[The effect of an unfavorable epizootic situation on the basic epidemiological indices for tuberculosis]. Analysis is given of the basis of epidemiological parameters in two districts of the Novosibirsk region, depending on the duration of the unfavourable epizootic situation. Subjects with extensive residual changes were registered 10 times as often in the district with the unfavourable epizootic situation as in the district with fresh tuberculosis outbreak in animals. Studies of infectivity among children and adolescents at the height of tuberculosis outbreak in animals showed that reversion was established in 8.6%, while the share of children with hyperergic reactions increased by 4 times and exceeded the average regional index by 8 times. Children and adolescents from the district with the unfavourable situation for tuberculosis had a low level of reversion (0.3%), but the level of infectivity in children of the decreed ages was high. The complex of health-improvement, prophylactic and veterinary measures has been suggested.


[The structure of newly detected tuberculosis in persons confined to correctional work institutions]. Tuberculosis morbidity in penitentiary-labour establishments (PLE) is scores of times higher than that among the population on the formation of which it has an influence. Study of the epidemiologic process patterns in PLE and specific features of tuberculosis in convicts is a necessary condition for the development of effective antituberculous measures. Analysis of the structure of newly-diagnosed tuberculosis in convicts has demonstrated that tuberculosis prevailed among subjects aged 30 years (49.2%) and in those at the age of 30-39 years (38.4%). The clinical structure is predominated by infiltrative (57.4%) and focal (36.4%) forms, while fibrocavernous and cirrhotic forms are absent. The organization of measures aimed at the timely detection of tuberculosis in convicts was found to have a number of defects, which contribute to tuberculous infection spread among subjects staying in PLE.


[The organization and efficacy of the hospital treatment of patients with newly detected pulmonary tuberculosis in Siberia]. Analysis of the clinical observations of 2049 patients with newly diagnosed pulmonary tuberculosis has demonstrated that 54.3% of them had the destructive phase, 52.2% bacilli excretion, 20.7% the neglected forms, and 64.3% attendant diseases. The absence of bacilli was found in 82% of the patients with the destructive forms (in 5 months' period after hospitalization), and elimination of caverns in 74.5%. The most serious defects were found in the organization of a diagnostic and therapeutic process. The complex of measures has been suggested to promote heightening of treatment effectiveness in newly detected patients at the hospital stage.


[Primary disability as a consequence of tuberculosis and the factors that contribute to its development]. Analysis is given of a high level of invalidity in 508 patients in four regions to whom invalidity due to tuberculosis was first established in 1987-1989. The main factors responsible for invalidity included progress of a tuberculous process, ineffective chemotherapy, untimely diagnosis, the presence of serious attendant diseases, functional disorders of the affected organs, complication of the disease, asocial way of life (chronic alcoholism, narcomania), and insufficient material provision of large families. Most invalids had a combination of the above factors.


[Primary disability in patients with tuberculous spondylitis and the ways for its decrease]. Causes responsible for invalidity were analysed in 167 patients with a circumscribed form of tuberculous spondylitis. The causes were divided into 4 groups: diagnostic errors; errors in treatment; prognostic errors (late indications to surgical treatment); organizational errors. Heightening of the quality of early diagnosis of tuberculous spondylitis at a primary application to a medical institution and timely high-quality specific therapy in the antituberculous institutions will contribute to an increase in treatment effectiveness and invalidity reduction.


[Tuberculosis morbidity in medical workers and the measures for their social protection]. Tuberculosis morbidity among the medical workers has been studied in 39 territories of Russia. It has been established that medical personnel contract tuberculosis much frequently than the population of Russia on the whole. Morbidity is particularly high among the personnel of institutions of the antituberculous service, being 293.3 per 100,000 working subjects. Tuberculosis morbidity is higher among females (78.8%) and in subjects aged before 50 years (81.4%). Success of tuberculosis control among the medical personnel can be provided by actively solving the problems of tuberculosis prevention, including the organization of health improvement measures under conditions of sanatorium and measures aimed at social protection.


[Risk factors in the development of pulmonary tuberculosis and the characteristics of its course in people over 50]. Study of the onset and course of pulmonary tuberculosis in 121 patients between the ages of 50 and 75 years showed that 31.4% of the patients belonged to a high risk group of tuberculosis. Study also revealed a high frequency of occurrence of disseminated and fibrocavernous tuberculosis, the predominance of disseminated processes, frequent destruction of lung tissue, massive bacilli excretion and marked clinical manifestations of the disease, which develops in more than half of the patients in the period between the established terms of prophylactic fluorographic examination.


[The plastic repair of the residual axillary cavity following the open treatment of a cavern with the tissue from its wall and from the deep subcutaneous fat]. A variant of plastic surgery of the residual cavities after cavernotomy of armpit localization had been elaborated. Cicatricial tissue of the residual cavity wall is preserved and only the upper part of the residual cavity wall is used in combination with deeply-lying fatty tissue of the axillary fossa. Plastic closure of the residual armpit cavities after open treatment was successfully performed in 27 patients. The necessary condition for this operation performance is cessation of excretion of bacilli, sputum and discharge from the residual cavity on condition that the patient is in a satisfactory condition.


[The importance of thoracostomy in treating pleural empyema with bronchial fistulae in patients with pulmonary tuberculosis]. In contrast to the nonspecific pleural empyemas, which are managed effectively by closed methods of débridement, management of patients with tuberculous pleural empyema and bronchial fistulas requires early application of thoracostoma, which allows cavity débridement, long-term antituberculous chemotherapy and preparation to radical surgery. This was confirmed by the comparative analysis of the results of radical operations after closed and open methods of management of empyema cavity in 139 patients. The site of thoracostoma application is determined by the location and size of an abscess and the forthcoming radical operation. Long-action bandages with chlorhexidine bigluconate and ultraviolet radiation are prescribed for the débridement of open pleural empyemas.


[The solitary tuberculoma as a "mask" of a lung tumor]. The results are given of the clinical and X-ray examination of 56 patients who underwent surgery for granuloma which had the course of a "masked" blastoma. Taking into consideration the objective difficulties encountered in differential diagnosis, measures must be taken to perform the intraoperative express diagnosis which will help to avoid tactical errors in relation to the volume of surgical intervention.


[The use of plasmapheresis in treating the broncho-obstructive syndrome in patients with pulmonary tuberculosis]. Examination included 81 patients with the broncho-obstructive syndrome, which in 45 patients was combined with active pulmonary tuberculosis. Plasmapheresis was used in 43 patients. Treatment proved to be effective in patients suffering from bronchial asthma who underwent plasmapheresis; attacks fully discontinued in 70.9 x 8.15 patients. Plasmapheresis had no unfavourable influence on the specific process, it promoted fuller restoration of external respiration parameters and reduction of the level of acute-phase proteins.


[The tuberculosis control work of a general medical network under the conditions of budgetary insurance medicine]. The first results are given of the elaboration of the specific features of antituberculous measures control in the general medical network under conditions of the budget-insurance medicine. The clinico-economic standards have been compiled, which are the obligatory programs of actions of medical prophylactic establishments as well as the required final results (quality standards). Systematization of the tasks of antituberculous work and methods of their solution for feldsher's station is presented as an example. A characteristic is given to the approaches to quality standards compilation A preliminary determination of a necessary volume of knowledge concerning tuberculosis is given as well as the list of the practical skills that a general practitioner should master. The documents elaborated make the basis for the medico-prophylactic establishments to be accredited, for certification of doctors and the evaluation of their work by the insurance companies.


[Tele-electrometry of the respiratory musculature in healthy subjects and patients with obstructive ling diseases]. Respiratory muscles fatigue is a common symptom typical for chronic obstructive pulmonary diseases. The authors were the first to use an original diagnostic system of distant electrometry "Briz-1" and examination techniques. The principle of the diagnostic system operation is based on a contactless measurement of magnitudes of trunk surface excursions during respiratory movements with the help of a system of electromagnetic field transducers located near the trunk. The electromagnetic field is induced by a special generator. Examination included 75 patients with chronic obstructive pulmonary diseases and 21 healthy volunteers (the norm has been elaborated). The results obtained on the diagnostic system were compared with the clinico-functional studies. The method is simple, harmless, easy for patients in terms of load, informative and allows numerous measurements. Diagnostic criteria of obstructive pulmonary diseases and diaphragm fatigue have been developed.


[The assessment of bronchial patency by conducting broncholytic and loading tests in patients with pulmonary pathology]. Reproducibility of the parameters of bronchial patency was studied in 31 patients with nonspecific pulmonary diseases, changes in the parameters of bronchial patency during the berotek and loading tests--in 28 healthy subjects, the dynamics of bronchial patency in these tests and the value of separate methods of study of bronchial patency--in 119 patients with active pulmonary tuberculosis. The parameters of spirography, forced expiration flow-volume and general plethysmography were used. Assessment of the results of the pharmacological and loading tests require consideration of reproducibility of the parameters and their changes in healthy subjects in connection with a broncholytic action on the tone of bronchial muscles. The table of limited diagnostically insignificant functional changes in bronchial patency in given. When evaluating the results of functional tests, it is expedient to use a combination of the parameters of spirography, the curve of forced expiration flow-volume and general plethysmography and in the choice of method preference should be given to the registration of the curve of forced expiration flow-volume. The most sensitive parameters of the dynamics of bronchial patency in the broncholytic and loading tests have been developed.


[The validation of the adequacy of chemotherapy in bladder tuberculosis based on a study of bacteriostatic activity]. Study of the bacteriostatic activity (BA) of the blood, urine and tissue of the tuberculosis-affected urinary bladder after the administration of two tuberculostatic combinations (isoniazid + cycloserine and isoniazid + rifampicin) has demonstrated the difference in the BA curves that were formed in the above media. Use of isoniazid + cycloserine gives rise to a high BA level by 6-9 h with further gradual decrease of the parameters. The combination of isoniazid + cycloserine produces a typical double-humped curve with titre prolongation. The data obtained give evidence on the experience of the use of the first combination of the preparations in patients with fresh circumscribed urinary bladder lesions. The second combination (isoniazid + rifampicin) is indicated in the presence of ulcerous-cicatricial changes in association with a more prolonged circulation of the preparations in the organism (specific features of rifampicin metabolism).


[Experimental models of combined tuberculosis-opisthorchiasis pathology]. An experimental model of the combined course of tuberculosis and opisthorchiasis is presented in the following variants: pulmonary tuberculosis-chronic opisthorchiasis, acute and chronic opisthorchiasis in combination with tuberculosis contamination, BCG and opisthorchiasis. Specific changes in the combined pathology are shown which differ from those that accompany each of the nosological forma. Data obtained in bacteriologic, parasitologic, immunologic and pathomorphologic studies were used to describe characteristic features of the models. The results obtained allow a suggestion that parasitocenosis of mycobacteria and Opisthorchis organisms has an influence on the pathogenesis, clinical picture, diagnosis, treatment, epidemiology and prevention of tuberculosis-opisthorchiasis combined pathology.


[Tuberculosis in the rural population as a public health problem during the organizational perestroika of medical care]. The results of 5 years' observation of the epidemiologic situation for tuberculosis in the northwest region of the Russian Federation have shown that tuberculosis prevalence among the rural population is less than in Russia, on the average. There is a tendency towards disappearance of the epidemiologic differences between the rural and urban locality, which enables one to regard tuberculosis as a single epidemiologic problem. At the same time, high level of tuberculosis contingents is maintained in rural settlements, which can be ascribed to the insufficient effectiveness of treatment or dispensary follow-up. A negative influence of social factors also grows. In conditions of the multivariant character of the organization of the public-health service optimization of work can be achieved by the creation of interregional scientific-practical centres.


The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation. Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activation for the most potent carcinogenic PAH, whereas monooxygenation to form bay-region diol epoxides is generally a minor pathway. For benzo[a]pyrene and 7,12-dimethylbenz[a]-anthracene, 80% and 99%, respectively, of the DNA adducts formed by rat liver microsomes or in mouse skin arise via the radical cation. Therefore, studies of PAH activation should begin by considering one-electron oxidation as the primary mechanism.


Actin mediated regulation of muscle contraction. Striated and smooth muscles have different mechanisms of regulation of contraction which can be the basis for selective pharmacological alteration of the contractility of these muscle types. The progression in our understanding of the tropomyosin-troponin regulatory system of striated muscle from the early 1970s through the early 1990s is described along with key concepts required for understanding this complex system. This review also examines the recent history of the putative contractile regulatory proteins of smooth muscle, caldesmon and calponin. A contrast is made between the actin linked regulatory systems of striated and smooth muscle.


Intensity dependence of auditory evoked potentials and clinical response to prophylactic lithium medication: a replication study. A predictor of clinical response to prophylactic lithium treatment in affective psychoses would be of considerable importance. In a pilot study, responders to prophylactic lithium medication, as compared with nonresponders, were characterized by a steeper slope of the amplitude/stimulus-intensity function (ASF slope) of the N1/P2 component of the auditory evoked potential. We tried to replicate this finding in 34 stabilized outpatients with affective illness who had been treated with lithium for at least 3 years. As in the pilot study, responders were again characterized by steeper ASF slopes than nonresponders. Since a steep ASF slope seems to indicate low central serotonergic function, it is speculated that a steep ASF slope characterizes those patients with a serotonin deficit who respond to serotonin agonists like lithium.


Evaluation of a new instrument for the detection of eating disorders in community samples. The aim of this study was to develop and evaluate an instrument to detect the various forms of clinical eating disorder that exist among young women in the community. A subsidiary aim was to test an alternative instrument based directly on the DSM-III-R criteria for eating disorders. Participants were 285 young adult women listed in the case registers of two general practices. Receiver operating characteristic analysis showed that the new (statistically derived) instrument performed well and was better at case identification than the only other instrument currently available. In contrast, the instrument based directly on the DSM-III-R criteria performed poorly. It was not possible to assess the ability of the new instrument to detect cases of anorexia nervosa since there were no cases in the sample.


Visual information decoding deficits in schizophrenia. Schizophrenic and control subjects were tested on two-flash fusion (TFF) and visual backward masking (VBM) tasks in a repeated measures design. Each subject was tested in a single session. Both tasks used the same equipment and stimuli. There was no difference between the groups in their ability to detect the presence of two separate stimuli in the TFF task. Schizophrenic subjects did require longer interstimulus intervals (ISI) than control subjects to accurately report one of the two targets in the VBM task. Analysis of individual targets reveals that the VBM deficit is a function of the similarity of the target and mask. The more feature detail discrimination necessary, the longer an ISI is required in VBM. The data are interpreted as supporting the conclusion that since the groups did not differ in their performance of the TFF task, which would also have been affected by a sensory abnormality, the deficit in VBM must be explained by reference to a higher level of information processing. The VBM deficit is a failure to decode the target stimulus, and is not simply a function of abnormalities due to an overactive transient channel system.


Melatonin and cortisol secretion in patients with primary obsessive-compulsive disorder. Plasma levels of melatonin and cortisol were measured over a 24-hour period in seven patients with primary obsessive-compulsive disorder (OCD) and seven matched healthy control subjects. In OCD patients, the 24-hour secretion of melatonin was reduced as compared with that in healthy control subjects, whereas its circadian rhythm was preserved. In addition, in OCD patients, the overall secretion of cortisol was higher than that in control subjects, but there was no change in the circadian pattern of cortisol secretion. No correlation was found between clinical parameters and hormone levels.


Relationship of object loss during development to hypothalamic-pituitary-adrenal axis function during major affective illness later in life. Although many studies have attempted to determine whether early object loss influences the risk of developing major affective illness in adulthood, there are few empirical data relating early loss to subsequent hypothalamic-pituitary-adrenal (HPA) axis dysfunction in adulthood. Forty-five psychiatric inpatients admitted for an active major affective illness, all of whom had a previous history of a significant permanent object loss (by death only), were studied retrospectively in this preliminary investigation to examine whether the type and timing of object loss experienced earlier in life would discriminate affectively ill patients who exhibit HPA dysfunction. Several loss variables were found to be statistically significant predictors of cortisol responses following glucocorticoid challenge. A median split of the distribution was used to classify patients into early loss (< or = 19 years) and late loss (> or = 20 years) groups. Analyses for all subjects, early and late loss combined, showed that late loss was associated with higher 11 p.m. cortisol levels. Within the early loss group, however, age of first loss was the most significant predictor of 4 p.m. cortisol levels after dexamethasone challenge. Consistent with the hypothesis that childhood object loss may be associated with long-term alterations in HPA axis function, younger age of loss correlated significantly with higher 4 p.m. cortisol responses. These preliminary data suggest that future prospective investigation of the neurobiological as well as psychosocial consequences of various types of early loss warrant further study.


Cortisol response to intramuscular desipramine in patients with major depression and normal control subjects: a replication study. The authors conducted a double-blind study evaluating the cortisol response to 75 mg of desipramine (DMI), administered intramuscularly to 20 patients with major depressive disorder (MDD) and 20 age- and sex-matched normal control subjects. A blunted placebo-corrected cortisol response to DMI was found in MDD patients in comparison with the normal control subjects. Since the behavioral/side effect and pharmacokinetic profiles of DMI were similar for patients with MDD and normal control subjects, these findings suggest that patients with MDD have an underlying biological insensitivity of the hypothalamic-pituitary-adrenal axis to DMI. It is hypothesized that these findings are consistent with a norepinephrine deficit, an alpha 1-adrenergic receptor insensitivity, or both. Further use of DMI as a neuroendocrine probe for the noradrenergic system is indicated.


Neuroleptic malignant syndrome: results of a prospective study. The occurrence of neuroleptic malignant syndrome was examined in a prospective study of 335 neuroleptic-treated inpatients. It was not possible to identify a single unequivocal case of neuroleptic malignant syndrome. It appears to be a very rare condition in patients who are judiciously treated with relatively low doses of neuroleptics. The concept of incomplete forms of neuroleptic malignant syndrome could not be supported.


Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine. A double-blind clinical trial was carried out to evaluate the efficacy of S-adenosyl-L-methionine (SAMe) in speeding the onset of action of imipramine (IMI). SAMe is a naturally occurring substance that has been shown to possess antidepressant activity with a rapid mode of onset and minimal side effects. Sixty-three outpatients with moderate to severe depression were included in the study. After an initial 1-week placebo period, only 40 patients entered the active treatment phase. During the first 2 weeks of the trial, half of these patients received 200 mg/day of SAMe intramuscularly, while the other half received placebo. Simultaneously, oral IMI was administered to all patients at a fixed dose of 150 mg/day. The onset of clinical response was determined by evaluating patients every second day. By the end of week 2, the parenteral treatment was suppressed and IMI was adjusted according to individual needs. Depressive symptoms decreased earlier in the patients who were receiving the SAMe-IMI combination than in those who were receiving the placebo-IMI combination.


Some refinements of the separation-individuation concept in light of research on infants. The separation-individuation concept, though clinically useful, has been called into question in a critique based on systematic infant research. While an effective rejoinder to the critique can be offered, the critique plus the rejoinder nonetheless require some modifications of the initial separation-individuation concept. Following a summary of the argument, I offer those modifications here.


Thinking through the hungry baby. Toward a new pleasure principle. Freud's metapsychological paradigm and his conception of the neonate were closely linked. The vignette of the "hungry baby" epitomizes Freud's pain-centered, pragmatic understanding of primary motivational forces. Within the range of mainstream psychoanalytic theory, this point of view has remained essential, although in recent decades it has been supplemented in important ways by a more object-centered, moral perspective on character development. But psychoanalysis still lacks a positive metapsychological formulation of pleasure as a motivation in its own right. This paper explores the problem in the light of recent infant research and of Hartmann's systematic reflections on metapsychology.


Did Dora have an oedipus complex? A reexamination of the theoretical context of Freud's "fragment of an analysis". A careful review of the Dora case refutes the commonly held view that it reflects Freud's adoption of his classical oedipal model. Through Dora, Freud examined some of the theoretical and emotional underpinnings of the seduction theory and began a complex and very gradual move toward an oedipal model, never reaching his classical formulation. The transitional nature of this case allows for an understanding of some of Freud's difficulties in adopting the oedipal model and the considerations that, nevertheless, eventually determined the move. How and why this was overlooked in all later studies of the case has important implications for the process of development of psychoanalytic theory and the writing of its history.


Attachment and separateness. A theoretical context for the integration of object relations theory with self psychology. The aims of attachment and of separateness, and their experiential counterparts within the overall sense of self identity, guide the individual throughout the life cycle. Multiple forms of relatedness, based on varying degrees of self-object differentiation and instinctual drive involvement, enable the individual to establish and consolidate a sense of self both as a cohesive and autonomous entity and as inherently attached to others through loving relationships. This theoretical orientation provides a context for integrating Kohut's major conceptual contribution with classical object relations theory. The essence of this integration requires resolution of the challenges that Kohut's concept of "self-object" poses to conventional understanding of the relationship between relatedness and self development.


Winnicott's antitheory and Winnicott's art. His significance for adult analysis. The significance of Winnicott's work for the theory and practice of adult analysis is examined. Winnicott's most valuable contribution was to discern important new clinical phenomena. This is a crucial aspect of theory development, but not the same as explicating new theory, and partly accounts for the difficulty integrating his ideas with traditional psychoanalytic theory. Winnicott left the theoretical revisions possibly necessitated by his discoveries for others to accomplish, and some of this new work is discussed and synthesized. The nature of Winnicott's discoveries, especially the phenomenological field of transitional or intermediate experience, is elusive to define, and is also related to his clinical stance and his attitudes to theory for the purposes of clinical work. His work demonstrates the limits of theorizing and of our theories, and also an attitude toward theory that facilitates clinical and theoretical progress. He also provides conceptual language to discuss what is often called the art of psychoanalysis. Both the value and limitations of studying Winnicott are considered.


What does psychoanalysis have to contribute to the understanding of character? While character is an indispensable term in psychoanalytic discourse, it is not primarily a psychoanalytic term. The psychoanalytic theories of neurosis and development are built around the idea of the "complementary series." While psychoanalysis has powerful theories about the "accidental" complement, it only recognizes the "constitutional" complement, and psychoanalysis has nothing to say about it. Current research may shed more light on this latter component and also provide the data for future psychoanalytic theorizing about character and personality.


The development of a capacity for imagination in early childhood. Imagination as a mental capacity is part of a line of development that begins in the earliest symbiotic interactions between mother and infant, takes further shape as the child moves from dyadic to triadic relations, and culminates in a fully mature capacity to reflect upon in thought one's wishes and feelings vis-à-vis multiple others. Particularly for the 3- to 5-year-old child, imagination represents a special mode of mental functioning which allows him to expand his internal object world, motivates him toward increasingly complex relationships with others, and is a central precondition for the creation of the self-defining fantasies characteristic of the oedipal phase. The central neurocognitive precondition for an imaginative capacity is the ability to distinguish thought from action and understand that others as well as oneself are motivated to act because of mental states such as feelings, beliefs, and fantasies. In this paper, we present a view of imagination that integrates observations from psychoanalytically informed studies of the emergence of fantasy play in the oedipal phase with findings from recent work on how children acquire an understanding of their own and others' mental processes.


Maturational and experiential components of character formation. This paper explores the concept of character from the point of view of its use both in everyday language and in psychoanalytic literature. It also examines, with clinical illustrations, some of the complex interactions of maturation and experience in the formation of character.


Confronting dilemmas in the study of character. Distinctive dilemmas in the psychoanalytic study of character are described. What they are and how they have been addressed illuminate the past achievements and some of the future directions of clinical research.


Narcissistic disorders in children.

Narcissistic disorders in children. This paper discusses children who initially may seem suitable for psychoanalytically oriented treatment but who do not respond in the anticipated manner. Such difficulties in treatment may suggest the presence of a narcissistic disorder. Clinical material from a latency-aged girl is presented to demonstrate the typical difficulties encountered in maintaining a working relationship with such children, and the special frustrations and countertransference issues that are apt to arise. A set of criteria is proposed to help in the diagnosis of a narcissistic disorder, and a treatment approach is suggested.


Rescue fantasies and the secret benefactor. The concept of rescue fantasies is traced from Freud's earliest idea of the rescue of the mother as the fallen woman to later ideas of ambivalent rescue of the father, siblings, and children. Clinical vignettes from work with children and adults illustrate these points as well as reparative rescue fantasies in response to trauma and narcissistic hurt. The contemporary family romance myth of the secret benefactor as rescuer is described. An analytic case presentation explores the narcissistic-masochistic and the positive and negative oedipal meanings of the secret benefactor rescue fantasy. Application to countertransference enactments in the analyst is suggested.


The boy from outer space. An exploration of psychotic catastrophe. This is an account of the initial stages in the analysis of Morton, a latency-age boy. Morton is an unusually interesting case for the exploration of fantasy, to which "we must look for the study of early mental phenomena because phantasy is the lingua franca of that period" (Grotstein, 1977, p. 412).


The function of humor in a four-year-old. A child's attempt at humor in the midst of a psychoanalytic session is examined. A joke is told that began as a dream which the 4-year-old analysand attempted to modify. The joke is not entirely successful from a formal standpoint. This "failure" is examined from the point of view of the anxiety that may have derailed the joke and the developmental immaturity that may have compromised it. A developmental line of the symbolic process is suggested, double meanings and multiple meanings becoming more complex as development proceeds.


Transformations of transference.

Transformations of transference. Transference can be understood to have complementary aspects: the experience in the here-and-now of the relationship with the analyst and the repetition of old relationships. The concept of an enactment is proposed to describe the vivid reexperience of childhood relationships in the here-and-now of the analytic relationship. Countertransference contributions to the enactment are discussed. Transference transformation results from the juxtaposition of the regressive transference enactment and transference experiences that are new and novel to the patient. The analyst can promote such changes by his interpretation of resistances both to the reexperience of the transference repetition and to awareness of the new and novel elements that spontaneously appear in the relationship with the analyst.


The moment of recognition. Rabbinic discourse, infancy, and psychoanalysis. Professionals and educated laymen agree that the past 30 years have brought about a revolution in our understanding of infant development during the very first months of life. The inchoate "blooming buzzing confusion" once felt to characterize the neonate has given way to a well-documented realm of finely tuned perceptions and highly complex interactions. These shifts in our thinking are generally assumed to imply that periods chronologically more remote from our own are conceptually more remote from our modern achievements. But in fact, they are not. I here examine ancient and medieval rabbinic texts and find these "modern" issues discussed. The formulations of these texts, I suggest, sharpen the psychoanalytic focus on the role of the integrative function in very early development.


Some psychoanalytic implications of Chinese philosophy and child-rearing practices. An examination of Chinese philosophy serves to highlight the differences between Chinese and Western Europeans with regard to beliefs about the nature of man, the ideal man, and general world view. These guide child rearing practices which in turn encourage specific personality traits and values. This paper deals with some implications that these differences have for psychoanalytic theory.


Hilda Doolittle and creativity. Freud's gift. The problem of work inhibition in a woman is addressed in terms of a specific case. The paper investigates the patient's view of how such an inhibition was cured in a brief analytic treatment of the American poet Hilda Doolittle conducted by Freud in 1933-34.


Dreams. A developmental and longitudinal perspective. In young children's dreams the infantile wish appears almost undisguised. Freud used this prototypical expression and representation of the infantile wish in a child's dream to bolster his conviction that the infantile wish was at the genetic root of adults' dreams as well. As development proceeds, a child's dream grows in disguise and complexity. This study of one analysand's dreams at age 5, 13, and 20 addresses the complexity from a longitudinal point of view and attempts to track the infantile wish through all of its developmental vicissitudes and disguises.


On feeling and being felt with.

On feeling and being felt with. The development of feelings in early childhood is traced, with special emphasis on the mother's role during the toddler phase when she facilitates her child's transition from sensorimotoric discharge to the mental experience, ownership, and use of modulated affects. Many child analytic patients use defenses to ward off feelings, many have not even reached the developmental level of experiencing feelings. How this difficulty manifests itself, the reasons for the developmental lag, and the analytic means of helping such patients are discussed and illustrated.


Latency development in children of primary nurturing fathers. Eight-year follow-up. This paper is an 8-year follow-up of 17 families in which fathers began as primary caretakers early in the lives of their children. The emphasis is on the developmental consequences for the children, now in the latency period, as well as their psychological experience of the father's increased significance.


Extending the use of rubber dam isolation: alternative procedures. Part I. Most dentists are well aware of the value of the rubber dam in allowing technical excellence; however, few recognize the potential for protecting the dentist and staff against the ever-growing number of carriers of the hepatitis and human immunodeficiency viruses. The effectiveness of the rubber dam as an isolation barrier is dependent on the consistency of its application. Sporadic rubber dam application is therefore a weak link in an infection control program. This paper describes additional modified utilizations of rubber dam, uses that are generally not attempted with restrictive orthodox application methods. In addition, practical hints on other means of retention are offered, with the emphasis on nuisance-free and easy application.


Restorative decision-making behavior with magnification. Assessment of occlusal fissure systems and restorations of amalgam in 100 extracted teeth were carried out by four examiners. An initial assessment, made with the naked eye, was repeated with binocular magnification (x 3). The data indicated that restorative decision-making behavior was modified when magnification was used, with an increase in the number of restorations planned for replacement and an increase in the number of tooth surfaces planned for restoration. Statistical analysis indicated that one of the examiners was particularly sensitive to the use of magnification and modified his treatment planning behavior considerably. As part of the process of adapting to the use of magnification, clinicians should review their decision-making behavior.


Bleaching the natural dentition to match the color of existing restorations: case reports. Vital tooth bleaching has become a popular and successful treatment. This treatment may be performed under controlled conditions in the dental office or it may be used under monitored, prescribed conditions with a 10% or 15% carbamide peroxide solution, applied by the patient at home. This paper presents the use of both types of systems in a unique application to modify the color of the natural dentition to match that of existing restorations.


Visible light-hardened glass-ionomer-resin cement restorations for primary teeth: new developments. Bonded glass-ionomer-silver-cement cement and visible light-hardened glass-ionomer liner and base material have proven to be reliable dentinal and enamel restoratives since the mid-1980s. When used within their limitations, they offer advantages over mechanically interlocked silver amalgam material. A light-hardened glass-ionomer-resin cement restorative material, which appears to have greater wear resistance and fracture toughness than prior glass-ionomer cements, has been introduced. This paper describes use of the new material and discusses its potential future implications.


Dentigerous cyst associated with trauma to a primary incisor: a case report. Trauma to primary incisors is common and poses a challenge to dentists who treat children. Often, the clinical appearance of such teeth does not indicate the underlying pathosis. In this case, a dentigerous cyst developed in association with an injured primary incisor, resulting in loss of a permanent tooth.


Incisor spacing: a sequential orthodontic restorative treatment approach. For those patients presenting with one or more missing incisors, a sequential technique utilizing specific arch wires to level and align the irregular incisor teeth may be used. Auxiliary coil springs are then fitted to redistribute the space prior to the preparation of a prosthesis, the fabrication of which is facilitated by parallel and upright abutments. The space obtained allows esthetically proportioned pontics. Two cases that illustrate this technique are presented.


A concept of restorative treatment during orthodontic therapy. Orthodontic therapy with fixed appliances bears a high risk of plaque accumulation, resulting in demineralization and new carious lesions. Rather than treat incipient lesions in orthodontic patients, most general dental practitioners decide to await future developments. A new concept for comprehensive restorative and endodontic treatment is presented, and its orthodontic implications are discussed.


A unique manual for self-assessment by dental practitioners. The Self Assessment Manual and Standards is produced by the Faculty of General Dental Practitioners of the Royal College of Surgeons of England and the Department of Health as part of a clinical audit program. It is a self-help manual containing a set of clinical standards in 15 aspects of patient care. The standards are concerned with clinical outcomes, rather than techniques, and are intended to be educational, not regulatory. The book's contents and applications are described in detail, together with its political background and possible use in an international context.


Clinical performance of posterior composite resin restorations. Two formulations of posterior composite resin (P-30 and Bisfil-P) were evaluated and compared to a high-copper, dispersed-phase amalgam (Dispersalloy). One hundred twenty-eight restorations were placed in 27 patients so that each patient received at least one of each material. After 3 years of clinical service, all three restorative materials produced clinically acceptable restorations, according to US Public Health Service and Leinfelder criteria. The amalgam restorations, however, underwent less wear (44 microns) than did the posterior composite resin restorations (60 to 74 microns). Stratification of data by type of tooth, class of restoration, and size of restoration produced the same ranking of wear from lowest to highest: Dispersalloy, Bisfil-P, and P-30. Resin restorations showed 45% more wear in molars than in premolars, and more wear was associated with moderately sized restorations than with conservative restorations. The surface texture of restorations of composite resin with porous strontium glass filler was nearly as smooth as that of enamel and was significantly smoother than that of the restorations of composite resin with zinc glass filler or of unpolished amalgam.


Postextraction hemostasis in patients on anticoagulant therapy: the use of a fibrin sealant. A simple and safe method of achieving hemostasis after tooth extraction in patients on anticoagulant therapy is described. The use of a tissue sealant turns a complicated, difficult, and risky dental procedure into a simple one, suitable for any dental clinic. Sixty-one teeth were extracted in 23 sessions. Only four cases of very slight postsurgical bleeding were reported. Dental treatment of the majority of these medically compromised people can be performed by private practitioners, without referring the patients to specialty care centers.


The use of hypnosis with eating disorders. This paper reviews the literature on the use of hypnosis in the assessment and treatment of eating disorders. It proposes that patients with eating disorders ought to be investigated as to the underlying dynamics behind the eating disorders symptoms. Following a thorough assessment, a number of hypnotherapeutic techniques are explained and discussed, such as: general relaxation and calmness, guided imagery, teaching self-hypnosis, ego-strengthening, direct and indirect suggestions for healing and recovery, cognitive restructuring and reframing, symbolic guided imagery, age progression ("back from the future" technique), metaphorical prescriptions, age regression and abreactions, and ego state therapy. Verbatim examples of these techniques are given as illustrations of how to use them.


Untoward effects associated with hypnosis. There are numerous reports of untoward effects associated with hypnosis but no reports of hypnosis per se causing a serious untoward effect. The context and manipulations performed are markedly different in the various settings where hypnosis is used. The various settings such as stage hypnosis, amateur hypnosis, clinical hypnosis, and research hypnosis must be considered separately when discussing untoward effects. Although the incidence of untoward effects has been studied in the research setting, the incidence of untoward effects is difficult to assess in some settings (such as stage and amateur hypnosis) and has not been adequately assessed in the clinical setting. After reviewing the literature on untoward effects in these various settings, I conclude that amateur and stage hypnosis should not be done because the risk is not balanced by possible benefits. Research hypnosis and clinical hypnosis by well-trained practitioners are safe procedures if certain guidelines are followed.


Uses of hypnosis in treating anxiety states. Hypnosis has come to be recognized as a potent antianxiety intervention which can be incorporated into a wide variety of psychotherapeutic models. It can play an important role in facilitating treatment of anxiety states, whether the treating clinician's orientation is biological, dynamic, interpersonal, cognitive or behavioral. The primary focus of this article is one the use of hypnosis in treating generalized anxiety disorder. An emphasis is placed on a behavioral or learning perspective. A specific treatment approach using this orientation is outlined and a case example is presented.


The use of hypnosis with dissociative disorders. The dissociative disorders are characterized by difficulties in the integration of memory and/or identity. Typically this is manifested by amnesia and either the development of alternate identities or an estrangement from one's own identity. Spontaneous and self-generated dissociative states and phenomena sharing much in common with those that can be induced with hypnosis are thought to play a major role in their development, symptomatology, and perpetuation. Medical heterohypnosis offers a powerful tool to reestablish a functional continuity of memory and identity in many such cases. The application of hypnotic interventions in the treatment of such conditions will be discussed, explored, and illustrated with clinical vignettes.


The use of hypnosis with hemophilia.

The use of hypnosis with hemophilia. The Colorado program to treat hemophiliacs using hypnosis has been described. Those using hypnosis have realized a reduction in the need for transfusions, which results in a decrease in the development of inhibitors, less potential exposure to the AIDS virus and a lower incidence of liver and kidney damage. A decrease in the frequency and severity of bleeding episodes results in less morbidity and better coping in the face of HIV infection. Self-hypnosis has provided many bleeders with increased feelings of control and confidence and improved the quality of their lives. The field of psychoneuroimmunology gives a scientific rationale for what we have clinically recognized and implemented for years: self-hypnosis to alleviate stress has the potential to improve immune functioning. In bleeders and others who are HIV positive, it may augment medical attempts to impede the onset of AIDS.


Presence and release of immunoreactive atrial natriuretic peptide in granulosa cells of the pig ovarian follicle. Atrial natriuretic peptide (ANP) has been reported to be locally synthesized in the ovary although its physiological roles are still unknown. To define the origin of ovarian ANP, we demonstrated the presence and release of immunoreactive (ir) ANP in pig granulosa cells and characterized its biochemical properties. Serial dilution curves made with the extracts of pig granulosa cells, their perfusates and follicular fluid were paralleled to the standard curve of ANP. The amount of irANP in the granulosa cell was 2 fg/cell. The total amount of irANP in granulosa cells significantly correlated with the levels of irANP in follicular fluid. Additionally, the total content of irANP in the follicle negatively correlated with the follicular size. On reverse phase HPLC, the major form of irANP in granulosa cells and follicular fluid was high molecular weight but that in perfusate was low molecular weight. In Northern blot analysis, ANP mRNA was detected in the pig granulosa cells. Immunohistochemistry showed ANP prohormone location in granulosa cells of rat ovary. These data strongly suggest that the granulosa cells synthesize and secrete ANP.


Vasodilator action of guinea pig vasoactive intestinal polypeptide (VIP): comparison with common mammalian VIP. The vascular activity of guinea pig (gp) and common mammalian (p) VIP were compared in anesthetized guinea pigs and dogs. In the guinea pig, intravenous injections of gpVIP and pVIP increased pancreatic blood flow and reduced the systemic arterial pressure and pancreatic vascular resistance in a dose-related manner. There were no significant differences in the vasodilator actions of these two VIPs, indicating that the overall cardiovascular actions of gpVIP and pVIP are similar in guinea pigs. In the dog, gpVIP, when given intra-arterially, was less potent (about 1/4) than pVIP in its action on femoral blood flow, suggesting that the blood vessels of the dog hind leg are more sensitive to its own VIP than to gpVIP. Oxidation of pVIP and gpVIP with H2O2 greatly reduced their vasodilator effects on the femoral arterial blood flow. The vascular effects were restored to control levels by reduction of the oxidized peptides with mercaptoethanol, which suggests that methionine residues of gpVIP and pVIP are important in the vasodilator effect on the femoral arterial bed in dogs.


[Arthroscopic meniscectomy. Comparison of the functional results of meniscectomy in patients above and under 45 years of age. Apropos of 107 cases]. A comparative retrospective study of 107 cases of arthroscopic meniscectomies performed between December 1985 and December 1988 on 52 operated patients under 45 (P1 = 54 knees) and 52 operated patients over 45 (P2 = 53 knees). Those two populations have been selected among 292 isolated meniscal lesions files (without anterior cruciate ligament tear) operated for arthroscopic meniscectomy between 1985 and 1988. There were 81 medial meniscus lesions, 16 lateral meniscus lesions and 10 bi-meniscal lesions. The follow-up was for 1 to 5 years with a score of 70.3 per cent functional satisfactory results for the above 45 years (P2) and a score of 89.4 per cent below 45 (P1). Regarding the medial meniscus lesions only, we count 76 per cent (P2) satisfactory results versus 87.5 per cent (P1). This assessment can be easily explained by the variety of meniscal lesions (8 degenerative meniscal lesions among P2 namely 15 per cent), by associated cartilage lesions of the medial compartment of the knee (medial condyle: P2 = 37.75 per cent, medial tibial plateau: P2 = 41.5 per cent) and by genu varum deformity. However, in spite of this significant statistical difference (alpha < 0.05), we don't think we should condemn the arthroscopic meniscectomy over 45: the morbidity is very low and if some patients were not cured, the majority of them said that they improved after the operation. The cartilaginous degenerations of the medial compartment, discovered during arthroscopy, in a context of genu varum, don't need any tibial osteotomy at first, especially if they are asymptomatic and without tibia varum.


[Meniscal injury in the plastic reconstruction of the anterior cruciate ligament. Meniscal suture or abstention]. The purpose of this study was to observe the change of the meniscal lesions, which are conservable by suture or simply by leaving-in-place within the frame of operated anterior instability. Forty-six knees which had been operated by the free transplant of bone-patellar tendon-bone, presented the associated lesions of conservable meniscus. These lesions were treated by suture of the meniscus in 15 cases and left in place in 31 cases. The programme of rehabilitation was the same in the two groups. All the patients have been followed-up for 26 months in average (12-40 months). In the group of meniscal suture, only one secondary meniscectomy was carried out. 8 patients presented moderate pain on the corresponding femorotibial joint line and 5/13 of the sportive patients recovered to the same level of activity. In the group of leaving-in-place, no meniscectomy has been carried out. Only 4 patients complained of pain and 23/27 recovered to the same activity level. The arthrographic and arthroscopic observations have been carried out in 23 cases. They confirmed the cicatrization of the sutured meniscus but also showed the possibility of total or partial cicatrization of the lesions left in place (12 on 13). The authors conclude that the peripheral meniscal lesions associated with the operation of the chronic anterior instability do not always require suture. The abstention on the meniscal lesion is possible if it is limited on the posterior segment: Then the functional results seem better.


[Recurvatum in arthritic genu valgum. Contraindication for osteotomy and unicompartmental prosthesis]. Nine lateral gonarthroses were accompanied by a preoperative recurvatum. The recurvatum of arthritic origin is rare. It appears only at a late stage of the arthritis evolution in the genu valgum. Considering the series results, it constitutes a contraindication to the treatment by osteotomy or by unicompartmental prosthesis.


[Instability and misdiagnosed or neglected dislocations of the upper cervical spine in children. Apropos of 20 cases]. Neglected instabilities or luxations of the upper cervical spine in children are rare if one discards conditions such as chondrodysplasia, Down Syndrome or others, were the spine is known to be at high risk of instability. We have studied twenty cases of neglected luxations and the delay in diagnosis is explained either by the asymptomatic character of some of these lesions, or by the difficulty in diagnosis. At the occipito-atlantal level we have reviewed: an instability in translation which required an occipito-axial fusion; two compensatory counter occipito-atlantal luxation of an atlanto-axial rotatory fixation. The diagnosis was best made with computed tomography scan and the treatment was not much different from the isolated atlanto-axial rotatory luxation. An instability in flexion extension, which was merely followed at regular intervals. At the atlanto-axial level 9 cases of sagittal instabilities in kyphosis and translation with a distance between atlas and axis of more than 5 mm were observed. These instabilities were most often associated with a malformation of the cranio-cervical junction; their treatment was usually surgical by means of an atlanto-axial or occipito-axial arthrodesis depending on the case. 9 other cases of atlanto-axial rotatory luxations were either isolated (7 cases) or associated with a counter occipito-atlantal rotatory subluxation (2 cases). Their diagnosis was made on routine X-rays, but the complete or incomplete aspect of the luxation, as well as its fixed aspect, was best appreciated with dynamic CT scan. Their treatment was always started with collar neck or halo traction in order to obtain, reduction of the dislocation, or at least the disparition of the torticollis and the head straight up on shoulders. The stability of the spine was achieved with a minerva cast jacket, halo cast or spine fusion depending on the case.


[Surgical treatment of scoliosis in bed-ridden patients with cerebral palsy]. Thirty-two scoliosis in total body involved children with cerebral palsy (CP) were reviewed. Mean preoperative angle was 13. Average follow-up was four years. Surgery included a single posterior (11 cases) or anterior (3 cases) approach and a double stage anterior and posterior procedure in 18 cases. Fusion was extended to the sacrum in 15 cases. Complications were numerous: 3 deaths, 15 postoperative complications in 10 patients. Most of them were septic and cutaneous. Cobb angle was 78 degrees before surgery, 28 degrees after surgery and 32 degrees at follow-up. Functional status was improved in most of cases. Pain disappeared in 2/3 of cases. Sitting position was acquired in all cases at follow-up; motor possibilities were improved in 1/4 of cases; associated medical pathologies (mainly respiratory) were reduced in 2/3 of cases.


[Treatment of metastases of thoracic and lumbar vertebrae with predominant corporeal involvement by osteotomy of the vertebral body and anterior approach with cement and screwed plate]. Forty-seven patients with predominant corporeal thoracic, thoraco-lumbar or lumbar vertebral metastases were treated surgically by corporectomy. The vertebral body was replaced by acrylic cement sustained by a vertebral U shaped plate screwed to the adjacent vertebral bodies: this corporectomy was completed in 17 cases by a posterior approach. In 9 cases it allowed to treat a posterior epiduritis. The spinal metastases were symptomatic in 45 cases (pain and/or neurologic deficit); 22 of the operated patients were bed-ridden, either due to an important pain (16), or due to a severe neurological deficit (6). In 36 cases, the intervention was done on the spinal lord segment (7 times on the upper thoracic column). The patients were authorized to get up the fifth or sixth postoperative day. The functional results, at a price of 15 per cent of mortality during the first two postoperative months, were satisfactory and stable in time (particularly, 70 per cent of the operated patients with neurologic deficits were improved and 13 of the 21 bed-ridden became autonomous). The intracanalar decompressions controlled by a postoperative myelography, were nearly always total. The sets were stables in time when the block of cement was sustained by a metallic device. The mortality and the functional failure with pain and neurological impairment occurred essentially, when there was spreading of the tumor to the peri-vertebral soft tissues and when there was epiduritis extending beyond the bone lesion. Thus, to be perfectly efficacious, the anterior surgery of the vertebral metastasis, which gives durable and better results than the posterior one, should be soon enough integrated, in the global treatment of the metastatic disease.


[Supracondylar fractures of the humerus associated with ipsilateral fractures of the forearm]. We report 20 cases of ipsilateral supracondylar elbow fracture and forearm fracture in childhood. The mean follow-up was 20 months. For an analysis of the results, we used a global rotation of the upper limb. We appreciated the motion and the carrying angle of the elbow and the wrist. 15 cases were very good or good; there were 4 cubitus varus without functional impairment and 1 failure after one open Monteggia fracture. The therapeutic strategy is discussed. If one does not want to increase the damage to periosteum in the elbow during the forearm reduction, one must first reduce the supracondylar fracture and fix it by 2 pins like in Judet procedure. Then, the forearm fracture should be treated conservatively.


[Screwed acetabulum: results of 72 cases with a mean follow-up of 5 years]. Ninety-seven threaded acetabular prostheses (44 cups of Lord and 53 Motta, type cups) were implanted among which 72 were examined at an average follow-up of 5.9 years. After an initial phase of good tolerance, the results became rapidly degraded. Clinically, the lack of fixation was translated by a start up pain. On examination, the pain provoked by the opposed hip flexion was pathognomonic. A radiographic analysis of our checks allowed us to classify them in four types: Type I: painful hip, normal radiography or presence of a radiolucent line in one of the DeLee's zones; increased uptake at bone scanning. Type II: total radiolucent demarcation; Type III: axial migration; Type IV: migration and tilting; Finally analysis of our series with Kaplan-Meier method showed a survivorship rate at five years of 59.3 per cent. It is concluded that this kind of implant must be abandoned.


A V(D)J site-specific recombination model involving no compulsory double-stranded break formation at the coding segments. Complete immunoglobulin and T-cell-receptor genes are assembled by site-specific recombination of separately encoded gene segments. We present a novel recombination model which accounts for all the characteristics of V(D)J recombination that have been described. The sequence of events proposed implies no formation of double-stranded breaks at the coding ends, ensuring continuity between the recombination partners during the reaction, and solves the problem of the ligation of extremities which have no complementarity. According to this recombination model, the formation of covalently sealed coding ends does not constitute a compulsory step in the recombination process.


Human monoclonal IgM antibodies from foetal B-cell hybridomas directed against a surface antigen on human tumour cells. In order to assess the existence of B lymphocytes capable of producing anti-tumour antibodies in non-tumour-bearing individuals, human lymphocytes derived from foetuses and adults were fused with the heteromyeloma cell line CB-F7. By indirect immunofluorescence, 29 out of 4,472 IgM-producing hybridomas (from 8 foetuses and 8 adults) were shown to produce antibodies which bind to colon carcinoma lines Colo205 and SW620, Raji lymphoma cells and small cell carcinoma of the lung. In vitro growth of tumour cells recognized by these antibodies was inhibited. The antibodies also mediated complement-dependent cytotoxicity. All antibodies tested recognized a cell surface molecule of 55 kDa. Southern blot hybridization analysis of hybridoma DNA with a human JH probe showed that the hybridomas were derived from clonally unrelated B cells. These results demonstrate that human foetal and adult B cells from non-tumour-bearing individuals are able to produce IgM antibodies recognizing defined cell surface molecules expressed on some tumour cells.


Molecular architecture of helicoidal proteinaceous eggshells. I will not attempt to summarize this chapter, which is already a summary. I merely wish to point out that experimental and theoretical evidence to date clearly suggests that antiparallel beta-pleated sheet dictates self-assembly in helicoidal proteinaceous eggshells. Molecular details of this process have started to become clear after the development of the specific, most probably correct, protein structural models in the case of the silkmoths, where amino acid information is available and with the help of several experimental techniques. However, for people seeking universal mechanisms the picture should still be far from complete. Several analogous systems should be studied before providing final answers.


Ultrastructural changes in mouse peritoneal mast cells in response to L-leucine methyl ester or anti-IgE. We studied the ultrastructural features of mouse peritoneal mast cells in response to a non-immunologic lysosomotropic agent, L-leucine methyl ester (Leu-OMe), as compared to well-known immunologic stimulation mediated by anti-IgE antibodies. Total peritoneal exudate cells were collected from CBA/J mice, with mast cells representing 3 to 8% of total cells. The secretory granules in unstimulated mast cells were heterogeneous in size and shape, but intragranular material displayed a homogeneous electron-dense appearance. Stimulation with either Leu-OMe, for Leu-OMe doses lower than 1.5 mM, or anti-IgE was associated with fusion of the granule membranes with one another and with the plasma membrane, as evidenced by morphologic changes noted by electron microscopy. Ultrastructurally, electron density characterizing the granular matrix decreased to varying degrees in the granules, as did its homogeneity, even within a given mast cell. At higher Leu-OMe doses (> 1.5 mM), the effect of this lysosomotropic compound on mast cells was associated with an apparent loss of membrane and cellular integrity, suggesting high Leu-OMe dose-mediated cytotoxicity. These results show that activation induced in mouse peritoneal mast cells by Leu-OMe and anti-IgE may have distinct characteristics, as assessed by morphologically different patterns. Furthermore, high Leu-OMe doses (> 1.5 mM) induced cytotoxicity targeted toward mast cells.


Secretory proteins of Chironomus salivary glands: structural motifs and assembly characteristics of a novel biopolymer. Salivary glands of Chironomus synthesize a family of at least ten secretory proteins that can be grouped into three size classes: the large (about 1000 kDa), intermediate (100- to 200 kDa), and small (less than 100 kDa). After synthesis, secretory proteins undergo a dramatic transformation to form a novel biopolymer. Secretory proteins accumulate in the central lumen of the gland, forming dissociable complexes that appear as a network of smooth fibrils and multistranded beaded fibers. When secretory protein complexes are extruded through the secretory duct, the fibers become oriented in parallel arrays; when these parallel arrays of fibers emerge from the mouth of larvae they are an insoluble, silk-like thread. Regulation of secretory protein-coding gene expression determines which secretory proteins are synthesized, thus, the composition of silk threads. At least two types of threads are produced: larval silk is used to construct tubes for protective housing and assist with feeding; prepupal silk is used to construct tubes for larval/pupal ecdysis (pupation). Variations in composition presumably contribute to different mechanical properties of larval and prepupal silk threads. Since the macroscopic physical properties of polymerized silk most likely reflect the microscopic structure and interaction of secretory proteins, it becomes important to learn the principles which govern secretory protein assembly at the molecular level. Which secretory proteins interact and what are the sites used for intraportein and protein-protein interactions during the assembly of this biopolymer? All eight secretory proteins characterized thus far contain tandemly repeated peptide sequences (ranging from 14-90 amino acids in length) and/or a periodic distribution of Cys residues. These motifs appear to be unique; no other biopolymer has either the repeated peptide sequences or composite structure of chironomid silk threads. The evolutionary conservation of motifs within repeats and among different secretory proteins suggests that the sequences and three-dimensional structures of the motifs may be important for assembly of secretory proteins into complexes, oriented fibers, and silk threads. Further study of secretory protein assembly will bring us closer to understanding how this silk assembles in vivo. By learning principles that nature employs to construct such a novel composite biopolymer, it may become feasible to design and produce new classes of fibers or biomolecular materials with distinctive properties that are currently unavailable.


Detection of autologous antiidiotypic antibody-forming cells by a modified enzyme-linked immunospot (ELISPOT). We describe here the utilization of a modified enzyme-linked immunospot assay (ELISPOT) in order to detect an autologous antiidiotypic response in mice at the level of single antibody-forming cells (AFC). Severals assays have been routinely used to detect anti-Id producing cells; however, these approaches often produce contrasting data. We present results obtained with the modified ELISPOT, using as a model system the antiidiotypic response in mice after immunization with a vaccine from Streptococcus pneumoniae R36a, expressing the immunodominant epitope phosphorylcholine (PC). The response to PC is mediated by a large fraction of antibodies bearing the public idiotype T15. Mice of different genetics make up were immunized with a single injection of the vaccine. We observed that one mouse strain (D1.LP) out of three was able to mount a significant anti-T15 response during the primary anti-phosphorylcholine response. BALB/c and C57BL/6 mice did not produce significant levels of anti-T15 antibody following a single injection of the antigen. In contrast, BALB/c mice which were repeatedly stimulated showed a specific anti-Id response. Experimental controls were performed using either specific anti-T15 monoclonal antibodies (mAb) or splenocytes from mice immunized with TEPC15 myeloma protein in complete Freund's adjuvant.


Clinical and family studies in Hungarian patients with gout. In this study we examined 22 Hungarian male probands with gout and 105 of their first degree relatives. This was the first family study in Hungary in which the characteristics of distribution of gout and hyperuricaemia among patients with gout and their first degree relatives, as well as the possible correlation between the prevalence of the disease and MHC class I antigens was investigated. Our gout patients showed the following characteristics: (1) There was a typical onset after age 40, benign oligoarticular form of arthritis, underexcretion of uric acid, moderate hypertension without evidence of reduced renal function, and a relatively high frequency of hyperostosis. (2) The prevalence of hyperuricaemia and gout exceeded the general population level in the first degree relatives of our gout patients. (3) The distribution of MHC class I antigens among the first degree relatives of our patients with gout showed no characteristic patterns. (4) There was no correlation between HLA B27 antigens and prevalence of gout or hyperostosis in family sibling studies. (5) The high frequency of gout and hyperuricaemia, as well as the lack of characteristic HLA patterns among the first degree relatives of gout patients in our family studies, point to the possible cumulative effect of several genes and environmental factors in the etiopathogenesis of this disease.


MHC associations of autoantibodies against recombinant Ro and La proteins in systemic lupus erythematosus. Results of a multicenter study. SLE Study Group. Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies.


Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis. German Lymphokine Study Group. The controlled clinical trial reported here is part of a multicenter clinical and basic research project, sponsored by the German Federal Minister of Science and Technology, directed by a standing commission of the president of the Max-Planck-Gesellschaft, and coordinated by the Max-Planck-Institut für Biochemie, München. Overall, 249 patients with rheumatoid arthritis (RA) were enrolled by 16 participating hospitals. In addition to NSAID treatment, patients were randomly given either interferon gamma (IFN-gamma) or placebo. In the IFN-gamma group, 107 patients were evaluated and in the control group, 116 patients were evaluated. The response rate after 3 months of treatment, according to joint pain indexes, was significantly higher in the IFN-gamma group with an error probability of 1%. IFN-gamma was able to reduce the quantity of corticosteroids administered. Compared with the control group, the IFN-gamma group benefited considering all parameters measured. Most important side effects were transient fever and transient influenza-like symptoms; all other adverse events were comparable in both groups.


The relative roles of C4A and C4B in prevention of immune precipitation, solubilisation and immune adherence. C4A and C4B levels were measured in serum from 246 normal individuals. Complement-mediated solubilisation, assayed using alkaline phosphatase anti-alkaline phosphatase immune complexes (IC), correlated with both C4A and C4B levels. However, C4A and C4B levels showed no correlation with solubilisation of bovine serum albumin (BSA) ICs, or with the prevention of immune precipitation of BSA or alkaline phosphatase ICs, nor with immune adherence assayed using thyroglobulin and BSA ICs.


Abnormal galactosylation of serum IgG in patients with systemic lupus erythematosus and members of families with high frequency of autoimmune diseases. Gas chromatographic carbohydrate analyses of IgG from 30 patients with idiopathic systemic lupus erythematosus (SLE) revealed lower content of galactose when compared to that in 36 controls of similar ages (mean +/- SD, 3.18 +/- 0.66 vs 3.82 +/- 0.41 galactose residues/mole of IgG, P < 0.001). Abnormal galactosylation was observed in 60% of SLE patients. Analyses of IgG from 58 members of five families, characterized by a high frequency of SLE and other autoimmune diseases and serological abnormalities, and 51 controls of similar age range revealed that IgG galactose deficiency was detectable not only in some members with clinical and serological abnormalities (P < or = 0.001), but also in those without evidence of autoimmune diseases or abnormal serologies (P < or = 0.001). These data indicate that abnormal galactosylation of IgG frequently occurs in asymptomatic members of families with a high frequency of SLE and other autoimmune diseases and suggests that this abnormality may be an indicator for the development of these diseases.


Transferrin microheterogeneity in rheumatoid arthritis. Relation with disease activity and anemia of chronic disease. We studied the relation between disease activity in rheumatoid arthritis (RA) and the microheterogeneity of transferrin. Using crossed immuno isoelectric focusing, transferrin microheterogeneity patterns were analyzed in sera of healthy individuals, nonanemic RA patients, iron deficient RA patients and RA patients with the anemia of chronic disease (ACD). In all RA groups a significant shift in the microheterogeneity pattern was observed, reflecting increased synthesis of transferrins with highly branched glycan chains. Increased disease activity correlated with both the induction of ACD and the change in transferrin glycosylation, which was, therefore, most pronounced in ACD. Generally, an increased synthesis of glycoproteins is accompanied by alterations in their glycosylation pattern. Since transferrin is a negative acute phase protein, our results indicated that changes in synthetic rates and changes in glycosylation induced in the acute phase response are regulated independently.


Osteocalcin in patients with rheumatoid arthritis--effect of anatomical stages, inflammatory activity and therapy. The aim of this study was to investigate whether the degree of inflammatory activity, the anatomical stage and various treatments have an influence on bone turnover in patients with rheumatoid arthritis (RA). Osteocalcin (OC) and other parameters of bone turnover were measured in 131 patients with RA. The mean values of alkaline phosphatase (AP), but not of OC were significantly (P < 0.01) higher in our patients compared to controls. In contrast to AP, OC values increased and correlated significantly (r = +0.33, P < 0.01) with ascending anatomical stage in women not on glucocorticoid treatment. As regards therapy, we found significantly lower OC levels in women receiving steroids compared to controls (P < 0.03) and those being treated with non-steroidal anti-inflammatory drugs (NSAIDs) (P < 0.03), methotrexate (MTX) (P < 0.05), or gold (P < 0.01). Females treated with gold had higher OC levels than patients receiving no antirheumatic drugs (P < 0.03). Furthermore, there was a significantly negative correlation between OC and inflammatory activity [C-reactive protein (CRP)] (r = -0.25, P < 0.003). In conclusion, OC levels were significantly higher (P < 0.032) in patients with advanced (anatomical) stages of RA. In contrast to AP, changes in bone turnover, such as suppression of bone formation by steroids and high inflammatory activity in patients with RA, were easily detected.


Studies on carrageenan-induced arthritis in adult rats: presence of nerve growth factor and role of sympathetic innervation. Recent studies effected by our Institute indicate that various forms of human arthritis express both immunohistochemically and biologically active nerve growth factor (NGF) in the synovium. In the present study, we used a model of carrageenan-induced arthritis to further evaluate the effects of joint inflammation on NGF level. These studies showed that experimentally-induced arthritis in rats caused a significant increase in NGF in the perivascular area of the synovium. We also showed that injection into the synovium of purified NGF did not cause inflammation per se and that the destruction of peripheral sympathetic innervation significantly reduced both the inflammation and the level of NGF following carrageenan injection.


A prospective study of tumor markers CA 125 and CA 19.9 in patients with epithelial ovarian carcinomas. In a prospective study, CA 125 and CA 19.9 serum levels were measured in 229 patients with ovarian cancer [121 with active disease, 108 in complete remission (CR)], and in 20 patients with other malignancies. Abnormal levels of CA 125 were found in 90% of patients with active ovarian cancer, in 1.8% of those in CR and in 38% of cases with other malignancies. Abnormal CA 19.9 serum levels were found in 36, 9 and 48% of these groups, respectively. Serum levels of both tumor markers were related to tumor stage and histological type. The highest levels of CA 125 were found in serous adenocarcinoma and the lowest in the mucinous type (p < 0.0001). In contrast, significantly higher CA 19.9 values were found in mucinous carcinoma than in other histologies (p < 0.0001). CA 125 and CA 19.9 were useful for monitoring disease activity in 88.3 and 32%, respectively, while one or other tumor marker was useful in 92% of patients. At the time of the second-look operation, abnormal CA 125 serum levels were found in 32% (6/19) of patients with active disease and in none of those with CR (0/38). CA 125 sensitivity was 83% (5/6) in those patients with residual tumor > 2 cm and in 8% (1/13) in those with tumor < 2 cm. CA 19.9 values were abnormally high in 16% of cases with persistent disease and in 11% of CR patients. In conclusion, our results confirm that CA 125 is a useful marker in ovarian carcinoma. CA 19.9 improves the results obtained with CA 125 alone only in mucinous adenocarcinomas.


Combined evaluation of serum CA 125 and CAM 29 in patients with epithelial ovarian cancer. We examined 92 patients with epithelial ovarian cancer and 262 patients with benign ovarian diseases undergoing laparotomy. On the basis of a nonparametric method, antigen levels corresponding to prefixed 95% specificity values in a group of 674 women with benign gynecologic diseases were taken as cutoff limits (88.8 U/ml for CA 125 and 13.7 U/ml for CAM 29). Moreover, CA 125 and CAM 29 levels were measured serially during and after chemotherapy in 26 women selected from the patients with advanced epithelial ovarian cancer. At diagnosis, serum CA 125 was as sensitive as serum CAM 29 for nonmucinous tumors, but more sensitive than serum CAM 29 for mucinous tumors. The association of the two markers seemed to give no advantage over the CA 125 assay alone in the diagnosis of epithelial ovarian cancer. In monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer, changes in CA 125 levels correlated with the clinical course of disease better than changes in CAM 29 levels, and the serum CA 125 assay was more reliable than the serum CAM 29 assay in the early detection of tumor progression. In conclusion, serum CAM 29 did not seem to represent a complementary assay to serum CA 125 in the management of patients with epithelial ovarian cancer.


Immunohistochemical analysis of pancreatic secretory trypsin inhibitor expression in pulmonary adenocarcinoma: its possible participation in scar formation of the tumor tissues. The expression of pancreatic secretory trypsin inhibitor (PSTI) was examined immunohistochemically in pulmonary adenocarcinoma. Of 86 carcinomas examined, 65 (76%) showed immunoreactivity for PSTI. Cases with the papillary subtype and those with early stage disease contained PSTI in cancer cells more frequently and were more strongly positive. There was a slight tendency to strong expression of PSTI in cases with the histologically well-differentiated type, tumor size of approximately 30 mm maximum diameter, and marked scar formation. Furthermore, 37 cases, which were the majority of the PSTI-positives, appeared to contain PSTI predominantly in cancer cells within the central or subpleural scar tissue and/or its surrounding tissue. Thus, pulmonary adenocarcinoma may commonly express PSTI and, considering previous reports that PSTI acts as a growth factor-like substance on fibroblasts in vitro in addition to the present findings of its immunohistochemical distribution in the tumor tissues, it is suggested that PSTI expressed in cancer cells of some pulmonary adenocarcinomas may possibly participate in tumor scar formation.


Differences in messenger RNA expression of carcinoembryonic antigen in surgical specimens of colorectal carcinoma. Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. Plasma CEA levels have been variably associated with prognosis. Since plasma CEA level is multifactorial, CEA gene expression in tumors may provide one precise mechanism to evaluate its functional role. This study evaluated CEA expression at the messenger RNA (mRNA) level in 22 human colorectal carcinomas and their adjacent normal mucosae by Northern blot hybridization using a 32P-labeled CEA probe (a loop-domain specific cDNA, LV7). Both tumor and normal mucosa displayed three mRNA species of 4.0, 3.6, and 3.0 kb in length. The expression of 3.6-kb mRNA which encodes for CEA was dominant and it was correlated with another 4.0-kb CEA mRNA expression. The expression of 3.0-kb mRNA which encodes for nonspecific cross-reacting antigen was weak and not detectable in 8 of 22 colon tumors and 12 of 22 normal colon mucosae. In only one tumor, a 4.5-kb mRNA (which might encode for a new family member of CEA) was expressed. A two- to fourfold higher expression of CEA mRNA (3.6 kb) was observed in 11 of 22 colorectal tumors (2 of 9 proximal colon tumors and 9 of 14 rectosigmoid tumors) when compared with morphologically normal adjacent mucosae. Preoperative plasma CEA levels and Dukes' staging had no correlation with this CEA mRNA expression. CEA mRNA did not appear to correlate with metastasis because its expression in the primary colon cancers with metastases (Dukes' stage D tumor) was not always increased. These data also imply that factors other than mRNA expression in tumor might be important in regulating plasma CEA levels.


Expression of mRNA of SCC antigen in squamous cells. The expression of SCC antigen mRNA was studied by Northern blot analysis and in situ hybridization in human gynecologic tissues. Northern blot analysis revealed that mRNA of SCC antigen was expressed strongly in normal squamous epithelium and columnar epithelium of the uterine cervix, but not in the endometrium, fallopian tube or ovarian tissue. Among gynecologic malignancies, squamous cell carcinoma of the uterine cervix expressed mRNA of SCC antigen, whereas endometrial and ovarian adenocarcinoma were negative. With in situ hybridization, mRNA of SCC antigen is located in the basal and parabasal layers of the normal squamous epithelium, in dysplasia, and also in carcinoma in situ and invasive squamous cell carcinoma. These results confirmed the previous findings by immunohistochemical studies that SCC antigen is closely related to squamous cells, but also raised a new puzzle regarding the different localization of mRNA and its product, SCC antigen, in the normal squamous epithelium.


Ontogeny of pancreatic oncofetal antigen. Serum concentration of pancreatic oncofetal antigen (POA) was determined in human fetuses, newborns and pregnant women. The mean fetal concentration of POA (mean = 5.27 micrograms/ml) changed very little with gestational age. Also, only a weak correlation was found between POA concentration of newborns (mean = 5.15 micrograms/ml) and their birth weight. It appears that between the 19th and 40th weeks of gestation POA exhibits no fetospecific features, i.e. POA concentration did not exceed significantly the concentration of nonpregnant adults (mean = 6.10 micrograms/ml). A number of pathophysiological variables was correlated with POA concentrations of newborns. The most striking statistical differences were found between American black and white newborns and adults; the mean concentration of POA in sera of black full-term newborns was 5.38 micrograms/ml as compared to white newborns, where the mean concentration was 3.58 micrograms/ml. Similarly, black mothers had a mean concentration (mean = 12.21 micrograms/ml) significantly greater than white mothers (mean = 5.62 micrograms/ml).


Serum neuron-specific enolase in diagnosis and follow-up of gastrointestinal neuroendocrine tumors. Neuron-specific enolase (NSE), the glycolytic isoenzyme of the enolase gamma-gamma dimer, is a specific marker for the diffuse neuroendocrine system and derivative tumors (NET). Serum levels of NSE were measured in 39 patients with NET of the gastrointestinal tract (including 3 gastric and 13 intestinal carcinoid tumors, 6 gastrinomas, 3 insulinomas, 1 glucagonoma, 2 mixed islet cell tumors, 11 neuroendocrine pancreatic carcinomas), in 15 healthy subjects and in 15 nonendocrine gastric, pancreatic, and intestinal tumors. Thirty-six of the 39 patients had elevated circulating levels of NSE, 2 insulinomas and 1 gastrinoma had values below 12 ng/ml like healthy subjects and nonendocrine tumors. No significant difference of serum NSE was found between 23 'functioning' and 16 'nonfunctioning' NET. Fourteen of the NET were malignant, and NSE circulating values were significantly higher than those of nonmalignant forms. After curative surgery serum NSE decreased significantly. NSE can be considered a reliable marker in the differential diagnosis between endocrine and nonendocrine neoplasms, in the clinical detection of silent endocrine tumors and in the follow-up of NET.


Comparison of mitogen- and virus-induced interferon production in whole blood cell cultures of patients with various solid carcinomas and controls. Using a sensitive immunoassay, the mitogen-induced production of interferon-gamma (IFN-gamma) and virus-stimulated IFN-alpha production was investigated in whole blood cell cultures of 115 control subjects and 225 untreated patients with various solid carcinomas. In the cultures of the tumor patients, significantly lower levels of IFN-gamma were found as compared to the controls (p < or = 0.001) and the differences were most evident in those tumor groups containing mostly patients with advanced clinical stages. IFN-alpha values were only slightly lower in the cultures of the carcinoma patients, with p values < or = 0.05. Statistically, there was no correlation between IFN-alpha and IFN-gamma values. Since the IFN-gamma differences between tumor and controls and the correlation to groups with higher tumor stages were much clearer than IFN-alpha differences, we conclude that IFN-gamma measurements after polyclonal induction may be the better parameter for showing a depressed cellular immunological activity in patients with malignancies than virus-induced IFN-alpha secretion.


Divergence in patterns of invasion among subpopulations derived from a human carcinoma clone: roles of intercellular contacts and of cell-substratum adhesion. In tumor progression, populations of cancer cells with different patterns of growth and invasion arise within the same tissue and within individual neoplasms. We tested the hypothesis that, even in histologically undifferentiated carcinomas, such diversity may be influenced by differentiation-dependent adhesive mechanisms. We used as prototypes two cell lines that originated in the same clone of a poorly differentiated cervical carcinoma, but express strikingly different phenotypes. Cells of line C-4I express select characteristics of the spinous stage of stratified squamous epithelial differentiation while cells of line C-4II resemble basal cells. C-4I cells form rapidly expanding compact tumors in vivo and multilayered cohesive colonies in culture, while C-4II cells form slow-growing infiltrating tumors in vivo and dispersed, monolayered colonies in culture. In suspension culture which prevented any cell-substratum interactions, C-4I cells formed aggregates that were significantly larger and more compact than those formed by C-4II. Thus, greater intercellular adhesion between the 'spinous' C-4I cells contributed significantly to the phenotypic divergence of the lines. Upon disruption of intercellular adhesion with the glutamine analogue 6-diazo-4-oxo-norleucine (DON), C-4I cultures on plastic and in suspension assumed forms resembling C-4II. On plastic, single 'basal' C-4II cells adhered more rapidly and migrated more slowly than C-4I cells, in keeping with the capacity of C-4II, but not C-4I, to secrete fibronectin (FN) substrata. However, on exogenous FN matrices, migration and cell dispersion were accelerated in both lines. Both lines expressed similar integrin profiles. Thus, the lines had diverged in extracellular matrix production, but not in the receptors for extracellular matrix components. The properties of the C-4 lines mimic those of specific cell types in normal stratified squamous epithelia, where intercellular adhesion increases but FN secretion diminishes with progression from the basal to the spinous stage of differentiation. Our results demonstrate a direct influence of differentiation-associated adhesive mechanisms on growth patterns and suggest that similar mechanisms may be responsible for variations in invasiveness among neoplastic clonal subpopulations. An awareness of these correlations may help to interpret the modes of local invasion by poorly differentiated carcinomas in terms of specific, well-defined cell properties.


[Vasomotor disorders in the atherosclerotic coronary artery. Are there practical repercussions today?]. The 1980s have brought increasing evidence that coronary vasomotricity has a major role in the pathophysiology of stable angina pectoris. Specifically, it has been shown that mediators such as serotonin have opposite effects on normal and atherosclerotic coronary arteries, resulting in vasodilation and increased coronary blood flow in the former and vasoconstriction with decreased flow in the latter. Other studies have shown that, even in patients with stable angina, coronary vaso-constriction is likely to trigger clinical episodes of angina. In this regard, the adjunction of coronary vasodilator medications to medications reducing myocardial demand might prove useful in patients with stable angina.


[Hemostatic anomalies and coronary risk]. The main role of thrombosis in the acute coronary event is now well documented. Numerous hemostatic factors are involved in thrombosis. Among them, fibrinogen, factor VII, leucocytes and platelets have been shown by epidemiology, to be closely related to the acute coronary event. The key role seems to be reserved to platelets since the close relationship of their activity as evaluated by platelet aggregation tests, to both coronary episodes and the main risk factors such as smoking, diabetes and dietary habits, has been recently demonstrated. In addition, the role of platelets has been confirmed by the marked protective effect against coronary events, of drugs such as aspirin, inhibiting platelet aggregation.


[Thrombolytic agents in myocardial infarction: results of large mortality studies]. Large studies involving several thousand patients have clearly established the effectiveness of thrombolytic therapy in reducing mortality in the acute phase of myocardial infarction: the earlier the treatment, the greater this reduction. The value of late thrombolysis remains to be determined by further studies. This technique can be extended to the oldest subjects who benefit most from this type of treatment, bearing in mind that they are at a greater risk of neurological complications. The effectiveness of thrombolysis is partially dissociated from its effects on left ventricular function. Since the thrombolytic agents (streptokinase, anistreplase and recombinant tissue plasminogen activator) are equally effective in reducing mortality and neurological complications, it seems reasonable to use the cheapest of these drugs as initial treatment, except in some special cases.


[The promises of new antithrombotic agents]. Most new antithrombotic drug development projects are focused on the improvement of myocardial infarction treatment at the acute phase. New thrombolytic drugs do not seem to be as attractive as adjunctive therapy, such as antiplatelet and antithrombotic agents, as well as inhibitors of thrombin generation. The current tendency is to select very specific molecules. The difficulty in developing these drugs must not be underestimated: they will be compared to very active drugs, such as aspirin, heparin or streptokinase; the therapeutic margin of antithrombotic therapy is very narrow; a clinical benefit will have to be shown.


[Ischemic cardiomyopathy: remodeling, hypertrophy, subendocardial risk. Can processes be controlled?]. Ischaemic cardiomyopathy reflects the myocardial dysfunction caused by coronary disease. It results from the association of 1. segmental infarction(s) responsible for ventricular "remodelling", i.e. expansion of the necrotic area(s) and hypertrophy-dilatation of the rest of the ventricle, eventually concurring to heart failure; 2. areas which are viable but with a function that is reversibly compromised by severe acute or chronic ischaemia (myocardial sideration or hibernation) affecting mainly the subendocardium. The spontaneous course of cardiomyopathy towards the worst can be arrested by 1. revascularisation of the myocardium at risk by coronary reperfusion performed either as an emergency in case of infarct in the process of formation, or after detection of the viable myocardial areas by isotopic methods; 2. prevention or limitation of ventricular remodelling by coronary reperfusion and improvement of the ventricular load by administration of angiotensin-converting enzyme inhibitors and nitroglycerin. The Survival and Ventricular Enlargement study (SAVE) has been the first to demonstrate the relationship between limitation of ventricular remodelling and improvement of the secondary prognosis of infarction obtained by angiotensin-converting enzyme inhibitors.


[Should coronary angiography be practiced in patients with recent myocardial infarction?]. As a rule, infarction results from an occlusive thrombosis in a pre-existing atherosclerotic stenosis. Contrary to intravenous thrombolysis, coronary arteriography with immediate removal of obstruction can only be performed in a minority of patients. Similarly, "salvage angioplasty", performed if thrombolysis has failed, does not justify early coronary arteriography, except in certain cases of infarction at very high risk. In 80% of the cases the first days are uneventful, but the mortality in the first year (about 10%) will depend upon the presence or absence of latent residual ischaemia and/or left ventricular dysfunction. A noninvasive evaluation carried out before the patient is discharged and including clinical and echocardiographic data as well as the results of stress tests (sometimes coupled with isotopic studies) may isolate an important group of patients (40%) whose mortality rate at one year is below 3%. Systematic coronary arteriography, therefore, is not justified, especially since it facilitates the "easy" decisions of angioplasty the benefits of which has not been demonstrated in the absence of residual ischaemia during exercise.