Dhanjoo N. Ghista (Ed.)

Biomedical and Life Physics

Dhanjoo N. Ghista (Ed.)

Biomedical and Life Physics

Proceedings of the Second Gauss Symposium, 2-8th August 1993, Munich

Die Deutsche Bibliothek - CIP-Einheitsaufnahme

All rights reserved © Friedr. Vieweg & Sohn VerJagsgeselIschaft mbH, BraunschweiglWiesbaden, 1996

Softcover reprint of the hardcover 1 st edition 1996

Vieweg is a subsidiary company of Bertelsmann Professional Information.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, mechanical, photocopying or otherwise, without prior permission of the copyright holder.

Printed on acid-free paper

ISBN-13: 978-3-322-85019-5

001: 10.1007/978-3-322-85017-1

e-ISBN-13: 978-3-322-85017-1

Preface

D. N. Ghista

(Based on the Opening Address at the International Conference on Biomedical Physics & Mathematics of the Gauss Symposium, August 2, 1993 at Ludwig Maximillians Universitiit, Munchen, Germany)

The traditional practice of Biomedical physics has now expanded to involve

multiple aspects of medical practice: development of systems and

technology in medical monitoring (e.g., PET visualization of brain receptors

to identify neuronal dysfunction), diagnosis (e.g., computer-aided

echocardiographic texture analysis to detect myocardial infarcts), organ­

support (e.g., peritoneal dialysis), and therapeutic function (e.g.,

encapsulation of insulin-producing pancreatic islet cells for treatment of

diabetes). However, is Biomedical Physics a relatively new field? Not really,

although we may have opened up new vistas of it, as presented in this book.

Let us recall some early and well-known physician-cum-biomedical

physicists. Both physical and physiological scientists will know of Jean

Poiseuille (1799-1869), physician and physiologist; he measured blood

pressure with a mercury manometer while being a medical student in Paris,

received his medical degree in 1928, and then went on to describe the law

of viscous flow (applicable to arteriolar flow). Hermann Von Helmholtz

0821-1894), who was the first to measure the speed of a nerve impulse, was

a physician and physiologist, physicist and mathematician; in 1858, he

became professor of anatomy and physiology at University of Bonn, and in

1871 he was appointed to the Chair of physics at University of Berlin; he

had a remarkable insight into the physics of biological systems, notably in

physiological optics and acoustics, with his masterpiece book on

'Sensations of Tone' providing the physiological basis of the theory of

music.

VI D. N. Ghista

William Harvey (1578-1658); who is credited with the discovery of blood

circulation, first studied medicine at Cambridge, then received his doctor-of­

medicine diploma at the University of Paduo, and thereafter worked as a

physician at St. Bartholomem's & St. Thomas'; he reasoned that if the heart

is pumping 5 litres of blood every minute, where can this come from and

where can it go, except go around I. However, it seems that the Indian sage

and physician, Charaka, noted for his encyclopaedic works on Ayurveda (the knowledge of life) dating back to 1000 BC, has clearly described the

systemic circulation: "from the great centre (the heart) emanate vessels

which carry blood into all parts of the body - an element that nourishes life

of all animals, and without which life would be extinct; it is that element

which goes to nourish the fetus in the uterus, and which flowing into its body

returns to the mother's heart."

On the German 10 DM note is depicted (along with the familiar bell-shaped

probability distribution curve) the portrait of Carl Friedrich Gauss (1777-

1855), who this Symposium commemorates. Ranking as one of the greatest

mathematicians of all times, he also made important contributions to

astronomy, geodesy and electromagnetism. It is this spirit that constituted

the theme of this Symposium: to explore mathematical, physical, biological,

and medical sciences in a unified fashion.

A more recent and biomedically intrinsic endeavour of Biomedical Physics,

dealt with in the Conference is that of Organ ~m phyma, entailing

analyses of organ functional mechanisms and processes. This can yield

new concepts and theories to deal with the intricacies and complexities of

organ processes. The development of biomedical physics of macro and

micro body processes can eventually lead to a wider and more rational

diagnostic methodology. For instance, in this book. in the section on

metabolic pathways regulation (by Reinhart Heinrich), Systems and control

theory has been employed to, for instance, model the adrenal cortex system

and the dynamics of cortisol levels in healthy and diseased states. On the

topic of Glucose metabolism and insulin delivery (developed herein by

Eugenio Sarti) the pathophysiology of non-insulin dependent diabetes can

be depicted in terms of a glucose-insulin metabolism modeL whose

pammetric simulation of glucose tolemnce tests can yield information

regarding B-cell sensitivity for glucose and hepatic glucose production; the

optimal control theory application to diabetes therapy then entails

minimizing fluctuations of blood glucose from a preset level while

accounting for large rates of insulin delivery.

Preface

Yet another case of organ systems physics is the mechanism of coordinated

motility of the small intestine (by R!JSlem Miftakhov), entailing the following

sequence of events: triggered propagation of electrical signals in the enteric

nervous system network in the intestinal wall, activation of L-type Co ion

channels located in the smooth-muscle syncytim membrane, propagation of

depolarization waves in the syncytium, stress and deformation waves in the

intestinal wall; this model can be employed to simulate drug action on

motility and also the synaptic neurotransmitter-receptor disorders causing

pathological motility. The examples, treated in this book, illustrate an

approach to organ system process modelling and parametric estimation, for

disease diagnosis. Another aspect of disease, discussed in this

Conference, is genetic disease, featurlpg a new DNA sequencing

technology, recognition of DNA sequences by multi-site ligands, and design

of drugs capable of inhibition of retrovirus infection.

A relatively new realm of coDSCiowmess (the faculty of mental awareness

and experiencing) was introduced in the Conference by Nobel-laureate

Brian Josephson. Consciousness cannot be regarded as just an

epiphenomenon of complex brain processes, as asserted by Beverly Rubik.

In fact how consciousness also affects the body aqd disease processes

leads us to the concept of Mind-Body medicine. This then requires a new

science paradigm for Holistic medicine.

The aspects of Biomedical Physics, presented and discussed in this Conference, may in fact be categorized as follows:

a Biomedical Technological Physics, as exemplified herein (by Masatoshi Itoh) with: Invivo measurements of neurotransmitter functional changes in dimentia brain by PET. and cerebral metabolic rates for glucose to detect multi-focal damage in the brain after stroke using 18FDG & PET; Targeted drug delivery systems (by Arend Hoekstra).

o Organ Functional Physics, involving: Metabolic pathways and regulation in diabetes and cancer, Remodelling of nerve synapses and neuromuscular junctions in growth and aging (by Mohamed Fahim): Simulation of small-bowel motility under the action of cholinergic and adrenergic agonists and antagonists, and Reconstruction of cardiac electrical excitation maps from body surface data for more precise electrocardiographic diagnosis (by Milan Horacek).

vn

VIII D. N. Ghista

o A hitherto relatively unexplored aspect, Life " Behavioural Physics. involving Cosmic or Absolute Consciousness as the fundamental entity behind the physical universe, vitalization of matter into mind, concept of evolution based on unfolding of consciousness, and the role of mind in health and disease; this approach has in fact been a long-standing tradition in Eastern systems of medicine.

The concept of mind-body interaction owes its origins in Ayurveda,

practiced earlier than 1000 Be, wherein life is defined as the union of body,

senses, mind and soul. According to Ayurveda, a human being is a

microcosm within the Macrocosm; so the human body is considered to be a

matrix of the five fundamental elements forming the basic tissues and the

basic humors. A healthy person is one in whom there is an equilibrium of

body humors and tissues, as well as control over the senses by the mind.

The somatic, autonomic and mental activities are controlled by plexii, the

activation of which can not only effect healthy function of associated organ

systems but also enable liberation from psychic ailments and propensities.

This concept, overlooked in Newtonian medicine, indeed constitutes the

basis of mind-body interaction for the mechanisms, diagnosis and

treatment of psycho-somatic diseases in Behavioural Medicine and

Psychiatry. It is now time for us enunciate the science basis for Mind-Body

medicine.

The basic concept of the science paradigm for holistic medicine is that

Absolute Consciousness is indeed the fundamental entity, with matter as its

derivative. as all along asserted in the ancient Science of Yoga Cosmology.

Absolute Consciousness incorporates two principles. the Cognitive principle

and the Operative principle. It is the Operative principle that qualifies

absolute consciousness into the fine fundamental factors (etherial. aerial.

luminous. liquid and solid) which provide the constituents of the physical

universe. Thus matter is metamorphosed consciousness.

Part and parcel of this science paradigm is the recognition of the existence

of microvita. revealed by the modern-day sage Prabhat R. Sarkar (1921-

1990) to be responsible for synthetic reactions infusing energy into matter

(derived from Consciousness), and structuring primitive mental forms; the

emergence of mind is when life originates. Thereafter, augmentation of the

biopsychic field of the mind results in increased complexity of organismic

Preface

structures. Development in lower life forms as well as in human beings

entails increased unfolding of consciousness and higher states of mind. In

this process (according to Richard Gauthier), microvita are the information

carriers, causing genetic modifications of living organisms. These new

concepts of Life Physics, presented at the Conference, were embellished by

Nobel laureate Manfred Eigen's narration on the principles and algorithms

of the creation and organization of genetic information.

Since Behavioural Medicine deals with psychosomatic diseases, it requires

the understanding of the mechanism of mind-body interaction associated

with psychosomatic disease process, prevention and treatment. Linking the

mind and the physical body are subtle psychic glands (Chalcras), through

which the propensities and behavioural traits are expressed. The Chalcras

control the endocrine glands, and hence regulate organ function through

the hormonal secretions of the endocrine glands. Because the mind and its

emotions affect the chalcras, which in tum influence the endocrine glands'

secretions and hence organ functions, mental stress can also cause organ

dysfunction. Now when the mind gets dilated by the ideation of Cosmic

Consciousness carried out at the site of these glands, these sentimental

instincts are also controlled, and this also contributes to physical well-being

and health. This is the basis of psychic therapy for mental ailments and

psychosomatic diseases.

In this setting, and in a spirit of exploration and forward vision, it was also

appropriate for this Conference to revisit Medical education. In a problem­based curriculum, biomedical sciences are taught in relation to clinical

taxonomy. However (as pointed out herein by Vimla Patel), the key role of

the study of basic medical sciences principles, in defining chains of causal

mechanisms, could well be in developing the ability of coherent medical

reasoning in diagnosis and intervention. Further, the above enunciated

paradigm of Consciousness could provide an impetus to a holistic

approach to health and disease in Medical education. If is hoped that this

book can not only provide impetus for new methodologies in internal

medicine and rethinking in medical education, but also help lead to new

approaches in psychiatry inVolving mental rejuvenation as an aspect of the

integration of physical and psychic aspects of health and disease.

IX

Authors' adresses

M.A. Andrade, Dpto. de Bioqufmica y Biologi'a J. Delgado, Texas A&M University, Dept. ofChem­Molecular I, Facultad de CC. Quimicas, Universi- ical Engineering, College Station, Texas, 77843-dad Complutense, E-28040 Madrid 3122, USA

R. Bafunno, Dept. of Electronics, Computer and Sys­tem Science, University of Bologna, Italy

DJ. Benor, 19 Fare Street, Bishopsteignton, South

K. Denner, Humboldt-Universitllt Berlin, Intitute of Biology, Experimental Biophysics, Invalidenstr. 42, 10115 Berlin, Germany

Devon TQ14 9QR, U.K. W. Dilchting, Universitllt Siegen, Dept. of Electrical

I. Bernhardt, Humboldt-Universitllt Berlin, Institute Engineering and Computer Science, HOlderlinstr. 3, of Biology, Experimental Biophysics, Invalidenstr. 57068 Siegen, Germany 42, 10115 Berlin J.A. Edens, Institut de G6nie Biom6dical, Universit6

E. Biermann, Institut fi1r Diabetesforschung, Koh- de Montr6al, Montr6al, Qu6., Canada nerplatz 1, 80804 MUnchen, Germany M.A. Fahim, Dept. of Physiology, Faculty of

M. Bier, Section of Plastic and Reconstructive Surgery, Dept. of Surgery, MC 6035, University of

Medicine and Health Sciences, U.A.E. University, P.O.Box 17666, Al-Ain, United Arab Emirates

Chicago, 5841 South Maryland Av., Chicago, IL D.A. Fell, School of Biological and Molecular Sci-60637, USA ences, Oxford Brookes University, Haedington, Ox-

G. Borst, Section of Neurophysiology, Dept. of Biol- ford OX3 OBP, U.K. ogy, Vrije Universiteit, de Boelelaan 1087, NL-1081 P. Colli Franzone, Instituto di Analisi Numerica, HV Amsterdam Consiglio Nazionale Ricerche, Corso Carlo Alberto

R. Carroll, Dept. of Mathematics, Statistics and 5,1-27100 Pavia Computig Science, Dalhousie University, Halifax, R.F. Gauthier, Microvita Research Institute, Weise-N.S., Canada nauer Weg 4, 55129 Mainz, Germany

M. Casolaro, Dept. of Chemistry, University of D. N. Ghista, Dept. ofBio Medical Engineering, Uni­Siena, Italy versity College of Engineering, Osmania University,

P. Ciaccia, Dept. of Electronics, Computer and Sys- Hyderabad-500 007, India tem Science, University of Bologna, Italy T. Ginsberg, Universitllt Siegen, Dept. of Electrical

J.C. Clements, Dept. of Mathematics, Statistics and Engineering and Computer Science, HOlderlinstr. 3, Computing Science, Dalhousie University, Halifax, 57068 Siegen, Germany N.S., Canada L. Guerri, Faculty of Engineering, University of

C. Coltelli, Dept. of Electronics, Computer and Sys­tem Science, University of Bologna, Italy

D.L. Delanoy, Dept. of Psychology, University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, U.K.

Trento

R. Heinrich, Humboldt-Universitllt Berlin, Institute of Biology, Theoretical Biophysics, InvalidenstraBe 42, 10115 Berlin, Germany

R. Heinrich, Freie Universitllt Berlin, Institute of

Authors' adresses XI

Biochemistry, Dept. of Chemistry, Thielallee 63, 77843-3122, USA 14195 Berlin, Germany D. Lorimer, Scientific and Medical Network, Lesser C. Hilgetag, Humboldt-Universitl1t Berlin, Institute Halings, TIlehouse Lane, Denham, Nr. Uxbridge, of Biology, Theoretical Biophysics, Invalidenstr. 42, Middlesex UB9 500, UK 10115 Berlin, Germany

A. Hoekstra, Cordis Europa N.V. P.O. Box 38, NL-9300 AA Roden

H.-G. HolzhUtter, Humboldt-Universitlit Berlin, In­stitute of Biochemistry, Hessische Str. 3-4, 10115 Berlin, Germany

B.M. Horarek, Dept. of Physiology and Biophysics,

E. MeI6ndez-Hevia, Dpto. de Bioquimica, Facultad de Biologia, Universidad de La Laguna, E-38206-Tenerife, Canary Islands

P.E. Micevych, Dept. of Anatomy and Cell Biology and Laboratory of Neuroendocrinology of the Brain Research, Institute UCLA, School of Medicine, Los Angeles, CA 90024, USA

Dalhousie University, Sir Charles Thpper Medical P. Moniz-Barretto, School of Biological and Molec­Building, Halifax, Nova Scotia, Canada B3H 4H7 ular Sciences, Oxford Brookes University, Haeding-

G. Huiskarnp, Dept. of Medical Physics ad Bio- ton, Oxford OX3 OBP, UK physics, University of Nijmegen, Geert Grooteplein F. Montero, Dpto. de Bioquimica y Biologia Mole­noord 21, NL-6525 EZ Nijmegen cular I, Facultad de CC. Quimicas, Universidad

F. Greensite, Dept. of Radiology, UCI Medical Cen- Complutense, E-28040 Madrid ter, 101 City Drive, Orange, CA 92668, USA F. Monm, Dpto. de Bioquimica y Biologia Molecu­

P.R. Jensen, Dept. of Microbiology, Technical Uni- lar I, Facultad de CC. Quimicas, Universidad Com-versity of Denmark,DK-2800 Lyngby plutense, E-28040 Madrid

B.D. Josephson, Cavendish Laboratory, Madingley J. Nenonen, Dept. of Technical Physics, Helsinki Road, Cambridge CB3 OHE, U.K. University of Technology, Rakentajanaukio 2C, SF-

02150Espoo B.N. Kholodenko, E.C. Slater Institute, BioCentrum University of Amsterdam, PlantageMuidergracht 12, NL-1018 TV Amsterdam and A.N. Belozersky In­stitute of Physico-Chemical Biology, Moscow State University

K. Kits, Section of Neurophysiology, Dept. of Biol­ogy, Vrije Universiteit, de Boilelaan 1087, NL-I081

J.C. Nufto, Dpto. de Bioquimica y Biologia Molecu­lar I, Facultad de CC. Quimicas, Universidad Com­plutense, E-28040 Madrid

A. van Oosterom, Dept. of Medical Physics and Bio­physics, University of Nijmegen, Geert Grooteplein Noord 21, NL-6525 EZ Nijmegen

HV Amsterdam M. Pennacchio, Instituto di Analisi Numerica, Con­E. Klipp, Humboldt-Universitlit Berlin, Institute of siglio Nazionale Ricerche, Corso Carlo Alberto 5,

1-27100 Pavia Biology, Theoretical Biophysics, Invalidenstr. 42, 10115 Berlin, Germany

V.A. Kolombet, The Institute of Theoretical and Ex­perimental Biophysics, Russian Academy of Sci­ences, Pushchino, Moscow Region, Russia

J. Lankelma, Dept. of Oncology, FreeUniversity

C. P6rez-Iratxeta, Dpto. de Bioquimica y Biologia Molecular I, Facultad de CC. Quimicas, Universi­dad Complutense, E-28040 Madrid

J.-J. Qian, Dept. of Radiology, UCI Medical Center, 101 City Drive, Orange, CA 92668, USA

Hospital, NL-Amsterdam P. Richard, DBCM, Section of Bioenergetique, Bft. A.P.M. Jongsma, The Netherlands Cancer Institute, 532, CEo Saclay, F-91191 Gif-sur-Yvette Cedex H5, Plesmanlaan 121, NL-I066 CX Amsterdam S. Richter, Humboldt-Universitlit Berlin, Intitute of Y. Lenbury, Mahidol University, Dept. of Mathe mat- Biology, Experimental Biophysics, Invalidenstr. 42, ics, Faculty of Science, Rama 6 Rd., Bankok 10400, 10115 Berlin, Germany Thailand B. Rubik, Center for Frontier Sciences, Temple Uni­L.l. Leon, Institut de G6nie Biom6dical, Universit6 versity, Ritter Hall 003-00, Philadelphia, PA 19122, de Montr6al, Montr6al, Qu6., Canada USA J.C. Liao, Texas A&M University, Dept. of E. Sarti, Dipartimento di Elettronica Informatica e Chemical Engineering, College Station, Texas, Sistematica, UniversitA degli studi di Bologna, Viale

XII Authors' adresses

Risorgimento, 2, 1-40136 Bologna Sant Leorenc 21, E-43201 Reus (Tarragona)

R. Schuster, Humboldt-Universitllt Berlin, Institute M. Towsey, Biophysics Dept., Faculty of Medicine of Biochemistry, Hessische Str. 3/4, lOllS Berlin, and Health Science, United Arab Emirates Univer­Germany sity, P.O.Box 17666, Al Ain, United Arab Emirates

S. Schuster, Humboldt-Universitllt Berlin, Institute W. Ulmer, Max-Planck-Institute of Biophysical of Biology, Theoretical Biophysics, Invalidenstr. 42, Chemistry, 37073 Gtittingen, Germany 10115 Berlin, Germany

N.N. Vasilyev, Dept. of Solid State Physics, Sci­J. Sicilia, Universidad de La Laguna, Departamento entific Research Institute of Physics, St. Petersburg de Estadlstica, e 1.0., Facultad de Matemliticas, E- University, St. Petersburg, Russia 38206 Tenerife, Canary Islands

E.C. Spoelstra, Dept. of Oncology, Free University­Hospital, NL-Amsterdam

Y. Takahashi, Mikuni R &D Corp., Berkeley, CA, USA

J. Tomas, Unitat d'Histologia i Neurobiologia (UHN) Facultad de Medicina i Ciencies de la Salut, Universitat de Catalunia, Rovica i Virgilii (URV),

T.G. Waddell, University of Tennessee at Chat­tanooga, Dept. of Chemistry, 615 McCallie Avenue, Chattanooga, TN 37403, USA

H.V. Westerhoff, The Netherlands Cancer Institute, H5, Plesmanlaan 121, NL-1066 CX Amsterdam and E.C. Slater Institute, BioCentrum University of Ams­terdam, Plantage Muidergracht 12,NL-I 0 18 TV Am­sterdam

Contents

Metabolic Control, Gowth, and Optimization

Introduction to Session Metabolic Regulatory Systems ........................... . R. Heinrich

Metabolic Control Analysis Using Transient State Data. . . . . . . . . . . . . . . . . . . . . . . . . . . 7 J. G. Liao and J. Delgado

Control of Dynamics and Steady State: Applications to Multidrug Resistance. . . . . . . . 25 H. V. Westerhoff, M. Bier, D. Molenaar, E.G. Spoelstra, J. Lankelma, A.P.M. Jongsma, P.R. Jensen, P. Richard, and and B.N. Kholodenko

Parameter Space Classification of Solutions to a Mathematical Model for the Cortisol Secretion System in Normal Man . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Y. Lenbury

Optimization of Glycogen Design in the Evolution of Metabolism. . . . . . . . . . . . . . . . . . 49 E. Mellndez-Hevia, T.G. Waddell, and J. Sicilia

Tumor Growth and Treatment Planning: A Novel Simulation Approach. . . . . . . . . . . . . 61 W. Diichting, T. Ginsberg, and W. Ulmer

Maximization of Enzymic Activity under Consideration of Various Constraints. . . . . . 71 E. Klipp

Metabolic Control Theory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 R. Heinrich

Determining Elementary Modes of Functioning in Biochemical Reaction Networks at Steady State. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 S. Schuster, G. Hilgetag, and R. Schuster

On Inferring the Kinetic Scheme of an Ion Channel from Postsynaptic Currents.. . . . . 115 M. Bier, G. Borst, K. Kits

Mathematical Modelling of Red Blood Cell Enzyme Deficiencies as an Example for Large-Scale Parameter Changes in Biochemical Reaction Systems. . . . . . . . . . . . . . . . . . 125 R. Schuster and H. -G. Holzhiitter

XIV Contents

Simulation of Dioxygen Free Radical Reactions: Their Importance in the Initiation of Lipid Peroxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 137 P. Moniz-Barreto and D.A. Fell

Residual Sodium and Potassium Fluxes Through Red Blood Cell Membranes. . . . . . . . 145 I. Bernhardt, S. Richter, K. Denner, and R. Heinrich

Electrocardiography: Processes and Analyses

The Role of Natural Selection and Evolution in the Game of the Pentose Phosphate Cycle........................................................................ 155 F. Montero, J.e. Nuflo, M.A. Andrade, e. Perez-lratxeta, F. Moran, E. Melendez-Hevia

The Forward and Inverse Problems of Electrocardiography ........ .. ........ .... . . 169 B.M. Horacek

Simulation of the Spread of Excitation in the Myocardial Tissue. . . . . . . . . . . . . . . . . . . . 173 P. Colli Franzone, L. Guerri, and M. Pennacchio

A Hybrid Model of Propagated Excitation in the Ventricular Myocardium. . . . . . . . . . . 181 B.M. Horacek, J. Nenonen, J.A. Edens, and LJ. Leon

Extracardiac Field due to Propagated Excitation in the Ventricular Myocardium.. . . . . 191 J. Nenonen and B.M. Horacek

Spatio-Temporal Constraints in Inverse Electrocardiography. . . . . . . . . . . . . . . . . . . . . . . 203 A. van Oosterom and G. Huiskamp

When is the Inverse Problem of Electrocardiography Well-Posed.. . . . ....... . .... .. 215 F. Greensite and J. -J. Qian

Local Regularization and Adaptive Methods for the Inverse Problem. . . . . . . . . . . . . . . 223 e.R. Johnson and R.S. MacLeod

On Regularization Parameters for Inverse Problems in Electrocardiography. . . . . . . . . 235 J.e. Clements, R. Carroll, and B.M. Horacek

Gastrointestinal Mechanisms and Disorders

The Forces Exerted on the Duodenum and Sphincter of Oddi During ERCP, and Sphinc-terotomy ... .... ... ... . .. ... .... ..... ... . ....... . ........ . .......... . ........ . 247 R. Ratani and P. Swain

Small Bowel Propulsion: Transport of a Solid Bolus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 R. Miftakhov and G. Abdusheva

Regulatory Role of the Adrenergic Synapse Within a Neural Circuit. . . . . . . . . . . . . . . . 261 R. Miftakhov, G. Abdusheva, A. Mougalli

Duodenal Bioelectrical Waxing and Waning Activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 S. Salinari and R. Mancinelli

Conren~ xv

Drug Delivery Systems Drug Delivery Sysrems: Technology and Clinical Applications.. . . . . . . . . . . . . . . . ... . 281 A. Hoekstra

Recent Developments in Drug Delivery Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 A. Hoekstra

Port-Catheter Systems: Design, Advantages, and Applications. . . . . . . . . . . . . . . . . . . . . 297 A. Hoekstra

Hydrocephalus Management With a Flow-Control Shunt: Overdrainage and Proximal Obstruction: Controllable Complications of Shunting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311 A. Hoekstra and M. Sussman

Subtle Energies Introduction to the Microvita Section. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 R.F. Gauthier

The Origins of Mind. .......................................................... 335 M. Towsey and D.N. Ghista

Microvita: A New Approach to Matrer, Life and Health. . . . . . . . . . . . . . . . . . . . . . . . . . . 347 R.F. Gauthier

The Quantum Field of the Healing Force. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 N.N. Vasilyev

Is Another Physics Needed to Explain Fundamental Fluctuations in Physical Measure-men~?............................................... ....................... 367 V.A. Kolombet

Consciousness Scientific Research into Consciousness. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 B.D. Josephson

The Challenge of Consciousness Study. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375 B. Rubik

First-Person Experience and the Scientific Exploration of Consciousness. . . . . . . . . . . . 383 B.D. Josephson

The Near-Death Experience and the Nature of Consciousness ...................... 391 D. Lorimer

Experimental Evidence Suggestive of Anomalous Consciousness Interactions . . . . . . . 397 D.L. Delanoy

Theoretical Speculations and Energy Phenomena Associared with Spiritual Healing. . 411 D.J. BenoT

XVI Contents

Towards a Science of Consciousness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417 M. Towsey and D.N. Ghista

Glucose Metabolism and Insulin Delivery Glucose Metabolism and Insulin Delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429 E. Sarti

Recent Developments and Open Problems in Feedback Control of the Glucose System in Diabetes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431 E. Sarti and C. Cobelli

Autonomic Dysfunction in Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445 I. T. El Mugamer, K.D. Desai, M. Towsey, and D.N. Ghista

Physiologic Modelling of Type-2-Diabetes for Medical Education. . . . . . . . . . . . . . . . . . 457 E. Biermann

Rechargeable Glucose Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469 E. Wilkins and P. Atanasov

The Influence of Temperature on pH-Responsive Chemical Valve Systems: Thermody-namic Aspects for Drug Delivery... .... ....... ......... ........ ...... .. ..... ... 477 M. Casolaro

Control Algorithms for a Wearable Artificial Pancreas. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483 P.G. Fabietti, L. Tega, and S. Allegrezza

Adaptive Glycaemia Control Using Neural Networks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 R. Bafunno, C. Coltelli, P. Ciaccia, and Y. Takahashi

Neuromuscular Remodelling in Development and Ageing Neuromuscular Remodelling During Development and Aging. . . . . . . . . . . . . . . . . . . . . . 505 M.A. Fahim

Synaptic Plasticity During Aging of the Neuromuscular Junction. . . . . . . . . . . . . . . . . . . 507 M.A. Fahim

Neuromuscular Remodelling in the Adult Induced by Small Physiologic Changes in the Locomotor Activity.. ... ......... ......................................... .... 521 M.R. Fenoll-Brunet, J. Tomas, M. Santa/e, and M.A. Lanuza

Anabolic-Androgenic Steroid Regulation of Gene Expression in Spinal Motoneurons . 533 P.E. Micevych, P. Popper; and C.E. Blanco