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Biomedical subjects

H P Wiedemann

Publications and source records attributed to H P Wiedemann.

At least 19 recordsLinked to original sources

Coccidioidomycosis in non-endemic areas: a case series.

Coccidioidomycosis is a systemic infection caused by the soil fungus Coccidioides immitis, which is endemic to the south-western United States. Manifestations range from flu-like illness to pneumonia and septic shock. Diagnosis may be delayed or missed in non-endemic areas because of the low index of suspicion. We describe a series of 23 patients with coccidioidomycosis at one institution in a non-endemic area. Diagnosis was often delayed. In two patients, the route of exposure could not be determined, but 20 patients had a history of residence or travel to endemic areas, and the remaining patient had an occupational history of exposure to fomites from an endemic region. Five patients were immunosuppressed. Most patients responded well to medical therapy, surgery, or both. Although coccidioidomycosis is rare in non-endemic areas, physicians must keep it in mind when evaluating patients who have traveled to endemic areas or who are immunosuppressed.

Adult↗

Major histocompatibility locus genetic markers of beryllium sensitization and disease.

Hypersensitivity to beryllium (Be) is found in 1-16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only approximately 50% of BeLPT-positive workers present with lung granulomas (i.e. berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation. A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-alpha polymorphism TNF-alpha-308 in 23 individuals presenting as "sensitized" (i.e. BeLPT-positive without lung granulomas) and in 22 presenting as "diseased" (i.e. BeLPT-positive with granulomas in the lung biopsy). The HLA-DPGlu69 marker was associated with "disease" (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4-10.0), whilst the high TNF-alpha production-related TNF-alpha-308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p<0.0001, 95% CI 3.2-19.1) with no difference between "sensitization" and "disease". Furthermore, the HLA-DRArg74 marker was associated with "sensitization" without disease (OR 3.96, p=0.005, 95%, CI 1.5-10.1). The data indicate that tumour necrosis factor-alpha, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.

Adult↗

A study of consecutive autopsies in a medical ICU : a comparison of clinical cause of death and autopsy diagnosis.

OBJECTIVE: To determine the degree of concordance between clinical cause of death and autopsy diagnosis in a medical ICU (MICU) setting. DESIGN: Retrospective medical chart and autopsy report review. SETTING: MICU in a tertiary referral hospital. PATIENTS: Consecutive admissions to an MICU over a 2-year period from January 1, 1994, to December 31, 1995. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One thousand eight hundred patients were admitted to the MICU during the study period. There were 401 in-ICU deaths (22.3%). The autopsy rate was 22.7% (91 of 401). The mean +/- SD age of the autopsied patients (55.1 +/- 13.5 years) was lower than those without autopsy (62.4 +/- 15.2 years; p < 0.001). The two groups were otherwise similar with regard to sex, race, APACHE (acute physiology and chronic health evaluation) III scores, and lengths of stay in the MICU and hospital. The discordance between clinical and postmortem diagnoses was 19.8% (95% confidence interval, 12 to 29%). There were no differences in age, sex, APACHE III scores, predicted mortality, and lengths of stay in MICU hospital between patients with concordant and discordant diagnoses. In 44.4% (8 of 18) of the discordant cases, management would have been modified had the autopsied diagnosis been made premortem. Seven of the autopsied patients had organ transplantation. Three of the patients who had organ transplantation had discordant diagnoses, including two patients with disseminated fungal infection that was not diagnosed clinically. Although the observed discordance in transplant patients (43%) was higher than in those without transplant (19%), the difference was not statistically significant (p = 0.15). CONCLUSION: Younger patients tended to have a higher autopsy rate than older patients. The discordance between the clinical cause of death and postmortem diagnosis was 19.8%. In 44.4% of the discordant cases, knowledge of the correct diagnosis would have altered therapy.

APACHE↗

Gas embolism.

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Animals↗

Partial liquid ventilation for acute respiratory distress syndrome.

PLV represents an intriguing alternative paradigm in the approach to the patient with ALI. Within the past decade, substantial information has become available regarding this technique. Clearly, PLV is feasible in patients with ALI and ARDS, and it appears to be safe with respect to short-term effects on hemodynamics and lung physiology, as well as long-term toxicity (although further research in this area is warranted). Although PLV has not yet been proven to be superior to traditional mechanical ventilation for patients with ALI or ARDS, PLV possesses an intriguing combination of physical, physiologic, and biologic effects: "Liquid PEEP" effect--e.g., more effective recruitment of dependent lung zones than achieved by gas ventilation Anti-inflammatory effects Lavage of alveolar debris Mitigation of ventilator-induced lung injury Direct anti-inflammatory effects--e.g., decreased macrophage release of proinflammatory cytokines, etc. Prevention of nosocomial pneumonia Combination with other modalities--e.g., exogenous surfactant replacement, inhaled NO, prone position Enhanced delivery of drugs or gene vectors into the lung. The results of ongoing and future clinical trials will be necessary to establish whether PLV improves clinical outcomes in patients with ALI or ARDS, or specific subgroups of such patients. Significant work also remains to be done to define the optimum dose level of PLV and the most appropriate ventilatory strategies.

Clinical Trials as Topic↗

Acute respiratory distress syndrome: low-stretch ventilation improves survival.

In a recent major study, patients with acute respiratory distress syndrome or acute lung injury were randomly assigned to have their respirators set to deliver tidal volumes of either 6 mL/kg or a more-traditional 12 mL/kg. Mortality in the low-tidal-volume group was 31.0%, compared with 39.8% in the traditional-tidal-volume group, a 22% difference (P = .007).

Humans↗

Complications of hemodynamic monitoring.

The uses of the pulmonary artery catheter have been expanded from its original use, helping to assess the cardiac output and left ventricular filling pressure of patients with cardiac disease, to include the management of patients with trauma, septic shock, respiratory failure, and those undergoing high-risk surgeries. Although more than 1 million pulmonary artery catheters are inserted each year in the United States, clear evidence establishing that they improve outcome remains hard to find. This article discusses the complications of invasive hemodynamic monitoring.

Cardiovascular Diseases↗

Listeria monocytogenes tricuspid valve endocarditis with septic pulmonary emboli in a liver transplant recipient.

Listeria monocytogenes has long been known as a pathogen of immunocompromised hosts, including solid organ and bone marrow transplant recipients. Its principal manifestations include bacteremia and meningitis. Endocarditis due to Listeria is far less common and in general affects the left side of the heart. We here report an unusual case of Listeria tricuspid valve endocarditis and septic pulmonary emboli in a sulfa-intolerant liver transplant recipient with a history of relapsing cytomegalovirus (CMV) hepatitis and an indwelling Hickman catheter. The literature on Listeria endocarditis and infections in transplant recipients is reviewed. The possible relationship between susceptibility to Listeria infection and the discontinuation of trimethoprim-sulfamethoxazole prophylaxis is of interest.

Adult↗

The relation of pneumothorax and other air leaks to mortality in the acute respiratory distress syndrome.

BACKGROUND: In patients with the acute respiratory distress syndrome, pneumothorax and other air leaks - any extrusion of air outside the tracheobronchial tree - have been attributed to high ventilatory pressures or volumes and linked to increased mortality. METHODS: We analyzed data from a prospective trial of aerosolized synthetic surfactant in 725 patients with the acute respiratory distress syndrome induced by sepsis. We compared the ventilatory pressures and volumes in the patients without any air leaks (the highest values during the five-day study) with the pressures and volumes in those with pneumothorax or with any air leaks (the highest values during the 16- and 24-hour periods before the complication developed). RESULTS: Fifty patients (6.9 percent) had pneumothorax and 77 (10.6 percent) had pneumothorax or other air leaks. There were no significant differences between patients with air leaks and those without air leaks in any pressure or volume examined. Overall mortality at 30 days was 40.0 percent (95 percent confidence interval, 36.4 to 43.6); among the patients with pneumothorax, it was 46.0 percent (95 percent confidence interval, 32.2 to 59.8), and among those without pneumothorax, it was 39.3 percent (95 percent confidence interval, 35.6 to 43.0; P=0.35). The mortality rate was 45.5 percent (95 percent confidence interval, 34.4 to 56.6) in the group with any air leaks and 39.0 percent (95 percent confidence interval, 35.3 to 42.8) in the group without air leaks (P=0.28). CONCLUSIONS: In patients with sepsis-induced acute respiratory distress syndrome who were receiving mechanical ventilation with conventional pressures and volumes, there were no significant correlations between high ventilatory pressures or volumes and the development of pneumothorax or other air leaks. Pneumothorax or other air leaks were not associated with a significantly increased mortality rate.

Adult↗

Pulmonary manifestations of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that primarily affects young women. The respiratory system is more commonly involved in SLE than in any other collagen vascular disease. SLE may affect virtually all components of the respiratory system, including the upper airway, lung parenchyma, pulmonary vasculature, pleura, and respiratory muscles. Respiratory system involvement ranges from symptomatic to fulminant and life threatening. This article reviews the pulmonary manifestations of SLE, including drug-induced SLE.

Adult↗

Erosion of implantable cardioverter defibrillator patch electrode into airways: an unusual cause of recurrent hemoptysis.

A 74-year-old man presented with a 9-month history of recurrent hemoptysis. He had implantable cardioverter defibrillator (ICD) patch electrodes placed 4 years before. A chest x-ray film showed crinkling of his posteriorly placed ICD patch which also appeared to have separated from his ventricle on a CT scan of the chest. Bronchoscopy localized the ICD patch electrode to the lower lobe of the left lung. He underwent a lobectomy and was treated with antibiotics at home. In patients with known ICD implantation, patch erosion into the airways should be considered in the differential diagnosis of recurrent hemoptysis.

Aged↗

Systemic pharmacologic therapy of ARDS.

The increased understanding of the pathophysiology of acute lung injury that has been achieved over the last decade has led to several new pharmacologic approaches for the prevention and management of ARDS. Based on in vitro information and animal models, many of these strategies are quite compelling. Nevertheless, to date, no specific pharmacologic approach for the prevention or treatment of ARDS has been validated conclusively in clinical trials. Active basic and clinical investigations are continuing, and it is hoped that these will lead to new therapies that can be applied by the clinician in the management of future ARDS patients.

Adrenal Cortex Hormones↗

Perflubron decreases inflammatory cytokine production by human alveolar macrophages.

OBJECTIVE: To determine whether inflammatory cytokine production by stimulated human alveolar macrophages is affected by perflubron exposure. DESIGN: Controlled laboratory investigation of alveolar macrophage function in vitro. SETTING: Research laboratory. SUBJECTS: Cultured alveolar macrophages obtained by bronchoalveolar lavage from eleven normal volunteers. INTERVENTIONS: Endotoxin-stimulated alveolar macrophages were treated with perflubron. MEASUREMENTS AND MAIN RESULTS: Alveolar macrophages were stimulated for 1 hr with lipopolysaccharide and then treated with perflubron for 23 hrs. Cell-free supernatants were collected and cytokines were assayed by enzyme-linked immunosorbent assay. Tumor necrosis factor-alpha, interleukin-1, and interleukin-6 were stimulated by lipopolysaccharide (endotoxin) and all of these cytokines were significantly (p < .05) inhibited by perflubron. Cell viability was not affected by perflubron. Basal cytokine concentrations from unstimulated alveolar macrophages were not altered by perflubron. CONCLUSIONS: Exposure of stimulated human alveolar macrophages to perflubron in vitro decreases cytokine production. This observation suggests that perflubron may have anti-inflammatory activity.

Bronchoalveolar Lavage↗

Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant. Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival. METHODS: We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiological and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter, 364 patients) or placebo (o.45 percent saline; 361 patients) in aerosolized form for up to five days. RESULTS: The demographic and physiologic characteristics of the two treatment groups were similar at base line. The mean (+/- SD) age was 50 +/- 17 years in the surfactant group and 53 +/- 18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4 +/- 25 and 70.5 +/- 25, respectively. Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups. Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups. CONCLUSIONS: The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function.

Administration, Inhalation↗

Lung disease due to alpha 1-antitrypsin deficiency.

The association between alpha 1-antitrypsin deficiency and heritable emphysema was discovered in 1963. Subsequent epidemiologic evidence suggested that a serum alpha 1-antitrypsin level of 11 mumol/L (about 80 mg/dL by the still-used "commercial standard"), which is about 35% of the normal level, represents a "threshold" value, below which the risk of developing emphysema is increased and above which the emphysema risk is not increased. Recently, the ability to isolate and purify the alpha 1-antitrypsin protein from human blood has made "specific" augmentation therapy possible. Intravenous infusion of alpha 1-antitrypsin raises serum and alveolar levels above the putative thresholds, but clinical efficacy (i.e., decreased rate of decline in lung function and/or improved survival) remains presumptive. Based on available evidence, the American Thoracic Society recommends augmentation therapy for individuals with both a documented severe deficiency of alpha 1-antitrypsin and fixed airflow obstruction.

Airway Obstruction↗

Surfactant downregulates synthesis of DNA and inflammatory mediators in normal human lung fibroblasts.

The initial inflammatory event in the adult respiratory distress syndrome (ARDS) is followed by fibroproliferation and a cascade of fibroblast-derived mediators. Because lung fibroblasts may be exposed to surfactant as well as inflammatory cytokines during ARDS, we hypothesized that surfactant might modulate fibroblast activity. We previously demonstrated that surfactant inhibited production of inflammatory cytokines from endotoxin-stimulated human alveolar macrophages. In the current study the effects of surfactant on normal human lung fibroblast proliferative capacity and mediator production were examined. Both synthetic (Exosurf) and natural (Survanta) surfactant inhibited fibroblast [3H]thymidine incorporation. Examination of pre-S-phase events indicated stimulation of the immediate response gene, c-fos, and no effect on the G1/S cyclin, cyclin D1, suggesting that the surfactant block occurred elsewhere before S phase. The antioxidant N-acetyl-L-cysteine (NAC), like surfactant, inhibited [3H]thymidine incorporation. Furthermore, menadione, a generator of intracellular H2O2, stimulated fibroblast [3H]thymidine incorporation, and this was inhibited by surfactant. Interleukin-1 (IL-1)-stimulated secretion of the inflammatory mediators, IL-6 and prostaglandin E2, was also inhibited by surfactant. These data suggest that surfactant may modify lung fibroblast participation in ARDS sequelae by downregulating DNA synthesis and secondary inflammatory mediator production.

Antioxidants↗

Surfactant suppresses NF-kappa B activation in human monocytic cells.

In addition to biophysical properties, pulmonary surfactant has immunomodulatory activity. We previously demonstrated that both synthetic (Exosurf) and modified natural surfactant (Survanta) downregulated endotoxin-stimulated inflammatory c ytokine mRNA levels and protein products (tumor necrosis factor-alpha [TNF], interleukin-1-beta [IL-1], interleukin-6 [IL-6]) in human alveolar macrophages. In this study, we report that both Exosurf and Survanta suppress TNF mRNA and secretion (85 +/- 4% mean percent inhibition +/- SEM by Exosurf; 71 +/- 6% by Survanta) by endotoxin-stimulated THP-1, a human monocytic cell line. Because surfactant downregulated inflammatory cytokine production similarly in both normal human alveolar macrophages and the THP-1 cell line, we used this cell line to investigate whether surfactant affected transcriptional mechanisms. Specifically, we examined nuclear factor-kappa B (NF-kappa B) activation because it is crucial in transcriptional regulation of many inflammatory cytokine genes including TNF, IL-1, and IL-6. Electrophoretic mobility shift assays showed that both surfactants decreased activation of NF-kappa B. The presence of both p65 and p50 NF-kappa B components in LPS-activated THP-1 cells was confirmed by specific antibody induction of supershifts in mobility assays. These results are the first to suggest that surfactant's suppressive effects on inflammatory cytokine production may involve transcriptional regulation through inhibition of NF-kappa B activation.

Base Sequence↗