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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although aerosolized pentamidine (AP) has recently been approved for prophylaxis and is undergoing clinical trials for treatment of pneumocystis, pneumonia (PCP), factors important in the deposition of AP have not been described. Using radioaerosol techniques, deposition was measured in 22 patients receiving AP for prophylaxis or treatment of PCP. In all patients total and regional deposition of pentamidine, breathing pattern, pulmonary function (PFT), regional ventilation, and type of nebulizer were analyzed. Bronchoalveolar lavage (BAL) was performed 24 h after inhalation to assess the relationship between pentamidine levels in BAL fluid and measured aerosol deposition. The nebulizers tested were the Marquest Respirgard II and the Cadema AeroTech II, both previously characterized in our laboratory. The aerosol particles consist of water droplets containing dissolved pentamidine and technetium 99m bound to albumin. Analysis of particles sampled during inhalation via cascade impaction confirmed a close relationship between radioactivity in the droplets and the concentration of pentamidine as measured by HPLC (r = 0.971, p less than 0.0001; n = 18). Deposition was measured by capturing inhaled and exhaled particles on absolute filters and measuring radioactivity. This technique allows the determination of the deposition fraction (DF, the fraction of the amount inhaled that is deposited), which provides information on factors strictly related to the patient. To confirm the filter measurements, pentamidine deposition was also measured by gamma camera. The camera measurement was possible because each patient's thoracic attenuation of radioactivity was determined by a quantitative perfusion scan (mg pentamidine deposited via both techniques, r = 0.949, p less than 0.0001; n = 26). Regional lung volume and ventilation were determined by xenon 133 equilibrium scan and washout. Pentamidine deposition varied markedly between patients, but BAL levels of pentamidine significantly correlated with measured deposition (r = 0.819, p less than 0.01; n = 9). DF averaged 0.621 +/- 0.027 (SEM) and did not correlate with any measured lung parameter, including breathing pattern and PFT. Regional deposition did not correlate with regional ventilation. The major factor influencing pentamidine deposition was aerosol delivery (mg deposited versus mg inhaled; r = 0.963, p less than 0.0001; n = 26). The nebulizer was an important determinant of aerosol delivery, with the AeroTech delivering between 2.5 and 5 times more drug than the Respirgard. These observations are important in assessing treatment failure and cost of therapy.
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PMID:Factors determining pulmonary deposition of aerosolized pentamidine in patients with human immunodeficiency virus infection. 200 84

Alpha-difluoromethylornithine (DFMO) is being used to treat Pneumocystis carinii pneumonia despite a lack of in vitro evidence supporting its antipneumocystis activity. DFMO is a specific inhibitor of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis. To investigate polyamine metabolism in P. carinii, extracts of the organism were analyzed for polyamine content and ornithine decarboxylase activity, and [3H]ornithine and [14C]arginine incorporation into polyamines during short-term culture was determined. P. carinii extracts contained putrescine and spermidine in a ratio of 0.17:1; traces of spermine were detected. Although ornithine decarboxylase activity was not detected, P. carinii incorporated ornithine and arginine into putrescine and spermidine but not into spermine, suggesting that the spermine detected derived from contaminating host cells. Uninfected rat lung incorporated ornithine minimally. Pentamidine, DFMO, and alpha-monofluoromethyldehydroornithine methyl ester inhibited ornithine incorporation by up to 86% at clinically achievable concentrations. These data provide a rationale for using polyamine synthesis antagonists in P. carinii pneumonia and a method for screening antipneumocystis drugs in vitro.
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PMID:Polyamine metabolism in Pneumocystis carinii. 201 60

The onset of a pneumonia by P. carinii in AIDS patients have force scientist to look for others therapies against this parasite. It is more necessary when the first line treatment which is cotrimoxazol produced secondary effects or not therapeutic effects. Pentamidine which is an agent usually used to treat leishmaniasis and trypanosomiasis, but it is an alternative for P. carinii infection. The problems are the frequent and severe secondary effects when administered by continuous infusions and less when it is inhaled. Between those effects are the changes in carbohydrate metabolism which are 9% of them. It is frequent observe hypoglycemia during infusion following by hyperglycemia in 5% of the cases which convert the patients in diabetic insulinodependent. A case of a patient who developed diabetes mellitus insulinodependent, 10 days after the end of pentamidine treatment, without previous episodes of hypoglycemia, is presented. The medical literature is reviewed.
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PMID:[Diabetes mellitus induced by pentamidine, without previous episodes of hypoglycemia, in patients with AIDS]. 213 78

Pneumocystis carinii pneumonia is one of the most frequent infectious complications in patients with the acquired immunodeficiency syndrome (AIDS). A prospective trial was initiated to compare azidothymidine alone with azidothymidine plus aerosolized pentamidine as a secondary prophylaxis for pneumocystis carinii pneumonia. 27 patients (24 male, three female, average age 39 years) were enrolled, 14 patients receiving azidothymidine and pentamidine aerosol and 13 azidothymidine alone. After 166 days of follow-up, this trial had to be terminated prematurely, since the efficacy of pentamidine aerosol in the prevention of pneumocystis carinii pneumonia was clearly demonstrated in two recently published studies. Two patients died during the study period, one in either group, but neither due to pneumocystis carinii pneumonia. Two patients developed histologically proven pneumocystis carinii pneumonia; both patients were allocated to the azidothymidine arm. Pneumocystis carinii pneumonia was suspected clinically but not proven in four patients, three were randomized in the azidothymidine arm. Pentamidine was well tolerated and produced no severe side effects. The sample size is too small to draw definitive conclusions concerning the efficacy of pentamidine aerosol in AIDS patients.
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PMID:[Randomized comparative study of secondary prevention of Pneumocystis carinii pneumonia in patients with acquired immunologic deficiency syndrome]. 219 38

This is a report on the clinical courses and pathological findings in two gay male patients with acquired immunodeficiency syndrome (AIDS) infected in Japan. Case 1. A 39 year-old Japanese homosexual male was diagnosed as amebic dysentery complicated with liver abscess on admission. He was placed on Metronidazole with complete relief. Serological tests was positive for AIDS. On second admission, he was found to have pneumocystis carinii pneumonia (PCP) and cytomegalo-viral uveitis. Administration of Pentamidine was partially effective, however the therapy with Azidothimidine was discontinued by bone marrow suppression. On his third admission, he suffered from cryptococcal meningitis and therapy-resistant fungusemia. Finally he died of recurrent pneumonia regardless of appropriate therapies. Autopsy proved extended cryptococcal infection in the brain, meninx, lungs, liver and kidney, and cytomegalo-infection in the lungs, liver and kidney. Furthermore, atypical mycobacteriosis was found in the lymph nodes. There was no active findings compatible with PCP. Case 2. A 44 year-old Japanese homosexual male was admitted with oral candidiasis and diagnosed as AIDS related complex. He suffered from pneumonia with marked improvement on sulfamethoxazole-Trimethoprim. On his second admission, he developed diarrhea and was found to be infected with Giardia lambia. In addition, cytomegalo-viral infection damaged his eye sight. He died of pneumonia and meningitis shortly there after. Autopsy proved a cytomegalo-viral infection in the lung and colon, old lesions possibly caused by PCP in the lungs, and suppurative meningitis in the meninx. These experiences confirm that AIDS patients can be exposed to several opportunistic infections at the same time in the multiple organs. Furthermore, it is suggested that homosexual patients with AIDS may have unique opportunistic infections such as amebic dysentery or Giardia lamblia unlike other AIDS patients related to hemophilia.
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PMID:[Clinical courses and pathological findings in two gay male patients with acquired immunodeficiency syndrome infected in Japan]. 233 6

AIDS is one of the most perplexing diseases to confront modern medicine today. AIDS will rank just behind accidents, heart disease and cancer as a major cause of potential life lost in the USA by 1991. Over half million AIDS cases are predicted by 1993 in the United States alone. There has been a great improvement in the understanding and treatment of opportunistic infections in AIDS. The most important concept is prophylactic treatment of the most common infectious complications as the immune system deteriorates. The major advance has been the prophylactic treatment of Pneumocystic Carinii Pneumonia (PCP) with either aerosolized Pentamidine or low dose Bactrim. Some experts advocate a low dose antibiotic prophylaxis for latent toxoplasma and cryptococcal infection in those patients whose immune systems are deteriorating. Prophylaxis would be instituted as the T4 helper lymphocyte count decreases. Finally, any patient found to be lately infected with either tuberculosis or syphilis, while HIV positive, must be thoroughly treated for these infections prior to any immunocompromise. The minimum follow-up of HIV positive individuals should include T4 lymphocyte counts and perhaps P24 antigen levels as well as beta 2-microglobulin levels. As these parameters worsen, patients should be directed to explore safe available treatments such as Antabuse, Naltrexone and Dextran sulfate. Any healthy patient with T4 helper counts under 400 should be directed to AIDS treatment evaluation units for enrolment in research protocols. At present over 100 drugs are being tested for the treatment of AIDS. However, researchers predict that no more than one or two drugs will be discovered over the next three years that will be helpful in the treatment of AIDS. If ever there was a more powerful argument to institute a new way of evaluating research drugs, it is this prediction. Due to the epidemic proportions of this disease, it seems reasonable to test epidemic proportions of this disease, it seems reasonable to test drugs shown to have some effect in groups of three of four drugs per patient. It is well demonstrated that AZT (Zidovudine) loses its anti-retroviral effect at about twelve to eighteen months. Drug resistance is seen in the treatment of a similar infectious agent, M. tuberculosis. Acute infection of MTB necessitates the use of three antibacterial agents. In AIDS infection, it seems logical to test two or three anti-retrovirals combined with one immunostimulant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acquired immunodeficiency syndrome: molecular biology and its therapeutic intervention (review). 251 41

The chemistry, spectrum of activity, mechanism of action, pharmacokinetics, adverse effects, and dosage and administration of pentamidine are reviewed, and the role of the drug in treating Pneumocystis carinii infections in immunocompromised patients is discussed. Pentamidine isethionate, an aromatic diamidine compound, is active against certain protozoan organisms. Used extensively in the tropics in the treatment of Trypanosoma and Leishmania infections, its value in the management of Pneumocystis carinii infections has been demonstrated in infected immunosuppressed children and adults. Recently, interest in pentamidine has increased with the rising number of patients with acquired immunodeficiency syndrome (AIDS) who have P. carinii pneumonia. Pentamidine's mechanism of action and pharmacokinetic profile are not completely understood. Pentamidine is distributed extensively after i.v. or i.m. administration, with a volume of distribution of 3 L/kg. Appreciable quantities of pentamidine concentrate in the urine, and drug levels are detectable for up to six to eight weeks after cessation of therapy. After aerosol administration, the drug is almost exclusively recovered from the lung, with little extrapulmonary distribution. Available data suggest that approximately 50% of patients who receive the drug by the i.v. or i.m. route will experience some drug toxicity (local pain, sterile abscesses at the intramuscular injection site, hypoglycemia, hypotension, or azotemia), while adverse effects after aerosol therapy include bronchial irritation but little systemic toxicity. Regardless of the route of administration, pentamidine has emerged as a mainstay of therapy in the management of P. carinii pneumonitis in AIDS patients, especially in those who are allergic to the sulfa component of trimethoprim-sulfamethoxazole.
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PMID:Update on pentamidine for the treatment of Pneumocystis carinii pneumonia. 304 30

After reviewing the immunological anomalies provoked by the human immuno-deficiency virus (HIV) as well as their implications in pulmonary pathology, the authors enumerate the diagnostic and therapeutic methods currently available in the treatment of patients suffering from AIDS and pulmonary diseases. The clinical features as well as the chest radiograph--an essential first line tool--may lead to atypical features. Respiratory function tests and scintigraphy to Gallium may be a useful additional diagnostic technique but for a full pulmonary investigation a bronchoalveolar lavage is required and/or transbronchial biopsy. Open lung biopsy is rarely required, and then only as a last resort. The treatment of pneumocystis remains centred on Trimethoprim sulfamethoxazole and Pentamidine, with a similar efficacy (80% care) but both have side-effects which are less frequent but more severe with Pentamidine. Administration of Pentamidine by aerosol, Eflornithine and Trimetrexate are under study. The level of lactic dehydrogenase (LDH) seems to be a prognostic factor. The value of prophylaxis is discussed. If the treatment of tuberculosis, an infection which is seen more and more frequently, still rests on classical triple therapy, the treatment of atypical mycobacterial infections is even more deceptive than in non-immuno-suppressed hosts. The same is true with pneumonia due to cytomegalovirus. The treatment of lymphoid interstitial pneumonia which is probably a direct result of HIV infection, remains controversial. On the other hand, pulmonary Kaposi's sarcoma is associated with an elevated mortality, and all treatment (interferon and chemotherapy) is disappointing.
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PMID:[Pulmonary manifestations of acquired immunodeficiency syndrome]. 306 2

Pentamidine pulmonary pharmacokinetics were studied in 13 patients receiving once-daily inhaled therapy and 4 patients receiving low-dose intravenous treatment for Pneumocystis carinii pneumonia. Twenty-four hours after inhaled or intravenous therapy, the mean (+/- standard deviation) concentrations of pentamidine in serial bronchoalveolar specimen fluid ranged from 28.6 +/- 10 to 177.5 +/- 28 ng/ml and 6.05 +/- 2.29 to 21.4 +/- 15.7 ng/ml, respectively. Pentamidine concentrations in brochoalveolar fluid were generally higher after 2 weeks than after day 1 of therapy; however, the differences were not statistically different (P greater than 0.05). The pulmonary half-life after inhaled therapy is long; pentamidine was detectable in bronchoalveolar fluid at 33 (one patient), 69 (one patient), and 115 (one patient) days following the completion of 2 weeks of therapy. Systemic absorption of pentamidine was minimal; the mean (+/- standard deviation) plasma concentration at the completion of inhalation was 13.84 +/- 11.8 ng/ml, or 5% of the mean peak plasma concentration achieved after intravenous administration. Accumulation in the plasma did not occur with repeated inhalation as has been described with multiple intravenous dosing. Cumulative urinary excretion 24 h after the first dose was 5% of that observed with intravenous administration. These data may have importance in designing dosage regimens for the further investigation of inhaled pentamidine for treatment or prophylaxis of P. carinii pneumonia.
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PMID:Concentrations of aerosolized pentamidine in bronchoalveolar lavage, systemic absorption, and excretion. 326 32

The efficacy and tolerance of pentamidine aerosol were evaluated in the prophylaxis and therapy of murine Pneumocystis carinii pneumonia. P. carinii pneumonia was induced in rats by corticosteroid immunosuppression. Pentamidine was administered three times weekly via a Bird micronebulizer. The actual amount of pentamidine inhaled was estimated by monitoring the ventilation of the rats during the aerosol administration. Pentamidine levels in blood, lung, liver and kidney samples were determined by high-pressure liquid chromatography after completion of the treatment. Efficacy was evaluated by examination of lung imprints. In the prophylactic treatment, 4.8- and 8.6-mg/kg doses of aerosolized pentamidine administered three times weekly for 7 weeks were effective in preventing P. carinii pneumonia in 80 and 100% of the rats, respectively. In the therapeutic studies, a 14.6-mg/kg dose of aerosolized pentamidine administered three times weekly for 3 weeks was effective both in curing the pneumonia and in clearing P. carinii cysts in 70% of the rats. In the remaining animals, although the pneumonia was cured, the cysts persisted. A dose-dependent effect of the drug was demonstrated in both prophylactic and therapeutic treatments. High lung/kidney and lung/liver ratios of pentamidine levels were demonstrated and were associated with good clinical, biological, and histologic tolerance.
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PMID:Pentamidine aerosol in prophylaxis and treatment of murine Pneumocystis carinii pneumonia. 349 16


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