Menoci: lightweight extensible web portal enhancing data management for biomedical research projects.

BACKGROUND: Biomedical research projects deal with data management requirements from multiple sources like funding agencies' guidelines, publisher policies, discipline best practices, and their own users' needs. We describe functional and quality requirements based on many years of experience implementing data management for the CRC 1002 and CRC 1190. A fully equipped data management software should improve documentation of experiments and materials, enable data storage and sharing according to the FAIR Guiding Principles while maximizing usability, information security, as well as software sustainability and reusability. RESULTS: We introduce the modular web portal software menoci for data collection, experiment documentation, data publication, sharing, and preservation in biomedical research projects. Menoci modules are based on the Drupal content management system which enables lightweight deployment and setup, and creates the possibility to combine research data management with a customisable project home page or collaboration platform. CONCLUSIONS: Management of research data and digital research artefacts is transforming from individual researcher or groups best practices towards project- or organisation-wide service infrastructures. To enable and support this structural transformation process, a vital ecosystem of open source software tools is needed. Menoci is a contribution to this ecosystem of research data management tools that is specifically designed to support biomedical research projects.

Optimising magnetic resonance imaging-based evaluation of the ossification of the medial clavicular epiphysis: a multi-centre study.

Evaluation of the ossification of the medial clavicular epiphysis plays a key role in forensic age estimation, particularly in determining whether the age of 18 has been attained. A key research objective in the forensic age estimation field at present is to establish non-X-ray methods for investigating the clavicle. This paper looks at the use of magnetic resonance imaging for evaluating the developmental state of the medial clavicular epiphysis. Clavicle specimens obtained from autopsies of 125 female and 270 male subjects aged from 10 to 30 were examined using a 3-T magnetic resonance scanner. One FFE-3D-T1 gradient echo sequence and one 2D-T2 turbo spin echo sequence were acquired. In each case, two investigators undertook a consensual determination of the ossification stage of the medial clavicular epiphysis using recognised classification systems. To determine intra-observer and inter-observer agreement, 80 clavicle specimens were subjected to repeat evaluation. We present statistics relating to the ossification stages. The inclusion of established sub-stages of clavicular ossification offers an additional option for determining whether a subject has attained the age of 18 which is applicable in both sexes. For both sexes, the minimum ages for ossification stages 4 and 5 allow conclusions to be drawn about a subject's age at a point in time lying several years in the past. Magnetic resonance imaging is a valid investigatory procedure for determining the ossification stage of the medial clavicular epiphysis. This paper makes a contribution to expanding the range of methods available for forensic age estimation.

Strength and endurance training in the treatment of lung cancer patients in stages IIIA/IIIB/IV.

PURPOSE: This randomized controlled trial tested the effects of a specially designed strength and endurance training on the independence and quality of life in lung cancer patients in stages IIIA/IIIB/IV during palliative chemotherapy. METHODS: Between August 2010 and December 2011, 46 patients were randomized into two groups receiving either conventional physiotherapy or special physiotherapeutic training. The Barthel Index served as primary endpoint. The secondary endpoints were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ C-30/LC-13) questionnaire, the 6-Minute Walk Test (6MWT), stair walking, the Modified Borg Scale, and muscle strength. Nonparametrical data were analyzed with the Wilcoxon and Mann-Whitney U test. For parametric, data student t tests were used. A p value of ≤.05 was accepted. RESULTS: Twenty-nine patients completed the trial (Intervention group (IG), n = 18; control group (CG), n = 11). Significant differences were detectable in the Barthel Index (IGmean = 92.08; CGmean = 81.67; p = .041), in single scores of the EORTC QLQ C-30/LC-13 questionnaire (physical functioning, p = .025; hemoptysis, p = .019; pain in arms or shoulder, p = .048; peripheral neuropathy, p = .050; cognitive functioning, p = .050), in the 6MWT, stair walking, strength capacity, and in the patient's dyspnoea perception during submaximal walking activities (IG > CG). CONCLUSION: According to these findings, lung cancer patients should receive enhanced physical activity intervention during palliative chemotherapy.

Self-sampling in the diagnosis of recurrent vulvovaginal candidosis.

OBJECTIVE: This study aimed to determine the accuracy and feasibility of self-sampling in patients suspected of having recurrent vulvovaginal candidosis (RVC). MATERIALS AND METHODS: Of 441 patients with symptoms suggestive of RVC presenting during an 8-year period (January 2000 to December 2007) at a dermatology clinic, 277 were instructed to perform weekly vaginal self-sampling for a period of up to 8 weeks. Demographic charactervistics, medical history, physical examination, culture results, and therapeutic efficacy were analyzed with Fisher exact, χ test, or Student t test. RESULTS: When only considering the results of the culture taken at consultation, 17.1% (20/117) of RVC cases could be confirmed. Positive cultures from self-sampling confirmed another 97 cases of RVC (82.9%). The sensitivity of a single Candida culture ranged from 18% to 53%, depending on the cutoff level of growth intensity of the yeast recovered. Specificity ranged from 97% to 100%, and the positive predictive value ranged from 92% to 100%. The number of positive cultures obtained was not associated with the duration of earlier vaginal complaints or with the efficacy of prophylactic treatment. Prophylactic treatment was equally effective in patients taking fluconazole once (8/13, 61.5%) or twice (48/74, 64.9%) a month, but treatment regimes were not randomized. CONCLUSIONS: The diagnosis of RVC can be improved dramatically by self-sampling, enabling a sooner start of adequate treatment. Multiple positive cultures were not associated with disease of longer duration or more severe disease and did not influence the response to prophylactic treatment.

Patients with cervical cancer: why did screening not prevent these cases?

OBJECTIVE: The objective of the study was to assess the screening history of women with cervical cancer and review normal cervical smears 5 years preceding the diagnosis. STUDY DESIGN: Cytological and histological results of 401 women treated for invasive cervical cancer between 1991 and 2008 at the Radboud University Nijmegen Medical Center were studied. Ninety-eight normal smears were reviewed. RESULTS: Of the 401 women, 269 (67%) received at least 1 invitation for the national screening program for cervical cancer (NCSP). One- third fell outside the target age of the NCSP. Seventeen percent never responded to the invitation(s). Twenty-one percent had 1 or more normal smears within 5 years preceding the diagnosis. After review, only 39% of those smears were reviewed as a normal smear. CONCLUSION: Half of the women with cervical cancer were never screened because of the limited target age range or nonattendance. Twenty-one percent had a normal smear within 5 years preceding the diagnosis, caused by interpretation and/or sampling errors.

[Illustrations of visceral referred pain. "Head-less" Head's zones]. / Illustrationen zum übertragenen Schmerz. Wie viel von Head steckt in den Head-Zonen?

Reviewing anatomical, physiological and neurological standard literature for illustrations of referred visceral pain only one type of illustration can frequently be found, which is referred to as Treves and Keith. In fact, the original illustration as a model for most current pictures stems from the German edition of Sir Frederick Treves' famous book "Surgical Applied Anatomy" from 1914, which was reillustrated for didactical reasons for the German readership. While neither Treves and Keith nor the German illustrator Otto Kleinschmidt ever published any work on referred pain this illustration must have been adapted or copied from older sources by the illustrator. Therefore the comprehensive systematic original works before 1914 were reviewed, namely those of Sir Henry Head and Sir James Mackenzie. Due to the name of the phenomenon in the German literature of Head's zones, the illustrations were expected to be based mainly on Head's work. However, a comparison of all available illustrations led to the conclusion that Kleinschmidt chiefly used information from Mackenzie as a model for his illustration. Due to the inexact reproduction of Mackenzie's work by the illustrator some important features were lost that had been reported by the original authors. These include the phenomenon of Head's maximum points, which nowadays has fallen into oblivion.Therefore current charts, based on the illustration by Kleinschmidt from 1914, lack experimental evidence and appear to be a simplification of the observational results of both Head's and Mackenzie's original systematic works.

Identification and partial characterization of angiogenesis bioactivity in the lower respiratory tract after acute lung injury.

Survival after acute lung injury (ALI) depends on prompt alveolar repair, a process frequently subverted by the development of granulation tissue within the alveolar airspace. Immunohistochemical examination of the intraalveolar granulation tissue confirmed that capillaries as well as myofibroblasts were the principal cellular constituents. We therefore hypothesized that angiogenesis factors would be present on the air-lung interface after ALI. To evaluate this hypothesis, bronchoalveolar lavage fluid from patients with ALI (n = 25) and patient controls (n = 8) was examined for angiogenesis bioactivity by its ability of induce endothelial cell migration. While lavage fluid from controls had no bioactivity, lavage fluid from 72% of patients with ALI promoted endothelial cell migration. Heparin affinity, ion exchange, and gel filtration chromatography resolved the bioactivity into at least two moieties. One appeared identical to the well characterized endothelial cell growth factor, basic fibroblast growth factor. The other was a 150-kD non-heparin binding protein that mediated endothelial cell migration and attachment in vitro, and the growth of new vessels in vivo. These data are consistent with the hypothesis that the growth of capillaries into the alveolar airspace results from angiogenesis factors present on the alveolar surface of the lung after ALI.

Role of mesenchymal cell death in lung remodeling after injury.

Repair after acute lung injury requires elimination of granulation tissue from the alveolar airspace. We hypothesized that during lung repair, signals capable of inducing the death of the two principal cellular elements of granulation tissue, fibroblasts and endothelial cells, would be present at the air-lung interface. Bronchoalveolar lavage fluid obtained from patients during lung repair induced both fibroblast and endothelial cell death, while fluid obtained at the time of injury or from patient controls did not. The mode of cell death for endothelial cells was apoptosis. Fibroblast death, while morphologically distinct from necrosis, also differed from typical apoptosis. Only proliferating cells were susceptible to the bioactivities in lavage fluid, which were trypsin sensitive and lipid insoluble. Histological examination of lung tissue from patients after lung injury revealed evidence of apoptotic cells within airspace granulation tissue. Our results suggest that cell death induced by peptide(s) present at the air-lung interface may participate in the remodeling process that accompanies tissue repair after injury.

Acute lung injury fibroblast migration and invasion of a fibrin matrix is mediated by CD44.

Fibrosis results when myofibroblasts invade the wound fibrin provisional matrix. Extracellular matrix receptors on the cell surface mediate cell adhesion, migration, and invasion. Recent work with transformed cells indicates that these cells use the cell surface matrix receptor CD44 for migration and invasion. In this study, we examine whether lung fibroblasts, isolated from patients dying with acute alveolar fibrosis, use CD44 to invade a fibrin matrix. Consistent with a role for CD44 in mediating fibroblast invasion and subsequent tissue fibrosis, immunohistochemical analysis of lung tissue from patients who died from acute alveolar fibrosis after lung injury reveals CD44-expressing mesenchymal cells throughout newly formed fibrotic tissue. PCR, Western, and immunoprecipitation analysis demonstrate that the 85-kD CD44 isoform is expressed by acute lung injury fibroblasts. Consistent with a role in mediating matrix adhesion and migration ultrastructurally, CD44 was found uniformly over the cell surface and was found densely labeling filopodia and lamellipodia, highly motile structures involved in cell migration. To determine if lung injury fibroblasts use CD44 to invade fibrin, a fibrin gel model of fibrosis was used. By blocking the function of CD44 with monoclonal antibodies, fibroblast invasion into a fibrin matrix was inhibited. To examine the mechanism by which CD44 mediates fibroblast invasion, the role of CD44 in fibroblast migration and adhesion was evaluated. Anti-CD44 antibody blocked fibroblast migration on the provisional matrix proteins fibronectin, fibrinogen, and hyaluronic acid. Additionally, fibroblast CD44 mediated adhesion to the provisional matrix proteins fibronectin, fibrin, and hyaluronic acid, but not to laminin, a component of the basement membrane. These findings support the hypothesis that fibroblast CD44 functions as an adhesion receptor for provisional matrix proteins and is capable of mediating fibroblast migration and invasion of the wound provisional matrix resulting in the formation of fibrotic tissue.

CD44-related chondroitin sulfate proteoglycan, a cell surface receptor implicated with tumor cell invasion, mediates endothelial cell migration on fibrinogen and invasion into a fibrin matrix.

Microvascular endothelial cell invasion into the fibrin provisional matrix is an integral component of angiogenesis during wound repair. Cell surface receptors which interact with extracellular matrix proteins participate in cell migration and invasion. Malignant cells use CD44-related chondroitin sulfate proteoglycan (CSPG) as a matrix receptor to mediate migration and invasion. In this study, we examine whether cell surface CSPG can mediate similar events in nonmalignant wound microvascular endothelial cells or whether use of CSPG for migration and invasion is a property largely restricted to malignant cells. After inhibiting CSPG synthesis with p-nitrophenyl beta-d xylopyranoside (beta-d xyloside), wound microvascular endothelial cells were capable of attaching and spreading on the surface of a fibrin gel; however, their ability to invade the fibrin matrix was virtually eliminated. To begin to examine the mechanism by which endothelial cells use CSPG to invade fibrin matrices, cell adhesion and migration on fibrinogen was examined. Endothelial cell adhesion and migration on fibrinogen were inhibited by both beta-d xyloside and after cleavage of chondroitin sulfate from the core protein by chondroitinase ABC. We have determined that wound microvascular endothelial cells express the majority of their proteoglycan as CSPG and that the CSPG core protein is immunologically related to CD44. PCR studies show that these cells express both the "standard" (CD44H) isoform and an isoform containing the variably spliced exon V3. In addition, anti-CD44 antibody blocks endothelial cell migration on fibrinogen. Affinity chromatography studies reveal that partially purified microvascular endothelial cell CSPG binds fibrinogen. These findings suggest that CD44-related CSPG, a molecule implicated in the invasive behavior of tumor cells, is capable of binding fibrinogen/fibrin, thereby mediating endothelial cell migration and invasion into the fibrin provisional matrix during wound repair.

Acute lung injury. Pathogenesis of intraalveolar fibrosis.

In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth-promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth-promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38-kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication.

Anthropometric approximation of body weight in unresponsive stroke patients.

BACKGROUND AND PURPOSE: Thrombolysis of acute ischaemic stroke is based strictly on body weight to ensure efficacy and to prevent bleeding complications. Many candidate stroke patients are unable to communicate their body weight, and there is often neither the means nor the time to weigh the patient. Instead, weight is estimated visually by the attending physician, but this is known to be inaccurate. METHODS: Based on a large general population sample of nearly 7000 subjects, we constructed approximation formulae for estimating body weight from simple anthropometric measurements (body height, and waist and hip circumference). These formulae were validated in a sample of 178 consecutive inpatients admitted to our stroke unit, and their accuracy was compared with the best visual estimation of two experienced physicians. RESULTS: The simplest formula gave the most accurate approximation (mean absolute difference 3.1 (2.6) kg), which was considerably better than the best visual estimation (physician 1: 6.5 (5.2) kg; physician 2: 7.4 (5.7) kg). It reduced the proportion of weight approximations mismatched by >10% from 31.5% and 40.4% (physicians 1 and 2, respectively) to 6.2% (anthropometric approximation). Only the patient's own estimation was more accurate (mean absolute difference 2.7 (2.4) kg). CONCLUSIONS: By using an approximation formula based on simple anthropometric measurements (body height, and waist and hip circumference), it is possible to obtain a quick and accurate approximation of body weight. In situations where the exact weight of unresponsive patients cannot be ascertained quickly, we recommend using this approximation method rather than visual estimation.

Neutralizing epitopes on the extracellular interferon gamma receptor (IFNgammaR) alpha-chain characterized by homolog scanning mutagenesis and X-ray crystal structure of the A6 fab-IFNgammaR1-108 complex.

The extracellular interferon gamma receptor alpha-chain comprises two immunoglobulin-like domains, each with fibronectin type-III topology, which are responsible for binding interferon gamma at the cell surface. The epitopes on the human receptor recognized by three neutralizing antibodies, A6, gammaR38 and gammaR99, have been mapped by homolog scanning mutagenesis. In this way, a loop connecting beta-strands C and C' in the N-terminal domain was identified as a key component of the epitopes bound by A6 and gammaR38, whereas gammaR99 binds to the C-terminal domain in a region including strands A and B and part of the large C'E loop. The epitope for A6 was confirmed in a crystal structure of a complex between a recombinant N-terminal receptor domain and the Fab fragment from A6, determined by X-ray diffraction to 2.8 A resolution. The antibody-antigen interface buries 1662 A2 of protein surface, including 22 antibody residues from five complementarity determining regions, primarily through interactions with the CC' surface loop of the receptor. The floor of the antigen binding cavity is formed mainly by residues from CDR L3 and CDR H3 while a surrounding ridge is formed by residues from all other CDRs except L2. Many potential polar interactions, as well as 13 aromatic side-chains, four in VL, six in VH and three in the receptor, are situated at the interface. The surface of the receptor contacted by A6 overlaps to a large extent with that contacted by interferon-gamma, in the ligand-receptor complex. However, the conformation of this epitope is very different in the two complexes, demonstrating that conformational mobility in a surface loop on this cytokine receptor permits steric and electrostatic complementarity to two quite differently shaped binding sites.

Polypharmacy among patients attending an AIDS clinic: utilization of prescribed, unorthodox, and investigational treatments.

The objective of this study was to describe the utilization and characteristics associated with the use of prescribed, over-the-counter, investigational, and unorthodox treatments among AIDS clinic patients. This report is derived from cross-sectional data obtained using structured telephone surveys. Study participants (n = 197) were recruited from the University of California, San Francisco, Medical Center AIDS clinic. One hundred eighty-nine participants (96%) received 1-24 prescription medications during the 3 months prior to interview. Those with an AIDS diagnosis received a relatively greater number of prescription drugs (p = 0.0001); an average of 5.6 prescribed medications were used by AIDS patients versus 4.8 among AIDS-related complex and 2.3 among asymptomatic patients. Thirty-one percent participated in drug trials during the 3 months before interview, including 18% who were in multiple studies. Twenty-nine percent used unorthodox treatments. Seventy-five (40%) received prescription medication from a provider other than their primary provider. A more advanced stage of illness was associated with the use of unorthodox treatments (p = 0.003): users of these treatments had a greater educational attainment than nonusers (p = 0.03) and were significantly less likely to report that their primary provider was aware of all the treatments they used (odds ratio = 2.1, p less than 0.03). We conclude that use of polypharmacy among some AIDS clinic patients is common, could create an increased risk for adverse drug reactions, and may affect clinical drug trials. Despite having decided to obtain care at a university-based clinic, many of the participants of this study also chose to receive unorthodox therapies and care from nonprimary medical providers.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs of acid-related disorders to a health maintenance organization.

BACKGROUND: Little is known about the economic impact of the acid-related disorders (ARDs), which include dyspepsia, gastritis, gastroesophageal reflux disease (GERD), and peptic ulcer disease (PUD), in managed care patient populations. OBJECTIVES: To describe the prevalence of medically attended ARDs, and their direct medical costs from the perspective of a large health maintenance organization (HMO). METHODS: A total of 1,550 ARDs subjects (age > or = 18 years), were randomly sampled from outpatient diagnosis and pharmacy databases of the Kaiser Permanente Medical Care Program of Northern California and verified by chart review. Five age- and gender-matched controls were identified per subject. One-year prevalence, excess annual costs, and initial 6-month costs for incident cases were estimated using the HMO cost accounting system. RESULTS: Total ARDs prevalence (5.8%) increases with advancing age. GERD is the most common ARD (2.9% overall prevalence). Annual per person attributable costs were $1,183, $471, and $431 respectively for PUD, GERD, and gastritis/dyspepsia. Excess inpatient costs for PUD explain its higher costs. Outpatient costs were somewhat higher for GERD ($279) than for PUD or gastritis/dyspepsia. Pharmacy costs were relatively low for each condition, in part because many patients were treated with generic cimetidine. Total annual HMO expenditures for ARDs were $59.4 million, with 40.6%, 36.8%, and 22.6% respectively for GERD, PUD, and gastritis/dyspepsia. CONCLUSIONS: Acid-related disorders, particularly GERD and PUD, contribute substantially to the direct costs of medical care in this managed care population.

Lung transplant pathology. A comparative study of pulmonary acute rejection and cytomegaloviral infection.

This article describes a comparative study performed to determine the histologic features of pulmonary rejection and cytomegaloviral (CMV) infection following lung transplantation. Rejection was defined clinically by findings of new pulmonary symptoms or radiographic changes or decreased oxygenation in the absence of documented infection in patients who were treated for rejection and improved. These patients also had negative CMV cultures. CMV infection was studied in a group of non-lung and non-bone marrow transplant patients and was defined by the presence of characteristic nuclear inclusions in lung biopsies. Ten rejection biopsies and nine CMV biopsies were examined. No histologic feature was unique to rejection, however; perivascular lymphocytic infiltrates occurred more frequently and more intensely in rejection than in CMV infection (p = 0.0029). Endothelialitis also occurred more frequently in rejection (p = 0.0331), but it was always seen in association with perivascular lymphocytic inflammation. In rejection, the inflammatory infiltrate was primarily perivascular, with extension into the interstitium in several cases. In contrast, CMV infection was characterized predominantly by interstitial inflammation with involvement of associated vessels. We conclude that although overlapping features are present in both processes, pulmonary rejection can be distinguished from CMV infection on the basis of histology.

A pharmacoeconomic model of divalproex vs. lithium in the acute and prophylactic treatment of bipolar I disorder.

BACKGROUND: Divalproex and lithium are the two most rigorously studied pharmacologic treatments for acute mania in bipolar I disorder in randomized, controlled trials. The differences between the drugs in their time course of onset, predictors of response, and side effects have potentially important pharmacoeconomic implications. METHOD: Utilizing data from published studies, the University of Cincinnati Mania Project, and a consensus panel of psychiatrists, we developed a decision-analytic model to estimate the costs of treating patients with bipolar I disorder, acutely and prophylactically, for 1 year with divalproex or lithium. RESULTS: In the overall group of patients with bipolar I disorder, initial treatment with divalproex led to costs that were 9% lower than costs for initial treatment with lithium. Cost savings associated with divalproex were greatest for patients with mixed mania and rapid cycling, whereas cost savings for patients with classic mania were greater for lithium. CONCLUSION: According to the decision-analytic model developed in this study, divalproex, possibly because of a more rapid rate of antimanic activity associated with oral loading, is a less costly treatment than lithium in the acute and prophylactic treatment of patients with bipolar I disorder over 1 year.

Single lung transplantation for severe emphysema.

UNLABELLED: Lung transplantation is effective therapy for patients with severe obstructive lung disease. We reviewed seven patients with severe emphysema (age, 48 +/- 5 years; forced expiratory volume in 1 second [FEV1] 0.76 +/- 0.26 liters) who received single-lung transplants (SLT) at our institution between August 1989 and September 1990. Studies to assess the adequacy of cardiac function before transplantation showed moderately reduced right ventricular function (by multiple gated acquisition, 34 +/- 6%), moderately elevated pulmonary artery pressure (25 +/- 3 mm Hg), and normal left ventricular function (by multiple gated acquisition 65% +/- 12%) and coronary arteriograms. Time on the waiting list before transplantation was reduced compared with heart-lung transplant (HLT) recipients (waiting time, 2.9 +/- 1.5 months for SLT, 9.6 +/- 10.2 months for HLT). Six of the SLT recipients are currently alive (after transplantation interval, 17 +/- 5 months); the remaining recipient died of pulmonary embolism 21 days after SLT. Number of ventilator days, intensive care unit days, and days to hospital discharge after transplantation did not differ significantly from HLT recipients. Cardiopulmonary bypass was necessary in four SLT recipients. Pulmonary function was markedly improved after SLT (FEV1, 1.78 +/- 0.73 L/min after SLT versus 0.75 +/- 0.3 L/min before SLT; p less than 0.01), and functional status is correspondingly improved. CONCLUSIONS: SLT constitutes effective therapy for patients with severe emphysema, including those with moderate reduction of right ventricular function; and SLT offers distinct advantages over HLT, including decreased waiting time before transplantation, improved donor organ utilization, and less frequent need for cardiopulmonary bypass.