HLA and RBC immunization after filtered and buffy coat-depleted blood transfusion in cardiac surgery: a randomized controlled trial.

BACKGROUND: WBC reduction of all blood components is being introduced in many countries. Prevention of immunologic side effects of transfusions is part of the motivation. To compare the immunogenicity of before- or after-storage WBC-reduced RBCs with RBCs without buffy coat, a randomized clinical trial was performed. STUDY DESIGN AND METHODS: Cardiac surgery patients were randomly assigned to receive either RBCs without buffy coat (PCs), WBC-reduced RBCs that were filtered before storage (FFs), or WBC-reduced RBCs that were filtered after storage (SFs). Serum samples for antibody analyses were collected before and after surgery. RESULTS: Sera of 404 patients were tested. Of the 317 patients with negative preoperative screening, 12.6 percent developed anti-WBC antibodies (PC, 14.5%; FF, 9.6%; SF, 13.3%). Of the 87 patients with preoperative anti-WBC antibodies, 28.7 percent showed a marked increase in panel reactivity (PC, 31.3%; FF, 29.0%; SF, 25.0%). ELISA showed the newly formed antibodies to be of IgG class and directed against HLA class I in more than 90 percent of the samples tested. Newly formed anti-RBC antibodies appeared in 5.3 percent (PC, 7.1%; FF, 3.4%; SF 5.4%). Alloimmunization against WBCs and RBCs was strongly correlated (p < 0.01). The differences in newly formed anti-WBC antibodies and anti-RBC antibodies between the trial arms did not show significance. CONCLUSION: Buffy coat removal, and additional WBC reduction by filtration, either before or after storage, result in similar posttransfusion alloimmunization frequencies after a single transfusion event with multiple RBCs.

Cognitive and motor functioning in gene carriers for Huntington's disease: a baseline study.

The aim of this study was to investigate the first changes in cognitive and motor functioning in Huntington's disease. Forty-six gene carriers, not clinically diagnosed for HD, were compared with 88 non-gene carriers. Gene carriers performed significantly worse on the Benton Visual Retention Test. This result was due to a minority of participants who had already developed cognitive impairment. Marginal differences appeared on the motor times of single reaction time measures after correction for motor signs. The findings are discussed in the context of inconsistencies in previous studies and underscore the need for longitudinal research.

DNA ploidy status as a prognostic marker and predictor of lymph node metastasis in laryngeal carcinoma.

In patients with laryngeal carcinoma, nodal metastasis, recurrence after radiotherapy, and prognosis are important factors in clinical decision-making. Parameters such as tumor stage are considered insufficient for predicting these important items. The DNA ploidy status of the tumor may be a useful additional marker. The DNA ploidy status of 38 laryngeal cancers was determined by flow cytometry. Correlations were studied with TNM stage, differentiation, survival rate, relapse risk, recurrence after radiotherapy, and nodal metastasis. A positive correlation of DNA ploidy status with the development of lymph node metastases was found for diploid and peridiploid versus aneuploid tumors (DNA index, <1.4 versus > or = 1.4; p = .007). No correlation was found between ploidy status and recurrence after radiotherapy. The overall survival rate (p = .01), but not the disease-specific survival rate or the relapse risk, showed a correlation with the ploidy status. The DNA ploidy status may be a useful marker for metastatic behavior in head and neck squamous cell carcinoma and may therefore be helpful in decision-making concerning elective treatment of the neck.

Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT).

A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the simultaneous occurrence of red cell fragmentation, laboratory findings of haemolysis, red cell transfusion requirement and de novo or persistent thrombocytopenia caused by consumption, in the absence of disseminated intravascular coagulation. Forty-five centres reported all patients (n = 406) transplanted between July and December 1996. Twenty-three patients developed TTP; the risk of developing TTP was 6.7% at 2 years (95% CI: 4.1% to 9.3%). The median time of onset was 44 d (range 13-319) post transplantation. Significant risk factors for the development of TTP were female gender (P = 0.005) and an unrelated donor (P = 0.046). To treat TTP, cyclosporin administration was discontinued in 10 cases, plasma exchanges were performed in five cases and 12 patients received plasma infusions without plasma exchange. TTP resolved in 13 of the 23 patients (57%). The only factor predictive of resolution of TTP was the absence of nephropathy. Seven patients (30%) were alive at follow-up of 38-45 months from the onset of TTP. Sixteen patients died; the causes were multiple, only three patients had TTP as a central factor. The median time to death was 41 d (range 1-762 d) from the onset of TTP. TTP is a relatively frequent complication of allogeneic stem cell transplantation and it is associated with high mortality, though death is usually caused by multiple factors.

Short-term preoperative radiotherapy interferes with the determination of pathological parameters in rectal cancer.

Short-term preoperative radiotherapy in combination with surgery has been shown to decrease the rate of local recurrence in rectal cancer patients. The effects of this type of radiotherapy on the histopathology of rectal carcinoma has been hitherto unknown. Since various histopathological factors are associated with prognosis, the study of alterations induced by irradiation is an important issue. This paper examines the histopathology of resection specimens from 1306 patients who were treated in a randomized trial that evaluated the benefits of preoperative radiotherapy. In this trial, patients were treated with short-term radiotherapy (5 x 5 Gy) and operated on within 5 days after radiation. Histopathological parameters were determined by the Pathology Review Committee of the trial and we compared tumours of patients with and without preoperative radiotherapy. Tumours of patients who were treated with preoperative radiotherapy were smaller, more often mucinous carcinomas (13% versus 7%, p < 0.001) and more often poorly differentiated (35% versus 24%, p<0.001). After radiotherapy, there was less inflammatory reaction around the tumour (extensive in 7% versus 18%, p<0.001), which was mainly caused by a decrease in T lymphocytes and neutrophil granulocytes. The fibroblastic reaction was more pronounced in the radiotherapy group (extensive in 22% versus 10%, p <0.001). Remarkable histological alterations occurred within a week after 5 days of irradiation of rectal carcinomas. The prognostic value of these factors therefore needs to be re-evaluated for irradiated patients.

Markers for nodal metastasis in head and neck squamous cell cancer.

OBJECTIVE: To identify markers that are relevant as predictors of lymph node metastasis in head and neck squamous cell cancer. DESIGN: Expression of p53, Rb, cyclin D1, E-cadherin, and epithelial cell adhesion molecule was examined using immunohistochemical analysis and traditional histological parameters, and the correlation of these markers with the histologically verified presence of regional metastases was determined. SUBJECTS: The study sample comprised 121 patients with head and neck squamous cell cancer from whom paraffin-embedded material of primary tumors was used. RESULTS: Lymph node metastasis was correlated with the loss of expression of Rb (P =.04) and marginally correlated with the loss of expression of E-cadherin (P =.06). If the results are broken down to subsites, loss of E-cadherin expression in oral cancer (P =.04) and absence of eosinophilic infiltration in laryngeal cancer (P =.003) correlated with nodal metastasis. None of the other markers correlated. A combination of relevant parameters did not result in a much stronger correlation. CONCLUSIONS: The expression of the investigated genetic markers and histopathological features of primary tumors can supply limited information on the metastatic behavior of tumors. Although the use of markers for regional metastasis would be a welcome additional tool, these results do not warrant the use of these parameters for clinical decision making concerning the treatment of the neck in patients with head and neck squamous cell cancer.

Partial matrix excision or segmental phenolization for ingrowing toenails.

OBJECTIVE: To decide whether partial nail extraction with phenolisation or with partial excision of the matrix should be the standard treatment in patients with ingrowing toenails of the hallux. DESIGN: Randomized clinical trial with 12-month follow-up evaluations performed by observers who did not know which procedure was applied. SETTING: Outpatient department of a surgical teaching hospital. PATIENTS: Fifty-eight consecutive patients with a total of 63 ingrowing toenails were randomized. INTERVENTION: Thirty-four partial matrix excisions ("matrix" group) and 29 phenolizations ("phenol" group) were performed. MAIN OUTCOME MEASURES: Recurrence rate, postoperative morbidity (pain, wound exudates, and scar discomfort), and time to complete recovery (wearing shoes, performing normal activities/work). RESULTS: Recurrences were seen after 7 procedures in the matrix group and also after 7 procedures in the phenol group, of which patients were symptomatic and required a second operation in 4 and 3 instances, respectively. None of the observed differences in wound healing, postoperative pain, and recovery were statistically significant. CONCLUSIONS: Partial matrix excision and phenolization are equally effective in treating ingrowing toenails. Because the use of the toxic agent phenol should be avoided, partial matrix excision is the preferable procedure. But in view of the high recurrence rate, there is a need for further improvement of the treatment of ingrowing toenails.

Proliferation in Adrenocortical Tumors: Correlation with Clinical Outcome and p53 Status.

There appears to be a relationship between mitotic activity and malignant behavior in adrenocortical tumors, and carcinomas with a high mitotic index may have a poorer prognosis. This has been investigated further by quantifying and comparing the Ki-67 index using antibody MIB-1 in a series of 14 adrenocortical adenomas and 40 carcinomas. The levels have been correlated with survival and disease-free survival in carcinomas and with evidence of abnormal p53 expression as detected by immunohistochemistry. Nevertheless, many carcinomas have a low level of proliferation that may reflect varying abnormalities within the regulation of both cell division and apoptosis. Expression of bcl-2 protein, an inhibitor of apoptosis has therefore also been examined. The Ki-67 index in carcinomas was significantly higher than in adenomas, but below 4% there was overlap. There was no significant difference in survival between carcinomas with MIB-1 index <3% and those greater, but the lower group had significantly longer disease-free survival (p = 0.02). There was no significant difference between p53 immunopositive and p53 immunonegative carcinomas. No tumor showed immunopositivity for bcl-2 protein. It is concluded that MIB-1 index may contribute additional prognostic information in adrenocortical tumors. Inhibition of apoptosis by bcl-2 does not appear to play a role in tumor growth.