HER2 and tau expression as potential markers for response and survival to first line taxane plus cisplatin therapy in non-small cell lung cancer

Aim:   The aim of this study was to assess the role of various HER2 , tau and bcl2 as prognostic markers of responsiveness to taxane and cisplatin therapy in patients with advanced NSCLC.
Methods:   Amplification of HER2 gene determined by chromogenic in situ hybridization (CISH) and HER2 , tau and bcl2 protein expression determined by immunohistochemistry were assessed in 49 patients with NSCLC enrolled in our four clinical trials of taxane plus cisplatin chemotherapy.
Results:   The patients were classified as responders or non-responders, a negative tau expression was associated with a significantly higher rate of response compared to a positive tau expression ( OR 3.33, 95% CI 1.01–10.97, P  = 0.043). Patients with more than stable disease compared to those with progressive disease showed that negative amplification of the HER2 gene was associated with a significantly higher rate of disease control compared to positive amplification ( OR 7.35, 95% CI 0.83–65.21, P  = 0.048). Furthermore, HER2 gene amplification was strongly associated with the overall survival: 20 months (95% CI 9.007–30.993) in patients with negative amplification of the HER2 gene versus 12 months (95% CI 6.584–17.416) in patients with positive amplification of the HER2 gene ( P  = 0.040). A multivariate analysis with the Cox proportional hazards model confirmed that HER2 gene amplification was a significant independent prognostic factor with a hazard ratio of 2.334 (95% CI 1.060–5.142, P  = 0.035).
Conclusion:   Tau protein expression and HER2 gene amplification are the prognostic factors in NSCLC patients treated with a taxane and cisplatin combination.     

Morphologic findings in "zero-hour" biopsies of renal transplants.

The extreme lack of renal grafts for transplantation stimulated us to analyze how strict the selection criteria of kidney donors must be. We investigated therefore if preexisting lesions in renal grafts influence initial and late renal function. 147 zero-hour biopsies of 101 donors (mean age 33, from 6-64 years) were examined. By ligh microscopy 38% of biopsies showed no, 44% showed nonspecific and 18% specific lesions. Nonspecific lesions comprised intimal fibrosis of small arteries in 44%, interstitial fibrosis in 8% and an arteriolar hyalinosis in 29%. Out of 102 immunohistologically examined biopsies 74.5% showed nonspecific IgM/C3 deposits in glomeruli and/or arterioles. An age dependent decrease of normal renal biopsies was found which was most evident in donors older than 40 years. Specific findings consisted of glomerulosclerosis (n = 4), glomerulonephritis (n = 11), intravascular coagulation (n = 10) and eclamptic kidney (n = 1). In case of nonspecific immunohistologic findings and in glomerulonephritis rebiopsies showed that antigen deposits usually disappeared within 4 months. Independent of morphologic findings 82% of transplant recipients had a good initial and late renal function. Since donor age, glomerulosclerosis, glomerulonephritis, intravascular coagulation or eclamptic changes seem not to compromise renal function after transplantation a more liberal choice of donors should be considered.     

Factors influencing vertebral bone density after renal transplantation

To improve our understanding of the mechanisms underlying osteoporosis following renal transplantation, we compared bone mineral density (BMD) in 158 transplant recipients and in 293 patients undergoing maintenance hemodialysis with age- and sex- matched normal controls. Observations in graft recipients were made up to several years following transplantation. Dual-energy X-ray absorptiometry was used to measure BMD. Correlations with clinical variables including serum concentration of parathyroid hormone (PTH) and steroid therapy were evaluated. Lumbar BMD was lower in transplant patients than in dialysis patients at all ages, and continued to decrease with increasing interval posttransplant until the second year after transplantation. Persistent hyperparathyroidism and daily prednisolone dosage were both associated with decreased BMD. Age and creatinine clearance were independent long-term predictors of BMD by multiple regression analysis. Treatment of renal graft recipients with calcium and vitamin D supplements or calcitonin may be indicated in the early months after transplantation.     

Differential diagnosis of kidney transplant rejection and cyclosporin/tacrolimus nephropathy using urine cytology

Abstract: A total of 9000 urine samples from 69 kidney transplant recipients were studied for differential diagnoses of transplant rejection and cyclosporin/tacrolimus toxicity. New–Sternheimer and Papanicolaou staining were used to differentiate cells in urine. We also employed an immunocytochemical technique for further identification of exfoliated cells. With New–Sternheimer and Papanicolaou staining, the predominance of proximal tubular cells was useful to differentiate cyclosporin/tacrolimus toxicity from acute rejection in cases of increased serum creatinine level. During rejection episodes, an increased number of mononuclear cells and renal epithelial cells were found. Immunocytochemical analysis showed a significant increase of CD2-, CD4- CD8-, CD25- and HLA-DR-positive cells with rejection. However, there was no relationship between Banff criteria rejection grade and the increase of mononuclear cells.     

Psychological resilience and active social participation among older adults with incontinence: a qualitative study

Objectives: Incontinence restricts participation in social activities among older adults. However, some older adults participate in social activities despite this condition. This study aimed to describe how older adults with incontinence could be resilient and actively participate in social activities.

Methods: We conducted semi-structured interviews with 11 socially active older adults with incontinence (age 70–90; nine women and two men) at their homes or in private areas of day-service centres in Chiba, Japan. We coded salient narratives by using thematic analysis and extracted themes. Finally, we developed a conceptual model and illustrated the interactions among themes.

Results: We identified seven themes that affected active social participation; five of these pertained to psychological characteristics (‘motivation to be socially active’, ‘psychological stress of incontinence’, ‘desire to interact with others’, ‘willingness to perform physical exercise’, and ‘confidence in managing incontinence’) and the remaining two pertained to supporting environmental factors (‘assistive devices’ and ‘accessible toilet’). Three psychological themes (‘desire to interact with others’, ‘willingness to perform physical exercise’, and ‘confidence in managing incontinence’) were intertwined with supporting environmental factors and increased the participants’ ‘motivation to be socially active’.

Conclusion: Older adults with incontinence can actively participate in the society when they have desire to interact with others, willingness to perform physical exercise, and confidence in managing incontinence. These psychological characteristics are important for being resilient in the face of incontinence and for active social participation.