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At least 775 records · Page 43Linked to original sources
PubMed2001

Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus.

Posttransplantation lymphoproliferative disease (PTLD) is a major complication of current clinical transplantation regimens. The lack of a reproducible large-animal model of PTLD has limited progress in understanding the pathogenesis of and in developing therapy for this clinically important disease. This study found a high incidence of PTLD in miniature swine undergoing allogeneic hematopoietic stem cell transplantation and characterized this disease in swine. Two days before allogeneic peripheral blood stem cell transplantation, miniature swine were conditioned with thymic irradiation and in vivo T-cell depletion. Animals received cyclosporine daily beginning 1 day before transplantation and continuing for 30 to 60 days. Flow cytometry and histologic examination were performed to determine the cell type involved in lymphoproliferation. Polymerase chain reaction was developed to detect and determine the level of porcine gammaherpesvirus in involved lymph node tissue. PTLD in swine is morphologically and histologically similar to that observed in human allograft recipients. Nine of 21 animals developed a B-cell lymphoproliferation involving peripheral blood (9 of 9), tonsils, and lymph nodes (7 of 9) from 21 to 48 days after transplantation. Six of 9 animals died of PTLD and 3 of 9 recovered after reduction of immunosuppression. A novel porcine gammaherpesvirus was identified in involved tissues. Miniature swine provide a genetically defined large-animal model of PTLD with many characteristics similar to human PTLD. The availability of this reproducible large-animal model of PTLD may facilitate the development and testing of diagnostic and therapeutic approaches for prevention or treatment of PTLD in the clinical setting.

Amino Acid Sequence↗
PubMed2005

Controlled-release oxycodone-induced seizures.

BACKGROUND: The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. OBJECTIVE: The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. METHODS: A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. RESULTS: Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. CONCLUSIONS: A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

Analgesics, Opioid↗
PubMed1994

[Diagnosis and treatment of generalized forms of sarcoidosis].

A total of 132 patients with generalized sarcoidosis (GS) who amounted to 2.8% out of 4700 examinees and followed-up patients with respiratory sarcoidosis were studied. The pathomorphological study of biopsy specimens, X-ray functional, and immunological studies are of great importance in the diagnosis of GS. The latter in the examinees was characterized by the most common lesions to the skin, subcutaneous fat, peripheral lymph nodes, liver, spleen, central and peripheral nervous systems and eyes. The combined pathogenetic therapy developed, which involves corticosteroidal hormones and anabolic drugs, immunomodulators, antioxidants and antihypoxants has been shown to be effective in 62% of the patients.

Adolescent↗
PubMed2004

Gene doping in sports.

Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement.

Doping in Sports↗
PubMed2003

Treatment for chronic depression using Cognitive Behavioral Analysis System of Psychotherapy (CBASP).

The article presents an overview of the chronic depression construct in the Diagnostic and Statistical Manual of Mental Disorders (DSMs) since 1980, including developmental etiology and psychopathological patterns of the chronically depressed adult. Then the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), an empirically supported psychotherapy and the only therapy developed specifically to treat chronic depression, is described. CBASP addresses the idiosyncratic problems of the chronically depressed adult using Situational Analysis, the Interpersonal Discrimination Exercise, and Behavioral Skill Training/Rehearsal techniques. The first two techniques are illustrated using a verbatim case example.

Adult↗
PubMed2000

Long-term results with cyclosporine monotherapy in renal transplant patients: a multivariate analysis of risk factors.

There is little information on the long-term outcome of patients initially assigned to cyclosporine (CsA) monotherapy and requiring the addition of steroid therapy during follow-up. The aim of this report is to describe our experience with 143 first renal transplant recipients (120 cadaver transplants, 23 living donor transplants) randomized to receive CsA monotherapy as a treatment arm of three consecutive controlled clinical trials. Median follow-up was 86 months. Thirty-four percent of the patients remained on the original CsA monotherapy, whereas the remaining 66% required the addition of steroid therapy. Cumulative patient and graft survivals at 11 years were 0.89 (95% confidence interval [CI], 0.83 to 0.95) and 0.62 (95% CI, 0.52 to 0.72), respectively. The 11-year graft survival for converted patients was 0.53 (95% CI, 0.39 to 0.67). Cumulative graft half-life was 19.9 +/- 3.47 (SE) years. According to the Cox model, variables at transplantation that correlated with a lower 11-year graft survival were yearly increases in age (relative risk [RR], 1. 04; P = 0.039), monthly increases in hemodialysis duration (RR, 1.01; P = 0.029), no blood transfusion before transplantation (RR, 1.99; P = 0.043), CsA administration in a double daily dose (RR, 2.35; P = 0.008), and a cadaver donor transplant (RR, 4.76; P = 0.039). Multivariate analysis of time-dependent variables showed that delayed graft function recovery (RR, 2.20; P = 0.019) and the need to add steroid and/or azathioprine therapy (RR, 5.28; P = 0.000) were also correlated with a lower graft survival. Patients who added steroid therapy developed infections (P < 0.001), cataracts (P < 0.001), cardiovascular complications (P = 0.004), and arterial hypertension (P = 0.024) more frequently than patients remaining on CsA monotherapy. Patients administered CsA in a single daily dose received significantly less CsA over the years (P = 0.0042) than patients administered CsA in two divided doses. They also showed a trend toward greater creatinine clearance levels, although not statistically significant. In conclusion, this analysis showed that in patients assigned to CsA therapy alone, good long-term patient and graft survival probabilities can be obtained. In approximately one third of the patients, the use of steroids could be avoided for up to 11 years, and these patients had a better long-term outcome than those who required the addition of steroid therapy. Finally, in patients administered CsA in a single daily dose, the possibility of reducing CsA dosage probably led to better intrarenal hemodynamics with improving creatinine clearances.

Adult↗
PubMed2001

Participant supervision in co-therapy.

The present paper describes a model for supervision through co-therapy, developed in a training framework for interns of clinical psychology. The format presented includes a senior therapist and an intern as co-therapists. The model is conceptualized as one of participant supervision in psychodynamic psychotherapy. As such, the model is comprised of two elements. 1. Two therapists work together with one or more patient during a session. 2. The definition of the process as a supervisory situation, beyond the co-work in therapy of the two therapists. We offer the model as a significant and unique supplementary experience for both supervisor and supervise. The supervisory process is based on the principle of "reflection in action," and the actual participation of both partners in the clinical work, facilitating their mutual growth.

Adolescent↗
PubMedDate not supplied

Plantar fat pad atrophy after corticosteroid injection for an interdigital neuroma: a case report.

A case of bilateral interdigital (Morton's) neuroma treated with steroid injection therapy developed plantar fat pad atrophy, shown on magnetic resonance imaging. Some pathologic changes at the site of injection (such as subcutaneous fat atrophy, depigmentation of the skin, and telangiectasias) are well known disadvantages of local steroid injection for the treatment of the Morton's neuroma. Scientific literature reports these problems (mainly as an aesthetic problem) in the dorsal aspect of the foot. In this work, the authors describe a case in which the steroid injection therapy has caused some changes in the plantar aspect of the feet, with serious functional problems. Fat pad atrophy is a serious problem in the foot and can cause a painful metatarsal syndrome with some important effects on the gait.

Adipose Tissue↗
PubMed2003

New developments in electroconvulsive therapy and magnetic seizure therapy.

New findings regarding the mechanisms of action of electro-convulsive therapy (ECT) have led to novel developments in treatment technique to further improve this highly effective treatment for major depression. These new approaches include novel placements, optimization of electrical stimulus parameters, and new methods for inducing more targeted seizures(eg, magnetic seizure therapy [MST]). MST is the use of transcranial magnetic stimulation to induce a seizure. Magnetic fields pass through tissue unimpeded, providing more control over the site and extent of stimulation than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is at an early stage of development. Preliminary results suggest that MST may have some advantages over ECT in terms of subjective side effects and acute cognitive functioning. Studies designed to address the antidepressant efficacy of MST are underway. As with all attempts to improve convulsive therapy technique, the clinical value of MST will need to be established through controlled clinical trials. This article reviews the experience to date with MST, and places this work in the broader context of other means of optimizing convulsive therapy in the treatment of depression.

Animals↗
PubMed1996

Protein-losing enteropathy after Fontan operation: resolution after baffle fenestration.

A 4-year-old child with hypoplastic left heart syndrome and a 6-year-old child with tricuspid atresia had both undergone staged reconstructive operations culminating in a Fontan operation. Peripheral edema, ascites, and hypoalbuminemia refractory to dietary manipulation and steroid therapy developed in both patients. After hemodynamic assessment, each child underwent surgical creation of a 4.8-mm fenestration in the previously placed baffle that separated the systemic venous pathway from the pulmonary venous atrium. Peripheral edema and ascites promptly resolved and serum protein levels normalized within 2 weeks after operation. Systemic arterial saturation is 86% in each child, and both children remain clinically well with no evidence of protein-losing enteropathy on normal diets and without specific medical therapy.

Ascites↗
PubMed1975

Anticonvulsant-induced lymphoma.

Patients with cervical adenopathy of obscure etiology may present a diagnostic problem to the otolaryngologist. The hydantoin family of anticonvulsants is a rare cause of adenopathy that may range from histologically simple lymphoid hyperplasia to true lymphoma. Between these two extremes is a benign clinical entity with the histologic characteristics of lymphoma. A patient on diphenylhydantoin (Dilantin) therapy developed bilateral true vocal cord paralysis and cervical adenopathy. On pathological examination the lesion was interpreted first as malignant lymphoma and later as hydantoin-induced pseudolymphoma. He has now been followed for over two years. Hydantoin-induced adenopathy may vary clinically from a benign condition to a true lymphoma. The malignant form may present long after the anticonvulsant treatment is discontinued. A 10-fold increase in the expected incidence of malignant lymphoma in epileptic patients on hydantoin therapy has been reported; therefore, these patients required long-term follow-up. The otolaryngologist should be aware of this rare clinical entity as an unusual cause of cervical adenopathy associated with vocal cord paralysis.

Adult↗
PubMed2006

Resolving fibrosis in the diseased liver: translating the scientific promise to the clinic.

Liver fibrosis and its end-stage disease cirrhosis are a major cause of mortality and morbidity throughout the world. Fibrosis is a response to chronic liver injury or infection that if unabated leads to the replacement of normal functional liver tissue with scar tissue. Basic research over the past decade has generated a vastly improved knowledge of the cell and molecular biology of liver fibrosis that provides a framework on which to design and develop therapeutics. The field has also witnessed a genuine paradigm shift from the original dogma that liver fibrosis is only ever a progressive process, to the new understanding that liver fibrosis even in an advanced stage can be reversible. There is therefore renewed optimism that liver fibrosis may be cured providing that we develop therapies that halt the fibrogenic process and encourage the natural regenerative properties of the liver. The key to the design of effective therapeutics will be to exploit the ongoing discoveries pertaining to the biology and function of fibrogenic hepatic myofibroblasts and their interplay with other liver cells and with the hepatic extracellular matrix. This review provides a critique of those discoveries in basic research that provide the most promise for translation to the clinic. In addition, we review the latest developments in the search for minimal invasive diagnostic tests for fibrosis that will be essential for determining the efficacy of anti-fibrotic drugs.

Animals↗
PubMed2000

A unique case of central diabetes insipidus (DI) associated with transient pituitary stalk enlargement: close observation over several years using magnetic resonance imaging (MRI) and hypophysial endocrine tests.

We had the opportunity to closely observe a unique case of central diabetes insipidus (DI), in which dramatic changes in both radiological findings and hypophysial functions were seen. A 63-year-old female developed central DI, and magnetic resonance imaging (MRI) revealed a mild thickening of the pituitary stalk and lack of hyperintense signal associated with normal neurohypophysis on T1-weighted images. About three months later, the stalk was found to be remarkably expanded like neoplasm; however, anterior pituitary functions were almost normal on that occasion, except for the absence of GH response to an insulin tolerance test. About nine months after the onset of DI, secondary hypoadrenalism and hypothyroidism, which required replacement therapy, developed transiently, but recovered about one year later. Results of hypophysial endocrine tests during this period showed that the dysfunction was predominantly suprapituitary in nature. As time passed, the stalk lesion began to shrink spontaneously and another MRI, obtained five years after the onset of DI, disclosed normal findings for the infundibulo-hypophysial system, except for lack of the hyperintense signal of the neurohypophysis. The patient has since been healthy, except for the DI, which has been controlled by treatment with vasopressin. We report here a unique case of central DI associated with transient pituitary stalk enlargement.

Adrenocorticotropic Hormone↗
PubMed2006

[Advances in the treatment of lysosomal diseases in infancy].

AIMS: The treatment of lysosomal diseases has undergone a number of significant changes in recent decades. Here we review the different therapeutic approaches that can be used: the well-consolidated haematopoietic stem-cell transplants (HST) and enzyme replacement therapy (ERT), the new therapeutic strategies with small molecules such as substrate reduction therapy (SRT) or enzyme 'enhancement' therapy (EET) and experimental approaches like gene therapy. DEVELOPMENT: We review the status of ERT in general and more particularly in Gaucher disease, Fabry disease, mucopolysaccharidosis type I, Pompe disease and the first stages of Hunter disease and Maroteaux-Lamy syndrome. Their outcomes, indications, safety and side effects are also evaluated. We examine the value of HST in these diseases and more particularly in Hurler syndrome, Maroteaux-Lamy syndrome, globoid cell leukodystrophy, metachromatic leukodystrophy and Gaucher disease. The initial results from using SRT, EET and with gene therapy are briefly outlined. CONCLUSIONS: A great deal of progress has been made in the treatment of some lysosomal diseases in recent decades due to careful use of HST and ERT. Furthermore, the application of the latest therapeutic instruments such as SRT and EET opens up new perspectives in this field.

Child↗
PubMed2006

p27 Regulates the transition of beta-cells from quiescence to proliferation.

Diabetes results from an inadequate mass of functional beta-cells. Such inadequacy could result from loss of beta-cells due to an immune assault or the inability to compensate for insulin resistance. Thus, mechanisms that regulate the number of beta-cells will be key to understanding both the pathogenesis of diabetes and for developing therapies. In this study, we show that cell cycle regulator p27 plays a crucial role in establishing the number of beta-cells formed before birth. We show that p27 accumulates in terminally differentiated beta-cells during embryogenesis. Disabling p27 allows newly differentiated beta-cells that are normally quiescent during embryogenesis to reenter the cell cycle and proliferate. As a consequence, excess beta-cells are generated in the p27(-/-) mice, doubling their beta-cell mass at birth. The early postnatal expansion of beta-cell mass was unaffected in p27(-/-) mice, indicating that the main function of p27 is to maintain the quiescent state of newly differentiated beta-cells generated during embryogenesis. The expanded beta-cell mass was accompanied by increased insulin secretion; however, the p27(-/-) mice were glucose intolerant, as these mice were insulin insensitive. To assess the role of p27 to affect regeneration of beta-cells in models of diabetes, p27(-/-) mice were injected with streptozotocin (STZ). In contrast to control mice that displayed elevated blood glucose levels, p27(-/-) mice showed decreased susceptibility to develop STZ-induced diabetes. Furthermore, beta-cells retained the ability to reenter the cell cycle at a far greater frequency in p27(-/-) mice after developing STZ-induced diabetes compared with wild-type littermates. These data indicate that p27 is a key regulator in establishing beta-cell mass and an important target for facilitating beta-cell regeneration in therapies for diabetes.

Animals↗
PubMed2006

Gottron's papules-like eruption developing under hydroxyurea therapy.

A 57-year-old white female developed a Gottron's papules (GP)-like eruption, without any of the other clinical or laboratory signs of dermatomyositis (DM). She was under hydroxyurea treatment for chronic myeloid leukemia at the time. Skin biopsy was compatible with seborrheic keratosis. Conditions presenting with GP but unrelated to DM are reviewed, with emphasis on hydroxyurea-induced skin lesions.

Biopsy↗
PubMed2002

Development of gene therapy for hematopoietic stem cells using lentiviral vectors.

Lentiviral vectors are promising tools for the development of gene therapy since they can transduce both quiescent and dividing target cells. Lentiviral vectors may be particularly promising gene delivery tools for hematopoietic stem cells since these target cells tend to be quiescent and are therefore difficult target cells for vectors that require dividing targets. Human hematopoietic stem cells that can repopulate NOD/SCID mice have been efficiently transduced using HIV-1-based lentiviral vectors and similar vectors can also transduce murine hematopoietic stem cells. HIV-1 vectors that contain strong general promoters can generate high levels of transgene expression and very high expression levels can be generated in erythroid cells in vivo using beta-globin regulatory sequences to control the expression of the transgene. Current lentiviral vectors have a similar level of biosafety as oncoretroviral vectors and can therefore theoretically be used in clinical gene therapy protocols. Future challenges include the generation of lentiviral vectors that can express more than one transgene at high levels and the generation of safe permanent packaging cells for practical use in clinical gene therapy trials.

Animals↗