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Biomedical subjects

G Ferrari

Publications and source records attributed to G Ferrari.

At least 55 records · Page 3Linked to original sources

[Traumatic internuclear ophthalmoplegia].

The authors report a case of traumatic internuclear ophthalmoplegia and discuss its pathophysiologic mechanism. Internuclear ophthalmoplegia due to head trauma is uncommon, though it may be more common than reported since signs and symptoms typically resolve over weeks to months, and in multiple trauma patients other serious injuries overshadow disturbances of eye movements. A lesion involving medial longitudinal fasciculus was found by magnetic resonance imaging in the early post-traumatic period; this lesion was not seen when routine X-ray computed tomography was performed at the time of injury, confirming that magnetic resonance scanning is definitely superior to computed tomography for evaluating internuclear ophthalmoplegia.

Aged

Comparison of anti-HIV-1 ADCC reactivities in infected humans and chimpanzees.

Despite its shortcomings as a disease model, the chimpanzee is still the most relevant animal model for human immunodeficiency virus type 1 (HIV-1) infection. Previous studies have revealed qualitative differences between human and chimpanzee anti-HIV-1 responses. In this study, the development of specific anti-HIV-1 antibody-dependent cellular cytotoxic (ADCC) reactivities was evaluated in chronically infected chimpanzees and compared to the human response, because anti-HIV-1 ADCC represents a major component of anti-envelope cytolytic response found in infected patients. Ten HIV-1-infected chimpanzees up to 5 years after the infection were investigated. Anti-HIV-1 ADCC-directing antibodies were detectable in only three of 10 infected chimpanzees, and in these animals, activity was apparent only several months after the HIV infection. In some of the infected animals, ADCC reactivity against infected cells preceded reactivity against gp120-coated targets. When anti-gp120 ADCC-directing antibodies were apparent, they exhibited the same broad reactivity described in humans against different HIV isolates. The pattern of ADCC reactivities in infected chimpanzees is completely different from the well-characterized anti-gp120 cytotoxic reactivities present in HIV-1-infected patients. It is a relatively rare and late-occurring event that may have an important bearing on the lack of virus-induced pathogenesis in the chimpanzee model.

Animals

Regulation of base balance in bicarbonate hemofiltration.

The purpose of this study was to investigate the feasibility of bicarbonate as a substitute for acetate or lactate in hemofiltration solutions using a new bag for the bicarbonate substitution fluid. We analysed 24 hemofiltration sessions with different HCO3- concentrations (30, 35 and 40 mEq/L) in the substitution fluid. The increase in the HCO3- concentration in the substitution fluid resulted in a more positive HCO3- balance. The Net Base Gains (NBG) were, respectively, 73.7 +/- 92 with 30, 138.2 +/- 97 with 35 (p < 0.05 vs 30) and finally 201 +/- 65.9 with 40 mEq/L (p < 0.001 vs 30). The physical separation between the base losses and gains could facilitate the modelling approach in hemofiltration. By means of a stepwise regression analysis, we studied a series of variables that could influence end-treatment HCO3-, which was significantly and directly dependent (F = 6.003, r = 0.747, p = 0.0027) on the HCO3- concentration in the substitution fluid and the apparent HCO3- space. HCO3- values predicted by the statistical model correlated well with those actually measured (r = 0.757; p < 0.001). This mathematical modelling approach allowed us to predict the quantities and concentrations of HCO3- to be infused in order to obtain an ideal acidosis correction, tailored to individual patient needs.

Acid-Base Equilibrium

Alpha, beta I, beta II, delta, and epsilon protein kinase C isoforms and compound activity in the sciatic nerve of normal and diabetic rats.

Defective protein kinase C (PKC) has been implicated in impaired Na+,K(+)-ATPase activity in the sciatic nerve of streptozotocin-induced diabetic rats. In the present study, alpha, beta I, beta II, gamma, delta, and epsilon isoform-specific antibodies were used in parallel to the measurement of compound PKC activity for the characterization of PKC distribution and isoform expression in sciatic nerves of normal and diabetic rats. To distinguish isoform expression between the axonal and glial compartments, PKC isoforms were evaluated in nerves subjected to Wallerian degeneration and in a pure primary Schwann cell culture. alpha, beta I, beta II, delta, and epsilon but no gamma isoforms were detected in sciatic nerve. Similar immunoreactivity was observed in degenerated nerves 3-4 days after transection except for diminished beta I and epsilon species; in Schwann cell cultures, only alpha, beta II, delta, and epsilon were detected. In normal nerves, two-thirds of PKC compound activity was found in the cytosol and 50% of total enzyme activity translocated to the Na+,K(+)-ATPase-enriched membrane fraction with phorbol myristate acetate. Similar redistribution patterns were observed for the immunoreactivity of all isoforms with the exception of delta, which did not translocate to the membrane with phorbol myristate acetate. No abnormality in compound PKC activity, in the immunoreactive intensity, or in the distribution of PKC isoforms could be detected in rat sciatic nerve after 6-12 weeks of diabetes. Thus, defective activation rather than decreased intrinsic PKC activity may occur in diabetic neuropathy.

Animals

Combination treatment in M1 prostate cancer.

The treatment of advanced prostate cancer is based on hormone manipulation to eliminate the trophic effect of testosterone on sensitive androgen tissue of the tumor. In this study, we evaluated the efficacy of the partial androgen blockage versus the complete androgen blockage. One hundred, twenty-two patients were entered in this study and randomly were treated with buserelin alone or with buserelin and flutamide. The group that received buserelin was given cyproterone acetate (200 mg/day) during first 3 weeks of treatment to avoid "flare-up". During the follow-up (range 0-244 +/- 1 weeks), we evaluated 59 patients (61.4%) that had positive response and 37 patients (38.6%) that showed progressive disease: There were no statistically significant differences between the two treatment groups, not even in the evaluation of median time to response and of median time to treatment failure. In conclusion, the results emphasize that total androgenic blockage is as effective as a luteinizing hormone-releasing hormone analog used alone.

Aged

[New diagnostic and therapeutic prospects in peripheral nodules of the lung: surgical video thoracoscopy].

The new findings and results of laparoscopic surgery lead us to apply this technique in thoracic surgery. Thoracoscopy is an old diagnostic procedure, but advanced imaging techniques, improved optics and new classes of instrument have paved the way for many diagnostic and therapeutic approaches, before not feasible. Now it is possible to treat spontaneous pneumothorax, removal of mediastinal and peripheral tumors, with minimally invasive surgery. It is our belief that thoracoscopic surgery will be a valuable tool in the near future for a variety of chest disorders.

Anesthesia, General

Phenotype and function of stromal cells cloned from the ileal Peyer's patch of sheep.

The ileal Peyer's patch (PP) is the major site of B cell production and immunoglobulin diversification in lambs, but the factors which regulate these processes are poorly understood. As a first step toward identifying possible regulatory mechanisms, stable long-term cultures of ileal PP stromal cells were established at the clonal level. Four distinct cell types were identified by their phenotype and growth requirements. Immunohistochemical staining confirmed that all clones were mesenchymal (vimentin+; cytokeratin-) in origin and were negative for T cell, B cell, and macrophage markers. Three cell lines were negative for major histocompatibility complex (MHC) I and II molecules, but one cell line, SCN, expressed MHC I, MHC II and CD44 molecules, and a subpopulation of SCN cells expressed BAQ44A, a B cell differentiation molecule. The four cell lines produced different types and amounts of extracellular matrix proteins, and their growth was not influenced by exogenous human interleukin 1 (IL-1), IL-2, transforming growth factor beta 1 (TGF beta 1), or bovine fibroblast growth factor (FGF) but was influenced by serum. When tested for their capacity to support lymphocyte growth, all clones produced a soluble factor(s) that was mitogenic for ileal and jejunal PP cells and thymocytes. Similar growth promoting activity was observed with culture supernatants of murine, human and bovine fibroblasts but could not be reproduced using recombinant human cytokines. Furthermore, coculture of stromal cells with ileal PP follicular B cells elicited a proliferative response unique to each stromal cell line. Coculture with increasing numbers of SCN cells inhibited B cell proliferative responses, whereas coculture with SCG2 and SCF32 cells enhanced B cell proliferative response at both low and high stromal cell densities. Ileal PP follicular B cells rapidly bound to the surface of all stromal cell clones, and this interaction was specific when compared with thymocytes or peripheral blood lymphocytes. These results suggest that ileal PP stromal cells are a phenotypically and functionally heterogeneous population that may enhance or inhibit B lymphopoiesis in the ileal PP.

Animals

Simultaneous infection with three different S. enteritidis strains in a nursing home resident.

A culture taken from a nursing home resident as part of a S. enteritidis outbreak was found to have a mixed infection due to three different strains of S. enteritidis. One of the three strains belonged to phage type (PT) 4, one to PT6 and one reacted with phages but did not conform to any typing scheme (RDNC). All three strains had the 38.9 megadaltons (MDa) plasmid found in the isolates from the outbreak-related cases, in addition the PT6 and RDNC strains harboured a 69.9 MDa plasmid. The importance of phage typing and plasmid analysis for S. enteritidis strain characterization and their epidemiologic and bacterial significance are discussed.

Aged

Riboflavin uptake by rat small intestinal brush border membrane vesicles: a dual mechanism involving specific membrane binding.

The first step of riboflavin absorption was studied by determining the uptake of the vitamin by rat small intestinal brush border membrane vesicles. Vesicles were incubated at 25 degrees C in the presence of [3H]-riboflavin at concentrations within the physiological intraluminal range for rat. The time course of [3H]-riboflavin uptake was unaffected by Na+ or K+ gradients. The 5 sec uptake rate plotted as a function of the initial concentration of [3H]-riboflavin in the medium (0.125 to 7.5 microM) revealed the presence of a dual mechanism, with a saturable component (apparent kinetic constants: 0.12 microM for Km and 0.36 pmol.mg-1 protein x 5 sec-1 for Jmax) prevailing at low concentrations (< 2 microM), and a nonsaturable component prevailing at higher concentrations. The presence of a carrier-mediated system for riboflavin was validated by countertransport experiments. At equilibrium, uptake was almost completely accounted for by membrane binding, whereas at earlier times the transport component accounted for about 30% of total uptake. The plot of [3H]-riboflavin binding at equilibrium as a function of its concentration in the medium was quite similar to that of the 5 sec uptake rate in both intact and osmotically shocked vesicles and demonstrated the occurrence of a saturable component: binding constants were 0.07 (Kd in microM), 0.54 (Bmax in pmol.mg-1 protein), and 0.11 (Kd), 1.13 (Bmax), respectively, indicating the existence of specific riboflavin binding sites. The specificity of riboflavin binding to the membrane was confirmed by preliminary studies with structural analogues. Specific binding could represent the first step of a specific riboflavin entry mechanism in enterocytes.

Animals

Egg-related Salmonella enteritidis, Italy, 1991.

In recent years, Salmonella enteritidis has become an increasingly important public health problem in Italy. In some parts of the country, the fraction of total human salmonella isolates accounted for by S. enteritidis has risen from 3-4% in the mid-1980s to more than 30% in 1990. Between 1990 and 1991, the number of reported S. enteritidis outbreaks increased more than sixfold. The 33 outbreaks reported in 1991 occurred in seven contiguous regions in northern and central Italy and were clustered in time between June and October: in the majority, products containing raw or undercooked shell eggs were implicated. Five of the egg-related outbreaks that occurred within a 30 kilometre radius over a 7-week period were investigated in detail. A phage type 1 strain containing a 38.9 MDa plasmid appeared responsible for three of the outbreaks, while in the remaining two a phage type 4 strain, also with a 38.9 MDa plasmid was isolated. Efforts are being made to enhance epidemiological surveillance and laboratory evaluation, and the use of pasteurized eggs has been recommended for high-risk populations.

Disease Outbreaks

The impact of HIV-1 infection on phenotypic and functional parameters of cellular immunity in chimpanzees.

As a means of assessing the immunological impact of HIV infection in the chimpanzee, as well as the participation of the cellular components in the control of HIV infection in these animals, various aspects of cellular immunity were investigated in chronically HIV-infected chimpanzees. Eight HIV-1-infected chimpanzees were included in this study; two of them were infected for more than 5 years and six for nearly 3 years at the time of study. All of the chimpanzees received either 40 or 100 TCID50 of HTLV-IIIB. Circulating peripheral blood lymphocytes were studied by flow cytofluorimetric analysis in order to reveal possible alterations in the CD4:CD8 ratio, as well as in specific CD4+ and CD8+ cell subpopulations. Chronically infected chimpanzees did not present significant alterations in the percentage of CD4+ or CD8+ lymphocyte subsets. Interestingly, the CD8+/CD57+ cell subset was not detectable. The expression of markers for activation on circulating lymphocytes, usually higher in the HIV-infected patients, was not altered in infected animals. The functional aspects of specific anti-HIV-1 non-MHC and MHC-restricted cellular cytotoxic reactivities were also investigated. The results were compared with the findings in normal uninfected chimpanzees and in HIV-infected humans. Only one chimpanzee (881) developed a detectable, specific non-MHC-restricted anti-HIV-1- reactivity. Compared to that seen in humans, the ontogeny of this activity is delayed. Among the other infected chimpanzees, no specific anti-HIV cellular reactivities were detectable in the peripheral blood. In chimpanzees, HIV-1 infection evidently does not elicit the same strong cellular reactivity as that detected in infected patients. The absence of chronic cellular activation, despite continued viral replication, may highlight a key determinant in HIV-1-induced pathogenesis that is likewise absent in infected chimpanzees.

Animals

Transfer of the ADA gene into bone marrow cells and peripheral blood lymphocytes for the treatment of patients affected by ADA-deficient SCID.

Severe combined immunodeficiency (SCID) caused by deficiency of the enzyme adenosine deaminase (ADA) is the first genetic disorder considered for human somatic cell gene therapy. ADA-SCID patients can be cured by HLA-matched sibling donor bone marrow transplantation. Alternative transplantation strategies as well as enzyme replacement are being tested in those patients who do not have a suitable matched sibling donor. Some ADA-SCID patients may not be candidates for cytoablation due to infectious damage to the lung or liver, or may have a milder phenotype that does not justify the risks associated with haploidentical bone marrow transplantation. Replacement therapy with PEG-ADA has resulted in improvement in growth, a variable increase in the number of peripheral blood lymphocytes, and a decrease in the incidence of severe infections. Another approach to the treatment of severe genetic diseases is now represented by somatic cell gene therapy. We and others have conducted experiments in vitro and in vivo that have documented that T-lymphocytes are suitable vehicles for gene transfer. Although the pluripotent stem cell remains the ideal target cell for somatic cell gene therapy of disorders of the hematopoietic system, the use of T-lymphocytes as gene therapy vehicles is specifically indicated for ADA-deficient patients where they represent the affected cells. Furthermore, the selective engraftment of T-cells only, following bone marrow transplantation, has resulted in reconstitution of cellular and humoral immunity. A model for the functional analysis in vivo of the human immune system has been utilized for the preclinical evaluation of this approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase

Retroviral vector-mediated gene transfer into human primary myogenic cells leads to expression in muscle fibers in vivo.

Primary human myogenic cells isolated from fetal and adult muscle were infected with a high-titer, Moloney murine leukemia virus (MoMLV)-derived retroviral vector expressing a bacterial beta-galactosidase (beta-gal) gene under long terminal repeat (LTR) control. Gene transfer efficiency averaged 50% in both fetal myoblasts and adult satellite cells, as revealed by beta-gal staining. The reporter gene was stably integrated, faithfully inherited, and expressed at significant levels in myogenic cells for at least 10 generations under clonal growth conditions, and throughout the culture life span upon differentiation into myotubes. Comparable gene transfer efficiency was obtained in myogenic cells from muscle biopsies of patients affected by a number of genetic or acquired myopathies, including Duchenne muscular dystrophy. Transduced normal human satellite cells were injected into regenerating muscle of immunodeficient mice, where they formed new muscle fibers in which the product of the reporter gene was detectable for 2 months after injection. These results show that retroviral vectors can be used to transfer foreign genes with high efficiency into normal or abnormal primary human myogenic cells, leading to stable expression into mature muscle. Satellite cells engineered in this way might represent an effective tool for gene therapy of muscular dystrophies as well as for systemic delivery of recombinant gene products for correction of inherited and acquired disorders. The human-mouse model described here will allow in vivo testing of such gene therapy approaches.

Adolescent

Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression.

An eight-week double-blind, multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression (DSM-III-R). There were 108 out-patients, from nine Italian centres, entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine). The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg. Both treatment groups showed a statistically significant improvement from baseline at one week, and this was maintained until the end of treatment for all of the following measures: Hamilton Rating Scales for Depression and Anxiety, the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale, Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire. Although there was a numerical advantage for sertraline on several efficacy measures, there was no statistically significant difference found between the treatment groups. The incidence of adverse events was similar for both treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse events were generally rated by patients as of lower severity in the sertraline group. In addition, for the fluoxetine group, there was a higher incidence of agitation, anxiety and insomnia than for sertraline. Sertraline was considered to be better tolerated than fluoxetine overall, since only 9.6% of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline-treated patients discontinued prematurely because of clinical improvement, compared with 10.7% of fluoxetine-treated patients.

1-Naphthylamine

[Neuroleptic-induced dysphoric response in non-schizophrenic patients].

In 50 psychiatric inpatients treated with neuroleptics we observed neuroleptic-induced dysphoria in 4% and neuroleptic-induced akathisia in 18% of the cases. In our sample there was no schizophrenics among dysphoric responders. We discuss the implication of the findings and the relationship between dysphoric response and subjective phenomena of akathisia.

Adult