An outbreak of Serratia marcescens bloodstream infections associated with misuse of drug vials in a surgical ward.

We report an outbreak of Serratia marcescens bloodstream infection due to contamination of total parenteral nutrition solution by insulin or poligeline solution when single-use vials were used for multiple doses in a surgical ward. Four patients had severe sepsis, and no patient died. Multidose vials, used either correctly or incorrectly, may be associated with bloodstream infection.     

Perceptual-motor, visual and cognitive ability in very low birthweight preschool children without neonatal ultrasound abnormalities

Thirty-six children born preterm with very low birth weight without neonatal brain disorders and normal cerebral ultrasound findings were examined at pre-school age: visual, perceptual motor, attention, behaviour and cognitive assessments were performed in the study group as well as in a control group of term children matched for age, sex and parental educational and occupational status. The results showed a significant lower scoring in perceptual motor skills in the study group, associated with a defect of accuracy in spatial attention and a higher incidence of stereopsis impairment related with perceptual motor disabilities. Behavioural disorders, in terms of emotional maturation and hyperactivity, were significantly more frequent in the study group. To prevent behavioural and learning problems at school, a complete longitudinal assessment including visual functions and perceptual motor abilities seems mandatory in preterm born children, even in the absence of neonatal brain disorders including abnormal cerebral ultrasound findings.     

Targeted delivery of tumor necrosis factor-alpha to tumor vessels induces a therapeutic T cell-mediated immune response that protects the host against syngeneic tumors of different histologic origin.

PURPOSE: We sought to demonstrate that a single systemic administration of L19mTNFalpha (a fusion protein constituted by the scFv L19 specific for the oncofetal ED-B domain of fibronectin and tumor necrosis factor alpha, TNFalpha) in combination with melphalan induced complete and long-lasting tumor eradication in tumor-bearing mice and triggered the generation of a specific T cell-based immune response that protects the animals from a second tumor challenge, as well as from challenges with syngeneic tumor cells of different histologic origin. Experimental Design and RESULTS: Treatment with L19mTNFalpha, in combination with melphalan, induced complete tumor regression in 83% of BALB/c mice with WEHI-164 fibrosarcoma and 33% of animals with C51 colon carcinoma. All cured mice rejected challenges with the same tumor cells and, in a very high percentage of animals, also rejected challenges with syngeneic tumor cells of different histologic origin. In adoptive immunity transfer experiments, the splenocytes from tumor-cured mice protected naive mice both from C51 colon carcinoma and from WEHI-164 fibrosarcoma. Similar results were also obtained in adoptive immunity transfer experiments using severely immunodepressed mice. Experiments using depleted splenocytes showed that T cells play a major role in tumor rejection. CONCLUSIONS: The results show that the selective targeting of mTNFalpha to the tumor enhances its immunostimulatory properties to the point of generating a therapeutic immune response against different histologically unrelated syngeneic tumors. These findings predicate treatment approaches for cancer patients based on the targeted delivery of TNFalpha to the tumor vasculature.     

Increased resistance to systemic candidiasis in athymic or interleukin-10-depleted mice

Candida albicans produces a virulence-associated immunomodulatory protein (p43), which activates lymphocytes polyclonally, suppresses specific antibody responses to Candida antigens, and potentiates systemic growth of C. albicans. In this study, athymic, unlike euthymic, C57BL/6 mice were resistant to systemic candidiasis and produced lower serum levels of interleukin (IL)-4 and IL-10. Pretreatment with p43 stimulated the production of both cytokines. Depletion of IL-10, but not of IL-4, in euthymic animals reestablished resistance and abrogated p43-dependent suppression of the specific antibody response and facilitated C. albicans growth. In agreement with these results, both immunosuppression and p43-mediated facilitation of the fungus growth were abolished in IL-10 knockout mice. These observations demonstrate the relevance of IL-10 in facilitating systemic candidiasis and suggest a critical role for the immunosuppressive virulence factor p43 in the process.     

Anisotropic Mechanisms for Multiphasic Unipolar Electrograms: Simulation Studies and Experimental Recordings

The origin of the multiple, complex morphologies observed in unipolar epicardial electrograms, and their relationships with myocardial architecture, have not been fully elucidated. To clarify this problem we simulated electrograms (EGs) with a model representing the heart as an anisotropic bidomain with unequal anisotropy ratio, ellipsoidal ventricular geometry, transmural fiber rotation, epi-endocardial obliqueness of fiber direction and a simplified Purkinje network. The EGs were compared with those directly recorded from isolated dog hearts immersed in a conducting medium during ventricular excitation initiated by epicardial stimulation. The simulated EGs share the same multiphasic character of the recorded EGs. The origin of the multiple waves, especially those appearing in the EGs for sites reached by excitation wave fronts spreading across fibers, can be better understood after splitting the current sources, the potential distributions and the EGs into an axial and a conormal component and after taking also into account the effect of the reference or drift component. The split model provides an explanation of humps and spikes that appear in the QRS (the initial part of the ventricular EG) wave forms, in terms of the interaction between the geometry and direction of propagation of the wave front and the architecture of the fibers through which excitation is spreading. © 2000 Biomedical Engineering Society. PAC00: 8719Nn, 8710+e, 8719Hh     

Recurrent antiphospholipid-related deep vein thrombosis as presenting manifestation of systemic lupus erythematosus

Antiphospholipid antibodies (aPL) are frequently associated with thrombotic disorders in the so-called antiphospholipid syndrome. Together with anticardiolipin antibodies (aCL), lupus anticoagulant (LA) is the main diagnostic tool for aPL detection. Since LA determination is based on the finding of prolonged clotting time in vitro, concomitant anticoagulant therapy may significantly interfere with its detection. We report a case of a boy in whom recurrent aPL-related thrombosis heralded for several months the onset of systemic lupus erythematosus (SLE). Abnormally increased in vitro clotting times at the time of the second thrombotic event led to the suspicion of the presence of LA activity. However, this latter finding was difficult to interpret since the patient was already on heparin treatment at the time of our first observation. Thus, LA was assayed using a commercial kit in which a heparin neutralizer is included (Staclot LA). Two consecutive samples from the patient were compared with eight patients on anticoagulant therapy for non-aPL-related thrombotic events and 20 healthy controls. The study showed that, taking into account the concomitant anticoagulant treatment, Staclot LA was positive only in the propositus, raising the suspicion of a possible aPL-related origin of the thrombotic event. This issue was definitively confirmed in a subsequent follow-up. Conclusion The present report shows that aPL-related deep vein thrombosis can be the earliest clinical manifestation of pediatric SLE, and that Staclot LA may have a role in LA detection during the course of anticoagulant treatment. Received: 6 October 1998 / Accepted: 15 September 1999     

Bioavailability and pharmacokinetics of isradipine after oral and intravenous administration: half-life shorter than expected?

Isradipine is a calcium channel-blocking agent of the dihydropyridine type, used in the treatment of hypertension. A terminal half-life of 8-9 hr has been reported, in several pharmacokinetic studies after oral administration of isradipine. In a yet unpublished study a much shorter half-life was observed, and the present trial was therefore conducted in order to estimate the half-life after intravenous administration of isradipine. The bioavailability was estimated as well. In a randomised cross-over design ten healthy young volunteers were given either isradipine orally or an intravenous infusion. The two study periods were separated by at least 3 days. Blood samples for measurement of isradipine concentration were collected for 10-12 hr after administration and half-life and bioavailability were estimated. Mean terminal half-life after intravenous administration was calculated to be 2.8 hr, and the bioavailability to be 0.28. None of the 10 subjects suffered from side effects. In the present intravenous study the half-life of isradipine seems to be of much shorter than demonstrated in previous oral studies.     

From telescope to binoculars. Dyadic outcome resulting from psychological counselling for infertile couples undergoing ART

Objective: This longitudinal study aims to evaluate the effect of psychological counselling on quality of life, marital satisfaction and need for parenthood in couples undergoing fertility treatments (ART).

Background: Recent guidelines on the ART suggest that psychological counselling should target both members of the infertile couple in order to improve their conjoint management of the infertility-related stress. However, studies on the dyadic outcome of couples are scarce.

Methods: 262 patients were originally considered in the study and completed questionnaires on quality of life, need for parenthood and marital satisfaction, before treatment (T1) and at the day of intrauterine insemination/embryo transfer (T2). For the purposes of this study, 34 counselled couples were then matched to 34 non-counselled couples by propensity scores. The Common Fate Model (CFM) was used to examine dyadic changes.

Results: Couples receiving counselling had higher dyadic quality of life and lower dyadic stress due to the need for parenthood at T2 compared to non-counselled couples. No differences were found on marital satisfaction.

Conclusion: The findings provide support for the effectiveness of counselling on interpersonal outcome. The CFM allows researchers to examine how the dyad as a whole responds to counselling, highlighting the change in the couple’s relational dynamics.