[HIV infection: feasibility of a seroprevalence study with consent of hospitalized patients]. A pilot study was carried out in order to evaluate the feasibility of determining the seroprevalence rate of HIV infection and the prevalence of risk factors among selected hospital patients at the Centre Hospitalier Universitaire Vaudois (CHUV). Consent was obtained and only blood already obtained for other purposes was used for testing. Among 850 patients between 16 and 65 years of age and residing in Switzerland who were originally selected at random, only 200 patients were accessible for an interview and for whom blood was available in order to be included in the study. Of these, 165 (83%) accepted their blood to be tested. A seropositive result was identified in 2 patients already aware of their serostatus. The age distribution, diagnosis and behavioral risk factors (when available through the interview) were not different among those accepting the test and the ones refusing. However, foreigners were more likely to refuse the blood test than Swiss nationals, even though none of them came from a country with a high rate of endemicity for HIV infection. Reasons for refusal included the following: lack of risk factors 10 (29%), doubts about confidentiality 6 (17%), blood test already performed 5 (14%), language barrier 4 (11%) and others 10 (29%). We conclude that even though the data in our sample did not suggest that patients refusing the test were at an increased risk of being seropositive, it is unlikely that with such a refusal rate, a reliable measure of seroprevalence could be determined in the population of study with the methods used, especially when one is expecting a relatively low seroprevalence rate.


Infertility in industrialized countries: prevalence and prevention. We discuss the prevalence and aetiology of infertility and the relevance of this information for national infertility services and prevention programmes. The prevalence of infertility in industrialized countries has been said to be as high as 10-20%. This estimate, and the argument that little can be done to prevent infertility, have been used as justification for increased government investment in, or expansion of, services for medically assisted conception. However, population prevalence surveys indicate that far fewer couples of reproductive age are actually infertile. For example, a recent survey in the United States reported that 8.5% of married couples with a wife age 15-44 were infertile. 4% of the sample were childless and reported having a condition which impaired fecundity, while less than 2% were childless, had impaired fecundity and were over 35 years of age. Other studies show that nearly a third of couples have difficulty conceiving at some point during their reproductive lives but few actually remain childless. A significant proportion of infertility could be prevented through more aggressive application of standard public health measures.


Community involvement towards community objectives. The World Health Organisation "Health for all children by the year 2000" declaration presents an exciting yet timely challenge. If these aims are to be achieved, the role of the health worker must be broadened. There must be a recognition that families will determine the true health of their children--physical, mental and social. Families must be able to identify and realise their aspirations, to satisfy their needs and to cope with and adapt to their environments. Only by advocacy, by forming a partnership with families, and by empowering families to exercise greater control over their health and their environment, will health workers begin to see positive change in the community. There is a need to collect and collate data from the community in order that the true needs of families are met. New outcome measures which address "quality of life" must be developed; these will accord closely with the WHO aims, and will enable communities to set the high standards that must be achieved for our children. "Health", interpreted in its broadest meaning, should lead to health professionals concentrating on the promotion of a healthy lifestyle and the attainment of "quality of life". There must be a move away from the "medical model" of care to the empowerment of parents who are responsible for the care for their children and the need to work towards better community resources.


[Therapy for smoking: consensus in German-speaking countries]. The german speaking countries (Austria, Germany, Switzerland) are not the most advanced in the world when it comes to the control of tobacco related diseases. The medical system in these countries has yet to be convinced that smoking cessation is not only necessary but feasible. In order to provide a basic document for further activities, a consensus development process was initiated. The consensus development process forms part of the activities performed by the UICC (International Union Against Cancer) Project Smoking Cessation, which is a project within the framework of the UICC Tobacco and Cancer Programme. The 1988 Report of the US Surgeon General states very clearly, that the use of tobacco products is not a matter of free choice, but is the result of an addiction as scientifically valid as the addiction to heroin and other narcotics. The scientific literature provides informations on many methods and techniques for a smoking cessation, both pharmacological and non-pharmacological. Many pharmacological approaches have been tried to treat nicotine dependence in man. According to scientific standards and many controlled studies, nicotine has been the only drug found to be effective in treating nicotine dependence. Many techniques, ranging from self help to sophisticated combined therapeutic approaches including pharmacological interventions, are now available to deal with the nicotine addiction. Smoking cessation treatment uses time, effort and other resources and the question of reimbursement for these services has to be considered. As with any other form of treatment, costs needed to be paid either by the individual patient/client and/or by other sources including private and national health insurance systems.(ABSTRACT TRUNCATED AT 250 WORDS)


Different frequencies of diabetic complications in insulin-treated patients with diabetes of comparable duration, in relation to age at onset of diabetes. Diabetic complications such as retinopathy and nephropathy affect the quality of life of diabetic patients. The aim of this study was to find out whether there are differences in the development of these complications associated with the age at onset of diabetes and the different effects of diabetes onset before, during or after puberty. Therefore, we tested the hypothesis whether onset of insulin dependent diabetes in puberty was connected with an increased risk of developing diabetic microangiopathy. We found a significantly increased risk in patients with diabetes onset in puberty up to a diabetes duration of 20 years if compared with diabetes onset before but not with that after puberty. It seems that diabetes onset before puberty delays the development of early diabetic complications and that changes of the hormonal status during puberty may be responsible for an earlier development of retinopathy. After about 20 years of diabetes there are no significant differences between the groups. Our results emphasize the necessity of early ophthalmological diagnosis and adequate metabolic control, especially in patients with diabetes onset during or after puberty, in order to prevent or delay the development of diabetic complications.


Prevalence of mycoplasmas in the respiratory tracts of pneumonic calves. The prevalence of mycoplasmas in the respiratory tracts of 148 pneumonic calves originating from 25 herds in the Netherlands is reported. Four types of culture media were used to isolate mycoplasmas: solid modified Edward medium, 2 types of Friis media, and A7B differential agar medium. Mycoplasmas were isolated both from nasal swab specimens and lung lavage fluids collected from live calves and from nasal mucosa and lung tissue specimens collected post mortem. All of the mycoplasma strains isolated could be identified as either Ureaplasma diversum (isolated from 80% of 25 herds), Mycoplasma dispar (92%), M. bovirhinis (88%), M. bovis (20%), M. bovigenitalium (4%), M. arginini (16%), or M. canis (12%). Isolation rates of M. dispar and U. diversum were considerably higher from lung lavage fluids than from nasal swab specimens. M. bovis was detected only in fattening herds and not in dairy herds. The respiratory tracts of 75% of the calves examined contained at least 2 mycoplasma species. In total, 25 different combinations of mycoplasma species were detected in specimens collected from noses and lungs. The pathogenic species U. diversum and M. dispar had not been isolated before in the Netherlands.


Antibody responses to natural Dictyocaulus viviparus exposure in first year grazing cattle using vaccination or different kinds of anthelmintic treatment. In two field trials vaccination or different anthelmintic treatments against Dictyocaulus viviparus infections were used in 6 groups of first year grazing cattle. The antibody response to lungworm infections was determined using an ELISA. Cattle treated once or repeatedly at long intervals with levamisole developed clinical signs of dictyocaulosis. The detection of anti-D. viviparus antibodies at the end of the grazing season confirmed that these anthelmintic treatments were not able to prevent lungworm infections. Cattle that received strategically administered treatments with ivermectin remained clinically healthy. These cattle were seronegative until the end of the trial which proved the efficacy of the strategic control. Cattle that received an intraruminal slow release bolus did not develop clinical disease. However one animal shed lungworm larvae and the herd became seropositive at the end of the grazing season indicating a history of infection. The serological examination of a cattle herd at the end of the grazing season is able to demonstrate a history of lungworm infections and to determine the efficacy of anthelmintic control measures.


Canine distemper with spinal cord lesions. A case of distemper in a 6-month-old dog is described. The dog was presented with a history of tetraparesis suggestive of trauma. Neurological examination and clinical pathology findings of lymphopenia and pleocytosis suggested a viral cause. Microscopic findings of a nonsuppurative meningoencephalomyelitis with numerous intranuclear inclusions in the cerebellum, brain stem, and all parts of the spinal cord suggested a diagnosis of distemper.


[Infections with enteropathogenic Escherichia coli (EPEC) in cattle. 1. Comparison of different animal models and a cell culture system for the establishment of a detection system for "attaching and effacing" (AE) lesions]. In several animals species, enteropathogenic Escherichia coli (EPEC) were described as agents causing diarrhea. The histopathogenic pattern of EPEC is due to a typical adherence to enterocytes, called "attaching and effacing" (AE). This lesions are characterized by the formation of pedestals, cups and a marked loss of microvilli on enterocytes. In view of using an "in vitro system" (HeLa-cell culture) to test the adherence of EPEC, we first tested bovine EPEC in several laboratory animals. Various strains of mice, one day chicks (peroral) and a three day old calf (ligated intestinal loops) were inoculated with a bovine pathogenic EPEC (S 102-9). The adherence of EPEC "in vivo" was histologically, electron microscopically and bacteriologically investigated and compared to adherence to HeLa cell cultures. AE-lesions were found on calf enterocytes as well as on HeLa-cells, no lesions were seen in mice and chicks. The ligated intestinal loop test seems to be a useful model to compare "in vivo" to "in vitro" adherence.


Identification of a cyprinid fish, the tench Tinca tinca L., as a carrier of the bacterium Aeromonas salmonicida, causative agent of furunculosis in salmonids. A typical, pigment-producing strain of Aeromonas salmonicida (A. sal.), the causative agent of furunculosis in salmonid fish species, was isolated from a cyprinid species, the tench Tinca tinca L. with papilloma-like skin alterations. Histopathology of the papilloma-like skin alterations in tench revealed "round holes", distinctly lined by thick layers of epithelial cells, but no bacteria. The organism was isolated from skin, gills and fins, but not internal organs. The isolate proved highly virulent for both juvenile tench and brown trout Salmo trutta L. in experimental infection, but it did not reproduce the clinical picture. The causative role of A. sal. for the surface lesions remains questionable. However, there is a perceived risk of the organism's transmission between tench and other susceptible species of fish, especially farmed trout.


Bacillary haemoglobinuria diagnosis by the peroxidase-antiperoxidase (PAP) technique. A peroxidase-antiperoxidase (PAP) technique was used to diagnose bacillary haemoglobinuria in formalin-fixed, paraffin-embedded liver tissues of cattle. The PAP method revealed Clostridium haemolyticum in the zone of liver necrosis characteristic of the disease and also in culture smears of this microorganism, but C. novyi type B, C. chauvoei, C. septicum and C. perfringens types B and C remained unstained by the PAP reaction. The PAP technique performed provides a specific, simple and rapid method to diagnose bacillary haemoglobinuria.


The nasal mycoplasmal flora of healthy calves and cows. The nasal mycoplasmal flora of 270 healthy cows from 27 herds in the Netherlands and 35 healthy calves from 7 of these herds was examined. Various methods for isolating mycoplasmas were compared. The prevalence of the various species was as follows: Ureaplasma diversum in 3 (9%) calves; Mycoplasma dispar in 14 (40%) calves; M. bovis in 1 (3%) calf; M. bovirhinis in 23 (66%) calves and 16 (6%) cows; M. bovoculi in 8 (23%) calves and 53 (20%) cows; M. canis in 1 (3%) calf; M. equirhinis in 2 (1%) cows; M. conjunctivae in 2 (1%) cows; Acholeplasma laidlawii in 1 (3%) calf and 3 (1%) cows; and A. axanthum in 7 (3%) cows. The noses of healthy calves were less frequently colonized by the pathogenic species U. diversum and contained fewer U. diversum and M. dispar organisms than the noses of pneumonic calves. We concluded that the mycoplasmal flora of calves and healthy cows was quite different and also that cows play only a minor role in the epidemiology of pathogenic mycoplasma species of calves in the Netherlands.


Studies on the application of enzyme immunoassays for the Fusarium mycotoxins deoxynivalenol, 3-acetyldeoxynivalenol, and zearalenone. Polyclonal antisera against zearalenone (ZEA) were produced in rabbits after immunization with ZEA-oxime coupled to human serum albumin. Using these antibodies and a ZEA-oxime-horseradish peroxidase conjugate in a competitive direct enzyme immunoassay (EIA), the detection limit for ZEA was 70 pg/ml. The relative cross-reactivities of the assay with ZEA, alpha-zearalenol, beta-zearalenol, zearalanone, alpha-zearalanol, and beta-zearalanol, respectively, were 100%, 37.3%, 7.2%, 59.2%, 5.3%, and 3.9%, respectively. This EIA and two EIAs for deoxynivalenol (DON) and 3-acetyldeoxynivalenol(3-AcDON) (Usleber et al., 1991) were used to analyze wheat samples. The limits of determination for DON, 3-AcDON, and ZEA in wheat were 200 ppb, 50 ppb, and 20 ppb, respectively. The analysis of reference materials (wheat flour) containing DON by EIA showed good agreement with the nominal values. The EIA for ZEA was in addition used to analyze biological fluids, obtained during a feeding trial. Two lactating cows were administered 25 mg and 100 mg ZEA per day, respectively, over a period of 6 days. Serum, milk, urine, and feces were assayed in the ZEA-EIA with and without sample treatment with beta-glucuronidase prior to the analysis. Maximum toxin levels (ZEA-equivalents) found in milk were 0.4 and 1.2 ppb (glucuronides). The toxin concentration in milk decreased rapidly after the last toxin administration. In the urine, maximum levels of toxin-glucuronide conjugates were 23 ppb and 24 ppb, respectively. The serum toxin levels corresponded to those found in milk. In the feces, mean values were 150 ppb and 500 ppb, respectively, no conjugated toxins were found in feces.


Modelling of in vivo calcium metabolism. II. Minimal structure or maximum dynamic diversity: the interplay of biological constraints. The temporal behaviour of the nonlinear compartmental model we have developed for rat calcium metabolism is discussed with respect to the theoretical properties of the self-oscillating autocatalytic subunit around which the model is constructed. Depending on the approximations made, this subunit is described by a minimal two-variable model, SU2, or by a three-variable one, SU3. The diversity of the theoretical dynamic behaviours possible with SU2 is greatly increased with SU3. But the identification of SU3 parameter values in three different experimental situations reveals that biological constraints efficiently preserve a simple circadian rhythm for bone metabolism. This analysis indicates the significant contribution of the available bone crystal pool to the dynamic organization of this tissue, and hence to extracellular calcium homeostasis.


On the existence and the role of chaotic processes in the nervous system. Chaos theory is a rapidly growing field. As a technical term, "chaos" refers to deterministic but unpredictable processes being sensitively dependent upon initial conditions. Neurobiological models and experimental results are very complicated and some research groups have tried to pursue the "neuronal chaos". Babloyantz's group has studied the fractal dimension (d) of electroencephalograms (EEG) in various physiological and pathological states. From deep sleep (d = 4) to full awakening (d > 8), a hierarchy of "strange" attractors paralles the hierarchy of states of consciousness. In epilepsy (petit mal), despite the turbulent aspect of a seizure, the attractor dimension was near to 2. In Creutzfeld-Jacob disease, the regular EEG activity corresponded to an attractor dimension less than the one measured in deep sleep. Is it healthy to be chaotic? An "active desynchronisation" could be favourable to a physiological system. Rapp's group reported variations of fractal dimension according to particular tasks. During a mental arithmetic task, this dimension increased. In another task, a P300 fractal index decreased when a target was identified. It is clear that the EEG is not representing noise. Its underlying dynamics depends on only a few degrees of freedom despite yet it is difficult to compute accurately the relevant parameters. What is the cognitive role of such a chaotic dynamics? Freeman has studied the olfactory bulb in rabbits and rats for 15 years. Multi-electrode recordings of a few mm2 showed a chaotic hierarchy from deep anaesthesia to alert state. When an animal identified a previously learned odour, the fractal dimension of the dynamics dropped off (near limit cycles).(ABSTRACT TRUNCATED AT 250 WORDS)


Application of the metabolic control theory to the study of the dynamics of substrate cycles. Substrate cycles are ubiquitous structures of the cellular metabolism (e.g. Krebs cycle, fatty acids beta-oxydation cycles, etc...). Moiety-conserved cycles (e.g. adenine nucleotides and NADH/NAD, etc...) are also important. The role played by such cycles in the metabolism and its regulation is not clearly understood so far. However, it was shown that these cycles can generate multistationarity (bistability), irreversible transitions, enhancement of sensitivity, temporal oscillations and chaotic motions (Hervagault & Canu, 1987; Hervagault & Cimino, 1989; Reich & Sel'kov, 1981; Ricard & Soulié, 1982). [formula: see text] Fig. 1: Scheme of the open binary substrate cycle under study. The substrate S is converted into P with a net rate v2. Substrate P is converted in turn into S with a net rate v3. Step v2 is inhibited by excess of the substrate, S. In addition, the cycle operates under open conditions, that is zero-order input of S at rates alpha 0(v1) and first order outputs of S and P at rates alpha S and alpha P(v4), respectively. The metabolic control theory (see also Fell, 1990), which shows how a metabolic network reacts to small perturbations in the vicinity of a steady state, and is formulated with the so-called "control coefficients", was applied to such a cycle in order to get a better knowledge on the importance of each step at the regulatory point of view. The behaviour of a binary substrate cycle (fig. 1) in which one of the enzymes may be subjected to inhibition by excess of its substrate (v2) was studied theoretically.(ABSTRACT TRUNCATED AT 250 WORDS)


Flow cytometric analysis of the cell cycle: mathematical modeling and biological interpretation. Estimation of the repartition of asynchronous cells in the cell cycle can be explained by two hypotheses: the cells are supposed to be distributed into three groups: cells with a 2c DNA content (G0/1 phase), cells with a 4c DNA content (G2 + M phase) and cells with a DNA content ranging from 2c to 4c (S phase); there is a linear relationship between the amount of fluorescence emitted by the fluorescent probe which reveals the DNA and the DNA content. According to these hypotheses, the cell cycle can be represented by the following equation: [formula: see text] All the solutions for this equation are approximations. Non parametric methods (or graphical methods: rectangle, peak reflect) only use one or two phase(s) of the cell cycle, the remaining phase(s) being estimated by exclusion. In parametric methods (Dean & Jett, Baisch II, Fried), the DNAT(x) distribution is supposed to be known and is composed of two gaussians (representative of G0/1 and G2 + M) and a P(x,y) function representative of S phase. Despite the generality, these models are not applicable to all sample types, particularly heterogeneous cell populations with various DNA content. In addition, the cell cycle is dependent on several regulation points (transition from quiescence to proliferation, DNA synthesis initiation, mitosis induction) and biological perturbations can also lead to cytokinesis perturbations. Before the emergence of flow cytometry, the current view of cell cycle resided in the assessment of cell proliferation (increase in cell number) or the kinetic of molecules incorporation (DNA precursors).(ABSTRACT TRUNCATED AT 250 WORDS)


Measurement of efflux from G1-phase in a growth factor dependent cell line. In order to test a mathematical model of G1/S-phase transition, the proliferative response of the murine myeloid interleukin 3 (IL-3) dependent cell line NFS-78 to graded reduction of IL-3 levels was measured. Exponentially growing cells were exposed to bromodeoxyuridine (BUdR), which replaces thymidine (TdR) in the DNA double strands during DNA synthesis. After incubation periods ranging from 3 to 36 h the cells were fixed and stained with a fluorescence dye mixture of Hoechst 33258 and ethidium bromide (EB) and subsequently analyzed in a two-parametrical flow cytometer. The BUdR-quenched TdR-specific Hoechst 33258 fluorescence of each cell provides information on the cell cycle location at the start of incubation and on whether or not a cell has divided. The DNA-specific EB fluorescence provides information on the actual cell cycle location at the end of the incubation period. From the 2-dimensional fluorescence distributions the efflux from G1-phase was calculated. Upon IL-3 reduction the cells showed accumulation in the G1-phase along with a reduction in the progression rate through the other phases of the cell cycle. By staining with the vital dye Hoechst 33342 as well as with propidium iodide (PI) it was further possible to show that cell death after IL-3 withdrawal occurred in all phases of the cell cycle.


Growth factors and cell kinetics: a mathematical model applied to Il-3 deprivation on leukemic cell lines. We assume the existence of a specific G1 protein which is an initiator of DNA replication. This initiator is supposed to be synthesized according to Michaelis-Menten kinetics. In order to start DNA replication, it is assumed that this G1 specific protein must be produced in a required amount. Intra-cellular growth inhibitors and extra-cellular growth factors control the production of the initiator. This model allows to calculate the average G1 phase time as a function of the various chemical concentrations of nutrients, enzymes, growth inhibitors and growth factors. This model is compared to cell kinetics experiments on a leukemic cell line responding to Interleukin 3 deprivation. The curves giving the experimental average G1 phase times with respect to Interleukin-3 concentrations are fitted by the mathematical model with a quite good agreement.


Interpretation of epicardial mapping by means of computer simulations: applications to calcium, lidocaine and to BRL 34915. The aim of this work was to compare experimental investigations on effects of lidocaine, calcium and, BRL 34915 on reentries to simulated data obtained by use of a model of propagation based on the Huygens' construction method already described in previous works. Calcium and lidocaine effects are investigated on anisotropic conduction conditions. In both cases, reduction in conduction velocities are observed. In lidocaine case, a refractory area is located along the longitudinal axis. In agreement with experimental electrical mapping, the simulations show that the stabilization of reentrant excitation is mainly due to the existence of this refractory area around which the reentrant circuit can develop. The experimental study shows that BRL 34915 has both arrhythmogenic and antiarrhythmic effects. A detailed electrophysiological analysis has shown that drug infusion act on normal cardiac cells by decreasing the relative and absolute refractory period. BRL 34915 action is simulated by a decrease in the refractory period showing that the time frequency of the reentrant activity is increased and that the spatial size where the reentry is developing is becoming smaller. These two effects are arrhythmogenic, the simulated data being so in good agreement with the experimental ones.


Analytical modeling of the hysteresis phenomenon in guinea pig ventricular myocytes. In the present study, we have demonstrated hysteresis phenomena in the excitability of single, enzymatically dissociated guinea pig ventricular myocytes. Membrane potentials were recorded with patch pipettes in the whole-cell current clamp configuration. Repetitive stimulation with depolarizing current pulses of constant cycle length and duration but varying strength led to predictable excitation (1:1) and non-excitation (1:0) patterns depending on current strength. In addition, transition between patterns depended on the direction of current intensity change and stable hysteresis loops were obtained in stimulus:response pattern vs. current intensity plots in 14 cells. Increase of pulse duration and decrease of stimulation rate contributed to a reduction in hysteresis loop areas. Changes in amplitude and shape of the subthreshold responses during the transitions from one stable pattern to the other, suggested that activity led to an increase in membrane resistance, particularly in the voltage domain between resting potential, and threshold. Therefore, we modelled the dynamic behaviour of the single cells as a function of diastolic membrane resistance, using previously published analytical solutions. Numerical iteration of the analytical model equations closely reproduced the experimental hysteresis loops in both qualitative and quantitative ways. In particular, the effect of stimulation frequency on the model was similar to the experimental findings. The overall study suggests that the excitability pattern of guinea pig ventricular myocytes accounts for hysteresis and bistabilities when current intensity is allowed to fluctuate around threshold levels.


Modifiable automata self-modifying automata. One of the most important features of living beings that seems universal is perhaps their ability to be modified in a functional way. In order to modelize this characteristic, we designed automata with a finite number of instantaneous internal descriptions, with input(s) and output(s) and which are able to be functionally modified. The rules which govern the evolution of these automata (and the initial conditions) are randomly chosen at the beginning and once and for all. When such an automaton is linked by its input and output to a deterministic process, it always stabilizes and it then has the property to rebuild itself. Thus it made a function which is inverse of the external function. We demonstrate the prevalence of p = 1 length period and of tau = 0 transient length for automata with m instantaneous internal descriptions.


Automatic search for model to simulate the differentiation of T lymphocytes within the thymus. The differentiation of T Lymphocytes within the thymus is an important biological phenomenon during which these cell acquire their functions to further control the immune system. Numerous experiments under various conditions have been devised to understand the different mechanisms involved in this complex process. Nevertheless, interpretation of these experiments lead to still contradictory debatable hypotheses. Modelisation of this process through classical simulation methods cannot be envisaged because they are not adapted to modifications of the model structure, which is the point of interest. For these reasons, we proposed a new approach of automatic search for model. The program consists of four independent connected modules: The generator produces model, based on the rationale of formal grammars. Protocol and experimental data are stored in a set of experiments. The simulator using a protocol and a model provides simulated results. Finally, the supervisor by comparing simulated results and experimental data, adapts the model parameters to increase their fit and either chooses a new experiment to explore, or modifies the model structure. Change of the model structure is performed among still unexplored models according to their "promise" level, which is iteratively evaluated relatively to previously explored models through a proposed model distance. The generator is written in Prolog and the other modules in C++. The architecture of the program allows us to modify or complete a module without changing anything in the other modules. As a consequence, the proposed modeling approach conceived to study T lymphocyte differentiation within the thymus remains independent of this biological phenomenon and can be applied to other biological problems.


[The Catastrophe theory and membrane physiological functions]. This communication is based on a preliminary work which emphasized a topological model of biomembranes from Thom's Catastrophe Theory. In this model called swallowtail bifurcation set, the structural state of a biomembrane was within the control of two structural attractors. Then, the physiological act of this biomembrane resulted in a sudden transfer of weight from the hydrophilic attractor to the hydrophobic attractor. In this consecutive work, the physiological act appears to be one of the four stages which permit to describe the larger notion of cyclic membrane function. Two of these stages unfold in the structural axis of the swallowtail model. They prepare the two others (physiological act and refractory stages) which expand in the functional direction. This conceiving of cyclic membrane function is applied to physiological examples such as the action potential and the endocytosis. Then, changes in this function are discussed on the basis of pathological data.


[Spermatocyte and ovum symbiosis, origin of ontogenesis and phylogenesis of metazoans]. The origin of metazoa implies the passage from an eukarote protozoan to a protozygote ancestor of a metazoan zygote. The most probable hypothesis is that of a symbiotic origin of the first zygote by association of two protists one signifying a spherical oocell and the other a flagellated spermatozoan; this could be the first step of the metazoan ontogenesis and therefore also of the phylogenesis. The genesis can also be explained by two haploid genomes NX NY, three gametes (two spermatozoa and one ovule), NX apparently being able to create both forms, and two zygotes. A double symbiosis, a chromosomic crossing-over and a selective expulsion can prove it.


[Quasicrystal organization in extracellular matrixes]. In this note we argue that the theoretical approach, developed in the field of quasicrystals, may prove to be useful in a completely different area, namely biology, and more precisely for the transmission electron microscopy observation of biological structures this sections. Whatever the real three-dimensional structure is periodic, a generic cut will produce a quasiperiodic pattern. This is illustrated in a "theoretical" example inspired by the 3D organization of annelid cuticle. In addition, we discuss recent results on dislocations in quasicrystals, and their possible consequence about observation in biology. Finally, this analysis could be extended to images obtained from other technics, like freeze-fracture, and other materials, provided that certain length scale relations be satisfied.


Modelling of in vivo calcium metabolism. I. Optimal cooperation between constant and rhythmic behaviours. The relevance of nonlinear dynamics to calcium metabolism led us to reevaluate the role of Ca-regulating hormones in Ca homeostasis. We suggest that, firstly, the main Ca metabolic functions in rat-bone and gut--are organized as dynamic entities able to generate various temporal expressions, including self-oscillating patterns and, secondly, Ca homeostasis results from interaction between both metabolic and hormonal oscillators. Following this schema, a major role for the hormonal system, with its circadian pattern, could be to act directly on metabolic functions or indirectly through feeding behaviour, in order to optimize, coordinate and synchronize the Ca fluxes at ECF level.


Teflon/polyurethane arthroplasty of the knee: the first 2 years preliminary clinical experience in a new concept of artificial resurfacing of full thickness cartilage lesions of the knee. Thirty-seven full-thickness knee cartilage lesions were treated with a Teflon/polyurethane composite implant in 23 patients. The preoperative diagnoses were osteoarthritis, osteonecrosis and a traumatic osteochondral lesion. The implant was fixed to the subchondral bone with Tissucol (Immuno, Vienna), a human fibrin glue. The leg was immobilized for 6 weeks followed by 8 days of continuous passive motion in parallel with full weight-bearing. High tibial osteotomy to correct a varus or valgus deformity was performed on 16 patients approximately 6 weeks after implantation of the composite implant. Fourteen patients were arthroscoped after 1 year, which demonstrated good fixation and congruity of the implant with the adjacent cartilage. All 23 patients were available for clinical and radiographic follow-up at a minimum period of 2 years after implantation. Seventy-eight percent of the patients reported complete pain relief. Eleven patients were rated as good, 3 as fair, 4 as poor, while 4 were loosenings. All loosenings were from knees with unicompartmental bipolar implantations and required only arthroscopic removal. Moreover, 21% of the patients had reduced range of motion post-operatively. No clinical synovitis was seen. This high incidence of stiff knees may be reduced by shortening or altogether eliminating the post-operative immobilization period in conjunction with early application of CPM. We conclude that a Teflon/polyurethane composite implant has been successful as a prosthetic knee resurface implant and demonstrates good biocompatibility. However, the use of unicompartmental bipolar implants should be avoided.


[Classification of post-traumatic soft tissue lesions]. A successful treatment of fractures with soft tissue injuries depends on surgical principles and on the individual prognosis of each trauma. Classification systems are ment to be an aid in taking therapeutical decisions in the assessment of the prognosis and in comparising of different lesions. In the anglo-american literature the classification of Gustilo in open fractures grade 1 to 3 and the subclassification of grade 3 lesions in A, B and C are the most accepted. In the german-spoken countries the classification of Tscherne and Oestern, dividing open and closed fractures in 4 different categories is the most used.


[Functional sequelae in tibial shaft fractures with compartment syndrome following primary treatment with urgent fasciotomy]. In a retrospective study on 28 patients, the incidence, nature and severity of the sequelae after severe lower leg trauma were studied. All patients had a tibial shaft fracture with a complete or impending compartment syndrome, treated with an urgent stabilisation and an adequate decompressive fasciotomy. In a thorough clinical examination, performed 17 months after trauma, the mobility of the knee and ankle joint, the perimetry of the lower leg and foot, and the muscle strength of all lower leg muscles were measured. Contractures were noticed, superficial sensibility was tested and an evaluation of march was done. More than one fourth of the patients showed late functional disabilities, mainly because of limitation of the dorsiflexion of the ankle joint, reduction of the muscle strength of the foot extensors, contractures of the foot flexors and abnormal superficial sensibility. The more severe the primary soft tissue trauma was, the more severe the functional disabilities were. The severity of the soft tissue damage, resulting from the trauma itself, is the most important factor for the late functional result after lower leg trauma. The compartment syndrome is certainly an aggravating factor when it is not treated by urgent fasciotomy. But this does not mean that all patients with lower leg fracture and compartment syndrome, treated with urgent fasciotomy, will show excellent functional end results.


[Tolerance of adjuvant treatment combining postoperative intraportal chemotherapy and a systemic treatment based on 5-fluorouracil in colorectal carcinoma with a histologically poor prognosis]. From April 89 to October 90, 41 patients operated for a Dukes B or C colorectal cancer were randomized to receive 6 courses of adjuvant treatment with (A) 5-FU alone (440 mg/m2 IV bolus 5/21 days) or (B) folinic acid (200 mg/m2 IV bolus 5/21 days) preceding 5-FU (370 mg/m2 in short infusion 5/21 days). Ten patients received also one course of immediate post-operative continuous portal infusion (5-FU 500 mg/m2/day x 7 followed by a 2 hours infusion of mitomycin C 10 mg/m2). The portal treatment was well tolerated (1 case of GI tract disturbances, 1 catheter obstruction). The toxicity of adjuvant systemic treatment was evaluated on 232 courses (125 A, 107 B). Hematologic and skin toxicities, alopecia and nausea-vomiting were mild. The limiting toxicities (expressed as percentages of courses) were stomatitis (grades 2-3: 11.4% A; 22.6% B) and diarrhea (grades 3-4: 7.3% A; 14.2% B; one toxic death was to deplore in arm B from a grade 4 diarrhea). The pilot study has demonstrated the feasibility of the adjuvant treatment proposed; a multicentric randomized trial (expected accrual: 800 patients) has therefore been activated on 11.01.90; all patients will also receive levamisole while radio-therapy will be mandatory for rectal cancer.


Combined treatment of liver failure and hepatorenal syndrome with orthotopic liver transplantation. Hepatorenal syndrome (HRS) is a severe complication of liver failure with high mortality. The pathogenesis of this reversible functional renal failure is not yet clearly understood. Diagnosis is based upon the association of clinical and biological criteria. A patient was admitted to our institution for severe liver failure secondary to an exacerbation of cirrhosis, where he developed a fulminant hepatorenal syndrome. Both, the renal and hepatic failure were successfully treated by orthotopic liver transplantation. Special attention was paid to the immunosuppressive treatment with Cyclosporine whose use, we believe, should be delayed until function has partially recovered.


[Acute hepatitis and poisoning by Amanita phalloides]. We report the case of a 69-year-old woman who presented acute hepatitis due to Amanita Phalloides poisoning complicated of acute renal failure. Her clinical evolution was favorable under medical treatment whose actual modalities are discussed.


Blood-brain barrier and cerebrospinal fluid circulation. There are two distinctive regions in the central nervous system of all vertebrates: the common brain region possessing the blood-brain barrier, and a group of several brain regions (circumventricular organs (CVOs) including the choroid plexus) devoid of the blood-brain barrier. Of the first, the morphological basis in vertebrates higher than teleosts is the brain-type capillary endothelium, and in elasmobranchs the perivascular astrocytic end-feet sealed by tight junctions. Of the second, the morphological basis is the fenestrated capillary with perivascular space. The pial connective tissue directly continues to the propria of circumventricular organs, and thus offers sites of cerebrospinal fluid drainage through CVO venous capillaries of which the fenestrated endothelia are anchored to perivascular tissues by the microfibrils of elastic fibers. The arachnoid granulations, which increase in size and number in accordance with the increasing volume of the skull are safety balloons against a sudden rise in intracranial pressure. They are possibly also sites of immune responses.


Hepatobiliary cystadenoma with mesenchymal stroma: presentation of one case and review of the literature. We present one case of hepatobiliary cystadenoma with mesenchymal stroma (CMS) which is a very unusual tumor of the biliary tract. These rare neoplasms have been identified as a distinct clinicopathological entity. They occur exclusively in middle-aged women with an average age of 45 years, and are located on the right hepatic lobe. Histologically, CMS are characterized by the presence of a typical dense stroma between an inner epithelial lining and an outer loose connective layer. Malignant transformation may occur and therefore a complete surgical resection of these premalignant neoplasms is indispensable.


[A study on the communication between the pectoral nerve and the extramural nerve branches of the intercostal nerves]. Kumaki et al. (1979) defined the extramural nerve as the rudimentary sensory nerve which appeared on the upper thoracic wall; it branched off the root of the lateral cutaneous nerve of the second, third or fourth intercostal nerve, ran inferomedially adhering to the fascia of the intercostalis externus muscle and ended supplying the membrane covering the adjacent rib. They also stated that the extramural nerve (Rxm) occasionally became a cutaneous nerve which pierced the pectoralis muscles and supplied the skin covering the thoracic wall similar to the lateral cutaneous nerve (Rcl) or the anterior cutaneous nerve (Rca). Further, they proposed that the muscular nerves to the obliquus externus abdominis muscle which are usually situated below the fifth rib might be considered a part of this Rxm series. Although the definition of Rxm is still not widely accepted, Rxm is thought to be a key morphological factor influencing the variations of peripheral nerve arrangement on the thoracic wall. In the student course of gross anatomy dissection at Iwate Medical University School of Medicine during the years 1987-1991, three cases of Rxm communicating with the pectoral nerve and supplying the pectoralis major muscle were observed. Some cases have been reported in which Rcl innervates part of the pectoral muscles. However, the communication between the pectoral nerve and Rxm has not yet been discussed. Therefore, to clarify the morphological significance of the communication between Rxm and the pectoral nerve, the branching pattern and the distribution of the pectoral nerves were extensively investigated and the intramuscular nerve supply of some pectoral nerves, especially the pectoral nerves which communicated with Rxm, was examined in detail under a stereomicroscope. The results are summarized as follows: 1. In the first case, Rxm of the second intercostal nerve originated from Rcl, ran inferomedially adhering to the fascia of the intercostalis externus muscle and pierced the origin of the pectoralis minor muscle at the third intercostal space. Then Rxm turned superolaterally to communicate with a pectoral nerve which originated from the loop composed of the lateral and medial pectoral nerves and passed inferior to the pectoralis minor muscle. After communication, the pectoral nerve with Rxm supplied the caudalmost part of the sternocostal portion of the pectoralis major muscle. In the second case, a similar branch of Rxm of the second intercostal nerve passed inferior to the pectoralis minor muscle.(ABSTRACT TRUNCATED AT 400 WORDS)


Epicardial formation in staged human embryos. The manner of epicardial formation has been unequivocally clarified by electron microscopy in representative species of the vertebrates. In human embryology, however, information on the epicardial formation is still lacking. To fill the gap of knowledge, we performed the light microscopic observations on serial paraffin sections of human embryos at Carnegie stages 12 to 17. At stage 12, initial formation of the epicardium was seen in 2 of 6 embryos. As was seen in chick embryos, villous protrusions of the mesothelial cells extending from the sinus wall region touched the ventricle on the dorsal side to spread out on it as a simple squamous epithelium. At subsequent stages, the epicardial covering was extended concomitantly with histogenesis and organogenesis of the embryonic heart. Although the final stage was difficult to define at the light microscopic level, the epicardium was considered to cover the entire heart by late stage 16, on the basis of reference to the findings on chick embryonic heart.


[Prevention of bacterial infection using selective intestinal decontamination in patients with cirrhosis admitted to intensive care. Controlled study in 120 patients]. All cirrhotic patients admitted on a medical intensive care unit, were included in a randomized trial of selective intestinal decontamination provided there was no infection on admission. The selective intestinal decontamination consisted of a regimen of 3 oral, nonabsorbable antibiotics for the 74 first patients (Neomycin 1 gr, Colistin 1.500.000 U, Nystatin 1.000.000 U, every 6 hours), then of norfloxacin, 400 mg BID for the following patients. The duration of treatment was at least 5 days. Of the 120 patients, initially randomized to receive or not the treatment, 26 were ultimately excluded, mainly (18 cases) because of infection present but unrecognized at the time of admission. Ninety four patients were thus compared for the efficiency of the treatment, 45 in the treated group and 49 in the not treated group. The results showed a significant reduction of the episodes of septicemia in the treated group (4 versus 12, P = 0.044). This reduction was evident only for septicemia due to gram negative germs. Mortality was unaffected. When the risk factors were studied, bacterial infection was linked to the degree of hepatic failure. We recommend selective intestinal decontamination for cirrhotic patients admitted on intensive care unit, particularly when hepatic function is poor.


[Peptidergic innervation in the sinus hair follicles of several mammalian species]. In this study, the detailed distribution of peptidergic nerve fibers in the sinus hair follicle was immunohistochemically investigated by the avidin biotin-complex method using antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in the cat, dog, hamster, rat, mouse and guinea pig. The peptide-immunoreactive (IR) nerve fibers presented a fine varicose appearance. They entered the sinus hair follicle after penetrating the capsule (Cap) at various levels. Peptide-IR fibers in the sinus hair were classified into the 3 types described below based on their course of entry and terminal distribution. Type A: these fibers arrive at the orifice of the sinus hair follicle from superficial dermis and innervate the upper portion of the follicle. Most of them form a network around the vibrissal shaft (VS) in the outer and inner conical body (OCB and ICB, respectively), and some are distributed around the rete ridge collar (RRC) and the sebaceous gland (SG). Type B: these fibers enter the lower third of the sinus hair follicle after forming a nerve bundle together with myelinated fibers, or accompany an artery. After distribution in the trabeculae (Trab) of the cavernous sinus (CS), they form a dense plexus in the connective tissue follicle (CTF) at the level of the CS. Some ascend through the CTF and terminate at the level of the ring sinus (RS). Type C: these fibers enter the sinus hair follicle at its base. They innervate the hair papilla (HP) and the CTF of the hair bulb. CGRP and SP were detected in all types of nerve fibers in all species investigated. These peptidergic nerve fibers showed the same distribution pattern, but CGRP fibers were more numerous than SP fibers. They were distributed at high density in the OCB, ICB, CTF, ringwulst (Rw), the Trab of the CS and the HP. A moderate number of VIP- and NPY-IR fibers, mainly types B and C, were detected in these portions in the cat, dog and hamster, but few fibers were observed in other portions or in other species. Although the basic structures of the sinus hair follicle presented almost the same features as in the mammalian species, the connective tissue of the HP extended to the level of the RS in the cat, rat, hamster, and guinea pig. In these species, CGRP-, SP- and/or VIP-IR fibers extended to the top of the papillary connective tissue, and in the cat, were especially well developed.(ABSTRACT TRUNCATED AT 400 WORDS)


Relationship between the recurrent laryngeal nerve and the inferior thyroid artery in Japanese. The anatomical relationship between the recurrent laryngeal nerve and the inferior thyroid artery was studied on 784 sides of the necks of 309 male and 123 female Japanese cadavers. On the right side, the nerve passed anterior to the artery in 32.4%, posterior to it in 26.7%, and between the branches of the artery in 40.9%. On the left side, the nerve was found coursing anterior to the artery in 4.9%, posterior to it in 65.8%, and between the branches in 29.3%. There was a statistically significant difference in the percentage distribution of the three types between the right and left sides, while no significant difference existed between males and females. The side difference in the relationship could be attributed to the difference in the course of the recurrent laryngeal nerve between the two sides. The collaterally symmetric cases of the relationship between the nerve and the artery were found more frequently in males (40.0%) than in females (28.6%). The present study revealed that the relationship between the nerve and the artery in Japanese was essentially similar to those in Americans and Europeans reported in other previous studies.


[Critical study of digestive tract dysplasia]. Dysplasia designate the presence in a tissue of atypical architectural and cytological features similar to those observed in carcinogenesis. It must be clearly distinguished from metaplasia which is, in itself, a benign state characterized by the progressive replacement of a normal tissue by an other, normally foreign to this organ. Although the theoretical definition of dysplasia and its relation to carcinogenesis is well demonstrated, numerous difficulties remain regarding its classification and clinical applications. Recent research based on follow-up studies and on diagnostic reproducibility have somewhat clarified the problem, leading to a simplification of the classification in two tiers (high and low grade). High grade dysplasia can be considered as a high cancer risk necessitating a follow-up at short intervals and possibly requiring surgery. Low grade dysplasia, which can regress or progress very slowly represents a low cancer risk. After a first control at one or two months, it is suggested that endoscopic follow-up can be proposed at larger intervals (one or two years). The authors study the aspects of the dysplasia at the different levels of the gastrointestinal tract and summarise the clinical implication of this diagnosis.


[Nerve growth factor receptor (NGFR)-like immunoreactivity in the perineurial cells of the adult rat peripheral nerves: normal appearance and response to nerve section]. The expression of the nerve growth factor receptor (NGFR)-like immunoreactivity in the perineurial cells of normal rat sensory and sympathetic nerves and after surgical severance was analyzed using a specific anti-rat NGFR monoclonal antibody (192-IgG). The perineurial cells as well as axonal endings showed NGFR-like immunoreactivity in the terminal region of normal nerves and the immunoreactivity in the terminal perineurial cells was enhanced after nerve severance. In the nerve trunk region, no cellular elements exhibited NGFR-like immunoreactivity in normal rats, but immunoreactivity was induced in the innermost perineurial cells and all Schwann cells in portions distal to the severance. These findings suggest that the perineurial cells function to provide NGF for intact and regenerating axons by binding NGF to NGFR on the perineurial cell surface.


Bilateral anatomical anomaly of anterior bellies of digastric muscles. During the gross anatomy dissection of the submandibular region, both anterior bellies of the digastric muscles, especially the left one, were found to be enlarged. They were arranged as two parallel asymmetric bands extending from the hyoid bone to the chin. The posterior bellies of the digastric muscles were normal. The suprahyoid muscles showed no abnormalities. This anomaly represents an anatomical variation in the mylohyoid digastric muscle group in the floor of the mouth.


A Taiwanese with a pair of sternalis muscles. A pair of sternalis muscles have been found on both sides of the chest in an adult Taiwanese male. The muscles are located superficial to the medial part of the pectoralis major, arising from the sternum and are inserted into the sheaths of the rectus abdominis. They are innervated by the intercostal nerve. It should be emphasized that the sternalis muscle is rarely found in Taiwan.


Clarke's column in sporadic amyotrophic lateral sclerosis. Histological, ultrastructural and morphometrical observations on Clarke's column were carried out in 18 patients with sporadic amyotrophic lateral sclerosis (ALS) and 15 age-matched control subjects. Of the 18 ALS patients 6 had been on a respirator before death. Bunina bodies were found in the neuronal cytoplasm in 7 of the 12 non-respirator-supported ALS patients and in 3 of the 6 respirator-supported patients. The number of spheroids was significantly higher in the non-respirator-supported patients (P < 0.01) than in the control subjects; however, the number in the respirator-supported patients was about equal to that in the controls. The number of neurons in Clarke's column in the non-respirator-supported ALS patients was not reduced, but in the respirator-supported patients they tended to disappear with time after respiratory support. These findings suggest that Clarke's column neurons are also involved primarily in the disease process in sporadic ALS. However, they may begin to disappear only after the patients require respiratory support.


Vascular changes in the spinal cord in N-methyl-D-aspartate-induced excitotoxicity: morphological and permeability studies. Our previous studies have demonstrated toxicity in spinal cord neuronal systems of middle-aged rats with continuous intrathecal infusion of N-methyl-D-aspartate (NMDA). The present study was undertaken to determine when during the course of excitotoxicity vascular changes occur. The model used was intrathecal infusion of NMDA in the region of the lumbar enlargement of the spinal cord. Horseradish peroxidase (HRP) was used as a marker of vascular permeability alterations occurring in this model. Pathological changes were observed in the cord gray matter of all rats infused with 30-60 micrograms/min NMDA for 30 or 60 min. The changes consisted of swelling of dendrites which gave the neuropil a vacuolated appearance. There was expansion of the extracellular spaces in these areas and neurons were shrunken with pyknotic nuclei. These changes were more frequently encountered in the posterior than anterior horns and were specific for NMDA since they did not occur in NMDA-infused rats pretreated with MK-801, a specific NMDA antagonist. Endothelial dysfunction manifested as increased permeability to HRP. This was a consistent finding in all rats infused with the higher dose of NMDA and was less frequent in those infused with 30 micrograms/min and no vascular changes were observed in rats infused with NMDA for 30 min despite the presence of tissue changes. Increased permeability affected all types of vessels but principally, capillaries and venules. There was no evidence of endothelial necrosis or vascular occlusion. This study demonstrates that in excitotoxin-mediated tissue damage, breakdown of the blood-brain barrier follows the development of nervous tissue damage. Thus, edema is not a significant feature of early lesions in excitotoxin-induced brain injury.


Allocortical neurofibrillary changes in progressive supranuclear palsy. Silver techniques for intraneuronal cytoskeleton abnormalities (neurofibrillary tangles and neuropil threads) and extracellular A4-amyloid deposits were used to examine lesions of the cerebral cortex in six cases of progressive supranuclear palsy (three were mentally unimpaired and three showed moderate degrees of dementia). Deposits of A4-amyloid protein occurred in small numbers or were absent. Neurofibrillary tangles and neuropil threads were present in all cases and were largely confined to the allocortex. A characteristic pattern of changes was found in the entorhinal cortex. The three mentally unimpaired individuals had mild cortical changes virtually confined to the transentorhinal region while all of the demented patients showed severe destruction of the superficial cellular layer in both the transentorhinal and entorhinal region. This pattern of allocortical destruction closely resembles that seen in clinically incipient Alzheimer's disease or in mentally impaired cases of Parkinson's disease. The entorhinal region receives dense input from isocortical association areas and projects via the perforant path to the hippocampal formation. The cells of origin of major portions of the perforant path are located within the superficial entorhinal cellular layer. Destruction of this layer partially or totally disconnects the hippocampus from the isocortex. The specific pattern of entorhinal destruction is considered to contribute to cognitive impairment and personality changes, frequently seen in patients with progressive supranuclear palsy.


Immunotactoid-like endoneurial deposits in a patient with monoclonal gammopathy of undetermined significance and neuropathy. An 85-year-old man with a 2-year history of progressive lower limb weakness and paresthesia was found to have an IgG kappa monoclonal gammopathy of undetermined significance (mgus). Clinical and electrophysiological studies revealed a severe distal bilateral symmetrical polyneuropathy. A sural nerve biopsy showed extensive nerve fibre loss with the deposition of large amounts of amorphous material throughout the endoneurium. Electron microscopy showed the deposits to be composed of microtubular structures which were located diffusely throughout the endoneurium. The deposits were also located within the lumina of the vasa nervorum, some of which were undergoing disintegration and rupture with release of the proteinaceous material into the endoneurium. The regions of the nerve in which they appeared most numerous showed more severe nerve fibre damage than other areas. These microtubular structures were also observed in disintegrating vessels and adjacent endoneurium. On immunohistochemistry they stained with antibody to IgG. Identical deposits were found in the dermis in which there was a leucocytoclastic vasculitis. Located in linear arrays within the axons of myelinated and unmyelinated fibres were highly organised tubular structures resembling immunotactoids. Identification of immunotactoid-like structures within the nerve is unique and may be another mechanism by which monoclonal proteins can induce nerve fibre injury.


Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat. The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5 degrees C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular permeability was greatly reduced in hypothermic rats cooled to 30 degrees C (brain temperature) prior to injury. In hypothermic rats, albumin immunoreactivity was confined to the gray-white interface between cortex and hippocampi with no involvement of the overlying cortices and greatly reduced involvement of the underlying hippocampi. The acute hypertensive response in normothermic rats peaked at 10 s after TBI (187.3 mm Hg) and returned to baseline within 50 s. In contrast, the peak acute hypertensive response was significantly (P < 0.05) reduced in hypothermic rats (154.8 mm Hg, 10 s after TBI) and returned to baseline at 30 s after injury. These results demonstrate that moderate hypothermia greatly reduces endogenous vascular protein-tracer passage into and perhaps through the brain. This reduction may, in part, be related to hypothermia-induced modulation of the systemic blood pressure response to TBI.


The distribution of Challenge virus standard rabies virus versus skunk street rabies virus in the brains of experimentally infected rabid skunks. The proposal that the bizarre behavioral changes which occur during rabies infection are due to selective infection of limbic system neurons was further studied in skunks (a species important in naturally occurring disease). A detailed immunohistochemical study of brains of skunks experimentally infected with either Challenge virus standard (CVS) or street rabies virus revealed only trace amounts of viral antigen in many limbic system neurons and marked differences in viral distribution between street and CVS virus. These data were collected during early stage rabies when behavioral changes occur. Areas which contained heavy accumulations of street rabies virus but low amounts of CVS rabies virus were the neuronal perikarya and processes of the dorsal motor nucleus of the vagus, midbrain raphe, hypoglossal and red nuclei. In contrast, large accumulations of CVS virus were found in the Purkinje cells of the cerebellum, the habenular nuclei and in pyramidal cells throughout the cerebral cortex, while corresponding areas in all street virus-infected skunks contained minimal antigen. These findings were very consistent for animals of the same experimental group and between skunks inoculated both intramuscularly and intranasally with skunk street virus. Skunks inoculated intramuscularly with CVS rabies virus failed to develop rabies. Since, in this model, street virus infection generally produces furious rabies and CVS infection results in dumb rabies, we speculate that the behavioral changes which occur in these two different clinical syndromes are due to the heavy and specific accumulation of virus in different regions of the CNS. These results show that regions other than those of the limbic system may also be involved in the pathogenesis of behavior changes in rabid animals.


Ki-M1P as a marker for microglia and brain macrophages in routinely processed human tissues. The monoclonal antibody Ki-M1P recognizes a formalin/paraffin-resistant differentiation epitope of monocytes and their macrophage derivatives [Radzun et al., Lab Invest 65:306, 1991]. To evaluate its usefulness for neuropathology, we examined a variety of routinely processed tissues using immunohistochemistry. In normal brains, positivity was restricted to ramified microglial cells. Intense labeling of macrophages, ramified and ameboid microglial cells, and rod cells was seen in brains with various degenerative and inflammatory disorders. Astrocytes were negative as determined by double-immunofluorescence labeling using Ki-M1P and anti-glial fibrillary acidic protein (GFAP). Histiocytic lesions (histiocytosis X, xanthogranulomas, granulomatous inflammation) were immunopositive. Among 107 tumors, reactivity of Ki-M1P was observed with some schwannoma and meningioma tumor cells. In addition to macrophages, most gliomas contained small, elongated Ki-M1P-positive cells, which were negative for GFAP. Positivity was also found in two glioblastoma cell lines. Immunoblotting performed on spleen, meningioma and glioblastoma specimens revealed one to three bands in the range of 110 to 130 kDa. We conclude that Ki-M1P can serve as a reliable marker for brain macrophages and microglial cells in routinely processed normal and non-neoplastic tissues, whereas due to the unexpected immunoreactivities results obtained with neoplastic tissues should be carefully interpreted.


Induction of FOS and JUN proteins after focal ischemia in the rat: differential effect of the N-methyl-D-aspartate receptor antagonist MK-801. FOS and JUN proteins are transcription factors thought to be involved in coupling neuronal excitation to target gene expression. Cortical infarction of consistent size and location was produced by irradiating the rat brain with Xenon light through the intact skull for 20 min following systemic injection of the photo-sensitizing dye, rose bengal. To investigate the time course and distribution pattern of five cellular immediate early gene (IEG)-encoded proteins after focal ischemia, the expression of c-FOS, FOS B, c-JUN, JUN B and JUN D was studied immunocytochemically in sham-operated control animals and at different postischemic time intervals up to 24 h. A separate group of animals was pretreated with the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801. Photochemically induced focal ischemia caused a rapid induction of FOS and JUN proteins in the entire ipsilateral cortex apart from the ischemic focus. Immunoreactivity in the ipsilateral subcortical gray and white matter and in the entire contralateral hemisphere was indistinguishable from control animals. Individual IEG-encoded proteins were sequentially induced with increased levels of immunoreactivity persisting for different time periods up to 24 h. c-FOS, FOS B, c-JUN and JUN B exhibited a characteristic distribution pattern as reflected by different staining intensities in individual cortical layers. The rapid IEG induction in the entire ipsilateral sensorimotor and limbic structure-associated cortices after photochemically induced infarction most likely reflects spreading depression caused by ischemia and mediated by NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae. The ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (Tragelaphus angasi; subfamily Bovinae), or kudu (Tragelaphus strepsiceros; subfamily Bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (Bos taurus; subfamily Bovinae) with bovine spongiform encephalopathy (BSE). As fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these species. The effect of formalin fixation was compared with that of fresh brain in mice inoculated with fixed and unfixed brain tissue from cows with BSE. The nature and distribution of the pathological changes were similar irrespective of the source of inoculum or whether the inoculum was from fresh or previously fixed tissue. Vacuolation caused by loss of organelles and swelling was present in dendrites and axon terminals. Vacuoles were also seen as double-membrane-bound and single-membrane-bound structures within myelinated fibres, axon terminals and dendrites. Vacuoles are considered to have more than one morphogenesis but the structure of vacuoles in this study was nevertheless similar to previous descriptions of spongiform change in naturally occurring and experimental scrapie, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome and kuru. Other features of the ultrastructural pathology of the transmissible spongiform encephalopathies including dystrophic neurites and scrapie-associated particles or tubulovesicular bodies were also found in this study. Neuronal autophagy was a conspicuous finding. It is suggested that excess prion protein (PrP) accumulation, or accumulation of the scrapie-associated protease-resistant isoform of PrP, may lead to localised sequestration and phagocytosis of neuronal cytoplasm and ultimately to neuronal loss.


Immunohistochemistry and proliferative activity in Lhermitte-Duclos disease. We have evaluated a recurrence of Lhermitte-Duclos disease by immunohistochemistry for Purkinje cell markers and proliferative activity (proliferating cell nuclear antigen), by electron microscopy and for DNA ploidy (image analysis). While most of the abnormal neurons in the lesion appear to be derived from granule cells, several Purkinje cell specific polyclonal and monoclonal antibodies, including L7, PEP 19 and calbindin, labeled a minor subpopulation. Staining with monoclonal antibodies to proliferating cell nuclear antigen and measuring cell DNA index and ploidy with a cell image analyzer revealed no proliferative activity. Electron microscopy findings were similar to those previously reported. In spite of its recurrence, our findings support the notion that Lhermitte-Duclos disease is malformative, not neoplastic, and that the characteristic neurons are derived predominantly but not exclusively from a non-Purkinje cell source, probably the granule cell.


Myelination of two axons by a single Schwann cell. A Schwann cell can form only one internode of myelin around an axon. However, we observed the formation by a single Schwann cell of myelin around two axons of different diameters in the sural nerve of a 45-year-old man with mononeuritis multiplex. Schwann cell processes spiraled in the same direction around each axon, forming mesaxons. The findings in this case appear to be an undescribed type of aberrant myelination.


Anaplastic large cell Ki-1 lymphoma in the central nervous system: report of an autopsy case. A 45-year old immunocompetent man presented with multiple lesions in the brain. A histological examination of the tumors showed a diffuse infiltrate of lymphoid cells with cellular polymorphism and of multinucleated giant cells. These cells were immunolabeled with antibodies against B cell lineage and with a monoclonal antibody, Ber-H2 (CD30), which showed the presence of Ki-1 antigen. Recently, among systemic non-Hodgkin's lymphomas, attention has been given to Ki-1-positive lymphomas, which have been incorporated in the up-dated Kiel classification. We report here a case of Ki-1-positive lymphoma arising in the CNS and review previously reported cases.


Measurement, analysis, and modelling of the caloric response. 2. Evaluation of mental alerting tasks for measurement of caloric-induced nystagmus. Management of the patient's level of arousal is one of the most important variables in obtaining consistent and strong caloric responses. The patient may suppress the caloric response and/or exacerbate beat-to-beat variability if some type of mental alerting (MA) task is not used to focus the patient's attention from his or her dizziness. An experiment was undertaken to evaluate simple MA tasks in terms of associated caloric response strength and variability. Warm caloric responses were measured while each of 10 normal subjects performed eight different MA tasks. The mental exercises included two math tasks, two quizzing tasks, two hand-motor tasks, and two alphabet tasks. One of the tasks in each complementary pair required the subject to interact with the examiner throughout the caloric response. Minimal or no interaction was required for the companion task. The relative ordering among the eight MA tasks was compared in terms of total sum of ranks, summed across 15 performance measures taken from caloric response indices. The highest-ranked altering task was an exercise requiring subjects to name or list local cities, states in the U.S.A., colors, etc. The lowest-ranked tasks were backward counting exercises and reflexive quizzing, which are the traditional tasks used in the clinic.


Measurement, analysis, and modelling of the caloric response. 1. A descriptive mathematical model of the caloric response over time. A mathematical model for describing the caloric response over time offers many important advantages over the commercially-available qualitatively-fitted curves that are now used by the clinician for evaluating caloric results. In this report advances in the development of a nonlinear least-squares mathematical model are discussed and the roles and derivations of fitting parameters and curve-derived indices are outlined. This model provides a rigorous and objective description of the caloric response in its entirety with four continuous parameters. These fitting parameters make it possible to 1) describe individual caloric responses precisely and uniquely, 2) compare pairs of individual caloric responses or groups of caloric responses statistically, 3) extract information not previously available, 4) quantify variability within the caloric response, and 5) model physical properties of the caloric stimulus and physiological variables affecting the caloric response. Results from this model are compared with the results from our earlier models and with traditional multiparameter caloric results.


Middle ear gases.

Middle ear gases. The ex vacuo theory, claiming that air enters the middle ear through the Eustachian tube and oxygen leaves it into the blood by diffusion, does not provide a complete explanation and description of the mechanism of middle ear aeration. This study shows that both the gas diffusion between the middle ear and the blood and the flow of gas through the Eustachian tube are bidirectional processes for all the gases concerned N2, CO2, O2 as well as H2O.


Diagnostic value of tympanometry in otitis media with effusion. Three particular applications of tympanometry are stressed. In the first place, tympanometric screening fails to give any appreciation of the tubal dysfunction evolution. During general anaesthesia, nitrogen oxide diffusion in the middle ear can hide effusion. Secondly, the correlation between tympanometric curves and middle ear effusion is far lower than usually assumed.


[Otologic manifestations of Wegener's disease]. Two cases of otologic involvement in Wegener's granulomatosis are reported. Symptoms are referable to those of an acute otitis media with impaired hearing. The ANCA test is helpful in the diagnosis. Immunosuppressive therapy in association with corticosteroids is the treatment of choice.


[Etiology of deafness in children].

[Etiology of deafness in children]. A retrospective etiological study of 112 files of deaf children is presented. A prenatal etiology is found in 42.8%, a perinatal in 19.6% and a postnatal in 13.4% of the cases. No cause was suspected in 30.3% of the cases. These results emphasise existing literature.


[Proposal for an original method of high-frequency audiometry using mathematical equations]. Many studies have established high-frequency audiometry norms. Unfortunately the majority presents different averages for each decade, sex and frequency together with standard deviations. In order to solve these problems we established our norms on a widespread audiometer for each sex based on a strictly normal hearing sample. We calculated the linear regression between age and hearing loss for each frequency. We propose a set of equations to predict the "normal" threshold of a subject in function of age and sex.


[Evoked oto-acoustic emissions: results in at-risk newborn infants]. Fourty newborns (80 ears) from the intensive care unit were tested with evoked oto-acoustic emission (EOAE). The occurrence of EOAE was 93%.


A hairy polyp of the middle ear and mastoid cavity. A case of a 'hairy polyp', a dermoid tumor of the middle ear and the mastoid cavity is described, which is very unusual location. The radiological, surgical and histological features are discussed. Comment is made on the differentiation between dermoid cysts and teratomas and on the scarcity of both tumors in the area of the temporal bone.


[Endonasal dacryocystorhinostomy (95 cases)]. A series of 95 intranasal dacryocystorhinostomies for ophthalmologic problems were performed. The operative technique as well as the results are discussed. Success rate is about 95.8%, of which 82.1% with immediate results. Even if the results of both intranasal and external approaches are equivalent, the intranasal one presents a little advantage. No intraoperative complications are observed.


[Problems with flute playing: an otological problem? Case report of a peculiar cerebellar astrocytoma]. A rare case of cerebellar astrocytoma presenting as a cerebellopontine angle tumour is discussed. A 35-year old woman noticed a bizarre twitching and fatigability of the left upper lip while playing the flute. There was also a mild hearing loss on the left side and she sometimes felt unsure of herself when walking. A thorough examination by means of speech audiometry, electronystagmography, ABR, CT-scan and MRI revealed a large, partly calcified mass occupying the cerebellopontine angle. Only the histological examination of the surgical specimen revealed the true nature of the tumour. The special characteristics of this tumour and the unusual clinical course are discussed. The importance of a good histological diagnosis is stressed.


[Place of the otorhinolaryngologist in the multidisciplinary approach to neurofibromatosis]. Neurofibromatosis is one of the most common inherited human disorders. Two types have been recognized, NF 1 and NF 2. Clinical and genetic aspects of the disease clear the way to the aims and indications of the multidisciplinary approach of the neurofibromatosis patients and their families. To study the uniformity of patient management (protocol), a number of Belgian and Dutch medical centres were contacted. Great importance is attached to the common as well as the varying points of these protocols. We emphasize the part played by the ENT specialist in the multidisciplinary approach of neurofibromatosis type 1 and 2.


Hemangiopericytoma of the head and neck: a report of four cases and a literature review. Hemangiopericytoma is an infrequent vascular tumor that rarely appears in the head and neck. The nasal cavity and the paranasal sinuses are most often involved. Four cases are added to the literature and some important features are stressed. The clinical presentation is aspecific. Diagnosis is made only by careful histological examination with special stainings (reticulin, immunohistochemistry with Ulex Europaeus) and gives an idea about the grading. Treatment with radical surgery, if possible, is effective while preoperative embolisation can reduce the risk of hemorrhage. The median follow-up of the present cases is only 3 years. During this period no recurrence was observed. We suggest that more radical resections can probably reduce the local recurrence rate. However lifetime clinical follow-up is warranted since late recurrences have been reported in almost half of the patients.


On the role of global and local visual information in goal-directed walking. The aim of the present study was to determine what interactions occur between the visual information available to walking subjects in the global optical flow and those of a more local nature relating to the dilation rate of a target on the retina. A goal-directed walking task was used in which thirteen subjects were asked to stop spontaneously as near as possible to a stationary target. The experiment was carried out in a special room, by means of a texture flow generator with which the velocity and direction of the optical flow arising from the ground were varied. Twelve experimental conditions were tested, involving various combinations of target size and texture velocity. The results show that with both of the targets, modifications to the global flow significantly affected the subjects' performances (walking speed and time-to-contact with the target upon braking) in the fast-approaching texture situation, but not in the receding or slowly-approaching situations. The results are discussed as to what they reveal about the visual strategies used by an actively moving observer to anticipate a collision with a stationary target.


Dynamic decision making: human control of complex systems. This paper reviews research on dynamic decision making, i.e., decision making under conditions which require a series of decisions, where the decisions are not independent, where the state of the world changes, both autonomously and as a consequence of the decision maker's actions, and where the decisions have to be made in real time. It is difficult to find useful normative theories for these kinds of decisions, and research thus has to focus on descriptive issues. A general approach, based on control theory, is proposed as a means to organize research in the area. An experimental paradigm for the study of dynamic decision making, that of computer simulated microworlds, is discussed, and two approaches using this paradigm are described: the individual differences approach, typical of German work in the tradition of research on complex problem solving, and the experimental approach. In studies following the former approach, the behaviour of groups differing in performance is compared, either with respect to strategies or with respect to performance on psychological tests. The results show that there are wide interindividual differences in performance, but no stable correlations between performance in microworlds and scores on traditional psychological tests have been found. Experimental research studying the effects of system characteristics, such as complexity and feedback delays, on dynamic decision making has shown that decision performance in dynamic tasks is strongly affected by feedback delays and whether or not the decisions have side effects. Although neither approach has led to any well-developed theory of dynamic decision making so far, the results nevertheless indicate that we are now able to produce highly reliable experimental results in the laboratory, results that agree with those found in field studies of dynamic decision making. This shows that an important first step towards a better understanding of these phenomena has been taken.


Benefits from attention depend on the target type in location-precued discrimination. In previous research, we found that precuing of attention to a target location greatly improved discrimination of targets that differed in line arrangement, but had little effect on discrimination of targets that differed in line orientation. In the present research, a number of other targets that represent various feature differences were used. The new data are consistent with and extend our earlier findings by showing that (1) there is some effect of precuing with all targets tested, and (2) the size of precuing effects varies in a complex way with the nature of the target. Moreover, the difficulty of the discrimination cannot explain the size of the precuing effects. A framework for understanding the events occurring during trials in the location-cuing paradigm is presented and applied to these results.


The role of vision in the temporal and spatial control of handwriting. The general observation that handwriting is not noticeably impaired by the withdrawal of vision can be explained in two ways. One might argue that vision is not needed during the act of writing. Micro-analyses should then reveal that spatial as well as temporal writing features are identical in conditions of vision and no vision. Alternatively, it is possible that vision is needed during the act of writing, but that without vision possible errors and inaccuracies have to be prevented. Assuming that the latter would place an extra demand on movement control, this should be revealed by an increase in processing time. We have found evidence for the latter view in the present study in which 12 subjects wrote a nonsense letter sequence with and without vision. Close examination showed that writing shapes remained equally invariant under both vision conditions, suggesting that spatial control was unaffected by withdrawing vision. The prediction that invariance of shapes is preserved in the absence of vision at the expense of processing time increments was confirmed. The increase of reaction time observed when visual guidance was withdrawn suggests that more processing time was needed prior to the movement start. Moreover, the RT increment was larger when a short writing duration was instructed. The present findings will be discussed in light of the remarkable flexibility of writing as a motor skill in which writers appear to be able to employ specific strategies to preserve shape in the absence of visual guidance.


Does evidence of inflammation on Papanicolaou smears of pregnant women predict preterm labor and delivery? Preterm delivery is the most common cause of neonatal morbidity and mortality in the United States. There is evidence that cervicovaginal infection could predispose to preterm labor. This study explored a possible association of evidence of inflammation on an otherwise normal Papanicolaou smear obtained during pregnancy with subsequent preterm labor and preterm delivery. Using a retrospective matched cohort design, we studied women who gave birth to live singleton infants at the University of Missouri Hospital and Clinics during a 21-month period. Papanicolaou smears were obtained from 1 to 8 months before delivery and were interpreted in the same cytopathology laboratory. Data pertaining to outcome variables and potential confounding variables were collected from hospital charts. Incidence rates were 14.4 percent for labor < 37 weeks' gestation (preterm labor), 12.3 percent for hospitalization for preterm labor, 9.9 percent for delivery < 37 weeks (preterm delivery), 2.6 percent for delivery < 34 weeks, and 7.5 percent for birth weight < 2500 g. On univariate and multivariate analyses, there were no significant differences in any outcome between the 293 women with inflammation and the 284 women without inflammation on Papanicolaou smear. Results were unchanged when the analysis was limited to the 412 women who received no antibiotics during pregnancy. Among the 38 women with a history of preterm labor or preterm delivery, those with cervical inflammation had a higher rate of preterm labor than those without inflammation. In the sample as a whole, there was little evidence that findings of inflammation on Papanicolaou smear constituted a risk factor for preterm labor or preterm delivery. The data suggest that inflammation could be associated with an increased risk in a subgroup of women at higher risk by virtue of their obstetric history.


Community attitudes and knowledge about advance care directives. Patients and their physicians are increasingly being encouraged to discuss end-of-life decisions. The purpose of this study was to enhance understanding of the public's attitudes and knowledge about medical decision making and advance care directives. Eight focus groups of community members discussed their understanding of and attitudes about advance care directives. Transcripts of these discussions were analyzed using coding categories created from the transcripts. Eighty-three people attended the focus groups. Most discussions of advance care directives involved family members in the setting of family or personal illness. Elderly persons commonly confused wills with living wills. Most who had given advance directives did so either to make others follow their wishes or to ease family burdens. Among the great variety of reasons for not using advance directives was a perceived lack of personal relevance, as well as conceptual, moral, and practical difficulties. Participants were divided about whether it was appropriate for physicians to initiate discussions about life-sustaining care with their patients. We discerned three themes affecting individuals' opinions about personal decision making about advance directives: (1) trust in family and the medical system, (2) need for control, and (3) knowledge about advance directives. Although living wills are advocated by many authorities, and many of our participants endorsed their use, our participants also cited numerous cautions and impediments to their use. As the role of advance care directives changes, physicians will need to be aware of their patients' perceptions, as well as the legalities of these documents.


Survey and evaluation of newsletters marketed to family physicians. Newsletters are marketed to physicians to provide a concise, accurate, and timely overview of the medical literature. The goal of these newsletters seems to be to present information that can be a suitable substitute for reading the original article. The purpose of this paper is to describe and evaluate newsletters pertinent to family physicians. Newsletters appropriate for family physicians were selected by collecting newsletter advertisements and by searching newsletter directories. A 3-month sample and pertinent data were collected from the publishers. Evaluation criteria included accuracy and completeness of the abstracts, scope of coverage of the medical literature, and relevance of article sources. Eight newsletters were collected and evaluated. Accuracy was high for the evaluated abstracts. Abstract completeness averaged only 70 percent (range 55 percent to 92 percent). The type and source of abstracted articles varied widely among the newsletters. Newsletters available to family physicians vary widely; personal evaluation should supplement the results of the evaluation.


Teaching physicians to be patient: a hospital admission experience for family practice residents. A program has been developed to sensitize physicians to the discomforts, uncertainties, and anxieties experienced by patients on admission to the hospital, so that greater empathy and increased communication can be fostered with their own hospitalized patients. For the last 5 years, all incoming family medicine residents at Long Beach, California, Memorial Medical Center have been admitted incognito to the hospital during their first day in the residency. Hospitalized residents are assigned an admission diagnosis and an associated disability, given a pseudonym, and provided with fabricated insurance information (by the hospital administration) to facilitate their admission. Each incoming group of 6 residents is admitted over the course of an afternoon and evening and discharged the next morning. Residents evaluated the admission experience by means of before-and-after questionnaires. They and residency graduates also responded to a follow-up survey instrument that asked participants to assess the program's long-term educational impact (response rate, 100 percent; n = 30). Although the program is carried out annually, we have been able to admit the residents to this large (998 beds) medical center typically without their identities being discovered, resulting in a realistic educational experience. While diagnoses are contrived, the discomforts are real, and participants become acutely aware of the loneliness, pain (e.g., from intravenous lines), and uncertainty experienced by patients. Long-term effects on day-to-day practice attributed to the program by residents and graduates include minimizing orders for nonessential tests and middle-of-the-night examinations and keeping patients well-informed (especially letting them know when they will be seen by the physician). The effort, logistical problems, and costs associated with hospitalization of incoming residents disguised as patients appear to be offset by the admission program's long-term impact on participants' sensitivity regarding experiences undergone by hospitalized patients and their awareness of their role in helping to ameliorate discomforts associated with hospital admission. Strong support from the hospital administration, however, is essential to the success of this type of program.


Chronic headaches in family practice.

Chronic headaches in family practice. More than 11 million people in the United States have moderate or severe migraine resulting in much suffering and millions of lost work days annually. Staying abreast of current advances in headache management is important for family physicians, who care for most headache patients. MEDLINE files were searched from 1982 to the present using the key words "headache," "migraine," "serotonin," and "cerebral circulation." Also searched were the journals Headache and Cephalalgia and the published proceedings of meetings of the American Association for the Study of Headache, the International Headache Society, and the Migraine Trust. A new headache classification based on clinical symptoms has been published by the International Headache Society, which clarifies headache diagnoses. Though headaches with serious underlying disease occur only rarely in family practice, physicians must be familiar with the clinical signs indicating the presence of such problems, and any change in or unusual presentation of headache warrants investigation. Headache research has expanded in the past decade, much of which has been directed at raising the standards of treatment. Pharmacologic treatment falls into two categories: acute or abortive treatment and preventive treatment. Analgesic overmedication by headache patients is commonplace and leads to withdrawal symptoms and the development of chronic daily headaches, for which effective treatments are now available at both ambulatory and inpatient levels. At the more basic research level, serotonin receptor studies have provided an impetus for revealing underlying headache mechanisms. A new serotonin agonist, sumatriptan, has proved effective in treating acute migraine and will no doubt be followed by further serotonergic drugs. Patient education, relaxation therapy, and other nonpharmacological approaches, as well as good overall standards of care, are essential ingredients in headache management. Family physicians are well-equipped to offer these approaches to their patients with headache.


Premature labor, Part II: Management.

Premature labor, Part II: Management. As the second paper in a two-part series on preterm labor, this article discusses the management of preterm labor as it relates to risk reduction, tocolytic therapy, corticosteroids, and antibiotics. Published literature on the management of preterm labor was reviewed by searching MEDLINE files from 1983 to the present, using the terms "preterm labor," "premature labor," "preterm labor and antibiotics," "tocolytic agents," "tocolysis," "betamethasone," and "premature rupture of membranes." Additional references were obtained by cross-referencing bibliographies from available articles. Effective management of preterm labor and birth begins with an assessment and reduction of risks for all pregnant women. In addition, pregnant women should be screened and appropriately treated for urologic and gynecologic infections (e.g., syphilis, gonorrhea, Chlamydia, and bacterial vaginosis). Women who are at high risk for preterm birth should be enrolled in a preterm birth prevention program that includes frequent contact with health professionals, patient education about the signs and symptoms of preterm labor, home monitoring, and regular cervical examinations. For women who develop preterm labor that does not require immediate delivery, recommended management strategies include reduced activity, early tocolytic therapy, corticosteroids for up to 34 weeks' gestation (both for women with intact and ruptured membranes), and antibiotics for known infections. Early studies also suggest that prophylactic antibiotics can be beneficial for women with idiopathic preterm labor or preterm premature rupture of membranes.


Differences in the obstetric malpractice claims filed by Medicaid and non-Medicaid patients. Many physicians believe Medicaid patients are more likely than non-Medicaid patients to file malpractice claims. This study examines the accuracy of this belief in regard to obstetric malpractice claims. Claims filed between January 1982 and June 1988 from the major malpractice insurer in Washington State were used to compare obstetric malpractice claims filed on behalf of Medicaid and non-Medicaid patients. Eleven percent (7/62) of all closed obstetric claims were filed by Medicaid patients, whereas 19 percent of all births in Washington State were to Medicaid patients between 1982 and 1988. Failure to diagnose or treat a fetal condition was the most commonly alleged negligence in both Medicaid and non-Medicaid groups. Most claims in both groups were settled before the cases went to court; a substantial minority of claims were dropped. The mean cost of Medicaid claims ($406,984) was three times that of non-Medicaid claims ($133,743), suggesting that paid Medicaid claims were more severe than paid non-Medicaid claims. Medicaid patients appear no more likely to file obstetric malpractice claims than non-Medicaid patients. The low likelihood of filing claims, coupled with large settlements, suggests that Medicaid patients may have less access to legal services than non-Medicaid patients.