			Home About us Contact

Very Low Doses (very + low_dose)

Distribution by Scientific Domains

Medical Sciences	88%

Selected Abstracts

Lichen planus and leukocytoclastic vasculitis induced by interferon alpha-2b in a subject with HCV-related chronic active hepatitis

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2003
JM De Sousa Pinto
ABSTRACT Lichen planus (LP) has been reported in association with chronic active hepatitis, primary biliary cirrhosis and other chronic liver diseases. The occurrence of LP in persons with hepatitis C virus (HCV) was reported by Robert et al., and the possible relationship between LP and hepatitis virus has also been supported by cases of LP following hepatitis B vaccination. Exacerbation or appearance of LP during the treatment of chronic hepatitis C, lymphoproliferative diseases and melanoma with alpha-interferon (IFN-,) and improvement of these diseases after discontinuation of this drug indicate that IFN-, may possibly induce LP. We present a case of cutaneo-mucous LP in a woman with chronic active hepatitis treated with IFN-, and in whom local leukocytoclastic vasculitis was induced by the intradermal injection of a very low dose of IFN-,. [source]

Physical Medicine and Rehabilitation (88)

PAIN PRACTICE, Issue 1 2001
A. Suputtitada:
Managing spasticity in pediatric cerebral palsy using a very low dose of botulinum toxin type A: preliminary report. (Chulalongkorn University Hospital, Bangkok, Thailand) Am J Phys Med Rehabil 2000;79:320,326. This study was conducted to determine if very low doses of botulinum toxin type A (BTX-A) could reduce spasticity and improve gait in cerebral palsied children when combined with rehabilitation therapy. The trainable (IQ> 80), ambulatory, spastic diplegic or hemiplegic cerebral palsied children, with no fixed contractures in at least one limb, were selected for this study. Patients with a score of 3 on a modified Ashworth scale received 0.5 units of BTX-A/kg/muscle. Patients with an Ashworth score of 4 received 1.0 BTX-A/kg/muscle. After BTX-A injection, all patients received rehabilitation therapy and plastic ankle and foot orthoses for walking. Both groups exhibited improvement in Ashworth score and in gait within 72 h of injection with botulinum toxin. Beneficial effects persisted for 10 to 12 months in most patients, with 3 patients exhibiting benefits for at least 20 months. Conclude that a very low dose of BTX-A combined with rehabilitation therapy resulted in a long-lasting decrease in spasticity and an improvement in gait in children with cerebral palsy. [source]

Fumaric acid esters in severe psoriasis, including experience of use in combination with other systemic modalities

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2004
P. Balasubramaniam
Summary Background Fumaric acid esters (FAE) are used as a systemic treatment for severe psoriasis in Germany but there has been only very little published experience from the U.K. The potential for use in combination with other systemic drugs has not been explored. Objectives To present data relating to the efficacy of FAE in severe psoriasis and to examine the potential dose-sparing effect and safety issues when FAE are combined with other systemic agents. Methods We retrospectively analysed the records of patients who had received FAE for severe psoriasis either alone (in two cases) or along with other systemic medications (in 10 cases). We reviewed the efficacy of FAE and assessed whether dose reductions were achieved for other systemic drugs. Patients were monitored carefully for possible adverse effects. Results Of 12 patients treated with FAE one discontinued the drug very early, due to flushing, while on a very low dose. The other 11 patients all demonstrated an improvement in psoriasis after starting FAE. Nine patients received FAE in combination with other systemic therapies including ciclosporin, acitretin, hydroxyurea and methotrexate. Seven achieved useful overall reductions in the dose of the other drugs. In two patients severe psoriasis was controlled using FAE alone. The side-effect profile of FAE was similar to that previously reported. There was no evidence of drug interactions. Conclusions FAE appear effective and less toxic than other systemic treatments for psoriasis. FAE were used successfully in combination with other systemic agents and generally enabled the doses of the more hazardous drugs to be reduced. Extremely careful monitoring is required when using FAE in such combined regimens as experience is currently very limited. [source]

Sensitivity to sulphonylureas in patients with hepatocyte nuclear factor-1, gene mutations: evidence for pharmacogenetics in diabetes

DIABETIC MEDICINE, Issue 7 2000
E. R. Pearson
SUMMARY Introduction Maturity-onset diabetes of the young (MODY) is characterized by autosomal dominantly inherited, early-onset, non-insulin-dependent diabetes. Mutations in the hepatocyte nuclear factor (HNF)-1, gene are the commonest cause of MODY. Individual patients with HNF-1, mutations have been reported as being unusually sensitive to the hypoglycaemic effects of sulphonylurea therapy. We report three patients, attending a single clinic, with HNF-1, mutations that show marked hypersensitivity to sulphonylureas. Case reports In cases 1 and 2 there were marked changes in HbA1c on cessation (4.4% and 5.8%, respectively) and reintroduction (5.0% and 2.6%) of sulphonylureas. Case 3 had severe hypoglycaemic symptoms on the introduction of sulphonylureas despite poor glycaemic control and was shown with a test dose of 2.5 mg glibenclamide to have symptomatic hypoglycaemia (blood glucose 2 mmol/l) after 4 h despite eating. Conclusions HNF-1, MODY diabetic subjects are more sensitive to sulphonylureas than Type 2 diabetic subjects and this is seen in different families, with different mutations and may continue up to 13 years from diagnosis. This is an example of pharmacogenetics, with the underlying aetiological genetic defect altering the pharmacological response to treatment. The present cases suggest that in HNF-1, MODY patients: (i) sulphonylureas can dramatically improve glycaemic control and should be considered as initial treatment for patients with poor glycaemic control on an appropriate diet; (ii) hypoglycaemia may complicate the introduction of sulphonylureas and therefore very low doses of short acting sulphonylureas should be used initially; and (iii) cessation of sulphonylureas should be undertaken cautiously as there may be marked deterioration in glycaemic control. Keywords, genetics, HNF-1,, MODY, pharmacogenetics, sulphonylurea sensitivity [source]

Environmental carcinogens and p53 tumor-suppressor gene interactions in a transgenic mouse model for mammary carcinogenesis

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2002
Daniel Medina
Abstract Mouse mammary tumorigenesis is greatly influenced by a variety of exogenous agents, such as MMTV, chemical carcinogens (i.e., polycyclic aromatic hydrocarbons), and radiation, as well as by endogenous/physiological factors, such as steroid hormones, tumor-suppressor genes (i.e., Brca1/2,p53), and gene products of modifier genes. In the mouse model, the most frequently used chemical carcinogen has been 7,12-dimethylbenz[a]anthracene (DMBA), which activates the Ha- ras gene but does not alter the p53 tumor-suppressor gene. However, on an existing background of p53 gene alteration, low doses of DMBA are strongly cocarcinogenic. Using a transgenic model system, in which the p53 gene was deleted in the mammary gland, we examined the carcinogenic effects of a variety of external agents and internal factors given at either low doses or physiological doses. These agents/factors included DMBA, ,-radiation, Brca2 heterozygosity, and steroid hormones. All agents/factors increased the tumorigenic response of the p53 null mammary cells, even under conditions where no tumorigenic response was observed in the p53 wildtype mammary cell. The strongest cocarcinogenic effect was observed with the steroid hormone progesterone. The majority of tumors were highly aneuploid and composed of nuclear igh-grade cells. The mechanism for the aneuploidy and secondary events associated with high tumorigenicity were examined using array technology. These results demonstrate that, on a background of underlying genetic instability, very low doses of environmental mutagens and mitogens can produce strong cocarcinogenic effects. Environ. Mol. Mutagen. 39:178,183, 2002. © 2002 Wiley-Liss, Inc. [source]

Effects of oral commensal and pathogenic bacteria on human dendritic cells

MOLECULAR ORAL MICROBIOLOGY, Issue 2 2009
T. Chino
Background/aims:, The oral cavity harbors a diverse and complex microbial community. Bacteria accumulate on both the hard and soft oral tissues in sessile biofilms and engage the host in an intricate cellular dialog, which normally constrains the bacteria to a state of commensal harmony. Dendritic cells (DCs) are likely to balance tolerance and active immunity to commensal microorganisms as part of chronic inflammatory responses. While the role played by DCs in maintaining intestinal homeostasis has been investigated extensively, relatively little is known about DC responses to oral bacteria. Methods:, In this study, we pulsed human monocyte-derived immature DCs (iDCs) with cell wall extracts from pathogenic and commensal gram-positive or gram-negative oral bacteria. Results:, Although all bacterial extracts tested induced iDCs to mature and produce cytokines/chemokines including interleukin-12p40, tumor necrosis factor-,, and monocyte chemoattractant protein-1 (MCP-1), the most important factor for programming DCs by oral bacteria was whether they were gram-positive or gram-negative, not whether they were commensal or pathogenic. In general, gram-negative oral bacteria, except for periodontopathic Porphyromonas gingivalis, stimulated DC maturation and cytokine production at lower concentrations than gram-positive oral bacteria. The threshold of bacteria needed to stimulate chemokine production was 100-fold to 1000-fold lower than that needed to induce cytokines. In addition, very low doses of oral commensal bacteria triggered monocytes to migrate toward DC-derived MCP-1. Conclusion:, Oral commensal and pathogenic bacteria do not differ qualitatively in how they program DCs. DC-derived MCP-1 induced in response to oral commensal bacteria may play a role, at least in part, in the maintenance of oral tissue integrity by attracting monocytes. [source]

Physical Medicine and Rehabilitation (88)

ATG-Fresenius Treatment and Low-Dose Tacrolimus: Results of a Randomized Controlled Trial in Liver Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010
C. E. Benítez
We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end-point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG-Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier:NCT00436722. [source]

Liposomal gemcitabine (GemLip),efficient drug against hormone-refractory Du145 and PC-3 prostate cancer xenografts

THE PROSTATE, Issue 11 2009
Peter Jantscheff
Abstract BACKGROUND Gemcitabine (Gemc) is an efficient chemotherapeutic drug in various cancer types (e.g., pancreas) but has only limited effects on hormone-refractory prostate cancer (HRPCa). Since HRPCa cells are highly sensitive to even low doses of Gemc in vitro, the lack of clinical effects might be due to rapid degradation of Gemc by deaminases combined with impaired accumulation in tumor tissue and PCa cells. Liposomal formulation (GemLip) is expected to protect the entrapped cytotoxic substance from enzymatic degradation and furthermore augment its accumulation within tumor tissues due to an enhanced permeability of the tumor vessels. METHODS Anti-tumoral and anti-metastatic activity of GemLip and Gemc were investigated in two luciferase-expressing, human hormone-refractory PC-3 and Du145 HRPCa xenograft models in immunodeficient mice. Tumor growth was monitored by in vivo luminescence imaging (orthotopic) or callipering (subcutaneous). Anti-metastatic effects of treatment were determined by in vitro luciferase assay of the tissues. RESULTS Tumor growth of subcutaneous Du145 xenografts was significantly inhibited only by GemLip (8 mg/kg: P,=,0.014 and 6 mg/kg: P,=,0.011) but not by conventional Gemc (360 mg/kg). In contrast, growth of orthotopic PC-3 xenografts was significantly inhibited by both, GemLip (P,=,0.041) and Gemc (P,=,0.002). The drugs furthermore strongly reduced spleen and liver metastases in this model. CONCLUSIONS As shown by the very low efficient concentration of GemLip, liposomal entrapment of Gemc greatly enhances its activity. GemLip has, even at very low doses, a significant anti-tumoral and anti-metastatic therapeutic effect in HRPCa xenografts in vivo and was beneficial even when the conventional Gemc failed. Prostate 69:1151,1163, 2009. © 2009 Wiley-Liss, Inc. [source]