Masquerading Bundle-Branch Block—Electrophysiological Correlation

The term masquerading bundle-branch block has been used to describe a peculiar electrocardiographic abnormality in which the standard leads exhibit a left bundle-branch block pattern while the precordial leads manifest a right bundle-branch configuration. Autopsy studies of patients who have had this electrocardiographic pattern in life have shown diffuse conduction system disease, but direct recordings of conduction system function have never been reported. We recently cared for a man with masquerading bundle-branch block, and in this report we summarize the results of invasive electrophysiological testing. Our findings confirm that masquerading bundle-branch block can be associated with severe and diffuse conduction system disease, and that patients with this finding may require permanent pacemaker implantation, especially if they are symptomatic.     

Timing of the Upper Limit of Vulnerability is Different for Monophasic and Biphasic Shocks: Implications for the Determination of the Defibrillation Threshold

The upper limit of vulnerability (ULV) has been used in clinical studies to predict the DFT in patients with ICDs. Despite the ULV-DFT correlation, uncertainties about the optimal timing of the ULV determination remain. Previous studies using monophasic or biphasic shock waveforms reported differences in the ULV timing with respect to the electrocardiographic T wave. The purpose of this study was to directly compare the ULV timing for mono- versus biphasic T wave shocks. In ten isolated rabbit hearts, mono- and biphasic shocks were delivered randomly during the vulnerable window and at varying shock strengths to determine the ULV. The ULV timing was expressed as the coupling interval at the ULV, the myocardial repolarization state at the ULV measured by monophasic action potential recordings, and the relation between the ULV and the peak of the simultaneously recorded volume conducted T wave. The ULV for biphasic shocks occurred at longer coupling intervals than for monophasic shocks (188.0 ± 9.5 ms vs 173.5 ± 8.8 ms, P < 0.001). This resulted in a more repolarized myocardial state at the ULV for biphasic than for monophasic shocks (81.1%± 7.5% vs 66.9%± 9.0%, P = 0.002). The ULV for monophasic shocks occurred predominantly during the upslope of the T wave (8.0 ± 9.7 ms before the peak of the T wave) whereas the ULV for biphasic shocks occurred at or after the peak of the T wave (5.9 ± 9.3 ms after the peak of the T wave) (P < 0.001). Biphasic shocks delay the timing of the ULV as compared to monophasic shocks. This is important for the prediction of the DFT by ULV measurements.     

Distinct Expression of Cytokines and Mitogenic Inhibitory Factors in Semen of Fertile and Infertile Men

PROBLEM: To assess the effect of seminal plasma (SP) of fertile and infertile men on leukocyte mitogenic response, and the capability of sperm cells to produce IL-1. METHODS: This study included four groups: fertile men (donors, normal), infertile men with azoospermia (azoo), oligo-terato-asthenozoospermia (OTA), and OTA with genital infection (OTA-inf). Mouse spleen cell proliferation in response to lipopolysaccharide (LPS) or Concanavalin-A (Con-A) was examined in the presence of SP from the above four groups. Supernatants (sup) and lysates (lys) of sperm cells from fertile and oligoteratoasthenospermic (OTA) men were evaluated for IL-1 bioactivity by specific bioassay. RESULTS: Seminal plasma (SP) of the four groups were shown to inhibit the mitogenic response of mouse spleen cells to LPS and Con-A. SP of fertile men was significantly more inhibitory than SP from infertile men. Sperm cells from fertile and OTA infertile men constitutively produced IL-1. Sperm cells of both groups produced similar levels of IL-1 as examined in the supernatants and lysates. CONCLUSIONS: Seminal plasma of fertile men had more inhibitory mitogenic activity than that of OTA. Sperm cells constitutively produce IL-1. It is possible that the factors involved in this inhibition are not only anti-proliferative immune factors. Cytokines and inhibitory factors of mitogenesis in the seminal plasma may be involved in the physiology and pathophysiology of sperm functions and thus affect male fertility.     

Ki67 LABELLING INDEX: AN INDEPENDENT PREDICTOR OF PROGRESSION IN PROSTATE CANCER TREATED BY RADICAL PROSTATECTOMY

The clinical course of prostate cancer is highly variable and cannot satisfactorily be predicted by histological criteria alone. Both tumour cell proliferation and neuroendocrine differentiation have been suggested as additional prognostic parameters, neuroendocrine differentiation being considered to enhance tumour cell proliferation. This study investigated the prognostic value of tumour cell proliferation [Ki67 labelling index (LI), MIB 1] and neuroendocrine differentiation and their relationship to each other. One hundred and thirty-seven paraffin-embedded radical prostatectomy specimens were examined. Neuroendocrine differentiation was found in 58 per cent of cases, but was not associated with pTN stage, Gleason score, Ki67 LI, or tumour progression. Ki67 LI was not significantly associated with pTN stage or with Gleason score. High grade ( P =0·0005), advanced local stage ( P =0·0004), positive lymph nodes ( P =0·02), and high Ki67 LI ( P =0·0203) were predictors of tumour progression if univariate analysis was performed, but Cox stepwise regression showed that only advanced local stage ( P =0·0025) and Ki67 LI ( P =0·0105) were independent predictors of tumour progression, the relative risk being 3·6 and 2·5, respectively. It is concluded that Ki67 is an important prognostic marker in prostate cancer with a potential for routine application.     

THE SIGNIFICANCE OF B-CELL CLONALITY IN GASTRIC LYMPHOID INFILTRATES

The significance of the demonstration of a clonal B-cell population in gastric lymphoid infiltrates was investigated by analysis of immunoglobulin heavy chain (IgH) gene rearrangements using sensitive polymerase chain reactions, employing fluorescently labelled primers to target the FR3 and FR1 regions. Tissue blocks were studied showing different histological features (high-grade lymphoma, low-grade lymphoma, and chronic gastritis) from 12 gastrectomies for primary gastric lymphoma, together with blocks showing chronic gastritis from 13 cases of gastric adenocarcinoma and biopsies from 33 patients with active Helicobacter -associated chronic gastritis. Clonal IgH gene rearrangements were detected in lymphoma samples from eight of the gastrectomies for lymphoma (67 per cent). In four of these eight specimens, clonal rearrangements were also detectable in the samples showing only chronic gastritis. Three of 28 (11 per cent) informative biopsies showing active Helicobacter -associated chronic gastritis had detectable clonal populations. Clonal rearrangements were also demonstrated in two of eight (25 per cent) informative blocks showing chronic gastritis from eight gastrectomies for adenocarcinoma. It is concluded that the detection of a clonal population in a suspicious lymphoid infiltrate does not confirm the diagnosis of lymphoma, nor does the absence of such a population imply benignity.     

Effect of intrajejunal elemental diet perfusion on local secretion of soluble CD4 and CD8

The effects of nutrients on the mucosal immune system are poorly understood. The aim of this work was to study the cellular mucosal immune response to intrajejunal perfusion of an elemental diet (ED) or a control (C) electrolyte solution by measuring jejunal secretion of soluble CD4 (sCD4) and sCD8. sCD4 and sCD8 are markers of helper/inducer and suppressor/cytotoxic regulatory functions of T cells, respectively. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with C for 80 min and then with ED containing 21.3g/l of free amino acids and 104.2g/l of oligosaccharides for 100 min. Jejunal fluid and serum concentrations of sCD4 and sCD8 were measured and their jejunal outputs calculated. When compared with C perfusion, jejunal perfusion with the ED resulted in a significant increase of sCD8 but not sCD4 jejunal secretion rates. sCD8 jejunal values increased early after ED perfusion and stayed at roughly the same level during the perfusion. Serum concentrations of sCD4 and sCD8 were not modified during ED perfusion. These data support the hypothesis that ED suppresses the immunologic tone of the gut, which could explain its beneficial effect in the management of intestinal inflammatory disease.     

Viral Persistence in Neurons Alters Synaptic Plasticity and Cognitive Functions without Destruction of Brain Cells

Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury.