bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Lansoprazole in Eradicating Helicobacter pylori: A Meta‐Analysis
Authors: Bazzoli Franco , Pozzato Paolo , Zagari Maurizio , Fossi Stefania , Ricciardiello Luigi , Nicolini Gianni , Berretti Debora , De Luca Luca
Published: March 2003

Background.

The combination of lansoprazole with antibiotics either as double or triple therapy has demonstrated an H. pylori eradication rate of between 80 and 90%. With the aim of providing a complete revision of the results of these clinical studies and a quantification of the efficacy of lansoprazole in eradicating H. pylori and healing peptic ulcers, we have undertaken a meta‐analysis of all the controlled studies published in the literature.

Methods.

This meta‐analysis reviewed all randomized, controlled clinical trials published as full text articles in English between 1993 and 1996 that reported the efficacy of lansoprazole treatment as monotherapy or in combination with antibiotics in the treatment of peptic ulcer and in eradicating H. pylori. Articles were identified from the literature, which included both manual and computerized research (MEDLINE) and references provided by articles in this area. In order to compare the efficacy of triple therapy comprising lansoprazole vs. another PPI, data from abstracts (n = 5) were used, as no full text articles were located.

Results.

This systematic review of the literature documents that lansoprazole has a high degree of efficacy in eradicating H. pylori, above all when used within treatment schemes including amoxicillin or clarithromycin, and metronidazole or tinidazole. This efficacy is comparable to that of other PPIs.

Conclusions.

Triple therapy allows the eradication of H. pylori in more than 85% of cases in patients with peptic ulcer. In addition, there is a substantial comparability of the efficacy of lansoprazole and omeprazole when they are used together with other anti‐infective agents. Thus, lansoprazole appears to offer an option in the eradication of H. pylori.
Helicobacter pylori and Peptic Ulcer Disease Therapies: A Survey of Gastroenterologists in Israel
Authors: Fireman Zvi , Segal Aryeh , Moshkowitz Menachem , Kopelman Yael , Sternberg Amos
Published: March 2003

Background. Eradication of Helicobacter pylori has become a therapeutic option in the treatment of patients with peptic ulcer disease. The aim of this study was to evaluate the current management strategies of Israeli gastroenterologists in the diagnosis and treatment of H. pylori‐related peptic ulcer disease, 14 years after the discovery of H. pylori.

Materials and Methods. A questionnaire was mailed to all specialists in gastroenterology, members of the Israel Gastroenterological Association (IGA). Replies were received from 60% of Israel Board‐certified gastroenterology specialists.

Results. Over 89% of the gastroenterologists (89.1%) noted that they recommend anti‐H. pylori treatment. 94.5% said that they treat duodenal ulcer in the first presentation with anti‐H. pylori medication and 75% said that they do so in cases of recurrent duodenal ulcer. According to the replies received, there is a strong consensus towards triple treatment as the favored anti‐H. pylori treatment; no one noted the use of dual treatment. Seven‐day triple treatment was prescribed by 83.6% of the gastroenterologists who responded. Of these, the great majority, 89.1%, stated that they use proton pump inhibitors (PPI) in combination with any two of the following antibiotics: metronidazole (47.3%), tinidazole (29.1%), clarithromycin (61.8%), and amoxicillin (40%).

Conclusion. At the time of the survey, most Israel Board‐certified gastroenterology specialists prescribed triple anti‐H. pylori treatment of one‐week’s duration.
Comparison of Meal‐Stimulated Serum Gastrin Response in Helicobacter pylori–Positive Duodenal Ulcer and Asymptomatic Volunteers With and Without H. pylori Infection
Authors: Kamada Tomoari , Haruma Ken , Komoto Kunihiko , Mihara Mitsuhiro , Sumii Koji , Kajiyama Goro
Published: March 2003

Background. Duodenal ulcer (DU) patients exhibit raised postprandial gastrin release as compared to that in healthy controls. It is believed that serum pepsinogen I (PG I) concentration reflects the chief cell mass and that hyperpepsinogenemia I plays an important role in the pathogenesis of DU. Currently, strong evidence suggests that Helicobacter pylori (H. pylori) infection plays an important role in the pathogenesis of DU.

Materials and Methods. Subjects consisted of 15 patients with H. pylori–positive DU, 10 H. pylori–positive volunteers, and 35 H. pylori–negative volunteers. Blood samples were taken before and at 15, 30, and 60 minutes after eating the test meal, which consisted of 100 gm rice, 130 gm chicken, and 1 egg. The 1‐hour integrated gastrin response (IGR) was taken as the area under the serum gastrin time curve, calculated by the trapezoid method. Serum gastrin (SG) and fasting serum PG I concentrations were measured by radioimmunoassay.

Results. Meal‐stimulated SG response and fasting PG I concentration were significantly higher in DU patients than in H. pylori–positive and –negative volunteers. The DU patients were divided into two groups in accordance with their IGR levels as follows: hyper‐IGR and normo‐IGR. Serum PG I concentration was significantly higher in the hyper‐IGR than in the normo‐IGR group.

Conclusions. The DU patients differed in some way (other than H. pylori infection) from the H. pylori–positive healthy volunteers. The fact that hyper‐IGR DU patients had higher serum PG I concentrations suggests that patients in this group may be acid hypersecretors.
A Population‐Based Survey on Gastrointestinal Tract Symptoms and Helicobacter pylori Infection in Children and Adolescents
Authors: De Giacomo Costantino , Valdambrini Valeria , Lizzoli Francesca , Gissi Anna , Palestra Marina , Tinelli Carmine , Zagari Maurizio , Bazzoli Franco
Published: March 2003

Background.  Helicobacter pylori infection is a frequent infection mainly acquired in childhood. Even if the infection is almost invariably associated with mild to severe gastro‐duodenal lesions, no specific clinical picture has been identified. The aim of this study was to evaluate the presence of dyspeptic symptoms and their relationship with the presence of H. pylori infection in the first two decades of life.

Materials and Methods.  A school‐population sample size of 808 subjects from 6‐ to 19‐year‐olds was investigated for the presence of gastrointestinal tract symptoms and evaluated by a 13C‐urea breath test for H. pylori infection. The relationship between clinical findings and H. pylori infection was evaluated by χ2 statistic or Fisher's exact test, as appropriate.

Results.  Symptoms of dyspepsia were identified in 45% of subjects, while the picture of ulcer‐like and dysmotility‐like forms were present in 3–4%. H. pylori infection was demonstrated in 95 (11.8%) subjects, 49.5% of them without symptoms. Severe epigastric pain and ulcer‐like dyspepsia were significantly associated with H. pylori infection, while recurrent abdominal pain or dysmotility‐like dyspepsia were not.

Conclusions.  Dyspeptic symptoms are frequent in children, and its association with H. pylori infection is more evident than with recurrent abdominal pain. The age at which the infection is acquired seems to be under 6 years of age.
Cancer Screening and Early Detection Managing Malpractice Risk
Authors: Frank‐Stromborg Marilyn , Bailey Lara J.
Published: March 2003

purpose
: The purpose of this report is to educate healthcare professionals aboutthe legal risks of conducting cancer screening examinations and necessaryrisk reduction practices.

overview
: The authors describe the elements of a medical malpractice claim, thehealthcare professionals' legal standard of care, theories of malpractice liability, common factors related to missed or delayed diagnoses,malpractice defenses, and risk reduction practices.

clinical implications
: Healthcare professionals, including physicians, physician assistants,advanced practice nurses, and social workers, have been shown to be clinically effective in cancer screening, and early detection of many cancersleads to improved long‐term survival rates. Healthcare professionals who conduct cancer early detection examinations and counsel patients in cancerscreening programs need to be aware of the common legal theories under which lawsuits are brought related to cancer detection examinations. Importantsteps in reducing the risk of malpractice include developing creative strategies to address the theories of liability in the area of cancerscreening and early detection; keeping abreast of changes in national and international cancer screening recommendations; monitoring the literature forapproaches to decrease liability; and scrupulously maintaining documentation of all findings and interactions among providers and between providers and patients.
Genetic Testing for Prostate Cancer
Authors: Diefenbach Michael A. , Schnoll Robert A. , Miller Suzanne M. , Brower Lisa
Published: March 2003

Abstract

Purpose:

As researchers come closer to identifying the genes responsible for prostate cancer, the possibility of genetic testing for men at risk for prostate cancer becomes more likely. This study examined the following: 1) the degree to which men with (n = 43) or without (n = 83) a family history of prostate cancer would be interested in genetic testing; and 2) the degree to which interest in testing was associated with demographic, family history, and psychosocial factors.

Description of study:

Participants (N = 126) were accrued through patients who had been treated for prostate cancer at Fox Chase Cancer Center (n = 39) and through newspaper advertisements (n = 87). All participants completed a questionnaire sent by mail.

Results:

Seventy‐four percent of men were probably (50%) or definitely (24%) interested in testing. Participants with a family history of prostate cancer reported that they would be willing to pay substantially more for a genetic test compared with those without a family history. Elevated worry about prostate cancer and concerns about treatment‐related side effects were associated with greater interest in genetic testing.

Clinical implications:

Findings demonstrate a need for the development of genetic counseling protocols for at‐risk men who are interested in genetic testing, once this test becomes available.
Exercise and Weight Gain in Breast Cancer Patients Receiving Chemotherapy
Authors: Schwartz Anna L.
Published: March 2003

Purpose: Weight gain is a common side effect for women receiving adjuvant chemotherapy and may have negative long‐term implications for survival. The purpose of this study was to examine the effects of aerobic exercise on weight gain in women with breast cancer receiving adjuvant chemotherapy.

description of Study: Seventy‐eight women who had recently received a diagnosis of breast cancer and who were beginning adjuvant chemotherapy were enrolled in a home‐based exercise study during the first four cycles of chemotherapy. Weight change, body mass index, anorexia, nausea, fatigue, caloric expenditure during exercise, and functional ability were recorded.

Results: Women who adhered to the exercise program maintained their body weight, while nonexercisers steadily gained weight (P < .05). There were no differences in incidence or intensity of nausea or anorexia between the exercisers and nonexercisers. Women who exercised over the four cycles of chemotherapy improved their functional ability (mean 23%) compared to the nonexercisers who showed significant declines in functional ability (mean −15%).

clinical Implications: Exercise may be an effective intervention to minimize weight gain in women with breast cancer who are receiving adjuvant chemotherapy. Preventing weight gain in these patients may be important in preventing recurrent disease and other comorbidities associated with excess weight.
Using RNAi to investigate orthologous homeotic gene function during development of distantly related insects
Authors: Brown Susan J. , Mahaffey James P. , Lorenzen Marcé D. , Denell Robin E. , Mahaffey James W.
Published: March 2003

Gene product distribution is often used to infer developmental similarities and differences in animals with evolutionarily diverse body plans. However, to address commonalties of developmental mechanisms, what is really needed is a method to assess and compare gene function in divergent organisms. This requires mutations eliminating gene function. Such mutations are often difficult to obtain, even in organisms amenable to genetic analysis. To address this issue we have investigated the use of double‐stranded RNA interference to phenocopy null mutations. We show that RNA interference can be used to phenocopy mutations of the Deformed orthologues in Drosophila and Tribolium. We discuss the possible use of this technique for comparisons of developmental mechanisms in organisms with differing ontogenies.
Reproductive isolation inCaenorhabditis:terminal phenotypes of hybrid embryos
Authors: Baird Scott E. , Yen Wei‐Chih
Published: March 2003

SUMMARYSeveral interspecific combinations of the “elegans” group ofCaenorhabditisspecies are cross‐fertile. Most F1 hybrids from these crosses arrest during embryogenesis. Developmental defects observed in hybrid embryos include defects in gastrulation initiation, defects in embryonic compaction, and defects in embryonic elongation. These reproductive barriers have arisen multiple times in the evolution ofCaenorhabditis.
The scale independence of evolution
Authors: Leroi Armand M.
Published: March 2003

SUMMARYIn this paper, I argue that the ultimate causes of morphological, and hence developmental, evolution are scale independent. In other words, micro‐ and macroevolutionary patterns show fundamental similarities and therefore are most simply explained as being caused by the same kinds of evolutionary forces. I begin by examining the evolution of single lineages and argue that dynamics of adaptive evolution are the same for bacteria in test‐tube evolution experiments and fossil lineages. Similarly, I argue that the essential features of adaptive radiations large and small can be attributed to conventional forces such as mutation and diversifying natural selection due to competition. I then address recent claims that the molecular features of metazoan development are the result of clade‐level selection for evolvability, and suggest that these features can be more easily explained by conventional individual‐level selection for the suppression of deleterious pleiotropic effects. Finally, I ask what must be known if we are to understand the ultimate causes of molecular and developmental diversity.
Starting from fins: parallelism in the evolution of limbs and genitalia.
Authors: Burke Ann Campbell , Rosa‐Molinar Eduardo
Published: March 2003

SUMMARY The March/April 2002 issue of Evolution and Development focused on three presentations made at the Starting from Fins: Parallelism in the Evolution of Limbs and Genitalia symposium held as part of the 2001 Chicago meeting of the Society of Integrative and Comparative Biology. The intention of the symposium and the publication of the presentations was to extend discussion of the potential and the limits of using serial homologues to understand developmental aspects of morphological evolution. The March/April 2002 issue concentrated on unpaired fin to genitalia transitions. This issue focuses on paired fins to limbs and highlights the need for developmental data to be integrated with data from fossil material, phylogenetic analysis, and explicitly comparative studies. Coates et al. use phylogenetic methods to explore the limb/fin characters of taxa, but their analysis departs somewhat from the usual in that the reference group for organisms includes sister group taxa not usually considered true tetrapods. They state that including finned taxa from the stem group permits an attempt to distinguish the primitive condition of the characteristics demonstrated by the crown group, that is, “limbed tetrapods.” In focusing on limb characters specifically and including aspects of the appendicular girdles, Coates et al. highlight morphological details and trends within a given phylogeny. They also demonstrate the degree of relevance of limb characters during the establishment of lineages and their branching patterns by using only limb characters to generate a tree and use a direct comparison of serial versus special homologies to explore the degree of evolutionary parallelism between fore‐ and hindlimbs. The preliminary conclusions indicate a high level of independence between the serially homologous fore‐ and hindlimb. Innes et al. present outcomes from the use of cutting edge molecular genetic approaches to understand developmental aspects of limb morphology. In a manner conceptually similar to Coates et al.'s use of fossil characters, Innes et al. use the serial analysis of gene expression to sort differences from similarities in the gene expression profiles of fore‐ and hindlimbs of the same embryos. Although these gene expression patterns are likely to reflect the serial homology of the paired limbs, they are silent in terms of our understanding both the profound and subtle differences between fore‐ and hindlimbs in any given species. Innes et al. point out the volume of data generated by SAGE far exceeds our ability to interpret its biological meaning. The studies presented here and in the March/April issue are excellent examples of the need to interpret complex data in light of collective knowledge of evolutionary history. We hope the insights gained from the symposium and papers contribute to a dialogue on how to integrate different approaches and assist in moving forward the field of Evolution and Development.
Protection of DNA during early development: adaptations and evolutionary consequences
Authors: Epel David
Published: March 2003

SUMMARY The rapidly dividing cleavage stages of embryos do not have the typical responses to cell damage, such as induction of the heat shock response, use of mitotic checkpoints, or use of apoptosis to eliminate severely damaged cells. This could create problems with integrity of DNA, but the solution in these embryos appears to be a “be prepared” approach, in which specific adaptations are used to minimize DNA damage during cleavage and the use of apoptosis at the mid‐blastula transition to remove any cells that were nevertheless damaged. It has been assumed that this approach has evolved because of the advantage of rapid production of a motile larvae. Alternatively, this particular approach may have the selective advantage of increasing mutation rate when there are greater environmental stresses. This could provide more variants on which selective pressures could act and thus accelerate evolution during environmentally stressful periods.
Mechanical Circulatory Support for Severe Heart Failure After Operation
Authors: Koyanagi Hitoshi , Kitamura Masaya , Aomi Shigeyuki , Hachida Mitsuhiro , Nishida Hiroshi , Endo Masahiro
Published: March 2003

To evaluate the clinical results of circulatory support for severe heart failure after operation, we examined 62 patients (39 males and 23 females) who underwent circulatory support for postoperative heart failure from 1984 to 1996. Their ages ranged from 22 to 78 (mean 52) years. In 62 patients, 35 had valvular, 25 had ischemic, and 2 had congenital heart disease. Postoperation, 29 patients underwent venoarterial bypass (VAB), 20 had biventricular bypass (BVB), and 8 had left ventricular bypass (LVB). The remaining 5 patients received a pulsatile left ventricular assist device (LVAD). The weaning and discharge rates of the patients by type of support were 51.7% and 31.0% with VAB, 75.0% and 55.0% with BVB, 87.5% and 37.5% with LVB, and 60.0% and 40.0% with LVAD, respectively. The complete results of this series (64.5% weaning rate and 40.3% discharge rate) were acceptable.
Assisted Circulation for End‐Stage Chronic Heart Failure
Authors: Liotta Domingo
Published: March 2003

Despite the trend in the use of electromechanical left ventricular assist devices (LVAD), the highly compact, long lasting, and endurance characteristics of the new pneumatic system has its place in the treatment of end‐stage chronic heart failure. The ProCor Model 1 LVAD has an implantable pump which is small in size and has a double pusher plate design. The portable power pack is small, too. It is easy to carry, and it is synchronized to the ECG to pump during the patient's diastolic period. Constant driving conditions are set as follows: frequency rate, 60 bpm; systolic percentage, 25 (250 ms); dP/dt, 1,800 (45 ms) mm Hg s; and driving pressure, 250 mm Hg to have a basic 3.500 L/min pump output for prolonged circulatory assistance. The 6 mm internal diameter (ID) percutaneous multipurpose pneumatic tube contains within its wall both a spiral of MP35N alloy wire connected to the myocardial lead for ECG sensing and a spiral serving as mass ready to be used for cardiac pacing with an external pacemaker when necessary. The aortic porcine bioprosthesis maintains the aortic root and the sinus ridge.
Plasma Cytokine Levels and Coagulation and Complement Activation During Use of the Extracorporeal Liver Assist Device in Acute Liver Failure
Authors: Hughes Robin D. , Nicolaou Nicholas , Langley Peter G. , Ellis Antony J. , Wendon Julia A. , Williams Roger
Published: March 2003

Multiple organ failure frequently occurs in patients with acute liver failure, and this has been associated with increased cytokine production. Treatment by hemoperfusion with an extracorporeal liver assist device (ELAD) containing human liver‐derived cells was performed in 12 patients with acute liver failure. Over the first 6 h, there were significant increases in plasma tumor necrosis factor alpha (TNFα; from 114 ± 54 pg/ml [mean ± SEM] to 236 ± 161 pg/ml, p < 0.05) and interleukin (IL)‐6 (260 ± 121 pg/ml to 445 ± 149 pg/ml, p < 0.05) but not in interferon gamma (IFNγ). A similar pattern with a small peak increase was observed for complement C5b‐9 complex. Plasma C‐reactive protein (CRP) and thrombin antithrombin (TAT) III complex showed small peaks after 24 h of ELAD hemoperfusion. No such changes were seen in 12 control patients with acute liver failure who were treated with intensive care alone. These transitory effects, without changes in blood pressure, are likely to be due to the contact of the blood with the dialyzer membrane. There was no evidence of the clearance of cytokines by the ELAD.
Hepatocyte Attachment on Biodegradable Modified Chitosan Membranes: In Vitro Evaluation for the Development of Liver Organoids
Authors: Murat Elçin  , Dixit Vivek , Gitnic Gary
Published: March 2003

Extracellular matrix structures including glycosaminoglycans play a critical role in cell attachment, differentiation, and morphogenesis. We evaluated chitosan ([1 → 4] linked 2‐amino‐2‐deoxy‐β‐ D‐glucan) as a biomaterial for hepatocyte attachment because of its structural similarity to glycosaminoglycans. Freshly isolated rat and fetal porcine hepatocytes were seeded on chitosan membranes that had been previously blended with collagen, gelatin, or albumin to improve biocompatibility and surface roughness. The optimal cell density and attachment kinetics were quantified. The metabolic activity was investigated by measuring daily urea and total protein secretion by the cells for 2 weeks. While collagen blended‐chitosan membranes provided a good attachment surface for rat hepatocytes, albumin and gelatin blended chitosan membranes were superior for fetal porcine hepatocyte attachment. The optimal attachment was maintained with membranes of medium molecular weight (Mr= 750,000 daltons) chitosan, at 3–4 × 10 4 cells/cm2 after 3 h of incubation. In vitro experiments demonstrated that fetal porcine hepatocytes survived at least 14 days when seeded on the chitosan‐albumin matrix, demonstrating that this biomaterial can provide suitable cell attachment scaffolds for creating liver tissue organoids.
Evidence of Bacterial Biofilm in Tubing from Hydraulic Pathway ofHemodialysis System
Authors: Man Nguyen‐Khoa , Degremont Axel , Darbord Jean‐Claude , Collet Michel , Vaillant Patrick
Published: March 2003

Abstract: Biofilms consist of microorganisms immobilized at a substratum surface embedded in an organic polymer matrix of bacterial origin. Tubing drawn from the fluid pathways within dialysis machines of various models were investigated for biofilm. Scanning electron microscopy (SEM), performed on approximately 2 cm2 samples of the tubing inner surfaces revealed that the inner surfaces of the tubing were covered with biofilms consisting of numerous deposits and glycocalix at different stages of formation with components containing bacteria and algae. Evaluations of biomass were performed from tubing sections of various lengths and inner diameters put in tubes containing water for injection and immersed in an ultrasound washtub for 1 h to ensure sloughing of the biofilm. Living bacteria were identified by plating on nutrient agar media and incubation for 48 h at 37°C. Epifluorescent stains were used for the total bacteria count. Lipopolysaccharide levels were determined by the endotoxin activity measurements. Polyoside contents were determined by the colometric method, and the chemical oxygen demand was measured to evaluate the amount of organic substance. Biofilms detached from tubing samples drawn from the water path, bicarbonate path, and fresh dialysate path within dialysis machines contained approximately 1.103–1.106 total bacteria/cm 2, yet only some living bacteria were found. Endotoxin levels ranged from 1 to 12 EU/cm2. In contrast in the dialysate fluid, no bacteria were found, and the endotoxin content was under the detection level of the method. The polyoside content and chemical oxygen demand of the biomass ranged from 11 to 83 μg/cm2 and from 53 to 234 mg/cm 2, respectively. It is concluded that a germ‐ and endotoxin‐free dialysate does not exclude the risks and hazards of bacteria and endotoxin discharge from biofilm developed on the fluid pathway tubing, acting as a reservoir for continuous contamination, and efforts in the optimization of cleaning and disinfection procedures used for hemodialysis systems should aim to detach and neutralize biofilm when necessary.
Kinetics of131I‐β2Microglobulin in Hemodialysis Patients: Assessment Using Total Body Counting
Authors: Chanard Jacques , Caudwell Valérie , Valeire Jacques , Vincent Claude , Randoux Christine , Wuillai Anne , Wynckel Alain
Published: March 2003

Abstract:The kinetics of131I‐β2‐microglobulin (β2‐M) were studied using external total body gamma counting in a low noise chamber after administration of trace doses of radioactivity (4 μCi) in 14 uremic patients treated by either hemodialysis or hemofiltration. Data were collected over a 1 week period that included 3 dialysis sessions. The following artificial membranes were used: Cuprophan, polyacrylonitrile AN69, polysulfone, polymethylmethacrylate (PMMA), and polyamide. Radiolabeled β2‐M excretion by an extrarenal route was nearly nonexistent. The131I‐β2‐M half‐life was between 2.4 and 8 days, shorter in patients with residual diuresis. A mean removal of 153 ± 33 mg/L of β2‐M was obtained per dialysis session with a highly permeable membrane. A hemofiltration session (25 L exchange per session) was slightly more efficient in removing β2‐M than a 4 h hemodialysis session with the same AN69 highly permeable membrane. The amounts of131I‐β2‐M binding on the membranes, expressed as β2‐M equivalents, were 0, 16, 54, 58, and 59 mg/m2for Cuprophan, polysulfone, polyacrylonitrile AN69, polyamide, and PMMA, respectively. In conclusion, the decrease of total body gamma counting directly reflected the β2‐M breakdown and removal in hemodialysis patients. Intact β2‐M was removed by convection with synthetic, highly permeable membranes. In addition, membrane adsorption accounted for 15% (polysulfone) to near 100% (PMMA) of the β2‐M removal per session. Adsorption was of the same magnitude regardless of the dialysis technique in use, indicating a membrane saturability process. None of the currently available dialysis procedures based on a 3 sessions per week schedule can balance β2‐M generation.
Kolff's Credo: New Ways of Thinking!
Authors: Teschan Paul E.
Published: March 2003

Dr. Willem J. Kolff's imaginative venturesomeness in adopting “new ways of thinking” has served as an encouraging model for this author's research career. In appreciation of his leadership and beginning with the favorable results that attended the initial use of the Brigham‐Kolff artificial kidney at a renal center in the Korean war, this presentation summarizes four experiences to illustrate how “new ways of thinking” produced new results and new research, namely, the concept and use of prophylactic daily hemodialysis; the use of a model of acute renal failure in rats to examine mechanisms of pathogenesis and means of prevention; the recognition of patients' uremic illness as an encephalopathy that can be quantified by appropriate measures; and the use of daily peritoneal dialysis and quantified EEGs in rats to explore relationships between dialysis‐induced concentrations of potentially toxic solutes, quantified indices of symptomatic uremic encephalopathy, and concurrent, localized metabolic abnormalities in the brain. The results of these “new ways of thinking” suggest that we may ultimately come to understand the clinical uremic illness and its response to dialysis.
Plasmapheresis with a Substitution Solution of Human Serum Protein (5%) Versus Plasmapheresis with a Substitution Solution of Human Albumin (5%) in Patients Suffering from Autoimmune Diseases
Authors: Bambauer R. , Arnold A.
Published: March 2003

Abstract: Therapeutic plasma exchange (TPE) has been used extensively for over 2 decades to treat a variety of autoimmune and congenital diseases and is now widely accepted. The primary objective of this study was to compare the clinical efficacy of two plasma exchange preparations, human serum protein (HSP) and human albumin (HA). Twenty‐four patients in the following disease categories underwent TPE using either HSP (Biseko, 5%) or HA (5%): systemic lupus erythematosus, 8; glomerulonephritis, 8; myasthenia gravis, 2; Guillain‐Barré‐syndrome, 2; recurrent iritis, 1; pemphigoid, 1; uveitis, 1; and vascular retinitis, 1. There was no statistically significant difference in the average number of TPEs needed in the HSP group (13.5) and HA (13.8) measured over the first 6 weeks of treatment. The secondary parameters, in particular the immunological parameters IgG and IgA, provided evidence that plasma exchange with HSP may have some advantages over HA, and confirmatory studies in a larger group of patients are indicated. Adverse events during TPE occurred in both the HAS group (4 patients) and the HA group (4 patients). However, patients in the HSP group were older (12.3 years), were suffering from more complicated autoimmune diseases, and the number of occasions (days) on which these were reported (6 days) was less than in the HA group (11 days). One patient in the HA group died from septic‐toxic circulatory collapse on Day 49 due to an infection with resistant strains of Staphylococcus aureus. Infections in other patients did not occur; all showed considerable improvement in their symptoms and completed the study in good general condition.
Thoughts and Progress
Authors: Sauer  , Frank  , Bücherl
Published: March 2003

It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philosophy, suggestions, and/or thoughts for the future. Proposal of a New Electromechanical Total Artificial Heart: The TAH Serpentina

A new type of energy converter for an electromechanical total artificial heart (TAH) based on the principle of a unidirectional moving motor is described. Named the TAH Serpentina, the concept consists of 2 major parts, a pendulum shaped movable element fixed on one side using a joint bearing and a special shaped drum cam. Pusher plates are mounted flexibly to the crossbar of the pendulum. A motor drives the special shaped drum cam linked to the pendulum through a ball bearing. The circular motion of the unidirectional moving brushless DC motor is transferred into the linear motion of the pendulum to drive the pusher plates. Using a crossbar with a variable length, the stroke of the pendulum and therefore the displaced blood volume is alterable. To achieve a variable length, an electric driven screw thread or a hydraulic system is possible. Comparable to the natural heart, cardiac output would be determined by frequency and stroke volume.
Advantage of the Uncemented Total Hip System with Three Spiked Socket
Authors: Akamatsu Noriya , Hamada Yoshiki , Nakajima Ikumasa , Ide Takatoshi , Horiuchi Tadahiro
Published: March 2003

Abstract: A total hip arthroplasty was performed on 112 joints of 110 patients from November 1983 to January 1998 using three different types of uncemented total hip systems with a three spiked socket. The clinical results of 87 joints of 85 patients, followed up 5 years or more after operation, were evaluated with the comparison among the three different types (original type [JIAT] in 6, type Y in 24, and type Y2 in 57). In 73 of the 87 patients, the age at the time of the operation was more than 60. The preoperative diagnosis was osteoarthritis with acetabular hypoplasia in 61, rapidly destructive coxarthrosis in 17, and so on. We have been receiving excellent clinical results of patients who were implanted with type Y2 compared with the other types. There was no different clinical results between patients who were less than 60 and patients who were over 60. Injuries of neurovascular bundle relating to the penetration of the tip of the spike, which was a concern in this type of socket, were not encountered. The type Y2 uncemented total hip system shows an indication of being successful even if the patients have poor bone stock in acetabulum or are elderly.
Evaluation of the Optimal Driving Mode During Left Ventricular Assist with Pulsatile Catheter Pump in Calves
Authors: Mihaylov D. , Verkerke G.J. , Blanksma P.K. , Elstrodt J. , De Jong E.D. , Rakhorst G.
Published: March 2003

Abstract: The pulsatile catheter (PUCA) pump, a left ventricular assist device, was tested during acute experiments in calves using asynchronous and ECG‐synchronous assist modes. The aim of the study is to compare ECG‐synchronous and asynchronous assist and to find the optimal driving mode for the PUCA pump with respect to left ventricular myocardial oxygen consumption (LV MVO2), pump flow, and coronary flow. LV MVO2 decreased significantly during the asynchronous (from 7.77 to 6.46 ml/min/100 g) as well as during the ECG‐synchronous mode (from 8.88 to 7.84 ml/min/100 g). The pump flow was highest during the ECG‐synchronous assist (2.94 L/min), followed by the asynchronous assist (2.79 L/min). The peak coronary flow depended strongly on pump ejection timing and showed the best flow patterns during the ECG‐synchronous assist. We concluded that for PUCA pump support both asynchronous and ECG‐synchronous assists significantly reduce LV MVO2 and that the pump flow generated is enough to maintain the systemic circulation. However, we find the ECG‐synchronous mode preferable because this mode optimizes coronary flow patterns at the same time.
Evaluation of an Implantable Motor‐Driven Left Ventricular Assist Device
Authors: Kikugawa Daiki , Murakami Taiji , Endo Koichi , Fujiwara Takashi , Takatani Setsuo
Published: March 2003

A console based implantable motor‐driven left ventricular assist device (LVAD) was developed and tested. Ten sheep weighing 42–73 kg (mean, 54.4 kg) were used as the experimental animals. Four animals survived 5–12h (mean, 9.5 h). The mean pump flow was 1.63 L/min, ranging from 0.8 to 2.5 L/min. The cause of termination was respiratory failure in 3 animals, bleeding in 2, ventricular fibrillation in 2, vent tube obstruction in 1, thrombus formation in 1, and mechanical failure of the driving console in 1. Following the in vivo studies, the computer regulated controller was tested in a mock circulatory system. The LVAD provided 5.34 L/min of maximum output against a mean afterload of 80 mm Hg with a filling pressure of 15 mm Hg when the pump rate was 80 bpm in the fixed rate mode. With an increase in the pump afterload from 80 to 140 mm Hg, the total system efficiency varied from 7.81 to 8.34% when the pump preload was 15 mm Hg. An ultracompact, completely implantable electromechanical VAD has been under development. This device should fit in a 60 kg adult. As the next step, we are preparing to implant this ultracompact implantable VAD with an electronic controller in an animal model with better results being expected.
Motor Feedback Physiological Control for a Continuous Flow Ventricular Assist Device
Authors: Waters  , Allaire  , Tao  , Adams  , Bearnson  , Wei  , Hilton  , Baloh  , Olsen  , Khanwilkar
Published: March 2003

The response of a continuous flow magnetic bearing supported ventricular assist device, the CFVAD3 (CF3) to human physiologic pressure and flow needs is varied by adjustment of the motor speed. This paper discusses a model of the automatic feedback controller designed to develop the required pump performance. The major human circulatory, mechanical, and electrical systems were evaluated using experimental data from the CF3 and linearized models developed. An open‐loop model of the human circulatory system was constructed with a human heart and a VAD included. A feedback loop was then closed to maintain a desired reference differential pressure across the system. A proportional‐integral (PI) controller was developed to adjust the motor speed and maintain the system reference differential pressure when changes occur in the natural heart. The effects of natural heart pulsatility on the control system show that the reference blood differential pressure is maintained without requiring CF3 motor pulsatility.
Chronic Survival of Calves Implanted with the DeBakey Ventricular Assist Device
Authors: Fossum Theresa W. , Morley Deborah , Benkowski Robert , Tayama Eiki , Olsen Don B. , Burns Gregory , Miller Matthew W. , Franks Joanne , Martinez Elizabeth , Carroll Gwendolyn , Edwards John , Vinnerqvist Anders , Lynch Bryan , Stein Frank , Noon George P. , DeBakey Michael E.
Published: March 2003

The DeBakey ventricular assist device (VAD) is a miniaturized, electromagnetically driven axial flow pump capable of generating in excess of 10 L/min output. The VAD was evaluated in 19 calves during experiments designed to test iterative modifications in the system and to determine the safety of the DeBakey VAD for intermediate to long‐term implant. Five of the animals died or were euthanized during the perioperative period (i.e., Days 1–5) due to complications associated with bleeding (n = 3), sudden cardiac arrest (n = 1), or pump occlusion due to a muscle remnant associated with coring (n = 1). The remaining 14 animals survived from 7–145 days. Ten of the 14 animals survived 30 or more days, and 2 animals survived 93 and 145 days before elective euthanasia. Pump function was evaluated in the 14 calves that survived beyond the perioperative period. Pump output at implantation averaged 3 L/min while output at 100 days (n = 2) averaged 4.22 L/min. The electrical current did not change across time during the study, indicating normal operation of the bearings. Pumps consumed less than 10.5 W of power for all support durations. Hemolysis did not occur; the average daily plasma free hemoglobin varied from 2.0 to 8.0 mg/dl. Evaluation of serum biochemical data showed that implantation of the DeBakey VAD in calves with normal hearts did not impair end organ function; BUN, creatinine, and total bilirubin varied minimally within the normal range. The white blood cell count of implanted animals remained within the normal range throughout the study.
The Pathophysiology of Pulmonary Hypertension in Congenital Heart Disease
Authors: Steinhorn Robin H. , Fineman Jeffrey R.
Published: March 2003

Abstract: Congenital heart disease with increased pulmonary blood flow commonly leads to the development of pulmonary hypertension and increased vascular reactivity. These serious sequelae are associated with the following two major categories of congenital heart defects: those resulting in increased pulmonary blood flow and increased pulmonary arterial pressure and those resulting in increased pulmonary venous pressure. Recent evidence that the pulmonary vascular endothelium is an important determinant of vascular tone has led to the hypothesis that endothelial injury, secondary to congenital heart disease with increased pulmonary blood flow, disrupts these regulatory mechanisms and thereby plays a role in the development of pulmonary hypertension and its associated increased vascular reactivity. In many animal models, endothelial dysfunction is a precursor for smooth muscle dysfunction, and there is an apparent progression from endothelial dysfunction to smooth muscle dysfunction as vascular changes progress. We established a chronic model of pulmonary hypertension with increased pulmonary blood flow in young lambs by placing a systemic‐to‐pulmonary shunt in utero. In this model, we found significant physiologic and molecular alternations of both the nitric oxide (NO) and endothelin signaling pathways, two important mechanisms by which the endothelium regulates pulmonary vascular tone. These alterations occur extremely early and precede severe anatomic changes. Early endothelial damage may contribute to the development of pulmonary hypertension and its associated enhanced pulmonary vascular reactivity.
Aortopulmonary Collateral Artery Embolization During Postoperative Extracorporeal Membrane Oxygenation After Arterial Switch Procedure
Authors: Golej Johann , Trittenwein Gerhard , Marx Manfred , Schlemmer Michael
Published: March 2003

Abstract: Aortopulmonary collateral arteries sometimes complicate cyanotic congential heart defects. Combined with a relevant left‐right shunt, this could result in massive airway bleeding during and after corrective surgery. A preoperatively diagnosed 1.2 mm small aortopulmonary collateral artery in a newborn suffering from transposition of the great arteries caused life‐threatening airway bleeding during surgery. Postoperative extracorporeal membrane oxygenation (ECMO) was necessary, and coil embolization was performed on ECMO to terminate pulmonary bleeding.
Pathophysiology of Cardiac Extracorporeal Membrane Oxygenation
Authors: Fuhrman Bradley P. , Hernan Lynn J. , Rotta Alexandre T. , Heard Christopher M.B. , Rosenkranz Eliot R.
Published: March 2003

Abstract: The treatment of cardiogenic shock using inotropic agents and vascular volume expansion places an added burden on the heart. The resultant increase in cardiac work may cause myocardial ischemia and lead to cardiac arrest. Extracorporeal membrane oxygenation (ECMO) may be used to treat cardiogenic shock. It supports systemic circulation, assures diastolic perfusion of the myocardium, and reduces cardiac workload. The rise in blood pressure associated with restoring systemic circulation afterloads the heart and can cause left atrial hypertension and pulmonary edema. ECMO does not automatically reduce cardiac work, especially in the presence of residual shunts. Left atrial drainage or decompression may be essential in certain patients both to avert pulmonary edema and to reduce cardiac work.
Hydrodynamic Evaluation of Three Artificial Aortic Valve Chambers
Authors: Morsi Y.S. , Sakhaeimanesh A. , Clayton B.R.
Published: March 2003

Abstract: The effect of chamber geometry on the characteristics of turbulent steady flow through a newly designed artificial heart valve, “the jellyfish valve,” has been investigated for flow rates matching those of peak systole. Laser Doppler Anemometry (LDA) was employed to determine the velocity and shear stress distributions at various locations downstream of the jellyfish valve. Three geometrically different aortic valve chambers have been investigated: namely, a chamber with sinuses of Valsalva, an ellipsoidal chamber, and a cylindrical chamber. The results of this investigation indicated that the aorta with sinuses of Valsalva model had the highest turbulent shear stresses whereas the ellipsoidal model gave the highest‐pressure drops. However, for the various flow rates examined, including the systole peak value of 26 L/min, it appears that the ellipsoidal model displays better hydrodynamic characteristics in terms of shear stress and uniformity of axial velocity distributions downstream of the jellyfish valve.
DALI Apheresis in Hyperlipidemic Patients: Biocompatibility, Efficacy, and Selectivity of Direct Adsorption of Lipoproteins from Whole Blood
Authors: Bosch T. , Lennertz A. , Schmidt B. , Fink E. , Keller C. , Toepfer M. , Dräger J. , Samtleben W.
Published: March 2003

Abstract: Recently, the first apheresis technique for direct adsorption of low‐density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60–80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL‐cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL‐cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, β‐thromboglobulin, interleukin‐1β, and IL‐6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL‐C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.
Nonstoichiometric Hydroxyapatite‐Anionic Collagen Composite as Support for the Double Sustained Release of Gentamicin and Norfloxacin/Ciprofloxacin
Authors: Amaro Martins Virginia Conceição , Goissis Gilberto
Published: March 2003

Abstract: This work studied the sustained release of ciprofloxacin or norfloxacin and gentamicin from nonstoichiometric hydroxyapatite (nHA) and anionic collagen composite. Within the first 24 and 48 h, the total antibiotic supply was significantly higher than the minimal inhibitory concentration required for the majority of the gram‐negative bacteria. Although gentamicin was completely released from the matrix after 48 h by a normal diffusion mechanism, ciprofloxacin or norfloxacin release was characterized by a 2‐phase release mechanism due to binding to nHA by complexation with calcium ion. Under the conditions studied, most of the norfloxacin or ciprofloxacin only will be disposable due to bioresorption or dissociation of the complexes. In conclusion, due to its biocompatibility nHA‐anionic collagen composite may be a convenient support for the double sustained release of the antibiotics gentamicin and ciprofloxacin/norfloxacin for the control of bone infection while promoting bone tissue growth.