Morphine or oxycodone for cancer-related pain? A randomized, open-label, controlled trial.

Context: There is wide interindividual variation in response to morphine for cancer-related pain; 30% of patients do not have a good therapeutic outcome. Alternative opioids such as oxycodone are increasingly being used, and opioid switching has become common clinical practice.

Objectives: To compare clinical response to oral morphine vs.

Constipation in cancer patients on morphine.

Goals Of Work: Constipation is a significant problem in patients taking morphine for cancer pain. The aims of this study were (1) to assess the magnitude of constipation in this study cohort, (2) to analyse the constipation treatment strategies and (3) to look for evidence of inter-individual variation in both susceptibility to constipation and response to treatment with laxatives in this patient group.

Materials And Methods: This was an observational study carried out in a tertiary referral cancer hospital.

Donor and recipient CMV serostatus and antigenemia after renal transplantation: an analysis of 486 patients.

Background: Cytomegalovirus infection in renal transplant recipients is a major clinical problem, with both short and long term sequelae. Infection can occur as a result of reactivation of latent virus or new infection from donor tissues. The impact of donor and recipient serostatus on viremia is well recognised, with seronegative recipients at greatest risk after transplantation of an organ from a seropositive donor.

Endothelin axis polymorphisms in patients with scleroderma.

Objective: To evaluate the distribution of polymorphisms in the endothelin 1 (EDN1), endothelin receptor A (EDNRA) and endothelin receptor B (EDNRB) genes in systemic sclerosis (SSc; scleroderma) and SSc subsets.

Methods: Two hundred five patients with SSc and 255 healthy controls were screened for polymorphisms in EDN1, EDNRA, and EDNRB, using sequence-specific primer-polymerase chain reaction. The polymorphisms studied were at the following positions: for EDN1, -1370 (T-1370G) of the promoter, +138 of exon 1 (+138 A/-), +85 of exon 3 (E106E), and +23 of exon 5 (K198N); for EDNRA, -231 of exon 1 (G-231A), and +69(H323H) and +105 (E335E) of exon 6; for EDNRB, +2841 of exon 2 (EDNRB-3), -2547 of exon 3 (EDNRB-2), and -2446 of exon 3 (EDNRB-1).

Clinical pharmacology and pharmacotherapy of opioid switching in cancer patients.

Pain is one of the most common and often most feared symptoms in patients with cancer. Ongoing or progressive pain is physically debilitating and has a marked impact on quality of life. Since a third of the population will die from cancer, and of these, 80% will experience severe pain in their final year of life, effective treatment of cancer-related pain remains both a high priority and an ongoing challenge in clinical practice.

No pain relief from morphine? Individual variation in sensitivity to morphine and the need to switch to an alternative opioid in cancer patients.

Goals Of Work: The aims of this study were (1) to prospectively evaluate the clinical benefits of switching from morphine to an alternative opioid, using oxycodone as first-line alternative opioid, in patients with cancer, (2) to evaluate the consistency of the clinical decision for the need to switch by comparing two hospital sites, and (3) to evaluate whether there were objective predictors that would help identify morphine non-responders who require switching to an alternative opioid and from this to construct a clinical model to predict the need to switch.

Patients And Methods: One hundred eighty-six palliative care patients were prospectively recruited from two hospital sites. Responders were patients treated with morphine for more than 4 weeks with good analgesia and minimal side effects.

Analysis of KL-6 and SP-D as disease markers in bird fancier's lung.

Background And Aim: KL-6 and SP-D are potential serum markers in interstitial lung diseases. Their discriminative value, and ability to reflect pulmonary disease activity and prognosis in bird fancier's lung were analyzed.

Methods: We studied 49 patients, 38 unexposed and 9 exposed controls.

The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation.

Azathioprine metabolism is influenced by activity of the enzyme thiopurine S-methyltransferase (TPMT), which varies markedly between individuals. In this study we examined the influence of TPMT gene polymorphisms on azathioprine dose 1 year after renal transplantation. TPMT coding and promoter genotypes were determined using PCR-based assays.

The Clara cell10 adenine38guanine polymorphism and sarcoidosis susceptibility in Dutch and Japanese subjects.

CC10 (CC16, uteroglobin) is a pulmonary protein postulated to play a counter regulatory role in sarcoidosis pathogenesis. The adenine38guanine (A38G) polymorphism of the encoding CC10 gene (SCGB1A1) is functional. Recently, an association between the low CC10 producing 38A allele and sarcoidosis susceptibility has been reported in Japanese patients from Hokkaido.

Oxygen free radical scavenger enzyme polymorphisms in systemic sclerosis.

We performed a case-control study of polymorphisms of glutathione S-transferase (GST) isoenzymes and manganese superoxide dismutase (MnSOD) in black South Africans with systemic sclerosis (SSc). The frequency of the GSTM1*B phenotype was significantly decreased in the overall SSc group compared with controls (OR=0.19, p(corr)<.

Influence of MHC class II in susceptibility to beryllium sensitization and chronic beryllium disease.

A glutamic acid at residue 69(Glu(69)) in the HLA-DPB1 gene (Glu(69)) is associated with chronic beryllium disease (CBD) and possibly beryllium sensitization (BeS). This study tested the hypothesis that MHC class II polymorphisms are important in susceptibility to BeS and CBD and that the Glu(69) variant is related to markers of disease severity. Genomic DNA was obtained from BeS (n = 50), CBD (n = 104), and beryllium-exposed nondiseased (Be-nondiseased) (n = 125) subjects.

The impact of endothelial nitric oxide synthase polymorphisms on long-term renal allograft outcome.

A major manifestation of chronic allograft failure (CAF) is the accelerated onset of atherosclerotic lesions within the graft. Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been implicated in the pathogenesis of native atherosclerosis. This study tested the hypothesis that polymorphisms in eNOS are associated with susceptibility to CAF after cadaveric renal transplantation.

HLA associations with occupational sensitization to rat lipocalin allergens: a model for other animal allergies?

Background: Laboratory animal allergy is a common occupational health problem affecting between 11% and 44% of exposed researchers. Allergy to rats and mice is most common, probably because these are the animals most frequently used.

Objective: We hypothesized that HLA class II molecules, involved in the presentation of allergen to the T cell and likely candidates for controlling the immune response, might be associated with sensitization to rat urinary proteins among laboratory animal handlers.

Mapping the HLA association in Behçet's disease: a role for tumor necrosis factor polymorphisms?

Objective: Experimental evidence suggests that inappropriate regulation of tumor necrosis factor alpha (TNF alpha) may play a role in the pathogenesis of Behçet's disease (BD). This is supported by recent reports highlighting the efficacy of anti-TNF alpha agents in the treatment of this disease. The TNF gene is encoded in the class III region of the HLA complex adjacent to HLA-B.

Haplotype-specific linkage disequilibrium patterns define the genetic topography of the human MHC.

Detailed knowledge of linkage disequilibrium (LD) is regarded as a prerequisite for population-based disease gene mapping. Variable patterns across the human genome are now recognized, both between regions and populations. Here, we demonstrate that LD may also vary within a genomic region in a haplotype-specific manner.

Differential immunogenicity of HLA mismatches: HLA-A2 versus HLA-A28.

The immunogenicity of human leukocyte antigen (HLA)-A2 versus HLA-A28 was analyzed by antibody production, cytotoxic T-lymphocyte (CTL) induction, and graft survival. We observed that an HLA-A2 mismatched child in HLA-A28 women leads to HLA-A2 specific antibodies in 32% of the women (n=31), whereas in the case of an HLA-A28 child and HLA-A2 women (n=30), no HLA-A28 specific antibodies were found ( P<0.002).

HLA class II polymorphisms and susceptibility to recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is characterised by multiple laryngeal papillomas. Left untreated, the lesions enlarge, spread, and endanger the airway. Medical treatments are unsatisfactory, and repeated surgery remains the mainstay of therapy.

Characterization of cytochrome P450 2D6 alleles using the Invader system.

The cytochrome p450 (CYP) superfamily comprises enzymes that play an essential role in the transformation of medically relevant compounds. Accurate genotyping of polymorphisms in members of this family is drawing increasing interest because certain allelic variants may result in either loss of efficacy or toxic accumulation of therapeutic agents. Debrisoquine 4-hydroxylase, or CYP2D6, is among the most widely studied of the CYPs.

The molecular classification of the clinical manifestations of Crohn's disease.

Background & Aims: Crohn's disease is a common inflammatory disorder of the gut characterized by variation in both location and behavior. Chromosome 16 and the HLA region on chromosome 6 have been implicated in susceptibility to disease. Mutations in the NOD2/CARD15 gene, recently identified on chromosome 16, have been associated with disease overall but are found in only 25% of patients.

Candidate T cell epitopes of the human La/SSB autoantigen.

Objective: To identify T cell epitopes of the human La autoantigen involved in the generation of anti-Ro/La autoantibodies.

Methods: Molecular techniques were used for HLA typing of 219 white patients with systemic lupus erythematosus and 125 white patients with primary Sjögren's syndrome. Anti-Ro/La antibody levels were measured by enzyme-linked immunosorbent assay.