Int J Clin Pharm Th
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Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by deficiency of the lysosomal enzyme arylsulfatase A. Deficiency of this enzyme results in intralysosomal storage of sphingolipid cerebroside 3-sulfates (sulfatides), which are abundant in myelin and neurons. A pathological hallmark of MLD is demyelination and neurodegeneration, causing various and ultimately lethal neurological symptoms. This review discusses the potential therapeutic application of hematopoietic stem cell gene therapy and intracerebral gene transfer (brain gene therapy) in patients with MLD.
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Int J Clin Pharm Th · May 2008
ReviewBovine colostrum as a biologic in clinical medicine: a review--Part II: clinical studies.
The value of bovine colostrum as a biologic in medicine is documented in clinical trials and supported by relatively large databases containing case reports and anecdotal findings. The main actions include an antibacterial effect and modulation of the immune response. The ability of bovine colostrum concentrates (BCC are polyvalent bovine colostrum concentrates produced from the colostrums of several 100 cows) to neutralize lipopolysaccharides, i.e. endotoxins arising from Gram-negative bacterial pathogens and to inhibit enterogenic endotoxemia in animal models as shown in the last review to have its counterpart in patient therapy. ⋯ In contrast, elevated systemic levels with concentrations > 300 pg/ml are common in patients with severe Gram-negative sepsis and septic shock. Raised LPS levels occur mainly in patients with Gram-negative bacterial infections who have been treated with bacteriocidal antibiotics. The LPS-lowering effects of BCC are probably due to the numerous active components present in BCC which have their origin in the innate humoral and adaptive immune system of their biologic source, the cow.
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Int J Clin Pharm Th · Oct 2006
ReviewZiconotide--a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain--a short review.
Worldwide a large number of patients suffer from severe chronic pain even after treatment with opioids following the 3-step analgesic ladder developed by the WHO. Intraspinal agents, including morphine, have been tried as a fourth step. However, approximately 20% of cases remain refractory. ⋯ Following intrathecal infusion ziconotide is distributed within the cerebral spinal fluid (CSF) where its clearance (0.38 ml/min) corresponds to the rate of turnover of the CSF. Negligible amounts of ziconotide are present in the systemic circulation where it is rapidly degraded by proteolysis. In conclusion, ziconotide is a new and valuable alternative analgesic for the acute and long-term treatment of severe pain, especially in patients refractory to opioids.
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Int J Clin Pharm Th · Jul 2006
ReviewGlucocorticoid treatment in patients with septic shock: effects on vasopressor use and mortality.
Corticosteroids were proposed for the treatment of sepsis as early as 1940. Several RCTs cast serious doubts on the usefulness of high dose corticosteroids and doubt still persists regarding the efficacy of replacement therapy. Adrenal insufficiency (non-responders to the 250 microg corticotropin test: increase in cortisol < 9 microg/dl) is present in about half of patients with septic shock and is associated with higher rates of refractory hypotension and mortality. ⋯ On the other hand, analysis of studies where low doses of glucocorticoids were given for prolonged periods showed a 24% reduction in the risk of all-cause mortality at 28 days in treated patients (RR = 0.76, 95% CI: 0.64 - 0.90; p = 0.002) without heterogeneity across the trials (p = 0.28). In conclusion, in severe sepsis, high doses of corticosteroids should not be given. Septic shock should be treated with a replacement dose of hydrocortisone.
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Owing to the great progress in clinical chemistry connected with utilization of applied mathematics, pharmacokinetics came into being. The unknown objective methods of research of drugs in human were discovered, among them controlled clinical trials (CCT). These new methodologies generated a new clinical discipline called clinical pharmacology (CPH) which has its roots in basic pharmacology but was applied in clinical specialties. ⋯ There is also an urgent necessity of new legislative acts. These proposals are very general and deficient. They were presented here to conclude this article on the present status of clinical pharmacology with the statement that the real threat for this discipline exists.