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PubMed1995

Orphans of the 'Real': II. The future of object relations theory in the treatment of the psychoses and other primitive mental disorders.

Objective relations theory is a broad, multifaceted concept that covers a number of differing paradigms. The author highlights the historical development of this concept. Originally developed by Freud and Abraham, it gradually became a shibboleth that identified both the Kleinian and the Independent schools in Great Britain and the object relations school within the American school of ego psychology. The two British schools differed between each other and from the American school. Among these schools of thought, two major paradigms have emerged: (1) the one-person psychoanalytic model, and (2) the two-person model. More recently, derivatives of the two-person model have emerged as the schools of relationism, self psychology, and intersubjectivity. In addition, the contributions of the Lacanian school have altered concepts about the fundamental nature of object relations. What is consequently at issue in terms of the psychoanalytic conception and treatment of psychoses and primitive mental disorders (with patients suffering from being "orphans of the 'Real'") is (1) the differing conceptions of what is meant by internal objects, part-objects, selfobjects, and object-representations, and (2) the differing conceptions of unconscious mental life.

Freudian Theory↗
PubMed1995

[Psychoanalytic theory and therapy of neurotic anxieties].

In the author's view anxiety is a psychosomatic phenomenon that develops into neurotic anxiety when unconscious psychic components come into play. He regards it as impossible to make a clear-cut distinction between neurotic anxiety and real anxiety given that anxiety neuroses also display an element of historical and continuing actuality and can thus be said to have "real" foundations. In his discussion of treatment techniques, Thomä introduces following Weiss and Sampson the concept of "mastering" to refer to the necessity of understanding the repetitions and transferences of the patient as an attempt to master traumatic situations with the assistance of the analyst. In his view it is not sufficient to make the patient aware of libidinous and aggressive drives but rather to broaden the scope of action available to the patient.

Anxiety Disorders↗
PubMed1998

The analyst's subjectivity and the analyst's objectivity.

The author suggests that, increasingly, contemporary psychoanalysts have been acknowledging and examining the intersubjectivity of the clinical encounter and that this trend has sometimes been misunderstood as necessitating the conclusion that objectivity is impossible to achieve in clinical psychoanalysis. In contrast to this, the author proposes a pragmatic definition of the analyst's objectivity that is entirely consistent with acceptance of the analyst's irreducible subjectivity, and illustrates his view by means of a clinical example. He suggests that objectivity concerns both objects and objectives, and indicates that a pragmatic conception of objectivity is employed throughout modern science. He explains why he regards psychoanalysis as a science, rather than as a hermeneutic discipline. He takes up the way in which implicit positivist assumptions can disadvantageously influence our thinking about the relation between an analyst's subjectivity and an analyst's objectivity. Finally, he discusses the important role of consensus in objectivity generally and in psychoanalytic objectivity particularly, as well as some of the differences that exist among analysts with regard to the specific objectives that take priority in clinical work.

Adult↗
PubMed1999

Biologic therapy for lymphoma.

Biologic approaches to lymphoma treatment are now a practical reality rather than a vaguely perceived hope for the future. Interferon alfa seems to have been established as a life-extending therapy for selected patients with follicular lymphoma. Humanized anti-CD20 monoclonal antibody (rituximab) has an authentic 50% response rate in patients with follicular lymphoma, frequently works when given a second time, and is demonstrating what seems to be synergistic activity when combined with chemotherapy. Radioimmunoconjugates using iodine-131 and yttrium-90 as payload are producing responses in refractory and aggressive lymphomas. Vaccines and adoptive cellular therapies are also showing promising results in early phase clinical testing.

Antibodies, Monoclonal↗
PubMed1997

Working through the experience of time in time-limited therapy.

The experience of time is a component in the psychic reality that can be understood from four standpoints: the cognitive, the dynamic, the existential-affective, and the life-span linked. This article presents a time-limited therapy in which the stress was on the constant interaction between the therapeutic content, which focused on the topic of time, and the singular setting of time-limited therapy. The discussion addresses the requisite conditions for turning short-term therapy into an active container for working through the sense of time, its meanings and its derivatives.

Adult↗
PubMed2001

Enzyme replacement and beyond.

During the last decade, enzyme replacement therapy for lysosomal storage diseases became a reality with the demonstration of its safety and effectiveness in type 1 Gaucher disease. Currently, enzyme replacement and several other potential therapeutic strategies are being developed for selected lysosomal storage diseases, including Fabry disease due to the deficient activity of alpha-galactosidase A (alpha-Gal A). The development and clinical evaluation of these new therapies require a stepwise process, each step being rigorously reviewed and approved by national or international regulatory agencies. For lethal disorders that affect small populations, such as many inherited metabolic diseases, this process can be accelerated by 'orphan drug' and 'fast track' regulations. As an example of the drug development process, the development of recombinant human alpha-Gal A (r-halphaGal A) replacement for Fabry disease is presented, including the preclinical studies in the 'Fabry mouse' model, and the clinical phase 1/2, phase 3, and phase 3 extension studies, which demonstrate the safety and efficacy of this new therapy.

Animals↗
PubMed1999

Gene therapy for dyslipidemia: clinical prospects.

Current approaches to the treatment of lipid disorders are inadequate for a substantial number of patients with severe hyperlipoproteinemia, isolated low high-density lipoprotein (HDL) cholesterol levels, or other molecular disorders of lipoprotein metabolism. Therefore, dyslipidemias remain important targets for the development of novel therapies. Gene therapy is a logical therapeutic approach to monogenic lipoprotein disorders, such as homozygous familial hypercholesterolemia, familial lipoprotein lipase deficiency, familial lecithin-cholesterol acyltransferase deficiency, and abetalipoproteinemia, for which current therapies are inadequate. Gene therapy could also be used to increase expression of certain proteins, such as apolipoprotein A-I as a strategy to raise HDL cholesterol levels or apoE as a strategy for severe combined hyperlipidemia. With further progress in the development of vectors, gene therapy for severe dyslipidemia is likely to become a clinical reality.

Gene Transfer Techniques↗
PubMed2001

Gene therapeutic approaches to oxidative stress-induced cardiac disease: principles, progress, and prospects.

Heart and vascular diseases continue to rank among the most frequent and devastating disorders to affect adults in many parts of the world. Increasing evidence from a variety of experimental models indicates that reactive oxygen species can play a key role in the development of myocardial damage from ischemia/reperfusion, the development of cardiac hypertrophy, and the transition of hypertrophy to cardiac failure. The recent dramatic increase in availability of genomic data has included information on the genetic modulation of reactive oxygen species and the antioxidant systems that normally prevent damage from these radicals. Nearly simultaneously, progressively more sophisticated and powerful methods for altering the genetic complement of selected tissues and cells have permitted application of gene therapeutic methods to understand better the pathophysiology of reactive oxygen species-mediated myocardial damage and to attenuate or treat that damage. Although exciting and promising, gene therapy approaches to these common disorders are still in the experimental and developmental stages. Improved understanding of pathophysiology, better gene delivery systems, and specific gene therapeutic strategies will be needed before gene therapy of oxyradical-mediated myocardial damage becomes a clinical reality.

Animals↗
PubMed2002

[Quality of life of a population of 54 ambulatory children with cerebral palsy. A cross-sectional study].

UNLABELLED: To evaluate the impact of handicap on quality of life in children with cerebral palsy and living in family. METHOD: A descriptive study by investigation was conducted in children with cerebral palsy, with the ability to walk, from 4 to 12 years of age, and in their family. Quality of life was evaluated with the AUQUEI questionnaire. Another questionnaire was given to the parents to collect the different variables, which could influence quality of life of the child. RESULTS: The mean age was 9 years. Associations between the studied variables and the quality of life were observed for motor function, number of siblings and the quantity of hours of reeducation given by the family. Parents evaluated their quality of life on the visual scale at 72.23 mm (95CI: 51.60-92.84). There was no correlation between the assessment of quality of life of parents and children. DISCUSSION-CONCLUSION: The better the child's motor function the less satisfied he was. This result shows the poor correlation between quality of life and general condition, impairment or disability. The greater the number of children in the family the less satisfied the child was within the family and the more satisfied the child was at school. A handicapped child has perhaps a more difficult place in the close family and an easier time in a school where the environment is more neutral. The more time that is devoted by the family to reeducation the less the child is satisfied. Quality of life seems to be influenced negatively by the demands of physical therapy, which do not correspond to the reality of the abilities of the child.

Adolescent↗
PubMed1999

[Treatment of intimal hyperplasia by gene therapy: an update].

Injury to the vessel wall leads to smooth muscle cell (SMC) activation followed by intimal hyperplasia (IH). This process contributes to restenosis following balloon angioplasty--particularly with stenting--occlusion of vascular bypasses, and transplant arteriopathy. Genetic interventions affecting the cell cycle or early postinjury events have been successful in limiting SMC proliferation in vitro and in animal models. Gene therapy strategies have included the use of antisense oligonucleotides that block protein synthesis, transduced "suicide" genes that cause cytotoxicity, and cells engineered genetically to reduce the response to injury. The clinical application of gene therapy in vascular diseases should become a reality with the development of new delivery systems permitting efficient gene transfer to the injured vascular wall (J Mal Vasc 1999; 24: 349-355).

Angioplasty, Balloon, Coronary↗
PubMed2004

Obstacles to successful antiretroviral treatment of HIV-1 infection: problems & perspectives.

Mutations in human immunodeficiency virus type 1 (HIV-1) are a major impediment to successful highly active antiretroviral therapy (HAART) and the design of anti-HIV vaccines. Although HAART has made long-term suppression of HIV a reality, drug resistance, drug toxicity, drug penetration, adherence to therapy, low levels of continued viral replication in cellular reservoirs and augmentation of host immune responses are some of the most important challenges that remain to be sorted out. Continuing viral replication in the face of HAART leads to the accumulation of drug resistance mutations, increase in viral loads and eventual disease progression. Patients who fail therapy have minimal options for their clinical management. Therefore, a clear understanding of the pathogenesis of drug-resistant HIV-1, and all of the issues that influence the success of HAART is urgently needed. In the present article, we discuss various obstacles to HIV therapy, and provide perspectives relating to these issues that are critical in determining the success or failure of HAART.

Anti-HIV Agents↗
PubMed1995

[Therapeutic immunomodulation in neurology: from hope to reality. Exemplified by multiple sclerosis].

Multiple strategies for specific therapies are presently attempted in multiple sclerosis, in which an autoimmune reaction leads to demyelinisation within the central nervous system. Similar approaches are generally used in other potential autoimmune diseases. They try to interfere with the presentation and recognition of putative autoantigens by the immune system and also with the inflammatory process that gives rise to the demyelinating lesion. The authors review extensively these various prospects and their immediate implications for multiple sclerosis patients.

Autoantigens↗
PubMed1987

Epistemological confusion in family therapy and research.

Family therapy began as a movement sparked by a small group of behavioral scientists who challenged the orthodoxies of medical and psychodynamic therapies. This movement signalled the beginning of an epistemological shift, the roots of which can be found early in this century in the physical sciences. As the field has grown and become for many a means of livelihood rather than an experimental thrust, though exploration of epistemological issues has continued, a split has developed in the field that mirrors the epistemological split currently visible in Western society. The predominant reality system of the Western world remains rooted in Cartesian/Newtonian, nineteenth-century mechanistic and reductionistic "common sense," even though the basis for a new, nonmechanistic and nonreductionistic reality system has been emerging in the twentieth century. The juxtaposition of both reality systems in the field of family therapy has produced much confusion. This article attempts to clarify the basis for that confusion.

Family Therapy↗
PubMedDate not supplied

Phenytoin-folic acid interaction.

OBJECTIVE: To review information regarding the dual and interdependent drug-nutrient interaction between phenytoin and folic acid and other literature involving phenytoin and folic acid. DATA SOURCES: Information was retrieved from a MEDLINE search of English-language literature conducted from 1983 (time of the last review) to March 1995. Search terms included folic acid, phenytoin, and folic acid deficiency. Additional references were obtained from Current Contents and from the bibliographies of the retrieved references. STUDY SELECTION: All human studies examining the effects of phenytoin on serum folate concentrations and folic acid supplementation on serum phenytoin concentrations were selected. These included studies of patients with epilepsy and healthy volunteers as well as case reports. Case reports were included because of the extensive length of time needed to study this drug interaction. DATA EXTRACTION: Data extracted included gender, dosing, serum folate concentrations if available, pharmacokinetics, and adverse events. DATA SYNTHESIS: Serum folate decreases when phenytoin therapy is initiated alone with no folate supplementation. Folic acid supplementation in folate-deficient patients with epilepsy changes the pharmacokinetics of phenytoin, usually leading to lower serum phenytoin concentrations and possible seizure breakthrough. Folate is hypothesized to be a cofactor in phenytoin metabolism and may be responsible for the "pseudo-steady-state," which is a concentration where phenytoin appears to be at steady-state, but in reality, is not. Phenytoin and folic acid therapy initiated concomitantly prevents decreased folate and phenytoin obtains steady-state concentrations sooner. CONCLUSIONS: Folic acid supplementation should be initiated each time phenytoin therapy commences because of the hypothesized cofactor mechanism, decreased adverse effects associated with folate deficiency, and better seizure control with no perturbation of phenytoin pharmacokinetics.

Anticonvulsants↗
PubMed2002

Evaluation of the efficiency of chemotherapy in in vivo orthotopic models of human glioma cells with and without 1p19q deletions and in C6 rat orthotopic allografts serving for the evaluation of surgery combined with chemotherapy.

BACKGROUND: Malignant gliomas of the central nervous system remain associated with dismal prognoses because of their diffuse invasion of the brain parenchyma. Very few experimental models that mimic clinical reality are available today to test potentially new therapies. The authors set up experimental in vivo glioma models of anaplastic astrocytomas of human and rat origins and anaplastic oligodendroglioma of human origin. Standard hospital chemotherapies were employed to test the validity of these models. METHODS: Three glioma cells lines obtained from the American Type Culture Collection (i.e., human Hs683 and U373 cells and rat C6 cells) were implanted into nude mouse brains (Hs683 and U373 cells) and rat brains (C6 cells). The astrocytic nature, as opposed to the oligodendrocytic nature, of the Hs683 and U373 models was investigated by using quantitative (computer-assisted microscopy) immunohistochemical characterizations of nestin, vimentin, glutathione-S-transferase alpha (GSTalpha), GSTmu, GSTpi, and p53 expression. Comparative genomic hybridization (CGH) was employed to investigate 1p19q losses. Chronic administrations of carmustine (BCNU), fotemustin, or temozolomide were assayed in the xenografted U373 and Hs683 models. Both BCNU-related chemotherapy and surgery were assayed in the C6 model. RESULTS: The quantitative phenotypic analyses pointed to the oligodendroglial nature of the Hs683 cell line and the astrocytic nature of the U373 cell line. The Hs683 cells exhibited 1p19q losses, whereas the U373 cells did not. BCNU, fotemustin, and temozolomide dramatically increased the time of survival of the Hs683 oligodendroglioma-bearing mice, whereas temozolomide only induced a weak but nevertheless statistically significant increase in the U373 glioma-bearing mice. In the C6 rat glioma model, surgery and BCNU chemotherapy were more efficient than either treatment alone. CONCLUSIONS: The in vivo models of gliomas of the central nervous system developed in the current work best mimicked clinical reality. They can be used either to identify new therapies against human gliomas or to optimize existing therapies.

Animals↗
PubMed2000

The potential use of anti-enteroviral drugs in the immunocompromised.

Therapy for enteroviral infection is now a reality, and one compound, pleconaril, has been successfully used in a number of clinical trials, with others likely to follow over the next few years. Antibody-deficient patients are particularly prone to chronic enteroviral infection, and have proved to be a useful model in which to examine the efficacy of new drugs. Apart from polioviruses, immunization and immunotherapy to prevent and treat infection is probably impracticable because so many different strains are involved. Ultimately, combination drug therapy will probably be the best strategy to treat chronic infection.

Journal Article↗
PubMed1998

[Gene therapy of restenosis].

Although angioplasty has undergone considerable development, restenosis remains an unsolved problem. No drugs have been proved effective in the prevention of restenosis. Prophylactic stenting is the only treatment with some efficacy. The pathophysiology of restenosis involves both intimal hyperplasia with a major proliferative component at the dilated site and geometric constrictive remodeling of the artery. Stenting seems to prevent the remodeling but does not prevent and may even worsen the intimal hyperplasia. Gene therapy may be effective in preventing the proliferative component of the intimal hyperplasia: therapeutic genes can be delivered locally to the arterial wall cells at the dilated site during or immediately after angioplasty, using viral (e.g., adenoviruses) or nonviral vectors. The main candidate genes stimulate a variety of endogenous mechanisms whose effects consist in inhibition of smooth muscle cell proliferation (Rb gene); sensitization of proliferating cells to the effects of cytotoxic substances, thus allowing selective chemotherapy (HSV-tk gene); or stimulation of reendothelization (VEGF gene). Other genes have also yielded promising results (ecNOs, p21, Coxl, etc.). Clinical application of these techniques cannot be envisioned until studies are available proving that the delivery methods (transfer vectors or local delivery systems) are completely safe, and that the candidate genes are effective in "realistic" models. If these hurdles are cleared successfully, preventive gene therapy for gene restenosis may well become a clinical reality.

Angioplasty, Balloon, Coronary↗
PubMed2000

Review article: the continuing dilemma of dyspepsia.

Dyspepsia drains a substantial proportion of healthcare resources in industrialized countries and an appropriate management strategy is needed. An aetiological role for Helicobacter pylori infection has been demonstrated in a number of pathological conditions associated with dyspepsia, such as peptic ulcer and gastric malignancies, but not in functional dyspepsia. Endoscopy and diagnosis-based treatment, H. pylori testing and eradication therapy, history taking and empirical therapy, are the main tools that are currently available for managing patients with upper gastrointestinal symptoms. Endoscopy identifies malignancies and organic diseases of the proximal gut and therefore provides reassurance to both doctors and patients. It should be recommended in older patients with suspicious symptoms and it has proven to be more cost-effective than empirical H2-receptor antagonists in patients with ulcer-like symptoms. Empirical eradication in all dyspeptics without suspicious symptoms is a cost-effective approach that cures the majority of peptic ulcers. Nevertheless, it does not control symptoms in the majority of patients, it may exacerbate gastro-oesophageal reflux disease, and it encourages antibiotic resistance. The realities of current clinical practice require empirical therapy in most, if not all, the dyspeptics seen by general practitioners. A detailed history taking can help to diagnose gastro-oesophageal reflux disease and to identify suspicious symptoms. Furthermore, identification of dyspepsia subgroups may provide guidance for empirical therapy. Nevertheless, even analysis of individual symptoms does not provide a sufficient diagnostic yield to differentiate functional from organic dyspepsia and appropriate investigations are needed in patients with poor response to short-term therapy or frequent relapses.

Dyspepsia↗