Hollow fiber hemodialyzers for partial respiratory support

Acute respiratory failure is still characterized by a high mortality rate, in spite of the development of ingenious treatment modalities involving mechanical ventilation and extracorporeal respiratory support. The coexistence of renal failure further complicates the outlook for respiratory failure patients. In this paper the development of the blood oxygenator and current aspects of its application are described. The concept of applying dialysis membranes for partial respiratory support is presented. An experimental animal model which was performed with A-V cannulation using dialysis membranes for partial respiratory support and simultaneous dialysis is analyzed. It is concluded that dialysis membranes are efficient for blood gas exchange and that their use in the management of the above-mentioned types of critically ill patients is promising.     

Dialysate flow distribution in hollow fiber hemodialyzers with different dialysate pathway configurations

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, since this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different dialysate compartment designs on dialysate flow distribution and urea clearances. Eighteen hollow fiber 1.3 m2 hemodialyzers were studied, 6 each of 3 designs: Type A--standard fiber bundle (PAN 65DX Asahi Medical, Tokyo, Japan); Type B--spacing filaments external to the fibers (PAN 65SF Asahi Medical, Tokyo, Japan); Type C--fibers waved to give Moiré structure (FB130 Nissho-Nipro, Osaka, Japan). In vitro studies: 3 dialyzers of each type were studied following dye injection into the dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer were undertaken, using a new generation helical CT scanner (X-Press/HS1 Toshiba Corporation, Tokyo, Japan). In vivo studies: 3 dialyzers of each type were studied, in randomized sequence, in 3 different patients under standardized dialysis conditions. Blood- and dialysate-side urea clearances were measured at 30 and 150 minutes of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with Moiré structure (Type C) and least homogeneous in the standard dialyzer (Type A). Space yarns (Type B) gave an intermediate dialysate flow distribution. Significantly increased urea clearances (p<0.001) were seen with Types B and C, compared to the standard dialyzer. Type C (Moiré) had the highest clearances although these were not significantly greater than Type B (space yarns). In conclusion, more homogeneous dialysate flow distribution and improved small solute clearances can be achieved by use of spacing yarns or waved (Moiré structure) patterns of fiber packing in the dialyzer. These effects are achieved probably as a result of reduced dialysate channeling resulting in a lower degree of mismatch between blood and dialysate flows. The new radiological technique using the helical CT scanner allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design.     

Spaceflight alters the fiber composition of the aortic nerve in the developing rat

Hydrostatic pressure gradients due to the gravitational force in blood vessels disappear under conditions of microgravity during spaceflight, and the ability of the baroreceptor reflex to control arterial pressure and blood distribution may be altered. We hypothesized, on the basis of the results obtained in our previous experiments using the head-down tilt method in rats and rabbits, that the range of increase in arterial pressure caused by animal behavior narrows under conditions of microgravity, affecting the development of high-threshold unmyelinated fibers in the rat aortic nerve which sends signals from baroreceptors located in the aortic wall to the reflex center. We verified this hypothesis using 9-day-old rat neonates housed with their dams for 16 days on the space shuttle Columbia in outer space (STS-90, Neurolab Mission). Age-matched neonatal rats with the dams remained on the ground as controls. After breeding was carried out in the three experimental groups (FLT, spaceflight; AGC, asynchronous ground control; VIV, vivarium ground control), specimens of the 25-day-old rats were excised and five left aortic nerves in each group were examined by electron microscopy. The number of aortic unmyelinated fibers was significantly less in the FLT group than in each ground control (mean+/-S.D.; 139+/-37 in the FLT, 207+/-36 in the AGC, 283+/-121 in the VIV; P<0.05), which may be related to the weakness of the baroreceptor reflex under conditions of microgravity in space. This result may contribute to understanding of the several cardiovascular issues which occur under microgravity and after reexposure to gravity in human.     

Matrix metalloproteinase-9 deficiency results in decreased fiber cross-sectional area and alters fiber type distribution in mouse hindlimb skeletal muscle

Matrix metalloproteinases (MMPs) play a major role in the degradation of the extracellular matrix (ECM) of skeletal muscle, and the inducible gelatinase MMP-9 in particular appears to be critical for the remodeling of muscle ECM during growth and repair. Here we determined the effects of MMP-9 gene inactivation on fiber type and size in the tibialis anterior (TA), gastrocnemius (GAST), and soleus (SOL) muscles in female mice. In the TA, the cross-sectional area (CSA) of the myosin heavy chain (MyHC) IIb-expressing fibers was significantly smaller in MMP-9 null mice while in the GAST, CSA of all three fast fiber types was decreased. In the SOL, MyHC type I-expressing fibers were significantly smaller in the MMP-9 null mice. The percentage of MyHC type IIb-expressing fibers was significantly increased in the TA and GAST of MMP-9 null mice, while the percentage of MyHC IId-expressing fibers significantly decreased in the GAST of MMP-9 null mice. Fiber percentages in the SOL were not significantly different between the two lines. Despite these changes in fiber size and type, in vivo hindlimb force production was not changed in MMP-9 null mice. Meanwhile, neither expression of the constitutive gelatinase MMP-2 nor immunohistochemical staining for type IV collagen was significantly altered by MMP-9 inactivation in any muscles examined. The present study demonstrates that MMP-9 inactivation results in changes in fiber size and type in adult mouse hindlimb muscles that may depend on indirect mechanisms involving reduced bone growth or nerve changes in response to MMP-9 inactivation.     

Prenatal smoke exposure alters growth in limb proportions and head shape in the midgestation human fetus

The objective of this study was to examine the effects of smoke exposure on the growth patterns of the head, limbs, and torso of the midgestation human fetus. Four hundred maternal/fetal pairs contributed to this analysis: 366 individuals were assessed cross‐sectionally (87 smokers and 279 nonsmokers) at approximately 20 and 32 weeks, and 34 individuals were followed longitudinally at 23, 27, and 32 weeks (10 smokers, 24 nonsmokers). Ten body parameters were measured by fetal ultrasound. In both samples, controlling for day of measurement, smoke exposure was significantly associated with early growth acceleration in head and abdominal diameters at 20–27 weeks (P < 0.05). This was followed by altered head shape (a significantly smaller biparietal to occipital frontal diameter ratio at 32 weeks, P < 0.01), and a proximal/distal growth gradient as proportionately long arms (P < 0.05 at 27 and 32 weeks) and short legs were apparent by 32 weeks, with a significant reduction in the tibia/femur ratio (P = 0.04). These fetal body growth patterns, expressed in terms of size and proportionality, are consistent with the presence of chronic hypoxia associated with maternal smoking. The growth pattern differences identify that prenatal smoking is not merely an insult resulting in consistent size and growth rate reduction across developmental ages. Instead, smoke exposure alters the growth rate of individual body segments at variable developmental stages as the fetus experiences selective growth restriction and augmentation. We hypothesize that the growth patterns observed here reflect the unique pattern of fetal blood flow favoring upper body oxygen distribution and extraction, together with genetically based adaptive strategies that permit the fetus to adjust the timing and magnitude of its growth to local environmental resources. It is possible that dolichocephaly is a previously unappreciated marker of fetal hypoxia. Reduced tibial growth may be a good marker for shortfall and a useful proxy for the adequacy of circulating resources more generally. Am. J. Hum. Biol. 15:533–546, 2003. © 2003 Wiley‐Liss, Inc.     

The shape of high fertility in a traditional Mennonite population

Background: The Wenger Mennonites, a traditional horse-and-buggy group, are one of at least 30 embedded Anabaptist religious groups in the USA.

Aim: This first study of Wenger fertility documents, explains, and compares Wenger fertility to three other Anabaptist groups: the Amish, the Hutterites, and the Old Colony Mennonites.

Subjects and methods: The 1997 Wenger church directory provides household and fertility data for 14?530 individuals. This directory was transformed into an SPSS database so that age-specific birth rates could be analysed.

Results: From 1966 to 1996, total fertility ranged from 10.68 to 8.31 for married women, and age-specific fertility rates for 20–24-year-old women never dropped below 0.500. For similar time periods, no higher rates were found in any of the comparison groups. Even so, fertility has dropped over 22% in the last 30 years, suggesting increasing regulation of fertility.

Conclusion: Wenger fertility has been very high, at least since the 1960s, and continues to be higher than the comparison groups, even though there is some evidence of fertility decline, especially in older women. This high fertility is powered by high economic and social capital, and a farming community with a strong pro-natalist ideology.     

The shape of high fertility in a traditional Mennonite population

BACKGROUND: The Wenger Mennonites, a traditional horse-and-buggy group, are one of at least 30 embedded Anabaptist religious groups in the USA. AIM: This first study of Wenger fertility documents, explains, and compares Wenger fertility to three other Anabaptist groups: the Amish, the Hutterites, and the Old Colony Mennonites. SUBJECTS AND METHODS: The 1997 Wenger church directory provides household and fertility data for 14530 individuals. This directory was transformed into an SPSS database so that age-specific birth rates could be analysed. RESULTS: From 1966 to 1996, total fertility ranged from 10.68 to 8.31 for married women, and age-specific fertility rates for 20-24-year-old women never dropped below 0.500. For similar time periods, no higher rates were found in any of the comparison groups. Even so, fertility has dropped over 22% in the last 30 years, suggesting increasing regulation of fertility. CONCLUSION: Wenger fertility has been very high, at least since the 1960s, and continues to be higher than the comparison groups, even though there is some evidence of fertility decline, especially in older women. This high fertility is powered by high economic and social capital, and a farming community with a strong pro-natalist ideology.     

Asymmetric triacetate membrane keeps high water flux during ultrafiltration: in vitro study

Membrane fouling is a primary challenge encountered during the administration of hemodialysis (HD) and hemodiafiltration (HDF). A high-flux membrane is suitable for dialyzer reuse, since it is used repeatedly. Water flux is a benchmark used to assess the effectiveness of the dialysis membrane during treatment and it is usually evaluated to determine whether membrane fouling has occurred. Polysulfone (PS) membrane has good biocompatibility and solute permeability; however, polyethersulfone (PES) is often used as a hemodiafilter membrane because of better hydrophilicity compared to PS. We evaluated water flux across hemodiafilters using newly developed asymmetric triacetate (ATA) and PES as conventional membranes in vitro. Water flux of across ATA and PES membranes significantly decreased 30 min after the start of the experiments and thereafter showed stabilization. Water flux across the ATA membrane consistently showed significantly higher values of greater than 100 mL/m²/h/mmHg, compared to lower values observed across the PES membrane. These results suggest that the ATA membrane has a potential use not only for HDF, but also for long-time therapies of HD and HDF.     

Initial fiber alignment pattern alters extracellular matrix synthesis in fibroblast-populated fibrin gel cruciforms and correlates with predicted tension

Human dermal fibroblasts entrapped in fibrin gels cast in cross-shaped (cruciform) geometries with 1:1 and 1:0.5 ratios of arm widths were studied to assess whether tension and alignment of the cells and fibrils affected ECM deposition. The cruciforms of contrasting geometry (symmetric vs. asymmetric), which developed different fiber alignment patterns, were harvested at 2, 5, and 10 weeks of culture. Cruciforms were subjected to planar biaxial testing, polarimetric imaging, DNA and biochemical analyses, histological staining, and SEM imaging. As the cruciforms compacted and developed fiber alignment, fibrin was degraded, and elastin and collagen were produced in a geometry-dependent manner. Using a continuum mechanical model that accounts for direction-dependent stress due to cell traction forces and cell contact guidance with aligned fibers that occurs in the cruciforms, the mechanical stress environment was concluded to influence collagen deposition, with deposition being the greatest in the narrow arms of the asymmetric cruciform where stress was predicted to be the largest.     

A comparison of bicarbonate kinetics and acid-base status in high flux hemodialysis and on-line post-dilution hemodiafiltration

Objectives: To compare bicarbonate kinetics and acid base status in HD and HDF for the same patient; and to investigate the effect of patient physiologic parameters on these kinetics. Methods: In order to monitor HCO3- kinetics during dialysis, acid-base parameters, pH, blood gases partial pressures, and HCO3- concentrations were recorded during 3 regular dialysis (HD) and 3 on-line post-dilution HDF sessions performed on 12 patients, using same dialysis fluid with a 38 mmol/l HCO3- concentration. HCO3- mass transfers through the hemodialyzers membranes and into the patients were continuously calculated during the sessions from HCO3- concentrations, together with HCO3-dialysance. The"apparent" HCO3-gain was calculated by integrating over time the instantaneous mass transfer from dialyzer and re-infusion fluid to the patient. A second method consisted in calculating the patient apparent bicarbonate space (ABS) and HCO3- mass (ABS times plasma concentration) at beginning and end of session. Results: No significant differences were observed between acid base parameters at the end of HD and HDF sessions. In contrast to urea clearances, HCO3- dialysances decayed with time during sessions from 110 to 140 ml/min to about 40 ml/min after one hour. The net HCO3- gain was taken as the difference between final and initial HCO3-masses. This net gain was in average 63% of apparent gain in HD and 74% in HDF. Conclusions: Uremic acidosis was well corrected without risk of alkalosis. An unexpected result was the continuous decay of bicarbonate dialysance both in HD and HDF during runs.     

高通量透析对慢性肾病患者生物活性物质的影响

目的血清肌酐(Scr)、血管紧张素Ⅱ(Ang Ⅱ)、内皮素-1(ET-1)和一氧化氮(NO)水平升高是慢性肾病的主要标志。机体淋巴细胞和血管内皮细胞均可通过分泌上述活性分子,参与慢性肾病的发病过程。本实验通过观察高通量透析(HFHD)对维持性血液透析(MHD)患者血管活性物质的影响,从而探讨HFHD改善MHD患者体内这些生物活性物质分泌的作用,为临床治疗提供理论依据及新思路,也为进一步研究机体免疫系统参与慢性肾病的发生机制奠定基础。方法将MHD患者20例随机分为低通量血液透析(LFHD)组和高通量血液透析(HFHD)组各10例。选取尿毒症非透析患者20例,另选取20例正常健康体检者作为健康对照组。HFHD组改用可重复使用高通量透析器Polyflux17R,LFHD组继续采用可重复使用透析器Polyflux8LR。分别检测HFHD组及LFHD组患者单次治疗前后及3个月透析前检测的Scr、Ang Ⅱ、ET-1和NO;另抽取尿毒症非透析组和健康对照组各20例的清晨空腹肘静脉血标本同时检验。NO测定用硝酸还原酶法,ET-1、Ang Ⅱ检测均采用放免法。Cr的测定采用常规生化法。透析组患者同时监测血压变化。结果两组患者单次透析后HFHD组Ang Ⅱ、ET-1水平较LFHD组显著降低(P<0.05)。治疗3个月后,HFHD组患者NO、ET-1、平均动脉压与治疗前显著下降(P<0.05)。结论高通量血液透析可以提高上述生物活性物质的清除,使MHD患者高血压得到改善;本实验结果为将来进一步研究淋巴细胞和内皮细胞参与慢性肾病发病的机制提供临床实验依据。     

Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus

BACKGROUND: The effect of increasing the intake of dietary fiber on glycemic control in patients with type 2 diabetes mellitus is controversial. METHODS: In a randomized, crossover study, we assigned 13 patients with type 2 diabetes mellitus to follow two diets, each for six weeks: a diet containing moderate amounts of fiber (total, 24 g; 8 g of soluble fiber and 16 g of insoluble fiber), as recommended by the American Diabetes Association (ADA), and a high-fiber diet (total, 50 g; 25 g of soluble fiber and 25 g of insoluble fiber), containing foods not fortified with fiber (unfortified foods). Both diets, prepared in a research kitchen, had the same macronutrient and energy content. We compared the effects of the two diets on glycemic control and plasma lipid concentrations. RESULTS: Compliance with the diets was excellent. During the sixth week, the high-fiber diet, as compared with the the sixth week of the ADA diet, mean daily preprandial plasma glucose concentrations were 13 mg per deciliter [0.7 mmol per liter] lower (95 percent confidence interval, 1 to 24 mg per deciliter [0.1 to 1.3 mmol per liter]; P=0.04) and mean median difference, daily urinary glucose excretion 1.3 g (0.23; 95 percent confidence interval, 0.03 to 1.83 g; P= 0.008). The high-fiber diet also lowered the area under the curve for 24-hour plasma glucose and insulin concentrations, which were measured every two hours, by 10 percent (P=0.02) and 12 percent (P=0.05), respectively. The high-fiber diet reduced plasma total cholesterol concentrations by 6.7 percent (P=0.02), triglyceride concentrations by 10.2 percent (P=0.02), and very-low-density lipoprotein cholesterol concentrations by 12.5 percent (P=0.01). CONCLUSIONS: A high intake of dietary fiber, particularly of the soluble type, above the level recommended by the ADA, improves glycemic control, decreases hyperinsulinemia, and lowers plasma lipid concentrations in patients with type 2 diabetes.     

Hollow fiber integrated microfluidic platforms for <Emphasis Type=Italic>in vitro</Emphasis> Co-culture of multiple cell types

This study demonstrates a rapid prototyping approach for fabricating and integrating porous hollow fibers (HFs) into microfluidic device. Integration of HF can enhance mass transfer and recapitulate tubular shapes for tissue-engineered environments. We demonstrate the integration of single or multiple HFs, which can give the users the flexibility to control the total surface area for tissue development. We also present three microfluidic designs to enable different co-culture conditions such as the ability to co-culture multiple cell types simultaneously on a flat and tubular surface, or inside the lumen of multiple HFs. Additionally, we introduce a pressurized cell seeding process that can allow the cells to uniformly adhere on the inner surface of HFs without losing their viabilities. Co-cultures of lung epithelial cells and microvascular endothelial cells were demonstrated on the different platforms for at least five days. Overall, these platforms provide new opportunities for co-culturing of multiple cell types in a single device to reconstruct native tissue micro-environment for biomedical and tissue engineering research.     

Analysis of the shape changes of muscle fiber cross sections in guinea pigs raised at 22°C and 5°C

Seven control and nine cold-acclimated guinea pigs were selected over a wide range of body weights (256–960 g and 239–1.074 g, respectively) from two larger groups of animals chronically exposed to 22°C or 5°C. Thin cross sections of the frozen soleus muscles were treated by the ATPase method to visualize fibers and capillaries. Photomicrographs of the sections were magnified and a total of 1,067 fiber profiles were cut out and weighed to determine individual fiber cross sectional areas (FCSA). Since most fibers are assumed to be cylinders with a circular cross section, the area of the fiber was compared to the area of a circle with the same diameter as the longest axis of the fiber. The longest axis within the fiber was measured and divided by two (LD/2). The LD/2 of each fiber was treated as the radius of a circle and the calculated area of the circle compared to the real area of the fiber. LD/2 and FCSA were positively correlated in both groups of animals by power functions FCSA=a(LD/2) ^b , wherea is the intercept andb is the regression coefficient. The values forb (1.58 for the 22°C and 1.59 for the 5°C animals) were both significantly less than 2 (b in the formula for the area of a circle), and the regression lines moved from a line representing a circle towards a line representing an ellipse, indicating that as the fibers grow they tend to become more and more elliptical. The adjusted mean of the 5°C regression line was significantly lower than that for the control line, indicating that the fibers of the cold-acclimated animals were more elliptical at the same FCSA than were the fibers of the control animals.Supported by PHS Grant No. HL18145 from the National Heart Lung and Blood Institute     

Polymyxin B-immobilized fiber hemoperfusion in a high school football player with septic shock caused by osteitis pubis

A 17-year-old male high school football player treated by polymyxin B-immobilized fiber (PMX-F) hemoperfusion for mild-moderate septic shock caused by osteitis pubis is described in this study. He was admitted for inguinal pain, gait disturbance, and high fever (40.6°C). His white blood cell (WBC) count and C-reactive protein (CRP), endotoxin, and procalcitonin (PCT) levels were significantly elevated. His blood pressure was 76/46 mm Hg. Magnetic resonance imaging showed bone and muscle injury at the pubic symphysis. Septic shock with high blood endotoxin and PCT concentrations was diagnosed, and the patient was treated with antibiotics, γ-globulin, and dopamine on the admission day. However, the septic shock did not improve. On day 3, we performed direct hemoperfusion twice using a PMX-F column. After the second PMX-F treatment, the patient's temperature decreased to 37.0°C, and his WBC count, CRP levels, blood endotoxin, and PCT levels decreased. The inguinal pain diminished, and the patient's blood pressure increased to 112/76 mm Hg. He was discharged on day 10 after admission. This case reflects association of PMX-F with decreased endotoxin, PCT, and CRP, suggesting the association of PMX-F with clinical improvement in mild-moderate sepsis in a young athlete.     

Fiber composition,fiber size and enzyme activities in vastus lateralis of elite athletes involved in high intensity exercise

Summary In order to determine the influence of an extensive history of participation in high intensity activity on muscle fiber type, fiber size, and metabolic profile, elite ice hockey players were selected for investigation from three different leagues. Biopsy samples from the vastus lateralis muscle were obtained from different groups of players prior to and following the season and compared with control subjects. No significant differences were found in the percentage (49.6 vs. 43.8%) or the size of the ST fibers between the elite athletes and the control group, nor was there any significant alteration following the season of play in these variables. For the FT fiber subgroups, a reduction in the FTb (12.2 vs. 3.9%) and an increase in FTa (38.0 to 45.2%) fiber populations occurred over the season. Similarly, increases in fiber area were observed for both FT subgroups pre to post season. Of the enzymes studied only 3-hydroxyacyl CoA dehydrogenase was elevated in the post season measures, while total phosphorylase and phosphofructokinase were significantly lower. The metabolic pattern exhibited does not appear to be substantially different from what would be expected from an untrained group of similar fiber distribution.This study was supported by grants from National Health and Welfare and the National Research Council     

Hyperbaric exposure with high oxygen concentration improves altered fiber types in the plantaris muscle of diabetic Goto-Kakizaki rats

Hyperbaric exposure with high oxygen concentration inhibits a growth-related increase in the glucose and insulin of diabetic rats. In this study, 5-week-old diabetic Goto-Kakizaki rats were exposed to a hyperbaric environment (1.25 atmospheric pressure) with a high oxygen concentration (36%) for 6 h daily. Fiber type distributions and oxidative enzyme activities in the fast-twitch plantaris muscle of Goto-Kakizaki rats were examined after hyperbaric exposure for 4 weeks. The percentages of high-oxidative type I and type IIA fibers increased and that of low-oxidative type IIB fibers decreased after hyperbaric exposure. Furthermore, the fiber oxidative enzyme activity increased after hyperbaric exposure, regardless of fiber type. It is concluded that altered patterns of fiber types in the plantaris muscle of diabetic rats shift toward normal, which is observed in nondiabetic rats, following hyperbaric exposure with high oxygen concentration.