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

We studied the tissue distribution and in vivo antifungal effect of itraconazole, incorporated into pure dipalmitoylphosphatidylcholine (DPPC) multilamellar liposomes and administered intravenously. Eighty percent of the itraconazole was associated with DPPC. Drug levels in lung, brain, and liver, obtained after intravenous administration of tritiated itraconazole, were higher when the drug was administered intravenously as liposomal than when it was dissolved in cyclodextrin. Administration of the liposomal formulation also led to higher and sustained levels of intact itraconazole in serum. Efficacy was assessed in DBA/2 mice infected intravenously with 3 x 10(6) Cryptococcus neoformans, an inoculum responsible for early fatal pneumonia, or 3 x 10(5) C. neoformans, leading to delayed meningitis. In pneumonia, 20 mg/kg of liposomal itraconazole was more effective on survival than the same dose given intravenously in cyclodextrin or twice the dose administered orally dissolved in polyethylene glycol 200. In meningitis, liposomal itraconazole was also more efficient than the drug dissolved in cyclodextrin. These results were confirmed by colony counts in the brain and lung of infected mice. In immunosuppressed OF1 mice infected after inhalation of Aspergillus fumigatus spores, liposomal itraconazole (20 mg/kg x 3) was the only effective treatment. We conclude that intravenous liposomal delivery of itraconazole enhances both concentrations in infected tissues and the in vivo efficacy of the drug. Such passive targeting of antifungal agents other than amphotericin B might be helpful in the treatment of severe systemic mycoses, especially in the case of lung or brain involvement.
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PMID:Tissue distribution and antifungal effect of liposomal itraconazole in experimental cryptococcosis and pulmonary aspergillosis. 131 May 77

Animal models for Pneumocystis carinii, for the most part, have been limited to immunosuppressed rats and ferrets, while a dependable mouse model has been more difficult to develop. A P. carinii mouse model has now been established with several strains of mice, including C3Heb/FeJ, C3HeN, BALB/c, DBA/2N, and BALB/c nu/nu (athymic). In lieu of using invasive methods for initiating P. carinii infections, mice harboring P. carinii transmitted the disease to mice without latent infection via short-term cohabitation. After the exposure period, the seed mice were sacrificed to confirm the presence of acute P. carinii pneumonia. Acute infections in recipient mice developed at approximately 7 to 8 weeks, while control unseeded littermates remained uninfected. All recipient mice and their littermates were maintained in isolation hoods to eliminate the possibility of exposure to other sources of P. carinii. This approach allows investigators to consistently transmit P. carinii to mice and to select the strain of mouse desired for use in a particular study. The results presented here suggest that more attention should be given to the potential for patient-to-patient transmission of P. carinii in immunocompromised patients such as those with AIDS.
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PMID:Mouse model for Pneumocystis carinii pneumonia that uses natural transmission to initiate infection. 154 65

Current therapy of cryptococcosis is unsatisfactory, particularly in patients with AIDS. Experimental cryptococcosis models in DBA/2 mice were used to determine whether the murine monoclonal anticryptococcal antibody (designated E1) might potentiate the chemotherapeutic effect of amphotericin B (AmB). According to the inoculum size, these mice died spontaneously from acute pneumonia (high inoculum) or from brain swelling (lower inoculum). AmB and E1 together significantly improved the survival of mice in both models compared with AmB alone. The mechanisms by which E1 might potentiate AmB activity were investigated in vitro. When cryptococci were preincubated with AmB or another polyene antibiotic, nystatin, there was an augmented binding of E1. AmB enhanced phagocytosis by unstimulated peritoneal macrophages in the presence of E1 or normal rabbit immunoglobulins. Normal and immune IgG deserve further study to determine under what circumstances the chemotherapeutic effect of AmB can be enhanced.
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PMID:Improved amphotericin B activity by a monoclonal anti-Cryptococcus neoformans antibody: study during murine cryptococcosis and mechanisms of action. 201 59

Although cellular immunity has a crucial role during cryptococcosis, several in vitro studies have pointed out the importance of IgG anti-Cryptococcus neoformans antibodies and complement components during phagocytosis of the yeast by polymorphonuclear leucocytes and monocytes. We investigated the role of complement and specific antibodies in host defences against experimental cryptococcosis, using a monoclonal IgG1 antibody (E1) specific for cryptococcal capsular polysaccharide, and mice congenitally sufficient or deficient in the fifth component of complement (C5). During in vitro experiments, E1 and the normal mouse serum from C5-sufficient and -deficient mice were unable to inhibit the growth of C.neoformans. However, E1 was an efficient opsonin for the ingestion of C. neoformans by mouse peritoneal macrophages, acting in synergy with normal mouse serum. In vivo, E1 was protective in heavily infected C5-deficient mice (DBA/2) dying from an early acute pneumonia, but not in C5-sufficient mice (BALB/c) and in DBA/2 mice infected with a smaller inoculum dying from a late progressive meningo-encephalitis. Although protection against pneumonia is attributed to a local recruitment of phagocytes in C5-sufficient mice, this was not observed in C5-deficient mice protected with E1. In this case, IgG anti-C. neoformans antibodies seem to be an alternative for an efficient opsonization of the yeasts. Altogether, these data suggest that two main mechanisms may protect infected mice from an early fatal pneumonia: the efficient opsonization of the yeast by complement and the recruitment of phagocytes in infected tissues.
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PMID:Role of IgG and complement component C5 in the initial course of experimental cryptococcosis. 261 53

C 57 BL/6J mice are resistant to lethal Sendai virus pneumonia and have lower lung virus titers than susceptible DBA/2J mice. Linkage between these phenotypes was tested indirectly in segregant hybrids. Sas-1, B2m, and b on chromosomes 1, 2, and 4 were linked to significant (P less than .05) differences in virus-induced mortality; d on chromosome 9 was associated with a similar but smaller difference (.1 greater than P greater than .05). Mean lung virus titers were higher in F1 X DBA/2J mice that were homozygous for DBA alleles at B2m, b, and d than in heterozygotes. The difference in lung virus titers was larger between mice that were dihomozygous/diheterozygous for paired combinations; B2m-d (P less than .02), B2m-b (P less than .06), and b-d (P less than .05) and largest between mice that were trihomozygous/triheterozygous for B2m-b-d (P less than .001). The distribution of virus titers among 22 recombinant inbred strains derived from C 57 BL/6J and DBA/2J progenitors indicated 1) that the loci linked to B2m, b, and d are among at least 4 loci that regulate lung virus titers, 2) that Sas-1 may be linked to a fourth locus, 3) that the C 57 BL/6J genome contains at least one susceptibility locus, possibly within H-2, and 4) that some of these loci may be expressed through natural killer cell activity.
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PMID:Genetic determinants of lung virus titers and resistance to lethal Sendai virus pneumonia. 282 61

Mycobacterium tuberculosis produces latent infection or progressive disease. Indeed, latent infection is more common since it occurs in one-third of the world's population. We showed previously, using human material with latent tuberculosis, that mycobacterial DNA can be detected by in situ PCR in a variety of cell types in histologically-normal lung. We therefore sought to establish an experimental model in which this phenomenon could be studied in detail. We report here the establishment of such a model in C57Bl/6 x DBA/2 F1 hybrid mice by the intratracheal injection of low numbers of virulent mycobacteria (4000). Latent infection was characterized by low and stable bacillary counts without death of animals. Histological and immunological study showed granulomas and small patches of alveolitis, with high expression of tumour necrosis factor alpha (TNFalpha), inducible nitiric oxide synthase (iNOS), interleukin 2 (IL-2) and interferon gamma (IFNgamma). In contrast, the intratracheal instillation of high numbers of bacteria (1 x 106) produced progressive disease. These animals started to die after 2 months of infection, with very high bacillary loads, massive pneumonia, falling expression of TNF-alpha and iNOS, and a mixed Th1/Th2 cytokine pattern. In situ PCR to detect mycobacterial DNA revealed that the most common positive cells in latently-infected mice were alveolar and interstitial macrophages located in tuberculous lesions, but, as in latently-infected human lung, positive signals were also seen in bronchial epithelium, endothelial cells and fibroblasts from histologically-normal areas. Our results suggest that latent tuberculosis is induced and maintained by a type 1 cytokine pattern plus TNFalpha, and that mycobacteria persist intracellularly in lung tissue with and without histological evidence of a local immune response.
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PMID:Immunological and pathological comparative analysis between experimental latent tuberculous infection and progressive pulmonary tuberculosis. 1198 12

The authors describe three infants with Diamond-Blackfan anemia receiving corticosteroids who were diagnosed with Pneumocystis carinii pneumonia. Two patients exhibited intermittent neutropenia as well. Each child had been receiving relatively high doses of corticosteroids for at least 2 months, and two were having prednisone tapered when pneumonia developed. One child responded to trimethoprim/sulfamethoxazole and pentamidine, but the other two patients died. Infants with Diamond-Blackfan anemia receiving prolonged corticosteroid therapy should receive P. carinii pneumonia prophylaxis, such as trimethoprim/sulfamethoxazole, and prophylaxis should continue during corticosteroid tapering.
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PMID:Pneumocystis carinii pneumonia in patients with Diamond-Blackfan anemia receiving high-dose corticosteroids. 1214 94

Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 yr of age. It is assumed that host factors influence the severity of the disease presentation and thus the need for hospitalization. As a first step toward the identification of the underlying genes involved, this study was undertaken to establish whether inbred mouse strains differ in susceptibility to pneumonia virus of mice (PVM), the murine counterpart of RSV, which has been shown to accurately mimic the RSV disease of children. With this purpose in mind, double-chamber plethysmography and carbon monoxide uptake data were collected daily for 7 days after inoculation of PVM in six inbred strains of mice. In parallel, histological examinations and lung viral titration were carried out from day 5 to day 7 after inoculation. Pulmonary structure/function values reflected the success of viral replication in the lungs and revealed a pattern of continuous variation, with resistant, intermediate, and susceptible strains. The results suggest that SJL (resistant) and 129/Sv (susceptible) strains should be used in crossing experiments aimed at identifying genes controlling pneumovirus replication by the positional cloning approach. Similarly, crossing experiments using BALB/c or C57BL/6 (resistant) and DBA/2 or 129/Sv (susceptible) will allow the identification of the genes involved in the control of pulmonary inflammation during pneumovirus infection.
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PMID:Differential resistance/susceptibility patterns to pneumovirus infection among inbred mouse strains. 1655 25

We have shown previously that there is a direct correlation between IL-10 levels and susceptibility to Coccidioides immitis peritonitis in C57BL/6 (B6), DBA/2, and BXD recombinant inbred mice. We now show that B6 mice are also more susceptible to C. immitis pneumonia and that interleukin-10 (IL-10)-deficient (IL-10-/-) B6 mice are more resistant to C. immitis pneumonia. In addition, we established that high levels of IL-10 are sufficient to make genetically resistant mice susceptible to both C. immitis peritonitis and pneumonia by infecting h.IL-10 transgenic mice. Infected h.IL-10 transgenic mice express lower levels of gamma interferon, IL-12 p40, and inducible nitric oxide synthetase 2 (NOS2) mRNA in their lungs, implicating inducible NOS as a defense mechanism in this disease. We treated DBA/2 mice with aminoguanidine, and they became more susceptible to C. immitis peritonitis and pneumonia. We conclude that high levels of IL-10 are both necessary and sufficient to make mice susceptible to C. immitis, regardless of the genetic background of the mice, and that IL-10 impairs resistance to C. immitis in part by suppressing NO synthesis.
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PMID:High levels of interleukin-10 impair resistance to pulmonary coccidioidomycosis in mice in part through control of nitric oxide synthase 2 expression. 1671 69

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia or hypoplasia presenting in infancy as a macrocytic anemia. It has been linked to a gene defect resulting in the absence of specific ribosomal proteins that enable erythroid maturation. Treacher Collins syndrome is also associated with defective ribosomal biogenesis. Fifty percent of patients with DBA also present with additional physical abnormalities including growth delay, craniofacial abnormalities, upper limp abnormalities, cardiac defects, urogenital malformations, and cleft palate. Upper airway obstruction may be a complication from craniofacial disorders and may be responsible for life-threatening sleep apnea that may result in pneumonia or respiratory failure. This report is of a patient with DBA who presented at birth with respiratory distress secondary to tongue-based obstruction of the airway due to mandibulofacial dysostosis leading to need for intubation. In an effort to avoid a tracheostomy, the patient underwent bilateral internal mandibular osteodistraction on day 4 of life with a latency period of 0 days and a distraction at a rate of 2 mm/d for 10 days until a class 3 dental occlusion existed with 5 mm of overcorrection. In addition, the patient was born with choanal atresia that was repaired at day 30 of life. After completion of the mandibular distraction, the patient has avoided tracheostomy and is now 6 months of age. Recent polysomnogram has demonstrated no significant apnea or hypopnea.
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PMID:Curvilinear mandibular distraction in a patient with mandibulofacial dysostosis associated with Diamond-Blackfan anemia. 1981 70


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