EPSTEIN–BARR VIRUS (EBV) INFECTION IN INFECTIOUS MONONUCLEOSIS: VIRUS LATENCY,REPLICATION AND PHENOTYPE OF EBV-INFECTED CELLS

Primary Epstein–Barr virus (EBV) infection may manifest itself as a benign lymphoproliferative disorder, infectious mononucleosis (IM). EBV infection has been characterized in lymphoreticular tissues from nine patients with IM using the abundantly expressed EBV-encoded nuclear RNAs (EBERs) as a marker of latent infection. Expression of the virus-encoded nuclear antigen (EBNA) 2 and of the latent membrane protein (LMP) 1 was seen in variable proportions of cells in all cases. Double labelling revealed heterogeneous expression patterns of these proteins. Thus, in addition to cells revealing phenotypes consistent with latencies I (EBNA2⁻/LMP1⁻) and III (EBNA2⁺/LMP1⁺), cells displaying a latency II pattern (EBNA2⁻/LMP1⁺) were observed. Cells expressing EBNA2 but not LMP1 were also detected; whilst this may represent a transitory phenomenon, the exact significance of this observation is at present uncertain. EBER-specific in situ hybridization in conjunction with immunohistochemistry revealed expression of the EBERs mainly in B-lymphocytes, many of which showed features of plasma cell differentiation. By contrast, convincing evidence of latent EBV infection was not found in T-cells, epithelial or endothelial cells. Double-labelling immunohistochemistry revealed expression of the replication-associated BZLF1 protein in small lymphoid cells, often showing plasmacytoid differentiation. There was no unambiguous expression of this protein in other cell types. These results suggest that B-cells are the primary target of EBV infection and that plasma cells may be a source of infectious virus found in the saliva of IM patients. © 1997 John Wiley & Sons, Ltd.     

Is There an Advantage to Venlafaxine in Comparison with Other Antidepressants?

The purpose of this article is to compare and contrast the benefits and limitations of antidepressant drugs. Several different classes of antidepressants are available for treatment of major depressive disorder, each with its own benefits and limitations as a result of its pharmacological profile. Tricyclic antidepressants (TCAs) and monoamine oxidase (MAO) inhibitors are effective in a large proportion of depressed patients, but their use is often limited by short- and long-term safety/tolerability problems. Selective serotonin reuptake inhibitors (SSRIs) exhibit comparable efficacy to TCAs in most patients, but may be less effective in certain patients. Additionally, SSRI use may by impacted by clinically significant drug interactions. Venlafaxine is a selective serotonin-noradrenaline reuptake inhibitor (SNRI) with unique pharmacological properties that may enhance its efficacy as well as its safety profile. In clinical trials, venlafaxine exhibits antidepressant activity in a broad range of patients with major depression, including those with melancholia, agitated or retarded symptoms, anxiety symptoms, and refractory or resistant depression. Venlafaxine has shown potential for an early onset of action and offers dose flexibility that may allow recruitment of additional responders at higher dosages. Because of its lack of affinity for muscarinic cholinergic, histaminergic, and alpha₁-adrenergic receptors, venlafaxine has a safety profile that is superior to that of TCAs. Venlafaxine also is devoid of the drug interactions characteristic of SSRIs. © 1997 John Wiley & Sons, Ltd.     

Transvenous Atrial Cardioversion Threshold in Patients with Implantable Cardioverter Defibrillator: Influence of Active Pectoral Can

Recent studies have shown that transvenous atrial cardioversion is feasible with lead configurations primarily designed for implantable cardioverter defibrillators (ICD). The purpose of this study was to examine the influence of an active pectoral ICD can on the atrial cardioversion threshold (ADFT). Forty consecutive patients received a transvenous single lead system (Endotak DSP 0125, CPI, St. Paul, MN, USA) in combination with a left subpectoral ICD (Ventak Mini, CPI) for treatment of malignant ventricular tachyarrhythmias. Patients were randomized into two groups: 21 received a Hot Can 1743 and 19 patients a Cold Can 1741. Step-down testing of the ventricular defibrillation threshold (VDFT) was performed intraoperatively and evaluation of the ADFT for induced atrial fibrillation (AF) at predischarge. After testing, each patient received a 2-J shock and was asked to quantify discomfort on a numerical scale ranging from 0 to 10. Both groups were comparable with regard to all clinical parameters studied. The mean VDFT in patients with a Hot Can device was significantly lower than in patients with a Cold Can (7.5 ± 2.3 J vs 9.8 ± 3.8 J; P < 0.03). The mean ADFT in the Hot Can group tended to be lower than in the group with Cold Cans (3.4 ± 1.4 J vs 4.5 ± 2.4 J; P = 0.07), and the proportion of patients in whom atrial cardioversion was accomplished at low energies (≤ 3 J) was higher in patients with active compared with patients with inactive pulse generators (57% vs 26%; P < 0.04). The mean discomfort reported after delivery of a 2-J shock was comparable in both groups (Hot Can 5.2 ± 1.9; Cold Can: 5.3 ± 2.1; P = NS). We conclude that the inclusion of an active left subpectoral can in the defibrillation vector of a ventricular ICD seems to reduce the energy requirements for atrial cardioversion without increasing the discomfort caused by low energy shocks.     

Discrimination of Sinus Rhythm, Atrial Flutter, and Atrial Fibrillation Using Bipolar Endocardial Signals

Discrimination of NSR, AFL, and AF. Introduction : Analysis of endocardial signals obtained from an electrode located in the right atrium as realized in newly designed dual chamber, implantable cardioverter defibrillators might be used to provide additional therapeutic options, such as overdrive pacing or low-energy atrial cardioversion for the treatment of concomitant atrial flutter (AFL) or atrial fibrillation (AF). Therefore, we developed a computer algorithm for discrimination of normal sinus rhythm (NSR), AFL, and AF that may lead to adequate differential therapy of atrial tachyarrhythmias in an automated mode.
Methods and Results : During an electrophysiologic study, bipolar endocardial signals from the high right atrium were obtained in 28 patients during sustained AFL or AF and after restoration of NSR. A total of 286 data segments of 5-second duration were recorded (NSR: 96, AFL: 86, AF: 104). Mean atrial cycle length (MCL), standard deviation of mean atrial cycle length (SDCK), and index of irregularity (IR). defined as the ratio between MCL and SDCL, were calculated for each data segment. A cutoff of 315 msec for MCL allowed discrimination of NSR from atrial tachyarrhythmias with 100% sensitivity and specificity. For discrimination of AF from AFI- by using SDCL, a cutoff value of 11.5 msec led to a sensitivity of 99% and a specificity of 90%. Best discrimination of AF from AFL was found for the criterion IR ≥ 7.5%, resulting in a sensitivity of 100% with a specificity of 95% for AF detection.
Conclusion : The investigated algorithm provides discrimination of NSR, AFL, and AF with high sensitivity and specificity. Incorporation of this algorithm in an implantable automated antitachycardia device may lead to adequate differential therapy in patients suffering from spontaneous episodes of AF and AFL.     

Haemophilia Utilization Group Study: assessment of functional health status in haemophilia

The purpose of this study was to assess the relationship between health care and utilization of that health care, and to provide a base measurement of health status in patients with haemophilia. Provider interview and retrospective chart review of 336 patients with haemophilia treated during 1995 at one of five comprehensive haemophilia treatment centres was conducted to measure patient health status characteristics and utilization of health care. Two health status scales were included. The first, the Self-Care Measure, was a four-point single item scale measuring the patient's ability for basic self-care, which was scored by a chart review and an interview with the health-care provider. The second, the Haemophilia Utilization Group Study (HUGS) Functional Status Measure, is a four-item, 10-point scale developed specifically for patients with haemophilia. Our sample represents 27% of actively treated patients in region IX. The mean score on the HUGS Functional Status Measure was 8.7 (SD=2.4). The HUGS scale exhibited a ceiling effect across all four scales: attitude (n=269, 80.1%), overall wellbeing (n=263, 78.3%), working (n=254, 75.6%) and orthopaedic status (n=195, 58.0%). Both higher total health-care costs and factor VIII annual costs were significantly associated with lower scores on the HUGS Functional Status Measure. Health status is a critical component in the assessment of the utilization and outcomes of care. In the absence of the availability of a patient interview, the HUGS Functional Status Measure can be used as one characteristic that explains the variation in the utilization of health care by patients with haemophilia.     

Risk factors of institutionalization in an elderly disabled population

Due to increased life expectancy and demographic ageing an increasingnumber of elderly people have to spend the eve of their lifein institutional settings, which is often associated with adversepsychosocial and financial consequences. The purpose of thisprospective study is to assess the extent and determinants ofinstitutionalization in a population sample of severely disabledelderly people from south Germany. The study population includedall non-institutionalized persons in a defined region who metthe criteria of permanent nursing dependency set by the Germanstatutory health insurance system. Study participants were recruitedin 1991–1993 and followed for a mean of 1.7 years. Rateratios of Institutionalization for potential risk factors werecalculated using Cox's proportional hazards model. Out of 1,583study participants 159 aged 60 years or older were admittedto a nursing home during the follow-up period. Old age, femalegender, living In urban compared to rural areas, professionalprovider of nursing care compared to family members as maincare givers and cognitive impairments independently increasedthe rate of institutionalization In multivariable analysis.There was no relationship between limitations in basic activitiesof daily living and the rate of institutionalization. Theseempirical data extend the scarce database in Germany, whichis needed for further planning of nursing care facilities inthe community in order to improve the situation of disabledpeople, in particular to prevent nursing home admission.