymes, non-hepatic-type and liver-type enzymes, which are the products of two different genes. We have examined the expression of two AdoMet synthetase isozyme proteins and mRNAs in rat hepatomas induced by 3'-Me-DAB. The levels of non-hepatic-type enzyme protein and mRNA are clearly induced by 3'-Me-DAB feeding. On the other hand, the levels of liver-type enzyme protein and mRNA are nearly the same or slightly decreased during hepatocarcinogenesis. These results indicate that the expression of the non-hepatic-type isozyme gene is obviously influenced with the progression of carcinogenesis and that the non-hepatic-type isozyme is useful as a oncodevelopmental marker in the liver.

Effects of prostaglandin on experimental bone malignancy and on scintigrams of bone and marrow.

The correlation between prostaglandin E (PgE) and scintigrams of bone (Tc-99m MDP) and bone marrow (Tc-99m SC) was investigated in normal and VX-2-bearing rabbits. PgE in plasma of normal rabbits was 486.2 +/- 185.7 pg/ml (n = 86) and the maximum-to-minimum (max/min) ratio was 1.85 +/- 0.26 at 4 wk after tumor implantation. In rabbits with VX-2 transplanted into femoral muscles, PgE was in the normal range unless the tumor invaded bone. PgE did not increase significantly in rabbits when the tumor was transplanted into the marrow cavity. When tumor invaded bone, PgE increased markedly (to 1335 +/- 584 pg/ml). Elevation of PgE did not necessarily coincide with the appearance of positive bone scans. PgE in an indomethacin-treated group was not higher than in the untreated group. There was no significant difference between the two groups regarding the time of appearance of abnormal bone scans. However, when the number of transplanted cells in the bone marrow was reduced, the treatment with indomethacin delayed the increase in tracer uptake in the affected bone and resulted in a photon-deficient area. Indomethacin may suppress the local acceleration of calcium metabolism.

Radiotherapy after hyperbaric oxygenation for malignant gliomas: a pilot study.

The results of radiotherapy combined with hyperbaric oxygen in 9 patients with malignant glioma were compared with those of radiotherapy without hyperbaric O2 in 12 patients. This is the first report of a pilot study of irradiation immediately after exposure to hyperbaric O2 in humans. All patients receiving this treatment showed more than 50% regression of the tumor, and in 4 of them, the tumors disappeared completely. Only 4 out of 12 patients without hyperbaric O2 showed decreases in tumor size, and all 12 patients died within 36 months. So far, this new regimen seems to be a useful form of radiotherapy for malignant gliomas.

Identification of neuropeptide-degrading enzymes in the pancreas.

Neutral endopeptidase (NEP) and aminopeptidase M (APM) were identified in the pancreas by enzymatic assays and Western blotting. The NEP activity, assessed by the phosphoramidon- and DL-thiorphan-inhibitable degradation of glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamine, was 28.8 pmol/h/micrograms of pancreatic membrane protein and 124 pmol/h/10(6) pancreatic acinar cells. The APM enzymatic activity, assessed by the actinonin- and amastatin-inhibitable degradation of Ala-4-methoxy-2-naphthylamine, was 633 pmol/h/micrograms pancreatic membrane protein and 17.4 nmol/h/10(6) pancreatic acinar cells. Proteins corresponding to NEP (95 kDa) and APM (140 kDa) were identified in membranes by Western blotting. Both NEP and APM on acinar cells may degrade neuropeptides and regulate their effects on exocrine secretion.

Esophageal carcinoma with nonrecurrent inferior laryngeal nerve.

Occurrence of a nonrecurrent inferior laryngeal nerve is quite rare. We present the case of a 70-year-old man with carcinoma of the esophagus. An abnormal right subclavian artery was detected preoperatively. This anomaly suggested that the right inferior laryngeal nerve branched directly from the vagal trunk. A carcinoma of the esophagus was resected, and lymph nodes were dissected. The right inferior laryngeal nerve was fully preserved, and the esophagus was primarily repaired.

Effects of cholecystokinin and gastrin antagonists on pancreatic exocrine secretion stimulated by gastrin-releasing peptide.

The effects of a specific cholecystokinin (CCK) receptor antagonist (L364,718) and a gastrin receptor antagonist (L365,260) on gastrin-releasing peptide-10 (GRP-10)-stimulated pancreatic secretion were investigated in the anesthetized rat. GRP-10 stimulated pancreatic exocrine secretion in a dose-dependent manner. A dose of 1.0 nmol/kg/h elicited a significant increase in pancreatic protein output. L364,718 (2.0 mg/kg/h), at a dose that completely inhibited the stimulatory effect of exogenous CCK-8 (3.0 nmol/kg/h) on pancreatic secretion, did not suppress the excitatory effect of GRP-10. L365,260 (5.0 mg/kg/h), at a dose that completely inhibited the stimulatory effect of exogenous gastrin (20 micrograms/kg/h) on gastric acid secretion, did not suppress the excitatory effect of GRP-10 either. We concluded that CCK or gastrin do not mediate the excitatory mechanism of bombesin/GRP on pancreatic secretion. Since CCK and gastrin are the most probable candidates for excitatory mediator of bombesin/GRP, these results support the hypothesis that bombesin/GRP directly stimulates the exocrine pancreas in the rat.

Purification and characterization of aminopeptidase M from muscle and mucosa of the pig intestine.

The aim of this investigation was to purify aminopeptidase M (APM) from the muscle layer of the small intestine, to compare it with APM of the mucosa and kidney, and to examine the degradation of gastrointestinal neural and hormonal peptides by muscle APM. APM was purified from the muscle and mucosa of the pig small intestine by DEAE-Sepharose and immuno-affinity chromatography. The specific activity of APM from muscle, mucosa, and kidney was 3900, 3000, and 3800 nmol/min per mg protein, respectively (substrate [Leu5]enkephalin). Muscle and mucosa APM contained four protein bands with apparent molecular weights of 150, 110, 73, and 52 kDa. Kidney APM contained three protein bands of 150, 110, and 56 kDa. The 150, 110, and 52/56 kDa bands cross-rected with an APM antiserum. APM from each tissue degraded [Leu5]enkephalin and [Met5]enkephalin, but not cholecystokinin-8, gastrin releasing peptide-10, somatostatin-14, substance P, and vasoactive intestinal peptide. The enzymes were identically inhibited by APM antiserum, amastatin, bestatin, actinonin, and 1, 10 phenanthroline. Non-mucosal APM may degrade enkephalins and terminate their biological actions.

Enhanced absorption of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets for colon-specific drug delivery.

The objective of this study was to estimate colon-specific delivery of insulin and (Asu(1,7))eel-calcitonin using novel azopolymer-coated pellets. In vitro drug-release experiments from the azopolymer-coated pellets containing fluorescein isothiocyanate dextran (MW 4400; FD-4) were carried out by the Japanese Pharmacopoeia (J.P.) XIII rotating basket method with some slight modifications. Little release of FD-4 from the pellets was observed in phosphate buffered saline. However, the release of FD-4 was markedly increased in the presence of rat cecal contents. The intestinal absorption of insulin and (Asu(1,7))eel-calcitonin after oral administration of the azopolymer-coated pellets containing these peptides with camostat mesilate was evaluated by measuring the hypoglycemic and hypocalcemic effects, respectively. A slight decrease in plasma glucose levels was observed following the oral administration of these pellets containing 12.5 IU of insulin compared with the same dose of insulin solution. Camostat mesilate, a protease inhibitor that is incorporated with insulin in these pellets, further decreased the plasma glucose levels in a dose-dependent manner. Similar results were also obtained with the oral administration of pellets containing (Asu(1,7))eel-calcitonin. These findings suggest that azopolymer-coated pellets may be useful carriers for the colon-specific delivery of peptides including insulin and (Asu(1,7))eel-calcitonin.

Apolipoprotein C-II modifications associated with an infusion of artificial lipid particles.

Artificial lipid particles used as parenteral nutrition solution do not contain any apolipoproteins when they are infused into the circulation. Despite the absence of apolipoproteins, the metabolism of artificial lipid particles is similar to that of chylomicrons which contain various kinds of apolipoprotein. Of the known apolipoproteins, apolipoprotein C-II (apo C-II) is important in the hydrolysis of triglyceride-rich lipoproteins via involvement in the activation of lipoprotein lipase. Modifications of apo C-II associated with intravenous infusion of a lipid emulsion were investigated in eight patients. Changes in apo C-IIs in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) together with the plasma level of triglycerides, were quantified before and for 90 min after a bolus injection of a 10% lipid emulsion (1 ml/kg of body weight). Immediately prior to the injection, 54% of the total amount of apo C-II was present in HDL, while 27% was present in VLDL. After 5 to 10 min, the amount of apo C-II in HDL decreased to 29% of the total, while that in VLDL increased to 62%. Subsequently, the amounts of apo C-II in HDL and VLDL began to return to the preinjection levels. These variations in apo C-II were closely correlated with the plasma clearance of triglyceride. The result indicates that the injected lipids are not inert particles during their short intravascular life, but that they acquire apo C-II from HDL.

Non-Hodgkin lymphoma and coexisting primary cancers: a retrospective clinical analysis of 10 patients.

The simultaneous occurrence of non-Hodgkin lymphoma (NHL) and primary cancers is rare, and the treatment strategy for both malignancies is unclear. The authors analyzed the clinical records of 10 patients with NHL and coexisting primary cancers. All patients initially had symptoms of NHL, and all carcinomas were found at the initial workup of NHL by chance. The most common primary sites of coexisting cancers were the stomach (six patients) and the colon (two). Histologically, the majority of NHLs were intermediate grade, and all lesions were B-cell type. All primary cancers were adenocarcinoma. Initially, NHL was treated with radiotherapy or chemotherapy. Six primary cancers were resected surgically or endoscopically after the remission of NHL. The remaining four patients received no treatment for primary cancers because of advanced stages or early relapse of NHL. Three patients died of NHL, one died of cancer, and six were still alive, five without evidence of disease and one with disease. The authors conclude that early detection of a coexisting cancer and appropriate treatment after the remission of NHL may increase the possibility of a cure.

Colon-specific delivery of budesonide with azopolymer-coated pellets: therapeutic effects of budesonide with a novel dosage form against 2,4,6-trinitrobenzenesulphonic acid-induced colitis in rats.

The objective of this study was to achieve colon-specific delivery of budesonide using azopolymer-coated pellets and to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. After oral administration of azopolymer-coated pellets containing budesonide, a significant increase was observed in the therapeutic effects of the drug accompanied by a decrease in its systemic adverse effects when compared with oral administration in saline or rectal administration by enema. In addition, with the use of the colon-specific oral dosage form the dose of budesonide could be reduced. These results suggested that azopolymer-coated pellets may be a useful dosage form for the colon-specific delivery of budesonide as an anti-inflammatory steroid drug to bring about the healing of TNBS-induced colitis in rats.

A case of cystic lymphangioma extending from the neck to the tongue. Management of the lesion remaining after surgery.

A case of cystic lymphangioma in a child is reported. The lesion extended bilaterally from the neck to the tongue. Complete removal of the tumour in the floor of the mouth and the tongue was impossible. Later, swelling in these regions caused dyspnoea. The residual lesion was treated by external irradiation (60 Co total dose of 30 Gy). During a three-year follow-up period, no recurrence of the swelling, respiratory distress, or side-effects of radiation were observed.