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1.
Eur Rev Med Pharmacol Sci ; 18(2): 190-3, 2014.
Article in English | MEDLINE | ID: mdl-24488907

ABSTRACT

Hydroxyurea is a cytotoxic agent widely used in the treatment of myeloproliferative disorders. It is considered a-well-tolerated antineoplastic drug, with a dose-related bone marrow suppression as main adverse effect. This report describes a patient with essential thrombocythemia who developed an interstitial pneumonitis and respiratory failure within 4 years from beginning therapy with hydroxyurea (HU). After discontinuing of HU. both clinical and radiological resolution of pneumonitis occurred. In conclusion, HU-induced pulmonary toxicity is a potentially life-threatening side effect.


Subject(s)
Antineoplastic Agents/adverse effects , Hydroxyurea/adverse effects , Lung Diseases, Interstitial/chemically induced , Aged , Antineoplastic Agents/therapeutic use , Female , Humans , Hydroxyurea/therapeutic use , Respiratory Insufficiency/chemically induced , Thrombocytosis/drug therapy
2.
Microbiol Immunol ; 45(8): 605-11, 2001.
Article in English | MEDLINE | ID: mdl-11592634

ABSTRACT

Several studies have indicated that the serine protease urokinase-plasminogen-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (BAL) samples of immunosuppressed rats both with and without PCP, we observed a decrease in uPA activity as well as a decrease in cell number. Urokinase-PA production by AMs was reduced in rats treated with cortisone alone. However, an increase in cell-associated uPA was observed in rats with PCP. This increase appears to be produced in response to P carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed uninfected rats were challenged with P carinii, a significant increase in PA activity in cell lysates was observed, though a lower response was obtained in cortisone-treated animals. Our results suggest that healthy AMs respond to the presence of P carinii with an increase in uPA production and that this response in immunodepressed rat-AMs is partially impaired.


Subject(s)
Macrophages, Alveolar/immunology , Pneumonia, Pneumocystis/immunology , Urokinase-Type Plasminogen Activator/metabolism , Adrenal Cortex Hormones/adverse effects , Animals , Diet, Protein-Restricted/adverse effects , Immunosuppression Therapy/methods , Male , Rats , Rats, Sprague-Dawley
5.
J Antimicrob Chemother ; 43(2): 301-4, 1999 Feb.
Article in English | MEDLINE | ID: mdl-11252340

ABSTRACT

Terbinafine is a synthetic antifungal agent which has recently been found to be highly effective against Pneumocystis carinii. This study evaluated the efficacy of terbinafine on rat P. carinii antigenic profile and the immune response by Western blot analysis, in comparison with atovaquone and co-trimoxazole in rats with pneumocystosis. Terbinafine was shown to target two specific major antigens, particularly those of 116 and 35-40 kDa. Antibodies reactive against these moieties were found in all rats treated with atovaquone and co-trimoxazole, but not in those treated with terbinafine. These surface antigen modifications could be related to disease severity and could provide additional information for monitoring the efficacy of this treatment.


Subject(s)
Antifungal Agents/pharmacology , Antigens, Fungal/chemistry , Naphthalenes/pharmacology , Pneumocystis/immunology , Pneumonia, Pneumocystis/drug therapy , Animals , Antigens, Fungal/drug effects , Atovaquone , Blood/immunology , Blood/microbiology , Blotting, Western , Bronchoalveolar Lavage Fluid/immunology , Bronchoalveolar Lavage Fluid/microbiology , Disease Models, Animal , Electrophoresis/methods , Immunosuppression Therapy , Male , Naphthoquinones/pharmacology , Pneumocystis/drug effects , Pneumonia, Pneumocystis/immunology , Pneumonia, Pneumocystis/mortality , Rats , Rats, Sprague-Dawley , Survival Rate , Terbinafine , Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology
7.
J Med Microbiol ; 45(2): 149-52, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8683552

ABSTRACT

Pulmonary infection with cytomegalovirus (CMV) is a well recognised complication of AIDS. It is often possible to detect CMV-infected cells in bronchoalveolar lavage (BAL) specimens with monoclonal antibodies, but the clinical significance of their presence remains unclear. To investigate this, 24 AIDS patients were tested for CMV antigenaemia and viraemia, in addition to CMV detection in BAL. CMV was detected in the BAL of nine patients (38%), five with clinical and laboratory evidence of pulmonary infection and four without pulmonary involvement. Blood samples positive for CMV antigen were observed in two patients with CMV-positive BAL specimens and, in both cases, antigenaemia resolved without therapy. No case of viraemia was detected. Pneumocystis carinii was detected concomitantly with CMV in the BAL of four of the patients with pulmonary involvement and in one without signs of pulmonary infection. These data suggest that CMV-positive BAL results are of limited significance in the diagnosis of CMV pneumonia in AIDS patients, unless associated with high levels of antigenaemia or viraemia and compatible clinical symptoms.


Subject(s)
AIDS-Related Opportunistic Infections/virology , Antigens, Viral/blood , Bronchoalveolar Lavage Fluid/virology , Cytomegalovirus Infections/virology , Cytomegalovirus/isolation & purification , Viremia/virology , AIDS-Related Opportunistic Infections/diagnosis , Adult , Cytomegalovirus/immunology , Cytomegalovirus Infections/diagnosis , Female , Humans , Male , Middle Aged
8.
Br J Dermatol ; 134 Suppl 46: 30-2; discussion 40, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8763466

ABSTRACT

The anti-Pneumocystis carinii response of terbinafine together with that of three other compounds, trimethoprim sulphamethoxazole (TMP-SMX), atovaquone (ATQ) and albendazole (ALB), has been investigated in immunosuppressed Sprague-Dawley rats with established pneumocystosis. Drugs were administered orally (terbinafine in dosages of 40 and 80 mg/kg per day, TMP 12.5 mg/kg per day plus SMX 62.5 mg/kg per day, ATQ 100 mg/kg per day and ALB 600 mg/kg per day) to six rat groups except one which served as a control. P. carinii pneumonia (PCP) was identified post-mortem in nine (90%) of the control rats which exhibited a marked P. carinii burden, and mean lung weights were higher with respect to the other treatment groups. During treatment, five rats in the control group died, whereas between 11 and 13 rats in all treatment groups survived. In the terbinafine groups (40 mg and 80 mg/kg per day), a mild P. carinii infection developed in three and two rats (27.2 and 18%), respectively, and almost the same infectivity score was obtained for those treated with 40 mg and 80 mg/kg per day. Histological changes in the lungs in animals receiving terbinafine treatment were minimal. Among the remaining compounds the rate of infection was seven (58.3%) for the ALB treatment group and five (45.4%) for the ATQ group (mean score 19.4 +/- 7.1 and 23 +/- 2.1, respectively). In the TMP-SMX treatment group, there were 13 surviving rats and P. carinii organisms were found in two (15.3%, mean infection score 8 +/- 1.1).


Subject(s)
Antifungal Agents/therapeutic use , Naphthalenes/therapeutic use , Pneumonia, Pneumocystis/drug therapy , Administration, Oral , Albendazole/therapeutic use , Animals , Atovaquone , Drug Administration Schedule , Immunosuppression Therapy , Lung/pathology , Naphthoquinones/therapeutic use , Pneumonia, Pneumocystis/pathology , Rats , Rats, Sprague-Dawley , Terbinafine , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use
9.
AIDS ; 10(3): 283-90, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8882668

ABSTRACT

OBJECTIVE: To reveal a possible impairment of the plasminogen activator system in the pulmonary infections of AIDS patients. DESIGN: To test the plasminogen activator system functionality in alveolar macrophages and bronchoalveolar lavage fluid (BALF) in control subjects and AIDS patients. Procedures were designed to detect the presence of imbalance in plasminogen activator activity and to ascertain if this imbalance is due to a direct effect of the HIV virus on macrophages or to superimposed opportunistic infection. METHODS: Alveolar macrophages obtained by bronchoalveolar lavage (BAL) were either lysed with Triton X-100 or cultured for 24 h. Plasminogen activators and plasminogen activator inhibitors (PAI) were measured by chromogenic substrate assay and binding to 125I-urokinase followed by 10% sodium dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE), respectively. RESULTS: Plasminogen activator activity in BALF and in alveolar macrophages from AIDS patients was decreased. This reduction was independent of the presence of an infectious pulmonary process. In contrast, free PAI was increased in AIDS patients with Pneumocystis carinii infection. This increase is possibly caused by a different glycosylated form of PAI-2. CONCLUSIONS: Our data support the view that the pulmonary fibrogenic response is in part secondary to an imbalance within the plasminogen activator system and provide the basis for clarifying the role of these alterations in the pathophysiology of AIDS-related pulmonary infections.


Subject(s)
Acquired Immunodeficiency Syndrome/metabolism , Macrophages, Alveolar/metabolism , Plasminogen Activators/biosynthesis , Plasminogen Inactivators/biosynthesis , Acquired Immunodeficiency Syndrome/complications , Adult , Bronchoalveolar Lavage Fluid , HIV Seronegativity , Humans , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/metabolism
10.
Eur Respir J ; 4(6): 639-42, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1889489

ABSTRACT

Alveolar lymphocytosis, in the face of blood lymphopenia, is a common finding among patients with AIDS. We studied by bronchoalveolar lavage (BAL), the alveolar cell profile of 43 human immuno deficiency virus (HIV) seropositive patients divided into three groups involving the advanced stages of the disease: group A (n = 9; CDC III), ambulatory individuals without systemic or respiratory symptoms; group B (n = 15; CDC IV) patients admitted for evaluation of fever of unknown origin (FUO) without pulmonary involvement; group C (n = 19; CDC IV), patients admitted for evaluation of an acute pulmonary condition. Sex, age and risk factor were comparable among the groups. Alveolar lymphocytosis was found in no group A patients, in 2 out of 15 group B patients (both with P. carinii lung infection) and in all group C patients, where pulmonary involvement was due to opportunistic infection or to nonspecific interstitial pneumonitis. Our findings suggest that in patients with advanced HIV infection alveolar lymphocytosis may be an expression of a concomitant process within the lungs either clinically manifest or inapparent, or possibly related to HIV primary lung involvement.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Lymphocytosis/complications , Pulmonary Alveoli/pathology , Acquired Immunodeficiency Syndrome/pathology , Adult , Bronchoalveolar Lavage Fluid/pathology , Female , Humans , Lymphocytosis/pathology , Male , Opportunistic Infections/complications , Opportunistic Infections/pathology , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/pathology , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/pathology
11.
Chest ; 93(4): 790-4, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3349836

ABSTRACT

A rise in cardiac output and a fall in arterial oxygen tension are well known side effects of bronchodilator drugs, particularly beta-adrenergic agonists. In recent years, fenoterol (Berotec), an effective beta-adrenergic agonist, has been used at increasing rates in asthmatic subjects, as well as in patients with chronic obstructive pulmonary disease (COPD). The effects of fenoterol on systemic hemodynamics or arterial oxygenation (or both) in patients with COPD have not been investigated; in these individuals, who often have increased sympathetic tone and hypoxemia even at rest, cardiovascular stimulation and a fall in arterial oxygen tension would be particularly undesirable side effects. In 14 patients with COPD (seven without a reversible component of airflow obstruction [group 1]; and seven with a reversible component of airflow obstruction [group 2]), we studied all of the important parameters of oxygen transport before and 60 minutes after administration of fenoterol. Studies were performed at rest and after exercise. At baseline, group 1 showed a faster heart rate, a lower cardiac output, a lower arterial oxygen flow, a wider arteriovenous oxygen content difference (C[a-v]O2), and a higher fraction of oxygen extracted by the tissues from a given arterial oxygen flow. In both groups, all measured parameters, including cardiac output and arterial oxygen pressure (PaO2) remained statistically unchanged one hour after administration of fenoterol; with exercise, the heart rate, blood pressure, minute ventilation, oxygen consumption, C(a-v)O2, and the percentage of oxygen extracted from arterial oxygen flow, as well as cardiac output and PaO2, increased in all instances; the exercise responses were not affected by the drug. These results suggest that at the time of its maximal effect on the airways (60 minutes), fenoterol has no untoward effect on the oxygen transport system, at rest or during exercise, in patients with COPD with or without a reversible component.


Subject(s)
Fenoterol/therapeutic use , Hemodynamics/drug effects , Lung Diseases, Obstructive/drug therapy , Oxygen/blood , Aged , Female , Humans , Lung Diseases, Obstructive/physiopathology , Male , Physical Exertion , Pulmonary Gas Exchange/drug effects , Time Factors
14.
Respiration ; 50 Suppl 2: 218-21, 1986.
Article in English | MEDLINE | ID: mdl-2951809

ABSTRACT

Fenoterol with ipratropium bromide (Duovent) is a recently used combination between an anticholinergic and a beta-adrenergic drug useful in obtaining a more effective bronchodilatation and/or reducing the single drug doses. It has been suggested that, as in the case of beta-agonists, its clinical efficacy may be limited by the development of tolerance. We studied the effects of inhaled Duovent in 15 asthmatic patients for 3 months, using a rigidly controlled protocol. Appropriate serial physiological measurements were made at regular intervals during the 90-day study. In all instances the day-one bronchodilator response was significant, prompt and sustained: at 1, 4, 8 and 12 weeks the response was statistically the same as on day 1. It is concluded that, when the important variables are properly controlled, no evidence of tolerance to long-term therapy with Duovent is demonstrable.


Subject(s)
Atropine Derivatives/administration & dosage , Fenoterol/administration & dosage , Ipratropium/administration & dosage , Adult , Drug Combinations/administration & dosage , Drug Combinations/adverse effects , Drug Combinations/therapeutic use , Drug Tolerance , Fenoterol/adverse effects , Fenoterol/therapeutic use , Forced Expiratory Volume , Humans , Ipratropium/adverse effects , Ipratropium/therapeutic use , Longitudinal Studies , Lung Diseases, Obstructive/drug therapy , Lung Diseases, Obstructive/physiopathology , Nebulizers and Vaporizers
15.
Am Rev Respir Dis ; 129(6): 1014-6, 1984 Jun.
Article in English | MEDLINE | ID: mdl-6732039

ABSTRACT

Fenoterol ( Berotec ; Th 1165a , Boehringer- Ingelheim , Spa., Firenze , Italy) is an effective, widely used bronchodilator. It has been suggested by some investigators that, as in the case of other beta-adrenergic agonists, its clinical usefulness may be limited by the development of tolerance; others have found no tolerance. These conflicting results appear to be related to differences in study designs. We studied for 3 months the effects of inhaled fenoterol in 15 asthmatics, using a rigidly controlled protocol. Appropriate serial physiologic measurements were made at regular intervals during the 90-day study. In all instances the day 1 bronchodilator response was significant, prompt, and sustained: at 1,3,4,8 and 12 wk the response was statistically the same as on day 1. It is concluded that, when the important variables are properly controlled, no evidence of tolerance to long-term therapy with fenoterol is demonstrable.


Subject(s)
Asthma/drug therapy , Ethanolamines/therapeutic use , Fenoterol/therapeutic use , Adult , Drug Tolerance , Female , Fenoterol/administration & dosage , Forced Expiratory Volume , Humans , Male , Middle Aged , Respiratory Therapy , Time Factors , Vital Capacity
16.
G Ital Cardiol ; 14(2): 101-7, 1984 Feb.
Article in Italian | MEDLINE | ID: mdl-6714547

ABSTRACT

When an alternating current of high frequency is applied to the thorax, the first derivative of the impedance (dZ/dt) is affected by the cardiac cycle, resulting in a characteristic wave form. The maximum negative of this wave occurring during systole together with the length of ejection time (VET), the blood resistivity, the basal impedance (ZO) and the distance between the inner detecting electrodes (L) makes it possible to calculate stroke volume (SV) and related parameters, as cardiac output (CO) and cardiac index (Cl) by a formula developed by Kubicek. Thoracic electrical impedance has been proposed as a non invasive technique to evaluate cardiac emodinamics. In the present study we have evaluated thoracic electrical impedance by comparing it with thermodilution, simultaneously performed in 21 catheterized patients. Reproducibility was assessed by comparing Cl measured several times in the same patient during ten minutes of rest in the supine position: coefficient of variation, expressed as CV = SD/m X 100 was 8,5 +/- 4,2% and 9,4 +/- 3,2% (p = NS) for thermodilution and thoracic electrical impedance respectively. Cl values obtained by both methods correlated well, with little scatter either baseline (r = 0,784, n = 40, p less than 0,001), either after an handgrip manoeuvre (r = 0,629, n = 15, p less than 0,05). This degree of correlation is similar to that observed comparing invasive techniques (Fick, thermodilution, dye dilution) either among them, or with noninvasive methods (echocardiography, gated equilibrium blood pool scintigraphy and ultrasonic Doppler).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Cardiac Output , Cardiography, Impedance , Heart Diseases/physiopathology , Plethysmography, Impedance , Thermodilution , Adult , Aged , Cardiac Volume , Female , Humans , Male , Middle Aged
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