Glucocorticoid resistance in dialysis patients may impair the kidney allograft outcome

This study examines in vitro steroid sensitivity in chronic renal failure ( CRF) patients and its influence on the allograft outcome. We determined the inhibitory effect of dexamethasone ( DEX) on concanavalin A ( Con-A)-stimulated peripheral blood mononuclear cell ( PBMC) proliferation, and glucocorticoid receptor` ( GR) number of binding sites ( B-max) and affinity ( K-d) in 28 CRF patients and 40 normal healthy controls. Based on K-d values > 95th percentile from controls, patients were divided into two groups: glucocorticoid resistant ( n = 11) and glucocorticoid sensitive ( n = 17). Patients were followed during 18 months post-transplantation observing acute rejection episodes ( ARE), chronic allograft nephropathy ( CAN), allograft failure and death. The DEX concentration that caused 50% inhibition of Con-A-stimulated PBMC proliferation ( IC50) was higher in CRF than in healthy controls ( 2.2 x 10(-5) +/- 1.0 x 10(-5) versus 8.3 x 10(-6) +/- 4.2 x 10(-6) mol/ L, P = 0.02). Values of Kd ( 12.4 +/- 1.8 versus 7.2 +/- 0.9 nM) and Bmax ( 7.7 +/- 1.1 versus 4.1 +/- 0.3 fmol/ mg protein) were higher in CRF patients ( P = 0.02 and P = 0.001, respectively). There were higher incidences of ARE ( P = 0.02) and CAN ( P = 0.002) in the glucocorticoid-resistant group. Univariate and multivariate logistic regression showed that Kd was an independent predictor of ARE ( OR 8.8, P= 0.03) aswell as of CAN ( OR 16.5, P= 0.01). In conclusion, we observed glucocorticoid resistance in a subgroup of CRF patients undergoing dialysis, which led to a higher morbidity due to ARE and CAN in an 18-month follow-up period.

Frequency of insertion/deletion polymorphism in exon 8 of HLA-G and kidney allograft outcome

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib molecule predominantly expressed in cytotrophoblasts, where it acts as a specific immunosuppressor. Literature data have shown that grafts in some settings, such as cardiac and liver/kidney-associated transplantations, express HLA-G and this expression is associated with less severe rejection and also reduces the incidence of rejection. Fourteen-base pair deletion/insertion polymorphism has been reported in exon 8 of the 3`-untranslated region of HLA-G. This polymorphism within exon 8 of the HLA-G gene might influence transcription activity, which in turn may influence the stability of HLA-G transcripts. This influences the stability of the HLA-G protein and therefore is of potential functional relevance. In order to determine a possible correlation between the 14-bp insertion/deletion polymorphism and kidney allograft outcome, we isolated genomic DNA from 83 patients who had received isolated kidney allografts, and we classified the 83 specimens into two groups, grafts presenting Banff features of rejection group and a non-rejection group, and compared them with a control group of 97 healthy subjects. The 14-bp polymorphism at exon 8 was genotyped in all groups. There was no significant difference in allelic frequencies of 14-bp insertion/deletion polymorphism between normal controls and kidney transplant patients. In the RG, the homozygous genotype +14/+14 bp (P = 0.0238) was significantly increased in the group with acute rejection compared with the healthy control group. Analysis of other HLA-G polymorphisms and functional studies on immune regulation are essential to elucidate the role of HLA-G in kidney allografts.

The broad effects of the functional IL-10 promoter-592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome

Periodontal diseases are infectious diseases, in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. It occurs through the generation of metalloproteinases and the activation of bone resorption mechanisms. Anti-inflammatory cytokines such as IL-10 seem to attenuate periodontal tissue destruction through the induction of tissue inhibitors of metalloproteinases (TIMPs) and the inhibitor of osteoclastogenesis osteoprotegerin (OPG). A high individual variation in levels of IL-10 mRNA is verified in periodontitis patients, which is possibly determined by genetic polymorphisms. In this study, the IL-10 promoter -592C/A single nucleotide polymorphism ( SNP), which is associated with a decrease in IL-10 production, was analyzed by RFLP in 116 chronic periodontitis (CP) patients and 173 control (C) subjects, and the IL-10, TIMPs, and OPG mRNA expression levels in diseased gingival tissues were determined by real-time-PCR. The IL-10-592 SNP CA (P=0.0012/OR=2.4/CI:1.4-4.1), AA (P=0.0458/OR=2.3/CI:1.1-4.9), and CA+AA (P=0.0006/OR=2.4/CI: 1.4-3.4) genotypes and the allele A (P=0.0036/OR=1.7/CI:1.2-2.4) were found to be significantly more prevalent in the CP group when compared with control subjects. Both CA and AA genotypes were associated with lower levels of IL-10, TIMP-3, and OPG mRNA expression in diseased periodontal tissues and were also associated with disease severity as mean pocket depth. Taken together, the results presented here demonstrate that IL10-592 SNP is functional in CP, being associated with lower levels of IL-10 mRNA expression, which is supposed to consequently decrease the expression of the downstream genes TIMP-3 and OPG, and influence periodontal disease outcome. J. Leukoc. Biol. 84: 1565-1573; 2008.

Outpatient cognitive behavioural therapy programme for alcohol dependence impact of naltrexone use on outcome

Objective: Cognitive-behavioural therapy (CBT) has been effectively used in the treatment of alcohol dependence. Clinical studies report that the anticraving drug naltrexone, is a useful adjunct to treatment. Currently, few data are available on the impact of adding this medication to programmes in more typical, outpatient, and rehabilitation settings. The objective of this study was to examine the impact on outcome of adding naltrexone to an established outpatient alcohol rehabilitation program which employed CBT. Method: Fifty patients participated in an established 12-week, outpatient, 'contract'-based alcohol abstinence programme which employed CBT. They also received naltrexone 50 mg orally daily (CBT + naltrexone). Outcomes were compared with 50 historical, matched controls, all of whom participated in the same programme without an anticraving medication (CBT alone). All patients met DSM-IV criteria for alcohol dependence. Results: Programme attendance across the eight treatment sessions was lower in the CBT alone group (p < 0.001). Relapse to alcohol use occurred sooner and more frequently in the CBT alone group (p < 0.001). Rehabilitation programme completion at 12 weeks was 88% (CBT + naltrexone) compared with 36% for (CBT alone) (p < 0.001). Alcohol abstinence at 12 weeks was 76% (CBT + naltrexone) compared with 18% (CBT alone) (p < 0.001). Conclusion: When employing the same outpatient rehabilitation programme and comparing outcomes using matched historical controls, the addition of naltrexone substantially improves programme attendance, programme completion and reported alcohol abstinence. In a typical outpatient programme, naltrexone addition was associated with significantly improved programme participation, better outcomes and was well tolerated.

Low level expression of human papillomavirus type 16 (HPV16) E6 in squamous epithelium does not elicit E6 specific B- or T-helper immunological responses, or influence the outcome of immunisation with E6 protein

Mice transgenic for E6/E7 oncogenes of Human Papillomavirus type 16 display life-long expression of E6 in lens and skin epithelium, and develop inflammatory skin disease late in life, which progresses to papillomata and squamous carcinoma in some mice. We asked whether endogenous expression of E6 induced a specific immunological outcome, i.e. immunity or tolerance, or whether the mice remained immunologically naive to E6. We show that prior to the onset of skin disease, E6 transgenic mice did not develop a spontaneous E6-directed antibody response, nor did they display T-cell proliferative responses to dominant T-helper epitope peptides within E6. In contrast, old mice in which skin disease had arisen, developed antibodies to E6. We also show that following immunisation with E6, specific antibody responses did not differ significantly among groups of EB-transgenic mice of different ages (and therefore of different durations and amounts of exposure to endogenous E6), and non-transgenic controls. Additionally, E6 immunisation-induced T-cell proliferative responses were similar in E6-transgenic and non-transgenic mice. These data are consistent with the interpretation that unimmunised Eb-transgenic mice that have not developed inflammatory skin disease remain immunologically naive to E6 at the B- and Th levels. There are implications for E6-mediated tumorigenesis in humans, and for the development of putative E6 therapeutic vaccines. (C) 2001 Elsevier Science B.V. All rights reserved.

Outcome of the acute abdomen in patients with previous spinal cord injury

Background: Patients with spinal cord injury (SCI) have always posed difficulties for the diagnosis of an acute abdomen. The aim of the present study was to define this problem retrospectively at Princess Alexandra Hospital and to assess the results of treatment for these patients. Methods: A retrospective review was conducted of 133 SCI patients admitted with an acute abdomen in the 16 years prior to this analysis at the Spinal Injuries Unit (SIU) of Princess Alexandra Hospital. There were 21 patients who conformed to the study criteria. All the patients had sustained traumatic SCI at or above the level of T11, more than 1 month prior to admission. Results: There were 13 male and eight female patients. The time lapse between SCI and the onset of an acute abdomen ranged from 1.5 months to 27 years. The age range was 26-79 years. The majority of patients had C6 injuries (six patients). There were 18 patients with injury levels above T6 and three patients with injuries below this level. The time taken to diagnose the cause of the acute abdomen ranged between 1 day and 3 months. Investigations were found to be useful in making the diagnoses in 61.9% of cases. There were 14 patients who had surgical interventions. Five patients had surgical complications and there were two deaths in the study. The length of follow up was 1-132 months. The mortality in the study was 9.5%. Conclusion: An aggressive approach to the diagnosis and treatment of the acute abdomen in SCI patients with suspicious symptoms is recommended. A high index of suspicion should be maintained in those patients with pre-existing SCI who present with abdominal trauma.

Phyllodes tumors of the breast: Correlation of nucleolar organizer regions with histopathological malignancy grading, flow cytometric DNA analysis and clinical outcome

To examine whether nucleolar organizer regions detected by argyrophilia (Ag-NOR counts) can be used as a prognostic indicator in phyllodes tumors of the breast, and to compare its usefulness with that of DNA flow cytometric analysis, 28 cases of breast phyllodes tumors (including 15 benign, two borderline and 11 malignant tumors) were subjected to Ag-NOR staining and counting as well as DNA flow cytometric analysis. S-phase fraction and DNA ploidy analysis showed useful trends for improving outcome predictions in malignant phyllodes tumors. However, high Ag-NOR counts were significant in predicting survival status (P = 0.013) and reached near statistical significance in predicting survival times (P = 0.07). In predicting survival status, results for Ag-NOR counts were significantly better than those for ploidy analysis (P = 0.02) and S-phase fraction (P < 0.01). Only S-phase fraction was significantly predictive of survival times (P = 0.025). It is concluded that Ag-NOR counts and DNA flow cytometric analysis, easily performed using paraffin sections, give information that can improve predictions made by histopathological classification. Ag-NOR counts are significant in predicting survival in the presence of histopathological features of malignancy.

Couple distress after sudden infant or perinatal death: A 30-month follow up

Objective: To examine, using a 30-month prospective study, patterns of anxiety, depression and alcohol use in couples following stillbirth, neonatal death or sudden infant death syndrome. Methodology: One hundred and thirty-eight bereaved and 156 non-bereaved couples completed standardized interviews at 2, 8, 15 and 30 months post-loss. Results: At all interviews, bereaved couples were significantly more likely than non-bereaved couples to have at least one distressed partner. Rarely were both partners distressed in either group. For bereaved couples, 'mother only' distress declined from 21% to 10% during the study. 'Father only' distress ranged from 7% to 15%, peaking at 30 months. Bereaved mothers who were distressed at 2 months reported significantly lower marital satisfaction at 30 months. Conclusions: At the couple level, the experience of a baby's death is multifaceted. Gender differences are common and partners' needs may change over time. Early recognition of these differences may facilitate longer-term adjustment for both partners.

Treatment outcome in individuals with chronic pain: is the Pain Stages of Change Questionnaire (PSOCQ) a useful tool? Jenny StrongCorresponding Author Contact Information, E-mail The Corresponding Author, a, Kym Westburya, Glen Smithb, Ian McKenziec and William Ryan

The efficacy of psychological treatments emphasising a self-management approach to chronic pain has been demonstrated by substantial empirical research. Nevertheless, high drop-out and relapse rates and low or unsuccessful engagement in self-management pain rehabilitation programs have prompted the suggestion that people vary in their readiness to adopt a self-management approach to their pain. The Pain Stages of Change Questionnaire (PSOCQ) was developed to assess a patient's readiness to adopt a self-management approach to their chronic pain. Preliminary evidence has supported the PSOCQ's psychometric properties. The current study was designed to further examine the psychometric properties of the PSOCQ, including its reliability, factorial structure and predictive validity. A total of 107 patients with an average age of 36.2 years (SD = 10.63) attending a multi-disciplinary pain management program completed the PSOCQ, the Pain Self-Efficacy Questionnaire (PSEQ) and the West Haven-Yale Multidimensional Pain Inventory (WHYMPI) pre-admission and at discharge from the program. Initial data analysis found inadequate internal consistencies of the precontemplation and action scales of the PSOCQ and a high correlation (r = 0.66, P < 0.01) between the action and maintenance scales. Principal component analysis supported a two-factor structure: 'Contemplation' and 'Engagement'. Subsequent analyses revealed that the PSEQ was a better predictor of treatment outcome than the PSOCQ scales. Discussion centres upon the utility of the PSOCQ in a clinical pain setting in light of the above findings, and a need for further research. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Debiasing the outcome effect: The role of instructions in an audit litigation setting

The outcome effect occurs where an evaluator, who has knowledge of the outcome of a judge's decision , assesses the quality of the judgment of that decision maker. If the evaluator has knowledge of a negative outcome, then that knowledge negatively influences his or her assessment of the ex ante judgment. For instance, jurors in a lawsuit brought against an auditor for alleged negligence are informed of an undetected fraud, even though an unqualified opinion was issued. This paper reports the results of an experiment in an applied audit judgment setting that examined methods of mitigating the outcome effect by means of instructions. The results showed that simply instructing or warning the evaluator about the potential biasing effects of outcome information was only weakly effective. However, instructions that stressed either (1) the cognitive non-normativeness of the outcome effect or (2) the seriousness and gravity of the evaluation ameliorated the effect significantly. From a theoretical perspective, the results suggest that there may both motivational and cognitive components to the outcome effect. In all, the findings suggest awareness of the outcome effect and use of relatively nonintrusive instructions to evaluators may effectively counteract the potential for the outcome bias.