Therapy of Selected Diseases
crease in arteriolar resistance, ensuring adequate myocardial perfusion. During exercise, further dilation of arterioles is impossible. As a result, there is ischemia associated with pain. Pharmacological agents that act to dilate arterioles would thus be inappropriate because at rest they may divert blood from underperfused into healthy vascular regions on account of redundant arteriolar dilation. The resulting “steal effect” could provoke an anginal attack. (3) The intramyocardial pressure, i.e., systolic squeeze, compresses the capillary bed.
I’ve spent the last 28 years studying, practicing,
teaching, and evolving as a naturopathic
physician. Two themes have been consistent:
natural medicine and the health care of women.
Alternative medicine has come to be the
popular term used to distinguish natural, noninvasive
therapies from conventional medicine.
Dr. Sharon Rounds, the editor for this series who invited us to write a book on rare
lung diseases, developed the idea after attending the 2004 Lymphangioleiomyomatosis
(LAM) Foundation annual research meeting. She was a keynote speaker at that event
(during her tenure as the president of the American Thoracic Society) and was witness
to the power of patient advocacy and the mission-based scientific effort that had
brought this rare disease of women from obscurity to clinical trials with targeted molecular
therapies in under a decade.
Atherothrombosis describes the occurrence of both
atherosclerosis and thrombosis in an artery, a
common feature of peripheral arterial disease.1
It is estimated that 1 in 16 U.S. residents who were
at least 40 years of age in 2000 (approximately 8.5
million persons) had peripheral arterial disease.
Resistance towards the responsible pathogens are also seen in developed countries. The
situation has worsened often due to limited resource available to investigate and provide
reliable susceptibility data on which rational treatments can be based as well as means to
optimize the use of antimicrobial agents. The emergence of multi-drug-resistant isolates in
tuberculosis, acute respiratory infections and diarrhea, often referred to as diseases of
poverty, has had its greatest toll in developing countries.
The general meaning of gene therapy is to correct defective genes that are responsible
for disease development. The most common form of gene therapy involves the
insertion, alteration or removal of genes within an individual's cells and biological
tissues. Many of gene transfer vectors are modified viruses. The ability for the delivery
of therapeutic genes made them desirable for engineering virus vector systems.
Recently, the viral vectors in laboratory and clinical use have been based on RNA and
DNA viruses processing very different genomic structures and host ranges.
Autoimmune disease represents a group of more than 60 different chronic autoimmune
diseases that affect approximately 6% of the population. It is the third major category of
illness in the United States and many industrialized countries, following heart disease
and cancer. Autoimmune diseases arise when one’s immune system actively targets and
destroys self tissue resulting in clinical disease. Common examples include Systemic
Lupus Erythematosus, Type 1 Diabetes, Rheumatoid Arthritis and Multiple Sclerosis.
Other Diseases The power and versatility of gene transfer approaches are such that there are few serious disease entities for which gene transfer therapies are not under development. Besides those already discussed, other areas of interest include gene therapies for HIV and for neurodegenerative disorders.
Celiac Disease (CD) or Gluten Sensitive Enteropathy (GSE) is a life‐long disorder. It is
characterized by inflammation in the small intestine of genetically predisposed
individuals caused by inappropriate immune response to gluten, a protein enriched in
some of our common grains (wheat, rye and barley). The toxicity of gluten is
manifested by the autoimmune action of T‐lymphocytes on mucosal cells in the small
intestine, disrupting its vital function of absorbing nutrients from food.
Long-Term Expression in Genetic Disease: In Vivo Gene Transfer with Recombinant Adeno-Associated Viral (AAV) Vectors
Recombinant AAV vectors have emerged as attractive gene delivery vehicles for genetic disease. Engineered from a small replication-defective DNA virus, they are devoid of viral coding sequences and trigger very little immune response in experimental animals. They are capable of transducing nondividing target cells, and the donated DNA is stabilized primarily in an episomal form, thus minimizing risks associated with insertional mutagenesis.
Nonsteroidal antiandrogens such as flutamide, bicalutamide, and nilutamide block the binding of androgens to the receptor. When an antiandrogen is given alone, testosterone levels remain the same or increase. Compared to testosteronelowering therapies, antiandrogens cause fewer hot flashes, less of an effect on libido, less muscle wasting, fewer personality changes, and less bone loss. Gynecomastia remains a significant problem but can be alleviated in part by tamoxifen.
Although limited prospective randomized clinical trials showed no statistical differences among treatment agents for cessation of diarrhea (the primary outcome endpoint; Table 123-2), later observational studies suggest that response rates to metronidazole may have decreased. The clinical response rate for bacitracin is 10–20% lower than that for vancomycin; therefore, bacitracin use for first-line therapy is discouraged. All drugs, particularly vancomycin, should be given orally if possible.
Intermediate-risk patients are those
with any of the following criteria: microscopic tumour invasion into the perithyroidal
tissues at initial surgery, cervical lymph node metastases or 131I uptake outside the thyroid
bed on the initial post-treatment scan, or tumour with aggressive histology or vascular
invasion. Finally, high-risk patients have macroscopic tumour invasion, incomplete tumour
resection, distant metastases or elevated thyroglobulin out of proportion to what is seen on
the post-treatment scan (Cooper et al., 2009).
According to the most recent updates, retroviral and lentiviral vectors represent 23% of all
the vector types and 33% of the viral vectors used in Gene Therapy clinical trials. Moreover,
retroviral vectors are currently the blockbuster vectors for the treatment of monogenic and
infectious diseases and gene marking clinical trials (Edelstein 2010).
Retroviruses are double stranded RNA enveloped viruses mainly characterized by the
ability to “reverse-transcribe” their genome from RNA to DNA.
It has been said that the control of disease has three goals, which, in
increasing order of attraction are palliation, cure, and prevention. For most types
of disseminated cancer, medical science has achieved only the first of these
objectives, while for some malignancies the side effects of the therapeutic agents
employed rival the disease itself in precluding a desirable quality of life.
Tham khảo sách 'erectile dysfunction – disease-associated mechanisms and novel insights into therapy edited by kenia pedrosa nunes', y tế - sức khoẻ, y học thường thức phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả
Indications in gene therapy clinical trials. The chart divides clinical gene transfer studies by disease classification. A majority of trials have addressed cancer, with monogenic disorders and cardiovascular diseases the next largest
categories. (Reproduced with permission from J Gene Med. New Jersey, Wiley, 2006.)
Gene Transfer for Genetic Disease
Gene transfer strategies for genetic disease generally involve gene addition therapy. This approach most commonly involves transfer of the missing gene to a physiologically relevant target cell. ...
For patients with a rising PSA after radiation therapy, salvage prostatectomy can be considered if the disease was "curable" at the outset, if persistent disease has been documented by a biopsy of the prostate, and if no metastatic disease is seen on imaging studies. Unfortunately, case selection is poorly defined in most series, and morbidities are significant. As currently performed, virtually all patients are impotent after salvage radical prostatectomy, and ~45% have either total urinary incontinence or stress incontinence.
Other Hepatitis Viruses Hepatitis A virus is rarely transmitted by transfusion; infection is typically asymptomatic and does not lead to chronic disease. Other transfusion-transmitted viruses—TTV, SEN-V, and GBV-C—do not cause chronic hepatitis or other disease states. Routine testing does not appear to be warranted.
West Nile Virus
Transfusion-transmitted WNV infections were documented in 2002. This RNA virus can be detected using NAT; routine screening began in 2003, and more
than 1000 blood donors have tested positive.
The answers to questions with high discriminating value can quickly narrow the range of potential causes of diarrhea and help determine whether treatment is needed. Important elements of the narrative history are detailed in Fig. 122-1.
Physical Examination The examination of patients for signs of dehydration provides essential information about the severity of the diarrheal illness and the need for rapid therapy. Mild dehydration is indicated by thirst, dry mouth, decreased axillary sweat, decreased urine output, and slight weight loss.