Primary biliary cirrhosis. Histological evidence of disease recurrence after liver transplantation

Histological evidence of primary biliary cirrhosis (PBC) recurring after orthotopic liver transplantation (OLT) was looked for in a 'blinded' study of 353 biopsies from 188 patients, 12-100 months post-transplant. Biopsies (172) were obtained from 83 patients transplanted for PBC and 181 biopsies from 105 patients with other liver diseases. Sixteen biopsies from 13 PBC patients (16%) had features suggestive of recurrent disease. The main diagnostic findings were: mononuclear portal inflammatory infiltration (n = 16), portal lymphoid aggregates (n = 14), portal epithelioid granulomas (n = 14) and bile duct damage (n = 15). This combination of changes was not seen in any biopsy from the non-PBC group. Additional features supporting a diagnosis of recurrent disease were ductopenia (n = 7), bile ductular proliferation (n = 7), portal fibrosis (n = 6) and copper deposition (n = 5). Thirteen biopsies from 12 patients were classified as stage I or II histologically. The other patient developed progressive damage in three serial biopsies resulting in an early micronodular cirrhosis, 5 years post-transplant. These observations provide further evidence that PBC recurs after OLT. More studies are required to determine the natural history and clinical significance of the predominantly early histological changes documented so far.     

Influence of left ventricular function on survival and mode of death after implantable defibrillator therapy (Cleveland Clinic Foundation and Montefiore Medical Center experience)

To determine the influence of left ventricular (LV) function on survival and mode of death in patients with an implantable cardioverter-defibrillator (ICD), sudden death, surgical mortality, total arrhythmia-related death, total cardiac death and total death were retrospectively evaluated in 377 consecutive patients. The outcomes were also compared between patients with an LV ejection fraction > or = 30% (214 patients, group 1) and < 30% (148 patients, group 2). Surgical mortality was 3.9% (1.8% in group 1, 7% in group 2). During the follow-up of 25 +/- 20 months, actuarial survival rates of all patients at 3 years were 96% for sudden deaths, 81% for total cardiac deaths and 74% for total mortality. When the 2 groups were compared, survival rates of groups 1 and 2 at 3 years, respectively, were 99 and 90% for sudden death (p < 0.05), 97 and 84% for sudden death and surgical mortality (p < 0.01), 94 and 80% for the total arrhythmia-related death (p < 0.001), 88 and 68% for total cardiac death (p < 0.0001), and 81 and 62% for total mortality (p < 0.002). In group 2, 73% of total cardiac deaths within 1 year were causally related to the arrhythmia. Thus, in patients with an ICD, sudden death rates were very low. However, total cardiac death and total death rates were relatively higher. The outcomes of patients with an ICD were strongly influenced by the degree of LV dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical correlates of circulating immune complexes and antibody reactivity in squamous cell carcinoma of the head and neck. The Department of Veterans Affairs Laryngeal Cancer Study Group

PURPOSE: To evaluate the correlation between the presence and titer of host-derived antibody reactivity, circulating immune complexes, and clinical course and prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Serum samples, obtained from untreated patients with squamous cell carcinoma of the larynx entered onto a multiinstitutional trial, were evaluated for the presence of elevated circulating immune complexes (221 patients) and host-derived antibody directed against two SCCHN cell lines (107 patients). RESULTS: Patients had significantly elevated levels of circulating immune complexes as measured by C1q binding compared with normal controls. Patients with higher levels of circulating immune complexes were less likely to respond to chemotherapy. No correlations were noted between immune complex levels and stage of disease, nodal status, site of disease, recurrence, or survival. Evaluation of native antibody titers for their relationship to clinical correlates showed no statistically significant associations. In sera subjected to immune complex dissociation, patients with moderately or poorly differentiated tumors had significantly higher antibody titers when compared with patients with well-differentiated tumors. Because marked variation in the increase of antibody titers following immune complex dissociation was noted, the ratio of immune complex-dissociated to native antibody titer was examined. Patients with a high ratio had a lower proportion of complete and partial responses to chemotherapy. CONCLUSION: Our results support the conclusion that the formation of tumor-associated immune complexes in patients with SCCHN is associated with a decreased response to chemotherapy.     

Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel

To better understand why sensory neurons express voltage-gated Na+ channel isoforms that are different from those expressed in other types of excitable cells, we compared the properties of the hNE sodium channel [a human homolog of PN1, which is selectively expressed in dorsal root ganglion (DRG) neurons] with that of the skeletal muscle Na+ channel (hSkM1) [both expressed in human embryonic kidney (HEK293) cells]. Although the voltage dependence of activation was similar, the inactivation properties were different. The V1/2 for steady-state inactivation was slightly more negative, and the rate of open-state inactivation was approximately 50% slower for hNE. However, the greatest difference was that closed-state inactivation and recovery from inactivation were up to fivefold slower for hNE than for hSkM1 channels. TTX-sensitive (TTX-S) currents in small DRG neurons also have slow closed-state inactivation, suggesting that hNE/PN1 contributes to this TTX-S current. Slow ramp depolarizations (0.25 mV/msec) elicited TTX-S persistent currents in cells expressing hNE channels, and in DRG neurons, but not in cells expressing hSkM1 channels. We propose that slow closed-state inactivation underlies these ramp currents. This conclusion is supported by data showing that divalent cations such as Cd2+ and Zn2+ (50-200 microM) slowed closed-state inactivation and also dramatically increased the ramp currents for DRG TTX-S currents and hNE channels but not for hSkM1 channels. The hNE and DRG TTX-S ramp currents activated near -65 mV and therefore could play an important role in boosting stimulus depolarizations in sensory neurons. These results suggest that differences in the kinetics of closed-state inactivation may confer distinct integrative properties on different Na+ channel isoforms.     

Cost-effectiveness of detecting breast cancer in lower socioeconomic status African American and Hispanic women through mobile mammography services

A new method based on jackknifing is presented for measuring the difference between two conditions in the onset latencies of the lateralized readiness potential (LRP). The method can be used with both stimulus- and response-locked LRPs, and simulations indicate that it provides accurate estimates of onset latency differences in many common experimental conditions.