[Cystic fibrosis: current therapy. Antibiotics].
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Administration, Oral↗
Biomedical subjects
M Tamm
Publications and source records attributed to M Tamm.
[Cystic fibrosis: current therapy. Indications for lung transplantation].
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Cystic Fibrosis↗
Blood eosinophilia in tacrolimus-treated patients: an indicator of Pneumocystis carinii pneumonia.
BACKGROUND: Pneumocystis carinii pneumonia (PcP) in immunocompromised patients is suggested if the following symptoms develop: dyspnea, fever, and interstitial infiltrates on chest x-ray. We observed a significant blood eosinophilia in kidney recipients with PcP under immunosuppressive treatment with tacrolimus. METHODS: Blood eosinophil counts of kidney recipients under immunosuppression with tacrolimus suffering from PcP were compared to eosinophil counts of patients without evidence of PcP and to patients showing PcP under immunosuppression with cyclosporine. RESULTS: PcP-positive patients treated with tacrolimus showed a significantly higher blood eosinophil count compared to PcP-positive patients treated with cyclosporine (P=0.01), and to patients under immunosuppression with tacrolimus without PcP, respectively (P=0.006). Eosinophilia preceded the time of a definitive PcP diagnosis by bronchoalveolar lavage and decreased after successful treatment. CONCLUSIONS: An increasing blood eosinophil count can be an indicator of P. carinii pneumonia in patients under immunosuppressive therapy with tacrolimus.
Adult↗
Calcium channel blockers activate the interleukin-6 gene via the transcription factors NF-IL6 and NF-kappaB in primary human vascular smooth muscle cells.
BACKGROUND: Calcium channel blockers (CCB) of all subclasses: the dihydropyridines, benzothiazepines, and phenylalkylamines, at nanomolar concentrations, have been shown to up-regulate interleukin-6 (IL-6) mRNA. We investigated the underlying molecular mechanism responsible for IL-6 induction in response to the CCB amlodipine, diltiazem, and verapamil in primary human vascular smooth muscle cells (VSMC). METHODS AND RESULTS: All 3 CCB directly activated transcription of the human IL-6 gene in primary human VSMC in a time- and dose-dependent manner, as demonstrated by luciferase reporter gene assays using a 651-bp fragment of the human IL-6 gene promoter. Deletion analysis of the IL-6 promoter revealed that CCB inducible promoter activity was localized to a 160-bp fragment directly upstream of the transcriptional start site of the IL-6 gene. Known transcription factor consensus sequences within this fragment include a NF-IL6 and a NF-kappaB site. Site-directed mutagenesis suggested that both transcription factors had positive regulatory activity and cooperatively transmitted induction of the IL-6 gene by CCB. The data are confirmed by electrophoretic mobility shift analyses using nuclear extracts from CCB-stimulated and control primary VSMC. CCB of all subclasses increased DNA binding of NF-IL6 and NF-kappaB as early as 30 minutes after stimulation with the drugs. This effect was independent of intracellular calcium concentrations because calcium-free medium did not increase NF-IL6 or NF-kappaB activity. CONCLUSIONS: The results demonstrate that CCB of all 3 subclasses are capable of activating NF-IL6 and NF-kappaB. CCB may thus directly regulate cellular functions by affecting the activity of transcription factors independent of changes of intracellular calcium concentrations, an observation that is of interest considering the biological effects induced by CCB.
CCAAT-Enhancer-Binding Proteins↗
Transforming growth factor-beta1 induces interleukin-6 expression via activating protein-1 consisting of JunD homodimers in primary human lung fibroblasts.
Transforming growth factor (TGF)-beta1 induces extracellular matrix deposition and proliferation of mesenchymal cells. We recently reported that interleukin (IL)-6 is an essential mediator of growth factor-induced proliferation of lung fibroblasts. Here, we demonstrate by reverse transcriptase polymerase chain reaction and enzyme-linked immunoassay that TGF-beta1 is a potent inducer of IL-6 mRNA and protein in primary human lung fibroblasts. Transient transfections of fibroblasts with a luciferase reporter gene construct containing nucleotides -651 to +1 of the human IL-6 promoter revealed that TGF-beta1 also potently activated IL-6 promoter activity. Progressive 5'-deletions and site-directed mutagenesis of the parental construct located the TGF-beta1-responsive cis-regulatory element to a known activating protein-1 (AP-1) sequence (nucleotides -284 to -276). Gel shift analyses revealed that AP-1 DNA binding activity in nuclear extracts was increased 30 min after stimulation with TGF-beta1. In contrast, neither CCAAT enhancer-binding protein-beta, NF-kappaB, nor Sp1 were activated by TGF-beta1. Supershift analyses demonstrated that the AP-1 complex induced by TGF-beta1 was composed of Jun isoforms and absent of Fos isoforms. Moreover, this complex was found to be a JunD homodimer. Our data thus demonstrate that TGF-beta1 is a potent inducer of IL-6 in primary human lung fibroblasts. The TGF-beta1-activated JunD homodimer may be essential for a majority of the biological effects induced by TGF-beta1 in this cell type, such as proliferation and extracellular matrix synthesis.
Base Sequence↗
Surgical aspects of resection for suspected invasive pulmonary fungal infection in neutropenic patients.
BACKGROUND: Morbidity and mortality of early resection of invasive pulmonary fungal disease in neutropenic patients are still considered prohibitive for surgical treatment. METHODS: We retrospectively analyzed results of 28 (16 men, 12 women; mean age, 38.9 years) consecutive neutropenic hematologic patients who had lung resections for suspicion of invasive pulmonary fungal disease. RESULTS: We did 28 lung resections (19 lobectomies, one bilobectomy, eight single or multiple wedge resections including three video-assisted wedge resections). The disease was proved histologically in 22 (78.6%) cases. Intraoperative difficulties, such as diffuse oozing or mycotic infiltration, and solid postinflammatory adhesions were encountered in 5 (17.8%) and 6 (21.4%) patients respectively. In one case (3.6%) it lead to a major intraoperative hemorrhage. There were no intraoperative deaths, overall 30-day mortality rate was two of 28 (7.1%), overall 90-day mortality rate was seven of 28 (25%), with one death (3.6%) possibly related to surgery. Minor surgery-related complications were seen in ten (35.7%) cases, major surgery-related complications occurred in three (10.7%) cases. Twelve of 22 patients (54.5%) with proven invasive fungal infection are currently alive (mean follow-up, 32.3 months). CONCLUSIONS: Surgery-related complications and mortality are acceptable for this high risk group of patients. Resection should be carried out early for diagnostic as well as therapeutic reasons.
Adolescent↗
Diagnostic yield of bronchoscopy in histologically proven invasive pulmonary aspergillosis.
Invasive pulmonary aspergillosis (IPA) is a life-threatening infectious complication in neutropenic patients after high-dose chemotherapy or hematopoietic stem cell transplantation. Its diagnosis is mainly based on clinical symptoms, and radiological signs on thoracic CT scan. The value of bronchoscopy is controversial. We analyzed the diagnostic yield of bronchoscopy in 23 consecutive patients with histologically proven invasive pulmonary aspergillosis. In seven patients (30%) bronchoscopically obtained specimens were diagnostic for pulmonary fungal infection. Typical hyphae were detected by cytology in six patients and fungal cultures were positive in four cases. Patients with a positive bronchoscopic result presented more often with multiple changes on thoracic CT scan (71%; 5/7), but had received a lower median cumulative dose of amphotericine B (300 mg; 168-3010 mg) compared to patients with non-diagnostic bronchoscopy (25% multiple lesions (4/16); amphotericine dose 1100 mg, 260-2860 mg). The diagnostic yield of bronchoscopy was not associated with clinical symptoms or duration of neutropenia. Bronchoscopy allows the diagnosis of IPA in about one third of patients. Fungal cultures and cytological examination of intrabronchial specimens obtained during bronchoscopy have a high specificity, but its sensitivity is low. It is advisable to perform diagnostic bronchoscopy before starting antifungal therapy. Better diagnostic tools are urgently needed.
Adolescent↗
What does a home mean and when does it cease to be a home? Home as a setting for rehabilitation and care.
PURPOSE: This article addresses three issues: (1) what does a home mean to a person? (2) what happens when the patients are rehabilitated in the home? and (3) can the home become a workplace for a professional? METHOD: A literature review based on research literature and on the author's research project in the north of Sweden 'Rehabilitation in a home setting--ethical, psychological and occupational therapeutic aspects,. RESULTS: For most people, the home is an important and meaningful place, where ultimate goals can be cultivated, sheltered from the intrusions of public life. In connection with chronic illness, functional impairment and rehabilitation in the home, the individual will often lose the home as a private territory and much of his/her own autonomy. No longer is the home an existential centre for the family, but a place where many unfamiliar people come and go. Rehabilitation in a home setting means, furthermore, that the public sector is moved into the home, and the home has to function as a public workplace, ensuring a good working environment. CONCLUSIONS: The question for the future is: can the combination of home and public workplace work at all? More research is needed to answer this question. Prior documented experiences show that it is difficult.
Family↗
Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from CMV disease by limiting the systemic virus load.
The role of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTLs) and T helper cells (Th) in controlling CMV infection, as detected by antigenemia assay and polymerase chain reaction (PCR) in blood leukocytes, and CMV disease was investigated in 20 renal transplant recipients. Within 3 months after transplant, CMV-specific CTL and Th responses were demonstrable in 11 (55%) and 15 (75%) patients, respectively; CMV infection was detected by antigenemia and PCR in 19 (95%) patients each. During the month of first CMV detection, there was an inverse correlation between CTL response and antigenemia at >/=20 positive cells/105 leukocytes (P=.007) but no association with lower antigenemia levels or PCR positivity. CMV disease developed in 7 (35%) patients and was associated with high-level antigenemia but was inversely correlated with detection of CTLs (P=.04). After renal transplantation, CMV-specific CTLs limit the systemic virus load as reflected by antigenemia levels and thereby mediate protection from CMV disease.
Adult↗
The lung in the immunocompromised patient. Infectious complications part 2.
Pulmonary infections decisively contribute to morbidity and mortality in immunocompromised patients. Bacterial, mycobacterial and infections with Pneumocystis carinii have been reviewed in an article in the last issue of Respiration. In this review, viral and fungal pulmonary infections are discussed in HIV-positive patients and in patients treated with high-dose chemotherapy, stem cell or solid-organ transplantation.
Drug-Related Side Effects and Adverse Reactions↗
Prospective evaluation of an algorithm for the functional assessment of lung resection candidates.
Patients with impaired pulmonary function are at increased risk for the development of postoperative complications. Recently exercise testing and predicted postoperative (ppo) function have gained increasing importance in the evaluation of lung resection candidates. We prospectively evaluated an algorithm for the preoperative functional evaluation that was developed at our institution. This algorithm incorporated the cardiac history including an electrocardiogram (ECG), and the three parameters FEV1, diffusing capacity of the lungs for carbon monoxide (DLCO), and maximal oxygen uptake (VO2max), as well as their respective ppo values (FEV1-ppo, DLCO-ppo, and VO2max-ppo) calculated based on radionuclide perfusion scans. A consecutive group of 137 patients (mean age 62 yr; range 23 to 81; 102 males, 35 females) with clinically resectable lesions underwent assessment according to our algorithm. Five patients were deemed functionally inoperable, 132 passed the algorithm and underwent pulmonary resections with standard thoracotomy: 9 segmental or wedge resections, 85 lobectomies (inclusive 3 bilobectomies), and 38 pneumonectomies. All patients were extubated within 24 h. The mean stay in the ICU was 1.4 (+/- 1.8) d, and the mean hospital stay was 14.6 (+/- 5) d. Postoperative complications (within 30 d) occurred in 15 patients (11%), of whom two died (overall mortality rate 1.5%). In comparison to our previous series this meant a 50% reduction in complications whereas the percentage of inoperable patients remained unchanged (4% now, 5% before). We conclude that adherence to our algorithm resulted in a very low complication rate (morbidity and mortality), and excluded more rigorous patient selection as a bias for the improved results.
Aged↗
The value of transbronchial needle aspiration in the diagnosis of peripheral pulmonary lesions.
BACKGROUND: Transbronchial needle aspiration (TBNA) is a bronchoscopic sampling technique used for the diagnostic workup of mediastinal lymph nodes, but the value of its routine use in evaluating peripheral pulmonary lesions is not yet firmly established. DESIGN: Retrospective analysis of routine diagnostic bronchoscopies. SETTING: University teaching hospital. PATIENTS AND METHODS: One hundred seventy-two consecutive patients (126 with malignant and 46 with nonmalignant disease) who underwent bronchoscopy for a peripheral pulmonary lesion. RESULTS: In 87 patients (51%), a final diagnosis was established by bronchoscopy; diagnoses included 81 malignant lesions (69 lung cancer and 12 pulmonary metastases) and 6 benign lesions (all tuberculosis). TBNA was used in 152 of the 172 patients (89%). Other endoscopic techniques included bronchial washing (100%), bronchial brushing (45%), and transbronchial biopsy (TBB) (27%). Concerning the different bronchoscopic sampling techniques, TBNA showed a positive result in 35% of cases, in comparison to 17% for TBB, 22% for bronchial washing, and 30% for bronchial brushing. While TBNA was diagnostic in 27.5% of the malignant lesions < 3 cm in diameter, the success rate in lesions > 3 cm was 65.5% (p = 0.03). Endoscopy-related complications included pneumothorax (n = 1), self-limiting bleeding (n = 12), prolonged coughing (n = 2), and vasovagal reactions (n = 2). None of these complications required further treatment. CONCLUSION: TBNA is an effective bronchoscopic sampling technique in the diagnosis of peripheral pulmonary lesions. In our study, the use of TBNA increased the diagnostic yield of bronchoscopy from 35 to 51% without additional risk. The use of TBNA in the clinical routine should be encouraged.
Aged↗
Transmission of human herpesvirus 8 infection from renal-transplant donors to recipients.
BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all forms of Kaposi's sarcoma, including transplantation-associated Kaposi's sarcoma. To investigate the possibility of transmission of HHV-8 through allografts, we measured the seroprevalence of HHV-8 before and after renal transplantation. METHODS: Using an enzyme-linked immunosorbent assay with the recombinant HHV-8 protein orf 65.2, we analyzed serum samples from 220 renal-transplant recipients for the presence of antibodies to HHV-8 on the day of transplantation and one year later. Positive results were confirmed by an indirect immunofluorescence assay that detects antibodies to latent antigen and by Western blotting. Follow-up lasted at least four years. RESULTS: The seroprevalence of HHV-8 in graft recipients increased from 6.4 percent on the day of transplantation to 17.7 percent one year after transplantation. Seroconversion occurred within the first year after transplantation in 25 patients, and Kaposi's sarcoma developed in 2 of them within 26 months after transplantation. Sequential serum samples were obtained from 10 of the patients with seroconversion, and in 8 of these patients, IgM antibodies to HHV-8 appeared within three months after transplantation. In the case of six patients who seroconverted, serum samples from the donors were available, and five (83 percent) tested positive for HHV-8. In a control group of eight patients who were seronegative at the time of transplantation and who received allografts from HHV-8-negative donors, none seroconverted within the year after transplantation. CONCLUSIONS: HHV-8 is transmitted through renal allografts and is a risk factor for transplantation-associated Kaposi's sarcoma.
Adolescent↗
Human herpesvirus 8 variants.
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DNA, Viral↗
Pulmonary infiltrate in an asymptomatic kidney donor.
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Humans↗
Characteristic lesions on CT scan and progressive dyspnea.
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Dyspnea↗
Diagnosis of pulmonary Kaposi's sarcoma by detection of human herpes virus 8 in bronchoalveolar lavage.
Human herpes virus 8 (HHV8) DNA has recently been detected in sarcoma tissue of patients with Kaposi's sarcoma. HHV8 DNA could also be found in bronchoalveolar lavage (BAL) fluid of patients with tracheobronchial Kaposi's sarcoma. To determine the specificity, sensitivity and predictive values of HHV8 DNA detection in the BAL for the diagnosis of pulmonary Kaposi's sarcoma, 100 consecutive BAL were prospectively analyzed for the presence of HHV8 DNA using a nested PCR assay. In addition, 19 BAL samples of 14 AIDS patients with cutaneous or visceral Kaposi's sarcoma were retrospectively investigated. The prospective group consisted of 79 BAL performed in immunocompromised and of 21 BAL in nonimmunocompromised patients. Four patients of the prospectively analyzed group undergoing six BAL showed tracheobronchial Kaposi's sarcoma at five bronchoscopies. All of the five BAL samples performed in these patients with endoscopically visible Kaposi's sarcoma were positive for HHV8 DNA. Following chemotherapy and antiretroviral treatment tracheobronchial Kaposi's sarcoma was no longer detectable at a subsequent bronchoscopy and HHV8 DNA in BAL became negative in one patient. One BAL sample of a HIV-positive patient with no evidence of Kaposi's sarcoma was HHV8 DNA-positive. The sensitivity, specificity, positive and negative predictive values of HHV8 detection for the diagnosis of tracheobronchial Kaposi's sarcoma were 100%, 98.9%, 83.3%, and 100%, respectively. Twelve of 19 BAL samples of the retrospective group were HHV8 DNA-positive. In this group, 10 patients undergoing a total of 14 BAL suffered from pulmonary Kaposi's sarcoma. HHV8 DNA was documented in 10 of these 14 BAL samples. In three BAL of this group HHV8 DNA was positive, but pulmonary Kaposi's sarcoma was diagnosed at a later stage. In conclusion, the detection of HHV8 DNA in BAL is restricted to patients with Kaposi's sarcoma and is highly sensitive and specific for pulmonary involvement of Kaposi's sarcoma.
Adult↗
Lung resection for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases.
Invasive pulmonary aspergillosis (IPA) is associated with a high mortality. In 27 consecutive neutropenic patients who underwent lung resection for suspected IPA, we analyzed preoperative diagnostic evaluation, operative procedure, perioperative management, histological findings, outcome concerning recurrence of aspergillosis, and survival to evaluate the morbidity and mortality of a surgical treatment of IPA. Seventeen patients with hematologic diseases had previously undergone high-dose chemotherapy and four stem cell transplantation. Six patients with aplastic anemia were treated with antilymphocyte globulin. IPA was suspected if localized infiltrates developed on thoracic CT scan, and fever persisted under antibiotic therapy in neutropenic patients. In only one case a diagnosis of IPA could be made preoperatively. Twenty patients underwent lobectomy and seven wedge resection. At day of surgery the neutrophil count was below 500 x 10(9)/L in 78% of patients, and the platelet count below in 50 x 10(9)/L in 58% of patients. Invasive fungal infection was confirmed histologically in 22 of 27 patients (81.5%); in five patients no fungal infection was documented. The median duration of surgery was 120 min. Postoperatively, patients stayed one night in the intensive care unit, and chest tubes were removed after 2 d. Within 7 d a median of four erythrocyte packs and two platelet packs per patient were replaced. Major surgical complications occurred in two patients (bronchial dehiscence; pleural aspergillosis). Minor surgical complications included prolonged chest tube drainage (recurrent pneumothorax, n = 2; air leakage, n = 1; hematothorax, n = 1), pleural effusion (n = 4), and seroma (n = 2). Postoperatively, two patients suffered from histologically proven disseminated aspergillosis (pleural aspergillosis, renal aspergilloma) and another patient from suspected orbital aspergillosis. At 30 d postoperative mortality was 11% and 3-mo survival was 77%. After lung resection, seven patients underwent stem cell transplantation without recurrence of IPA. In conclusion, we suggest lung resection is a therapeutic option for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases and is associated with a low surgery-related morbidity and mortality.
Adolescent↗