ABSTRACT
Abdominal cancer is commonly associated with pain needing medical attention. Effective pain management is available to control pain. Oral opioids are the foundation of analgesic therapy. With adequate implementation of therapeutic guidelines into clinical practice including the use of co-analgesics, adjuvants and non-pharmacological treatment options the quality of life of abdominal cancer patients can be considerably improved. Only in a minority of patients with refractory pain more sophisticated options of pain management will be necessary, e. g., epidural, intrathecal or neurolytic techniques. In this situation the consultation of a pain therapist is recommended.
Subject(s)
Abdominal Pain/etiology , Abdominal Pain/prevention & control , Analgesics, Opioid/therapeutic use , Gastrointestinal Neoplasms/complications , Palliative Care/methods , Terminal Care/methods , Gastrointestinal Neoplasms/drug therapy , Humans , Practice Guidelines as Topic , Practice Patterns, Physicians'ABSTRACT
To study the genetics of atopy systematically we established a mouse model that provides the general phenotype of atopy: the early response characteristic of IgE-dependent eczema or atopic dermatitis, and the diagnostic test of atopy, the skin-prick test. Using an immediate cutaneous hypersensitivity test (ICHS) against birch pollen extract we could classify A/J and C57BL/6 (B6) inbred mouse strains respectively as high responder and low responders. The F1 hybrids were found to be high responders with incomplete penetrance. Backcrossing F1 mice to the low responder B6 strain yielded three classes of responders, high, intermediate, and low. A genome-wide microsatellite screen of the backcross progeny disclosed suggestive linkage to a microsatellite marker on chromosome 6 close to the locus of the IL-5 receptor alpha chain. Its allelic variation in A/J and B6 strains was investigated and two major differences were detected. Firstly, a nucleotide exchange in the 5' untranslated region of B6 mRNA resulted in increased transcription/translation of a reporter construct. Higher expression of the receptor on the cell surface would be expected to favor an allergic immune response. Secondly, the two alleles are differentially spliced so as to yield two soluble isoforms in A/J mice versus one in B6 mice. Higher expression of soluble IL-5R would be expected to reduce the level of allergy through capture of IL-5. Thus both findings conform to the expectation based on susceptibility to atopy and thus identify the IL-5R alpha chain as a likely contributor to the genetics of atopy.
Subject(s)
Hypersensitivity, Immediate/genetics , Polymorphism, Genetic , Receptors, Interleukin/genetics , Alternative Splicing , Animals , Cell Membrane/metabolism , Chimera , Chromosome Mapping , Crosses, Genetic , Cytoplasm/metabolism , Disease Models, Animal , Genetic Linkage , Genotype , Hypersensitivity, Immediate/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Phenotype , Protein Isoforms/genetics , RNA, Messenger , Receptors, Interleukin/metabolism , Receptors, Interleukin-5ABSTRACT
Genetic predisposition and environmental factors modulate the expression of allergic phenotypes. The frequent allergic phenotype 'immediate cutaneous hypersensitivity' was established in mice as a model for atopy. Genetic dissection of this trait requires a robust procedure to assess the allergic phenotype. To this end, different mouse strains were immunized with birch pollen extract. Immediate cutaneous hypersensitivity reactions were induced through intradermal allergen exposure. Wheel formation was quantitated and expressed as a hypersensitivity score according to the bonitur method. This procedure identified A/J and C57BL/6 mice as high- and low-responder strains, respectively. Crosses of A/J and C57BL/6 mice should allow the characterization of mendelian factors responsible for the two extreme phenotypes identified here.
