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Biomedical subjects

A Bernardo

Publications and source records attributed to A Bernardo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Stereotactic Radiotherapy of Central Nervous System and Head and Neck Lesions, Using a Conformal Intensity-Modulated Radiotherapy System (Peacocktrade mark System).

The objective of this article is to evaluate single-fraction or fractionated stereotactic radiotherapy of central nervous system (CNS) and head and neck lesions using intensity-modulated radiotherapy (IMRT) with a commercially available system (Peacocktrade mark, Nomos Corporation, Sewickley, PA). This system allows tomotherapeutic delivery of intensity-modulated radiation, that is, the slice-by-slice treatment of the volume of interest with an intensity-modulated beam, making the delivery of highly conformal radiation to the target possible in both single or multiple fractions mode. During an 18-month period, 43 (21 males and 22 females) patients were treated, using a removable cranial screw-fixation device. Ages ranged from 10 to 77 years (mean, 52.2; median, 53.5). Intra- and extra-axial lesions, including head and neck malignancies and spine metastases, were treated. Clinical target volume ranged from 0.77 to 195 cm(3) (mean, 47.8; median, 29.90). The dose distribution was normalized to the maximum and was prescribed, in most cases, at the 80% or 90% isodose line (range, 65 to 96%; median, 85%; mean, 83.4%) and ranged from 14 to 80 Gy (mean, 48; median, 50). The number of fractions ranged from 1 to 40 (mean, 23; median, 25). In all but one patient, 90% of the prescription isodose line covered 100% of the clinical target volume. The heterogeneity index (the ratio between the maximum radiation dose and the prescribed dose) ranged between 1.0 and 1.50, whereas the conformity index (the ratio between the volume encompassed by the prescription isodose line and the clinical target volume) ranged between 1.0 and 4.5. There were no complications related to the radiation treatment. With a median follow-up of 6 months, more than 70% of our patients showed decreased lesion size. Stereotactic IMRT of CNS and head and neck lesions can be delivered safely and accurately. The Peacock system delivers stereotactic radiation in single or multiple fractions and has no volume limitations. It has been used to treat intracranial, head and neck, and spinal lesions. The option of fractionation, the lack of volume constraint, and the capability of treating intracranial, head and neck, and spinal pathology make stereotactic IMRT a valuable adjunct to established stereotactic radiotherapy systems delivering convergent-beam irradiation using the Linac or Gamma Knife. In a clinical setting that offers Linac, Gamma Knife radiosurgery, and conformal stereotactic radiotherapy, the latter may have advantages for treating large (> 25-cm(3)) and irregular lesions, especially when fractionation is considered useful.

Journal Article↗
PubMed2001

[Isoprostanes and oxidative stress in brain damage in newborns].

Isoprostanes are a family of biologically active molecules recently characterized, which is emerging as a new class of specific and reliable markers of in vivo and ex vivo lipid peroxidation and oxidative damage. These molecules are stable, relatively abundant and easily detectable by sensitive and specific analytical methods. In the last years, the measurement of their levels in tissue homogenates or biological fluids has significantly improved our knowledge on the involvement of oxidative stress in several neurological diseases. Here we present evidence indicating that isoprostanes can be successfully used also to study the mechanisms involved in free radical brain damage following hypoxic-ischaemic or inflammatory conditions in newborns and preterm infants.

Brain Damage, Chronic↗
PubMed2000

Presence and inducibility of peroxisomes in a human glioblastoma cell line.

We investigated the effect of the peroxisomal proliferator (PP) perfluorodecanoic acid (PFDA), alone or in combination with 9-cis-retinoic acid (RX) on the human glioblastoma cell line Lipari (LI). Cell proliferation, apoptotic rate, peroxisome morphology and morphometry, peroxisomal enzyme activities and the presence of peroxisome proliferator-activated receptors (PPARs) were examined. We show that PFDA alone produces pleiotropic effects on LI cells and that RX enhances some of these effects. Peroxisomal number and relative volume, as well as palmitoyl-CoA oxidase activity and protein, are increased by PFDA treatment, with a synergistic effect by RX. The latter, alone or in association with PFDA, induces catalase activity and protein, increases apoptosis and decreases cell proliferation. PPAR isotypes alpha and gamma were detected in LI cells. While the former is apparently unaffected by either treatment, the latter increases in response to PFDA, independent of the presence of RX. The results of this study are discussed in terms of PPARalpha activation and PPARgamma induction by PFDA, by either a direct or an indirect mechanism.

Acyl-CoA Oxidase↗
PubMed2000

[Background and evaluation plan of a study on self-management of anticoagulation in patients with non-valvular atrial fibrillation (SMAAF Study)].

The objective of this open, randomized, multicenter study is to investigate the benefits and economic efficiency of self-management of oral anticoagulation in patients with atrial fibrillation (SMAAF study) in comparison with a group of patients given conventional care by a general practitioner or specialist. Two thousand patients suitable for self-management will be assigned at random to either the self-management group or the control group. The numbers of thromboembolic and hemorrhagic complications requiring treatment during the 2-year follow-up period will be recorded as the primary end point. The secondary endpoint variables will be maintenance of the INR value in the individual target range, INR variance, the course of complications over time, and the cost efficiency of self-management compared with the routine procedures. The last of these parameters will include the diagnostic and/or therapeutic measures carried out, the duration of inpatient hospital treatment, and the social consequences (subsequent rehabilitation treatment, inability to work, forced retirement). The estimate of the required number of patients was based on the assumption that during long-term anticoagulant therapy within the framework of primary and secondary prevention 4% of patients with chronic non-valvular atrial fibrillation would have severe thromboembolic of hemorrhagic complications each year. Since this rate can be halved by self-management, a one-tailed chi 2-test of 80% power and a 5% significance threshold would require n = 997 patients per group. The results of the SMAAF study will establish the socioeconomic benefits of self-management in patients with non-valvular atrial fibrillation.

Administration, Oral↗
PubMed2000

Role of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and its natural ligand 15-deoxy-Delta12, 14-prostaglandin J2 in the regulation of microglial functions.

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of a large group of nuclear receptors controlling the proliferation of peroxisomes that is involved in the downregulation of macrophage functions. Here, we report that PPAR-gamma was constitutively expressed in rat primary microglial cultures and that such expression was downregulated during microglial activation by endotoxin (LPS). The presence of the PPAR-gamma natural ligand 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) counteracted the repression of PPAR-gamma expression caused by LPS. In microglial cultures stimulated by LPS, interferon-gamma (IFN-gamma) or by their combination, 15d-PGJ2 reduced the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS). The inhibitory effect was dose-dependent and did not involve an elevation of cyclic AMP, a second messenger known to inhibit NOS expression in microglia. In addition, 15d-PGJ2 down-regulated other microglial functions, such as tumour necrosis factor-alpha (TNF-alpha) synthesis and major histocompatibility complex class II (MHC class II) expression. The effects of 15d-PGJ2 occurred, at least in part, through the repression of two important transcription factors, the signal transducer and activator of transcription 1 and the nuclear factor kappaB, known to mediate IFN-gamma and LPS cell signalling. Our observations suggest that 15d-PGJ2, the synthesis of which is likely to occur within the brain, could play an important role in preventing brain damage associated with excessive microglial activation.

Adenine↗
PubMed1999

Thermal inactivation of Bacillus cereus spores formed at different temperatures.

The effects of the sporulation temperature in the range 20-45 degrees C on the D and z values of three isolates of Bacillus cereus (ATCC 4342, 7004 and 9818) were investigated. The strains were found to differ in their response. Higher D100 values (around 10-fold) were obtained with isolates 4342 and 9818 when the sporulation temperature increased from 20 to 45 degrees C. With isolate 7004 (the least heat resistant of the three strains), however, the most thermal tolerant spores were obtained at 35 degrees C. The z values were not significantly modified (P > 0.05) by the sporulation temperature. Mean z values of 7.46+/-0.22 degrees C for isolate 4342, 7.80+/-0.40 degrees C for 7004 and 8.09+/-0.33 degrees C for 9818 were obtained.

Bacillaceae Infections↗
PubMed1999

Management of skull base chordoma.

Two management modal-ities appear to be important in treating skull base chordomas: surgery and radiation therapy. Radical resection of lesions of the distal sacrum (S3-S5) and coccyx may be curative, as total removal is often achieved. In contrast, complete resection of chordomas of the base of the skull is rarely successful because of the inability to achieve a true complete surgical resection. On the other hand, treatment of skull base chordomas by radiation therapy alone is often difficult owing to the large size of the lesion and the dose limitation imposed by the sensitivity of the adjacent structures. Local relapse is the predominant type of treatment failure of skull base chordoma. Skull base surgery and radiation therapy have significantly improved over the last 20 years. The following papers review the most significant recent analyses of therapeutic options in treating skull base chordomas. It seems that the combination of aggressive surgery followed by combined proton-photon radiation therapy offers the best chance of long-term local control to patients harboring cranial chordomas.

Journal Article↗
PubMed1999

Cost-effectiveness of self-managed anticoagulant therapy in Germany.

In this study, the cost-effectiveness of anticoagulation self-management--which is now established in Germany--was compared with the conventional method of monitoring oral anticoagulant therapy by the patient's family physician or by a specialist. Costs were determined based on the usual conditions in Germany such as frequency of testing and control testing, scope of the tests, and diagnostic and therapeutic standards for thromboembolic or bleeding complications. In addition to direct monitoring costs, we determined the costs for treating minor and serious complications and used them to calculate overall therapy costs. The incidence of complications was estimated based on the results of more recent studies. The only costs considered in this study were those covered by the primary cost carrier--the government-controlled health insurance funds--and included outpatient visits and, in cases of serious complications, acute inpatient treatment and rehabilitation. It was shown that the costs to treat minor complications only slightly affected annual, overall treatment costs. The potential reduction in incidences of serious bleeding and thromboembolic complications due to anticoagulation self-management--which is independent of the indication for oral anticoagulation--reduced overall therapy costs from DM 2,061.48/patient-year for conventional therapeutic methods to DM 1,342.46/patient-year for patients under self-management of anticoagulation.

Anticoagulants↗
PubMed1999

Heat resistance of Bacillus cereus spores: effects of milk constituents and stabilizing additives.

Heat resistance of Bacillus cereus spores (ATCC 7004, 4342, and 9818) heated in different types of milk (skim, whole, and concentrated skim milk), skim milk containing stabilizing additives (sodium citrate, monopotassium phosphate, or disodium phosphate, 0.1%), and cream was investigated. Thermal resistance experiments were performed at temperatures within the range of 92 to 115 degrees C under continuous monitoring of pH. For strain 4342 no significant differences (P < 0.05) in D values were detected in any case. For strains 7004 and 9818 higher D values of about 20% were obtained in whole and concentrated skim milk than those calculated in skim milk. From all stabilizing additives tested, only sodium citrate and sodium phosphate increased the heat resistance for strain 9818. However, when the menstruum pH was measured at the treatment temperature, different pH values were found between the heating media. The differences in heat resistance observed could be due to a pH effect rather than to the difference in the substrates in which spores were heated. In contrast, when cream (fat content 20%) was used, lower D values were obtained, especially for strains 7004 and 9818. z values were not significantly modified by the milk composition, with an average z value of 7.95+/-0.20 degrees C for strain 7004, 7.88+/-0.10 degrees C for strain 4342, and 9.13+/-0.16 degrees C for strain 9818.

Animals↗
PubMed1998

Nuclear factor kB-independent cytoprotective pathways originating at tumor necrosis factor receptor-associated factor 2.

Most normal and neoplastic cell types are resistant to tumor necrosis factor (TNF) cytotoxicity unless cotreated with protein or RNA synthesis inhibitors, such as cycloheximide and actinomycin D. Cellular resistance to TNF requires TNF receptor-associated factor 2 (TRAF2), which has been hypothesized to act mainly by mediating activation of the transcription factors nuclear factor kB (NFkB) and activator protein 1 (AP1). NFkB was proposed to switch on transcription of yet unidentified anti-apoptotic genes. To test the possible existence of NFkB-independent cytoprotective pathways, we systematically compared selective trans-dominant inhibitors of the NFkB pathway with inhibitors of TRAF2 signaling for their effect on TNF cytotoxicity. Blockade of TRAF2 function(s) by signaling-deficient oligomerization partners or by molecules affecting TRAF2 recruitment to the TNF receptor 1 complex completely abrogated the cytoprotective response. Conversely, sensitization to TNF cytotoxicity induced by a selective NFkB blockade affected only a fraction of TNF-treated cells in an apparently stochastic manner. No cytoprotective role for c-Jun amino-terminal kinases/stress-activated protein kinases (JNKs/SAPKs), which are activated by TRAF2 and contribute to stimulation of activator protein 1 activity, could be demonstrated in the cellular systems tested. Although required for cytoprotection, TRAF2 is not sufficient to protect cells from TNF + cycloheximide cytotoxicity when overexpressed in transfected cells, thus indicating an essential role of additional TNF receptor 1 complex components in the cytoprotective response. Our results indicate that TNF-induced cytoprotection is a complex function requiring the integration of multiple signal transduction pathways.

Animals↗
PubMed1998

Technology and true presence in nursing.

If there is to be a future for nursing in the next millenium, it must be dictated not by technologic advances directly but by the manner in which technology relates with persons in health and illness. Technology enables nurses to care for persons in a more efficient and cost-effective manner. True presence, as articulated in the human becoming theory, affords members of the profession opportunities to be with persons in ways that make a difference to their quality of life. The article illustrates the recognition of the link between technology and true presence through the use of a nurse-person encounter.

Aged↗
PubMed1998

Analytical evaluation of complex anterior approaches to the cranial base: an anatomic study.

OBJECTIVE: The purpose of the present study was to evaluate the anatomic areas of the cranial base exposed by different complex anterior approaches. METHODS: Using 20 embalmed cadaveric heads, we executed five different anterior approaches, i.e., Le Fort 1 approach with splitting or down-fracturing of the hard palate, extended maxillectomy, median mandibulotomy with glossotomy, and mandibular swing transcervical approach. Each approach was performed a minimum of three times. The areas of the intra- and extracranial cranial base exposed by each approach were analytically examined by using a numerical grading system to assess the exposure of major anatomic and neurovascular structures. RESULTS: Good exposure of the midline compartment of the cranial base was provided by the median mandibulotomy with glossotomy and by the Le Fort 1 approach with splitting of the hard palate, whereas the mandibular swing transcervical and extended maxillectomy approaches provided good exposure of the lateral compartment of the cranial base. CONCLUSION: Use of the numerical grading system allowed quantification of the exposure afforded by each approach, with respect to the different compartments (midline and lateral) of the intra- and extracranial cranial base, highlighting the differences among the approaches examined.

Cadaver↗
PubMed1998

Synergistic stimulation of MHC class I and IRF-1 gene expression by IFN-gamma and TNF-alpha in oligodendrocytes.

In order to understand the molecular basis of the synergistic action of interferon gamma (IFN-gamma) and tumour necrosis factor alpha (TNF-alpha) on rat oligodendrocyte development, we studied some aspects of the signalling pathways involved in the regulation of the major histocompatibility complex (MHC) class I and the interferon regulatory factor 1 (IRF-1) gene expression. Two well-defined inducible enhancers of the MHC class I gene promoter, the MHC class I regulatory element (MHC-CRE) and the interferon consensus sequence (ICS), were analysed. Neither IFN-gamma nor TNF-alpha was capable of inducing MHC-CRE binding activity when administrated alone. Following the exposure of oligodendrocytes to IFN-gamma, TNF-R1 expression was transcriptionally induced by the binding of signal transducer and activator of transcription (STAT-1) homodimers to the IFN-gamma activated site (GAS) present in the gene promoter. The upregulation of TNF-R1 allowed TNF-alpha to induce the binding of nuclear factor-kappaB (NF-kappaB) to the MHC-CRE site. With respect to ICS element, IFN-gamma induced IRF-1 binding, that was further enhanced upon co-treatment with TNF-alpha. The existence of a synergism between IFN-gamma and TNF-alpha in stimulating IRF-1 expression at the transcriptional level was supported by IRF-1 promoter analysis: IFN-gamma directly induced the binding of STAT-1 homodimers to the GAS element, while NF-kappaB binding to the kappaB sequence was activated by TNF-alpha only after IFN-gamma treatment. This transcriptional regulation of IRF-1 gene by IFN-gamma and TNF-alpha was confirmed at the mRNA level. The synergism demonstrated in the present study highlights the importance of cytokine interactions in magnifying their biological effects during brain injury and inflammation.

Animals↗
PubMed1998

[Optimizing long-term anticoagulation by patient self-management?].

An active role of the patient in managing his own therapy leads to an optimized quality of long-term anticoagulation and to a reduction of hemorrhagic or thromboembolic complications of treatment. Our study shows that patients could be easily trained in the self-management of oral anticoagulation and that they achieve superior anticoagulation control. In 10 years 1244 patients were trained in the self-management of oral anticoagulation at the Cardiac Rehabilitation Center in Bad Berleburg, Germany. With regard to their self-determined prothrombin times (PT) 387 patients could be followed up. The results were within the target range in 81.5% of the PT measurements taken by the patients themselves. Only 18.5% PT's were outside of the target range. The incidence of more important bleedings was 0.33% per year and of thromboembolic complications was 0.25% per year. Self-management of oral anticoagulation is associated with a reduced risk of hemorrhagic and thromboembolic complications and an improvement of prognosis and quality of life.

Administration, Oral↗
PubMed1997

HIV-gp120 affects the functional activity of oligodendrocytes and their susceptibility to complement.

The aim of this study was to assess whether the HIV protein gp120 can induce direct or/and indirect damage to oligodendrocytes (OL). Using highly purified cultures of rat OL, we report that gp120 binds to OL and induces functional alterations in these cells. Indeed, the percentage of cells expressing myelin basic protein (MBP) and the levels of all four MBP isoforms were substantially reduced after a 3-day treatment with 10 nM gp120. As gp120 depressed the ability of OL to reduce the tetrazolium salt MTT (a sign of mitochondrial impairment), the alteration of MBP production may be a consequence of decreased metabolic activity. The above effects were accompanied by a small increase in the number of apoptotic nuclei (from 4.3% in controls to 17.6% in cells treated for 3 days with gp120). As complement can lyse OL and gp120 is known to activate complement, we also studied the interaction between these two factors using OL cultures. The viral protein potentiated (by about 25%) the lytic effect of complement, when administered to the cultures 5 hr after complement, and depressed it (by about 30-40%), when added 5 hr before complement. Heat denaturation and anti-gp120 antibodies prevented the direct effect of gp120 on OL, but did not influence the interactions between gp120 and complement. Some gp120 non glycosylated peptides (V3 loop, 254-274 and 415-435 peptides) mimicked the ability of gp120 to antagonize the lytic effect of complement, but not that of potentiating complement lytic activity. In conclusion, our study indicates that gp120 can alter OL functional activity directly and can interfere with OL susceptibility to complement mediated lysis.

Animals↗
PubMed1997

Effects of sporulation pH on the heat resistance and the sporulation of Bacillus cereus.

Spores of Bacillus cereus ATCC 7004, 4342 and 9818 were obtained in nutrient agar at several pH from 5.9 to 8.3. The optimum pH for sporulation was around 7, but good production of spores was obtained in the range 6.5-8.3. With all three strains, D-values clearly dropped with sporulation pH, decreasing by about 65% per pH unit. z-Values were not significantly modified (P > 0.05) by this factor. Mean z-values of 7.13 degrees C +/- 0.16 for strain 7004, 7.67 degrees C +/- 0.04 for 4342 and 8.80 degrees C +/- 0.64 for 9818 were obtained.

Bacillus cereus↗