Eligibility for palivizumab prophylaxis in a cohort of children with severe bronchiolitis

In 2014, the American Academy of Pediatrics (AAP) updated their recommendations for palivizumab prophylaxis for children who are at high risk for severe respiratory syncytial virus (RSV) infection. To investigate the potential impact of the more restrictive 2014 criteria on the eligibility for palivizumab prophylaxis, we applied the 2012 and 2014 AAP recommendations for palivizumab prophylaxis to a multicenter cohort of 2207 US children hospitalized for bronchiolitis. According to the 2012 AAP recommendations, 215 children (9.7%) were eligible for palivizumab prophylaxis, while 140 children (6.3%) would have been eligible based on the 2014 updated recommendations (34.9% relative decrease; 95%CI: 28.5–41.7%). The decrease was largely driven by the restriction of eligibility to preterm infants with gestational age <29 weeks. Further development of and refinement of cost‐effective approaches for the prevention of severe RSV infection are needed.     

Ileal schwannoma developing into ileocolic intussusception

Intussusception is rare in adults. We describe a 47-yearold man with ileal schwannoma that led to ileocolic intussusception. Abdominal ultrasonography, abdominal CT scan and barium enema confirmed an ileal tumor. Colonoscopy revealed a peduncular submucosal tumor （SMT） 75 mm long with an ulcerated apex at the ascending colon. The provisional diagnosis was a gastrointestinal stromal tumor of the terminal ileum. Ileocecal resection was carried out and the tumor was histologically diagnosed as schwannoma. Abdominal pain resolved postoperatively. This case reminds us that ileal schwannoma should be included in the differential diagnosis of intussusception caused by an SMT in the intestine.     

An extramural gastrointestinal stromal tumor of the duodenum mimicking a pancreatic head tumor

We report the case of a 53‐year‐old woman with a gastrointestinal stromal tumor (GIST) of the duodenum that showed only extramural growth, mimicking a pancreatic tumor. Preoperatively, computed tomography (CT) and angiography revealed a hypervascular mass, 3.0 cm in diameter, in the pancreatic head. Hypotonic duodenography showed compression of the second and third portions of the duodenum by the pancreatic lesion. Endoscopic examination showed no specific mucosal abnormalities in the duodenal lumen. The pancreatic head tumor was diagnosed preoperatively as a nonfunctioning islet cell tumor of the pancreas, and the patient underwent pylorus‐preserving pancreaticoduodenectomy. A hard mass was palpated intraoperatively in the pancreatic head region, and neither peritoneal dissemination nor metastasis was detected. Histologically, the tumor was composed of spindle‐shaped cells with a fascicular growth pattern, and only a few mitotic features were seen. Immunohistochemically, most of the tumor cells were positive for c‐kit oncoprotein and CD34, but negative for alpha‐smooth muscle actin and S‐100 protein. Therefore, this neoplasm was finally diagnosed as a duodenal GIST of the uncommitted type. This is a rare case of a duodenal GIST with exclusively extramural growth mimicking a pancreatic head tumor.     

Efficient protective activity of a planar catechin analogue against radiation-induced apoptosis in rat thymocytes

About two thirds of biological damage due to low linear energy transfer (LET) radiation, such as X-rays and the plateau region of heavy-ion beams, is known to be caused by the hydroxyl radical (˙OH), the most powerful reactive oxygen species (ROS), generated via ionisation and excitation of water molecules. Thus, compounds having an efficient scavenging activity against ROS are expected to exhibit a radioprotective activity. A planar catechin analogue, where an isopropyl fragment was introduced into the catechol ring of (+)-catechin, showed an efficient protective effect against X-ray induced apoptosis in rat thymocytes compared to (+)-catechin. The planar catechin scavenged 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH˙) solubilised in water by β-cyclodextrin about 10-fold faster than (+)-catechin in phosphate buffer (0.1 M, pH 7.4) at 298 K. Furthermore, the experimental log P value of the planar catechin (1.22) is reported to be significantly larger than that of (+)-catechin (0.44). The higher radical-scavenging activity and lipophilicity of the planar catechin than those of (+)-catechin may contribute in part to the higher protective activity against X-ray-induced apoptosis in rat thymocytes.

A planar catechin analogue showed a significant higher protective activity against X-ray induced apoptosis in rat thymocytes than (+)-catechin.     

Mid‐term results of bariatric surgery in morbidly obese Japanese patients with slow progressive autoimmune diabetes

Introduction

Bariatric surgery is recognized as an effective treatment for type 2 diabetes mellitus, but data on its efficacy for type 1 diabetes mellitus, especially slowly progressive insulin‐dependent diabetes mellitus, are limited.

Methods

We investigated five Japanese patients with slowly progressive insulin‐dependent diabetes mellitus who underwent bariatric surgery at our center.

Results

Five morbidly obese glutamic acid decarboxylase antibody‐positive diabetic patients underwent two different types of bariatric surgery. The mean titer of anti‐glutamic acid decarboxylase antibody was 4.6 U/mL, and the mean preoperative bodyweight and BMI were 113 kg and 39.6 kg/m², respectively. The mean hemoglobin A1c was 8.4%. The mean fasting serum C‐peptide was 5.0 ng/mL. Laparoscopic sleeve gastrectomy was performed in two patients, while laparoscopic sleeve gastrectomy with duodenojejunal bypass was performed in three patients. At one year after surgery, the mean bodyweight and BMI significantly dropped, and the mean percentage of excess weight loss was 96.4%. The mean hemoglobin A1c was 5.7%. This favorable trend was maintained at mid‐term.

Conclusion

Bariatric surgery for morbidly obese patients with anti‐glutamic acid decarboxylase antibody–positive type 1 diabetes mellitus, especially slow progressive autoimmune diabetes, seemed effective in achieving mid‐term glycemic control. Longer follow‐up with a larger number of patients, as well as validation with more advanced patients with slowly progressive insulin‐dependent diabetes mellitus, will be needed.

     

Knee joint angle and vasti muscle electromyograms during fatiguing contractions

We compared vasti muscle electromyograms for two knee joint angles during fatiguing tetanic contractions. Tetanic contraction of the knee extensors was evoked for 70 s by electrical stimulation of the femoral nerve at knee joint angles of 60° (extended, with 0° indicating full extension) and 110° (flexed) in eight healthy men. Surface electromyography was recorded from the vastus intermedius (VI), vastus lateralis (VL) and vastus medialis (VM) muscles. Knee extension force and M‐wave amplitudes and durations were calculated every 7 s, which were normalized by the initial value. Normalized knee extension force was decreased at the flexed knee joint angle compared with that of the extended knee joint angle (P<0·05). Decreased normalized M‐wave amplitude and increased normalized M‐wave duration of the VI were greater at the flexed knee joint angle than the extended knee joint angle (P<0·05), whereas those for the VL and VM were similar (P>0·05). These results suggest that peripheral fatigue profiles of the VI might be greater at the flexed than the extended knee joint angles, but that of VL and VM might be similar in the tested range of knee joint angles (i.e. 60°–110°) during continuous tetanic contraction induced by electrical stimulation. Therefore, greater reduction of knee extension force at the flexed knee joint angle than the extended knee joint angle may reflect fatigue development of the VI more than other quadriceps femoris components.     

Evaluation of the cell survival curve under radiation exposure based on the kinetics of lesions in relation to dose-delivery time

We have investigated the dose rate effects on cell damage caused by photon-beam irradiation. During a relatively long dose-delivery time with a low dose rate, lesions created in cells may undergo some reactions, such as DNA repair. In order to investigate these reactions quantitatively, we adopted the microdosimetric–kinetic (MK) model and deduced a cell surviving fraction (SF) formula for continuous irradiation. This model enabled us to estimate the SF from dose and dose rate. The parameters in the MK model were determined so as to generate the SF, and we attempted to evaluate the dose rate effects on the SF. To deduce the cell-specific parameters in the SF formula, including the dose rate, we performed a split-dose experiment and a single-dose experiment with a constant dose-delivery time (10 min) (to retain the condition for equivalent behavior of cell lesions) by means of a clonogenic assay. Then, using the MK model parameters, the SFs were reproduced for a variety of dose rates (1.0, 0.31, 0.18, 0.025 and 0.0031 Gy/min) and were compared with reported experimental data. The SF curves predicted by the MK model agreed well with the experimental data, suggesting that the dose rate effects appear in the kinetics of cell lesions during the dose-delivery time. From fitting the analysis of the model formula to the experimental data, it was shown that the MK model could illustrate the characteristics of log-SF in a rectilinear form at a high dose range with a relatively low dose rate.     

Rapidly progressive sarcomatoid malignant mesothelioma of the pleura mimicking pulmonary empyema

Refractory empyema occasionally reflects hidden malignant disease. We presented a rare case of rapidly progressive malignant mesothelioma of the pleura (MPM) mimicking empyema. Physicians should be aware of MPM when patients with empyema are refractory to the standard treatment, and PET‐CT may be helpful in establishing a precise diagnosis in such cases.     

κ Opioid receptor ligands regulate angiogenesis in development and in tumours

Opioid systems mainly regulate physiological functions such as pain, emotional tone and reward circuitry in neural tissues (brain and spinal cord). These systems are also found in extraneural tissues (ganglia, gut, spleen, stomach, lung, pancreas, liver, heart, blood and blood vessels), and recent studies have elucidated their roles in various organs. The current review focuses on the roles of opioid systems in blood vessels, especially angiogenesis, during development and tumour malignancy. The balance between endogenous activators and inhibitors of angiogenesis delicately maintains a normally quiescent vasculature to sustain homeostasis. Disturbance of this balance causes pathogenic angiogenesis and, especially in tumours, several activators such as VEGF are highly expressed in the tumour microenvironment and strongly induce tumour angiogenesis, the so-called angiogenic switch. Recently, we demonstrated that κ opioid receptor agonists function as anti-angiogenic factors, which impede the angiogenic switch, in vascular development and tumour angiogenesis by inhibiting the expression of receptors for VEGF. In clinical medicine, angiogenesis inhibitors that target VEGF signalling such as bevacizumab are used as anti-cancer drugs. Although therapies that inhibit tumour angiogenesis have been highly successful for tumour therapy, most patients eventually develop resistance to this anti-angiogenic therapy. Thus, we must identify novel targets for anti-angiogenic agents to sustain inhibition of angiogenesis for tumour therapy. The regulation of responses to κ opioid receptor ligands could be useful for controlling vascular formation under physiological conditions and in cancers, and thus could offer therapeutic benefits beyond the relief of pain.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2