Restenosis rates following bifurcation stenting with sirolimus-eluting stents for de novo narrowings

The percutaneous treatment of coronary bifurcation stenoses is hampered by an increased rate of subsequent restenosis. The present study reports on the outcomes of a consecutive series of 58 patients with 65 de novo bifurcation stenoses treated with sirolimus-eluting stent implantation in both the main vessel and side branch. At 6 months, the incidence of major adverse cardiac events was 10.3% (1 death and 5 target lesion revascularizations) with no episodes of acute myocardial infarction or stent thrombosis.     

Decreased TNF-alpha and NK activity in obsessive-compulsive disorder

BACKGROUND: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune system, and whether these changes are related to particular clinical characteristics. METHODS: Ex vivo production of TNF-alpha, IL-4, IL-6, IL-10, and IFN-gamma in whole blood cultures, and NK-cell activity and peripheral blood NK cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 50 medication-free outpatients with OCD and 25 controls. RESULTS: In OCD patients, we found a significant decrease in production of TNF-alpha (p < 0.0001) and NK-activity (p = 0.002) in comparison with controls. No significant differences were observed in the other immune variables. Patients with first-degree relatives with OCD had significant lower NK-activity than patients who had no relatives with OCD (p = 0.02), and patients with a childhood onset of OCD had significantly lower number of NK-cells than patients with a late onset (p= 0.003). CONCLUSIONS: Changes in TNF-alpha and NK activity suggest a potential role of altered immune function in the pathophysiology of obsessive-compulsive disorder.     

Chemically synthesized protein as tumour-specific vaccine: immunogenicity and efficacy of synthetic HPV16 E7 in the TC-1 mouse tumour model

Many successful candidate vaccines capable of combating tumours in animal models come to an untimely end because of the costs associated with the approval and production of the GMP-grade materials, which are usually of biological origin, for use in humans. We have used a GMP-compatible method to chemically synthesize a pure synthetic E7 protein of the human papillomavirus type 16 (HPV16-E7). This oncogen-derived protein is constitutively expressed in cervical cancer and its precursors and is thus considered as an excellent target for tumour-specific immunity. Injection of a mixture of the synthetic HPV16-E7 protein and the synthetic adjuvant CpG in mice resulted in strong functional HPV16-specific cytotoxic T-lymphocyte responses as measured by CD8+ MHC class I-tetramer staining, the detection of antigen-specific intracellular IFNgamma production and the ability to protect mice against a challenge with HPV16-E7+ TC-1 tumour cells in both prophylactic and therapeutic vaccination regimens. Our results demonstrate the potential use of pure synthetic vaccines that can be efficiently produced under GMP at low cost, which will stimulate the translation of new vaccination strategies into phase I/II clinical trials.     

The use of spermHALO-FISH to determine DAZ gene copy number

The AZFc region of the human Y chromosome is frequently deleted in men with spermatogenic failure and contains many multicopy genes. The best-characterized gene family within this region is the Deleted in AZoospermia (DAZ) gene family, which is present in four nearly identical copies. Recent reports claim deletions of some but not all DAZ genes. The assays used in these studies, however, are unable to provide conclusive evidence on the number of DAZ genes. In this study we show that with the use of highly decondensed sperm nuclei with large DNA domains (spermHALO) it is possible to determine the number of DAZ genes accurately. Using this fluorescent in-situ hybridization (FISH) technique, which has both high resolution and high range, we show that in 10 normospermic men, in which PCR digest assays indicated a deletion of one or more DAZ genes, all four DAZ genes were present. Also we confirmed previous findings of a deletion of two DAZ genes in two men and identified a man with six DAZ genes. Our results indicate that spermHALO-FISH allows an accurate determination of DAZ gene copy number, while PCR digest assays do not. Therefore, confirmation of positive results from PCR digest assays with spermHALO-FISH is essential. Furthermore, the spermHALO-FISH technique should prove useful as a genetic mapping technique in other regions of the Y chromosome and similar repetitive regions throughout the genome.     

The status of HPV16-specific T-cell reactivity in health and disease as a guide to HPV vaccine development

Human papilloma viruses (HPV) are among the most common sexually transmitted pathogens in young adults. In the majority of individuals, anti-viral immunity is capable of suppressing viral infection but in a minority of patients viral infection is not cleared in time to prevent the development of malignancies. In these cases, HPV16-specific immunity may develop too late, is not strong enough, and/or is possibly of the wrong type. The influence of pre-existing immunity on the efficacy of vaccines is largely unknown. Nor has it been studied what the effect is of vaccines on the various types of pre-existing HPV-specific T-cell immunity. Animal models showing that vaccines are able to protect against a subsequent tumor challenge and even to treat transplantable tumors, are not qualified to address this point because tumor development is not preceded by persistent viral infection. Therefore, the comparison between fully characterized pre-existing HPV-specific immunity in patients and healthy subjects is a prerequisite for the full appreciation of vaccine-efficacy as well as for further development of next-generation vaccines.     

Sorption of thiotepa to polyurethane catheter causes falsely elevated plasma levels

Central venous access catheters are commonly used in clinical oncology. The double lumen variant is applied in pharmacokinetic studies for simultaneous administration and blood sampling when frequent blood collections are necessary. Occlusion of one lumen, a common complication, necessitates the investigator perform blood sampling through the administration lumen after interrupting the infusion. Plasma concentrations measured in this sample can be influenced by sorption of the previously infused compound to the catheter lumen. In this study, the quality of cyclophosphamide, thiotepa, and carboplatin plasma concentrations is investigated when sampling is performed through the administration lumen.     

Latent Cerebral Venous and Sinus Thrombosis

The incidence of cerebral venous and sinus thrombosis (CVST) is still unknown. Several assumptions of the incidence have been made. In the one and only series of consecutive brain autopsies series by Towbin in1973 CVST was found in 10,9 % of patients aged 60 years or more. These findings suggest that the true incidence of CVST is higher than generally thought, but there are no other reports supporting these findings. Therefore in order to determine the incidence of latent CVST we conducted a new prospective post mortem study. All brain autopsies performed in our hospital between 1996 and 1998 on patients 60 years of age or older were examined for the presence of CVST in a prospective way. We examined the sagittal sinus, the torcula, the straight sinus, both transverse sinuses, and both sigmoideal sinuses for the presence of thrombosis. The clinical condition, medication, brain-imaging results, clinical cause of death, general findings from the body autopsy and definite cause of death were recorded. Additionally we requested the annual mortality figures of CVST at the department of the National Agency for Statistics of the Netherlands (CBS). A consecutive and prospective series of 102 brain autopsies was performed in our general hospital during a period of two years. We found one case of latent CVST in our series of 102 patients. Comparison with the findings of Towbin using a chi-square test yielded a significant difference in the incidence of latent CVST (χ₂ = 7.65, p < 0.01) between the two studies. The present autopsy study demonstrates that latent CVST is rare. Received: 7 June 2002, Received in revised form: 14 October 2002, Accepted: 21 October 2002 Correspondence to H. P. Bienfait, MD     

The identification of trends in the utilisation of mental health services by elderly: a Dutch case register study

OBJECTIVE: In view of the rapid ageing of the population any changes in the use of mental health services by the elderly became increasingly important for policy development. This study aimed at the supply of information about trends in the numbers of elderly clients, the services they used and the volume and pattern of service utilisation. METHODS: Details of elderly users and their use of community- and hospital-based services between 1990 and 1999 were retrieved from the Groningen case register. Developments in population size and age distribution in the register area were taken into account, as were the unit costs of mental health services. RESULTS: Large age specific changes were found that caused only the expenditures on the oldest elderly to increase due to a shift from outpatient clinics to prolonged psychogeriatric day treatment and inpatient care. Comparatively young elderly used fewer inpatient services and more community care. The number of new elderly clients declined progressively. In some age groups treated prevalence also decreased, but to a lesser extent, because of a prolonged use of mental health services. CONCLUSIONS: Study results seemed well in accordance with mental health policy as to deinstitutionalization and active ageing. Research on the effect of mental health care on life expectancy and the time lag between the intake of mental health providers and treated prevalence was proposed in order to improve the prediction of future service use by elderly.