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Definition, measurement, and classification of the syndromes of obesity.

The definition and risks of obesity have been reviewed and a nomogram provided for reference. Organization of information about the syndromes of obesity has been approached from several points of view. An anatomic classification has been developed, in which generalized and localized forms of fat accumulation can be separated. Hypercellularity of the adipose tissue in the childhood-onset forms of obesity is usually, but not always, present. Etiologic mechanisms are also useful in classifying obesity. This nosologic approach has been derived largely from experimental studies but has contributed significantly to understanding of pathogenetic mechanisms in man. Hypothalamic obesity is now thought to result from augmented secretion of insulin. The recessively inherited forms of obesity, on the other hand, appear to result from loss of a thermogenic system involving the ouabain-suppressible thyroid-induced (Na+ + K+) -ATPase which, in turn, accounts for the myriad of defects in these animals. Techniques of cybernetic engineering provide a third approach to classification of the syndromes of obesity. The control of body fat was analyzed as an analogy to the control of temperature in a building. These various approaches, and the new insights which they have provided for understanding the syndromes of obesity, promise to provide new pathways for pharmacologic intervention in the treatment of this problem.

Adipose Tissue↗

[Schizophrenia and addiction].

The relationship between schizophrenia and drug abuse has been approached using physiopathological, psychopathological, and cybernetics communicational techniques. The hypotheses which have been proposed with regard to the physiological mechanism involved in schizophrenia and drug abuse all have in common, among other things, the idea that neurotransmitters play a role in the development of these behaviors. Likewise, the psychopathological symptoms presented by schizophrenia and drug abuse offen many similarities. The mechanism by which drug abuse may lead to schizophrenia is discussed. The analysis of the communicational system reveals the correlation between there two syndroms. None of the three techniques which have been described should be exclused from clinical practice.

Adult↗

[To the process of registration of ageing process (author's transl)].

A cybernetical scheme and a corresponding system of differential equations, describing the dehydration and the diminishing metabolism rate of the aging cell as well as of the whole of the organism, are generalised to adapt them also to other phenomena of aging. The resulting expressions are tested by comparison with a number of representative theoretical and experimental dates of various aging processes.

Adaptation, Biological↗

[Present state of pain surgery].

This report presented to the Société de Neurochirurgie de Langue Française is based on 34 years of unique practice in neurosurgical management of pain; during that long period the author and his associates have collected an unusually large experience in almost every field of neurosurgical management of pain; they have improved or fully devised several new techniques which allow them to ground an appreciation of the procedures still worthy to be used in various pain syndromes. The first part of the report deals with "Cybernetics of pain". This rather long chapter is based both on classical data and personal observations on man during and following operations, meant to relieve pain. Though supporting HEAD and HOLMES, theory on Control of protopathic by epicritic Stimuli, the authors consider that the type of pain associated with noxious stimulation as representative of just one among other types of pain, not induced by nociception and not associated with protection reflexes. Sensory deafferentation as can be produced by amputations, herpes zoster, dorsal column or medullary lesions, cannot be included in Sherrington's scheme of psychical mechanisms associated with protection reflexes and yet is responsible for most of the chronic unbearable and often intractable pain. Moreover, an important modulation of pain as such depends on conditioning, on inherited and acquired patterns of behaviour and on a multiplicating factor which is provisionally named "algogenic neurosis". The fact that an intact nucleus ventralis posterolateralis is a necessity for a "no pain status" tends to prove that this thalamic nucleus acts as a major inhibiting relay on the pain integrating system and for several additional reasons is the level of integration of epicritic versus protopathic stimuli in case of true nociception...

Analgesia↗

The Mallory body: theories on development and pathological significance (Part 2 of a literature survey).

Drawing on data from a previously published literature survey on the clinical and experimental epidemiology of the Mallory body, we discuss current theories on its development in a pro et contra manner. Conclusions have been largely left open to the interpretations of the reader because many are still speculative. The main results of this study characterize Mallory bodies as stereotypical histological byproducts to diverse hepatic injuries (mostly alcohol associated) of questionable pathogenic importance. The temporal characteristics of Mallory bodies cast doubt on their role in hepatic neoplasia both as a disease marker and a causative agent, and prognosis studies suggest that they may be considered preterminal markers in some nonalcoholic liver diseases but remain prognostically unimportant in most studies on alcoholic patients. By similar line of inquiry, no consistent relationships may be found with disease severity or duration in alcoholic liver diseases. The roles of vitamin A deficiency and protein-calorie malnutrition are circumstantial. Drugs known to have calcium-antagonist properties and the physiological characteristics of the stress-response protein ubiquitin support the concept of defective protein systems in Mallory body pathogenesis. Disproportionate hepatic copper accumulation seems both epidemiologically and topographically associated with Mallory bodies, but these connections are largely unsupported by exposure studies. Many arguments still downplay the importance of uncoordinated changes in hepatic oxygen delivery and consumption, but ischemia-reperfusion studies suggest a role of oxygen-derived free radicals in the liver injuries under scrutiny. Finally, the role of Mallory bodies in the control system of hepatocyte function is addressed, and indirect evidence lends credence to a cybernetic approach in future study designs. It is reasonable to assume that different elements of a multifactorial setting operate with varying intensity over time as this may account for some of the controversies that exist. In conclusion, the biological significance of Mallory bodies is still mystery. It is not known whether Mallory bodies represent an epiphenomenon or play a role themselves in the initiation and continuation of liver damage.

Animals↗

[The training of military physicians].

The article proposes to regard the training of military physicians as a cybernetic command system with an instructor as a command body, and a student as an object of command. During curriculum planning it is necessary to take into consideration the correlative factors of this system. The analysis of elements which form within students the concept of goal of study has shown that in some cases it was important to make corrections and take into account various motivations. The course of training has a number of new aspects, including computer application, which inevitably need adaptative period.

Career Choice↗

[Social change and sciences in the 20th century].

The symbiotic interdependence of state, economy and science is one of the most significant structural characteristics of the 20th century. This development results from inherent scientific as well as from social procedures and needs, and it has been favoured by the two World Wars, culminating in the Cold War. This led to new structures: institutions of large scale research, think tanks, and the military-industrial complex. Big government, big business, and big science are depending on each other. Parallel to the new way of thinking in physics (Einstein, Bohr and others), finally accomplished by the revolution in cybernetics (Wiener), the traditional borders between disciplines have been overcome. The production of new knowledge is now of primary importance. Today, information proves to be one of the strategic resources which determines prosperity, power and prestige as well as success in economic and political markets.

Cybernetics↗

Effectiveness of 1alpha-hydroxyvitamin D2 in inhibiting tumor growth in a murine transgenic pigmented ocular tumor model.

OBJECTIVE: To study the effectiveness of the vitamin D analogue 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)) in inhibiting ocular tumor growth in transgenic "Tyr-Tag" mice that developed pigmented ocular tumors produced with the simian virus 40 T and t antigens under the control of the mouse tyrosinase gene. These animals develop pigmented intraocular tumors primarily from the retinal pigment epithelium that closely resemble the histologic features and growth pattern of human choroidal melanoma. METHODS: A total of 73 Tyr-Tag transgenic mice between 6 and 7 weeks old were randomly assigned by sex and litter to 3 treatment groups to receive 0.05 microg/d, 0.1 microg/d, or 0.2 microg/d of 1alpha-OH-D(2); a control group received vehicle (coconut oil). The drug was administered by oral gavage 5 times a week for 5 weeks. The animals were then euthanized and their eyes were enucleated and processed histologically. Three serial sections from each eye were examined microscopically and the mean tumor area measured using Optimus software version 6.5 (Media Cybernetics LP, Silver Spring, Md). Toxic adverse effects were assessed on the basis of mortality, weight loss, and serum calcium levels. RESULTS: The mean tumor size in the 0.1- microg/d and 0.2- microg/d dose groups was smaller than in the controls (P<.001). No significant difference was seen between the 0.05- microg/d dose group and the control group (P =.64). Survival for the 0.1- microg/d and 0.2- microg/d dose groups was lower than for the controls (95% in the controls vs 85.7% and 73.7%, respectively; P<.01). CONCLUSION: In the Tyr-Tag transgenic mouse, 1alpha-OH-D(2) inhibits pigmented ocular tumor growth at moderate drug levels with relatively low mortality. Clinical Relevance Vitamin D analogues merit further preclinical study in the treatment of ocular melanoma.

Animals↗

Magnetic resonance imaging in patients with low-tension glaucoma.

OBJECTIVE: To study diagnoses and anatomic findings found on magnetic resonance imaging in patients with low-tension glaucoma. PATIENTS: We included in this study magnetic resonance images of 20 consecutive patients with low-tension glaucoma. We individually matched each patient with low-tension glaucoma to a control with normal ocular findings who had magnetic resonance imaging for reasons unrelated to the visual pathway. DESIGN: We studied axial and coronal images of the orbit and optic nerve with digitizing software (Image-Pro Plus, Media Cybernetics, Silver Spring, Md). Statistical evaluation was with a Wilcoxon Signed Rank Test for anatomic findings and a McNemar Test for diagnosis. RESULTS: We found no difference between groups in the optic nerve diameter or length, the carotid artery area, or the distance from the optic nerve to the carotid artery (P > .05). Left optic nerve area was greater in the control patients than patients with low-tension glaucoma (P = .026). The prevalence of intracranial abnormalities, including meningioma, aneurysm, and arteriovenous abnormality, was similar between groups (P > .05). However, diffuse cerebral small-vessel ischemic changes were found more in patients with low-tension glaucoma (n = 8) than control patients (n = 1) (P = .0196). CONCLUSIONS: This study proposes a hypothesis that cerebral small-vessel ischemia is more common in patients with low-tension glaucoma and potentially reflects indirectly a vascular cause of the optic nerve head damage at least in a subgroup of patients. Importantly, further research still is required to provide direct evidence for a vascular cause involved in low-tension glaucoma.

Aged↗

Regional variations in cortical modeling in the femoral mid-shaft: sex and age differences.

Modern lifestyle changes may result in site-specific alterations in the skeleton. Our aim was to determine sex and age differences in regional geometry at the mid-femur. Complete cross sections from 113 individuals aged 20-97 years from a modern Australian population were obtained. A further subsample of 24, in whom the precise orientation of specimens was known, was subsequently collected. Microradiographs were made of 100-microm sections and the bone was analyzed using image processing software (Optimas, Media Cybernetics). The periosteal boundary was extracted automatically and the centroid of the periosteal outline was calculated. Fourier shape analysis was used to delineate the endocortical surface. Radial and cortical widths in each quadrant were determined. The posterior was identified by the linea aspera, and the medial and lateral were indistinguishable and therefore grouped together. For analysis, the entire sample was divided into three groups: young (20-40 years), middle (41-60 years), and old (61+ years). Raw and height-normalized values were analyzed with SPSS using t-tests, analysis of variance, and Tukey's honestly significant difference (HSD) tests. The results show that with age the femoral mid-shaft in both sexes becomes larger and more circular, with a slight shift towards the anterior. Apposition is least on the posterior and resorption greatest on the anterior, the latter being particularly evident in postmenopausal females. The greatest sex differences are seen in the middle years, lessening again in the old. We conclude that differential circumferential modeling in response to functional and postural changes occurs in both sexes with age.

Adult↗

Computer assistance in multiparameter flow microphotometry of mammalian cells.

Flow system technology enables the biological and medical experimenter to investigate the distribution spectra of various cellular characteristics separately or in parameter combination on the basis of ultrarapid single cell measurements. A typical rate of recognition is about 1000 to 5000 cells per second and the precision of measurements and their statistical relevance has been previously unobtainable. According to the approach of the multiparameter analysis and high data rate, computer assistance in flow system technology is given primary consideration. In this study three different kinds of software controlled modes in data acquisition are demonstrated: normal acquisition and linear accumulation of single parameters, spectra accumulation of two correlated parameters of each single cell and documentation as linear, two- or three-dimensional distribution pattern, and linear accumulation of two correlated parameters simultaneously with their actual signal-to-signal ratio. A first attempt to analyze distribution spectra was the application of the entropy of the structure routinely used in cybernetics. This function seems to be a measure for determining the degree of synchrony in an appropriate pretreated cell population. A special mathematical strategy has been applied to the linear spectra cellular DNA content, whose advantage is the quantitative extraction of the fractions concerning the various phases of the life cycle cells. The validity of this special curve fitting procedure has been proven on various experimental cell populations.

Animals↗

Graduate and post-graduate medical education with the synchronous systems model.

Behavioral sciences have an important new role, particularly in medicine and prevention (Revans, 1990; Starr, 1982). A decade ago when the ideology of medical care shifted from a biomedical to a biopsychosocial model, behavioral and social factors ascended in importance in modern health concerns (see Engel, 1977). Now, a living systems model called Synchronous Systems (Jasnoski & Schwartz, 1985) incorporates environmental (including the social and physical) along with physiological and psychological factors into its structure. The environment has been gaining recognition as an important determinant in health, disease, and wellness (Daniel, 1990; Demick & Wapner, 1990; Lawton, 1990; Stokols, 1990). The phrase "Synchronous Systems" departs from the traditional linear thought patterns to depict contemporaneous occurrences. Synchrony refers to simultaneous experiences or events, with an emphasis on healthy, congruent process and function. Positive, beneficial process in human functioning emphasizes prevention as found in public health efforts but refers also to dysfunctional and recuperative foundation of medicine as a departure from the healthy norm. These process and functional dynamics in the Synchronous Systems Model derive conceptually from systems theory, specifically from control and cybernetic theories (Cannon, 1932; Weiner, 1948). The dynamic complexity of health in the whole human system, which also incorporates the environment, requires synthesis of knowledge from the biological, social, behavioral, and ecological sciences. This article provides the fundamentals of the structural and functional synthesis possible in the Synchronous Systems Model. Its direct application to multidisciplinary research is also presented along with its specific application to medical education, policy, research, and service delivery.

Curriculum↗

Polyploidy in differentiation and evolution.

Somatic and generative (germ-line) polyploidy are more widely spread phenomena among living organisms than generally thought. The occurrence of polyploidization and related events in normal and pathological differentiation, their recognized main functions, as well as the structural specificities of polyploid nuclei are reviewed, and the relationship between ontogenetic and phylogenetic events is discussed. The mechanisms leading to the polyploid state, as well as other processes resulting in a genomic condition different from the diploid one (such as DNA under-replication, gene amplification, and chromatin elimination), are briefly sketched. The various changes in chromosomal DNA described are, in conclusion, seen as evidence supporting the paradigm of a "fluid" or dynamic organization of the eukaryotic genome, as being part of a cybernetic feedback regulation system of gene expression. A model is proposed that unifies the aspects of DNA variation, chromatin structure, and diversification in ontogenesis and phylogenesis.

Animals↗

Vagus Nerve Stimulation in the Developmentally Disabled.

Vagus nerve stimulation (VNS) with the neuro cybernetic prosthesis (NCP) is an approved treatment of partial seizures for patients 12 years and older. Developmentally disabled or mentally retarded patients with epilepsy may also benefit from VNS; however, their evaluation and management pose greater problems. A retrospective chart review was conducted on all patients diagnosed with mild to severe mental retardation who had an NCP implanted. Records of these 21 patients, ranging in age from 3 to 56 years, were reviewed regarding VNS efficacy, side effects, behavioral changes, and alterations in antiepileptic drugs (AEDs). Seizure types included partial onset and generalized. Sixteen patients had clearly evaluable seizures both pre- and postimplant, with a greater than 50% reduction in seizures noted in 68% (11/16) after 6 months of implant. There were no adverse events that prevented chronic stimulation. Institutional staff and family members were provided with both pre- and postoperative education on VNS and magnet use. VNS appeared to be an effective and well-tolerated therapy in this group of developmentally disabled patients with refractory epilepsy.

Journal Article↗

A myocybernetic model of the lower urinary tract.

A biomechanical model of the lower urinary tract which is able to respond to input signals from a neural network is presented. The neural input is the starting point in the description of the relationships between the various physical parameters in the mechanical model of the bladder and the urethra. The cybernetics of the lower urinary tract are described on the basis of the muscle dynamics of simple models of both the detrusor in the bladder wall and the urethral sphincter. The urethral sphincter is not described as a variable resistance, like in other biomechanical models of the lower urinary tract, but is described on the basis of striated muscle dynamics. The forces produced by the detrusor and the urethral sphincter give rise to the bladder pressure and the urethral pressure. Using quasi-steady assumptions, the flow rate of urine is calculated as a result of the pressure difference between the bladder and the urethra. Parameters like the bladder volume, the flow rate and the pressure in the bladder can be compared with clinical data of urodynamic measurements. Simulation results show that the model is able to mimic both a filling and an emptying behaviour which resembles the behaviour of the lower urinary tract. By increasing the resistance of the urethra, a behaviour model of the lower urinary tract appears which is comparable with the pathology of urethral obstruction. A sensitivity analysis of various parameters in the model leads to a better understanding of the biomechanics of the lower urinary tract.

Biomechanical Phenomena↗

Positive and negative feedback: striking a balance between necessary antagonists.

Most biological regulation systems comprise feedback circuits as crucial components. Negative feedback circuits have been well understood for a very long time; indeed, their understanding has been the basis for the engineering of cybernetic machines exhibiting stable behaviour. The importance of positive feedback circuits, considered as "vicious circles", has however been underestimated. In this article, we give a demonstration based on degree theory for vector fields of the conjecture, made by René Thomas, that the presence of positive feedback circuits is a necessary condition for autonomous differential systems, covering a wide class of biologically relevant systems, to possess multiple steady states. We also show ways to derive constraints on the weights of positive and negative feedback circuits. These qualitative and quantitative results provide, respectively, structural constraints (i.e. related to the interaction graph) and numerical constraints (i.e. related to the magnitudes of the interactions) on systems exhibiting complex behaviours, and should make it easier to reverse-engineer the interaction networks animating those systems on the basis of partial, sometimes unreliable, experimental data. We illustrate these concepts on a model multistable switch, in the context of cellular differentiation, showing a requirement for sufficient cooperativity. Further developments are expected in the discovery and modelling of regulatory networks in general, and in the interpretation of bio-array hybridization and proteomics experiments in particular.

Animals↗

Why is epiluminescence microscopy important?

The new morphological information provided by epiluminescence microscopy (ELM) requires a fresh approach to the analysis of pigmented lesions. It necessitates a learning process that pertains to the recognition of hitherto unknown morphological features and is based on the discrimination of these features and their combination into two different patterns. ELM has been shown to improve the sensitivity and specificity of the diagnosis of melanoma and other pigmented lesions by 25-30%. Digitized ELM (DELM) provides an unlimited capacity for data storage and retrieval. It is a computerized imaging method, objective and noninvasive; it provides objective evidence of lesional changes on follow-up; documents growth and any changes in the structure and shape of lesions; and thus helps in decisions on whether to excise them or not. It provides for quality control by means of the aforementioned documentation, which may also serve as back-up in the case of medico-legal problems. In addition, the spectrum is widened by the dimension of teledermatology and cybernet computer-assisted diagnosis, which holds great promise for the future. ELM and DELM are thus the most important single development of the past three decades in the early diagnosis of melanoma.

Humans↗

On the interaction between the central nervous system and the peripheral motor system.

The problem of the control of voluntary human movements is considered from a cybernetic point of view. The human motor system is considered to be divided into a central part and a peripheral part. The peripheral part is relatively well known and may be regarded as a set of subsystems with well known input-output relations. The interaction between the peripheral part and the central part is related to the mechanisms of the peripheral motor part. With regard to the central part two different types of control mechanisms are possible, a) an intricate functioning of the central part which generates the control signals with regard to internal and extrenal dynamical factors, b) the central part has some degree of independence with respect to the dynamics of the peripheral motor part. In the latter case the central part prescribes the desired movement exactly, but the final performance of the movement is also brought about by peripheral feed-back mechanisms. As a functional form of the interaction between the central part and the peripheral part it might be that the control signals are encoded in a way that is related to the muscle lengths.

Central Nervous System↗