Biomedical subjects

A Muhs

Publications and source records attributed to A Muhs.

At least 19 recordsLinked to original sources

PubMed1996

Effects of single oral doses of lysine clonixinate and acetylsalicylic acid on platelet functions in man.

Lysine clonixinate is an analgesic drug with a so far unknown mechanism of action. We have determined its effect on platelet cyclooxygenase in man. Biosynthesis of thromboxane (TX)B2 and prostaglandin (PG)F2 alpha in clotting whole blood ex vivo as well as collagen-induced platelet aggregation measured before and at various time points after oral administration of 125 mg lysine clonixinate were compared to results obtained with 500 mg acetylsalicylic acid (ASA). While biosynthesis of both TXB2 and PGF2 alpha measured radioimmunologically was inhibited significantly 2.5 h, but not 6 h, after administration of lysine clonixinate, inhibition by ASA was much greater and still highly significant after 48 h. Similarly, collagen-induced aggregation of platelet-rich plasma was inhibited for a longer period and to a greater extent after administration of ASA than after lysine clonixinate. Our results indicate that lysine clonixinate is a cyclooxygenase inhibitor of moderate potency. It remains to be investigated whether mechanisms other than inhibition of cyclooxygenase contribute to the analgesic activity of lysine clonixinate.

Administration, Oral↗

PubMed1996

Functional antagonism between cAMP and cGMP on permeability of coronary endothelial monolayers.

The role of the intracellular second messengers guanosine 3', 5'-cyclic monophosphate (cGMP) and adenosine 3', 5'-cyclic monophosphate (cAMP) in the control of macromolecule permeability was studied in cultured monolayers of microvascular coronary endothelial cells from rat. Macromolecule permeability was determined as passage of fluorescein isothiocyanate (FITC)-labeled albumin across the monolayers. Activation of adenylyl cyclase by the beta-adrenoceptor agonist isoproterenol (Iso; 10(-5) M) and the A2-adenosine receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA; 10(-7) M) induced an increase in cellular cAMP contents that was accompanied by an increase in albumin flux. Effects of Iso and NECA on cellular cAMP level and albumin flux could be antagonized by a stimulator of the particular guanylyl cyclase, atrial natriuretic peptide (ANP; 10(-7) M), and stimulators of the soluble guanylyl cyclase, 3-morpholinosydnonimine (SIN-1; 10(-7) M) and sodium nitroprusside (SNP; 10(-6) M). ANP, SIN-1, and SNP also reduced cAMP content and basal macromolecule flux in unstimulated monolayers. 8-Bromoguanosine 3', 5'-cyclic monophosphate (8-BrcGMP; 5 x 10(-6) M), a stimulator of protein kinase G, reduced the increase in albumin flux under Iso (10(-5) M), NECA (10(-7) M), or 8-bromoadenosine 3', 5'-cyclic monophosphate (8-BrcAMP; 5 x 10(-6) M). The present study shows that cGMP and cAMP are functional antagonists in the control of macro molecule permeability.

Adenylyl Cyclases↗

PubMed1996

Results of the ICD-10 research criteria study in German-speaking countries in the field of psychosomatics and psychotherapy.

Selected results from the section psychotherapy/psychosomatics of the ICD-10 research criteria study are discussed. One hundred thirty diagnosticians from 11 psychosomatics centers took part in this section, assessing 16 video-documented patients in case conferences. The results of the study, which were based on 633 diagnostical assessments, demonstrated sufficient chance-corrected interrater reliability coefficients for the majority of the disorders (kappa ranged from 0.22 to 0.99). System-related problems of the ICD-10 approach were identified concerning depressive and psychosomatic disorders. The results are discussed, following some problematical aspects of the concept of comorbidity and multiaxial approaches. Special reference is given to the work group "Operational Psychodynamic Diagnoses' which has produced a multiaxial system covering important psychodynamic variables.

Adult↗

PubMed1995

Initiation of hyperpermeability in energy-depleted coronary endothelial monolayers.

How the initiation of energy depletion affects macromolecule permeability of a barrier of coronary endothelial cells was investigated. Cultured monolayers of adult rat coronary endothelial cells were exposed to 5 mM KCN and 5 mM 2-deoxy-D-glucose (2-DG). Transendothelial flux of albumin, cellular ATP content, and cytosolic Ca2+ concentration were monitored. Within the first minute, a merely partial loss (28%) of ATP reserves provoked a distinct increase (41%) in albumin flux. Rise of permeability was dependent on Ca2+ release from a thapsigargin- and ATP-sensitive endogenous store, and hyperpermeability was greatly attenuated when energy depletion was extremely rapid, as under sequential addition of 20 mM 2-DG and 5 mM KCN. Attenuation of hyperpermeability could also be achieved by use of 5-20 mM 2,3-butanedione monoxime, an inhibitor of actin-myosin interaction. This finding, together with dependence on Ca2+ and availability of residual energy, indicates that the rapid initiation of hyperpermeability is caused by a contractile mechanism.

Adenosine Triphosphate↗

PubMed1995

Influence of hereditary factors in psychogenic disorders.

As part of a research project, a sample of 50 pairs of twins (21 pairs of identical twins, 16 pairs of nonidentical twins of the same sex, and 13 pairs of male-female twins, n = 100 test persons) was examined between 1963 and 1969 and recently, 20 years later, followed up. The index twins were drawn from among the patients making use of the services of an outpatient clinic; they had been diagnosed as having psychoneurotic, character-neurotic of psychosomatic disorders. The question again looked into was that of nature versus nurture: identical twins displayed significantly higher similarity with regard to both severity of their neuroses and manifestation of neurotic symptoms than did nonidentical twins. The hereditary factor proved to be of greater import for the continuing childhood neuroses than for the subsiding childhood neuroses. Yet a certain hereditary factor effect was observed for the neuroses which first manifest themselves in adulthood. Our findings indicate that the hereditary factor is not more pronounced in childhood than in adulthood; it is equally effective in adults.

Adolescent↗

PubMed1995

Concepts of neurotic and personality disorders in ICD-10: results of the Research Criteria Study.

A discussion on personality disorders (F6) is conducted within the framework of the Research Criteria Study on the basis of one case each of borderline syndrome (F60.31), transsexualism (F64.0), and factitious disorder (F68.1). In the Research Criteria Study the main agreement achieved about personality disorders was 77%, for borderline disorders 94%, transsexualism 91%, and factitious disorders 53%. Additional diagnoses were given in the case of factitious disorder by 43%, for borderline disorders in 15%, and for transsexualism in only 3%. Alternative diagnoses improved the overall agreement about factitious disorders by 21%, about borderline disorders and about transsexualism by 3%. It appears justified to introduce a coding for an alternative main diagnosis. The diagnostic concepts are discussed with respect to practicality, suitability, adequacy and reliability. The raters felt fairly secure about the classification. The research diagnostic criteria proved to be very practical. The raters attributed a high reliability to ICD-10 and, with the exception of factitious disorders, a very valid image of patients.

Borderline Personality Disorder↗

PubMed1995

Concepts of psychosomatic disorders in ICD-10: results of the Research Criteria Study.

The multicenter study with the research criteria in the field of psychotherapy/psychosomatic medicine considered nine cases. One patient with cardiac neurosis (F45.3) and one patient with a persistent somatoform pain disorder (F54.4) were diagnosed in category F45.x. The rater agreement was 63-68%. 54% of the correct diagnoses made for three cases of colitis ulcerosa and Crohn's disease concurred (28%, 50%, and 80%). The case of anorexia nervosa (F50.0) was coded correctly by all of the raters, while the agreement for bulimia (F50.2) was 82%. Only 50% of the raters correctly assigned the dissociative disorder (F44.4). The agreement achieved for factitious disorder (F68.1) was 54%. Across all the psychosomatic disorders in ICD-10 there was an agreement of 65%. This result is markedly lower than the overall agreement of the Research Criteria Study (78%). Cardiac neurosis and bulimia were given a favorable prognosis. A more reticent psychotherapeutic commitment was seen for the classical psychosomatic disorders, persistent pain disorder, and factitious disorder. Anorexia nervosa and dissociative disorder assumed an intermediate position.

Humans↗

PubMed1995

[Structure and structural disorder].

One of the central tasks of psychodynamic diagnosis, next to determining intrapsychic conflicts, central relational patterns, and subjective forms of experiencing is assessing the psychic structure or the structural disorder. This article develops the structure term from object relationship theoretical, ego-psychological, and self-psychological concepts of psychoanalysis. This "Structure of the self in the relationship to others" thus obtained is described with six structural criteria (self-perception, self-control, defence, object perception, communication, attachment). In order to be able to distinguish the extent and the quality of structural disorders four structure levels of integration based on psychoanalytic experience in the out-patient and the in-patient setting are differentiated. A basis for an operationalization is then made; it is made in the system OPD (Operationalized Psychodynamic Diagnostics). First studies regarding practicalibility and reliability are promising.

Communication↗

PubMed1995

[10th revision of the International Classification of Diseases (ICD-10)--possibilities and limits for psychodynamically orientated diagnosis].

The present paper will discuss some selected results of the ICD-10 Research Criteria Study, section psychotherapy/psychosomatics, which was done between 1990 and 1993 involving 11 centers with 125 diagnosticians. During case conference 610 diagnostical assessments for 16 video-documentated cases were evaluated including an independent polydiagnostic rating (ICD-9, ICD-10, DSM-III-R) and subjective assessments of the diagnostic process. The results of the study could demonstrate sufficient chance-corrected interrater-reliability coefficients (Kappa values 0.69-0.99) for the majority of the disorders. Even on the level of the subjective ratings of the diagnostic process system-related problems of the classificatory approach could be identified concerning depressive and psychosomatic disorders. The results were discussed following some problematical aspects of the concept of comorbidity and multiaxial approaches. Special reference was given to the working group "Operational Psychodynamic Diagnosis (OPD)", which was founded in the Federal Republic of Germany.

Depressive Disorder↗

PubMed1993

Combined Betaseron R (recombinant human interferon beta) and radiation for inoperable non-small cell lung cancer.

PURPOSE: Based on in vitro evidence of radiosensitization by Betaseron (beta-IFN), a Phase I/II study was undertaken to determine toxicity and response using combined radiation (RT) and B-IFN in patients with unresectable Stage III and nonsmall cell lung cancer. METHODS AND MATERIALS: Varying doses of beta-IFN(10 to 90 x 10(6) IU) were administered IV immediately preceding RT on the first three days of weeks 1, 3, and 5. The RT dose was 1.8 Gy/day, 5 days/week for a total of 54 or 59.4 Gy. RESULTS: Thirty-nine patients were entered, 32 of whom were evaluable. The median follow-up time at time of analysis was 60 months. Responses were based on CT scan. The response rate for the total group was 81% with 44% achieving complete response. Seventy-eight percent of patients with complete response survived a minimum of 21 months. Twenty-six patients had Stage III A/B disease with a median tumor size of 6.5 cm. and median survival was 19.7 months. The 5-year actuarial survival for this group was 31%, with a plateau persisting after 3 years. There were no treatment related deaths nor any event of life threatening toxicity. Of eight patients surviving 3-5 years, no long-term toxicity has been observed. Karnofsky indices were 90-100 and respiratory symptoms were minimal. CONCLUSION: beta-IFN is well-tolerated. Response and survival rates are sufficiently encouraging to warrant further investigation in a randomized trial which has been accepted as an RTOG study awaiting drug availability.

Adult↗

PubMed1993

Disintegration of cytoskeletal structure of actin filaments in energy-depleted endothelial cells.

In a previous study [Watanabe, H., W. Kuhne, R. Spahr, P. Schwartz, and H. M. Piper. Am. J. Physiol. 260 (Heart Circ. Physiol. 29): H1344-H1352, 1991] metabolic inhibition (5 mM KCN + 5 mM 2-deoxy-D-glucose, for 2 h) was found to cause disintegration of F-actin filaments, cell retraction, and augmented paracellular macromolecule permeability in monolayer cultures of porcine aortic endothelial cells after a rapid depletion of ATP stores (90% in 5 min). These changes were reversible. In the present study, the nature of this cytoskeletal disintegration was investigated. 1) Disintegration of F-actin filaments within 2-h incubation under metabolic inhibition was accompanied by appearance of F-actin clumps in the cells, but total contents of F-actin remained unaltered. 2) Cytosolic Ca2+ levels rapidly rose in metabolically inhibited cells; after 2 h a 10-fold increase was observed. 3) Presence of the Ca2+ ionophore A23187 (10 microM) mimicked the reversible effect of metabolic inhibition on F-actin filaments and monolayer permeability but not the extensive depletion of ATP stores. 4) Existence of the Ca(2+)-activatable actin-severing protein gelsolin in endothelial cells was demonstrated. The results show that during the reversible phase of endothelial energy depletion disintegration of F-actin filaments is only partial, since it is based on their fragmentation and not depolymerization. Increase in cytosolic Ca2+ levels seems to be the primary cause for the fragmentation, possibly through the activation of gelsolin.

Actins↗

PubMed1993

Anorexia nervosa and Turner's syndrome.

Publications about Turner's syndrome and anorexia nervosa are extremely rare. All of them, including a new case, are listed up and discussed under psychodynamic aspects. The conclusions drawn from these 21 cases might be essential for genetic counseling, hormonal treatment and psychotherapy in Turner's syndrome. (1) There is a connection between the beginning of the hormonal treatment and the onset of anorexia nervosa in Turner's syndrome. The anxiety during hormonal treatment is due to sexual feelings and the confrontation with the gender role. As the manifestation of anorexia nervosa ought to be taken into account the beginning of a hormonal treatment should be decided in individual context. (2) The early childhood of girls with Turner's syndrome is striking with respect to psychosocial constellations. Short stature and other deficits mean narcissistic wounds. Therefore understanding and affectionate parents are most important to them as they particularly suffer from conflicts with the family.

Adult↗

PubMed1993

[Discordance analytic studies of monozygotic twins].

Discordance analyses of monozygotic twins make it possible to study the influence of neurotic pathogenic situations of early childhood upon later neurotic developments. The analysis offers the advantage of having a genetic double who was shaped by the same psychosocial macro influences and went through a sound development as a comparison for an examination of the course of psychogenic illnesses. However, two prerequisites are necessary: 1. the human genetic/anthropological or serological diagnosis in order to be able to definitely say whether the twins are monozygotic or not and 2. both twins must be alive. A strong discordance regarding markedness of characteristics or a varying degree of symptom manifestation as well as a longer period of observation are further conditions. With the example of four short casuistries of monozygotic twins the environmental variables which are decisive in the individual cases for the discordant development are described: A highly ambivalent early childhood relationship in contrast to a mostly balanced relationship is the foundation for a neurotic course in connection with pathological conspicuous behavior of the parents, sibling rivalry and differing attitudes of the parents regarding each of the twin siblings. As a result each twin identifies with a different parent, leads in development and dominance positions are also consequences. Later the course set in school and career, orientation regarding an intimate partner and the neurotically preformed personality structure, which is the basis for differing degrees of being able to cope successfully with threshold situations, become framing situations of discordant neurotic versus stable and sound development.

Adult↗

PubMed1992

Cytosolic Ca2+ overload and macromolecule permeability of endothelial monolayers.

It was investigated how cytosolic Ca2+ overload affects the cytoskeletal structure and macromolecule permeability (for albumin) of monolayers of endothelial cells (from porcine aorta). States of cytosolic Ca2+ overload were produced either 1. by metabolic inhibition (5 mM KCN plus 5 mM 2-deoxyglucose) or 2. by increasing membrane permeability with the use of a Ca2+ ionophore (10 microM A 23187). The effects of cytosolic Ca2+ overload on the structure of F-actin filaments and monolayer permeability were monitored. ATP stores were rapidly degraded (> 90% in 15 minutes) in the presence of metabolic inhibitors, but only partially reduced in the presence of A 23187 (30%) in two hours). Concomitantly with ATP loss, cytosolic Ca2+ levels were increased in metabolically inhibited cells. Two-hour exposure to the Ca2+ ionophore A 23187 mimicked the effect of two-hour metabolic inhibition on F-actin filaments and monolayer permeability, in spite of the divergence in energy metabolism. Disintegration of F-actin filaments in presence of metabolic blockers or ionophore was accompanied by appearance of F-actin clumps in the cells, but total contents of F-actin remained unaltered. Within three hours after removal of these agents, a normal F-actin structure and normal macromolecule permeability were re-established in the monolayers. The results show that cytosolic Ca2+ overload causes disintegration of F-actin filaments and a subsequent increase in macromolecule permeability. These changes are readily reversible as long as the dis-integration is based on fragmentation and not depolymerization of F-actin filaments.

Actins↗

PubMed1991

Effects of prenatal exposure to methylazoxymethanol (MAM) on brain weight, hypothalamic cell number, pituitary structure, and postnatal growth in the rat.

Congenital brain damage syndromes typically are described in terms of behavioral symptoms. Many brain functions are not reflected in behavior, however, and prenatal injury to the developing nervous system could alter these functions, as well. To test the hypothesis that prenatal brain injury can result in postnatal endocrine malfunction, rats were exposed in utero to 20 mg/kg of methylazoxymethanol acetate, a potent neuroteratogen, at two stages of gestation when different sets of growth-controlling neurons of the hypothalamus are forming. The growth hormone releasing factor (GRF) neurons stimulate release of growth hormone from the somatotropes of the anterior pituitary, contributing to rapid growth in the period between weaning and puberty. The somatotropin release inhibiting factor (SRIF) neurons have the opposite effect on the pituitary and can inhibit the GRF cells directly. Growth of treated animals was monitored daily from birth to 40 days and compared to that of controls. Treatment on the 14th day of gestation produced a small number of dwarf animals characterized by normal weight at birth and a sudden decrease in growth rate at the beginning of the fourth postnatal week that led to a body weight about 50% of normal. Treatment on day 16 yielded an acceleration of postnatal growth (significant in males). In each group, most treated animals were like controls in adult size and pattern of growth. As adults, both treatment groups demonstrated massive reductions in brain weight which characterized all the subjects, whether or not they exhibited growth anomalies. The animals treated on day 14 were confirmed to have a significant, selective reduction in growth hormone releasing factor neurons. Reductions were greatest in the middle and posterior levels of the GRF cell distribution, the regions forming most actively at the time of exposure. Unexpectedly, the same group also had increased numbers of periventricular SRIF neurons. Neither type of neurons was significantly altered in the later treatment group. Examination of pituitary structure indicated that dwarfs had very small pituitaries, with an immature pattern of somatotrope distribution, and giants had very large pituitaries, with some hypertrophy of somatotropes. The results suggest that endocrine anomalies which manifest themselves long after birth may originate as birth defects of the nervous system.

Animals↗

PubMed1991

[Aspects of the development and sex specific prevalence of psychogenic diseases in children and adults in relation to genetic and environmental factors].

We investigated a sample of one hundred twins as to their neurotic disturbances in childhood and adulthood. The hereditary factor was of greater effect with the continuing neuroses of childhood than with the weakening neuroses in childhood. But a certain effect of the hereditary factor could not be denied with neuroses manifesting themselves only in adulthood. According to our results the hereditary factor in childhood is not stronger than in adulthood, with adults it is as effective. Particular neurotic symptoms show influences of the hereditary factor in respect to depressive, maladaptive oral and maladaptive aggressive disturbances of behavior and difficulties in forming interpersonal relationships. In respect to stuttering, disturbances of the urogenital system and intelligence and occupational development a certain hereditary factor is very probable. Sex influences also have a certain effect: Behavioral disorders in childhood are found in the male sex, the female sex rather shows psychic symptoms.

Adolescent↗

PubMed1990

[A 20-year follow-up study of a sample of 50 pairs of twins with neurotic-psychosomatic disorders].

As part of a research project, examination was made of a sample of 50 pairs of twins (21 pairs of identical twins, 16 pairs of non-identical twins of the same sex, and 13 pairs of male-female twins [n = 100 test persons]) between 1963 and 1969 and again recently after a period of 20 years. The index twins were drawn from among the patients who made use of the services of an out-patient psychotherapeutic clinic, and they were determined to be either psychoneurotic, character neurotic, or psychosomatically ill. The question examined was again one of nature vs. nurture. Identical twins showed a significantly higher similarity with regard to the seriousness of their neuroses and the manifestation of neurotic symptoms than did non-identical twins. Noticeable similarities existed in cases of depressive disturbances, disturbances of oral and aggressive behavior, and disturbances of interpersonal contact. With regard to the influence of variables in the environment, we examined the effect of factors in early childhood on neurotic development. Lack of a reference person, a negative attitude on the part of parents toward the child, etc., frustration within and outside the family have an effect on the manifestation of neuroses and on the course of their development. The influence of early childhood factors on the degree of neurotic disorder is still to be noted in the current point prevalence.

Adult↗

PubMedDate not supplied

[Development of a model of operational psychodynamic diagnosis].

Since 1992 a working group called "Operationalized Psychodynamic diagnoses" conceptualized a model of operationalized psychodynamic diagnosis in Germany. This model includes the most important diagnostic dimensions from psychodynamic view which are: Axis I: Experience with illness and treatment preconditions. Axis II: Habituated relationships of the patient, Axis III: Intrapsychic conflicts of the patient, Axis IV: the structure of personality development of the patient, Axis V: The level of symptoms or syndromes. This axis is adapted to ICD-10. The development of these axis is done in special subgroups during 1992 and 1994 and in first empirical studies the reliability and other test-related dimensions of the model were proved. In this paper the essentials of the diagnostic model are shown and further developments are discussed.

Humans↗