Latex rush desensitization.
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Administration, Oral↗
Biomedical subjects
A Milani
Publications and source records attributed to A Milani.
Detection of a new Mycobacterium species in wild striped bass in the Chesapeake Bay.
Investigation into recent declines in striped bass health in the Chesapeake Bay in Maryland resulted in the isolation of a putative new species of Mycobacterium. This isolate was obtained from fish showing skin ulcers and internal granulomas in various organs. The isolate was slow growing at 28 degrees C; was nonchromogenic; showed no activities of nitrate reduction, catalase activity, Tween 80 hydrolysis, tellurite reduction, or arylsulfatase reduction; grew best at low salt concentrations; and was urease and pyrazinamidase positive. By PCR a unique insertional sequence was identified which matched nothing in any database. Analysis of the nearly complete 16S rRNA gene sequence also indicated a unique sequence which had 87.7% sequence homology to Mycobacterium ulcerans, 87.6% homology to Mycobacterium tuberculosis, and 85.9% homology to Mycobacterium marinum. Phylogenetic analysis placed the organism close to the tuberculosis complex. These data support the conclusion that the isolate probably represents a new mycobacterial species.
Animals↗
[Hepato-pulmonary syndrome and porto-pulmonary hypertension. Nosologic features and etiopathogenic considerations].
The liver controls pulmonary vascular tone by releasing vasoactive substances. In severe liver failure, the imbalance between vasodilator and vasoconstrictive mediators may lead to alteration of the respiratory function, called as hepatopulmonary syndrome (HPS, when a significant decrease of the vascular pulmonary resistance occurs, with development of intrapulmonary vascular dilatations) and portopulmonarv hypertension (PPH, when the vasoconstrictive prevalence, with an increase of the pulmonary vascular resistances). The clinical symptoms consist of various degree of dyspnea and hypoxemia. An overt "cor pulmonale" syndrome with right-side heart failure may be present in the most severe forms of PPH. The alteration of pulmonary vascularization may be diagnosed by means of pulmonary angiography, contrast-enhanced echocardiography and perfusion lung nuclear scanning of the lungs. Both clinical syndromes respond poorly to medical treatment, the unique therapeutical possibilities being represented by orthotopic liver transplantation (or combined heart-lung-liver or lung-liver transplantation in patients with severe PPH).
Hepatopulmonary Syndrome↗
Phase I and pharmacologic study of weekly gemcitabine and paclitaxel in chemo-naïve patients with advanced non-small-cell lung cancer.
BACKGROUND: Gemcitabine (GEM) and paclitaxel (TAX) are active, non-cross-resistant drugs in non-small-cell lung cancer (NSCLC). We performed a phase I study to determine the maximum-tolerated dose (MTD), antitumor activity and pharmacokinetics of GEM and TAX given weekly in chemo-naïve patients with advanced NSCLC. PATIENTS AND METHODS: Escalating doses of GEM (800-2000 mg/m2) and TAX (60-100 mg/m2) were administered on days 1, 8, 15 every 4 weeks to 35 patients with advanced NSCLC. Plasma pharmacokinetics of TAX and GEM was assessed at the three higher dose-levels. RESULTS: Dose-escalation was discontinued in absence of MTD because of increased cumulative toxicity leading to dose modification or treatment delay at levels 6 and 7 (TAX 100 mg/m2 plus GEM 1750 and, respectively, 2000 mg/m2). Hematological toxicity included grade 4 neutropenia in 3% of cycles, grade 3 thrombocytopenia in one cycle and febrile neutropenia in three cycles. Maximal non-hematological toxicity was grade 3 elevation in serum transaminases and grade 2 neuro-sensory toxicity in 8% and 5% of cycles, respectively. At the two higher dose-levels a non-linear pharmacokinetics of GEM was observed with a remarkable variability of Cmax and AUC. No pharmacokinetic interactions were reported. Objectives responses were seen at all dose levels, with an overall response rate of 43% (95% confidence interval (95% CI): 25.5%-62.6%) in 30 evaluable patients. CONCLUSIONS: The weekly administration of GEM and TAX is very well tolerated, and has shown promising antitumor activity in NSCLC. In view of the cumulative toxicity and of the pharmacokinetic profile of GEM, doses of 1500 mg/m2 of GEM and 100 mg/m2 of TAX are recommended for phase II studies.
Adult↗
Effects of lysine-acetylsalicylate (LAS) treatment in nasal polyposis: two controlled long term prospective follow up studies.
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Adolescent↗
Clinical usefulness of patch and challenge tests in the diagnosis of cell-mediated allergy to betalactams.
BACKGROUND: Literature reports dealing with cell-mediated allergy to betalactams have appeared with increasing frequency in the last years. OBJECTIVE: To evaluate patients with such reactions and to identify cross-reactivities among betalactams in order to provide safe guidelines for their further clinical management. METHODS: Thirty consecutive subjects with cell-mediated allergy to betalactams (history of adverse reactions to these antibiotics; serum total IgE within the normal range; absence of serum specific IgE antibodies to penicillin G and V, amoxicillin, and ampicillin; negative skin tests with a wide pattern of betalactam preparations; and positive patch-test to at least one betalactam antigenic determinant) were investigated. The subjects admitted to the study were patch tested with a wide variety of betalactam preparations in order to identify alternative molecules tolerated by the patient. To better evaluate the cross-reactivity pattern, tolerance challenges with patch-negative betalactams were also performed in each subject. RESULTS: Both specific IgE and skin tests were negative in all patients. The skin biopsies performed on the positive patch-tested area in four patients showed a clear T-lymphocyte, CD4+-type infiltrate, thus definitely proving the occurrence of a cell-mediated response. A total of 44 adverse reactions (mean: 1.47 episodes for each patient) were reported in history, with a mean interval of 15 hours after betalactam administration. The reported symptoms were mainly cutaneous (maculo-papular rash and urticaria) and the responsible drugs were chiefly aminopenicillins (86.4% of cases) and penicillin G (9.1%). We were able to identify three separate groups of patients on the basis of clinical history, patch-test, and tolerance challenge pattern: allergy to the side chain of aminopenicillins in 16 patients (53.3%); allergy to the thiazolidine ring in 3 patients (10.0%); undetermined specificity in the remainder 11 patients (36.7%). Cross-reactivity among different betalactam molecules (revealed by positive tolerance tests performed with patch-negative betalactams) was found in 4.8% of cases only (23.3% of all investigated patients). This fact demonstrates a very high (95.2%) predictive value of a negative patch-test in excluding the occurrence of a cross-reactivity. The mis-match between patch and tolerance tests was observed in 3 out of 178 cases only (1.7% of cases, 10.5% of patients) in groups A and B, and in as much as 12.2% of cases (45.5% of subjects) in group C (P < .05). CONCLUSIONS: Delayed allergy to betalactams (mainly to aminopenicillins) may be exerted by a cell-mediated response. Patch tests and tolerance challenges are extremely useful and safe for diagnosis and further clinical treatment of these patients, helping to identify safe alternative betalactam molecules that could be successfully tolerated by the allergic subjects.
Adolescent↗
[Dynamics of ascitic fluid in decompensated cirrhosis].
The ascitic fluid in decompensated liver cirrhosis constitutes a continuously circulating pool which carries on sustained water exchanges with plasma and extracellular fluids through the whole peritoneal membrane. The actual ascites volume results therefore from the steady-state between the formation and reabsorption transperitoneal water flows. The ascitic reabsorption concerns both the "iso-osmotic" (i.e. the portion bound to the ascitic proteins and solutes) and the "free-water" (i.e. the amount exceeding the osmotic bounding ability of the peritoneal solutes) fractions of total ascitic water. By means of a simple dilution test, it is possible an in vivo estimation of both the ascites volume and the rate of transperitoneal free-water reabsorption, which is the actual free-water peritoneal clearance (CPAL) and an evaluation of the total intra-abdominal pressure (PIA). PIA results from the sum of the ascitic hydrostatic pressure, and the tension of the abdominal wall. Diuretic administration is able to significantly reduce CPAL, inducing a negative sodium balance and thus leading to a readjustment of ascites steady-state. This fact may cause reductions of ascites volume and PIA only after several days of diuretic treatment. An acute diuretic treatment by itself, even if intensive and resulting in a rapid diuresis and a significant modification of CPAL, does not appear able to determine rapid and detectable modifications of PIA. CPAL has an intrinsic prognostic value in patients with decompensated cirrhosis, since the cumulative mortality was reported to be significantly higher in the patients with lower CPAL levels. The peritoneal clearance ability may be regarded as a compensatory mechanisms of portal hypertension, and its estimate may be a reliable index of patient's aptitude to a lower hydro-retentive trend, which is in turn correlated to a greater cirrhosis severity and a worse prognosis.
Ascites↗
Interleukin-15 triggers activation and growth of the CD8 T-cell pool in extravascular tissues of patients with acquired immunodeficiency syndrome.
The impairment of interleukin-2 (IL-2) production occurs very early after human immunodeficiency virus (HIV) infection as a consequence of the quantitative depletion of Th1 cells. Despite the shift in cytokine production, most individuals develop an oligoclonal expansion of major histocompatibility complex restricted, HIV-specific CD8+ cytotoxic T lymphocytes (CTL) in different organs, suggesting that other cytokines replace IL-2 in initiating the tissue infiltration of CD8+ T cells. In this study we show that IL-15, a product of monocyte-macrophages and non-T cells and which has overlapping biological activities with IL-2, is involved in local cell networks accounting for the activation and expansion of CD8+ T-cell pools in a highly affected organ, ie, the lung. IL-15 induced proliferation of T cells obtained from the lower respiratory tract of HIV-infected patients with T-cell alveolitis and severe depletion of CD4+ T cells. Lung lymphocytes were CD45R0+/CD8+ T cells spontaneously expressing activation markers (CD69 and HLA-DR) and equipped with the receptorial subunits which bind IL-15, notably the beta and gamma chains of the IL-2 receptor (IL-2R) and the recently identified IL-15 binding-protein termed IL-15R alpha. Similar phenotypic findings were obtained after incubation of normal T cells with IL-15, which induced CD8+ T cells to express activation markers and to proliferate. The block of the IL-2R beta/IL-2R gamma complex with specific monoclonal antibodies abolished the T-cell stimulatory activity of IL-15 while the combination of IL-15 and tumor necrosis factor-alpha upregulated the proliferative response of lung T lymphocytes. The hypothesis that the tissue growth of lung CD8+ lymphocytes may involve cytokines produced from cells other than T lymphocytes was confirmed by the evidence that pulmonary macrophages expressed high levels of IL-15 and that anti-IL-15 antibodies inhibited the accessory function of alveolar macrophages on mitogen-induced CD8+ T-cell proliferation. Together, these results suggest that macrophage-derived cytokines produced at sites of T-cell infiltration play a role in the activation of HIV-specific CD8+ T-cell-mediated immune response.
AIDS-Related Opportunistic Infections↗
Interleukin-15 triggers the proliferation and cytotoxicity of granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes.
The recently cloned cytokine interleukin-15 (IL-15) shares several functional activities with IL-2 in different cell systems. Although IL-15 does not show sequence homology with IL-2, it uses components of the IL-2 receptor (IL-2R) for binding and signal transduction, namely, p75 (beta) and the p64 (gamma) chains of IL-2R. To evaluate whether IL-15 is involved in the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), we evaluated the ability of IL-15 to stimulate GL proliferation, cytotoxic function, and the role of IL-2R beta and gamma molecules on relevant cells. Our results show that IL-15 stimulates cell proliferation and cytotoxic activity of GL in LDGL patients. Reverse-transcriptase polymerase chain reaction (RT-PCR) and phenotypic analyses using the anti-IL-2R gamma-chain-specific TUGh4 monoclonal antibody (MoAb) indicate that both CD3+ and CD3- GL express the p64 IL-2R, a result previously unknown. IL-15 activity was inhibited by antibodies against p75 and p64 IL-2R chains, while no inhibitory effects are detectable with anti-p55 IL-2R antibody. The association of anti-p75 and anti-p64 IL-2R MoAbs resulted in a nearly complete (95%) inhibition of IL-15-induced GL proliferation. Using RT-PCR analysis, we demonstrated that highly purified CD3+ and CD3- GL did not express mRNA for IL-15 or IL-2. By contrast, a clear-cut IL-15 mRNA signal was detected by RT-PCR in patients' peripheral blood mononuclear cells, with monocytes likely accounting for the source of IL-15 in LDGL patients. However, even in concentrated supernatants from enriched monocyte populations, we could not demonstrate the presence of IL-15 protein. Using anti-IL-15 specific MoAbs, a membrane-bound form of this cytokine was demonstrated both on CD3+ and CD3- LDGL cells. By RT-PCR analysis, purified GL from these patients were found to express the message for IL-15 receptor alpha chain. Taken together, these results indicate that both CD3+ and CD3- GL are stimulated by IL-15 and that this cytokine mediates its activity through the beta and gamma chains of the IL-2R, providing further suggestions for the interpretation of the mechanisms that lead to cell expansion in patients with LDGL.
Adult↗
Immunologic findings in Peyronie's disease: a controlled study.
OBJECTIVES: Recent literature suggests the hypothesis of an immune etiology of Peyronie's disease. In this controlled study, the immune response pattern of the disease is investigated. METHODS: Sixty-six patients with Peyronie's disease and 20 age-matched controls were studied. In all patients, skin test (multitest), in vitro lymphocyte transformation test (LTT), serum immunoglobulin (Ig) A, G, and M, anti-DNA, antinuclear and anti-smooth muscle cell antibodies, C3 and C4 complement fractions, antistreptolysin, and C-reactive protein titers were evaluated. RESULTS: A fair percentage (75.8%) of the patients with Peyronie's disease exhibited at least one abnormal immunologic test, in comparison to only 10% among controls (chi-square = 27.8, df = 1; P < 0.0001). Alterations of cell-mediated immunity (multitest, LTT) were observed in 48.5% of patients, alterations of humoral immunity (Ig) in 31.8%, and alterations of markers of autoimmune disorders (autoantibodies, complement activation) in 37.9% of the cases. CONCLUSIONS: Our results support the hypothesis that there is some involvement of the immune system in the pathogenesis of Peyronie's disease, although the available data still appear to be insufficient to formulate a definite pathogenetic hypothesis.
Adult↗
The CD5/CD72 receptor system is coexpressed with several functionally relevant counterstructures on human B cells and delivers a critical signaling activity.
The CD5 molecule is expressed on T cells and, at a lower density, on a minor B cell subset (CD5+ B cells). The pan-B Ag CD72 was recently identified as the CD5 counterstructure, and several data suggest the involvement of this ligand pair in T-B cell cognate interaction. However, the functional role of CD5 and CD72 molecules within the B cell compartment is still unknown. In this work we studied umbilical cord blood CD5+ B cells (B-1a), adult splenic CD5- B cells (B-2), and CD5+ B cells from patients with chronic lymphocytic leukemia. Flow cytometry analysis and proliferation assays were used to determine 1) the ability of B-1a and B-2 cells to coexpress functionally relevant counterligands other than CD5 and CD72, and 2) the signaling capacity of CD5 and CD72 in terms of B cell activation and proliferation. To this purpose, freshly isolated or preactivated normal and neoplastic B cells were cultured with agonistic anti-CD5 or anti-CD72 mAbs in the presence or the absence of cytokines equipped with B cell activity. Our data demonstrate that CD5 and CD72 molecules are coexpressed with other ligand pairs usually involved in T-B cell cognate interaction on B-1a cells, but not on B-2 cells. CD5 and/or CD72 engagement delivers critical costimulatory signals in B-1a, B-2, and B cells from patients with chronic lymphocytic leukemia, but with different requirements and patterns. Besides suggesting the potential involvement of B-1a lymphocytes in B-B cell interactions during T-independent B cell responses, our results indicate that CD5 and CD72 counterstructures play a functional role in the B cell compartment.
Adult↗
Skewing of the T-cell receptor repertoire in the lung of patients with HIV-1 infection.
OBJECTIVES: A bias of the use of T-cell receptor (TCR) V beta regions has been reported both in peripheral blood and in several tissues in patients with AIDS, including lymph nodes, spleen and salivary glands. Although the disease is frequently characterized by an infiltration of T cells in the lung interstitium, no information is presently available on the configuration of the TCR repertoire in this microenvironment. This study was performed to address the question of whether a bias in T-cell selection occurs in the lung of patients with AIDS. METHODS: TCR beta-chain variable region (TCR-V beta) repertoire was analysed by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 13 patients with HIV-1 infection at different stages of the disease. Blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins (SEA, SEB, SEC1, SEC2, SED and SEE). RESULTS: Flow cytometry analysis in AIDS patients demonstrated an overexpression of cells bearing V beta 2 and V beta 3 gene segments in the lung compared with peripheral blood of the same subjects, as well as to lung and blood lymphocytes of normal controls. PCR analysis performed in AIDS patients extended these observations and demonstrated a significant bias also in the use of T cells bearing V beta 7 and V beta 9 gene regions in the lung compartment with respect to the blood. Virtually all T cells bearing the overrepresented V beta segment belong to the CD8 subset. Interestingly, T-lymphocyte response to different superantigens demonstrated a low proliferative rate in the lung with respect to the blood in HIV-1-infected patients. CONCLUSIONS: These findings indicate a compartmentalization of cells bearing discrete V beta gene products in the pulmonary microenvironment of patients with AIDS and suggest that the expansion of specific-V beta region subsets occurring in the lung might result from triggering by a superantigen.
Adult↗
Expression of tumor necrosis factor-receptor superfamily members by lung T lymphocytes in interstitial lung disease.
Recently, a novel receptor superfamily has been identified whose members interact with a parallel family of ligands showing homology to tumor necrosis factor (TNF). To investigate the role of these receptor structures in the pulmonary environment, we evaluated the expression of some members of the TNF-receptor (CD27, CD30, CD40, CD95/Fas, CD120a, and CD120b) and TNF-ligand (CD40L, CD70/CD27L, CD30L, and mTNFalpha) superfamilies by bronchoalveolar lavage (BAL) T cells recovered from healthy subjects and patients with interstitial lung disease (ILD). Lung T lymphocytes recovered from control subjects showed a slight expression of CD27 but did not bear CD30, CD40, CD120a, or CD120b antigens. CD27 expression was restricted to normal CD4+ cells. Fas antigen (CD95), which is involved in activation-driven T-cell suicide, and the ligand for CD27 (CD70) were weakly expressed by normal BAL T-cell subpopulations. In patients with sarcoidosis, the majority of pulmonary T lymphocytes were CD4+ cells that expressed low levels of CD27 antigen and an upregulation of CD95 and CD70 molecules. When we characterized lymphocytes accumulating in the lung of patients with HIV infection and hypersensitivity pneumonitis, we demonstrated that T cells accounting for the CD8 alveolitis bore TNF-receptor type 2 (CD120b) at high density and were CD70+ while CD40L, CD30L, or mTNF-alpha expression were not found. The discrete surface expression of the TNF-receptors and TNF-ligands on alveolar T-cell subsets suggests that these molecules play a role in the immune regulatory mechanisms that ultimately lead to the alveolitis in the pulmonary microenvironment of interstitial lung disease.
Adult↗
[Therapeutic alternatives in the treatment of class T1N0 squamous cell carcinoma of the penis: indications and limitations].
At INT of Milan between 1964 and 1990, 204 consecutive native patients suffering from penile cancer have been treated. 101 (59%) patients out of 171 with invasive cancer (23 affected with Tis were excluded) have been classified T1N0M0. 74 patients have been treated with penis conserving methods, such as circumcision, radiotherapy, laser excision and primary chemotherapy + conserving surgery. Overall local failure and/or nodal relapses occurred in 27% (20/74). Relapses are significantly related with grading but there isn't any relationship with macroscopical aspect or size of the tumor. The conservative treatment had been possible in 80% of patients. In our experience T1N0 clinical stage conservative therapy does not worsen the prognosis.
Adult↗
Analysis of the T cell receptor in the lymphoproliferative disease of granular lymphocytes: superantigen activation of clonal CD3+ granular lymphocytes.
To investigate whether cell populations in CD3+ lymphoproliferative disease of granular lymphocytes (LDGLs) were skewed toward the use of specific V beta regions, we studied the repertoire of T-cell receptor (TCR) V beta gene products in 18 patients, as well as their relationship to the clonal bands in the Southern blot and the activation mediated by superantigens. Using a panel of monoclonal antibodies (mAbs) for conserved V beta segments and PCR, a dominant population expressing a specific V beta region was demonstrated in all patients. In five (27%) cases, granular lymphocytes (GLs) were found to express the V beta 13.1, while V beta 8 and V beta 6 were each expressed in three (17%) cases. The remaining cases were characterized by the proliferation of TCR V beta 2, V beta 3, V beta 4, V beta 9, V beta 12, V beta 16, and V beta 20. This finding indicates a biased usage of a limited TCR V beta in LDGLs, since nearly 60% of the cases utilized only three families of the TCR V beta genes. In all of the cases studied, we proved that the subset recognized by mAb and PCR was identical to that accounting for the extra band(s) of the Southern blot. This finding confirms the clonal nature of the population identified according to TCR V beta expression both by phenotype and PCR. On functional grounds, we evaluated whether GLs can be activated through the specific TCR using the superantigens recognizing discrete V beta families, such as staphylococcal proteins, including SEA, SEB, SEC1, SEC2, SED, and SEE. We demonstrated that the TCR-alpha/beta of clonal GLs in LDGL patients is functionally active in delivering cytotoxic and proliferative signals upon superantigen activation.
CD3 Complex↗
Erythropoietin secretion in liver disease.
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Erythropoietin↗
Expression of TNF receptors by T cells and membrane TNF-alpha by alveolar macrophages suggests a role for TNF-alpha in the regulation of the local immune responses in the lung of HIV-1-infected patients.
High amounts of TNF-alpha are released by alveolar macrophages (AMs) in the lungs of patients with HIV-1 infection. To investigate the role of this cytokine in the local immune response, we studied the expression of surface receptors for TNF-alpha (TNF-Rs) and the presence of the transmembrane form of TNF-alpha (mTNF-alpha) on bronchoalveolar lavage (BAL) cells recovered from 14 patients with HIV-1 infection. The role of TNF-alpha both in the events leading to the T cell alveolitis and as a mediator of cytotoxicity was also evaluated. TNF-R expression was determined by flow cytometry on BAL CD8 lymphocytes and AMs (i.e., the cells that account for the alveolitis in HIV-1 infection). We found that CD8 cells express the 75-kDa (CD120a) but not the 55-kDa (CD120a) TNF-Rs, whereas AMs were devoid of TNF-R expression. More than 90% of BAL T cells efficiently bound TNF-alpha; when T cells were tested for their proliferative capacity, an up-regulation of the IL-2-mediated proliferation by TNF-alpha was observed, suggesting that this cytokine may drive the in situ proliferation of CD120b+ T cells. As shown by flow cytometry analysis and immunoprecipitation with anti-TNF-alpha Ab, mTNF-alpha expression was observed on AMs but not on alveolar T cells. Fixed AMs showed high levels of killing against TNF-sensitive targets. Taken together, our data demonstrate the selective expression of TNF-Rs and mTNF-alpha on cells accumulating within the alveolar spaces of patients with HIV-1 infection, pointing to the compound role of TNF-alpha in the local immune responses.
Adult↗