Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations.

Breath biomarkers have the potential to offer information that is similar to conventional clinical tests or they are entirely unique. Preliminary data support the use of breath biomarkers in the study of liver disease, in particular non-alcoholic fatty liver disease (NAFLD). It was evaluated whether breath ethanol, ethane, sulfur compounds and acetone would be associated with hepatic histopathology amongst morbidly obese patients presenting for bariatric surgery. Breath samples were collected during a preoperative visit and compared with liver biopsies obtained during the surgery. A Student's two-tailed t-test was used to compare differences between the two groups. Linear regression was used to analyse associations between the concentrations of breath molecules and independent predictor variables. It was found that breath ethanol, ethane and acetone can be useful biomarkers in patients with NAFLD. In particular, breath ethanol can be associated with hepatic steatosis, and breath acetone can be associated with non-alcoholic steatohepatitis.

Abnormal exhaled ethane concentrations in scleroderma.

Scleroderma (systemic sclerosis) is a chronic multisystem autoimmune disease in which oxidative stress is suspected to play a role in the pathophysiology. Therefore, it was postulated that patients with scleroderma would have abnormally high breath ethane concentrations, which is a volatile product of free-radical-mediated lipid peroxidation, compared with a group of controls. There was a significant difference (p<0.05) between the mean exhaled ethane concentration of 5.27 pmol ml(-1) CO(2) (SEM=0.76) in the scleroderma patients (n=36) versus the mean exhaled concentration of 2.72 pmol ml(-1) CO(2) (SEM=0.71) in a group of healthy controls (n=21). Within the scleroderma group, those subjects taking a calcium channel blocker had lower ethane concentrations compared with patients who were not taking these drugs (p=0.05). There was a significant inverse association between lung diffusion capacity for carbon monoxide (per cent of predicted) and ethane concentration (b=-2.8, p=0.026, CI=-5.2 to -0.35). These data support the presence of increased oxidative stress among patients with scleroderma that is detected by measuring breath ethane concentrations.

Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection.

BACKGROUND: Obliterative bronchiolitis (OB) remains one of the leading causes of death in lung transplant recipients after 2 years, and acute rejection (AR) of lung allograft is a major risk factor for OB. Treatment of AR may reduce the incidence of OB, although diagnosis of AR often requires bronchoscopic lung biopsy. In this study, we evaluated the utility of exhaled-breath biomarkers for the non-invasive diagnosis of AR. METHODS: We obtained breath samples from 44 consecutive lung transplant recipients who attended ambulatory follow-up visits for the Johns Hopkins Lung Transplant Program. Bronchoscopy within 7 days of their breath samples showed histopathology in 21 of these patients, and we included them in our analysis. We measured hydrocarbon markers of pro-oxidant events (ethane and 1-pentane), isoprene, acetone, and sulfur-containing compounds (hydrogen sulfide and carbonyl sulfide) in exhaled breath and compared their levels to the lung histopathology, graded as stable (non-rejection) or AR. None of the study subjects were diagnosed with OB or infection at the time of the clinical bronchoscopy. RESULTS: We found no significant difference in exhaled levels of hydrocarbons, acetone, or hydrogen sulfide between the stable and AR groups. However, we did find significant increase in exhaled carbonyl sulfide (COS) levels in AR subjects compared with stable subjects. We also observed a trend in 7 of 8 patients who had serial sets of breath and histopathology data that supported a role for COS as a breath biomarker of AR. CONCLUSIONS: This study demonstrated elevations in exhaled COS levels in subjects with AR compared with stable subjects, suggesting a diagnostic role for this non-invasive biomarker. Further exploration of breath analysis in lung transplant recipients is warranted to complement fiberoptic bronchoscopy and obviate the need for this procedure in some patients.

Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis.

OBJECTIVES: Similarities between histological features of alcoholic hepatitis and obesity-related liver disease suggest a common pathogenic mechanism. Because intestinal bacteria can produce ethanol, it is conceivable that intestinally derived alcohol may contribute to fatty liver disease. An indirect way of measuring endogenous ethanol is to measure the breath ethanol concentration. In a previous study in ob/ob mice, breath ethanol decreased with a course of non-absorbable antibiotics, suggesting that the ethanol is derived from intestinal bacterial flora. The aims of this study were 1) to determine whether alcohol can be detected in the breath of human subjects, and 2) to assess whether there is any correlation between ethanol and obesity in patients with nonalcoholic steatohepatits (NASH) and control subjects without known liver disease. METHODS: Breath ethanol concentration was determined in 21 patients with biopsy-proven NASH and in 10 control subjects by gas chromatography. An abnormal breath ethanol level was defined as two standard deviations above the mean value of the breath ethanol of lean controls. RESULTS: Minute quantities of ethanol were detected in the breath of human subjects who had not consumed alcohol in the recent past. Patients who were obese were more likely to have higher breath ethanol concentrations. Women also had higher breath alcohol than men. However, there was no difference between patients with NASH and controls. Severity of liver disease, as evidenced by cirrhosis, did not influence the breath ethanol concentration. CONCLUSIONS: Higher breath ethanol concentrations are observed in obese subjects than in leaner ones. It is possible that intestinally derived ethanol may contribute to the pathogenesis of NASH.

Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis.

BACKGROUND & AIMS: Similarities in the hepatic responses to obesity and ethanol exposure suggest that these conditions evoke common pathogenic mechanisms. Thus, it is possible that ethanol exposure is increased in obesity. Given that intestinal bacteria can produce ethanol, the aim of this study was to determine if the intestinal production of ethanol is increased in obesity. METHODS: Breath was collected from genetically obese, ob/ob male C57BL/6 mice and lean male littermates at different ages (14, 20, and 24 weeks) and times of the day (9 AM, 3 PM, and 9 PM). Obese mice (24 weeks old) were then treated with neomycin (1 mg/mL) for 5 days, and sampling was repeated. RESULTS: Breath collected in the morning from 24-week-old obese mice had a higher ethanol content than breath from their lean littermates (271 vs. 78 pmol/mL CO(2); P < 0.0001). Subsequent studies in 14- and 20-week-old mice showed that exhaled ethanol increased with age in obese (from 26 to 107 pmol/mL CO(2); P < 0. 002) but not lean (29 and 12 pmol/mL CO(2)) mice and was greater in older obese mice than in older lean mice (P < 0.0006). Obese mice showed a diurnal increase in breath ethanol in the morning that decreased through the afternoon and evening (107 to 33 to 13 pmol/mL CO(2)). Neomycin treatment decreased morning breath ethanol levels by 50% (from 220 to 110 pmol/mL CO(2); P < 0.0003). CONCLUSIONS: Even in the absence of ethanol ingestion, ethanol can be detected in exhaled breath. In obesity, an age-related increase in breath ethanol content reflects increased production of ethanol by the intestinal microflora. Hence, intestinal production of ethanol may contribute to the genesis of obesity-related fatty liver.

Organizational features affecting the use of coercion in the administration of psychiatric care.

Historically, the use of coercion in psychiatric hospital admissions, and research on such use, have reflected social circumstances that impact on psychiatric care. Currently, the social emphasis on cost-saving in the U.S. and corresponding shifts in the organization, financing, and management of psychiatric and mental health care, have begun to affect research on the use of coercion in psychiatric admissions. Such research has begun to incorporate hospital organizational dynamics which affect the use of coercion in these admissions. The authors propose that this emphasis should be expanded into a comprehensive research agenda that examines the most pertinent organizational features affecting the use of coercion in psychiatric hospital admissions.

Interdisciplinary documentation of patient education: how collaboration can effect change.

Changing healthcare trends are affecting all healthcare providers today, including those at Hillside Rehabilitation Hospital. Computerizing the interdisciplinary documentation of patient information was one change Hillside's leaders implemented to remain competitive and cost-effective. The benefits of moving from a handwritten documentation system to a computerized system were many. However, unforeseen difficulties with retrieving data became evident because the system was not developed to accommodate information about patient education. Through interdisciplinary collaboration, staff identified areas for improvement and made changes to the documentation process. They developed a "traveling card" for documenting patient education and then met a new set of challenges. The new documentation system met departmental and Joint Commission on Accreditation of Healthcare Organizations requirements for comprehensive patient education and documentation.

A new immunocompetent murine model for oral cancer.

OBJECTIVE: To develop and characterize a new immunocompetent murine model that attempts to parallel the clinical and biological nature of head and neck cancer. DESIGN: The growth rate and histologic characteristics of the SCC VII/SF cell line were initially determined in tissue culture experiments. Animal experiments were subsequently performed on C3H/HeJ mice. Using direct injection, 5 x 10(5) SCC VII/SF cells were delivered to the floor of the mouth of each animal. Animals were killed after 1, 2, and 3 weeks, and tumor growth, invasion, and regional and distant metastases were evaluated. RESULTS: Squamous cell carcinomas that could be palpated and measured externally were identified in the floor of the mouth of C3H/HeJ mice after 5 to 7 days. Local invasion into the mylohyoid musculature and mandible was present. Cervical lymph node and pulmonary metastases were identified between 2 and 3 weeks. CONCLUSIONS: This study introduces a new oral cancer animal model that shows initial locoregional tumor invasion, direct extension into the neck, early cervical metastases, and pulmonary metastases. These clinical and histopathologic attributes reflect the biological behavior and tumor progression seen in human oral cancer and therefore provide a model for clinically applicable research for primary and metastatic head and neck cancer.

Combination gene therapy for oral cancer in a murine model.

Combination therapy involving adenovirus-mediated transfer of the genes for herpes thymidine kinase (tk) and murine interleukin 2 (mIL-2) was used to treat head and neck cancer in C3H/HeJ mice. Tumors were generated by transcutaneous injection of 5 X 10(5) murine squamous carcinoma cells into the floor of the mouth of these syngeneic mice. After 1 week, recombinant adenoviral vectors containing both therapeutic and control genes in various combinations were injected directly into the established tumors, and subsequently all mice were administered ganciclovir twice daily (25 mg/kg) for 6 days. Animals receiving either tk alone or tk + mIL-2 demonstrated significant tumor regression compared to mIL-2 alone or control vector-treated mice (P < 0.008). Mice receiving both tk + mIL-2, however, also demonstrated a significantly greater regression of tumors compared to those treated with tk alone (P<0.008), indicating a synergistic effect of the combination gene therapy. This synergism was confirmed in survival studies because tk + mIL-2 treated mice showed increased survivals (P=0.0002). Clinical and microscopic exam of regional surrounding tissues and distant organs showed no evidence of cytotoxicity for representative animals in each experimental group. These results suggest that combination tk and mIL-2 gene therapy may provide a powerful new modality for the treatment of head and neck cancer.

Nutritional status: a basic 'vital sign'.

The purpose of this article is to alert and inform the home healthcare nurse about the national focus on the unacceptably high levels of malnutrition in the elderly; its significance in patient outcome; the effort of the Nutrition Screening Initiative to help all healthcare professionals incorporate routine nutrition screening and intervention activities into healthcare practice; and the simple screening tools available to assist in evaluations.