Influence of alkaline pH on the direct lethal action of miconazole against Candida albicans.

The imidazole group of miconazole is subject to protonation (pKa approximately 6.5). Earlier we suggested that the direct lethal action (DLA) of miconazole against Candida albicans requires nonprotonated drug molecules. DLA declined in intensity as pH was decreased from 6.0. At pH > 6.5 most molecules of miconazole exist in the nonprotonated state, but drug also becomes less soluble. Viability studies were designed to assess DLA in relation to alkaline pH. DLA was clearly inhibited with increasing as well as decreasing pH (i.e., pH < 6.0 and > 7.0), suggesting that nonprotonated neutral drug molecules must be in solution or in extremely small aggregates to elicit DLA, and that the nonprotonated species itself is more soluble at pH 6.0-7.0 than under more alkaline conditions.


Role of cell-mediated immunity in the resistance to experimental sporotrichosis in mice.

Congenitally athymic nude (nu/nu) mice showed higher sensitivity to intratestical infection of Sporothrix schenckii than phenotypically normal littermates (nu/+). Active immunization with viable cells enhanced the resistance to intravenous (i.v.) infection of this fungus in BALB/c mice. Nu/nu mice transferred with immune spleen cells acquired the enhancement of resistance to the infection with S. schenckii, but not ones with normal spleen cells. Pre-treatment of OK-432 (Picibanil), one of the macrophage activating agents, enhanced resistance to i.v. infection of this fungus in BALB/c mice. On the other hand, pretreatment of carrageenan, one of the macrophage inhibitors, impaired the resistance. This fungus was intracellularly killed by peritoneal macrophage from OK-432 treated or immunized mice but not by those from normal mice in vitro. These results suggest that activated macrophage, that was mediated by T cells, play an important role in the resistance to S. schenckii in mice.


Immunodeficiency secondary to juvenile paracoccidioidomycosis: associated infections.

Four patients with acute paracoccidioidomycosis, hypoalbuminemia, ascites and associated infections are reported. They have been admitted to hospital 35 times, 4 of them due to active paracoccidioidomycosis, 14 to associated infections, 14 to ascites, edema and diarrhoea and 3 to herniorrhaphy. Two of them recovered after sepsis and central nervous system, muscular and subcutaneous cryptococcosis. The remaining two died. One had infectious diarrhoea (S. flexneri), peritoneal tuberculosis and sepsis (S. epidermidis); the other had bacterial meningitis, erysipelas, beta-hemolytic Streptococcus sepsis and miliary tuberculosis. Their immunodeficiency was attributed to enteric protein loss and/or malabsorption and malnutrition and was recognized by reduced response to delayed hypersensitivity skin tests in four patients and hypogammaglobulinemia in three of them. The authors discuss the need for prospective studies to be carried out, aiming at the mechanisms involved in secondary infections. Alternatives for maintaining the patients' adequate nutritional state should be investigated, to guarantee proper immune response and thus the ability to control intervening infections in patients with juvenile paracoccidioidomycosis.


Lobomycosis in Colombian Amer Indian patients.

Several foci of lobomycosis among Colombian Amer Indians population were described in the Casanare region of Colombia, near the Orinoco river on the Colombian-Venezuelan border. This paper reports 16 new patients. The prevalence of Lobo's disease was 8.5% in the Amoruas tribe. Nodular lesions were located on the elbow, scapular and lumbar regions, knees, feet and legs. Leg lesions were especially numerous, were confluent and tended to ulcerate. All cases were confirmed histologically. Two Negro patients were also described. The cases bring the total number of confirmed patients with lobomycosis in Colombia to 41. Twenty-five of these were Amer Indian patients from tribes living in the Orinoco and Amazon basins of the country.


An early effect of aflatoxin B1 administered in vivo on the growth of bone marrow CFU-GM and the production of some cytokines in rats.

Our data demonstrate the granulopoietic toxicity of aflatoxin B1 (AFB1) in vivo and show an impact of this mycotoxin on the production of some humoral regulatory factors dealing with the granulopoietic developmental pathway (CSA, IL-1, IL-2). The dose of AFB1 studied represented approximately 1/5 of LD50 for young male rats. An early suppressive effect of AFB1 towards CFU-GM was transient in treated animals. The peak in granulopoietic activity was preceded in time by an increased CSA and IL-1 formation. Elevated IL-2 synthesis and increased T cell activation paralleled the peak in granulopoietic activity.


Laboratory aids in the diagnosis of invasive candidiasis.

The laboratory diagnosis of candidiasis continues to be problematic; however, there have been several advances in the past decade which promise to enhance our ability to identify patients at high risk for infection and/or to document invasive candidiasis in critically ill and immunocompromised patients. The introduction of commercially available biphasic blood culture medium and subsequently the lysis-centrifugation procedure has markedly improved the ability of laboratories to detect fungemia. Although serologic methods have not been very successful in diagnosing candidiasis in immunocompromised patients, several antigen detection methods are now under investigation. In addition, detection of fungal metabolites such as D-arabinitol remains promising. Finally, application of the techniques of molecular biology for typing and detection of fungal pathogens has expanded our understanding of candidal infections and may offer the most sensitive and specific means of diagnosing invasive candidiasis.


Preliminary report on the isolation of a dysgonic variety of Microsporum canis together with the normal variety from a cattery.

The isolation of a dysgonic variety of Microsporum canis from a large number of cats and kittens in a cattery is described. The normal variety of this fungus was isolated at the same time from the same animals. Dysgonic varieties are thought to be mutants of normal strains, but this isolation of both forms together suggests that the relationship may be more complex.


The solid phase attachment of fungal hyphae in an ELISA to screen for antifungal antibodies.

A method to immobilize fungal hyphae onto the wells of 96-well microplates for use in an in-direct ELISA to screen for antifungal antibodies in sera and cell culture supernatants is described. The hyphae from three genera (Penicillium, Eurotium and Fusarium) were successfully attached by overnight drying onto wells precoated with poly-L-lysine and glutaraldehyde. Microscopy revealed that the hyphae remained attached to the wells throughout the ELISA and antiserum titrations showed that the attached hyphae were uniformly coated and remained reactive. Background absorbances were low and the plates could be stored at -20 degrees C without loss of reactivity.


The effect of selected human steroid hormones upon the growth of dermatophytes with different adaptation to man.

The inhibitory effect exerted by steroid hormones on the in vitro growth characteristics of dermatophytes is poorly understood. As a hypothesis this inhibition could result from fungal adaptation to the human host. Therefore, in this study the susceptibility of representative anthropophilic, zoophilic and geophilic dermatophytes to hormonal inhibition was compared. As a result, in agar dilution assays progesterone, testosterone, and estradiol proved to reduce fungal growth, whereas hydrocortisone had no such effect. In general, anthropophilic dermatophytes were shown to be more responsive to steroid hormones than geophilic species, suggesting a correlation of steroid susceptibility with adaptation to human skin. However, since fungal response to hormones consisted of growth inhibition and occurred only at steroid concentrations much higher than present in human skin, it cannot be assumed to contribute to this adaptation.


Application of glycerol to freezing bovine pancreas. Part 3. Effects of freezing rate and glycerol addition on changes in pancreas proteins.

Changes in protein solubility, amino nitrogen and activity of proteases in bovine pancreas frozen at -70 and -18 degrees C after soaking in various aqueous glycerol solutions were studied. Reduction of freezing temperature causes decrease of value in all studied parameters. Additionally, an inhibitory effect of glycerol on protease activity was demonstrated.


Feeding differently processed soya bean. Part 3. Effect on serum constituents and bone mineralization in the chicken.

The effect of feeding differently processed soya bean on serum constituents and bone mineralization in the chicken was investigated in growing chickens. The response parameters were total serum protein (TSP), albumin, globulin, albumin:globulin ratio and urea. Others were phosphorus, calcium and calcium:phosphorus ratio in the tibia and femur. The results indicated that TSP was significantly increased (P < 0.05) in the heat processed soya bean diets but decreased in the chicks fed raw soya bean diet. Albumin and globulin were not significantly affected. However, albumin:globulin ratio was significantly (P < 0.05) influenced. Serum urea was generally higher (P < 0.05) in the chicks fed processed soya bean diets. Significant (P < 0.01) decrease was observed in the total ash [%] of the bones in the chickens fed raw soya bean diet. The phosphorus [%] and Ca:P ratio in both tibia and femur were not significantly affected by dietary treatments.


Biological study on the effect of supplementing wheat flour with fish protein concentrate.

The protein quality of 4 Egyptian pastries made from different combinations of flour and fish protein concentrate (0%, 4% and 6%) was measured by rat growth study. Weight gain, feed consumption and PER were determined. Weight gain of rats fed cottage cheese crescents was higher than that fed date bars followed by that fed brouche, then rats fed salty sticks. Feed consumed by rats fed with the corresponding commercial pastries was low except in date bars group. Commercial pastries led to low weight gain and low PER values. Supplementing wheat flour with 6% fish protein concentrate gave the highest weight gain and the highest PER values.


Mycotoxic flora and mycotoxins in smoke-dried fish from Sierra Leone.

Examination of 20 samples of smoke-dried fish of the Ethmolosa sp. commonly called "Bonga", from homes and markets in Njala (Sierra Leone) revealed the presence of 4 Aspergilli species: A. flavus Links ex Fries, A. ochraceus Wilhelm, A. tamarii Kita and A. niger van Tieghem. Fresh or properly preserved smoke-dried fish showed no signs of fungal contamination. Mouldy fish extracts contained varying amounts of aflatoxins B1, G1, G2 and ochratoxin A. Isolates of A. flavus grown on yeast extract sucrose (YES) medium, produced considerable amounts of aflatoxin B1 and G1 and trace amounts of G2. On YES medium A. ochraceus produced large amounts of ochratoxin A but no penicillic acid.


[The prenatal toxicity of butenylisothiocyanate in rats].

Butenyl isothiocyanate (BylITC), the hydrolysis product of the glucosinolate gluconapin, present in various cruciferous vegetables and in rapeseed, was administered in oral doses of 0, 50, 100 and 150 mg/kg to pregnant rats on day 12 to 19 of gestation. Maternal toxicity was indicated by reduced body weight gain and increases in the weights of liver and kidneys. BylITC doses of 100 and 150 mg/kg caused retardation of fetal growth and ossification.


Mechanisms of electromagnetic interaction with cellular systems.

The question of how electromagnetic fields--static or low to high frequency--interact with biological systems is of great interest. The current discussion among biologists, chemists, and physicists emphasizes aspects of experimental verification and of defining microscopic and macroscopic mechanisms. Both aspects are reviewed here. We emphasize that in certain situations nonthermal interactions of electromagnetic fields occur with cellular systems.


Enhancing educational accessibility in rural areas through collaboration.

Limited access to baccalaureate nursing education for RNs in rural areas has restricted their career development. This paper describes an effective mobile educational program created through collaborative efforts of nursing administrators, nurse educators, and RN students.


Future health care workers camp.

Adolescents often make career decisions without ever having life experiences related to their choices. This paper describes an interdepartmental cooperative effort that led to the creation of a unique program for area teens. Based on a camp theme, the program serves as a health care recruitment tool while providing participants with on-site experiences, scheduled time with professional role models, and practical information related to a variety of health-related careers.


Polio nursing: the fight against paralysis.

Poliomyelitis epidemics occurred in this country with increasing frequency and severity for more than five decades. A frightening, highly contagious disease resulting in devastating paralysis, polio remains prevalent in much of the developing world. This paper describes the pathophysiology, clinical course, and treatment of polio and discusses the essential work of nurses in the years before an effective vaccine was available. The collaborative contributions of nurses, physicians, and scientists are presented.


Ethical decision making for nurse administrators.

The authors' purpose is to offer a theoretical perspective to help the nurse administrator make ethical decisions congruent with social policies in allocating scarce resources. The goal is approached in two ways: by exploring the philosophical principle of morality on which decisions to distribute scarce resources can be made and by clarifying the principles of justice and distributive justice in two classic moral theories. Principles of distributive justice that serve as guidelines for social justice policy are delineated. A case study illustrates the dilemma.


Nursing and JCAHO.

The joint commission is arguably the most powerful accrediting agency in health care today. Mahrenholz reviews the historical relationship of this organization with nursing and looks (longingly) at the future.


Health screening for the homeless.

The primary purpose of the project described in this paper is to detect actual or potential health problems in homeless persons and to help them gain entry into the public health care domain. A second purpose is to expose nursing students to a broader spectrum of patient needs than those encountered in traditional clinical settings. The community outreach program (COP) is based at a large southern university, where the nursing care center serves as executor of the project. The manuscript discusses funding, data collection, and future plans for the community outreach project.


M-I-D-D-L-E-G-R-O-U-N-D: Part II. Developing partnerships in practice.

This article describes the process for creating partnerships in nursing. It is Part II of the development of M-I-D-D-L-E-G-R-O-U-N-D, a model for the integration of nursing education and nursing service. Collaboration and community building are the activities that occur as nurses who are "Futuremakers" create the new partnership paradigm. Seven capacities (7 Cs) needed to develop these dynamic partnerships are defined. These capacities can advance caring and healing in nursing.


[Detection of diarrhea-causing Escherichia coli using DNA-probes].

To assess the role of enterovirulent Escherichia coli at home and abroad, faeces samples of patients with diarrhoea and of healthy controls in Tunisia, Seville (southern Spain) and the Netherlands were investigated. Enterovirulent E. coli were identified by hybridization with five different non-radioactively labelled DNA probes specific for enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC) and verocytotoxin producing E. coli (VTEC). ETEC was the main causative agent of travellers' diarrhoea in Tunisia. The isolation of ETEC in the Netherlands was shown to be related to travel in endemic areas. EPEC probe positive strains were isolated in children and in adults, but were not in all cases associated with intestinal disease. During this study no VTEC were detected. From an immunocompromised kidney transplantation patient with sepsis and diarrhoea ETEC were isolated from blood.


[Arthroscopic ankle arthrodesis: a new technique].

We report on 5 patients who successfully underwent an arthroscopic ankle arthrodesis in the department of Orthopaedics of the University Hospital in Nijmegen. Three patients had haemophilia, one rheumatoid arthritis, and one arthrosis following trauma. The results were satisfactory. The patients had surprisingly little postoperative pain. It appears from the literature that regarding morbidity in terms of infection, pseudarthrosis and consolidation time, arthroscopic arthrodesis compares favourable with the open procedures.


[Renal crisis in scleroderma].

A case is described of a 30-year-old woman with scleroderma renal crisis. She presented with classical symptoms: malignant hypertension of sudden onset and rapidly progressive renal failure. End-stage renal failure developed in spite of treatment with angiotensin converting enzyme inhibitors and the patient became dialysis-dependent. Five years later her condition was still stable. She lived in a nursing home, severely disabled but mentally healthy. A renal crisis is one of the most life threatening complications of scleroderma. By immediate treatment with ACE inhibitors, dependence on haemodialysis can be prevented in half the patients.


Nurses' attitudes towards the sexuality of older people: an investigative study.

This article outlines a small scale investigative study into what factors influence nurses' attitudes towards the sexuality of older people. Thirty three trained nurses completed questionnaires designed to focus on three main areas: respondents' background details, attitudes towards sexuality as a general concept, and knowledge and attitudes specifically about the sexuality of older people. Results of the study indicate that nurses' attitudes about sexuality in general were the most influential factor in predicting their attitudes to older people's sexuality. This would suggest that nurses should be given the opportunity to explore their feelings about their own sexuality in order to change attitudes and practice.


Nurse staffing levels and skill mix in accident and emergency departments.

This paper examines the history of nurse staffing and skill mix in accident and emergency (A&E) departments, and reports results from a study which examines numbers of staff and relates this to numbers of patients and organisation of work in A&E departments throughout one region. The types of procedures undertaken by nurses and the qualifications they held are also analysed. Conclusions about present variations in staffing in A&E departments are drawn, with recommendations for further study.


The single case experimental design: a quantitative method for everyday use.

Although the qualitative approach to research has become a dominant trend in nursing research, some commentators have argued the strengths of quantitative methods, particularly if the data are sensitively handled by investigators (1). This article argues for greater use in nursing research of a particular quantitative method: the single case experimental design. It traces the development of the methodology, describes the designs of which it consists and their associated statistical handling, and examines the relevance of the approach as a whole to nursing, particularly during the construction and testing of innovative approaches to client difficulties. The paper concludes by suggesting the potential impact of the adoption of single case methods for nursing practice and research.


'An active body, a healthy body': a new health survey for Northern Ireland.

The Northern Ireland Health and Activity Survey is the first survey of its type to take place in Northern Ireland. Its aim is to provide a detailed profile of the general level of physical activity in the province. The main advance in this survey is that it includes studies of blood components, such as various lipids levels. This exciting and far reaching project commenced in February 1992 and extends over a period of approximately one year.


The integration of research in the clinical setting: obstacles and solutions. A review of the literature.

One of the most influential factors in the successful genesis of any profession is the development and growth of research. Professions need to have their roots planted firmly in a fertile body of knowledge. Nursing is a developing profession; in order for it to progress, the utilisation of valid research findings is essential. In this paper, the author has reviewed some of the available literature on the subject of research utilisation, highlighting the obstacles and providing some possible solutions.


Visits to the wards by non ward-based personnel.

Fourteen acute hospital wards in five different hospitals were observed for three days. Observers recorded the number and type of non ward-based personnel coming onto the ward, the nature of their visit, the length of time they stayed and whether or not they contacted a member of staff. Wide differences between the wards were found, but the overall results indicate that the volume of visits to the wards was greater than even the ward sisters recognised. The author suggests that a clearer definition of the role of the ward clerk--and an upgrading of the role to prepare clerks for dealing with non nursing-related enquiries--could be of great assistance to sisters and would be a cost-effective investment.


Mammographic screening for breast cancer in women under fifty: a review.

There is currently insufficient scientific data to support the recommendation to begin mammographic screening before the age of 50. The balance of the evidence that does exist suggests that screening before the age of 50 is useless and possibly harmful. If we accept that it is unethical to screen in the absence of good data suggesting benefit, then screening under the age of 50 is unethical.


Electroencephalographic and vegetative correlates of the mental reproduction of emotional states.

The present investigation is devoted to an analysis of the changes in the bioelectrical and vegetative indices during the mental reproduction of emotional states by man. An analysis of the data of the mapping of intracortical interactions as a function of the time course of the changes in the R-R interval was carried out. Two stages in the mental reproduction of emotions were identified which are characterized by the presence of different centers of integration, in the frontal and temporal divisions of the cerebral cortex. It was demonstrated that in the presence of maximal emotional tension the center of integration shifts from the frontal regions to the temporal region of the left hemisphere.


Mechanisms of motoric learning.

The basic principles of motoric learning are analyzed in this paper. Arguments are given for the position that instrumental conditioning is the basis for motoric learning, but that the mechanisms of insight as well as the system of foresight in analysis of the result also play a substantial role in it. The hypothesis is advanced, in comparing certain theories of learning, of the possibility of a synthetic approach. Two stages can be distinguished in the process of motoric learning, the formation of notional and coordinational programs. The formation and realization of learned movements which are antagonistic to the initial coordinations takes place under the constant control of the motor cortex, which effects the inhibition of interfering coordinations that develop in the course of learning.


Intralimbic evoked potentials during the formation of an alimentary conditioned reflex in response to the electrostimulation of the hippocampus of dogs.

Instrumental alimentary conditioned reflexes (CR) in response to the electrostimulation of the hippocampus were developed in experiments on dogs with electrodes implanted in various divisions of the hippocampus, the amygdala, the septum, and the hypothalamus. During their development the evoked potentials (EP) were investigated in the hippocampus itself and in other limbic structures, as well as in the hippocampus during the testing of the latter for the purpose of verifying generalization. The formation and extinction of the CR was accompanied by changes in the amplitude-temporal characteristics primarily of late components of the EP picked up from the lateral hypothalamus and the amygdaloid complex in response to the hippocampal electrostimulation. During the carrying out of this stimulation of signal functions (pedal pressing to obtain food), the average amplitude of the trace positivity and of the late negative wave were found to be lower than by the end of extinction in the presence of ineffectiveness of the signal. The average amplitudes of the late components of the hippocampal EP which arose in response to electrostimulation of the amygdala were lower in those tests in which the instrumental movement appeared when the generalization of the CR was tested.


Certain methods of biomechanical description of various postural adjustment patterns during motoric learning in dogs.

Methods for the biomechanical description of spatial displacements of the center of mass of quadruped animal (dog), developed by the authors on the basis of an assessment of the vertical constituents of support pressures, as well as methods for the assessment of the postural adjustment pattern (coefficient of diagonality), are presented in this paper. The results are presented of an investigation of the role of the motor cortex in the accomplishment of the postural adjustment pattern of dogs, reorganized during learning, in the performance of an instrumental movement.


Correlation relationships of evoked activity of the auditory cortex and the amygdalae of cats during conditioned reflex activity.

The character of the interaction (Spearman's correlation coefficient) between the structures before, and during the development, extinction, and restoration of an instrumental food-procuring reflex, as well as during the automatization of the reflex was determined on the basis of the averaged sound-induced activity (AEP) of symmetrical points of the auditory cortex (AI) and the amygdalae (abl) of cats. The co-tuning of the cortex and the amygdalae during the adaptation of the animal was found to be individual in character; this was replaced by close interactions during the formation of the reflex and by the disruption of their correlatedness during its extinction. The consolidation of the reflex prior to the stage of automatization was accompanied by attenuation of the connections between the cortex and the amygdala. The results attest to the complex and dynamic character of the interdependence in the cortex-amygdala system during conditioned reflex activity.


Participation of nonlinear dynamic processes in the formation of the high-frequency EEG of the rabbit.

The informativeness of the high-frequency EEG for the assessment of the functional state of the brain has been proven by means of a new method of analysis of the EEG which is suitable, by contrast with the traditional spectral correlation analysis, for the description of nonlinear processes. Evidence has been obtained in favor of the hypothesis that a deterministic chaotic component, the parameters of which depend on the region of recording of the EEG and which changes conjointly with change in the functional state of the brain, is present in the EEG of the neocortex and hippocampus of the rabbit.


Brain death: practicability of evoked potentials.

Multimodally evoked potentials were registered in 85 patients who fulfilled the criteria for brain death. While somatosensory and visual evoked potentials have been found to be of limited value for the diagnosis of brain death, the stepwise abolition of brain stem auditory evoked potentials (BAEP) confirmed brain death in 26 out of 85 patients, i.e. 31%. Registration of the abolition of BAEP is concluded to be a safe and acceptable confirmatory test. It is, however, more feasible for institutions, in which BAEP are analysed routinely. In spite of all efforts sequential BAEP could not be used for the diagnosis of brain death in the majority of cases either because of absence of reproducible responses at the initial registration or because the patient was already apnoic at the time of the initial BAEP. Assuming that bilateral preservation of wave I has the same significance as the stepwise abolition of BAEP, since it also proves the integrity of the peripheral receptor, BAEP are relevant for the declaration of brain death in approximately 30% of patients.


Compensatory plasticity of the brain under conditions of its injury.

The possibility of the utilization of the galvanic skin response (GSR) as a test for the analysis of compensatory processes under the conditions of natural compensation and with the use of functional biofeedback was studied in experiments on cats anesthetized with chloralose and immobilized with flaxedil, as well as in clinical conditions in healthy children and children suffering from childhood cerebral palsy (CCP). It was demonstrated in this study that the habituation of the GSR is disturbed in the case of unilateral brain trauma. These differences level out a year after the brain trauma. When functional biofeedback is used to accelerate habituation processes of a compensatory character, the GSR of the right and left sides of the body equalize and approximate that observed in healthy children. This study is yet another confirmation of the advantage of functional biofeedback as compared with traditional treatment methods. The data obtained also make it possible to believe that the habituation of the GSR may be useful not only for the analysis of the depth and level of the injury of nerve tissue, but for the objective assessment of compensatory restorative processes as well.


Surgical observations in extremely lateral lumbar disc herniation.

About 10% of lumbar disc herniations are localized in an extreme lateral position referred to as "extracanalicular". The clinical syndrome is a typical one with compression signs of the lateral, extra-foraminal nerve root and minimal lumbar pain. A reliable diagnosis can be made only since high resolution spinal computed tomography has become available. Surgical treatment will be rendered difficult by the "hidden" localisation of the disc fragments. A total number of 15 patients has been operated on in our department during the last year. In 10 patients, we used the lateral microsurgical approach proposed by REULEN, in five cases a combined procedure with lateral sequestrotomy and medial nucleotomy. In the first group, re-sequestration occurred in three cases and further surgery including medial nucleotomy was performed then. A good result with remission could be achieved in 13 cases, whereas in two cases with additional spondylolisthesis, lumbar back pain continued, but the radicular symptoms were reduced.


Afferent control of cortically evoked reactions of spinal cord ventral horn interneurons.

The reactions of interneurons of the ventral horn (L6,7) of the spinal cord in response to stimulation of the motor zone of the cortex and of afferents of the hind limbs were investigated intra- and extracellularly in experiments on cats. It was demonstrated that cortically evoked reactions of the interneurons are modulated by the preceding afferent wave. Three types of effects were distinguished: intensification, suppression, and biphasic changes. Facilitation is brief (not more than 30-35 msec); the duration of suppression varied from 60-100 msec to 300-400 msec. A correlation between the effect of afferentation and the latent period of the cortically evoked reaction was established: facilitation was observed among the short-latency reactions; long-latency reactions were inhibited as a rule. Inhibition was more clearly manifested: for the responses from the ipsilateral than the contralateral hemisphere; during the conditioning of the contralateral afferents, than during the conditioning of the ipsilateral; of the high-threshold afferents than of the low-threshold. The mechanisms of afferent control of descending activity and the role of "polysynaptic loops" in the processes of the afferentation as a supplementary modulator of the excitability of motoneurons are discussed. It is proposed, on the basis of the analysis of the data obtained (the absence of IPSP in the interneurons investigated, etc.), that a principal role in the suppression of descending activity belongs to the mechanism of presynaptic inhibition, as well as to the disfacilitation caused by it (the decrease in depolarization and the increase in the critical discharge level) in the interneurons themselves due to the blocking of the background afferent influx from other inputs.


Comparative experimental biomechanical study of different types of stabilization methods of the lower cervical spine.

In a comparative experimental biodynamic study using thirty-two human cervical spines of cadavers the primary stabilization effect of different types of spondylodesis was examined. Whereas in flexion stress all methods showed a sufficient stability, the rotation tests proved, that in case of a dorsal instability of the lower cervical spine, posterior interlaminar wiring or anterior plate stabilization showed no reliable stabilization effect. However, the compression clamps by ROOSEN and TRAUSCHEL as well as the hook-plates by MAGERL are suitable dorsal stabilization methods with excellent rotation stability. In case of dorsal instability of the lower cervical spine a posterior spondylodesis is necessary and sufficient.


Contribution of thallium-201-SPECT to the grading of tumorous alterations of the brain.

Single photon emission computed tomography (SPECT) with thallium-201-chloride (201Tl) was used in 22 patients to assess the grade of malignancy of brain tumors. Low- and high-grade malignant gliomas could be well differentiated by calculating the Grade Index (GI), i.e., 201Tl uptake in the tumor area relative to a contralateral brain region. Low-grade gliomas (WHO-grade I-II) usually showed a GI of < 1.5. Tumors classified histologically as high-grade malignant (WHO-grade III-IV) had GI values greater than 1.42 and a mean value of 1.89. Until labelled amino-acid tracers for gamma-cameras become commercially available, thallium-201 brain-SPECT can provide an independent and complementary method to CT/MRI for the differential diagnosis of grading of brain tumors. This simple technique can help to reduce sampling errors during needle biopsies of brain tumors, particularly of high-grade lesions incorrectly graded as low-grade tumors due to inadequate biopsy material. In addition, pre- and post-therapy studies can influence the strategy of therapy itself and allow an early detection of recurrences.


An electrophysiological analysis of the hippocampal projections to the neurosecretory cells of the supraoptic nucleus of the hypothalamus and the neurons of the perinuclear zone of rats.

Impulse activity of antidromically identified neurosecretory cells, orthodromically activated neurons, and neurons not responding to this stimulation was recorded in the supraoptic area of the hypothalamus under conditions of the stimulation of the hypophyseal stalk. The reactions of all groups of cells to the stimulation of the ventral hippocampus were investigated; the number of responding cells came to 14, 59, and 46%, respectively. Short-latency excitatory reactions predominated substantially. It is conjectured that the influences of the hippocampus are most significant for the neurons of the perinuclear zone as compared with the neurosecretory cells of the supraoptic nucleus. Particular aspects of the morphofunctional organization of the supraoptic area are discussed, taking into account both the convergence of afferent inputs from the neurosecretory cells and the hippocampus on the orthodromically activated neurons and the features of the organization of the hippocampal projections to various groups of cells of the perinuclear zone of the supraoptic nucleus.


Osteosynthesis of injuries and rheumatic or congenital instabilities of the upper cervical spine using double-threaded screws.

The surgical treatment of instabilities of the upper cervical spine, independent of their cause, requires the use of differentiated procedures if functional anatomy is to be largely restored. Successful procedures have been the diagonal screw fixation of the axis from the anterolateral aspect in case of acute fractures of the odontoid process, transpedicular screw osteosynthesis of C2 in hangman's fractures with bony instability, and the transarticular screw fixation of C 1/2 with interarcual fusion for atlantoaxial instabilities. Compared with conventional screws, the use of double-threaded screws which are almost totally imbedded in the vertebral body has the advantage of eliminating local irritation, reducing the risk of surgery, and simplifying the operative procedure itself.


Intraoperative angiography and embolization in intracranial AVM's and aneurysms.

Intraoperative angiography allows for control procedures for exstirpation of arteriovenous malformations and clipping of problematic aneurysms during the entire operation. During intraoperative embolizations, it is especially helpful to see whether the occlusion of the nidus of an arteriovenous malformation is complete. The method is easy to perform; there were no complications in 19 cases.


C.N.S. tumors in eastern Saudi Arabia.

In Saudi Arabia, there were no attempts previously to describe a population based frequency or incidence, particularly so the age adjusted incidence of various CNS tumors. This paper presents the primary CNS tumors from a population based tumor registry over two years period, from January 1987 till December 1988. There was a total of 85 cases representing 5.4% of the total captured cases (1,568 cases of malignant tumors at all sites). The population of the Eastern Province is estimated to be 1.37 million, the Saudis forming 80% of the total population. Out of the 85 cases captured over two years, there were 64 cases diagnosed in indigenous Saudi population forming 75%. The remaining occurred in non-Saudi residents. The male/female ratio in Saudis was 1:1.1 with a slight predominance of the female, while the reverse is true in the non-Saudis (2:1). The total captured cases per annum is 43, making the incidence of primary CNS neoplasms in the Eastern Province of Saudi Arabia 3.1/100,000 of all the population and 2.9/100,000 in Saudi nationals. Comparing this incidence to the international figure, it was clear that it is far less than the incidence reported from North America and Europe, particularly in the Caucasian population, but similar to incidences reported in the Chinese, black Americans, Romanians and Yugoslavians, but certainly less than the Ashkenazi or Safari Jews, and slightly higher than the incidence reported in Japan and Southeast Asia. Malignant brain tumors of various types dominated the primary CNS neoplasms reported over these two years forming 69% of the cases and 52% of the primary brain tumors.


Meningiomas of the lateral ventricle. Report on six cases.

In this study 6 patients who had meningioma of the lateral ventricle are reviewed. The incidence is 1.8% of cases of meningiomas in our series. Microsurgical techniques were employed in all patients. There was no death and the follow-up period was between 5 months and 10 years. No recurrence was seen. Although the origin of these tumors is still not known, DUNN and KERNOHAN note that the choroid plexus has the potential for the production of meningothelial, fibrous, or mixed patterns. Our pathological results confirmed this suggestion.


Two undesirable results of wrapping of an intracranial aneurysm.

This article presents a rare case in which we experienced two undesirable results following wrapping of an internal carotid artery aneurysm. First, a muscle piece used for wrapping was absorbed completely and, therefore, could not prevent enlargement of the aneurysm. And second, muslin gauze wrapping induced a foreign-body granuloma at the site (parasellar region), and resulted in development of oculomotor palsy.


Cerebral reperfusion in brain death of a newborn. Case report.

A case of "sudden infant death" after 15 minutes of successful resuscitation of cardiovascular function is presented. While apnoic cranial nerve areflexia and electrocerebral silence persisted, angiography and transcranial Doppler sonography demonstrated nearly normal cerebral perfusion, which even increased day by day inspite of the persistence of other signs of brain death. The phenomenon "cerebral reperfusion" is concluded to be compatible with the diagnosis of brain death.


Hypophyseal metastatic hypernephroma mimicking a pituitary adenoma. Case report.

A patient with a remote history of nephrectomy for hypernephroma presented a visual field defect with hypopituitarism. Neuro-imaging studies showed a highly vascularized sellar mass with suprasellar extension. Surgery, which was performed via the subfrontal approach, disclosed the pituitary tumor to be a hypernephroma. Although anterior pituitary involvement is rare, chiasmal compression is much rarer in metastatic pituitary carcinomas, a review of previously reported cases of metastatic pituitary hypernephroma and our own case indicated that pituitary metastasis from this carcinoma, in contrast to other metastatic pituitary tumors, often mimics pituitary adenoma.


Intrasacral meningeal cyst demonstrated by magnetic resonance imaging.

Intrasacral meningeal cyst, first reported by Enderle in 1932, is a rare cause of low-back and leg pain . Non-invasive magnetic resonance imaging appears to be very useful for initial identification of intrasacral cystic masses.


[Hemodynamic reserve in carotid surgery and the use of "superselective" shunt].

The aim of this study is to establish whether a preoperative evaluation of the Cerebral Hemodynamic Reserve, carried out by means of transcranial Doppler and SPECT with provocative test (acetazolamide) can single out those patients who, because they are supplied with a poor cerebral reserve, are truly in need of intraoperative shunting after carotid clamping. All patients were intraoperatively monitored by means of Somato Sensitive Evoked Potentials (SSEPs). Those patients who were shunted due to abnormalities in SSEPs were also those who showed a perfusion and velocity increase below 15%, and therefore supplied, in our opinion, with a scanty cerebral reserve. No, but one, neurological deficit appeared on awakening in patients who were not shunted.


[Heterotopic splenic autotransplantation: a therapeutic option in splenic trauma].

The Authors report two cases of splenectomy for trauma, followed by heterotopic autotransplantation of splenic tissue in omental pockets. A follow-up nuclear scan and ultrasonography showed function and growth of the splenic implants. The pertinent surgical literature is reviewed.


[Thyroid pathology in the aged].

Following a review of the literature on this topic, the authors examine all patients with thyroid pathologies who were admitted to the 1st Institute of Surgical Pathology of the University of Pavia between 1-1-1974 and 31-12-1990. Only patients aged over 65 were included in the study and were subdivided into two groups, namely those aged between 65-74 (3rd age) and those over 75 (4th age). Particular attention was focused on the type of pathology (benign or malignant), other pathologies associated to the basic pathology, the type of operation performed and, in the case of malignant diseases, the histological type of tumour and any metastasis. The results of this series were then compared to those reported elsewhere. The Authors conclude that thyroid pathologies in geriatric patients are very important since, given that at this age the gland is becoming atrophic, the onset of disease often occurs before the age of 65 and symptoms in these patients are imprecise. In view of the good results obtained, it is always worth operating in order to give the patient a reasonable life expectancy, especially in those cases with collateral disorders (compression) caused by the thyroid mass.


[Current advances in the diagnosis of parotid masses].

The Authors first briefly describe the possible histological features of parotid masses, difficult to differentiate only on the basis of clinical signs. They report on imaging techniques for detecting this kind of pathology and suggest the best diagnostic protocol for correct evaluation of parotid masses, because of its great importance in planning optimal surgical management.


[A department of general surgery using the Diagnosis Related Groups (DRGs) system. Evaluation of the case series].

DRGs system allows the grouping in a single grad-bag code of a number of similar surgical procedures carried out in patients homogeneous for age, physical status, complication and so on with similar costs. Therefore this grouping method is useful for payment to hospitals. The Authors have coded with DRGs the surgical activity of a general surgery staff during a year to verify the image that DRGs bears. Seven hundred diagnoses of dismission were related to operated on patients while one hundred twenty seven were related to patients treated with medical therapy. The DRGs more numerous were 290, 258, 198, 162, related with thyroidectomy, mastectomy, cholecystectomy and herniorrhaphy.


[Removal of tattoos by CO2 laser and acetic acid].

The Authors pay attention to small tattoo removal by means of the utilization of the CO2 laser. Moreover, the Authors emphasize the drawback of double treatment which, usually, the patient suffers in tattoo removal by CO2 laser. Then, the pressure of the Authors is small sized tattoo removal in only one sitting achieving so an excellent esthetic result. Besides, the Authors, in this medical study, explains two methods for tattoo removal. In the study's results, the Authors describes the manner and the time of the two lesion recovery by the different manners of treatment. Finally, the Authors affirms the great consequence of the surgical CO2 laser, they don't fail, however, to affirm that the laser and acetic acid combination is an excellent procedure for small tattoo removal.


[Evolution of the bacteria responsible for surgical infection. n 8-year study in our department].

Since 1981 we monitored all the bacteria strains isolated from patients bearing a surgical infection and hospitalized in our department. We also tested the susceptibility of the isolated strains to different antibiotics. The observed results at three different intervals (1981, 1984, 1987-1988) reveal an increase in Gram+strains. Among the tested antibiotics Imipenem and Amikacin showed the highest antibacterial activity in recent years (1987-1988).


[Sulbactam-ampicillin in surgery. Our experience].

The bacterial infections constitute a serious problem for the surgeon: the choice of antibiotic drugs is really important and, as often as possible, should be guided by antibiotic sensitivity tests. In this study we used sulbactam-ampicillin (Unasyn) who is an antibiotic combination between sulbactam, inhibitor of beta lactam and ampicillin. The preliminary results were as follows: Unasyn was administered to 21 hospitalized selected patients, 16 women and 5 man, who had clinical signs of intraabdominal infection, wound infection and subphrenic abscess after digestive surgery. In these patients were isolated the following organisms: Staphylococcus epidermidis (8), Staphylococcus aureus (11), serratia (1), streptococcus (3), E. coli (3). The daily dosage of Unasyn was 3-12 g/die administered in three to four divided doses, and was determined by the severity of infection, the antibiotic susceptibility of the causative organism(s) and the condition of the patient. Each dose was given by slow i.v. infusion in 15-30 minutes. Our success rate was 100%, and neither systemic nor local side effects were recorded.


[Importance of cleansing in the topical treatment of skin lesions. A parallel study carried out in 20 patients and 30 rats].

There are frequent reports of the chronic nature of skin ulcers of varying etiology (burns, bedsores, wound diastasis, etc.); these heal with considerable difficulty probably due to problems related to the excessive use of disinfectants which, in spite of having a good bacterial action, interfere with re-epithelialisation processes. The aim of this study was to assess the value of simple wound cleansing instead of disinfection in those cases where there are no manifest signs of bacterial contamination. A widely sold solution, Katoderm (Devergè, Turin), was used in this study. The study was performed in two stages; the first in laboratory animals and the second in patients with small persistent lesions. The results of the study carried out in rats showed a significant prolongation of healing time in the group treated with polyvinylpyrrolidone-iodine compared to those in which lesions were only cleansed with Katoderm. The results of the clinical study also highlighted the faster speed of healing in patients treated with cleansing alone.


[Special problems in the surgical treatment of megaesophageal cardial achalasia. A clinical case].

The paper report the case of a patient brought to the Authors' attention suffering from megaesophageal cardial achalasia who had already undergone gastroduodenal resection according to BII. It was considered worthwhile to report this case due to the problems which arose concerning the choice of a thoracic rather than abdominal route owing to the impossibility of associating cardiomyotomy with anti-reflux plastica surgery because of the reduced dimensions of the stomach.


[Pseudoxanthoma elasticum. A rare cause of upper digestive hemorrhage].

Pseudoxanthoma Elasticum (PXE) is a rare inherited elastic tissue disorder with degeneration of elastic fibres involving mainly skin, eyes and the cardiovascular system. Upper gastro-intestinal hemorrhage occurs in 13% of cases and is often resistant to non-surgical methods of treatment. One case report involving recurrent gastric hemorrhage in a young patient with PXE and treated with total gastrectomy is presented. Diagnosis was made, after surgery, by biopsy of skin lesions of the neck. The characteristics of PXE are reviewed and the case is discussed.


[Stenosis of the celiac tripod due to extrinsic compression. A case report].

The Authors, starting from the observation of a case of stenosis of the celiac tripod, caused by compression "ab estrinseco", examine the physiopathological, clinical, aetiopathogenetic and therapeutical aspects of the pathology in question. In accordance with medical literature interpretative nosological doubts are also raised which, not with standing the improved research techniques, make it extremely difficult to suggest an accurate surgical procedure.


[Epithelial cysts of the spleen].

The Authors report a case of epithelial cyst of the spleen-observed in a 25 years old woman. After remembering the nomenclature and pathogenetic hypothesis, they consider clinical patterns of this rare disease of the spleen which is usually found in children and young adults. The Authors discuss pathological findings, diagnostic aids, especially non-invasive imaging. They also suggest considering the cysts in diagnosis of the diseases of the spleen and splenectomy as a treatment of choice.


[Giant benign and malignant pathology of the ovary].

After a discussion of ovarian tumour classification, two cases of giant neoplasm, one benign the other malignant are reported. Ultrasonography and CA125 research represent two irreplaceable investigations, for preoperative balance and for therapeutic strategy.


[Localized pleural mesotheliomas. Clinicopathological considerations on a case report].

Pleural mesotheliomas are rare, and their diagnosis and treatment not clear. The case observed in our Department leads us to an analysis of the literature. This showed that differential diagnosis with pulmonary carcinoma is very difficult, even in cases of parietal mesothelioma; however local treatment may be performed even in malignant mesothelioma.


[Arterial embolism, venous thrombosis, pulmonary embolism: a suggestive triad].

The aim of this study is to present a relatively rare case of paradoxical arterial embolism, found in a patient who was sent to us for serious pulmonary embolism. Taking into account that the foramen ovale, despite being functionally competent, remains anatomically patent in 30% of the adult population, we cannot neglect the possibility of a paradoxical embolism, in the presence of a sudden embolic limb ischemia unless heart pathology or aortic lesions can be held responsible. Furthermore it must not be forgotten that deep venous thrombosis in the lower limbs or in the pelvic plexus may go unobserved on a purely clinical evaluation.


[Moderate arterial hypertension in pregnancy: therapeutic aspects].

The treatment of hypertension in pregnancy is justified by the need to reduce blood pressure in order to avoid the onset of preeclampsia, eclampsia, retarded intrauterine growth and even neonatal, perinatal and maternal death. The value of using drugs to treat slight-moderate hypertension in pregnancy is, however, not clearly defined in the literature. In fact, from an etiopathogenetic point of view, the significance of increased blood pressure in pregnancy has not yet been satisfactorily explained, and above all the positive significance of increased blood pressure not be forgotten since, up to diastolic levels of 90 mmHg, it is accompanied by an increase in birth weight. The aim of the present study was to verify the efficacy of pharmacological treatment in cases of slight-moderate hypertension during pregnancy in a population of 121 pregnant women attending the Obstetrics-Gynecological Clinic of the "Istituto per l'Infanzia" in Trieste during the period from 14-11-1984 to 24-4-1991. Data for this retrospective study were extrapolated from an analysis of medical records and then memorized in a data-base file. The degree of hypertension was classified as slight, moderate and severe according to blood pressure levels measured on hospitalisation. Clinical signs taken into account included: edema, proteinuria and hypoprotidemia. Anti-hypertensive therapy was selected between one or more associated drugs belonging to the following classes: central action and peripheral action anti-adrenergic drugs, beta-blockers, calcium channel blockers, vasodilators, diuretics, ACE-inhibitors and sedatives. Moreover, patients also received non-pharmacological treatment in the form of low sodium diets and bed-rest.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cysts of the choroid plexus: personal experience].

Twenty-six cases of fetal choroid plexus cysts were diagnosed using ultrasonography at the Ultrasound Out-patients clinic of the University of Turin during the period 1989-1991. In 21 of these cases fetal karyotype was ascertained since, as has been reported in the literature, cysts of the choroid plexus may be associated with an anomalous karyotype (trisome 18 or 21). One of the 21 cases had an altered karyotype (trisome 21) (4.2%). The Authors stress the importance of a detailed ultrasound study of fetal morphology since, in the presence of structural anomalies, the incidence of trisome 18 is much higher. On the basis of these data, prenatal diagnosis in the event of the echographic presence of choroid plexus cysts appears to be valid since the risk of chromosome anomalies is much higher than in 35-year-old women.


[Urolithiasis in pregnancy].

Urolithiasis is a cause of abdominal pain occurring during pregnancy requiring hospitalization. Of 3793 deliveries in a 5-year period 11 were complicated by urinary calculi during pregnancy. The incidence was 0.29% and in 45% the calculi passed spontaneously. Conservative therapy was resolute in 100% of cases and didn't have any consequence on pregnancy and neonatal outcome. Pathogenesis, diagnostic and therapeutic approach are considered.


[Clobetasol vs. testosterone in the treatment of lichen sclerosus of the vulvar region].

The paper describes a study carried out in 40 patients affected by lichen sclerosus (LS) of the vulva. The mean age of patients was 60.9 years (range 27-83) and 31 were in menopause. Patients were divided randomly into two groups of 20. The symptoms (itching, burning, pain, dyspareunia), clinical aspects (atrophy, hyperkeratosis, sclerosis) and histological alterations (atrophy of the epithelium, edema, inflammatory infiltrate, fibrosis) were quantified in each patient by a score. The mean scores relating to the three parameters examined were then calculated for each group. One group was treated with testosterone propionate 2% and the other with a strong synthetic corticosteroid, clobetasol dipropionate 0.05%. After 24 weeks of treatment patients were again evaluated in relation to clinical (symptoms and clinical aspects) and histological parameters, following the procedure used before the start of treatment. The mean scores obtained were then compared with those before the start of treatment. Statistical analyses were performed using Student's t-test. Testosterone was found to be effective in relation to symptoms but no significant change was observed in relation to clinical aspects and histological alterations. It also caused major secondary effects which led to the suspension of treatment in one patient. Clobetasol was shown to be highly effective both in relation to symptoms and in terms of clinical aspects and histological alterations, and did not cause any noteworthy collateral effects, especially contact dermatitis. In the context of the objective parameters examined in this study, sclerosis and hyperkeratosis were easily modified by corticosteroid treatment in comparison to atrophy, especially in those patients with a longer duration of disease.(ABSTRACT TRUNCATED AT 250 WORDS)


[Benzidamine in the topical treatment of vaginitis caused by Gardnerella vaginalis].

The present clinical trial has been carried out in order to evaluate the efficacy of benzydamine in treatment of vaginitis caused by Gardnerella vaginalis. Fifty women affected by this specific pathology have been submitted to topical treatment with 0.5% benzydamine vaginal cream. The treatment has been carried out for 9 consecutive days using a local application of benzydamine twice a day. The clinical result was evaluated after 12 and 60 days. The following parameters were taken into consideration: symptoms (leucorrhea, itching, burning), clinical signs (oedema, hyperemia, vaginal secretion), instrumental data (pH, colposcopy, sniff test) and microbiological findings (searching of clue cells, Lactobacillus and Gardnerella vaginalis). At the first check point after 12 days 84% of patients have been considered healed; at the second check the percentage of healing rose to 92%. Therefore benzydamine was considered highly effective in 92% of vaginitis caused by Gardnerella vaginalis.


[Fetal outcome following "accidental" administration of a long-acting DTRP6 GnRh depot preparation during the first trimester of pregnancy].

In the case reported here, an injection of DTRP6 GnRh microcapsules was given in the 5th, 9th and 13th week of a spontaneous unsuspected multiple pregnancy. No deleterious effect of the embryo could be demonstrated at birth or six months later.


[Prophylactic and therapeutic use of ceftriaxone in cesarean section].

Authors did the antibiotic-prophylaxis with ceftriaxone in twenty cesarean sections (1 phial EV). Prophylaxis was sufficient in thirteen cases; on the other hand, in the remaining seven prophylaxis was followed by the three days therapy (1 phial EV). A good tolerance of the medicine was revealed in all cases. Moreover, it was tested a wide antimicrobial action with resolution of all the verified infections, except for one bacterial resistance case where some other antibiotic was used.


[Clinical study for the evaluation of the tolerability of O-(beta-hydroxy-ethyl)-rutoside in the treatment of hemorrhoids during the 3d trimester of pregnancy and in the postpartum period].

Hemorrhoidal disease is particularly frequent in the last trimester of pregnancy and immediately after birth. The aim of the present study was to evaluate the efficacy and tolerability of high doses of O-(beta-hydroxyethyl)-rutoside in patients affected by this pathology. Forty-two women with hemorrhoid varices of varying severity which had appeared during the last trimester of pregnancy or immediately post-partum were treated by administering 3 g/day of the substance in question for 14 consecutive days. At the start and end of treatment a series of clinical and objective parameters were measured and at the end of treatment efficacy and tolerability were assessed. The latter was found to be excellent; in fact, it was not necessary to suspend treatment in any of the subjects treated. Clinical efficacy, assessed by the researcher, was judged to be positive in 95% of cases treated. Clinical improvements in the parameters examined were statistically significant (p < 0.01). The results obtained confirm the value of oral therapy using O-(beta-hydroxyethyl)-rutoside in pregnant or puerperal patients since the preparation was found to be efficacious and easily managed, above all significantly reducing pain, subjectively the most urgent symptom to be treated.


[Effects of administration of 50 mg heparan sulfate tablets to patients with varicose dilatation of the hemorrhoid plexus (hemorrhoids)].

An experimental clinical study was performed using heparan sulfate in order to ascertain the effects of the drug in the treatment of 2nd or 3rd degree varicose dilatation of the hemorrhoid plexus. Forty female patients, mean age 37 years and suffering from varicose dilatation of the hemorrhoid plexus, were enrolled in the study. The study was carried out in an open comparison with oxerutin using parallel groups with random access. After a run-in period of 3 days, 20 patients commenced treatment with 1 50 mg tablet of heparin sulfate 3 times daily, whereas the other 20 patients were given 1,500 mg oxerutin tablet again 3 times daily. Subsequently, treatment was continued at the following doses: 1 50 mg tablet of heparin sulfate twice a day, and 1,500 mg tablet of oxerutin twice a day, for a duration of two weeks. At pre-established times (before treatment, after 1 week, after 2 weeks), a standard questionnaire was filled in relating to each patient in order to evaluate the efficacy and tolerability of treatment. No adverse or undesirable effects were reported. Each participant was also put on a personalized and computerised diet with the same fibre intake. 55% of patients treated with oxerutin reported persistent moderate or intense pain caused by defecation compared to 45% of the group treated with heparan sulfate. Both drugs induced the remission of skin rash and itching. Compared to the control drug, heparan sulfate was more efficacious in relation to the normalisation of hyperemia and mucoid secretion.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cerebral lesions in patients with ovarian cancer].

The Authors report the appearance of Central Nervous System lesions in three patients previously treated for ovarian carcinoma. In one case (Stage 1) the histological sample found a glioblastoma, in the others (Stage 3) the lesion was the metastases after systemic diffusion of the primary carcinoma. CNS metastases are rare and more frequently occur in advanced ovarian carcinoma. In patients at Stage 1, CNS isolated lesions may be primary tumors.


Sogn and Fjordane county community-based injury prevention: evaluation design.

The Sogn and Fjordane Injury Prevention Programme is a community-based research and demonstration project located in the Sogn and Fjordane county (S&F county) in Western Norway. The aim of the project is: (i) to further effective intervention; (ii) to be cost-effective; (iii) to provide information about local community based injury intervention. Liaison groups on injury prevention will be organised in 24 communities participating in the project. Starting 1 April 1993 they will be supplied with local specific injury rates obtained from the all-injury registration of the National Injury Surveillance System. The intervention design includes feedback of three types of information: (1) home and traffic injury rates; (2) sports, occupational, school, and outdoor injury rates; (3) both (1) + (2). The liaison groups will be asked to concentrate their activities only on the information-related injury areas. The hypothesis is that the results will be information-related. The intervention protocol will last for two years, until 1 April 1995. Evaluation will be based on a hypothetical causal intervention model. The model includes three groups of independent influences, two groups of mediator attributes, and desired end-result. A variety of data sources will be used including national and local data sources, two cross-sectional surveys on awareness, knowledge, behaviour and attitudes, interviews, observations, and self-reports from individuals. A mixed-model ANOVA will be used to test the main information-related effects. A combination of multivariate analytical methods will be used to test the hypothesised causal intervention model.


Observations on Pseudomonas aeruginosa proteolytic and toxic activity in experimentally infected rats.

To bypass natural resistance against Pseudomonas aeruginosa infection, a granuloma pouch model to be experimentally infected was established in rats. This experimental model also permitted easy collection of wound exudate. In general, the animals either died or became very ill and were consequently sacrificed within the first 12 days, or they (6 of 16) survived in good condition after 20 days. The virulence of recently isolated strains compared to twelve-months old subcultures of the same strains showed no major differences in clinical pattern. In the first seven days following the start of the infection, all animals presented a fall of elastase activity in the wound exudate. Toxin A was present in the exudate, sometimes in relatively high levels, but there was no correlation between toxin level and the clinical development. As a rule, spontaneous rupture of the granuloma pouch, apparently unrelated to the concentrations of either elastase or toxin A in the exudate, was beneficial to survival. In the present experimental infectious context, neither P. aeruginosa elastase nor toxin A seemed to play any isolated lethal nor pathogenetic role.


Do fast voluntary movements necessitate anticipatory postural adjustments even if equilibrium is unstable?

Anticipatory postural adjustments (APA) were studied in maximum velocity flexion of lower limb from two initial postures, a bipedal stance (Fbu) and unipedal stance (Fuu). In Fbu, the dynamics of center of gravity (CG) and ankle and hip muscle EMG activity showed large APA. In contrast, in Fuu there were no APA, the CG dynamics and the ankle EMG activity started at the same time as the intentional movement while the hip EMG activity started some 30 ms before the thigh flexion. The knee flexion velocity was lower in Fuu than in Fbu (7 rd/s versus 12 rd/s). These results suggest that fast voluntary movements do not require APA when the postural equilibrium is unstable, and that an alternative strategy is used. The absence of APA in Fuu, in contrast to the presence of APA in Fbu, suggests that the postural command and the focal one are time-locked and organized in a parallel process.


MDL 27,531 reduces spontaneous hindlimb contractions in rats with chronic transections of the spinal cord.

Disrupted glycinergic inhibition in the brainstem and spinal cord may contribute to some of the alterations in reflex control seen in patients with spastic disorders. MDL 27,531, which acts functionally like a glycine agonist in its capacity to selectively reverse seizures produced by the glycine antagonist strychnine, was evaluated in a model of spinal injury-induced reflex dysfunction. Rats recovering chronically from complete spinal cord transections exhibited intermittent contractions of the paralyzed hindlimbs, as measured with an automated apparatus. MDL 27,531 selectively decreased these hindlimb contractions, as did the clinically demonstrated antispastic agent clonidine. In its therapeutic dose range, clonidine, but not MDL 27,531, produced ataxia in non-transected rats. These data suggest that MDL 27,531 may be a useful therapeutic agent for the treatment of dysfunctions of reflex control seen in spastic disorders of spinal origin, with potentially fewer side effects than are seen with existing drug therapies.


Infection specific prion protein (PrP) accumulates on neuronal plasmalemma in scrapie infected mice.

Prion protein (PrP) is an abundant membrane-associated host protein which accumulates in abnormal, relatively protease-resistant forms in the brains of animals with scrapie and related diseases. Using correlative light and electron microscopy we determined the sites of subcellular localisation of PrP in mice infected with the 87V strain of scrapie. Disease specific accumulation of PrP was observed at light microscopy as amyloid plaques or as diffuse or granular staining within the neuropil, often clearly associated with individual neurons. Serial electron microscopical preparations were immunostained for PrP by the immunogold method. Gold particles were located on amyloid fibrils and on the plasmalemma of neurites at the periphery of plaques and in the neuropil, irrespective of the morphological form of PrP accumulation when viewed by light microscopy. This suggests that amyloid fibrils are formed following the accumulation and aggregation of sub-unit proteins at the plasmalemma and, furthermore, that normal PrP may be converted to its pathological form at this site.


Enhanced monoamine release in the median preoptic area following reduced extracellular fluid volume in rats.

The role of monoaminergic neural inputs to fluid regulatory systems in the median preoptic nucleus (MnPO) was investigated by examination of monoamine metabolism during reduction of systemic extracellular fluid volume in freely moving rats. Extracellular fluid volume was decreased iso-osmotically by subcutaneous polyethylene glycol (PEG), and extracellular noradrenaline (NA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured using intracerebral microdialysis techniques. PEG treatments significantly increased NA, DA and DOPAC release in the MnPO area. The results suggest that monoaminergic neural systems in the region of the MnPO are important in the control of extracellular fluid balance.


Intracellular free [Ca2+] and [Na+] in response to capsaicin in cultured dorsal root ganglion cells.

Intracellular free Ca2+ and Na+ concentrations in cultured rat dorsal root ganglion cells were studied using the intracellular fluorescent probes fura-2 and SBFI, respectively. Capsaicin increased both intracellular [Ca2+] and [Na+]. A rise in cytosolic free Ca2+ could still be seen if Na+ was removed from the outer medium. The results suggest that capsaicin opens up ion channels which are permeable both to Ca2+ and Na+.


Increase in synaptophysin immunoreactivity following cortical infarction.

Plasticity in the central nervous system has been demonstrated using lesions of the hippocampus and rhinal cortex but has not been well studied after cerebral ischemia. Focal cerebral ischemia creates an area of infarction that is surrounded by neuronal tissue that may respond to nearby damage by creating new synapses. To determine if synaptogenesis occurs, antibodies to synaptophysin, a calcium-binding protein found on synaptic vesicles, were used with immunohistochemical techniques to assess the level of synaptophysin immunoreactivity as a measure of changes in the number of synapses. Cerebral ischemia was induced in hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery. After 2 months recovery, the animals were perfused and the brains removed for immunohistochemical processing and evaluation. When comparing the cortex surrounding the infarcted area to similar areas on the contralateral side of the brain, the infarcted side had increased levels of anti-synaptophysin like activity that are statistically significant. We hypothesize that this increase in synaptophysin immunoreactivity is due to an increase in synapses in the cortex surrounding an area of infarction and supports the hypothesis of plasticity in the cortex following cerebral infarction.


Absence of dystrophin in two patients with Becker type Xp21 muscular dystrophy.

Two patients with Xp21 muscular dystrophy Becker type showed absence of dystrophin in muscle biopsy tested with 4 antibodies (polyclonal anti-60 kDa, monoclonal against the rod domain, the C-terminus and the N-terminus). DNA analysis did not detect any deletion in one patient and demonstrated deletion of exons 3-7 in the other. The cases represent an exception to the strict correlation between the dystrophin pattern in muscle biopsy and the clinical course of the disease: in fact both the patients are still walking at 14 and 15 years respectively. The possibility of similar cases must be considered not only in the prognosis of Xp21 muscular dystrophy but the more so in the evaluation of therapeutical trials.


Efficacy of D-CPPene, a competitive N-methyl-D-aspartate antagonist in focal cerebral ischemia in the rat.

The effect of a novel and potent competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPPene) upon ischemic brain damage has been examined in a rat model of focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). The animals were sacrificed 24 h after MCA occlusion and the amount of ischemic brain damage was assessed at 8 predetermined coronal planes. Pretreatment with D-CPPene (1.5, 4.5 or 15 mg/kg, i.v.), initiated 15 min prior to MCA occlusion (followed by constant infusion at 1, 3 or 10 mg/kg/h), produced dose-dependent reductions in the volumes of infarction; the dose of 4.5 mg/kg being the most effective (reduced by 37%; P < 0.01). These results indicate that systemic administration of the competitive NMDA antagonist D-CPPene has neuroprotective effects in a model of focal cerebral ischemia and define the dose dependency of its neuroprotective effects.


Intracellular injections of BAPTA block induction of enhancement in Hermissenda type B-photoreceptors.

Light paired with serotonin (5-HT) in vivo produces both short- and long-term enhancement of generator potentials in identified B-photoreceptors in Hermissenda. The role of intracellular Ca2+ in the induction of enhancement in B-photoreceptors was assessed by buffering intracellular Ca2+ with the iontophoretic injection of BAPTA. Blocking light-elicited photoreceptor desensitization with BAPTA loading prior to applying 5-HT was used as an indication of the effectiveness of Ca2+ buffering. Enhancement was blocked in preparations that received BAPTA loading prior to the application of 5-HT while typical enhancement was elicited by light and 5-HT in control preparations. These results indicate that enhancement involves a Ca(2+)-dependent process.


The effect of adenosine on spontaneous and evoked quantal secretion from different release sites of amphibian motor-nerve terminals.

The effects of adenosine on the spontaneous quantal secretion from different release sites along terminal branches of toad (Bufo marinus) motor-nerve terminals was studied. Terminal branches were visualized using 3,3-diethyloxardicarbocyanine iodide (DiOC2(5))-fluorescence to assist in the placement of extracellular electrodes along different release sites of terminal branches. The maximum rate of spontaneous secretions (fe) observed with an extracellular electrode within any 10 microns length of terminal branch declined towards the distal end of the terminal branch as does the average number of evoked quantal secretions (mE). Adenosine (1-50 microM) depressed both fe and me. The ED50 of adenosine in depressing me was 5 microM. Adenosine (10 microM) produced on average a 43% decrease in fe and a 63% decrease in me, regardless of the initial values of fe and me. It is suggested that adenosine has qualitatively similar effects on both fe and me, regardless of their initial size, at different release sites within motor-nerve terminals.


Dopa-decarboxylation in the striata of rats with unilateral substantia nigra lesions.

The source and site of the DOPA decarboxylation to dopamine in Parkinson's disease (PD) and animal models of PD are controversial. Since most of aromatic L-amino acid decarboxylase (AADC) are lost along with the degenerating dopaminergic neurons, we addressed the possibility that other decarboxylases or a novel protein that is structurally different from AADC decarboxylate L-DOPA in the denervated striatum. Immunotitration of the extracts from the denervated striatum with AADC antibody showed that all activity can be attributed to AADC-immunoreactive protein. We then investigated if there are non-dopaminergic intrinsic striatal neurons that express AADC. No evidence of such neurons was noted by immunocytochemistry and in situ hybridization.


Prion protein immunocytochemistry helps to establish the true incidence of prion diseases.

Creutzfeldt-Jakob disease (CJD) and Gerstmann-Strüssler-Scheinker disease (GSSD) are transmissible spongiform encephalopathies or prion diseases affecting man. It has been reported that prion diseases may occur without the histological hallmarks of spongiform encephalopathies: vacuolation of the cerebral grey matter, neuronal loss and astrocytosis. These cases without characteristic neuropathology may go undiagnosed and consequently the true incidence of transmissible dementias is likely to have been under-estimated. Immunocytochemistry using antibodies to prion protein gives positive staining of these cases, albeit the pattern of immunostaining differs from that seen in typical forms. Accumulation of prion protein is a molecular hallmark of prion diseases, and thus a reproducible, speedy and cost-efficient immunocytochemical screening of unusual dementias may help to establish the true incidence of prion diseases.


Residual effects of tracer in sequential double label deoxyglucose studies.

The validity of sequential double label deoxyglucose (DG) determinations of local metabolic rate for glucose (IMRglc) was examined by quantifying the degree of trapping of residual first DG tracer during the second experimental period. One sciatic nerve was repetitively stimulated for 25 min, beginning either at the time of the DG injection or 25 min later. IMRglc in the ipsilateral dorsal horn of the lumbar spinal cord was found to be 105% and 56%, respectively, greater than that of the contralateral unstimulated side. Attempts to lower the body burden of radioactive DG by exchange blood transfusion failed to reduce this delayed effect. These data indicate that residual effects of the first tracer could obscure possible differences in IMRglc between two sequential experimental states.


Chronic ethanol consumption reduces the neurotrophic activity in rat hippocampus.

The effect of chronic ethanol treatment (CET) for 21-26 weeks on the neurotrophic activity contained in the rat hippocampus (HPC) was determined with a bioassay in cultures of dissociated dorsal root ganglion cells (DRG) obtained from E7-8 chick embryos. Extracts of the HPC from CET or pair-fed control rats were used as experimental media, and neuronal survival and neurite-outgrowth of DRG cultures were determined. Both neuronal survival (-25%) and neurite-outgrowth (-50%) were reduced in the presence of HPC extracts from CET rats relative to controls. These data suggest that CET reduces the neurotrophic content of the HPC which may result in damage to septohippocampal neurons.


Developing corticorubral axons of the cat form synapses on filopodial dendritic protrusions.

Developing neurons transiently grow numerous spine- or filopodium-like dendritic protrusions (SLDPs). Electron microscopy on identified input and intracellular staining of postsynaptic cells were performed to gain insight into their significance. Newborn kitten-corticorubral axons, labelled with biocytin, commonly made synapses on SLDP, often multiply invaginated by the SLDPs. Correspondingly, intracellularly labelled kitten rubrospinal cells had numerous SLDPs. Taking into account that corticorubral synapses are largely formed on dendritic shafts in adult cats, it is likely that the SLDPs play some important role in the development of corticorubral synapses. We hypothesize that rubrospinal cells elongate SLDPs searching for corticorubral axons to form synapses.


Connections of the thalamic reticular nucleus with the contralateral thalamus in the rat.

The occurrence of thalamic projections to the contralateral side of the thalamus, and the origin of these projections from the thalamic reticular nucleus, were demonstrated with fluorescent retrograde tracing. After a relatively large tracer injection in the anterior third of the thalamus (involving the reticular, anterior, intralaminar and ventrolateral nuclei), labeled cells were detected in the rostral portion of the contralateral reticular nucleus. The location within the reticular nucleus of the neurons retrogradely labeled in the contralateral thalamus was confirmed by means of the combination of tracing with immunocytochemistry, using antibodies against the calcium binding protein parvalbumin.


Multiple sclerosis patients express increased levels of beta-nerve growth factor in cerebrospinal fluid.

We describe the measurement of beta-nerve growth factor (NGF) content in cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients compared with CSF from age-matched normal subjects using a specific sandwich immunoassay (ELISA). During acute attacks patients exhibit a significant increase of NGF content compared to controls. In contrast during remission the mean NGF levels in CSF markedly decrease. These results strongly indicate that increased NGF production in CSF is a characteristic feature of the MS inflammatory response.


Cellular and molecular effects of trimethyltin and triethyltin: relevance to organotin neurotoxicity.

Many of the neurotoxic aspects of organotin exposure have been described. Organotin exposure culminates in its accumulation in the CNS and PNS. The clinical picture is dominated by neurological disturbances; yet, the primary basis for their neurotoxicity is unknown. Trimethyltin (TMT) is primarily a CNS neurotoxin affecting neurons within the hippocampal pyramidal band and the fascia dentata. Triethyltin (TET) is a neurotoxin that produces a pathological picture dominated by brain and spinal cord edema. The first part of this review summarizes the current understanding of the interaction of TMT and TET with biologically active sites in the induction of neurotoxicity. In the second part, several hypotheses for the differential neurotoxic effects of these organotins and their shortcomings are discussed.


A novel approach to neural transplantation in Parkinson's disease: use of polymer-encapsulated cell therapy.

Transplantation of dopaminergic neurons derived from fetal or adrenal tissue into the striatum is a potentially useful treatment for Parkinson's disease (PD). Although initially promising, recent clinical studies using adrenal autografts have demonstrated limited efficacy. The use of human fetal cells, despite promising preliminary results, is complicated by tissue availability and ethical concerns. An attractive alternative is based on encapsulating dopamine-producing cells into polymer capsules prior to transplantation. Polymer capsules can be fabricated to surround the cells with a semi-permeable and immunoprotective barrier. The semi-permeable membrane allows nutrients to enter the capsule, so the encapsulated cells will survive and function, and dopamine and other low molecular weight constituents to diffuse out into the host tissue. Thus, the technique allows use of unmatched human tissue (allografts), or even animal tissue (xenografts) without immunosuppression of the recipient. Cell-loaded polymer capsules can also be retrieved if necessary or desired. The demonstration that striatal implants of encapsulated dopamine-producing cells promote behavioral recovery in rodent and primate models of PD further suggests that cellular encapsulation may be a useful strategy for ameliorating the behavioral consequences of PD.


Tourette syndrome: issues in diagnosis.

Information was accumulated by self-report questionnaire from 462 Canadian Tourette syndrome (TS) patients. The mean age of onset of the syndrome was 7.4 years, while the mean age of medical diagnosis was 15.2 years, suggesting that the mean lag between onset of symptoms and diagnosis was 7.8 years. Seventy-three percent of patients reported initial misdiagnosis by physicians and only 33% of the patients reported receiving their first information about TS from physicians. Respondents indicated that they were typically diagnosed as having Attention Deficit Disorder, Hyperactivity, or Minimal Brain Dysfunction prior to the establishment of the TS diagnosis. Factors involved in the delay in physician diagnosis of the syndrome, as well as the association between TS and other neuropsychiatric disorders, are also discussed.


Olfactory pathways and the sense of smell.

Rats were trained using operant conditioning to detect isoamyl acetate vapor generated by an olfactometer. They received lesions of olfactory pathways and were tested for retention of the odor detection task and trained on two-odor tasks. Deficits in odor detection and two-odor discrimination were related to the extent to which lesions disconnected the olfactory bulb from the forebrain. Transection of only the lateral olfactory tract, only the anterior limb of the anterior commissure, or lesions of the olfactory tubercle had little effect but combined lesions of these structures produced severe deficits in both odor detection and discrimination. Only rats with almost complete transection of the olfactory peduncle or cortex were anosmic; those with transections that spared a small segment of tissue between the olfactory bulb and olfactory cortex had detectable olfactory function. The results are discussed with regard to efferent connections of the olfactory bulb.


The measurement of extremely low environmental frequencies.

A magnetic sensing device, capable of recording frequencies in the extremely low range of near zero to 20 Hertz, was placed in a shielded room designed to reduce interference from ambient magnetic fields. Frequencies and intensities are presented on selected man-made magnetic fields that may effect the body. The effects of various frequencies emitted on human tissue are unknown, but the equipment and method for measuring extremely low frequencies sets the stage for determining body reactions to dominant frequencies that may entrain a person away from the earth's frequency of 7.83 Hertz. The most dominant frequency on 20 commonly used items is presented, including modalities used for treatment by doctors. In addition, the magnetic and electrical radiation levels are given using a hand-held meter designed for 50 to 60 Hertz. Future research using the new magnetic sensors, which can detect frequencies down to 100 nanogauss, will be used to measure the magnetic field of the human body.


Effects of d-amphetamine on arousal.

This article is a review of studies conducted on the effects of amphetamine on behavior in animals by the late Walter Isaac and his associates. The principle findings and hypotheses developed over the 20 or more years of research are outlined and discussed. d-Amphetamine is thought to affect an organism's behavior by influencing the arousal level, mainly via the visual system.


Sleep and memory. I: The influence of different sleep stages on memory.

A new approach to the sleep stages role in memory is discussed in the context of the two opposite patterns of behavior-search activity and renunciation of search. Search activity is activity designed to change the situation (or the subjects attitudes to it) in the absence of a definite forecast of the results of such activity, but with the constant consideration of these results at all stages of activity. Search activity increases general adaptability and body resistance while renunciation of search decreases adaptability and requires REM sleep for its compensation. Unprepared learning, which is often accompanied by failures on the first steps of learning, is suggested to produce renunciation of search, which decreases learning ability, suppress retention, and increase REM sleep requirement. A prolonged REM sleep deprivation before training causes learned helplessness and disturbs the learning process, while short REM sleep deprivation cause the "rebound" of the compensatory search activity that interferes with passive avoidance. REM sleep deprivation performed after a training session can increase distress caused by a training procedure, with the subsequent negative outcome on retention.


Sleep and memory. II: Investigations on humans.

The positive effect of delta-sleep on retention depends on REM sleep, which facilitates this positive effect, but at the same time has its own inhibitory effect on retention. The nature of this double influence of REM sleep on retention is discussed in the context of the restoration of search activity being the main REM sleep function. Such restoration can explain the indirect positive effect of REM sleep on retention, especially on retention of the unusual and emotionally meaningful information that can cause distress. Psychic activity in REM sleep (dreams) has a direct negative effect on retention, which may be due to the interference between dream images and learned material.


Suppression of sucrose drinking by chronic mild unpredictable stress: a methodological analysis.

Previous studies have demonstrated that chronic exposure of rats to a melange of ultra-mild stressors causes an antidepressant-reversible decrease in the intake of palatable weak sucrose solutions, as well as other evidence of insensitivity to rewards. In the present study, we analyzed some of the behavioral requirements for the suppression of consummatory behaviour by chronic mild stress. Rats exposed to our standard chronic mild stress protocol and tested following 20 h food and water deprivation showed a decrease in intake of 1% sucrose, but not of water or chow. The effect on sucrose intake was also present, but smaller, in non-deprived animals, and wa seen in both singly- and pair-housed animals. Experiments designed to identify the crucial elements of the stress procedure showed that one element, paired housing (in animals normally housed singly) was particularly potent. However, no one element was either necessary to cause the decrease in sucrose intake, or sufficient to maintain the impairment for longer than 4 weeks: Variety and frequency of microstressors appeared to be the essential features of procedures causing a prolonged anhedonia.


Decreased reactivity to sweetness following chronic exposure to mild unpredictable stress or acute administration of pimozide.

Consumption of a palatable wet mash was examined in rats subjected chronically (4-10 weeks) to unpredictable mild stress. Intake of mash containing 0, 10%, or 20% additional sucrose was normal in stressed animals. In control animals, the addition of 30% or 40% sucrose caused a decrease in the quantity of mash consumed, but increased the rate of eating. Both the increase in eating rate and the decrease in intake, at high sucrose concentration, were markedly attenuated in stressed animals (which therefore had higher intakes of very sweet mash and lower rates of eating, relative to control animals). Like chronic mild stress, the dopamine receptor antagonist pimozide (0.2 mg/kg) also increased the intake of a wet mash with 30% added sucrose, while decreasing the rate of consumption. Stressed animals were relatively insensitive to pimozide, though there were significant additive effects on duration of eating (increased) and on postprandial resting (suppressed). The failure of stressed animals to adapt their intake to increases in sweetness, and the similarities between the effects of chronic mild stress and acute pimozide, are compatible with the hypothesis that animals exposed to chronic mild stress are anhedonic.


Chronic mild stress-induced anhedonia: a realistic animal model of depression.

Chronic sequential administration of a variety of mild stressors causes a decrease in responsiveness to rewards in rats, which is reversed by chronic administration of antidepressant drugs. This paper reviews the validity of chronic mild stress-induced anhedonia as an animal model of depression, and the evidence that changes in hedonic responsiveness in this model are mediated by changes in the sensitivity of dopamine D2 receptors in the nucleus accumbens. The review opens with an analysis of the design features of animal models of depression, and ends with a brief account of other animal models of anhedonia.


Effect of drugs influencing 5-HT function on ethanol drinking and feeding behaviour in rats: studies using a drinkometer system.

In the present study, we have investigated how various 5-HT agonists (m-chlorophenylpiperazine (mCPP) (0.1-1 mg/kg), 8-hydroxy 2-(di-N-propylamino) tetralin (8-OH DPAT) (0.125-2 mg/kg) and 5-HT (0.5-2 mg/kg)), the 5-HT uptake blocker sertraline (1-10 mg/kg), and the 5-HT uptake blocker and releaser dexfenfluramine (0.5-2.5 mg/kg), affect ethanol intake in a continual access paradigm using Wistar rats. By means of a drinkometer system the effect of each drug on microdrinking parameters (e.g., drink latency, number, and duration of drinking bouts) was assessed. The effect of various 5-HT antagonists (metergoline, ritanserin, ondansetron, and xylamidine) against the dexfenfluramine-induced suppression was studied. Furthermore, threshold doses for the anorectic and the suppressant effects of mCPP, sertraline and dexfenfluramine on ethanol intake were identified. From these studies, it seemed that similar mechanisms may be responsible for the suppressant effects of the various 5-HT agonists studied (direct and indirect) on ethanol and food intake. The 5-HT3 receptor antagonist, ondansetron, also reduced ethanol (but not food) intake. However, the profile of this effect may suggest an alternative means by which 5-HT3 receptors regulate ethanol intake in the rat by comparison to the various 5-HT agonists studied.


Multifactorial regulation of the hypothalamic-pituitary-adrenal axis during development.

The hypothalamic-pituitary-adrenal system shows an overall diminished responsiveness throughout ontogeny. Thus, during this period, the sensitivity of the adrenal gland to ACTH is markedly reduced. Furthermore, basal and stress-induced concentrations of corticosterone (CORT), ACTH and hypothalamic secretagogues remain at very low levels. Both structural immaturity and active inhibitory processes appear to underlie this overall hyporesponsiveness. The available data indicate that the characteristic developmental pattern of the HPA system results from multiple regulatory factors acting in conjunction at various levels of the axis. The primary rate-limiting steps, however, are probably at the brain and adrenal levels. The ultimate "goal" appears to be to keep CORT levels within the narrow range of concentrations required for normal development.


Schedule-controlled brain self-stimulation: has it utility for behavioral pharmacology?

We review evidence that schedule-controlled intracranial self-stimulation (ICSS) has properties in common with conventional reinforcements, such as food and water, but unlike the latter, animals will respond for ICSS for long periods of time at a near-constant rate. Schedule-controlled ICSS has proven to be more sensitive to drug-induced changes than has ICSS on a continuous reinforcement schedule, and it permits a more fine-grained analysis of the pattern of responding that results in the reinforcement. Evidence is accumulating that the schedule of ICSS itself leads to neurochemical changes in areas of the brain, such as the nucleus accumbens, in which reward processes occur. Results obtained from schedule-controlled ICSS would complement those obtained by drug self-administration studies which generally use intermittent reinforcement. A systematic examination of ICSS schedules at different brain sites would greatly facilitate our interpretation of drug effects and this would have utility for behavioral pharmacology.


Role of dietary fat in calorie intake and weight gain.

This paper reviews the literature on the role of dietary fat in calorie intake and body weight gain in humans and laboratory animals. An overview of 40 animal studies which compared growth on high-fat (HF) and high-carbohydrate (HC) solid/powdered diets indicated that the HF diet elicited greater weight gain in 33 out of 40 studies. Enhanced growth on the HF diet was often, but not exclusively, attributable to greater caloric intake. Additional evidence for the growth-enhancing effect of HF diets emerges from "diet option" and "supermarket" feeding studies in rats, and experimental and epidemiological studies in humans. Three principal factors that contribute to the different responses to HF and HC diets are (a) caloric density, (b) sensory properties and palatability, and (c) postabsorptive processing. It is concluded that both calorie intake and metabolic energy expenditure are biased towards weight gain when a HF diet is consumed, and that the high caloric density of high-fat diets plays a primary role in weight gain. Humans may be biologically predisposed to gain weight when a HF diet is consumed.