The impact of late acute rejection after cadaveric kidney transplantation

BACKGROUND: Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long-term graft and patient outcome of AR occurring late in the post-transplant period. AIM: To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR). MATERIALS AND METHODS: 687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)-based immunosuppression, from 1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co-morbid conditions, HLA matching, rejection episodes, patient and graft survival. ANALYSIS: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared. RESULTS: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft failure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p<0.001). Seventy-eight patients (11.4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5-yr graft survival for those who had LAR was 45% and 10-yr survival was 28%. HLA mismatches were more frequent in those with EAR vs. NAR (zero mismatches in HLA-A: 36 vs. 24%, HLA-B: 35 vs. 23% and HLA-DR: 63 vs. 41%, p<0.003). There was no difference in mismatching frequency between NAR and LAR. CONCLUSIONS: AR had a deleterious impact on graft survival, particularly if occurring after 90 d. AR episodes should therefore be divided into early and late phases. In view of the very poor graft survival associated with LAR, it is important to gain further insight into the main aetiological factors. Those such as suboptimal CyA blood levels and non-compliance with medication should be further investigated with the aim of developing more effective immunosuppressive regimens in order to reduce the incidence of LAR.     

Information needs and sources of information for women with breast cancer: a follow-up study

This paper reports a study which examined the specific information needs and sources of information for 105 women with breast cancer at two time points, the time of diagnosis and a mean of 21 months from diagnosis At diagnosis the priority information needs concerned survival issues Further from diagnosis survival issues were still a concern, but information about the risk to family members of getting breast cancer showed a significant increase in importance Information about sexual attractiveness was ranked last at both the newly diagnosed and follow-up stages Information sources at the time of diagnosis centred around the specialist breast care service, while further from diagnosis few professional or voluntary sector sources were utilized, with women receiving most of their information from media sources such as women's magazines The relevance of these findings for nurses and other health care professionals is discussed     

Black tea constituents, theaflavins, inhibit 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice

The present study investigated the inhibitory activity against lung tumorigenesis by a group of characteristic black tea polyphenols, theaflavins. In a short-term study, female A/J mice were treated with a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK; 103 mg/kg b.w., i.p.) on day 0, and 0.1 and 0.3% theaflavins were administered as the sole source of drinking fluid starting 24 h after NNK treatment. The proliferation index of the lung tissues was measured by the incorporation of bromodeoxyuridine (BrdU) immunohistochemically. The highest NNK-induced proliferation rate of bronchiolar cells, observed on day 5, was significantly decreased by 0.3% theaflavins (proliferation index, 1.51 +/- 0.08 versus 2.35 +/- 0.16). In a long- term lung tumorigenesis study, pulmonary adenomas were observed in 100% (30/30) of the mice at week 16 after NNK treatment. Administration of theaflavins (0.1%) as the sole source of drinking fluid, starting 2 days after the NNK treatment until the termination of the experiment, significantly reduced the tumor multiplicity and volume by 23% (8.5 +/- 0.6 versus 6.5 +/- 0.6 tumors/mouse) and 34% (0.08 versus 0.05 mm3 per tumor), respectively. The proliferation index in lung adenomas was also significantly inhibited by theaflavins. The present work demonstrates the inhibitory action of theaflavins against NNK-induced pulmonary hyperproliferation and tumorigenesis.