O’Fallon, W. Michael

The purpose of this study was to assess the impact of decisions made at operation for primary neck tumor on survival and cause of death—specifically, whether bilateral dissection, unilateral dissection, or delayed dissection influences eventual outcome. Of 244 patients with primary cancer of the supraglottis who were treated surgically, 22 (9%) had no neck treatment, 188 (77%) had unilateral neck dissection, and 34 (14%) had bilateral simultaneous neck dissection. Dissection on one or both sides of the neck was required later in 6 (27%) of the 22 patients with no neck treatment and in 32 (17%) of the 188 patients who had unilateral dissection. There were no differences among the treatment groups in the incidence of death from any cause or in the incidence of death from cancer, although neck stage did differ from group to group. The influence of delayed metastasis on survival was analyzed to explain these findings. Multivariate analysis demonstrated that death occurred at a rate 1.81 times higher in a person with a positive neck stage than in a person of the same age who had a negative stage. Also, death occurred at a rate 1.5 times higher for a person 10 years older than for a person with the same stage of disease. The influence of stage on the probability of need for a second dissection indicated that a patient with a positive neck stage had a 6.3 times greater likelihood of requiring a subsequent neck dissection than a person with a negative neck stage.

Abstract Killer Ig-like receptors (KIRs) are expressed on CD4+CD28null T cells, a highly oligoclonal subset of T cells that is expanded in patients with rheumatoid arthritis. It is unclear at what stage of development these T cells acquire KIR expression. To determine whether KIR expression is a consequence of clonal expansion and replicative senescence, multiple CD4+CD28null T cell clones expressing the in vivo dominant TCR β-chain sequences were identified in three patients and analyzed for their KIR gene expression pattern. Based on sharing of TCR sequences, the clones were grouped into five clone families. The repertoire of KIRs was diverse, even within each clone family; however, the gene expression was not random. Three particular receptors, KIR2DS2, KIR2DL2, and KIR3DL2, had significant differences in gene expression frequencies between the clone families. These data suggest that KIRs are successively acquired after TCR rearrangement, with each clone family developing a dominant expression pattern. The patterns did not segregate with the individual from whom the clones were derived, indicating that peripheral selection in the host environment was not a major shaping force. Several models were examined using a computer algorithm that was designed to simulate the expression of KIRs at various times during T cell proliferation. The computer simulations favored a model in which KIR gene expression is inducible for a limited time during the initial stages of clonal expansion.

Abstract In rheumatoid arthritis (RA), tissue-infiltrating lymphocytes can be arranged in sophisticated organizations that resemble microstructures usually formed in secondary lymphoid organs. Molecular pathways and host risk factors involved in this process of lymphoid neogenesis remain to be defined. In a series of 64 synovial tissue biopsies, lymphoid follicles with germinal centers (GCs) were found in 23.4% of the patients. Follicular dendritic cells (FDCs) were exclusively present in tissues with GCs, suggesting that the recruitment or in situ maturation of FDCs is a critical factor for GC formation in the synovial membrane. Primary follicles were absent, emphasizing the role of Ag recognition in the generation of inflammation-associated lymphoid organogenesis. Multivariate logistic regression analysis of tissue cytokines and chemokines identified two parameters, in situ transcription of lymphotoxin (LT)-β and of B lymphocyte chemoattractant (BLC; BLC/CXCL13), that were predictors for FDC recruitment and synovial GC formation. LT-β and BLC/CXCL13 were found to be independent variables that could, in part, compensate for each other to facilitate GC formation. Prediction models incorporating in situ transcription of LT-β and BLC/CXCL13 had high negative yet moderate positive predictive values, suggesting that LT-β and BLC/CXCL13 are necessary but not sufficient. LT-β protein was detected on a subset of mantle zone and GC B cells, but also on T cells in follicular structures. BLC/CXCL13 was produced by FDCs in follicular centers, but was predominantly found in endothelial cells and synovial fibroblasts, suggesting heterotypic signaling between cells of the synovial membrane and infiltrating lymphocytes in regulating extranodal lymphoid neogenesis.

Clinical risk factors for nephropathy were assessed in a population-based study of Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort). The 1031 Rochester residents with non-insulin-dependent diabetes mellitus (NIDDM) were followed through their complete medical records in the community to 1 January 1982. The prevalence of persistent proteinuria was 8.2% at the diagnosis of NIDDM. Among those initially free of persistent proteinuria, the subsequent incidence was 15.3/1000 person-yr. Twenty years after the diagnosis of diabetes, the cumulative incidence of persistent proteinuria was 24.6%. A proportional hazards model identified the following risk factors for persistent proteinuria in NIDDM: elevated initial fasting blood glucose (P < .01); older age at onset of diabetes (P < .01); male gender (P = .05); and presence of macrovascular disease (P = .05), diabetic retinopathy (P = .05), or glycosuria (P = .07) at the diagnosis of diabetes. Separate analyses controlling for attained age indicated no association between duration of NIDDM and the incidence of persistent proteinuria. Stratified analysis of the two most significant risk factors (fasting blood glucose and age) indicated that hyperglycemia was a stronger risk factor for proteinuria in younger diabetic subjects, perhaps because of a competing risk of death in the elderly diabetic patient. In contrast to a recently described decreasing secular trend of proteinuria in Danish insulin-dependent diabetes mellitus patients, there was no decrease over the past 40 yr in proteinuria risk in this NIDDM incidence cohort.

This study is a retrospective analysis of the influence of previous cardiac surgery on the outcome of heart transplantation in 118 consecutive recipients from January 1988 to December 1996. Group 1 consisted of 67 patients who had no previous sternotomy, group 2 was 33 patients who had one previous sternotomy, and group 3 was 18 patients who had two or more previous sternotomies. The three groups were demographically similar apart from the indication for transplantation and the sex distribution. Preoperative hemodynamic data, except systolic pulmonary artery pressure, were similar among the three groups. There was no significant difference in hospital mortality, 1-year and 5-year actuarial survival rates, incidence of renal dysfunction requiring dialysis, prolonged respiratory support, elevated total bilirubin, re-exploration for bleeding, incidence of mediastinitis, or postoperative hospital stay between the groups. The rejection-free and infection-free survival rates were similar in the three groups. However, previous sternotomy resulted in significantly longer cardiopulmonary bypass times and increased requirement for blood and blood products. The use of a cell saver limited the need for stored red blood cells. This study demonstrated no survival disadvantage of previous sternotomy in patients undergoing heart transplantation.

Background —Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. Methods and Results —The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects ( P =0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. Conclusions —The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography.