The value of bronchoalveolar lavage for discrimination between healthy and diseased individuals.

BACKGROUND: Bronchoalveolar lavage (BAL) is standard diagnostic procedure. Procedural recommendations have been made by pneumological societies including normal values for interpretation of BAL cytology. These normal values derive from small studies in healthy volunteers and have never been analysed for their sensitivity and specificity. OBJECTIVES: This study aims to analyse sensitivity and specificity of these normal values by assessing lavage cell composition in healthy and diseased individuals. METHODS: More than 6000 BAL were retrospectively analysed for their cellular distribution including BALs of 250 healthy individuals. All BALs were obtained under similar conditions. RESULTS: Bronchoalveolar lavage cytology of healthy individuals mirrors data from previous studies with smoking being the most important manipulator of BAL cytology. Analyses of proposed normal values demonstrate specificity between 80% and 95%, whereas sensitivity ranges between 35% and 65%. Using different mathematical models, a value summing up the differences to ATS-proposed normal values of the cytological pattern was found to best discriminate between healthy and diseased individuals with a sensitivity of nearly 60% with a predefined specificity of 95%. CONCLUSION: In summary, our analysis confirmed prior results for healthy volunteers and enlarged these findings by analysing sensitivity and specificity of lavage results in an independent validation cohort of diseased individuals. Thereby, the study may influence the acceptance of BAL in the diagnostic workup of individuals with pulmonary diseases. Additionally, the study proposes a novel value that facilitates lavage interpretation and may therefore be useful in further studies.

[Sarcoidosis]. / Sarkoidose.

Sarcoidosis is a rare granulomatous disease mainly affecting lymph nodes and the lungs but joints, bones, muscles and other organs can also be affected. Sarcoidosis therefore represents an important differential diagnosis to various rheumatic diseases. For the diagnosis and differential diagnostic clarification, bronchoscopy including endobronchial ultrasound-guided fine needle aspiration of mediastinal and hilar lymph nodes represent the main procedures. Because of the high spontaneous remission rate initiating a therapy requires a therapeutic goal defined by sarcoidosis-associated functional organ impairment, especially for acute sarcoidosis. Cortisone represents the most commonly administered medication whereas methotrexate and azathioprine are well-established second-line medications. Antibodies which neutralize tumor necrosis factors (TNF) are a potential third-line therapy.

[New Pathogenetic Concepts and Early Pharmacological Studies in Sarcoidosis]. / Neue pathogenetische Konzepte und frühe pharmakologische Studien bei der Sarkoidose.

The etiology of sarcoidosis is still elusive, yet there has been considerable progress in various areas of basic and clinical research. This review focuses on mechanisms of granuloma formation and on new findings in autoimmunity and genetics of sarcoidosis. A new promising concept arose, where serum amyloid A and/or mycobacterial antigens serve as nidus for granuloma formation. Furthermore, autoimmunity in sarcoidosis was neglected for a long time, yet new studies found autoantigens and abnormalities in antigen presentation in sarcoidosis. Last but not least, large genome-wide association studies discovered several new predisposing genes, leading to new hypotheses on pathomechanisms of sarcoidosis.In the second part, we focus on ongoing or recently completed clinical-pharmacological studies in patients with sarcoidosis: Positive studies were published in well characterized and homogenous subcohorts of sarcoid patients. Several drugs have shown a positive effect on sarcoidosis-associated fatigue, on sarcoidosis of the skin and on pulmonary hypertension in sarcoid patients. It seems that the generation of clinically closely defined subcohorts is necessary to achieve positive outcomes in studies on sarcoidosis.

[Diagnosis and treatment of sarcoidosis. Current standards]. / Diagnostik und Therapie der Sarkoidose. Was ist gesichert?

Sarcoidosis is a granulomatous disease that mainly affects the lungs and intrathoracic lymph nodes; however, virtually any organ can be affected. As an orphan disease, recommendations are mainly based on observational or small randomized studies as well as experts' opinion. Diagnosing sarcoidosis requires proof of non-necrotizing granulomas in patients with a compatible symptomatic pattern and the exclusion of other granulomatous diseases. Granulomas can be detected best in the lungs or intrathoracic lymph nodes. Therefore, bronchoscopy and endobronchial ultrasound with biopsies of lymph nodes are the major tools to diagnose sarcoidosis. Frequently, close follow-up and symptomatic therapy are sufficient to allow for spontaneous resolution. In case of functional organ impairment, cardial or CNS involvement, or other complications, steroid therapy is necessary with a starting dose of 0.5 mg/kg body weight that should be tapered-off over 6-12 months. Steroid-refractory disease can be treated by adding methotrexate or azathioprine, two drugs long known in sarcoidosis treatment. Monoclonal antibodies against TNF and lung transplantation are further therapeutic options.

[Dialysis and ultrafiltration therapy in patients with cardio-renal syndrome: recommendations of the working group "heart-kidney" of the German Cardiac Society and the German Society of Nephrology]. / Dialyse- und Ultrafiltrationsverfahren bei kardio-renalem Syndrom. Empfehlung der Arbeitsgemeinschaft "Herz--Niere" der Deutschen Gesellschaft für Kardiologie--Herz- und Kreislaufforschung e.V. und der Deutschen Gesellschaft für Nephrologie e.V.

Renal failure is common in patients with severe heart failure. This complex pathophysiological interaction has been classified as cardio-renal syndrome. In these patients hydropic decompensation is the main cause of hospitalization. In patients with refractory heart failure, characterized by diuretic resistance and congestion due to volume overload, ultrafiltration has to be considered. In acute decompensated heart failure with worsening of renal function, extracorporeal ultrafiltration is the preferred treatment modality. On the other hand, patients suffering from chronic decompensated heart failure, particularly patients with ascites, will profit from the treatment specific advantages of peritoneal ultrafiltration. Prerequisite for an optimized care of patients with cardio-renal syndrome is the close collaboration among intensive care doctors, cardiologists and nephrologists.

[Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment]. / Interventionelle renale Sympathikusdenervation zur Behandlung der therapieresistenten Hypertonie.

This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time.

Marrow fibrosis and its relevance during imatinib treatment of chronic myeloid leukemia.

In chronic myeloid leukemia (CML), imatinib may reverse bone marrow fibrosis (MF). Whether the unfavorable prognosis of MF is also reversed and whether imatinib guarantees against evolution of MF are unclear as yet. Fifty-nine patients with Ph+ CML treated with > or = 400 mg imatinib/day were examined for MF in 6- to 12-month intervals. Imatinib effectively reversed initial MF (P<0.0005). However, during a follow-up period of up to 4.8 years, small foci with abnormal fiber increase (FFI) emerged in 8 of 30 pretreated and 6 of 29 non-pretreated patients. Patients with FFI showed a significantly lower probability of achieving a complete cytogenetic or major molecular response (36 versus 81%; P<0.007). During the further follow up, 57% of patients with FFI but none of the other patients suffered from full-blown MF (P=0.00005). None of the patients with FFI or MF showed a Janus kinase-2 mutation (V617F). Evolutions of FFI and MF were independent significant predictors of imatinib failure (P=0.0031), accelerated phase and death of patients (P=0.0001; multivariate analyses). Imatinib effectively reverses initial MF in CML, but neither eliminates its unfavorable prognosis nor guarantees completely against new evolution of MF.

Circulating ghrelin is sensitive to changes in body weight during a diet and exercise program in normal-weight young women.

Ghrelin is directly involved with short-term regulation of energy balance. Although circulating levels of ghrelin are elevated in anorexia nervosa and reduced in obesity, the role of ghrelin in regulating long-term energy balance in healthy women has not been investigated. We examined the effects of a 3-month energy deficit-imposing diet and exercise intervention on circulating ghrelin in normal-weight, healthy women. Body composition, resting metabolic rate, and serum ghrelin were measured at pre-, mid-, and postintervention in controls (n = 7), who performed no exercise, and exercising women who remained weight stable (n = 5) or lost weight (n = 10). Exercise training occurred five times per week, and subjects were fed a specific diet. Ghrelin significantly increased over time (770 +/- 296 to 1322 +/- 664 pmol/liter) in the weight-loss group compared with the controls and the weight-stable group (P < 0.05). Changes in ghrelin were negatively correlated with changes in body weight (r = -0.61; P < 0.05). Body fat, body weight, and resting metabolic rate significantly decreased in the weight-loss group before the increase in ghrelin. These findings suggest that ghrelin responds in a compensatory manner to changes in energy homeostasis in healthy young women, and that ghrelin exhibits particular sensitivity to changes in body weight.

Association between GSTM1*0 and squamous dysplasia of the esophagus in the high risk region of Linxian, China.

Individuals with specific phase I and phase II enzyme polymorphisms may be at increased risk for squamous cell carcinoma of the esophagus. However, to our knowledge there has been only one previous report that evaluates a potential role for these polymorphisms in increasing risk for preneoplastic squamous lesions of the esophagus. To explore this further, we examined polymorphisms in CYP1A1, CYP2E1, GSTM1 and GSTT1, both independently and in combination, for potential associations with the risk of biopsy-proven squamous dysplasia of the esophagus in asymptomatic adults from Linxian, a high risk region in China. Cases consisted of 56 individuals from an esophageal cancer screening study with an endoscopic biopsy diagnosis of mild or moderate squamous dysplasia. Each case was matched on age (+/- 1 year) and gender to a control. Controls were defined as screening study participants with an endoscopic biopsy diagnosis of normal mucosa or esophagitis. DNA was extracted from frozen cell samples obtained by cytologic balloon examination and genotyped using standard methods. Individuals who were GSTM1 null (homozygous for GSTM1*0) were found to have a tendency for an increased risk of esophageal squamous dysplasia (odds ratio=2.6, 95% CI, 0.9-7.4). No excess risks were observed for inheritance of other putative at risk genotypes CYP1A1*2B, CYP2E1*6 or GSTT1*0. The risk associated with the inheritance of combined genotypes was not significantly different than the risk estimates from the univariate analysis. These results are consistent with the notion that exposure to environmental carcinogens that are detoxified by GSTM1, such as polycyclic aromatic hydrocarbons, may contribute to the etiology of esophageal cancer in Linxian.

A Spectroscopic Redshift for the Cl 0024+16 Multiple Arc System: Implications for the Central Mass Distribution.

We present a spectroscopic redshift of z=1.675 for the well-known multiply lensed system of arcs seen in the z=0.39 cluster Cl 0024+16. In contrast to earlier work, we find that the lensed images are accurately reproduced by a projected mass distribution which traces the locations of the brightest cluster elliptical galaxies, suggesting that the most significant minima of the cluster potential are not dynamically erased. The averaged mass profile is shallow and consistent with predictions of recent numerical simulations. The source redshift enables us to determine an enclosed cluster mass of M(<100 kpc h-1&parr0;=1.11+/-0.03x1014 h-1 M middle dot in circle (Omega=1) and a mass-to-light ratio of M&solm0;LB(<100 kpc h-1&parr0;=320+/-30 h &parl0;M&solm0;LB&parr0; middle dot in circle (virtually independent of curvature), after correction for passive stellar evolution. The arc spectrum contains many ionized absorption lines and closely resembles that of the local Wolf-Rayet galaxy NGC 4217. Our lens model predicts a high magnification ( approximately 20) for each image and identifies a new pair of multiple images of a galaxy at a predicted redshift of z=1.3.

Use of the Watson-Glaser Critical Thinking Appraisal with BSN students.

The complexity and changing nature of nursing today requires proficiency in thinking skills to ensure knowledgeable, confident, creative, and sensitive decisions regarding client care. Nurse educators are faced with the task of promoting educational strategies to develop the abilities of nursing students to think critically in all health care settings (1). However, a lack of consensus on what characterizes critical thinking leads to difficulty in the development of instruments for adequate measurement. It is important to decide on a definition of critical thinking that faculty support and are willing to use in practice. The term is diversely defined in the literature. For example, Alfaro-LeFevre states that critical thinking in nursing "entails purposeful, goal directed thinking; aims to make judgments based on evidence (fact) rather than conjecture (guesswork); is based on principles of science and scientific method; requires strategies that maximize human potential and compensate for problems caused by human nature" (2). The authors of this study use a definition by Paul: "thinking about your thinking while you are thinking in order to make your thinking better, more clear, more accurate, more defensible" (3). The authors believe that the development and/or enhancement of critical thinking ability must be the result of conscious, deliberate activity throughout the nursing program. As the student matures, the ability to think critically will be manifested in decision making that reflects accurate assessment and resolution of problems. The nursing faculty selected an instrument to evaluate the critical thinking abilities of baccalaureate nursing students that had strong reliability and validity documented in the nursing literature: the total and subtest scores of the Watson-Glaser Critical Thinking Appraisal (WGCTA), Form A (4). The instrument was deemed to be congruent with the definition of critical thinking supported by the faculty.

Use of DNA amplification for diagnosis of cytomegalovirus enteritis after intestinal transplantation.

BACKGROUND & AIMS: Intestinal transplantation is a feasible therapy for patients with short-bowel syndrome. However, cytomegalovirus (CMV) enteritis can cause complications. The aim of this study was to investigate the value of polymerase chain reaction (PCR)-based detection methods for CMV in the management of patients with small bowel transplants. METHODS: Comparative evaluation of PCR with histopathology, shell-vial assay, and tube culture of intestinal biopsy specimens was used for the diagnosis of CMV enteritis in 21 patients. RESULTS: Ten patients experienced 21 episodes of CMV enteritis, diagnosed by histopathology, virology, or both. PCR had a sensitivity and specificity of 96% and 69%, respectively, compared with traditional methods, whereas the positive and negative predictive values were 35% and 99%, respectively. Three+ and 4+ signals corresponded to a specificity of 91% and positive predictive value of 59%, respectively. CMV was detected by PCR a median of 11 days (range, 0-32) earlier than other methods and lasted a median of 40 days (range, 21-80) in the 13 episodes, which became PCR-negative and in those patients who developed asymptomatic infection. In 8 episodes, CMV by PCR never became negative and was associated with a relapse of disease confirmed by other methods. CONCLUSIONS: PCR is a sensitive method for the early detection of CMV in intestinal biopsy specimens and can be used for preemptive therapy after intestinal transplantation.

Na+/H+ exchange during an oral glucose challenge in patients with essential hypertension.

To determine the effects of an oral glucose challenge on cellular Na+/H+ exchange in vivo we measured plasma glucose concentrations, plasma insulin concentrations, plasma C-peptide concentrations, arterial blood pressure, cytosolic pH (pHi) and cellular Na+/H+ exchange in 24 patients with essential hypertension (HT) and 41 age-matched healthy normotensive control subjects (NT) during a standardized oral glucose tolerance test. Under resting conditions, the plasma glucose concentrations, plasma insulin concentrations, plasma C-peptide concentrations and Na+/H+ exchange activity were significantly higher in HT compared with NT (P < 0.05 in each case). A significant increase in lymphocytic Na+/H+ exchange activity was only seen in NT (resting 0 h: (4.23 +/- 0.2) x 10(-3) pHi/s; mean +/- S.E.M.; 1 h after glucose administration: (6.00 +/- 0.56) x 10(-3) pHi/s; 2 h after glucose administration: (6.65 +/- 0.64) x 10(-3) pHi/s; P = 0.0003 by Friedman's two-way ANOVA), but not in HT (resting 0 h: (6.07 +/- 0.36) x 10(-3) pHi/s; 1 h after glucose administration: (6.72 +/- 1.02) x 10(-3) pHi/s; 2 h after glucose administration: (6.71 +/- 0.62) x 10(-3) pHi/s; P = 0.7470). During an oral glucose challenge the systolic (P < 0.0001) and diastolic (P < 0.0001) blood pressure significantly decreased in HT but not in NT. Essential hypertension shows abnormal in vivo regulation of Na+/H+ exchange and blood pressure following oral glucose intake.

Time to detection of cytomegalovirus (CMV) DNA in blood leukocytes is a predictor for the development of CMV disease in CMV-seronegative recipients of allografts from CMV-seropositive donors following liver transplantation.

In 35 cytomegalovirus (CMV)-seronegative recipients of livers from CMV-seropositive donors, 32 (91%) developed CMV infection and 24 of them (75%) experienced disease. Polymerase chain reaction for CMV DNA in leukocytes had the best positive and negative predictive values for the development of disease within 2 months from transplantation, and shell-vial or tube culture viremia was the best predictor thereafter. In patients who developed CMV disease, CMV DNA was first detected at 46 days (median; range, 13-128) after transplantation, significantly earlier than the 77 days (range, 46-174) for those who did not develop CMV disease (P = .02). By a semiquantitative method, the CMV DNA level in the first positive sample did not predict disease development. However, the maximum CMV DNA level during infection was significantly higher in patients who developed CMV disease. In CMV-seronegative recipients of livers from CMV-seropositive donors, the time to DNA positivity following transplantation may predict disease progression and be useful as a guide for the initiation of preemptive therapy.

Use of cultural themes in promoting health among Southeast Asian refugees.

PURPOSE: Vietnamese, Cambodian, and Hmong refugee populations in the United States face serious physical and psychosocial health issues. Literature on these populations is largely descriptive of illnesses and of cultural beliefs or behavior patterns related to illness. There is minimal literature linking beliefs and behaviors to the underlying cultural themes. The purpose of this paper was to search the literature for cultural themes from which culturally relevant health promotion strategies could be designed. SEARCH METHODS: Literature was reviewed from the fields of health, social, and political science, history, and Southeast Asian folklore. Search methods included review of 147 writings from library and MEDLINE search and 123 interviews with refugees and key professionals in the field. This manuscript includes 106 selections as well as content from 93 interviews. FINDINGS AND CONCLUSIONS: From the literature emerged two cultural themes common to these population, kinship solidarity and the search for equilibrium. The use of these cultural themes as carriers of health messages is suggested. Examples of ways to link the message with the cultural theme are presented, including the use of folklore, recognition of cultural illnesses, and use of cultural knowledge in addressing new situations such as inner city urban survival. Cultural themes are a means of conveying health messages addressing such issues as transition in family structure, depression, and substance abuse.

Circulating immediate-early mRNA in patients with cytomegalovirus infections after solid organ transplantation.

Polymerase chain reaction (PCR)-based amplification of cytomegalovirus (CMV) DNA has been demonstrated to be a sensitive tool for the diagnosis of CMV infection. However, PCR can detect the presence of viral DNA in some specimens from clinically asymptomatic patients. In an attempt to obviate this shortcoming, a reverse transcriptase-PCR-based assay (RT-PCR) was developed to look for CMV immediate-early (IE) mRNA in peripheral blood leukocytes from organ transplant recipients. The results of the PCR- and RT-PCR-based assays for CMV were correlated with clinical symptoms from 21 patients. Absence of circulating IE mRNA was associated with a lack of CMV-associated clinical symptoms in all 14 cases, irrespective of the presence or absence of CMV DNA. In contrast, all 7 RNA-positive samples were associated with CMV disease. Thus, RT-PCR appears to be more predictive than PCR for detection of clinically significant CMV disease in immunosuppressed patients.

Culture, stress and substance use in Cambodian refugee women.

Initial data were generated on the use of alcohol and other drugs by Cambodian refugee women and their families (N = 120) in two sites: Massachusetts and California. Information on frequency and situations surrounding use, and culturally specific use, was elicited. In those families where alcohol was perceived as a problem, the majority of problem drinkers were husbands. About 45% of the East Coast women, however, said they used alcohol for nervousness, stress, headaches, insomnia and pain. In addition, about 15% of the East Coast women reported that a family member used street drugs and was having dependency problems. While use of alcohol or street drugs was not perceived as problematic on the West Coast, over 58% reported using prescription drugs for self-treatment of illnesses other than those targeted by the prescription. When prescription drugs were misused by women, it was most frequently to get an altered state, or "street drug effect". Numerous stressors influence Cambodian women during the pressures of acculturation to the U.S. lifestyle. Some may turn to self-medication in the form of alcohol, prescription sleeping pills, or other drugs. A better understanding of how and why these women make coping choices is needed.

Cultural themes in family stress and violence among Cambodian refugee women in the inner city.

Cambodian refugee women frequently face the cumulative trauma of war experiences and cultural adaptation to the American inner-city environment. This qualitative study investigated cultural beliefs, coping strategies, and management of family stress among Cambodian refugee women living in the inner-city environment. Focused and open-ended interviews were conducted in the informants' homes using the Cambodian language. Stressful and violent events were managed by nonconfrontation and withdrawal. These two themes are hypothesized as the culturally identified means by which inner-city Cambodian refugee women control and harmonize situations of stress. Further study is needed to develop the theoretical base for developing culturally sensitive nursing intervention strategies with this high risk population.

Themes in managing culturally defined illness in the Cambodian refugee family.

The Cambodian (Khmer) refugee population in America is considered to be the Indochinese refugee population at highest risk for stress-related health problems resulting from traumatic physical and emotional experiences during the Khmer Rouge holocaust in this Southeast Asian country. In this study, koucharang, described as "thinking too much," was identified by informants as a culture-bound syndrome in response to the violence experienced in Cambodia. It is characterized by behavioral changes and somatic complaints. This study identified two cultural themes used by Cambodian families in the management of this disabling condition. The research is a follow-up from a prior study that examined cultural themes in health care decision making among Khmer women. This study of themes in family management of culturally defined illness was conducted with 120 Cambodian refugee women in Long Beach, California and Lowell, Massachusetts. These geographical areas were selected because the Khmer refugee population in America has relocated primarily to the low-income inner-city areas of southern California and Massachusetts. Nursing strategies for utilizing the identified cultural themes in intervening with the Cambodian family are identified. The community health nurse can build upon the strength of these themes and the resulting culturally dictated practices as he or she provides supportive counseling and health promotion to this highly traumatized population. The emotional risks to the community health nurse in working with the Cambodian refugee family are discussed in the context of maintaining self-integrity in the face of overwhelming tragedy.