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Objective: To create prescriptive growth standards for five fetal brain structures, measured using ultrasound, in healthy, well-nourished women at low risk of impaired fetal growth and poor perinatal outcome, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project.Methods: This was a complementary analysis of a large, population-based, multicenter, longitudinal study. The sample analyzed was selected randomly from the overall FGLS population, ensuring an equal distribution among the eight diverse participating sites and of three-dimensional (3D) ultrasound volumes across pregnancy (range: 15-36 weeks' gestation). We measured, in planes reconstructed from 3D ultrasound volumes of the fetal head at different timepoints in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle, atrium of the posterior horn of the lateral ventricle (PV) and cisterna magna (CM). Fractional polynomials were used to construct the standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards.Results: From the entire FGLS cohort of 4321 women, 451 (10.4%) were selected at random. After exclusions, 3D ultrasound volumes from 442 fetuses born without a congenital malformation were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures, except the PV, showed increasing size with gestational age, and the size of the POF, SF, PV and CM showed increasing variability. The 3rd , 5th , 50th , 95th and 97th smoothed centiles are presented. The 5th centiles for the POF and SF were 3.1 mm and 4.7 mm at 22 weeks' gestation and 4.6 mm and 9.9 mm at 32 weeks, respectively. The 95th centiles for the PV and CM were 8.5 mm and 7.5 mm at 22 weeks and 8.6 mm and 9.5 mm at 32 weeks, respectively.Conclusions: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcome. We recommend these as international standards for the assessment of measurements obtained using ultrasound from fetal brain structures. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To develop an objective image-scoring system for pulsed-wave Doppler measurement of maternal uterine and fetal umbilical arteries, and evaluate how this compares with subjective assessment.Methods: As an extension to the INTERGROWTH-21st Project, we developed a scoring system based on six predefined criteria for uterine and umbilical artery pulsed-wave Doppler measurements. Objective evaluation using the scoring system was compared with subjective assessment which consisted of classifying an image as simply acceptable or unacceptable. Based on sample size estimation, a total of 120 umbilical and uterine artery Doppler images were selected randomly from the INTERGROWTH-21st image database. Two independent reviewers evaluated all images in a blinded fashion, both subjectively and using the six-point scoring system. Percentage agreement and kappa statistic were compared between the two methods.Results: The overall agreement between reviewers was higher for objective assessment using the scoring system (agreement, 85%; adjusted kappa, 0.70) than for subjective assessment (agreement, 70%; adjusted kappa, 0.47). For the six components of the scoring system, the level of agreement (adjusted kappa) was 0.97 for anatomical site, 0.88 for sweep speed, 0.77 for magnification, 0.68 for velocity scale, 0.68 for image clarity and 0.65 for angle of insonation.Conclusion: In quality assessment of umbilical and uterine artery pulsed-wave Doppler measurements, our proposed objective six-point image-scoring system is associated with greater reproducibility than is subjective assessment. We recommend this as the preferred method for quality control, auditing and teaching. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess a comprehensive package of ultrasound quality control in the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project, a large multicenter study of fetal growth.Methods: Quality control (QC) measures were performed for 20 313 ultrasound scan images obtained prospectively from 4321 fetuses at 14-41 weeks' gestation in eight geographical locations. At the time of each ultrasound examination, three fetal biometric variables (head circumference (HC), abdominal circumference (AC) and femur length (FL)) were measured in triplicate on separately generated images. All measurements were taken in a blinded fashion. QC had two elements: (1) qualitative QC: visual assessment by sonographers at each study site of their images based on specific criteria, with 10% of images being re-assessed at the Oxford-based Ultrasound Quality Unit (compared using an adjusted kappa statistic); and (2) quantitative QC: assessment of measurement data by comparing the first, second and third measurements (intraobserver variability), remeasurement of caliper replacement in 10% (interobserver variability), both by Bland-Altman plots and plotting frequency histograms of the SD of triplicate measurements and assessing how many were above or below 2 SD of the expected distribution. The system allowed the sonographers' performances to be monitored regularly.Results: A high level of agreement between self- and external scoring was demonstrated for all measurements (κ = 0.99 (95% CI, 0.98-0.99) for HC, 0.98 (95% CI, 0.97-0.99) for AC and 0.96 (95% CI, 0.95-0.98) for FL). Intraobserver 95% limits of agreement (LoA) of ultrasound measures for HC, AC and FL were ± 3.3%, ± 5.6% and ± 6.2%, respectively; the corresponding values for interobserver LoA were ± 4.4%, ± 6.0% and ± 5.6%. The SD distribution of triplicate measurements for all biometric variables showed excessive variability for three of 31 sonographers, allowing prompt identification and retraining.Conclusions: Qualitative and quantitative QC monitoring was feasible and highly reproducible in a large multicenter research study, which facilitated the production of high-quality ultrasound images. We recommend that the QC system we developed is implemented in future research studies and clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background Research has identified associations between serum 25( OH) D and a range of clinical outcomes in chronic kidney disease and wider populations. The present study aimed to investigate vitamin D deficiency/insufficiency in dialysis patients and the relationship with vitamin D intake and sun exposure. Methods A cross-sectional study was used. Participants included 30 peritoneal dialysis (PD) (43.3% male; 56.87 ± 16.16 years) and 26 haemodialysis (HD) (80.8% male; 63.58 ± 15.09 years) patients attending a department of renal medicine. Explanatory variables were usual vitamin D intake from diet/supplements ( IU day−1) and sun exposure (min day−1). Vitamin D intake, sun exposure and ethnic background were assessed by questionnaire. Weight, malnutrition status and routine biochemistry were also assessed. Data were collected during usual department visits. The main outcome measure was serum 25( OH) D (n m). Results Prevalence of inadequate/insufficient vitamin D intake differed between dialysis modality, with 31% and 43% found to be insufficient (<50 n m) and 4% and 33% found to be deficient (<25 n m) in HD and PD patients, respectively ( P < 0.001). In HD patients, there was a correlation between diet and supplemental vitamin D intake and 25( OH)D (ρ = 0.84, P < 0.001) and average sun exposure and 25( OH)D (ρ = 0.50, P < 0.02). There were no associations in PD patients. The results remained significant for vitamin D intake after multiple regression, adjusting for age, gender and sun exposure. Conclusions The results highlight a strong association between vitamin D intake and 25( OH)D in HD but not PD patients, with implications for replacement recommendations. The findings indicate that, even in a sunny climate, many dialysis patients are vitamin D deficient, highlighting the need for exploration of determinants and consequences. [ABSTRACT FROM AUTHOR]

Objective: A small number of multichannel cochlear implant (CI) recipients require reimplantation. This study describes the causes of failure, surgical technique, and hearing outcomes in a consecutive series of 16 patients undergoing reimplantation of multichannel devices. We hypothesize that reimplantation is safe and that hearing results are at least as good as those measured following primary implantation.Study Design: Retrospective analysis of consecutive clinical series.Methods: Chart analysis of 191 consecutive CI operations performed at the University of Miami Ear Institute between 1990 and 1997 revealed 16 patients who received a second multichannel device. All but one had a minimum follow-up of 1 year after reimplantation. Ten of these patients had initial implantation performed by us, and six were initially operated on elsewhere. Main outcomes of the initial procedure were compared with those of the reimplantation, including electrode insertion length, number of channels programmed, and audiometric results. In addition, cause of failure and relevant surgical findings at the second procedure are described.Results: There were no surgical complications after reimplantation surgery. Device failure was the most frequent cause for reimplantation. Time between initial implantation and failure ranged from 0 to 46 months (mean, 22.4 mo; median, 23 mo). Common intraoperative findings include mastoid fibrosis, bone growth at the cochleostomy, and skin flap breakdown. Following reimplantation, mean length of insertion, number of channels actively programmed, and speech recognition scores were at least as good as findings before initial implant failure.Conclusion: CI reimplantation is safe and effective. [ABSTRACT FROM AUTHOR]

Background The assessment of competence for health professionals including nutrition and dietetics professionals in work-based settings is challenging. The present study aimed to explore the experiences of educators involved in the assessment of nutrition and dietetics students in the practice setting and to identify barriers and enablers to effective assessment. Methods A qualitative research approach using in-depth interviews was employed with a convenience sample of inexperienced dietitian assessors. Interviews explored assessment practices and challenges. Data were analysed using a thematic approach within a phenomenological framework. Twelve relatively inexperienced practice educators were purposefully sampled to take part in the present study. Results Three themes emerged from these data. (i) Student learning and thus assessment is hindered by a number of barriers, including workload demands and case-mix. Some workplaces are challenged to provide appropriate learning opportunities and environment. Adequate support for placement educators from the university, managers and their peers and planning are enablers to effective assessment. (ii) The role of the assessor and their relationship with students impacts on competence assessment. (iii) There is a lack of clarity in the tasks and responsibilities of competency-based assessment. Conclusions The present study provides perspectives on barriers and enablers to effective assessment. It highlights the importance of reflective practice and feedback in assessment practices that are synonymous with evidence from other disciplines, which can be used to better support a work-based competency assessment of student performance. [ABSTRACT FROM AUTHOR]

Background: Haemodialysis patients show signs of chronic inflammation and reduced appetite, which is associated with a worse clinical status and an increased mortality risk. Fish oil has anti-inflammatory properties and may be useful as a therapeutic treatment. There is limited evidence to indicate the feasibility and efficacy of this intervention in dialysis patients. The present study aimed to compare the effect of 12 weeks of supplementation with fish oil on markers of appetite and inflammation in male and female haemodialysis patients. Methods: The study was conducted in 28 haemodialysis patients. All patients were prescribed 3 g of fish oil per day for 12 weeks. Changes in appetite, plasma fatty acid profiles and inflammatory markers were measured at baseline and at 12 weeks. Results: The mean (SD) increase in percent plasma eicosapentaenoic acid was statistically significant [1.1 (0.8) to 4.1 (2.2), P < 0.001], which was a strong indicator of good adherence. There were trends towards reductions in peptide YY (−9%; P = 0.078) and an increase in subjective sensations of hunger (+12%; P = 0.406), which reflects an increase in motivation to eat. Males ( n = 13) experienced a more marked increase in hunger compared to females (+23% versus −6%), which was associated with maintenance in C-reactive protein and interleukin-6, and a reduction in soluble intercellular adhesion molecule-1. Conclusions: The results obtained demonstrate meaningful trends towards improvements in subjective appetite and certain inflammatory markers (although no change in dietary intake) and this effect was more pronounced in males. However, the levels of some inflammatory markers increased in females and this requires further study. The high level of adherence achieved indicates that an intervention requiring patients to consume four fish oil capsules per day is achievable. This was a short-term study and the effects need to be confirmed in a randomised controlled trial. [ABSTRACT FROM AUTHOR]

Background: Poor appetite is a marker of morbidity and mortality in haemodialysis patients, making it an important area for research. Visual analogue scales (VAS) can capture a range of subjective sensations related to appetite (such as hunger, desire to eat or fullness), but have not been commonly used to measure appetite in dialysis patients. The present study aimed to explore the association between retrospective ratings of appetite using VAS and a range of clinical variables, as well as biomarkers of appetite in haemodialysis patients. Methods: Twenty-eight haemodialysis patients [mean age 61 ± 17 years, 50% male, median dialysis vintage 19.5 (4–101) months] rated their appetite using VAS for hunger, fullness and desire to eat and a five-point categorical scale measuring general appetite. Blood levels of the appetite peptides leptin, ghrelin and peptide YY were also measured. Results: Hunger ratings measured by VAS were significantly ( P < 0.05) correlated with a range of clinical, nutritional and inflammatory markers: age ( r = −0.376), co-morbidities, ( r = −0.380) Patient-Generated Subjective Global Assessment score ( r = −0.451), weight ( r = −0.375), fat-free mass ( r = −0.435), C-reactive protein ( r = −0.383) and intercellular adhesion molecule ( r = −0.387). There was a consistent relationship between VAS and appetite on a five-point categorical scale for questions of hunger, and a similar trend for desire to eat, but not for fullness. Neither method for measuring subjective appetite correlated with appetite peptides. Conclusions: Retrospective ratings of hunger on a VAS are associated with a range of clinical variables and further studies are warranted to support their use as a method for measuring appetite in dialysis patients. [ABSTRACT FROM AUTHOR]

Background Knowledge of the patient's satisfaction with a service is important as satisfied patients are more likely to maintain appointments, return for review appointments and adhere to recommendations. Nutrition professionals need tools to confidently assess the service provision and educational materials provided as part of that service; however, validated satisfaction tools for dietetic services are limited. An outpatient satisfaction survey was developed and was used to assess previously developed inpatient factors of 'staff presentation', 'interpersonal skill', 'perceived health benefit', 'written information' and 'overall expectations' in an outpatient setting. Method An outpatient satisfaction survey was provided subsequent to initial dietetic consultations at a metropolitan hospital and rural health outpatient services. There were 25 statements in total with 24 scored from 1 (strongly agree) to 5 (strongly disagree). Satisfaction with overall service was assessed on a five-point scale from 'very good' scored as 1 to 'very poor' scored as 5. Results The age, gender and proportion of missing data was similar between metropolitan and rural respondents (n = 154). No metropolitan or rural differences were evident with regard to factor analysis or internal consistency. Four factors accounted for 81.3% of the variance, which compared well with the 83.3% achieved with the original tool designed for the inpatient setting. Conclusion The outpatient satisfaction tool represents a validated survey for outpatient nutrition services applicable to both rural and metropolitan settings. Patient satisfaction is simply one outcome measure of clinical service provision; however, in increasingly competitive environments the use of validated satisfaction survey results will contribute to measurement of the benefit of dietetic services. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Bioelectrical impedance analysis (BIA) is a useful field measure to estimate total body water (TBW). No prediction formulae have been developed or validated against a reference method in patients with pancreatic cancer. The aim of this study was to assess the agreement between three prediction equations for the estimation of TBW in cachectic patients with pancreatic cancer. METHODS: Resistance was measured at frequencies of 50 and 200 kHz in 18 outpatients (10 males and eight females, age 70.2 +/- 11.8 years) with pancreatic cancer from two tertiary Australian hospitals. Three published prediction formulae were used to calculate TBW - TBWs developed in surgical patients, TBWca-uw and TBWca-nw developed in underweight and normal weight patients with end-stage cancer. RESULTS: There was no significant difference in the TBW estimated by the three prediction equations - TBWs 32.9 +/- 8.3 L, TBWca-nw 36.3 +/- 7.4 L, TBWca-uw 34.6 +/- 7.6 L. At a population level, there is agreement between prediction of TBW in patients with pancreatic cancer estimated from the three equations. The best combination of low bias and narrow limits of agreement was observed when TBW was estimated from the equation developed in the underweight cancer patients relative to the normal weight cancer patients. When no established BIA prediction equation exists, practitioners should utilize an equation developed in a population with similar critical characteristics such as diagnosis, weight loss, body mass index and/or age. CONCLUSIONS: Further research is required to determine the accuracy of the BIA prediction technique against a reference method in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

The use of central venous catheters (CVC) for acute or chronic dialysis has been a relatively recent innovation in Nephrology. The first problem addressed has been how to allow removal and return of blood at high flow rates throughout a dialysis treatment. Four solutions have emerged: place the lumens within the right atrium; place the removal lumen on the inside of the catheter; use a large catheter size; or provide independent limbs with multiple blood-entry ports to draw and return blood in all directions. Many other requirements include resistance to infection, especially the passage of organisms around the catheter. A subcutaneous Dacron cuff within a tunnel has successfully accomplished this goal for most chronic CVC dialysis catheters, but other immobilizing devices such as plugs have also been successful. Materials for CVC dialysis catheters have improved, providing strength to allow the catheters to last for several years, with flexibility to avoid vein damage (in general). However, component and material failures still occur, and some materials are incompatible with medications placed at the exit site. CVC for dialysis will remain a necessary choice for many patients beginning and continuing dialysis therapy. [ABSTRACT FROM AUTHOR]

Research involving interviews of new graduate dietitians was conducted to investigate the nature of current dietetic practice, and comparisons were made with the existing competency standards for entry level dietitians. The aim of the interview methodology was to enable core activities and their underlying attributes, that is knowledge, skills and attitudes, to be described. Core activities, such as seeing patients and coordinating individual care, traditionally accepted as part of the dietitian's role, remain important. However, new graduates also need to be prepared to meet the demands of a variety of new work contexts where the performance of different core activities may be required. These include managing a private practice, managing a nutrition service and performing quality activities. To address these additional work activities the competency standards need to be modified to emphasise skills in management and communication including computer literacy and media skills, outcome evaluation and quality activities. A model is proposed to illustrate how the competency standards could be amended to encompass current practice. [ABSTRACT FROM AUTHOR]

A modified Delphi survey was forwarded to members of the dietetic profession to ascertain the current use and acceptance of the competency standards for entry level dietitians. Members of the profession identified as stakeholders were those involved in teaching and training dietitians, dietitians in tertiary hospitals, members of the Dietitians Association of Australia (DAA) committees, members involved in the competency standards development project and members of DAA special interest groups. The competency standards were considered to be a valuable professional document with varied uses including a reference standard for the accreditation of university courses, development of course curricula, student assessment and professional development. The importance of regularly reviewing the competency standards to ensure their ongoing validity was acknowledged. Stakeholders identified dietetic management skills as a potential gap in the existing standards. These included strategic planning, marketing, and performing quality assurance activities. Communication skills and conduct of outcome evaluations also were identified as requiring further attention. The survey also revealed a lack of stakeholder familiarity with the structure, function and terminology of the competency standards and a limited access to the standards. In general, stakeholders also indicated they would like to see further development of competency standards for dietitians to reflect advanced levels of practice and specialist areas. [ABSTRACT FROM AUTHOR]

Competency standards for entry level dietitians have been published since 1993. To determine their currency they were reviewed in 1998, by interviews with new graduates and surveys of stakeholders. The methodology used to develop the competency standards and the terminology used to describe them has not been published widely and this became clear during the review process. This paper explains the research methodology used, by a task force of members of the Dietitians Association of Australia, to develop the competency standards. It then defines in detail the underlying units, elements, performance criteria, range variables and evidence guide used to describe the standards. The issues surrounding the assessment of competence and competence of assessors is also discussed, and leads to the concept that competence is not relevant only to entry level practitioners. It is relevant to all professionals through the principle of lifelong learning. Our profession's future is dependent upon competent professionals actively engaging in professional development programs such as the Accredited Practising Dietitian program. [ABSTRACT FROM AUTHOR]

Fifty children who received a cochlear implant between 1991 and 1995 were evaluated for incidence of acute otitis media (AOM). Thirty-seven (74%) children had AOM before implantation and 8 (16%) after implantation. All children who had AOM after implantation had a history of AOM. A subgroup of 14 children required ventilating tubes for recurrent AOM before implantation. Five (35.7%) in this group had AOM after implantation. The incidence and severity of AOM decreased after implantation. All episodes of postimplant AOM were successfully treated with routine oral antibiotics, and no infectious complications occurred. A history of recurrent AOM should not inordinately delay cochlear implantation. [ABSTRACT FROM AUTHOR]

An abstract of the article "Ultrasound reproducibility for fetal biometry measurements: results from the INTERGROWTH-21st Project" by A. Cavallaro and colleagues is presented.

An abstract of the article "Image scoring system for quality control of umbilical and uterine artery Doppler measurement," by M. Molloholli and colleagues is presented.

An abstract of the article "Should we use the eeellipse'' or eetwo diameters'' method to measure fetal head and abdominal circumferences?" by R. Napolitano and others is presented.

This biography of serial inventor and medical doctor Willem J. ("Pim") Kolff is written by scientific/historical journalist Herman Broers. The book provides an objective and multi-perspective account of the life and work of Dr. Kolff, who put an undisputed mark on the history of organ-replacement devices by secretly inventing the first clinically functioning hemodialysis machine (in a Nazi-occupied Holland) and later in the United States leading the team that realized the first implantable fully artificial heart. Besides offering a solid historical account, the book also describes the present revival of innovation in the artificial kidney field and contains valuable lessons for a broad variety of readers. Suitable for an audience ranging from medical professionals interested in technology & technologists interested in medicine, to patients & their families, as well as policy makers & research funding parties. The review of this scientific/historic book was composed using the recommendations of Gupta for book reviews of scientific and technical books. Additionally, the reviewer team, composed of a biomedical engineer, a dialysis patient, and a nephrologist, tried to distil some lessons that may be learned from the book., (This article is protected by copyright. All rights reserved.)

Renal Solutions Allient Sorbent Hemodialysis System utilizes a two-chambered pneumatic pump (Pulsar Blood Pump, Renal Solutions, Inc., Warrendale, PA, USA) to avoid limitations associated with peristaltic pumping systems. Single-needle access is enabled by counter-pulsing the two pump chambers, thereby obviating compliance chambers or blood reservoirs. Each chamber propels 20 cc per pulse of 3 s (dual access) or 6 s (single access) duration, corresponding to a peak Reynolds number of approximately 8000 (based on inlet velocity and chamber diameter). A multimodal series of flow visualization studies (tracer particle, dye washout, and dye erosion) was conducted on a sequence of pump designs with varying port locations and diaphragms to improve the geometry with respect to risk of thrombogenesis. Experiments were conducted in a simplified flow loop using occluders to simulate flow resistance induced by tubing and dialyzer. Tracer visualization revealed flow patterns and qualitatively indicated turbulence intensity. Dye washout identified dwell volume and areas of flow stagnation for each design. Dye erosion results indicated the effectiveness and homogeneity of surface washing. Compared to a centered inlet which resulted in a fluid jet that produced two counter-rotating vortices, a tangential inlet introduced a single vortex, and kept the flow laminar. It also provided better surface washing on the pump inner surface. However, a tangential outlet did not present as much benefit as expected. On the contrary, it created a sharp defection to the flow when transiting from filling to ejection.

We report for the first time a child with chronic granulomatous disease (CGD) who developed acute lymphoblastic leukemia (ALL). The diagnosis of CGD was made at the age of 4 months, by studies of his neutrophil functions. The superoxide production of the cells was negligible, as was the bactericidal activity. He was found to have a deficiency of the gp91(phox) subunit of the leukocyte NADPH oxidase, with the X-linked inheritance of the disease. DNA analysis revealed a C nucleotide insertion between C1028 and T1029. This insertion has not been described before and causes a frameshift and a premature stop codon at amino-acid position 347. The mother was found to be a carrier of this mutation. At the age of 16 months, the patient developed T-cell ALL. He was treated for 2 years, and today, 10 years since the diagnosis, he is disease-free. During the course of ALL and later, he suffered from recurrent severe pyogenic infections, but careful detection of the etiological agent and promptly instituted specific treatment resulted in his complete recovery. Although primary immune deficiencies have been reported to have an increased tendency to develop malignancies, until now there have been no reports of CGD patients with ALL., (Copyright 2005 Wiley-Liss, Inc.)

An intrauterine origin of childhood acute lymphoblastic leukaemia (ALL) was proven by the identical clonotypic gene rearrangement in the concordant leukaemias of monozygotic twins, arising from a single clonogenic progeny. The monozygotic twins, presented at the age of 22 months with acute megakaryoblastic leukaemia (AML-M7) in one and myelodysplasia transformed to AML-M7 in the other. Leukaemic cells in both twins carried trisomy 21 and additional different clonal evolution changes of del(20q) in the first twin and trisomy 8 in the second. AML-M7 of late infancy with trisomy 21 may be included in the leukaemias of intrauterine origin, possibly a result of genotoxic insult.

The BioLogic-DTPF System (DTPF) combines the Biologic-DT hemodiabsorption system (DT) in series with the Biologic PF push-pull pheresis system (PF) in which PF membranes separate plasma for direct contact between plasma proteins and the sorbents. Preliminary studies conducted in bovine serum albumin (BSA) solution and in bovine plasma allowed charcoal and silica to be evaluated as adsorbents for the PF module. Equilibrium binding experiments in BSA showed a high capacity of cytokine (IL-1 beta, TNF alpha) binding by powdered charcoal, 70-90 ng/g. Kinetic binding studies in bovine plasma revealed relatively quick adsorption of IL-1 beta and IL-6 by charcoal with the capacity range of 1.2-2.0 ng/g for tested cytokines (IL-1 beta and TNF alpha). Further laboratory studies with plasma have shown that powdered silica has an even greater binding capacity, up to 13 ng/g for TNF alpha depending upon particle size, and more rapid binding for all tested cytokines than powdered charcoal. Cholestyramine is a more efficient sorbent for removal of endotoxin than either charcoal or silica. In vitro tests using whole blood have demonstrated that the DTPF, with powdered charcoal as the sorbent, clears cytokines (TNF alpha, IL-1 beta, and IL-6) at 12.6-23.4 ml/min, bilirubin at 17.8-34.7 ml/min, and creatinine at 53.6-82.6 ml/min. The removal of some cytokines during the first clinical trial is also discussed.

Hemodiabsorption is a selective chemical removal process during which blood passes through dialysis membrane packages surrounded by a suspension of fine sorbent particles. The BioLogic-DT system contains charcoal and cation exchangers in a suspension that passes through dialysate spaces of a cellulosic membrane plate dialyzer. The system has proven effective in treatment of patients with serious drug overdose and has demonstrated positive effects in treatment of stage 4 coma due to hepatic failure. Recently, the charcoal in this system has been preloaded with branch chain amino acids to return these acids to patients while aromatic amino acids are removed. Further improvements include addition of osmotically active agents to the priming fluid and sorbent to increase blood oncotic pressure and transfer of ascitic fluid to blood while ultrafiltration transfers fluid out of the blood. Clinical testing of these improvements is now beginning in patients with ascites and encephalopathy due to chronic hepatic insufficiency and cirrhosis. Future improvements will include protein permeable membranes to increase removal of protein-bound toxins and addition of hepatic cells downstream from the hemodiabsorption unit.

Previous theoretical analysis has indicated that adequate mass transfer is possible in a dialyzer with reciprocating membrane motion provided that the dialysate concentration of uremic substances is kept low. Earlier models have utilized a collection of sorbents (charcoal, urease, and a cation exchanger) constrained next to the dialyzer membranes. We have designed a new dialyzer with a sorbent suspension having free access from a reservoir to the spaces between membrane packages. At a treatment rate of 150 ml/min/m2, the in vitro creatinine clearance is 75 ml/min/m2, which agrees within experimental accuracy with the theoretical prediction. The creatinine clearance, flow resistance, and compliance of the dialyzer are constant during four to six hours of testing. In vivo tests have been performed during urea and creatinine infusion in a normal dog and in a dog with 3/4 nephrectomy. The in vivo creatinine clearance agrees within 10% with the in vitro clearance. Sodium, potassium, calcium, and bicarbonate fluxes are acceptable for patients in renal failure. The new design allows a higher capacity for urea and creatinine, since larger amounts of sorbent may be used.

Doppler ultrasound is a noninvasive technique for monitoring moving objects such as flowing blood while ignoring stationary objects such as shunt tubing. A Doppler system was investigated to determine its sensitivity in detecting particulate release in blood during hemodialysis. Seven hemodialysis procedures with dogs and six trials with humans were done using a sorbent suspension reciprocating dialyzer ( SSRD ). Two additional trials were done with humans using a cellulose acetate hollow-fiber dialyzer (HFD). A large increase (approximately twofold) was found in the reflected Doppler signal in outflowing blood from the SSRD and HFD in both dogs and humans. Numerous additional studies to characterize the nature of the particulate matter showed platelet aggregates in the dogs and fibrinogen-fibrin degradation products in the humans to be present in the outflowing blood. In vitro studies suggested microscopic air bubbles (less than 25 micron in diameter) may have contributed to the particulate matter detected during hemodialysis by this sensitive monitoring system.