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At least 55 records · Page 3Linked to original sources
PubMed2005

Gene therapy progress and prospects: fetal gene therapy--first proofs of concept--some adverse effects.

Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease based on the hypothesis that prenatal intervention may avoid the development of severe manifestations of early-onset disease, allow targeting of otherwise inaccessible tissues including expanding stem cell populations, induce tolerance against the therapeutic transgenic protein and thereby provide permanent somatic gene correction. This approach is particularly relevant in relation to prenatal screening programmes for severe genetic diseases as it could offer prevention as a third option to families faced with the prenatal diagnosis of a genetically affected child. Most investigations towards in utero gene therapy have been performed on mice and sheep fetuses as model animals for human disease and for the application of clinically relevant intervention techniques such as vector delivery by minimally invasive ultrasound guidance. Other animals such as dogs may serve as particular disease models and primates have to be considered in immediate preparation for clinical trials. Proof of principle for the hypothesis of fetal gene therapy has been provided during the last 2 years in mouse models for Crigler Najjar Disease, Leber's congenital amaurosis, Pompe's disease and haemophilia B showing long-term postnatal therapeutic effects and tolerance of the transgenic protein after in utero gene delivery. However, recently we have also observed a high incidence of liver tumours after in utero application of an early form of third-generation equine infectious anaemia virus vectors with SIN configuration. These findings highlight the need for more investigations into the safety and the ethical aspects of in utero gene therapy as well as for science-based public information on risks and benefits of this preventive gene therapy approach before application in humans can be contemplated.

Animals↗
PubMed2005

Clinical applications of stem cells for the heart.

Repair of the heart is an old dream of physicians caring for patients with cardiac disease. Experimental studies suggest that cardiac transfer of stem and progenitor cells can have a favorable impact on tissue perfusion and contractile performance of the injured heart. Some researchers favor stable stem cell engraftment by fusion or transdifferentiation into cardiomyocyte or vascular cell lineages as likely explanations for these beneficial effects. Others have proposed that transient cell retention may be sufficient to promote functional effects, eg, by release of paracrine mediators. Although the mechanistic underpinnings of stem cell therapy are still intensely debated, the concept of cell therapy has already been introduced into the clinical setting, where a flurry of small, mostly uncontrolled trials indicate that stem cell therapy may be feasible in patients. The overall clinical experience also suggests that stem cell therapy can be safely performed, if the right cell type is used in the right clinical setting. Preliminary efficacy data indicate that stem cells have the potential to enhance myocardial perfusion and/or contractile performance in patients with acute myocardial infarction, advanced coronary artery disease, and chronic heart failure. The field now is rapidly moving toward intermediate-size, double-blinded trials to gather more safety and efficacy data. Ultimately, large outcome trials will have to be conducted. We need to proceed cautiously with carefully designed clinical trials and keep in mind that patient safety must remain the key concern. At the same time, continued basic research to elucidate the underlying mechanism of stem cell therapy is clearly needed.

Animals↗
PubMed2004

Antenatal diagnosis of fetal heart disease.

Antenatal diagnosis of congenital heart disease is most commonly made at the routine 20-week anomaly scan. Not all abnormalities can be detected by prenatal ultrasound but detection can be improved by obtaining outlet views and by the use of colour Doppler. This article provides an overview of the uses and limitations of fetal echocardiography.

Echocardiography, Doppler, Color↗
PubMed2001

[The best in 2000 on clinical pharmacology].

The year 2000 provided many new articles in clinical pharmacology and therapeutics in the different fields of cardiology. The authors present some of them in this review. In the field of prevention, the statins were the object of complementary studies showing their value in high cardiovascular risk patients with benefits not only in the reduction of coronary but also cerebrovascular events. These benefits are maintained at long-term. The debate about the value of Vitamin E is still on-going with divergent results (HOPE, SPACE studies...). The absence of secondary coronary prevention by post-menopausal hormone replacement therapy seems to be confirmed. The arrhythmogenic risk of neuroleptic drugs is of increasing concern. New data also suggests the possibility of a venous thromboembolic risk. The NSAIDs are an important factor in the first episode of cardiac failure. The risk of thromboembolism with the 3rd generation of contraceptives has been confirmed. Some data has been published about the safety of drugs used in cardiology: the haemorrhagic risk of LMW heparin in renal failure and of aspirin, even at low doses, drug interactions, aspirin-ACE inhibitors interaction. Future perspectives include the potential value of vasopeptidase inhibitors, of cerebral natriuretic peptide and of therapeutic approaches to induce angiogenesis in ischaemic heart disease (gene therapy, recombining factors).

Aspirin↗
PubMedDate not supplied

HIV update.

Few diseases have spread so rapidly around the world or caused such severe morbidity and mortality as HIV/AIDS. After reading this review and update on the pandemic, readers will: Know the current status of HIV/AIDS in the United States and worldwide. Understand basic concepts of epidemiology and infectious disease and how these areas of study relate to HIV. Know basic concepts of immunology and the human immune system. Recognize major clinical manifestations of HIV/AIDS and their radiographic features. Understand the importance of universal precautions in protecting health care workers from blood-borne pathogens such as HIV. Understand the legal and psychosocial issues that affect people who have AIDS.

AIDS-Related Opportunistic Infections↗
PubMed2002

[Gene therapy of Gaucher's and Fabry's diseases: current status and prospects].

Gaucher disease and Fabry disease are lysosomal storage disorders characterized by the accumulation of sphingolipids. In both cases, the goal of gene therapy is to permanently provide tissues with enzyme levels allowing to avoid storage of the undigested substrates. Different gene therapy strategies must however be designed as Gaucher disease is due to a deficiency in the membrane-associated enzyme glucocerebrosidase, whereas Fabry disease is caused by a deficiency in the soluble enzyme alpha-galactosidase. Indeed, a soluble enzyme can be provided to tissues is trans by gene-modified cells whereas gene transfer has to target the most affected cells in the case of membrane-bound enzymes. Thus, in non-neurological Gaucher disease (type 1), the hematopoietic tissue has to be targeted as the deficiency affects the monocyte/macrophage lineage. Following promising preclinical studies, clinical protocols have been initiated to explore the feasibility and safety of retroviral transfer of the glucocerebrosidase gene into CD34+ cells from patients with type 1 Gaucher disease. Although gene-marked cells were detected in vivo, the level of corrected cells was very low, a finding indicating that improved vectors along with partial myeloablation may be necessary. Here, lentiviral vectors should enable more gene transduction into the hematopoietic target cells. As concerns the diffuse neurological lesions in types 2 and 3 of Gaucher disease, they will probably be especially difficult to target by gene therapy because of the non soluble nature of glucocerebrosidase. Finally, over the last few years, Fabry disease has become a compelling target for gene therapy as an etiology-based treatment strategy. Indeed, several recent studies aiming at creating a large in vivo source of alpha-galactosidase have yielded positive long-term results in the Fabry knock-out mouse model.

Animals↗
PubMed1987

Chronobiology and viral diseases: a search for a probe which may assist in forecasting the onset of a disease and enhancing its treatment.

Aspects of Chronobiology related to the diseases of the eye and infectious diseases of the eye--particularly those that are caused by viral agents are viewed. The possible biological rhythmicity as a tool to predict the onset of these pathological conditions is discussed. The natural history of the diseases which are caused by various strains of Herpes point to the involvement of a strong and an influential endogenous biological rhythm. Based on these findings the benefits of application of chronobiological techniques to the study of these diseases is stressed.

Biological Clocks↗
PubMed2005

Time-specific ecological niche modeling predicts spatial dynamics of vector insects and human dengue cases.

Numerous human diseases-malaria, dengue, yellow fever and leishmaniasis, to name a few-are transmitted by insect vectors with brief life cycles and biting activity that varies in both space and time. Although the general geographic distributions of these epidemiologically important species are known, the spatiotemporal variation in their emergence and activity remains poorly understood. We used ecological niche modeling via a genetic algorithm to produce time-specific predictive models of monthly distributions of Aedes aegypti in Mexico in 1995. Significant predictions of monthly mosquito activity and distributions indicate that predicting spatiotemporal dynamics of disease vector species is feasible; significant coincidence with human cases of dengue indicate that these dynamics probably translate directly into transmission of dengue virus to humans. This approach provides new potential for optimizing use of resources for disease prevention and remediation via automated forecasting of disease transmission risk.

Aedes↗
PubMed1999

On the application of integer-valued time series models for the analysis of disease incidence.

Statistical time series models are practical tools in public health surveillance. Their capacity to forecast future disease incidence values exemplifies their usefulness. Using these forecasts, one can develop strategies to trigger alerts to public health officials when irregular disease incidence values have occurred. Clearly, the better the forecasting performance of the model class used in the time series analysis, the more realistic are the alerts triggered. The time series analysis of disease incidence values has often entailed the Box and Jenkins model class. However, this class was designed to model real-valued variables whereas disease incidences are integer-valued variables. A new class of time series models, called integer-valued autoregressive models, has been developed and studied over the past decade. The objective of this paper is to introduce this new class of models to the application of time series analysis of infectious disease incidence, and to demonstrate its advantages over the class of real-valued Box and Jenkins models. The paper also presents a bootstrap method developed for the calculation of forecast interval limits.

Communicable Diseases↗
PubMed1990

Prevalence and prediction of osteopenia in chronic liver disease.

To obtain information on the prevalence and clinical and laboratory correlates of osteopenia in patients with chronic liver disease, we measured bone densities and 30 selected laboratory variables in 133 subjects (70 men, 63 women) with liver disease. Thirty-two had alcoholic liver disease, 18 had primary biliary cirrhosis, 16 had primary sclerosing cholangitis, 48 had other forms of cirrhosis (cryptogenic, posthepatic) and 19 had chronic hepatitis or fibrosis without cirrhosis. Bone densities of the lumbar spine and three sites of the proximal femur (neck, Ward's triangle, greater trochanter) were estimated by dual-photon absorptiometry. Bone densities at all sites were significantly correlated to one another (r = 0.4 to 0.9; 95% confidence intervals = 0.24-0.54 to 0.81-0.90; p less than 0.0001 for all). Compared with an age- and gender-matched reference group, patients with liver disease had highly significant decreases in bone densities (greater than 2 standard deviations below control values; p less than 0.0008 at all sites). Decreases were particularly marked (24% to 42%) at Ward's triangle, the site of the femoral neck particularly prone to fracture. The prevalence of decreased bone densities ranged from 10% to 56%, depending on the site studied and the nature of the liver disease. Among 30 laboratory variables studied, there were significant (p less than 0.05) correlations with bone densities at more than one site for urinary creatinine (r = 0.21, 0.25), urinary calcium (r = -0.18, -0.23), serum total alkaline phosphatase (r = -0.18, -0.27) and the liver-1 isozyme of serum alkaline phosphatase (r = -0.19, -0.26).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density↗