The effect of solvent dynamics on the low frequency collective motions of DNA in solution and unoriented films.

Infrared spectroscopy is used to probe the dynamics of in vitro samples of DNA prepared as solutions and as solid unoriented films. The lowest frequency DNA mode identified in the far-infrared spectra of the DNA samples is found to shift in frequency when the solvent influence in the hydration shell is altered. The lowest frequency mode also has characteristics that are similar to beta-relaxations identified in other glass forming polymers.

Urinary desmosine as a biomarker in acute lung injury.

Acute lung injury (ALI) is a complex disorder associated with an acute inflammatory response thought to contribute to tissue injury. Desmosine, a cross-linking amino acid present in elastin, is released during matrix degradation and cleared by the kidney. Results from animal models and human disease studies have suggested that ALI is associated with the release of desmosine, resulting in increased urinary desmosine. A radioimmunoassay was used to monitor urinary desmosine levels over 10 days in ten patients with ALI. The concentration of desmosine was measured with and without acid hydrolysis. Baseline urinary desmosine was increased in two of ten patients. The concentration of desmosine at baseline did not appear to be related to age, gender, neutrophil elastase (NE)/alpha(1)-antiprotease complex concentration or P(a)O(2)/F(i)O(2) ratio. No meaningful changes in desmosine levels were noted after removal from mechanical ventilation. Baseline desmosine concentrations did not appear to correlate with the risk of death. The limited sensitivity, predictive correlations and dynamic modulation would suggest that urine desmosine has a limited role as a biomarker for ALI. Hydrolysis of urine samples appears necessary for optimal measurement of urine desmosine.

The influence of chain dynamics on the far-infrared spectrum of liquid methanol.

Far-infrared-absorption spectroscopy is used to investigate the low-frequency (

The influence of chain dynamics on the far-infrared spectrum of liquid methanol-water mixtures.

Far-infrared-absorption spectroscopy has been used to study the low-frequency (

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.

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.

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.

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.

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).

Polytopic anomalies with agenesis of the lower vertebral column.

We describe clinical, pathological and radiological findings in 15 cases of sporadic and familial lower spine agenesis with additional anomalies of the axial skeleton and internal organs and speculate about the cause and pathogenesis of this malformation complex. We show that all of these findings are defects of blastogenesis, originate in the primary developmental field and/or the progenitor fields, thus representing polytopic field defects. This concept appears applicable in our cases and makes such terms such as "caudal regression syndrome" or "axial mesodermal dysplasia spectrum" redundant.

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.

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.

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.

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.

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.