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Biomedical subjects

F Colombo

Publications and source records attributed to F Colombo.

At least 37 records · Page 2Linked to original sources

Orbital involvement in cherubism.

PURPOSE: To demonstrate the clinical, radiologic, and histopathologic features of a patient with orbital involvement in cherubism that prompted surgical treatment. DESIGN: Single interventional case report. INTERVENTION: Findings of the ophthalmic evaluation, computed tomography (CT) scans, intraoperative examination, and light microscopy of the specimens were analyzed. MAIN OUTCOME MEASURES: Globe displacement, orbital bony lesions detected on CT scans, histopathology, and postoperative results were assessed. RESULTS: A 27-year-old female was seen with a slowly progressive superonasal globe displacement and a temporal orbital mass bilaterally of 6 years' duration. She had a history of cherubism, but her cheeks and jaws had a normal appearance instead of the bilateral fullness of the lower half of the face typical of the disease. CT scans demonstrated multicystic bony lesions arising from the orbital floors bilaterally. The masses were excised using an anterior transcutaneous transseptal orbitotomy. Histopathology demonstrated numerous giant cells in a fibrovascular stroma, confirming the clinical diagnosis of cherubism. Postoperative recovery was complete. CONCLUSIONS: Orbital involvement in cherubism may develop beyond puberty, after stabilization or regression of the lesions in the jaws. Patients with cherubism should be routinely evaluated by an ophthalmologist.

Adult↗

Cronkhite-Canada syndrome. A case of sustained partial-remission.

A case of Cronkhite-Canada syndrome is described. Few cases have been published and in most patients the prognosis is poor. A variety of medical measures have been attempted in those in whom remission has been reported. In the patient presented here, a sustained partial-remission has been achieved with steroids.

Anti-Inflammatory Agents↗

TGF-beta(1) and prepro-ANP mRNAs are differentially regulated in exercise-induced cardiac hypertrophy.

The induction of transforming growth factor (TGF)-beta and prepro-atrial natriuretic peptide (ANP) mRNAs represent hallmark features of pathological cardiac hypertrophy. The present study examined whether this pattern of mRNA expression was conserved in a physiological model of cardiac hypertrophy. To address this thesis, female Sprague-Dawley rats were individually housed and permitted to run freely. Voluntary exercise for 3 and 6 wk resulted in biventricular hypertrophy and increased cytochrome c oxidase activity in the triceps muscle. In the hypertrophied left ventricle, the steady-state mRNA level of the cardiac fetal gene prepro-ANP and the extracellular matrix proteins preprocollagen-alpha(1) and fibronectin were similar in exercise-trained and sedentary rats. By contrast, an increased expression of TGF-beta(1) mRNA was observed, whereas TGF-beta(3) mRNA level was unchanged in the hypertrophied left ventricle of exercise-trained compared with sedentary rats. These data highlight a heterogeneity in the regulation of TGF-beta isoforms, and the increased expression of ventricular TGF-beta(1) mRNA in physiological cardiac hypertrophy may contribute to myocardial remodeling.

Animals↗

Peyronie's disease: prevalence and association with cigarette smoking. A multicenter population-based study in men aged 50-69 years.

OBJECTIVES: We present a multicenter, population-based epidemiological survey aimed at assessing the prevalence of Peyronie's disease (PD) and its potential risk factors in the general population. METHODS: In each of the ten centers throughout Italy, a uroandrologist contacted all the men in the age range 50-69 years registered with a general practitioner (GP). The subjects recruited were evaluated on the basis of their medical history, including alcohol consumption and cigarette smoking. The following questionnaires were administered: IIEF, IIPSS symptom score, premature ejaculation and PD. RESULTS: All the subjects registered with a GP were invited to participate in the study. Of the 1,180 subjects, 647 (53%) entered over survey. In this population, 46 cases of PD were identified, accounting for a prevalence of 7.1%. The prevalence rate increased with age even if the trend is not statistically significant. The multivariate analysis showed a significant correlation between cigarette smoking and PD, with an odds ratio (OR) of 4.6 (CL 95%) confidence limit 1.506- 14.287). Smoking as single variable had an OR of 7.2 (95% CL 2.34-24.93). No significant association was observed between PD and the other variables such as cardiovascular diseases, diabetes, hypertension and alcohol consumption. CONCLUSIONS: PD is a much more frequent condition in the general population than previously reported. According to our results, cigarette smoking may be considered a risk factor for developing PD. If further and more targeted studies confirm that giving up smoking may reduce the risk of developing PD, then there will be new prospects for primary and secondary prevention and for curbing the progression of the disease.

Age Factors↗

Nitric oxide attenuates the expression of transforming growth factor-beta(3) mRNA in rat cardiac fibroblasts via destabilization.

Transforming growth factor-beta (TGF-beta) has been implicated in the development of interstitial fibrosis in cardiac hypertrophy. NO has been regarded as a potent inhibitor of cardiac fibroblast growth, albeit the modulation of cellular events associated with interstitial fibrosis remains undefined. In this regard, the regulation of TGF-beta mRNA expression by the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) was examined in neonatal rat cardiac fibroblasts. SNAP treatment for 4 hours decreased TGF-beta(3) mRNA levels, an effect mimicked by 8-bromo-cGMP. TGF-beta(3) mRNA, however, had returned to levels observed in the untreated cells after a 24-hour exposure to SNAP, whereas a decreased expression persisted with 8-bromo-cGMP. In contrast to TGF-beta(3), TGF-beta(1) mRNA levels were modestly increased in response to cGMP-generating molecules. The treatment with actinomycin D for at least 8 hours did not appreciably alter TGF-beta(3) mRNA levels. By contrast, SNAP treatment caused a rapid decrease of TGF-beta(3) mRNA with a half-life of 3.3+/-0.2 hours, thereby supporting a mechanism of destabilization. The pretreatment with SNAP inhibited angiotensin II-stimulated protein synthesis and the concomitant expression of TGF-beta(3) mRNA. These data reveal a disparate pattern of TGF-beta(1) and TGF-beta(3) mRNA regulation by NO and highlight a novel mechanism of destabilization contributing to the decreased expression of TGF-beta(3) mRNA. The modulation of both basal and angiotensin II-stimulated TGF-beta(3) mRNA expression provides a mechanism by which NO may influence the progression of interstitial fibrosis.

Angiotensin II↗

[Erectile dysfunction after non-nerve sparing radical pelvic surgery. Therapeutical experience with sildenafil and L-arginine evaluated by Buckling test].

BACKGROUND: Patients undergoing radical pelvic floor surgery are often find that sexual function is impaired. In this research hypothesis, we evaluated the efficacy of alternative therapy to conventional PGE 1 injections, such as the association of Sildenafil and L-Arginine. This association is based on the principle that L-Arginine, the precursor of nitric oxide, improves the effect of Sildenafil, which is effective in the presence of nitric oxide. METHODS: The experimental plan was to make a comparative study between 2 random groups of patients selected from those undergoing radical cystectomies and prostatectomies over the past three years. 116 patients were eligible (64 prostatectomies and 52 cystectomies). The first random group was treated with Sildenafil alone and the second with Sildenafil and L-Arginine. The efficacy of treatment was evaluated using the Buckling test (pressure threshold of cavernous flexation at penile axial rigidity) once after ambulatorial administration and then by telephone interview (subjective evaluation) after administration at domicile. RESULTS: The starter dose was 50 mg and was inefficient in both groups (Buckling test between 0 and 250). 100-mg doses gave significant results (Buckling test >500) in both groups, especially the second. Cardiopathic patients, diabetics and patients with retinal disorders or who were unmotivated were excluded from the study. The mean age of patients was 65. CONCLUSIONS: The resumption of relatively satisfactory sexual activity was demonstrated using non-invasive pharmacological treatment.

Aged↗

[Erectile disfunction after non nerve-sparing radical pelvic surgery].

BACKGROUND: The patients who undergo radical pelvic surgery often found that sexual function is impaired. In this research hypothesis, we evaluated the efficacy of alternative therapy to conventional PGE 1 injections, such as the association of Sildenafil and L-Arginine. This association in based on the principle that L-Arginine, the precursor of nitric oxide, improves the effect of Sildenafil, which is effective in the presence of nitric oxide. METHODS: The experimental plan was to make a comparative study of 2 random groups of patients selected from those undergoing radical cystectomies and prostatectomies over the past three years. 116 patients were illegible (64 prostatectomies and 52 cystectomies). The fìrst random group was treated with Sildenafil alone and the second with Sildenafil and L-Arginine. The efficacy of treatment was evaluated by the Buckling test (pressure threshold of cavernous flexation at penile axial rigidity) once-after ambulatorial administration and then by telephonic interview (subjective evaluation) after home administration. RESULTS: The starter dose was 50 mg and was inefficient in both groups (Buckling test between 0 and 250). 100-mg doses gave significant results (Buckling test > 500) in both groups, especially the second. Cardiopathic patients, diabetics and patients with retinal disorders were excluded from the study. The mean age of patients was 65 years. CONCLUSIONS: The resumption of relatively satisfactory sexual activity was demonstrated using non-invasive pharmacological treatment.

Aged↗

[Uro-andrologic prevention of male infertility].

The Authors analyze the more frequent uro-andrological pathologies correlated with male infertility and consider the causes of impoverishment in semen in industrialized countries. They analyze preventing possibilities to maintain the normal physiological level of fertility in young male in various uro-andrological pathologies.

Cryopreservation↗

T-lymphocyte maturation abnormalities in uninfected newborns and children with vertical exposure to HIV.

Cell-mediated immunity and T-lymphocyte maturation are impaired in HIV-infected children. These abnormalities would be detected in HIV-uninfected offspring of HIV women (seroreverters [SR]) if HIV or its soluble proteins could cross the placental barrier. Immunophenotypic analyses were performed in 20 healthy HIV-uninfected newborns of HIV-infected mothers (SR), and in 14 healthy newborns of HIV-negative women (UC). The same analyses were performed in 3 groups of older children: SR (n = 41); UC (n = 15); and HIV-infected children (n = 25). Antigen-specific cells were evaluated with ELISpot and fluorimetric analyses; IL-7 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). Results showed that in SR newborns: (1) the CD4/CD8 ratio was reduced, (2) CD4(+) and CD8(+) naive T-cell percentages were decreased, (3) percentage of activated CD8(+) T cells was increased, and (4) percentages of CD3(+)/4(-)/8(-) (DN) and DN/25(-)/44(+) were augmented. These abnormalities were partially retained in older SR children. CD4(+) and CD8(+) HIV-specific cells were detected in a portion of newborn SRs but not in older SRs. Serum IL-7 was augmented both in newborn and older SRs. Cell-mediated immunity and T-cell maturation are altered even in HIV-uninfected newborns of HIV-infected mothers; these abnormalities persist over time. The biologic significance of these observations and potential subsequent clinical events should be investigated in larger cohorts of seroreverters. (Blood. 2000;96:3866-3871)

Adult↗

Mucosal and systemic immune activation is present in human immunodeficiency virus-exposed seronegative women.

Immune parameters were analyzed in peripheral blood mononuclear cells (PBMC) and cervical mucosa biopsy specimens of human immunodeficiency virus (HIV)-seronegative women sexually exposed to HIV (exposed seronegative [ESN]), HIV-infected women, and healthy women without HIV exposure. HIV was not detected in PBMC or cervical mucosa biopsy specimens of ESN women. However, interleukin (IL)-6, IL-10, IL-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha and -beta mRNA were elevated in PBMC and cervical mucosa biopsy specimens of ESN and HIV-infected women; CCR5 and CXCR4 mRNA were augmented in cervical mucosa biopsy specimens, but not in PBMC, of ESN and HIV-infected women; HIV-specific IFN-gamma-secreting cells were detected in vaginal washes of ESN and HIV-infected women; and phenotypic alterations were present in PBMC of ESN women. These results suggest that active HIV infection is not required for T cell activation; immune alterations occur in women in whom HIV infection cannot be detected virologically or clinically.

Cytokines↗

Substitution of fish species detected by thin-layer isoelectric focusing and a computer-assisted method for the evaluation of gels.

Fourteen fish species susceptible to substitution were analysed by the thin-layer isoelectric focusing technique on polyacrylamide gels of pH 3.5-9.5. Four fish per species were run on the same gel to verify the possibility to differentiate them according to their protein banding patterns. The occurrence of intraspecific differences due either to electrophoretic variations or to protein polymorphism was also observed. In fact, some of them showed few dissimilarities among their protein profiles. However, the differentiation was possible for all species, even for those belonging to the same order, family and genus. Computer-based tools combined with statistical analysis were implemented and usefully applied to avoid a subjective evaluation of the isoelectric focusing gels, and to verify the reliability of the preliminary visual comparison of protein patterns.

Animals↗

Different immunologic profiles characterize HIV infection in highly active antiretroviral therapy-treated and antiretroviral-naïve patients with undetectable viraemia. The Master Group.

BACKGROUND: Suppression of human immunodeficiency virus (HIV) replication can be obtained in chronically infected individuals by highly active antiretroviral therapy (HAART) and can also be observed in antiretroviral-naïve patients. The immunological correlates of these two situations were examined. DESIGN AND METHODS: Cross-sectional study involving 32 HIV-infected patients with undetectable HIV plasma viraemia (< 500 copies/ml) and either antiretroviral-naive (n = 14) or undergoing HAART therapy with two nucleoside reverse transcriptase inhibitors (NRTI) plus one (n = 13) or two (n = 5) protease inhibitors (PI). CD4 counts, disease duration, and CDC clinical stage were comparable between the two groups of individuals. Immune parameters (antigen- and mitogen-stimulated proliferation and cytokine production; cytokine mRNA; beta chemokine production; HIV coreceptors mRNA) were analysed in all patients. RESULTS: Results showed immune profiles to be profoundly different in antiretroviral-naive in comparison with HAART-treated patients. Thus: (1) T-cell proliferation to HIV-specific and HIV-unrelated antigens is potent in antiretroviral-naive but suppressed in HAART-treated individuals; (2) interleukin-(IL)2, IL-12 and interferon gamma (IFNgamma) production is robust in naive patients; and (3) a high CCR5/low CXCR4 pattern of HIV coreceptors-specific mRNA is observed in naive but not in HAART-treated patients. In contrast with these observations, no clear differences were detected when beta chemokine production by either peripheral blood mononuclear cells or purified CD8+ T-cells was analysed. Results from HAART-treated patients undergoing therapy with one PI and two NRTI or two PI and two NRTI were in very close agreement. CONCLUSIONS: These data suggest that control over HIV replication can be independently achieved by pharmacological or immunologic means. HAART is associated with weaker HIV-specific and -non-specific immune responses.

CD8-Positive T-Lymphocytes↗

In vitro immunomodulatory properties of tucaresol in HIV infection.

The immunomodulatory properties of tucaresol (compound 589C80) were tested on in vitro antigen- and mitogen-stimulated proliferation and cytokine production by peripheral blood mononuclear cells (PBMC) of HIV-infected individuals and healthy controls (HC). Results showed that tucaresol: (1) increases influenza A virus-, gp 160 peptide-, and HLA alloantigen-stimulated proliferation as well as interleukin (IL)-2 and interferon gamma (IFN gamma) production by PBMC of HIV-infected individuals with higher CD4 counts (>500/microl) but had only a marginal immunomodulatory effect on PBMC of patients with lower CD4 counts (<500/microl); (2) did not modify IL-10 production; (3) augmented CD25 expression on mitogen-stimulated T cells of HC but not of HIV-infected individuals; and (4) marginally increased CTL activity. The immunomodulatory properties of tucaresol were confirmed by PCR analyses; additional data showed that tucaresol costimulated CD3-dependent triggering of T cells and that this stimulation was independent of CD28 costimulation. The immunomodulatory effects of tucaresol on T cell functions are characterized by a bell-shaped dose response curve; the action of the compound is optimal in the 100 to 300 microM range. Analyses of mitogen-stimulated apoptosis demonstrated that the lack of effect of tucaresol at higher doses is not the result of increased cell death, suggesting a role of functional impairment. These data confirm that tucaresol can stimulate T helper cell function and enhance the production of type 1 cytokines, thus eliciting cell-mediated immunity, and warrant its potential utility in the therapy of HIV infection.

Adjuvants, Immunologic↗

A farnesyltransferase inhibitor attenuates cardiac myocyte hypertrophy and gene expression.

The overexpression of either oncogenic ras or calmodulin in cardiac myocytes can elicit a hypertrophic response, albeit their recruitment by physiologically relevant stimuli remains unresolved. The present study utilized a pharmacological approach to examine the role of ras and calmodulin in norepinephrine- and endothelin-1-stimulated hypertrophy of neonatal rat cardiac myocytes. The pretreatment of cardiac myocytes with the farnesyltransferase inhibitor BMS-191563 (25 microM) increased the level of unfarnesylated ras in the cytosolic fraction, and caused a concomitant 42 +/- 2% decrease in immunodetectable farnesylated ras in the particulate fraction. In parallel, BMS-191563 pretreatment inhibited norepinephrine-mediated 3H-leucine uptake (80 +/- 10% decrease: n = 6; P<0.01), whereas a significant but less pronounced effect on the endothelin-1 response (46 +/- 6% decrease: n = 6; P<0.05) was observed. The calmodulin inhibitor W7 caused a 50 +/- 10% decrease (n = 8; P<0.05) of norepinephrine stimulated protein synthesis, whereas the endothelin-1 response was unaffected. Consistent with the recruitment of ras, BMS-191563 pretreatment attenuated norepinephrine and endothelin-1-stimulated extracellular signal-regulated kinase (ERK) activity. However, PD098059-mediated inhibition of MEK-dependent stimulation of ERK did not alter the hypertrophic response of either agonist. At the molecular level, the pretreatment with either BMS-191563 or W7 attenuated the norepinephrine-mediated increase of prepro-ANP and -BNP mRNA. Likewise, BMS-191563 caused a significant decrease of endothelin-1-mediated expression of the natriuretic peptide mRNAs, but to a lesser extent, as compared to norepinephrine. Thus, the present study has shown the treatment of neonatal rat cardiac myocytes with a farnesyltransferase inhibitor can attenuate the hypertrophic phenotype in response to physiologically relevant stimuli, thereby supporting a role of the small GTP-binding protein ras. Moreover, these data further suggest alternative ras-independent signaling pathways are also implicated in the hypertrophic response, albeit, there appears to exist a stimulus-specific heterogeneity in their recruitment.

Alkyl and Aryl Transferases↗

The role of decompressive craniectomy in the treatment of uncontrollable post-traumatic intracranial hypertension.

The benefit of decompressive craniectomy for the treatment of uncontrolled post-traumatic intracranial hypertension seems to be encouraging if medical management fails. We present our experience in 22 cases of cerebral edema due to head trauma. The edema alone was rarely the direct consequence of head trauma. Frequently it was associated with an acute subdural or extradural hematoma and contusion (with or without mass effect). First of all we treated the mass effect of the hematoma and contusion when the diameter was more than 3 cm. Intracranial pressure was monitored in the majority of patients. Bone decompression was performed in the operating theatre depending on the values of intracranial pressure. In our series 41% of patients had a good recovery, 18% a severe disability, 23% a vegetative state and 18% died. The findings showed that the bony decompression must be performed early before the situation becomes irreversible. We suggest that if intracranial pressure values remain greater than 30 mmHg with cerebral perfusion pressure below 70 mmHg, despite vigorous anti-edema therapy, decompressive craniectomy should be considered.

Adolescent↗

Effect of two different combinations of antiretrovirals (AZT+ddI and AZT+3TC) on cytokine production and apoptosis in asymptomatic HIV infection.

Nineteen HIV-seropositive antiretroviral therapy-naive and asymptomatic individuals (200-500 CD4/microl) were enrolled in a prospective study aimed at analyzing the immunologic and virologic effects of two different combinations of nucleoside reverse transcriptase inhibitors (AZT+ddI and AZT+3TC), and randomly assigned to one of the treatment group. Immunologic (CD4 and CD8 counts, mitogen-stimulated cytokine production, unstimulated and mitogen-stimulated apoptosis) and virologic (HIV viral load) determinations were performed pre-therapy and 15, 30, 90, 200 and 360 days after initiation of therapy. Results showed that the two combinations had comparable effects on increasing CD4 counts and the CD4/CD8 ratio and in reducing HIV viral load. In contrast, AZT+3TC was more efficient in improving interleukin-2 (IL-2) and interferon gamma (IFNgamma) production as well as the type 1/type 2 cytokine ratio and in down modulating the susceptibility of peripheral blood mononuclear cells to in vitro mitogen-stimulated apoptotic cell death. These data suggest that the combination of AZT+3TC has a stronger effect on potentially beneficial immune parameters (IL-2 production; reduction of apoptosis) than the one between AZT+ddI. The combination of AZT+3TC could be more advantageous in the therapy of HIV infection even when used in association with a protease inhibitor.

Anti-HIV Agents↗

LU135252, an endothelin(A) receptor antagonist did not prevent pulmonary vascular remodelling or lung fibrosis in a rat model of myocardial infarction.

The early intervention with endothelin(A) (ET(A)) receptor antagonists following coronary artery ligation has been shown to reduce the development of pulmonary hypertension, despite a lack of improvement in left ventricular function. The present study examined the contribution of pulmonary vascular remodelling and the progression of lung fibrosis in the development of pulmonary hypertension and the subsequent role of endothelin-1 in these processes in a rat model of myocardial infarction (MI). The administration of 60 mg kg(-1) per day of the specific ET(A) receptor antagonist LU135253 ((+)-(S)-2-(4, 6-dimethoxy-pyrimidin-2-yloxy)-3-methoxy-3,3-diphenyl-propionic acid) 24 h following coronary artery ligation, failed to improve left ventricular contractile indices, but reduced the extent of pulmonary hypertension, as reflected by the significant decrease in right ventricular systolic pressure. The medial wall thickness of small pulmonary arteries (50 - 200 microm) was significantly increased 4 weeks following MI, albeit LU135253 treatment did not ameliorate this pattern of vascular remodelling. The steady-state mRNA levels of collagen, fibronectin, transforming growth factor-beta(1), and -beta(3) were significantly increased in the lungs of MI rats. The treatment with LU135252 did not alter this pattern of gene expression. Thus, these data demonstrate pulmonary vascular remodelling and the increased expression of extracellular matrix proteins represent underlying mechanisms implicated in the development of pulmonary hypertension in the MI rat. Despite the amelioration of the pulmonary hypertensive state, ET(A) receptor blockade was insufficient to reverse pulmonary vascular remodelling, or the development of lung fibrosis in the MI rat.

Animals↗

[Eyelid tumor as a recurrence of a gastric MALT-lymphoma].

BACKGROUND: MALT Lymphoma of the conjunctiva, eyelid and orbit represents a primary manifestation of the disease in most of the cases. CASE REPORT: A 58-year-old male presented with a tumor in the left inferior eyelid. A full-thickness incisional biopsy was performed. Histopathologically, a lymphoid infiltrate involved the eyelid in its full width, with reactive follicles surrounded by small cells with irregular nucleus. Follicular colonization and lymphoepithelial lesions were detected. The tumor was CD20 positive. The molecular genetic analysis disclosed a monoclonal B-cell proliferation. The patient had a history of gastric MALT lymphoma treated 9 years ago and he had been otherwise in good health. The histopathologic features of the gastric tumor were identical to those of the eyelid lesion. Since the eyelid tumor represented a recurrence of the disease, treatment consisted of systemic chemotherapy. Complete tumor eradication was obtained. CONCLUSION: Ocular adnexal MALT-lymphomas may represent a recurrence of a distant primary MALT-lymphoma after a long disease-free period and, therefore, be an indication for systemic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗