Effects of the tip structure of temporary indwelling catheters on blood recirculation at various blood flow rates and diameters of the mock blood vessel.

AIMS: The aim of the present study was to determine the effects of the tip structure of the catheters used for hemodialysis on blood recirculation at varying blood flow rates and diameters of the mock blood vessel in a well-defined in vitro experimental system, focusing on reverse connection mode. METHODS: A mock circulatory circuit was created with silicon tubing (15 or 20 mm), a circulatory pump, connected through the catheter to dialysis circuit and dialyzer attached to dialysis machine. The tip of the inserted catheter was fixed to the center of the silicone tube, and 3 L of pig blood was poured into the blood side of the dialyzer and the recirculation rates were measured at blood flow rates of 100, 150, and 200 mL/min. Five types of commercially available catheters were used: (A) Argyle™, (B) Gentle Cath™ (Hardness gradient type), (C) Gentle Cath™, (D) Niagara™, and (E) Power-Trialysis®. RESULTS: In the case of reverse connection mode, (1) the recirculation rates were lower in the catheter with a relatively large side hole (catheter C, 17%), catheters with a greater distance between the end hole and side hole (catheters C and D, 25%), and catheter with a symmetrical tip structure (catheter E, 10%) as compared with those in catheters A and B (40% and 25%); (2) increase of the blood flow rate in the dialysis machine was associated with a reduced recirculation rate; and (3) a wider inner diameter of the mock blood vessel and faster flow rate in the vessel were associated with a reduced recirculation rate. CONCLUSION: The lowest recirculation was observed with the catheter with symmetrical holes, which produces a helical blood flow line that does not intersect with the blood streamline flowing out to the blood supply hole.

Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies.

Corpus callosum anomalies (CCA) is a common congenital brain anomaly with various etiologies. Although one of the most important etiologies is genetic factors, the genetic background of CCA is heterogenous and diverse types of variants are likely to be causative. In this study, we analyzed 16 Japanese patients with corpus callosum anomalies to delineate clinical features and the genetic background of CCAs. We observed the common phenotypes accompanied by CCAs: intellectual disability (100%), motor developmental delay (93.8%), seizures (60%), and facial dysmorphisms (50%). Brain magnetic resonance imaging showed colpocephaly (enlarged posterior horn of the lateral ventricles, 84.6%) and enlarged supracerebellar cistern (41.7%). Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs. This study, which analyzes CCA patients usung whole exome sequencing, demonstrates that comprehensive genetic analysis would be useful for investigating various causal variants of CCAs.

Clinical and genetic characteristics of patients with Doose syndrome.

OBJECTIVE: To elucidate the genetic background and genotype-phenotype correlations for epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy (MAE) or Doose syndrome. METHODS: We collected clinical information and blood samples from 29 patients with MAE. We performed whole-exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant. RESULTS: We newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic-atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention-deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology. SIGNIFICANCE: MAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic-atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.

Dermatologically challenging syphilis presentation.

An atypical early primary syphilis case presentation with multiple umbilicated papular lesions on the penis and a nonreactive syphilis serology was misdiagnosed as molluscum contagiosum. Over a period of eight weeks, prior to dermatologic consultation, the papules enlarged, ulcerated, and healed. New plaque and patch formation on the penis and scrotum led to a differential diagnosis of inverse psoriasis vs. syphilis. Histological examination of a shave biopsy specimen revealed numerous Treponema pallidum organisms and repeat syphilis serological test results confirmed a syphilis diagnosis. Lesions responded to treatment with benzathine penicillin. One must keep a high index of suspicion for syphilis in light of its diverse presentation and increasing incidence.

Continuous hemofiltration model using porcine blood for comparing filter life.

The purpose of the present study was to establish a continuous hemofiltration model using porcine blood to compare filter life. Continuous hemofiltration (CHF) experiments were performed using an in vitro hemofilter evaluation system utilizing porcine blood containing trisodium citrate in addition to nafamostat mesilate as anticoagulants. The lifetime of the hemofilter was evaluated using the transmembrane pressure and the pressure drop across the hemofilter at varying trisodium citrate concentrations. The porcine blood used in this experiment was considered to be in a slightly hypercoagulable state because of the continuous contact with non-biological materials and calcium inflow from substitution fluid. Blood containing 7 or 8 mM of trisodium citrate and nafamostat mesilate could be effectively used to compare the lifetimes of hemofilters utilized under the same conditions. In this CHF model using porcine blood, the plugging of the hollow fibers occurred shortly after the plugging of the membrane pores. In conclusion, a CHF model using porcine blood can be established by adjusting the concentration of trisodium citrate added to the blood.

Support for Dialysis Therapy in Vietnam, Cambodia, and Myanmar by Japanese Societies in the Field of Blood Purification.

With recent economic development in Southeast Asia, there have been improvements in medical services and healthcare provision. This has led to increased numbers of dialysis patients and increased numbers of dialysis facilities in the region. To assist economically developing countries in managing this change, support projects from Japan have been conducted in the region since around 2007. This article summarizes and discusses Japan's support activities, in which some of the authors were directly involved, in Vietnam, Cambodia, and Myanmar. Initial support was mainly organized by the non-governmental organization Ubiquitous Blood Purification International (NGO UBPI), and currently several organizations in the field of blood purification work together to offer ongoing support in the region. Many positive changes have resulted from these activities in Southeast Asia, but challenges remaining for the future are to establish an educational system for each dialysis specialty and develop dialysis techniques ensuring high treatment quality and safety.

Evaluation of the Biocompatibility of Dialysis Membranes.

BACKGROUND: Improvements in the biocompatibility of dialysis membranes have reduced biological responses elicited by blood-membrane interactions. In this article, recent technological developments in dialysis membranes with regard to biocompatibility and recent progress in the evaluation of the biocompatibility of dialysis membranes are reviewed. SUMMARY: The focus of investigation into dialysis membranes in recent years has focused on not only membrane materials, but also their surface textures, which have been changed, for example, by coating with vitamin E or by changing the amount and type of hydrophilizing agents used. Research and development is directed at altering the chemical and physical properties of membrane surfaces to suppress biological responses that are particularly elicited as a result of platelet activation. To develop membranes with excellent biocompatibility, biocompatibility should be evaluated on a like-for-like basis under conditions that are similar to those in clinical settings. Evaluation using actual dialyzers can be performed using porcine blood, platelet-rich plasma isolated from porcine blood (and platelet-rich plasma with leukocytes), or suspension of neutrophils isolated from porcine blood or cultured human monocytes. KEY MESSAGES: Highly biocompatible dialysis membranes can be developed when the overall correlations among biological reactions are examined by integrating all data on biological responses elicited by blood-membrane interactions or mutual interactions among blood cells.

Effects of increased surface coverage of polyvinylpyrrolidone over a polysulfone hemofilter membrane on permeability and cell adhesion during continuous hemofiltration.

The purpose of the present study was to evaluate the adhesiveness of blood cells and the solute removal performance change of modified polysulfone membranes which have increased polyvinylpyrrolidone (PVP) coverage over their surface. Continuous hemofiltration (CHF) experiments for 24 h were carried out using an ex vivo hemofilter evaluation system to compare a modified polysulfone hemofilter (SHG) with the conventional polysulfone hemofilter (SH). The 25 and 50 % cutoff values of the sieving coefficient of dextran after CHF and the protein concentration in the filtrate was higher in SHG, indicating that less fouling occurred in the SHG membrane. Adhesion of blood cells after 24 h of CHF was significantly higher in the case of SH than in the case of SHG. Blood cell adhesion and membrane fouling were reduced with the use of a polysulfone membrane modified with increased PVP coverage over the surface.

An infant with primary pulmonary vein stenosis, associated with fatal occlusion of intraparenchymal small pulmonary veins.

Primary pulmonary vein stenosis (PVS) is rare within the pediatric population and its pathophysiology remains unclear, especially as to how the histopathology relates to its refractoriness to treatment. We report the case of a 4-month-old girl with primary PVS. The lesion in this patient was characterized by fatal obstruction of intraparenchymal small pulmonary veins, associated with localized stenosis at the four pulmonary veno-atrial junctions. All four localized stenoses underwent transcatheter stent implantation. Although the procedure was technically successful, her clinical status failed to improve, and she died 2 months after stenting. Histopathological examination of lung specimens showed severe luminal obstruction by marked intimal proliferation with fibrosis in the intraparenchymal small pulmonary veins, and these findings were present in every lobe. To the best of our knowledge, the histopathological findings and clinical course in this case, including the response to treatments, are extremely rare. We suggest that the histological findings of the small pulmonary veins are important in deciding the indication and appropriate timing of intervention. .

Temporal change in IL-6 mRNA and protein expression produced by cyclic stretching of human pulmonary artery endothelial cells.

The time courses of interleukin (IL)-6 gene expression and protein production were examined in human pulmonary artery endothelial cells (HPAECs) subjected to cyclic stretching. IL-6 protein was increased even in cells without stretching. Fold changes determined by dividing the level of IL-6 protein in stretched cells by that in unstretched cells at the same sampling times indicated that IL-6 protein was increased by stretching. At least 1 h of stretching was necessary to elicit an increase of IL-6 protein, and the levels peaked at 3 h after the start of stretching. After withdrawal of stretching, there was no further increase of IL-6 protein. The expression levels of the IL-6 gene were significantly increased by stretching and peaked at 30 min after the start of stretching. The difference in the peak times of IL-6 gene and protein expression likely reflects the process of protein synthesis after the appearance of IL-6 mRNA.