The paradigm of biologically closed electric circuits (BCEC) and the formation of an International Association (IABC) for BCEC systems.

Matter is condensed energy. Matter derived from electromagnetic energy, supplied with the electrically powered BCEC systems (biologically closed electric circuits) inherits prerequisites to become biological matter. This is possible because mechanisms of BCEC systems contain the capacity to initiate structuring and functioning of matter. The principle of BCEC systems, their actual and potential importance for structure and function in biology and medicine, has been presented only in the form of a survey. Only few examples of the impact of the BCEC systems have been described. For detailed information, the reader is advised to take part of the original background articles by means of the reference list, which extends beyond the selected descriptions. Thereby it is hoped that the reader may get an understanding of the central biological role of the BCEC systems. They represent in this partial theory of the biological evolution a key mechanism which may provide the important primary steps that are necessary for the transfer of non-biological into biological matter. Second, also other factors are evidently contributing to biological differentiation, including for instance the principle of differential selection of species. Due to their basic role, the BCEC systems can nevertheless be recognized to be involved in the majority of structural and functional expressions in biology. This rests on the fact that our physical world once developed from energy and specifically its representation of electric energy. It has also been emphasised that electric energy is equivalent to the remarkable Oriental concept of Qi ("life energy"). Differences are predominantly a matter of semantics.

Impact of biologically closed electric circuits (BCEC) on structure and function.

The basis of our physical world is electrical. The unified Electromagnetic field can appear to us as particles, i.e., matter, at certain densities of wavelengths. A close interrelation therefore exists between matter and electric energy. This knowledge is extensively utilized in technology. Various tools and instruments are electrically powered, utilizing the exceedingly important principle of closed electric circuits. Corresponding closed electric circuits and functions also exist in biology but are more sophisticated and complex. Unfortunately, these aspects are almost unrecognized. The principle of Biologically Closed Electric Circuits (BCEC) and some of their structural and functional effects are described. The Vascular-Interstitial Closed Circuit (VICC) is one specific BCEC system. It functions as a circulatory system in addition to the mechanical circulation. Its efficiency partly depends on its capacity to provide bidirectional transport of ions. The VICC is an in vivo electrophoretic-dielectrophoretic system that is powered by metabolic energy or injury currents. A VICC activation leads to transports of metabolites, new structuring and healing of an injured tissue. Examples are also presented of the process of healing. An abnormal, e.g., prolonged activation of VICC may also induce pathology. Neoplastic formation of cells and tissue can also be healed by the use of artificially applied electrophoresis or an artificially applied electric field as will be described. Our world once developed from electrical energy. This is probably the reason why the BCEC systems make primary differences between nonbiological and biological matter.

Electrical pulses appear in the inferior vena cava and abdominal aorta at contraction of leg muscles.

A vascular-interstitial neuromuscular closed circuit is described anatomically and electrically. The neuromuscular unit has a high resistance due to its axons. The "outer" vascular-interstitial branch has a low resistance due to a large cross section area. When a rat spontaneously contracts leg muscles after pinching a toe, electric potential pulses appear inside the inferior vena cava, between vena cava and peritoneum, between aorta and peritoneum, between vena cava and peritoneum and between aorta and subcutis. Minor pulses between electrodes in the peritoneal fluid are interpreted as induced by the intravascular potential pulses. The use of Ag-AgCl electrodes or platinum electrodes does not appreciably change the results.

Potential differences in the inferior vena cava and between cava and extravascular electrode at leg contraction in man.

When a voluntary adult male contracted his leg muscles, electric potential differences were recorded between platinum electrodes positioned inside the vena cava or between the vena cava and the grounded skin. Two experiments confirm that potential differences at leg contractions in man have a similar appearance as those in the rat at pain-evoked contractions of leg muscles. Platinum electrodes were used in man. The potential differences obtained are thereafter compared with recordings with Ag-AgCl electrodes in salt-bridges in the rat. Slow potential waves with superimposed irregular potential oscillations are recorded in man as previously found in the rat using platinum or Ag-AgCl electrodes. The findings indicate that vascular-interstitial routes participate in a vascular-interstitial-neuromuscular closed circuit, which is activated at contraction of the muscles.

Electric modification of kidney function. The excretion of radiographic contrast media and adriamycin.

The body consists of systems of conductive pathways for ionic flow of current induced by metabolic or injury potentials among tissues and cells. In vivo electrophoresis in biologically closed electric circuits (BCEC) are coupled to the mechanical transports of blood and lymph. Connections also exist with conductive media such as cerebrospinal fluid, bile, and urine. Artificial induction of current was applied over the kidneys in order to study modification of kidney function. It is thought that studies of this kind will increase our understanding of kidney function from a new angle of view and possibly add new therapeutic possibilities. In anesthetized pigs, one kidney was made anodic (electropositive) and the other cathodic (electronegative). Current was applied between electrodes in each ureter. Intravascularly injected, electronegatively charged aminotrizoate and ioxaglate were excreted mainly by the anodic kidney. Nonionic iohexol was urographically excreted by both kidneys. Excretion of electropositively charged Adriamycin by the cathodic kidney was identified macroscopically and by chemical analysis. Functional effects on the kidneys can be induced electrophoretically without causing injury.

Effects of direct current on renal function. An experimental study in pigs.

Electric current from an external source was introduced between electrodes operatively placed into the ureters and positioned in the renal pelves of 13 pigs. Urinary excretion via the cathodic kidney showed a marked increase. The renal plasma flow and glomerular filtration rate diminished with increasing voltage, but no significant difference was found between the cathodic and the anodic kidney. The fractional sodium excretion by the cathodic kidney was 80% higher, indicating that the electric current mainly affected tubular function. A possible clinical application for electric fields in the kidneys is discussed.

Electrochemical treatment of cancer. III: Plasma pharmacokinetics of adriamycin after intraneoplastic administration.

Plasma pharmacokinetics of Adriamycin (doxorubicin) has been studied after intraneoplastic administration during electrochemical treatment to patients with lung cancer that is noncurable with radiotherapy, surgery, or chemotherapy. Intraneoplastic administration of Adriamycin via the anode resulted in a dramatic change of the pharmacokinetic pattern in plasma as compared with what has been previously observed after intravenous administration. A fivefold reduction of the area under the plasma concentration time curve and a 25-fold reduction of the maximum plasma concentration was observed.

Electrochemical treatment of cancer. IV: Leukocyte and platelet counts in peripheral blood after electrochemical treatment of solitary lung neoplasms.

The effects on hematological parameters in peripheral blood was measured by electronic cell counting after electrochemical treatment (n = 11), after electrochemical treatment with concomitant intraneoplastic injection of the chemotherapeutic agent doxorubicin (Adriamycin) (n = 13), and after electrochemical treatment with concomitant intravenous infusion of Adriamycin (n = 2). After treatment, a reduction in lymphocyte count (p less than 0.01) and an increase in total leukocyte count (p less than 0.01) was observed. There was a trend that during treatment the platelet count was reduced.

Electrochemical treatment of cancer. II: Effect of electrophoretic influence on adriamycin.

Electrochemical treatment of cancer with DC electrodes changes the microenvironment of the cancer cells by electrophoresis. They may deteriorate and resorb. In larger neoplasms, the effects can be enhanced by electrophoresis of a chemotherapeutic agent. Adriamycin delivered into an electropositive neoplasm electrode will move outwards in the neoplastic area in a high concentration. When given intravenously and the neoplasm electrode is electronegative, the systemic effects may be diminished. The agent is instead accumulated in the neoplastic region in a high concentration. This principle may be used to reduce systemic effects of charged chemotherapeutic compounds. In this preliminary study of cancer in 14 patients, incurable with surgery, radiation treatment, or chemotherapy, beneficial effects were obtained after combined electrochemical treatment and the use of Adriamycin.

Electrochemical treatment of cancer. I: Variable response to anodic and cathodic fields.

Percutaneous placement of an intraneoplasmic electrode in pulmonary metastases of three patients with extrathoracic primary cancers permitted electrochemical treatment of these lesions. These reacted variably to anodic and cathodic electrodes. One breast cancer metastasis disappeared after treatment with the anodic field. A small metastasis from a cancer of the urinary bladder was found to be resistant to both anodic and cathodic fields despite large doses of current. Two large metastases of about equal size from the leiomyosarcoma of the uterus showed progression of the cranial anodic neoplasm but regression of the caudal cathodic neoplasm. At reversed polarity the cathodic neoplasm showed a tendency to regress and the caudal neoplasm continued to disappear. It appears that different neoplasms may show a variable response to anodic or cathodic fields or may show poor sensitivity to both fields.

Slow and rapid electrical pulses in the caval vein at pain-evoked leg contraction in the rat.

Previous in vivo experiments in rats have shown that pulsed nerve stimulations of 20-50 mV require "external" electrical communication over vessels. This indicates that potential differences also should occur in associated vessels, at physiologic muscle contractions. Pinching toes of the hind leg of anaesthetized rats in the present study caused the animals to spontaneously pull the leg. This resulted in electric potential differences over two intracaval electrodes, as well as high frequency spikes. The slow potential pulses and high frequency spikes could be recorded dominantly in the vena cava compared with the extravascular tissue fluid. The electrical prerequisites and the previous experiments support the view that the vascular-interstitial fluid represents an "external" low resistant communication route of a closed circuit over the nerve cell bodies, the axons and the muscle fibers. A closed electrical circuit evidently increases our possibilities for explaining various structural and chemical events of the synaptic membranes.

The action potential: an effect of fuel cell reactions in the synapse.

The neuron and its vascular-interstitial communications form, in vivo, an electrophoretic closed circuit. It is charged by ionic pumps in the nerve cell membrane at rest. Electrophoretic products of reaction collect at biologic electrodes, represented by redox proteins. These are located in the pre- and postsynaptic membranes and also in associated capillary membranes in the vascular part of the closed circuit. Efferent brain impulses start a series of events preceding muscle contraction. They open ionic channels in the membrane of the nerve cell body. A short-circuiting is thereby created, and cations flow into the cell. The membrane pumps cannot withstand this ionic inflow and maintain the transmembranous potential difference. The circuit is no longer driven but starts selfdriving reactions by previously formed products of reaction at the biological electrodes. Fuel cell reactions start at these and create in the axon the peak of the action potential. In vivo, the action potentials preceding the contracting of a muscle are transmitted through the circuit. In the vascular pathway of the closed circuit, the action potentials appear, by summation, as the previously described slow potential waves. The function of nerve cell matrices, as well as the nodes of Ranvier, are discussed. The proposed theory is in accordance with the vascular-interstitial-neuromuscular closed circuit. It provides new possibilities to explain the development of the action potential, transport and disappearance of various synaptic structures and the neurotransmitter. Technical analogues are presented to illustrate a new possible background mechanism for understanding structure and function in neuromuscular transmission.

Neurovascular activation requires conduction through vessels.

In experiments on rats, a hind leg was transected except for the femoral nerve, artery and vein. The femoral nerve was stimulated by electrical pulses, with one electrode attached to the nerve in the amputation gap and another placed in the inferior caval vein. At each pulse of stimulation, contraction could be recorded in femoral muscles. Ligation of the femoral vessels suspended the contractions within a fraction of a second; contractions resumed when ligation ended. Propagation of neural stimuli to femoral muscles therefore required an intact electrical communication through associated vessels. This is possible because conducting blood plasma and its capillary junction with the interstitial fluid form an "external" closed circuit branch of low resistance with the neuromuscular unit. In testing the interstitial tissue fluid as an alternative to the vascular "outer" communication, a higher voltage of stimulation was required for muscle contractions.

Fleischner lecture. Biokinetic impacts on structure and imaging of the lung: the concept of biologically closed electric circuits.

The corona complex of the lung is a collection of radiographic features surrounding a pulmonary mass. Each of its 12 components may be explained by a recently described subset of biologically closed electric circuits, the vascular-interstitial closed electric circuit (VICC) system. This system is activated both by normal metabolism of tissue and by local degrading processes, such as spontaneous necrosis or hemorrhage, that lead to local electrochemical polarization of a lesion in relation to surrounding noninjured tissue. Ions, cells, and water are transported electrically in the VICC system, leading to the development of the corona complex. The VICC system is conceived to exist with the walls of arteries and veins functioning as insulators around the electrically conducting medium of blood, the plasma. Blood vessels therefore connect electrically the injured and noninjured tissues. At the capillary level, electric junctions connect plasma and interstitial fluid, which functions as an electrical conductor comparable to blood plasma. The interstitial fluid therefore completes the circuit. The VICC system can be regarded as an additional circulatory system for selective electrogenic transports, coupled directly to the mechanical circulation of blood and lymph. The injury potential represents an important energetic factor in the activation of the VICC system. It is a slowly fluctuating, attenuating, electrochemical potential inducing ebb and flow of time-dependent anionic and cationic transports. The corona structures are special effects of the healing of injured tissue. The 12 radiologic signs of the corona complex have each been produced experimentally in vitro in animals and in vivo in humans during electrochemical treatment of cancers. The "A" zone is characterized radiographically by radiolucency around an electrically polarizing focal lesion. Peripheral to the A zone, a "B" zone is seen as a radiopaque region. The A and B zones are predominantly the result of an electroosmotic outflow of water from a lesion during its electropositive phase. At the interface between the A and B zones, small arches sometimes form an arcade. This configuration develops when the polarizing lesion has small protrusions at its surface. As a result of electrical edge enhancement, various elements of the interstitial tissue are transformed into radiating fibrous structures. They grow out at right angles to the surface of the lesion and serve as supporting columns for the arches. When necrotic material from a tumor is evacuated through a bronchus, ensuing collapse of the tumor will displace those radiating structures already produced.(ABSTRACT TRUNCATED AT 400 WORDS)

Technical aspects of obtaining cellular material from lesions deep in the lung. A radiologist's view and description of the screw-needle sampling technique.

The technical aspects of obtaining cellular samples for cytologic diagnosis from lesions deep in the lung are discussed, with emphasis on the role of the radiologist and modern radiologic techniques in localizing lesions to be biopsied and in guiding the sampling needles. Fluoroscopically guided fine needle aspiration is covered, with attention paid to its diagnostic accuracy, the avoidance of complications and considerations of the needle gauge. The screw-needle biopsy instrument and its use are discussed in detail, especially its ability to obtain diagnostic samples from small or "hard" lesions that might be difficult to sample accurately with conventional needle aspiration techniques. The need for full collaboration between the pathologist/cytologist and the radiologist to maximize the benefits of these diagnostic techniques is stressed.