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Biomedical subjects

G Paone

Publications and source records attributed to G Paone.

At least 55 records · Page 3Linked to original sources

Use of discriminant analysis to assess disease activity in pulmonary tuberculosis with a panel of specific and nonspecific serum markers.

Several cell activation markers, acute phase reactants, enzymes, and antituberculous antibody serum levels have been proposed as possible markers to monitor disease activity in patients with tuberculosis. They have all shown limited sensitivity or specificity. The authors therefore attempted to generate a canonical variable using discriminant analysis, including sensitive and specific parameters, to be a reliable marker in classifying patients correctly during the course of pulmonary tuberculosis. The following parameters were selected: two soluble cell activation markers (soluble interleukin-2 receptor and sCD8); the levels of immunoglobulin (Ig) G and IgM antibodies against the A60 antigen complex; and the presence of specific antibodies directed to eight different A60 components, revealed by Western blot analysis. The tests were performed on sera from three groups of patients with pulmonary tuberculosis. The first group comprised 25 patients with onset tuberculosis, clinically active (OTCA), evaluated at the time of admission. The second group included 28 patients with chemotherapy-treated tuberculosis, clinically active (CTCA), 2 months after therapy had begun. The third group included 20 patients with tuberculosis, nonclinically active (TNCA), who had had at least 1 year of effective therapy. The authors obtained an 80.9% rate of correct classification for the three groups and a rate of 100% when OTCA and TNCA were compared. The patients with CTCA were scarcely differentiated and tended to be distributed into the two other groups. To improve the separation between patients with CTCA and those with OTCA, a second canonical variable was generated with a 91.7% rate of correct classification, as compared with 71% obtained using the sCD8 as the best single variable. The mean values of the last canonical variable were statistically different (Mann-Whitney test, P = .049) when stratified for acid fast bacilli-positive or negative CTCA patients (microscopic detection). Three patients, followed during the entire course their disease, were, as expected, correctly positioned with respect to the subsequent disease phases.

Adult↗

A histidine to tyrosine replacement in lysosomal acid lipase causes cholesteryl ester storage disease.

The genetic defect causing cholesteryl ester storage disease (CESD) has been investigated in an 11 year old patient. Lysosomal acid lipase (LAL) activity in cultured skin fibroblasts and peripheral lymphocytes was reduced to approximately 3% and approximately 4% of controls, respectively. The parents had low acid lipase activity in white blood cells. Using the polymerase chain reaction followed by ribonuclease protection assay, we examined the LAL mRNA from the liver of the affected patient to identify small deletion, abnormal splicing or missense mutation. Using this technique we identified a LAL mRNA cytosine to thymidine transition in position 923, predicting a missense substitution of tyrosine for histidine in codon 274. By differential oligonucleotide hybridization on an amplified white blood cell mRNA, the cytosine to thymidine transition was investigated in the family members and in the population. No normal mRNA coding for cytosine in position 923 was detectable in the propositus and mRNA from the phenotypically normal parents coded for both cytosine and thymidine. This can only be accounted for by assuming that the propositus is homozygote for the mutation. The mutation, segregated in the family with levels of acid lipase activity in white blood cells, was not detected in mRNA from 60 normal subjects. These data provide evidence that the cytosine to thymidine transition in position 923 in LAL mRNA causes the clinical expression of CESD in this patient. The predicted substitution of tyrosine for histidine in codon 274 suggests that this amino acid is involved in the structure-function of the lysosomal acid lipase enzyme.

Adolescent↗

Blood conservation in coronary artery surgery.

BACKGROUND: Most patients undergoing coronary artery bypass surgery receive homologous blood transfusions despite the availability of multiple pharmacologic and blood salvage conservation strategies. METHODS: The efficacy of defining strict transfusion criteria as the sole blood conservation strategy was adjudicated prospectively by comparing homologous blood product usage in 314 consecutive patients undergoing isolated primary coronary artery bypass surgery (group 2) with a retrospective group of 947 consecutive patients undergoing the same procedure but transfused without protocol (group 1). RESULTS: The incidence of red cell transfusion and plasma transfusion decreased from 40.5% to 25.8% and 23.8% to 13.4% in groups 1 and 2, respectively (p < 0.001). The percentage of patients receiving no homologous blood products increased from 47.6% in group 1 to 68.5% in group 2 (p < 0.001). Decreasing body weight and preoperative hematocrit were found to be highly significant predictors of the need for red blood cell transfusion (p < 0.001). Significant postoperative determinants included intensive care unit and hospital length of stay and reoperation for bleeding (p < 0.001 each). CONCLUSIONS: Because major determinant of homologous blood transfusion during coronary bypass surgery is the predictable and unavoidable dilution of a small red cell mass that occurs when instituting cardiopulmonary bypass, adherence to defined transfusion criteria alone is a simple, safe, and effective strategy for decreasing blood product utilization.

Blood Transfusion↗

[Pulmonary involvement in sclerodermia].

Progressive systemic sclerosis (PSS) is a connective tissue disease characterized by fibrosis and thickness of cutis and subcutis (scleroderma) and deterioration of small arteries and capillary vessels, with changeable visceral renal, cardiac, intestinal and pulmonary involvements. The disease is characterized by cutaneous sclerosis, that is to say by the increase of consistence and thickness of cutis that lose her usual elasticity. The sclerosis can be limited to the fingers (sclerodactyly) or can involve otherwise (acrosclerosis); many other time is diffuse also to upper limbs and to thorax (diffuse scleroderma). The disease is rare and its incidence is variable from 2 to 10 x 10(6); more frequently hits women than men in the ratio of 3 to 1 or 8 to 1 (according to certain Authors). In the elderly is more frequently represented by the CREST syndrome (calcinosis, Raynaud's phenomenon, oesophageal dismotility, sclerodactyly, teleangiectasia). The authors have considered nine patients with pulmonary involvement of progressive systemic sclerosis: five with CREST syndrome and four with diffuse scleroderma. In addition to the common routine examinations, we performed chest radiography (CXR), pulmonary function tests, fiberoptic bronchoscopy and bronchoalveolar lavage (BAL), Gallium 67 scanning and high resolution computed tomography (HRCT) with the purpose to consider the role of these medical examinations in diagnosis and the follow-up of pulmonary involvement in scleroderma. From the results we have observed that: 1) in early disease chest radiography may be silent even if the patient shows a restrictive syndrome and reduction of diffusion capacity of carbon monoxide (DLCO); 2) chest radiography, pulmonary function tests and Gallium 67 scanning have traditionally been used to measure the degree of lung involvement in SSP but unfortunately, none of these reliably predicts disease activity or future course; 3) bronchoalveolar lavage shows the degree of lung inflammation (alveolitis) characterized by the increase of total BAL cell counts and by higher neutrophil cells in the initial stage of the disease; 4) even HRCT shows in this stage, the typical aspect of higher endoalveolar cellularity with ground glass appearance. With the progression of anatomical damage, there can be found even appearance of complete destruction of pulmonary architecture with the typical alteration of honeycomb. These findings support the hypothesis that a ground glass appearance on HRCT is the radiographic equivalent of alveolitis found in BAL. Furthermore HRCT shows itself useful in the follow-up the disease and in detecting of its activity condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Bronchoalveolar Lavage Fluid↗

Prospective evaluation of malignant neoplasms in cardiac transplant recipients uniformly treated with prophylactic antilymphocyte globulin.

Although there is convincing evidence that prophylactic administration of high doses of the monoclonal antibody OKT3 predisposes patients to an increased prevalence of early posttransplantation malignancy, particularly posttransplantation lymphoproliferative disease, it is indeterminate whether polyclonal antilymphocyte globulin poses a similar hazard. We reviewed the outcome of 112 consecutive cardiac transplant recipients who received uniform immunosuppression, including induction therapy with antilymphocyte globulin, and were prospectively followed-up for a median duration of 41.5 months (range 1 to 81 months). No patients had posttransplantation lymphoproliferative disease. Nine malignant neoplasms (8%) were detected from 6 to 70 months after transplantation. Four patients with cutaneous neoplasms were alive and well at the time this article was written. Three patients died of disseminated adenocarcinoma 6 months, 17 months, and 60 months after transplantation. One patient was undergoing treatment of Kaposi's sarcoma at the time this article was written, and another was undergoing treatment of transitional bladder cell carcinoma. Actuarial survival for all patients was 88% at 1 year and 79% at 5 years. Moderate doses of induction antilymphocyte globulin may facilitate rapid reduction of maintenance cyclosporine and steroid doses, thereby decreasing the duration of intense immunosuppression and lowering the risk of posttransplantation lymphoproliferative disease. Testing this hypothesis would require the development of reliable and reproducible in vivo assays to prospectively assess immune status.

Adolescent↗

Antibody repertoire against the A60 antigen complex during the course of pulmonary tuberculosis.

The A60 antigen complex is a Mycobacterium bovis (BCG) highly immunodominant antigen containing both B and T-cell epitopes. Clinical-serological studies show that elevated anti-A60 titres are present during tuberculosis. We wished to analyze in detail antibody responses against A60 components during the course of tuberculosis. A mixed longitudinal study was designed including individuals at the onset of tuberculosis, during treatment and after resolution of the disease. The anti-A60 repertoire was analyzed using a western blot assay with A60 as the antigen. While PPD- normals recognized only the 65 kDa heat shock protein (HSP), PPD+ normal individuals displayed low levels of anti-A60 antibodies against dominant antigens. There were immunoglobulin M (IgM) and immunoglobulin G (IgG) consistent with response to a latent infection. Onset tuberculosis was characterized by IgM and IgG antibodies against 52 to 28 kDa antigens; IgM response being limited to earlier phases of the disease. In contrast, IgM antibodies against 25 to 14 kDa antigens appeared only 2-6 months after disease onset. The antibody repertoire of chemotherapy-treated, resolved tuberculosis was exclusively IgG in isotype, as for a memory-type response. Thus, western blot analysis with A60 identifies typical antibody patterns associated with different clinical phases of tuberculosis infection. Such approach may help in identifying new single antigens for serologic diagnosis of active tuberculosis.

Adult↗

Surveillance and treatment of liver transplant recipients for candidiasis and aspergillosis.

Between June 1988 and May 1991 88 orthotopic liver transplants and 1 liver and pancreas transplant were performed at the Liver Transplantation Department of the Ospedale Maggiore of Milan. All the patients underwent mycological surveillance and received antifungal prophylaxis with oral amphotericin B (6000 mg/day) or oral or intravenous fluconazole (200 mg/day) from the time of their transplant. The incidence of Candida colonization was 67%. Fluconazole was superior to oral amphotericin B in the treatment of C. albicans colonization (9/9 vs 6/15), but less effective in the treatment of colonization by other Candida spp. (0/3 vs 3/3). Deep-seated candidiasis developed in 5 patients, caused by C. albicans in 4 cases and C. krusei in 1. C. albicans infection resolved rapidly with fluconazole in 2 subjects, with intravenous amphotericin B alone in 1, and with amphotericin B plus flucytosine in the other. On the contrary, C. krusei infection did not respond to treatment with amphotericin B combined with flucytosine. Aspergillosis was diagnosed in 11 patients, of whom 4 died from invasive aspergillosis, despite 15 and 26 days of amphotericin B treatment in 2. In another patient invasive aspergillosis, diagnosed a few hours before retransplantation, improved with liposomal amphotericin B, but this man died from cytomegalovirus infection one month later. Aspergillosis was eradicated by itraconazole in 4 other patients and by topical amphotericin B in 2 whose infection was localized to surgical wound.

Adolescent↗

Changing profiles of failed coronary angioplasty patients: impact on surgical results.

As more high-risk patients undergo percutaneous transluminal coronary angioplasty (PTCA), the changing profiles of PTCA patients who may require emergent coronary artery bypass grafting may alter operative morbidity and mortality. This study compared profiles of recent patients undergoing emergent coronary artery bypass grafting after a failed PTCA with earlier patients to determine their impact on operative results. From 1980 to 1988, 53 patients underwent emergent coronary artery bypass grafting after a failed PTCA at the Boston University Medical Center. These patients were divided into two groups based on the year of the PTCA: group I, 1980 to 1985 (n = 18); and group II, 1986 to 1988 (n = 35). Group II patients tended to be older (age greater than or equal to 65 years, 47% group II versus 11% group I), were more likely to have unstable angina before PTCA (74% versus 33%), and had lower ejection fractions (0.53 +/- 0.02 versus 0.63 +/- 0.05) and more vessels with 50% or greater stenosis (2.1 +/- 0.2 versus 1.6 +/- 0.2). Nevertheless, there was no significant difference in the incidence of perioperative myocardial infarcts using enzyme and electrocardiographic criteria (37% in group II versus 39% in group I), 30-day operative mortality (11% in group II versus 11% in group I), or major postoperative complications (14% in group II versus 22% in group I). We conclude that despite the changing profiles of patients undergoing PTCA, which include older patients with more extensive coronary artery disease and lower ejection fractions, operative results after emergent coronary artery bypass grafting for failed PTCAs remain unchanged.

Age Factors↗

[Mycobacterium tuberculosis. From the gene to the diagnosis].

Pulmonary tuberculosis still in on the list of the world major health problems. Tuberculosis has not been eradicated yet, from developing countries. Furthermore, its incidence is increasing in the industrialized world, due to the human immunodeficiency virus (HIV) epidemic. In this regard, atypical clinical presentation of tuberculosis in individuals who have a deficient immune system, such as those at risk of tuberculosis because of HIV infection, makes the diagnostic process more difficult. Tuberculosis cases are often diagnosed later in HIV individuals compared to non-HIV individuals. The ensuing greater risk of contagion thus requires rapid and sensitive diagnostic protocols. In this context, several biotechnological tools have been developed that can be applied to the diagnosis of tuberculosis. M. tuberculosis genes have been cloned, monoclonal antibodies against pure proteins have been produced, thus enabling researchers to generate molecular and biochemical probes. As a consequence, DNA hybridization and DNA amplification techniques have been applied to the detection of mycobacteria, and ELISA kits of high sensitivity are been already made available. In regard to the latter, it is likely that monospecific and highly sensitive immunoassays will be developed that are directed against "active disease" immunodominant antigens. It may thus be expected that future new technologies will supplement the traditional tools for the diagnosis of tuberculosis and rapid diagnosis protocols will be available to chest clinicians in a foreseeable future.

Antibodies, Bacterial↗