Nerve mediated responses to drugs and electrical stimulation in aganglionic muscle segments in Hirschsprung's disease

The activity of isolated muscle strips from normal and aganglionic human large bowel was studied in vitro. The intrinsic nerves were stimulated electrically and by nicotinic agonists. The ganglionic preparations displayed a strong inhibitory response due to the release of both norepinephrine and a noncholinergic, nonadrenergic inhibitory neurotransmitter. In the aganglionic strips (obtained from patients with Hirschsprung's disease), nerve activation tended to evoke contraction, apparently due to enhancement in the release of acetylcholine. At the same time, the release of norepinephrine appeared to be less than normal. A particularly interesting finding in the aganglionic muscle strips was the presence of a substantial inhibitory response due to the release of a noncholinergic, nonadrenergic substance. These results provide further evidence for the importance of the innervation of the aganglionic segment in Hirschsprung's disease.     

Hospital readmission rates and risk factors for readmission following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies

Background

Cytoreductive surgery and Hyperthermic intra-peritoneal chemotherapy (CRS/HIPEC) for peritoneal surface malignancies is associated with high morbidity. The increased numbers of patients undergoing CRS/HIPEC in recent years mandates risk analysis and quality assurance. However, only scarce data exist regarding causative parameters for readmission.The aim of this study was to assess readmission rates and risk factors associated with readmission.

Radiotherapy for Patients with Cardiovascular Implantable Electronic Devices: A Review

Because cardiovascular implantable electronic devices are increasingly indicated in older patients, and the burden of cancer is rising with the growth and aging of the world population, the management of patients with cardiac devices who require radiotherapy for cancer treatment is a timely concern. Device malfunctions might occur in as high as 3% of radiotherapy courses, posing a substantial issue in clinical practice. A nonsystematic comprehensive review was undertaken. We searched PubMed and the MEDLINE database for randomized controlled trials, meta-analyses, systematic reviews, observational studies, in vitro/in vivo studies, and case reports. Articles were selected by 2 independent reviewers, and emphasis was given to information of interest to a general medical readership. The pathophysiology and predictors of cardiovascular implantable electronic device malfunction due to radiotherapy are reviewed, recommendations for the management of patients with such devices undergoing radiotherapy are summarized, and the clinical significance and future directions of this field are discussed. Radiotherapy-induced device malfunctions are rare, but because of the potential complications, the development of evidence-based guidelines for the management of patients with cardiovascular implantable electronic devices undergoing radiotherapy is a timely concern.     

Biomechanics and functional distortion of the human mandible

The reaction to the use of finite element analysis (FEA) in the study of the human body has been particularly enthusiastic. Of equal and challenging complexity is the investigation of load/stress distribution and morphological distortion of the human mandible under functional loads. Furthermore, the mandible also impacts directly on body function and esthetics, playing a vital role, such as mastication and speech. The application of FEA to the biomechanical investigation of the oral systems, such as human teeth and mandibular bone remodeling, began in the early 1970s. The clinical significance of jaw deformation is unknown. The primary concern is that deformation might result in an ill‐fitting superstructure or the creation of harmful strains in the patient–implant complex. Although mandibular implant treatment has a high success rate, the possibility of failure caused by these dimensional changes and the related micromotion cannot be ignored.     

Intestinal absorption of low molecular weight heparin in animals and human subjects

INTRODUCTION: We had previously shown that the use of bile salts, which act as surfactants, facilitates the intestinal absorption of large molecules such as those of heparin and insulin. However, the bioavailability of unfractionated heparin (UFH) administered through the large intestine was low. The aim of the present study was to evaluate the absorption of low molecular weight heparin (LMWH) combined with bile salts through the gut mucosa in animals and human subjects. MATERIALS AND METHODS: LMWH (Fragmin, Kabi-Pharmacia, Stockholm) or UFH with or without sodium cholate (Sch) was administrated rectally in rats and healthy volunteers via a microenema. Absorption was estimated by the activated partial thromboplastin time (aPTT), the plasma anti-factor Xa activity and the plasma lipoprotein lipase (LPL) activation. RESULTS: In groups of 6 rats, LMWH at doses of 100--1,000 U with sodium cholate (10--20 mg/ml) was readily absorbed through the gut mucosa, as indicated by both, anti-factor Xa levels of up to 1 U/ml and a dose-dependent activation of LPL. The absorption was significantly superior to that of UFH with Sch or LMWH given without Sch (p < 0.001). The plasma anti-factor Xa levels in the 6 healthy volunteers who received a microenema containing 25,000 U of LMWH with 20 mg/ml of Sch were 0.38 U/ml at 15 min and 0.1 U/ml at 240 min. LPL activation and aPTT prolongation were also observed in these subjects. The plasma LMWH levels after rectal application were in the same range as those obtained after subcutaneous administration, however the elimination time (t 1/2) was shorter. There were no adverse reactions. CONCLUSIONS: Intestinal absorption of LMWH facilitated by Sch is both feasible and safe. A slow release formulation will be needed to prolong the plasma half-life.