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Biomedical subjects

P Rossi

Publications and source records attributed to P Rossi.

At least 55 records · Page 3Linked to original sources

[Diagnostic kits in parasitology: which controls?].

The development of new diagnostic tools particularly for some parasitic "neglected diseases", is slowed or even hindered by limited resources assigned for basic and applied research in public institution and private sector. Even if the time-line and costs needed for developing a new In Vitro Diagnostic (IVD) test are generally lower compared to vaccines or new drugs, industry is poorly engaged in investing resources due to the perception of limited markets. To accelerate the development of diagnostics for the world's most deadly diseases, the World Health Organization's (WHO) Special Programme for Research and Training in Tropical Diseases (TDR), the United Nations Development Programme, the World Bank and the Gates Foundation, last year launched a new initiative, FIND (Foundation for Innovative New Diagnostics, www.finddiagnostics.org). The aim is to "apply the latest biotechnology innovations to develop and validate affordable diagnostic tests for diseases of the developing world". Ideally, a new diagnostic test should be accurately evaluated prior to use in medical practice. The first step would be a pre-clinical evaluation, an analytic study to determine its laboratory performance. A crucial point in this phase is the calibration of reagents (antigens, antibodies, DNA probes, etc.) against a standard reference preparation. WHO, through the WHO International Laboratories for Biological Standards, "provides International Biological Reference Preparations which serve as reference sources of defined biological activity expressed in an internationally agreed unit" (www.who.int/biologicals/IBRP/index.htm). Standardization allows "comparison of biological measurements worldwide" and ensures the reliability of diagnostic procedures. These preparations are generally intended for use in the characterization of the activity of secondary reference preparations (regional, national or in-house working standards). Unfortunately, international reference standards for parasitic diseases are not available at present, except for Toxoplasma antibodies. The first international standard reagent for Anti-Toxoplasma Serum was established in 1968 and at present, an international standard reference serum, Anti-toxoplasma serum, human TOXM is available at the National Institute for Biological Standards and Control (NIBSC) in UK. Several collaborative, multicenter studies were carried out to assess the performance of different methods and commercial tests for the diagnosis of toxoplasmosis, by providing to participating laboratories a panel of well-defined sera to be tested. A four-phase process following well-accepted methodological standards for the development of diagnostics, analogous to those internationally accepted for drugs and vaccines was recently proposed. The pre-clinical evaluation, the analytic study to assess sensitivity, specificity, predictive values in laboratory (phase I), should be followed by a proof of principle study to distinguish diseased from healthy persons in easily accessible populations (phase II). The evaluation of test performance in populations of intended use (phase III), and finally the delineation of cost-effectiveness and societal impact of new tests in comparison with existing tools (phase IV) should complete the validation procedure. In this context, national regulatory agencies play a major role in pre-market approval and post-market surveillance of IVDs. The European Community in 1998 approved a directive (Directive 98/79/EC) which rules the marketing of IVD medical devices, in order to harmonise the performance levels and standards in European countries. But, among IVDs for parasitic diseases, only those to detect congenital toxoplasmosis are submitted to defined procedures to provide the verification of products before their placing on the market and the surveillance after their marketing by a notified body, which perform appropriate examinations, tests and inspections to production facilities to verify if the device meets the requirements of the directive. In U.S.A., the Food and Drug Administration (FDA), through the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), provides a comprehensive and regulatory activity for IVDs through pre-market evaluation and post-market surveillance. In developing countries, the scarcity of resources limits the procedures through which the national control authority can assure safety, quality and efficacy of products marketed, both imported and locally manufactured.

Animals↗

[An atypical bone metastasis of hepatocellular carcinoma: case report and review of the literature].

Bone metastases are a quite frequent complication of hepatocellular carcinoma (HCC). They are a substantial fraction (about 14-28%) of the metastatic locations of this neoplasm. Recent studies are indicative of the clinical usefulness of local therapy of HCC bone metastasis, expecially if they are single locations. The presence of a single bone metastasis does not seem to influence short term prognosis of the primary neoplasm and, furthermore, its treatment by radiation, chemio-embolization or surgery may obtain long-term pain control, without the side effects of analgesic drugs. Most frequently, bone metastases of HCC appear in the spine, femur, humerus or ribs. In the last years, some atypical locations, as jaws, gums and skull, were reported. In this paper, we report the case of a painful bone metastasis of HCC, localized at the second phalanx of the second finger of the right hand. To our knowledge, until now only two cases of HCC metastatic location at the bones of the hand have been reported. The lesion has been treated by surgical ablation, obtaining long-term pain remission and the withdrawal of the analgesic drugs. Few weeks later, another bone metastasis appeared, located at the second phalanx of the third finger of the same hand, indicating in this subject a peculiar "metastatic tropism".

Bone Neoplasms↗

Whole-brain atrophy in multiple sclerosis measured by two segmentation processes from various MRI sequences.

Recent MRI and pathologic studies have drawn attention to the destructive nature of the multiple sclerosis (MS) disease process, including the early occurrence of axonal and neuronal loss, leading to macroscopic brain and spinal cord atrophy. Measurement of brain atrophy from MRI has emerged as a potential outcome measure and marker of disease severity in MS and neurodegenerative diseases such as Alzheimer's. However, the optimal method for quantifying atrophy has not been established, including the choice of pulse sequence and segmentation algorithm employed. Using two different MRI scanners to ensure generalizability of results, we compared the reproducibility of four pulse sequences and two analysis methods (fully automated [FA] and semi-automated [SA]) when obtaining brain parenchymal fraction (BPF), a normalized measure of whole-brain atrophy, in patients with MS (n=13) and normal controls (n=2). In order to ensure the validity of our fully automated analysis technique, we also used it to evaluate the atrophy rate over nine months in 57 MS patients from the placebo arm of a clinical trial. All pulse sequences were capable of yielding reproducibility of around 1% coefficient of variation (CoV) or better. The best reproducibility was obtained using 2D multi-slice sequences (conventional spin echo [SE] and fluid-attenuated inversion recovery [FLAIR]), with fully automated analysis. Fully automated analysis of the longitudinal data (conventional spin echo) showed an atrophy rate of -0.5% change in BPF per year, in line with previous findings from a similar cohort of patients. In conclusion, BPF measurement is affected by both pulse sequence and segmentation method. Automated measurement has high reproducibility especially when 2D sequences are used. Semi-automated measurement may have increased accuracy, but with a decreased efficiency and reliability.

Adult↗

Lack of habituation causes high intensity dependence of auditory evoked cortical potentials in migraine.

Migraineurs are characterized interictally by lack of habituation, or even potentiation, of cortical evoked potentials during repetitive stimulation and by a strong intensity dependence of auditory evoked potentials (IDAP). To determine whether these two features of sensory processing are interrelated, we have studied them simultaneously on the same recordings of auditory evoked potentials (AEPs). AEPs were obtained at four different stimulation intensities in 14 patients suffering from migraine without aura (MO) and 14 healthy volunteers (HV). For each intensity, 120 trials were averaged off-line globally and over four sequential blocks of 30 trials. IDAP was expressed by the amplitude/stimulus intensity function (ASF slope) for global and block averages. Habituation was calculated as the percentage amplitude variation between the first and fourth blocks for each stimulus intensity. The IDAP slope for global averages was higher in MO (1.05 +/- 0.27 microV/10 dB) than in HV (0.64 +/- 0.45 microV/10 dB) (P = 0.008), but IDAP slopes for block averages were greater in MO only at the fourth block (P = 0.048). First block amplitudes tended to be lower in MO, except at 80 dB. There was a potentiation of AEP amplitudes at every stimulus intensity in MO, contrasting with habituation in HV. IDAP slopes were negatively correlated with mean habituation percentages in pooled data from patients and controls (r = -0.610; P = 0.0006). This study confirms that IDAP is higher in migraineurs than in healthy controls. It also shows that the AEP habituation is replaced by potentiation at all stimulus intensities. The negative correlation found between IDAP and habituation suggests that the latter is able to have a strong influence on the former and perhaps even lead to it. In migraine, the habituation deficit amplifies the IDAP and may thus be the causal functional abnormality. We propose that it is due to a decreased pre-activation level of sensory cortices, a hypothesis also supported in this study by the lower amplitude of first AEP blocks in patients.

Acoustic Stimulation↗

Comparison of gravimetric and a double-indicator dilution technique for assessment of extra-vascular lung water in endotoxaemia.

OBJECTIVE: To compare a molecular double-indicator dilution technique with the gravimetrical reference method for measurement of extra-vascular lung water in porcine endotoxin shock. DESIGN: Open comparative experimental study. SETTING: Animal research laboratory. MEASUREMENTS AND RESULTS: In fourteen anaesthetised, mechanically ventilated landrace pigs, central and pulmonary haemodynamics as well as pulmonary gas exchange were measured. Extra-vascular lung water was quantitated gravimetrically as well as with a molecular double indicator dilution technique. Eight of these animals were subjected to endotoxaemia, the rest serving as sham controls. No difference in extra-vascular lung water was observed between the two methods in sham animals. Furthermore, extra-vascular lung water assessed with the molecular double-indicator dilution technique at the initiation of endotoxin infusion did not differ significantly from the corresponding values for sham animals. Endotoxaemia induced a hypodynamic shock with concurrent pulmonary hypertension and a pronounced deterioration in gas exchange. No increase in extra-vascular lung water was detected with the molecular double-indicator dilution technique in response to endotoxin, whereas this parameter was significantly higher when assessed with the gravimetric method. CONCLUSION: The molecular double-indicator dilution technique showed similar results as the gravimetrical method for assessment of extra-vascular lung water in non-endotoxaemic conditions. However, during endotoxin-induced lung injury the molecular double indicator dilution technique failed to detect the significant increase in extra-vascular lung water as measured by the gravimetric method. These data suggest that the molecular double indicator dilution technique may be of limited value during sepsis-induced lung injury.

Animals↗

A practice survey on vasopressor and inotropic drug therapy in Scandinavian intensive care units.

BACKGROUND: This practice survey was performed to analyse the indications for use of vasopressor/inotropic drugs, preferred drugs and doses as well as concomitant monitoring and desired haemodynamic target values in Scandinavian ICUs. An internet-based reporting system was implemented. METHODS: A total of 223 ICUs were identified in the Scandinavian countries and invited to participate in a one-day point-prevalence study. An internet-based database was constructed and a practice survey protocol designed to identify haemodynamic monitoring, indications for vasopressor/inotropic drug-therapy, fluids used for volume loading, pretreatment circulatory state, actual and targeted haemodynamic variables. Patients were eligible for the study if on vasopressor/inotropic drug-therapy for more than 4 h. RESULTS: A total of 114 ICUs participated. A total of 114 adult patients matched the inclusion criteria. Sixty-seven per cent of the patients had received vasopressor/inotropic drug-treatment for >24 h and 32% received more than one drug. Arterial hypotension (92%) and oliguria (50%) were most common indications. Fluid loading prior to therapy was reported in 87% of patients. Dopamine (47%) and noradrenaline (44%) were the most commonly used drugs followed by dobutamine (24%). No other drug exceeded 6%. Non-catecholamine drugs were rarely used even in cardiac failure patients. Invasive arterial pressure was monitored in 95% of patients, pulmonary artery catheters were used in 19%. Other cardiac output monitoring techniques were used in 8.5% of the patients. CONCLUSION: Dopamine and noradrenaline seem to be the most commonly used inotropic/vasopressor drugs in Scandinavia. Traditional indications for inotropic/vasopressor support as hypotension and oliguria seem to be most common. Invasive monitoring was used in almost all patients, whereas a limited use of pulmonary artery catheters was noted. The internet-based reporting system proved to be an efficient tool for data collection.

Adult↗

Muscular cramps: proposals for a new classification.

Muscle cramps are involuntary, painful, sudden contractions of the skeletal muscles. They are present in normal subjects under certain conditions (during a strong voluntary contraction, sleep, sports, pregnancy) and in several pathologies such as myopathies, neuropathies, motoneuron diseases, metabolic disorders, hydroelectrolyte imbalances or endocrine pathologies. There has been considerable uncertainty in the literature regarding the classification and nomenclature of muscle cramps, both because the term "cramp" is used to indicate a variety of clinical features of muscles, leading to its use as an imprecise "umbrella" term that includes stiffness, contractures and local pain, and because the spectrum of the diseases in which it appears is wide. The purpose of the present study is to propose a simple classification to provide a framework to better recognize the full spectrum of phenomenology of muscle cramps.

Drug-Related Side Effects and Adverse Reactions↗

Bruton's tyrosine kinase defect in dendritic cells from X-linked agammaglobulinaemia patients does not influence their differentiation, maturation and antigen-presenting cell function.

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency disease characterized by very low levels or even absence of circulating antibodies. The immunological defect is caused by deletions or mutations of Bruton's tyrosine kinase gene (Btk), whose product is critically involved in the maturation of pre-B lymphocytes into mature B cells. Btk is expressed not only in B lymphocytes but also in cells of the myeloid lineage, including dendritic cells (DC). These cells are professional antigen presenting cells (APC) that play a fundamental role in the induction and regulation of T-cell responses. In this study, we analysed differentiation, maturation, and antigen-presenting function of DC derived from XLA patients (XLA-DC) as compared to DC from age-matched healthy subjects (healthy-DC). We found that XLA-DC normally differentiate from monocyte precursors and mature in response to lipopolysaccharide (LPS) as assessed by de novo expression of CD83, up-regulation of MHC class II, B7.1 and B7.2 molecules as well as interleukin (IL)-12 and IL-10 production. In addition, we demonstrated that LPS stimulated XLA-DC acquire the ability to prime naïve T cells and to polarize them toward a Th1 phenotype, as observed in DC from healthy donors stimulated in the same conditions. In conclusion, these data indicate that Btk defect is not involved in DC differentiation and maturation, and that XLA-DC can act as fully competent antigen presenting cells in T cell-mediated immune responses.

Agammaglobulinaemia Tyrosine Kinase↗

Molecular mechanisms utilized by alternative c-kit gene products in the control of spermatogonial proliferation and sperm-mediated egg activation.

The c-kit proto-oncogene plays a dual role in the control of male fertility in mice through two alternative gene products: (1). c-kit [the transmembrane tyrosine kinase receptor for stem cell factor (SCF)], which is expressed and functional in differentiating spermatogonia of the postnatal testis, in which c-kit is essential for pre-meiotic proliferation; and (2). tr-kit, an intracellular protein which is specifically accumulated during spermiogenesis through the use of an alternative intronic promoter, and which is able to trigger mouse egg activation when microinjected into the cytoplasm of metaphase II arrested oocytes. Here, we summarize the most recent findings about the molecular pathways through which c-kit regulates cell cycle progression in mitotic germ cells, and those through which sperm-derived tr-kit triggers parthenogenetic completion of meiosis II and pronuclear formation in microinjected mouse eggs.

Alternative Splicing↗

Atopic dermatitis: molecular mechanisms, clinical aspects and new therapeutical approaches.

Atopic dermatitis (AD) is a genetically determinated, chronic inflammatory skin disorder associated with cutaneous erythema and severe pruritus, affecting 10-15% of children with increasing incidence and socio-economical relevance. Frequently, AD is associated with development of allergic rhinitis and/or asthma later in childhood. In most of patients AD is associated with a sensitization to food and/or environmental allergens and increased serum-IgE, while only a fewer percentage missed links to the classical atopic diathesis. Currently investigated pathogenetic aspects of AD include imbalanced Th1/Th2 responses, altered prostaglandin metabolism, intrinsic defects in the keratinocyte function, delayed eosinophil apoptosis, and IgE-mediated facilitated antigen presentation by epidermal dendritic cells. An inflammatory response of the two-phase-type and the effects of staphylococcal superantigens (SAgs) are also reported. At present a standardized cure of AD and a consensus on therapeutical approach of the severe form of the disease have not been established. Current management of AD is directed to the reduction of cutaneous inflammation and infection, mainly by S. aureus, and to the elimination of exacerbating factors (irritants, allergens, emotional stresses). Since patient with AD show abnormalities in immunoregulation, therapy directed to adjustment of their immune function could represent an alternative approach, particularly in the severe form of the disease. In this review, we analyse the clinical and genetic aspects of AD, the related molecular mechanisms, and the immunobiology of the disease, focusing our attention on current treatments and future perspectives on this topic.

Adjuvants, Immunologic↗

Significance of selective carotid angiography during complete cardiac catheterization in patients candidates to combined aortic valve and carotid surgery.

AIM: Association of aortic valve stenosis (AVS) with carotid artery disease (CD) constitutes a high risk clinical setting for combined surgery. Carotid angiography is still considered the gold standard for carotid artery imaging, but its use is confined in cases of dubious or inconclusive sonographic examination. Despite the widespread use of ultrasonography, selective angiography may be practical in patients undergoing complete routine cardiac catheterization for AVS due to characteristic abnormalities in flow velocity pattern due to aortic valve stenosis. The present retrospective study aims to estimate the feasibility and role of carotid angiography during complete routine cardiac catheterization in the assessment of CD associated with AVS in patients candidates for combined surgery, in whom Doppler ultrasonography was inconclusive. METHODS: In agreement with cardiac and vascular surgeons, patients aged >60 years, presence of risk factors, and inconclusive Doppler ultrasonographic examination underwent selective carotid artery angiography during complete cardiac catheterization. The angiographic and clinical records of these patients were reviewed. RESULTS: Sixty patients (male/female 28/32, mean age 64.5+/-10.6 years) underwent carotid angiography during left and right catheterization. Optimal visualization of carotid trunk anatomy and morphology was achieved in all patients. Forty-one patients (68.3%) had no carotid artery atherosclerotic involvement, whereas 4 (6.6%) had low grade CD. Fifteen patients (8.3%, male/female: 7/8, mean age 70+/-10.4 years) were diagnosed with critical stenosis of one (14 patients) or both (1 patients) internal carotid arteries. The mean lesion degree was 77.1+/-2.1%. Culprit plaques, bifurcation lesion and occlusion have been discovered in 6.6%, 20%, and 26.6% of patients, respectively. Two arterial spasms (3.3%), and no intrahospital complications were observed. CONCLUSION: In highly selected patients with combined CD and AVS and inconclusive Doppler ultrasonographic examination, selective carotid angiography during heart catheterization is safe, acceptably time-consuming and it may give an optimal anatomical picture of CD.

Aged↗

Modulation of blood circulating immune cells by radiofrequency tumor ablation.

Tumor ablation by radiofrequency (RFA) is an appealing therapeutical strategy for the treatment of liver tumors (hepatocarcinoma and metastatic lesions) to be used as valid alternative to the surgical resection that often is appropriate and feasible in only a minority of patients. RFA induces the localised and controlled disruption of the tumor by heating the tissue causing its coagulative necrosis. Such therapy results as a pathogenic "noxa" for the body, inducing a strong inflammatory response. We wanted to ascertain whether the inflammatory response induced by RFA was similar in patients with hepatocarcinoma and in patients with liver metastasis. We considered body temperature, leucocyte counts at different time points as inflammatory parameters. We observed that RFA treatment produced the inflammatory systemic effects as expected (fever, increase of neutrophils) only in the patients with liver metastasis, while no such effect could be seen in the HCC patients. On the other hand the circulating monocytes increased after RFA in both groups of patients. These preliminary results suggest that RFA tratment can exert different effects on the immune system depending the etiopathogenesis of the treated neoplastic liver lesions.

Body Temperature↗

Trichinella zimbabwensis n.sp. (Nematoda), a new non-encapsulated species from crocodiles (Crocodylus niloticus) in Zimbabwe also infecting mammals.

Since 1995, Trichinella larvae have been detected in 39.5% of farmed crocodiles (Crocodylus niloticus) in Zimbabwe. Morphological, biological, biochemical and molecular studies carried out on one isolate from a farmed crocodile in 2001 support the conclusion that this parasite belongs to a new species, which has been named Trichinella zimbabwensis n.sp. This species, whose larvae are non-encapsulated in host muscles, infects both reptiles and mammals. The morphology of adults and larvae is similar to that of Trichinella papuae. Adults of T. zimbabwensis cross in both directions with adults of T. papuae (i.e. male of T. zimbabwensis per female of T. papuae and male of T. papuae per female of T. zimbabwensis), producing F1 offspring which produce very few and less viable F2 larvae. Muscle larvae of T. zimbabwensis, like those of T. papuae, do not infect birds. Three allozymes (of a total of 10) are diagnostic between T. zimbabwensis and T. papuae, and five are diagnostic between T. zimbabwensis and Trichinella pseudospiralis, the third non-encapsulated species. The percentage of the pairwise alignment identity between T. zimbabwensis and the other Trichinella species for the cytochrome oxidase subunit I gene, the large subunit ribosomal-DNA (mt-lsrDNA) gene and the expansion segment five, shows that T. zimbabwensis is more similar to the two non-encapsulated species T. papuae (91% for cytochrome oxidase I; 96% for mt-lsrDNA; and 88% for expansion segment five) and T. pseudospiralis (88% for cytochrome oxidase I; 90% for mt-lsrDNA; and 66-73% for expansion segment five) than to any of the encapsulated species (85-86% for cytochrome oxidase I; 88-89% for mt-lsrDNA; and 71-79% for expansion segment five). This is the first non-encapsulated species discovered in Africa. The finding of a new Trichinella species that infects both reptiles and mammals suggests that the origin of Trichinella parasites dates back further than previously believed and can contribute to understanding the phylogeny and the epidemiology of the genus Trichinella.

Alligators and Crocodiles↗

Therapy of uncomplicated urinary tract infections.

This article deals with many options in utilizing drugs commonly used in the therapy of uncomplicated urinary tract infections (UTIs), their doses and recommended durations of treatment. In addition, it discusses general and specific accompanying measures related to the decrease in prevalence, relapses and recurrences of UTIs, including some of the factors involved in patient adherence or discontinuation of drug regimens.

4-Quinolones↗

Urinary tract infections in women.

Urinary tract infection (UTI) is one of the most frequent diseases in medical practice. Some definitions and epidemiology of UTI and bacteriuria are discussed, as well as host susceptibility and defense mechanisms. Aspects of infection in young women and in the elderly are reported, emphasizing microbiological, clinical and therapeutic aspects. Finally, epidemiologic and clinical aspects of fungal UTI are discussed.

Adolescent↗

Urinary tract infections in pregnant women.

Urinary tract infections are of great importance during pregnancy owing to undesirable complications such as fetal and maternal morbidity. This paper describes the functional alterations that occur in this condition and predispose to infection. Clinical presentation and subsidiary diagnosis are discussed, including asymptomatic bacteriuria, cystitis and pyelonephritis. In addition, the authors report drug options, and their safety and duration of treatment during pregnancy.

Anti-Bacterial Agents↗