Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3.

Chemokines are essential mediators of normal leukocyte trafficking as well as of leukocyte recruitment during inflammation. We describe here a novel non-ELR CXC chemokine identified through sequence analysis of cDNAs derived from cytokine-activated primary human astrocytes. This novel chemokine, referred to as I-TAC (interferon-inducible T cell alpha chemoattractant), is regulated by interferon (IFN) and has potent chemoattractant activity for interleukin (IL)-2-activated T cells, but not for freshly isolated unstimulated T cells, neutrophils, or monocytes. I-TAC interacts selectively with CXCR3, which is the receptor for two other IFN-inducible chemokines, the IFN-gamma-inducible 10-kD protein (IP-10) and IFN-gamma- induced human monokine (HuMig), but with a significantly higher affinity. In addition, higher potency and efficacy of I-TAC over IP-10 and HuMig is demonstrated by transient mobilization of intracellular calcium as well as chemotactic migration in both activated T cells and transfected cell lines expressing CXCR3. Stimulation of astrocytes with IFN-gamma and IL-1 together results in an approximately 400,000-fold increase in I-TAC mRNA expression, whereas stimulating monocytes with either of the cytokines alone or in combination results in only a 100-fold increase in the level of I-TAC transcript. Moderate expression is also observed in pancreas, lung, thymus, and spleen. The high level of expression in IFN- and IL-1-stimulated astrocytes suggests that I-TAC could be a major chemoattractant for effector T cells involved in the pathophysiology of neuroinflammatory disorders, although I-TAC may also play a role in the migration of activated T cells during IFN-dominated immune responses.

A multicenter pilot study of a bronchial valve for the treatment of severe emphysema.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affects millions of people and has limited treatment options. Surgical treatments for severe COPD with emphysema are effective for highly selected patients. A minimally invasive method for treating emphysema could decrease morbidity and increase acceptance by patients. OBJECTIVE: To study the safety and effectiveness of the IBV(R) Valve for the treatment of severe emphysema. METHODS: A multicenter study treated 91 patients with severe obstruction, hyperinflation and upper lobe (UL)-predominant emphysema with 609 bronchial valves placed bilaterally into ULs. RESULTS: Valves were placed in desired airways with 99.7% technical success and no migration or erosion. There were no procedure-related deaths and 30-day morbidity and mortality were 5.5 and 1.1%, respectively. Pneumothorax was the most frequent serious device-related complication and primarily occurred when all segments of a lobe, especially the left UL, were occluded. Highly significant health-related quality of life (HRQL) improvement (-8.2 +/- 16.2, mean +/- SD change at 6 months) was observed. HRQL improvement was associated with a decreased volume (mean -294 +/- 427 ml, p = 0.007) in the treated lobes without visible atelectasis. FEV(1), exercise tests, and total lung volume were not changed but there was a proportional shift, a redirection of inspired volume to the untreated lobes. Combined with perfusion scan changes, this suggests that there is improved ventilation and perfusion matching in non-UL lung parenchyma. CONCLUSION: Bronchial valve treatment of emphysema has multiple mechanisms of action and acceptable safety, and significantly improves quality of life for the majority of patients.

A microcontroller system for investigating the catch effect: functional electrical stimulation of the common peroneal nerve.

Correction of drop foot in hemiplegic gait is achieved by electrical stimulation of the common peroneal nerve with a series of pulses at a fixed frequency. However, during normal gait, the electromyographic signals from the tibialis anterior muscle indicate that muscle force is not constant but varies during the swing phase. The application of double pulses for the correction of drop foot may enhance the gait by generating greater torque at the ankle and thereby increase the efficiency of the stimulation with reduced fatigue. A flexible controller has been designed around the Odstock Drop Foot Stimulator to deliver different profiles of pulses implementing doublets and optimum series. A peripheral interface controller (PIC) microcontroller with some external circuits has been designed and tested to accommodate six profiles. Preliminary results of the measurements from a normal subject seated in a multi-moment chair (an isometric torque measurement device) indicate that profiles containing doublets and optimum spaced pulses look favourable for clinical use.

Bax cleavage is mediated by calpain during drug-induced apoptosis.

The anti-apoptotic molecule Bcl-2 is located in the mitochondrial and endoplasmic reticulum membranes as well as the nuclear envelope. Although its location has not been as rigorously defined, the pro-apoptotic molecule Bax appears to be mainly a cytosolic protein which translocates to the mitochondria upon induction of apoptosis. Here we identify a protease activity in mitochondria-enriched membrane fractions from HL-60 cells capable of cleaving Bax which is absent from the cytosolic fraction. Bax protease activity is blocked in vitro by cysteine protease inhibitors including E-64 which distinguishes it from all known caspases and granzyme B, both of which are involved in apoptosis. Protease activity is also blocked by inhibitors against the calcium-activated neutral cysteine endopeptidase calpain. Partial purification of the Bax protease activity from HL-60 cell membrane fractions by column chromatography revealed that a calpain-like activity was the protease responsible for Bax cleavage. In addition, purified calpain enzymes cleaved Bax in a calcium-dependent manner. Pretreatment of HL-60 cells with the specific calpain inhibitor calpeptin effectively blocked both drug-induced Bax cleavage and calpain activation, but not PARP cleavage or cell death. These results suggest that calpains and caspases are activated during drug-induced apoptosis and that calpains, along with caspases, may be involved in modulating cell death by acting selectively on cellular substrates.

Projection neurons with shared cotransmitters elicit different motor patterns from the same neural circuit.

Specificity in the actions of different modulatory neurons is often attributed to their having distinct cotransmitter complements. We are assessing the validity of this hypothesis with the stomatogastric nervous system of the crab Cancer borealis. In this nervous system, the stomatogastric ganglion (STG) contains a multifunctional network that generates the gastric mill and pyloric rhythms. Two identified projection neurons [modulatory proctolin neuron (MPN) and modulatory commissural neuron 1 (MCN1)] that innervate the STG and modulate these rhythms contain GABA and the pentapeptide proctolin, but only MCN1 contains Cancer borealis tachykinin-related peptide (CabTRP Ia). Selective activation of each projection neuron elicits different rhythms from the STG. MPN elicits only a pyloric rhythm, whereas MCN1 elicits a distinct pyloric rhythm as well as a gastric mill rhythm. We tested the degree to which CabTRP Ia distinguishes the actions of MCN1 and MPN. To this end, we used the tachykinin receptor antagonist Spantide I to eliminate the actions of CabTRP Ia. With Spantide I present, MCN1 no longer elicited the gastric mill rhythm and the resulting pyloric rhythm was changed. Although this rhythm was more similar to the MPN-elicited pyloric rhythm, these rhythms remained different. Thus, CabTRP Ia partially confers the differences in rhythm generation resulting from MPN versus MCN1 activation. This result suggests that different projection neurons may use the same cotransmitters differently to elicit distinct pyloric rhythms. It also supports the hypothesis that different projection neurons use a combination of strategies, including using distinct cotransmitter complements, to elicit different outputs from the same neuronal network.

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

PURPOSE: Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS: This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS: Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION: The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography.

Tumor proliferation has prognostic value in resected early-stage non-small cell lung cancer (NSCLC). We evaluated whether [F-18]fluorodeoxyglucose (FDG) uptake of NSCLC correlates with tumor proliferation and, thus, could noninvasively grade NSCLCs (refining patient prognosis and therapy). Thirty-nine patients with potentially resectable NSCLC underwent whole-body FDG positron emission tomography (PET) 45 min after i.v. injection of 10 mCi of FDG. Tumor FDG uptake was quantitated with the maximum pixel standardized uptake value (maxSUV). The lesion diameter from computed tomography was used to correct the maxSUV for partial volume effects using recovery coefficients determined for the General Electric Advance PET scanner. Thirty-eight patients underwent complete surgical staging (bronchoscopy and mediastinoscopy, with or without thoracotomy). One stage IV patient by PET underwent bronchoscopic biopsy only. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all of the 39 NSCLC specimens (35 resections, 1 percutaneous, and 3 surgical biopsies). The specimens were reviewed for cellular differentiation (poor, moderate, well) and tumor type. Lesions ranged from 0.7 to 6.1 cm. The correlation found between uncorrected maxSUV and lesion size (Rho, 0.56; P = 0.0006) disappeared when applying the recovery coefficients (Rho, -0.035; P = 0.83). Ki-67 expression (percentage of positive cells) correlated strongly with FDG uptake (corrected maxSUV: Rho, 0.73; P < 0.0001). The correlation was stronger for stage I lesions (11 stage IA, 15 stage IB): Rho, 0.79; P < 0.0001) and strongest in stage IB (Rho, 0.83; P = 0.0019). A significant association (P < 0.0001) between tumor differentiation and corrected SUV was noted. FDG PET may be used to noninvasively assess NSCLC proliferation in vivo, identifying rapidly growing NSCLCs with poor prognosis that could benefit from preoperative chemotherapy.

Biomechanical approaches applied to the lower and upper limb for the measurement of spasticity: a systematic review of the literature.

PURPOSE: To review and characterise biomechanical approaches for the measurement of spasticity as one component of the upper motor neurone syndrome. METHOD: Systematic literature searches based on defined constructs and a four-step review process of approaches used or described to measure spasticity, its association with function or associated phenomena. Most approaches were limited to individual joints and therefore, to reflect this trend, references were grouped according to which body joint(s) were investigated or whether it addressed a functional activity. For each joint, references were further sub-divided into the types of measurement method described. RESULTS: A database of 335 references was established for the review process. The knee, ankle and elbow joints were the most popular, perhaps reflecting the assumption that they are mono-planar in movement and therefore simpler to assess. Seven measurement methods were identified: five involving passive movement (manual, controlled displacement, controlled torque, gravitational and tendon tap) and two involving active movement (voluntary and functional). Generally, the equipment described was in an experimental stage and there was a lack of information on system properties, such as accuracy or reliability. Patient testing was either by cohort or case studies. The review also conveyed the myriad of interpretations of the concept of spasticity. CONCLUSIONS: Though biomechanical approaches provide quantitative data, the review highlighted several limitations that have prevented them being established as an appropriate method for clinical application to measure spasticity.

Theoretical and methodological considerations in the measurement of spasticity.

PURPOSE: To discuss the measurement of spasticity in the clinical and research environments, make recommendations based on the SPASM reviews of biomechanical, neurophysiological and clinical methods of measuring spasticity and indicate future developments of measurement tools. METHOD: Using the results of the systematic reviews of the biomechanical, neurophysiological and clinical approaches, methods were evaluated across three dimensions: (1) validity, reliability and sensitivity to change; (2) practical quality such as ease of use and (3) qualities specific to the measurement of spasticity, for example ability to be applied to different muscle groups. Methods were considered in terms of applicability to research and clinical applications. RESULTS: A hierarchy of measurement approaches was identified from highly controlled and more objective (but unrelated to function) to ecologically valid, but less objective and subject to contamination from other variables. The lack of a precise definition of spasticity may account for the problem of developing a valid, reliable and sensitive method of measurement. The reviews have identified that some tests measure spasticity per se, some phenomena associated with spasticity or consequential to it and others the effect of spasticity on activity and participation and independence. CONCLUSIONS: Methods appropriate for use in research, particularly into the mechanism of spasticity did not satisfy the needs of the clinician and the need for an objective but clinically applicable tool was identified. A clinical assessment may need to generate more than one 'value' and should include evaluation of other components of the upper motor neurone syndrome. There is therefore a need for standardized protocols for 'best practice' in application of spasticity measurement tools and scales.

Proctolinlike immunoreactivity and identified neurosecretory cells as putative substrates for modulation of courtship display behavior in the blue crab, Callinectes sapidus.

Pheromonally stimulated courtship display (CD) behavior in male blue crabs (Callinectes sapidus) is characterized by rhythmic waving of the fifth legs. The waving of the fifth legs is modulated by proctolin in freely moving crabs and in reduced preparations. To begin to identify an anatomical substrate for CD behavior we have localized putative proctolinergic cells and described the morphology of neurosecretory neurons known to oscillate during pheromonal stimulation of reduced preparations. Proctolin-induced CD occurs with developmental and seasonal dependence. Male crabs altered hormonally by eyestalk ligation spontaneously produce CD behavior. We have localized proctolinlike immunoreactivity (PIR) in the central nervous system (CNS) and compared this immunoreactivity across sexes, developmental stage, eyestalk ligation, and seasonal conditions to determine whether or not expression of PIR is correlated with CD behavior. PIR was found in most areas of the CNS. Clusters of PIR-positive cells were found in the sinus gland and eyestalk ganglia, olfactory neuropil with associated cell bodies, and in a large cell cluster in the subesophageal region of the ventral nerve cord. Three pairs of cell bodies in different cell body groups in the brains of adult crabs stained positively for PIR but did not stain in the youngest juvenile animals. Comparison of PIR distribution with toluidine blue studies of the ventral nerve cord indicated a high likelihood that cells in the PIR-positive cluster of the subesophageal ganglia were also members of the cluster of neurons identified as oscillatory neurosecretory neurons.

Cytokines increase neonatal cardiac myocyte calcium concentrations: the involvement of nitric oxide and cyclic nucleotides.

Neonatal rat cardiac myocytes were treated with cytokines, with or without the nitric oxide synthase (NOS) inhibitors N-monomethyl-L-arginine (LNMMA) and N-nitro-L-arginine methyl ester (LNAME), and systolic and diastolic calcium levels were measured by fluorescence spectrophotometry and confocal microscopy. Time-dependent changes following interferon-gamma (IFN-gamma) treatment revealed a continuing increase in intracellular calcium, which was reduced with LNMMA, but not with LNAME. Increases in calcium also occurred with interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), but not to the extent seen with IFN-gamma. Increased cyclic guanosine monophosphate (cGMP) was involved in the results described with short-term (2 hr) TNF-alpha and long-term (18 hr) IFN-gamma treatments. Short-term exposure to IFN-gamma produced an increase in cyclic adenosine monophosphate (cAMP) and also an initial increase in the myocyte-bearing rate, with calcium levels either (i) subsequently returning to control levels while maintaining a fast beating rate or (ii), retaining a high systolic calcium level, but beating at control rates. Treatment with both IL-1beta and IFN-gamma stabilized the beating rate of the cells on some occasions. Shortening of myocytes increased with isoproterenol and following treatment with IFN-gamma, while isoproterenol stimulation of IFN-gamma-treated cells revealed increased contractile activity after short, but not long, treatment. LNMMA, but not reduced the increased contractile response with short-term IFN-gamma treatment. Our findings suggest that TNF-alpha acts via a cGMP-dependent pathway, whereas the actions of IFN-gamma involve adenylate cyclase, and possibly a NO-forming mechanism and cGMP pathway as well. It is also apparent that the two NO inhibitors function via different mechanisms or that LNMMA has a direct effect on the calcium-signaling pathway.

Efficacy of a 6-week prophylactic ganciclovir regimen and the role of serial cytomegalovirus antibody testing in lung transplant recipients.

CMV is a frequently occurring pathogen in recipients of solid organ transplants, and those receiving lung transplants seem to be affected more frequently and more severely. Because the duration of prophylactic ganciclovir may influence the incidence of CMV disease in solid organ transplant recipients, we evaluated the efficacy of a 6-week prophylactic regimen in lung transplant recipients. We also evaluated the ability of a fourfold rise in CMV antibody titer to predict the development of CMV disease. Twenty-one consecutive lung transplant recipients were enrolled: 15 were CMV antibody-positive at the time of transplantation, and six were CMV antibody-negative and received a lung transplant from CMV-positive donors. Mean +/- SD follow-up was 430 +/- 157 days (range 178-730 days, median 449 days). The 6-week ganciclovir regimen prevented neither CMV infection (which occurred in 17/21 patients, 81%) nor CMV disease (seen in 8/21 patients, 38%). A fourfold rise in CMV antibody titer only preceded the onset of CMV disease in 3/13 instances (23%). We conclude that a 6-week regimen of ganciclovir prophylaxis does not prevent CMV infection or disease in lung transplant recipients and that a rise in serially obtained CMV antibody titers rarely precedes the development of CMV disease.

Bronchoscopic management of central airway obstruction.

OBJECTIVES: Patients with central airway obstruction are critically ill, with impending suffocation. They are seen with diverse anatomic and functional deficits caused by both benign and malignant obstructions. Such cases were reviewed to examine the indications, techniques, and outcomes of an algorithm approach to bronchoscopic management. METHODS: Between July 1992 and April 1996, 97 patients underwent bronchoscopic procedures for the management of central airway obstruction, and their cases were used for a retrospective review of the airway management. RESULTS: There were 48 male and 49 female patients, aged 13 to 85 years. There were 48 benign and 49 malignant pathologic conditions that gave rise to 108 stenoses. These were treated with 199 endoscopic procedures with an average of 1.7 interventions per endoscopy, including mechanical core-out (62), dilation (135), laser ablation (44), placement of brachytherapy catheters (9), and stent placement (88). Diagnoses included lung cancer, primary tracheobronchial tumors, tumors metastatic to the airway or mediastinum, and a variety of benign obstructions. In the group of 97 patients there were 2 (2%) perioperative deaths and 34 (34%) late deaths, 29 in the malignant group and 5 in the benign group. Median survival was 7.6 months (range 1 week-31 months). There were 7 (7%) complications among the group of 97, 4 in the malignant group, and 3 in the benign group. CONCLUSIONS: Endobronchial surgical techniques can be used safely and systematically for the relief of benign and malignant central airway obstructions; a diversity of approaches and interventions are required to produce and maintain palliation of airway symptoms.

Descending necrotizing mediastinitis: An analysis of the effects of serial surgical debridement on patient mortality.

OBJECTIVES: Descending necrotizing mediastinitis is a polymicrobial infection originating in the oropharynx with previously reported mortality rates of 25% to 40%. This investigation reviews the effects of serial surgical drainage and debridement on the survival of patients with descending necrotizing mediastinitis. METHODS: A retrospective review of patients from 1980 through 1998 with a diagnosis of descending necrotizing mediastinitis was performed. Their records were abstracted for personal demographics, hospital course, morbidity, and mortality. Also abstracted were all reports of patients with descending necrotizing mediastinitis published in English between 1970 and 1999. RESULTS: We treated 10 patients in whom descending necrotizing mediastinitis was identified. The mean age of the patients was 38 years. They underwent a mean of 6 +/- 4 computed tomographic imaging studies, 4 +/- 1 transcervical drainage procedures, and 2 +/- 1 transthoracic drainage procedures. Three patients required abdominal exploration and 4 underwent tracheostomy. No deaths occurred. In contrast, 96 patients with descending necrotizing mediastinitis were identified from the literature with a mean age of 38 years. They underwent a mean of 2 +/- 1 computed tomographic imaging studies, 2 +/- 1 transcervical drainage procedures, and 0.7 + 0.3 transthoracic drainage procedures. Sixteen (17%) patients required abdominal exploration and 34 (35%) underwent tracheostomy. Twenty-eight (29%) patients from the literature cohort died during their treatment. CONCLUSION: Descending necrotizing mediastinitis remains a life-threatening infection. On the basis of experience accrued in treating these patients, an algorithm incorporating computed tomographic imaging for diagnosis and surveillance and serial transcervical and transthoracic operative drainage is outlined in the hope of reducing the excessive mortality of descending necrotizing mediastinitis.

The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: A prospective study.

STUDY OBJECTIVES: Presently, surgical (open or thoracoscopic) lung biopsy (SLB) is the gold standard for the diagnosis of new-onset idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). The accuracy of a clinical diagnosis of IPF and other subsets of ILD has never been established in prospective studies. We investigated the accuracy and validity of a clinical diagnosis of IPF and ILD other than IPF. DESIGN: Prospective, independent evaluation of patients and clinical data by an ILD expert, of chest radiographic and high-resolution computed tomography (HRCT) features by a chest radiologist, and of histologic features of lung biopsy by a pulmonary pathologist in consecutive patients referred for a diagnostic evaluation of ILD. SETTING: Tertiary university medical center with recognized expertise in management of ILD. PATIENTS: Community patients referred for further definitive diagnostic evaluation of new-onset, untreated nonspecific ILD. INTERVENTION: By comparing the histologic features of SLB in 59 patients consecutively referred for further diagnostic evaluation of new-onset ILD with the clinical and radiologic diagnoses, we determined the sensitivity and specificity of clinical diagnosis and radiologic diagnosis (based on chest radiograph and HRCT features alone) of IPF and ILD other than IPF. A specific clinical diagnosis was independently made by the ILD expert after a thorough clinical assessment that included evaluation of an HRCT scan and bronchoscopic findings. The chest radiographs and HRCT scans were separately reviewed by the chest radiologist, who made a radiologic diagnosis independently. All patients underwent SLB within a month of preoperative "clinical" diagnosis. The clinician's and radiologist's diagnoses were then compared with the gold standard of histologic diagnosis. MEASUREMENTS AND RESULTS: Prior to the clinical evaluation at our center, 85% of patients who underwent SLB had nondiagnostic transbronchial biopsy. The diagnosis of IPF and ILD other than IPF was accurately made by clinical features alone in 62% of cases. The correct radiographic diagnosis of non-IPF ILD was made in 58% of the cases. The sensitivity and specificity of the clinical diagnosis of ILD other than IPF were 88.8% and 40%, respectively. The sensitivity and specificity of the radiographic diagnosis of ILD other than IPF were 59% and 40%, respectively. However, the sensitivity and specificity of the diagnosis of IPF on clinical grounds were 62% and 97%, respectively. The sensitivity and specificity of the radiologic diagnosis of IPF were 78.5% and 90%, respectively. CONCLUSIONS: In a center with recognized expertise in the management of ILD, the specificity of diagnosis of new-onset IPF based on a thorough clinical assessment or HRCT features alone is very high (97% and 90%, respectively), but the sensitivity is low (62% and 78.5%, respectively). Thus, not all patients with new-onset IPF require SLB for diagnosis, but a diagnosis of IPF will be missed in nearly one third of new-onset IPF cases despite evaluation by experts. The relatively low sensitivity and specificity of the diagnosis of ILD other than IPF also emphasizes that an SLB is indicated in patients with ILD in whom the diagnosis is unclear.

Dynamic pharyngoscopy in predicting outcome of uvulopalatopharyngoplasty for moderate and severe obstructive sleep apnea.

STUDY OBJECTIVE: We sought to determine whether preoperative fiberoptic pharyngoscopy (FOP) with Müller's maneuver (dynamic FOP) could be used to establish a subgroup of obstructive sleep apnea (OSA) patients with better outcome after uvulopalatopharyngoplasty (UPPP). DESIGN: Retrospective review of an observational cohort. SETTING: Tertiary care referral center. PATIENTS: Twenty-nine patients who underwent UPPP and nasopharyngeal surgery by one surgeon. INTERVENTION: The patients were divided into two groups based on the findings of preoperative dynamic FOP: group 1 (11 patients) had collapse of the velopharynx and the base of the tongue-epiglottis-hypopharynx (TEH) complex and group 2 (18 patients) had velopharyngeal collapse only. MEASUREMENTS AND RESULTS: Surgical success was defined using a conventional definition (> 50% reduction in the apnea-plus-hypopnea index [OAHI]), and a criterion for cure (> 90% reduction in OAHI and postoperative OAHI < 15). Both groups had a significant improvement in their OAHI. The success rate was significantly higher in patients with velopharyngeal collapse only compared with patients with additional collapse of the TEH complex (78 vs 36% with the conventional definition, and 50 vs 9% using the definition for cure, respectively). Predictive value of dynamic FOP in predicting cure failure when collapse of the TEH complex was present was 91%. CONCLUSIONS: Dynamic FOP may help establish a subgroup of OSA patients with greater likelihood of successful UPPP. The high negative predictive value of dynamic FOP when a criterion for cure is used suggests that this maneuver could best be used to exclude patients with TEH complex collapse from UPPP.

The cost-effectiveness of lung transplantation. A pilot study. University of Washington Medical Center Lung Transplant Study Group.

OBJECTIVE: Lung transplantation is one of the fastest-growing solid organ transplant procedures in the world, yet its cost-effectiveness is unknown. We compared the costs and outcomes of the first 25 patients who received lung transplants at the University of Washington with 24 patients currently on the lung transplant waiting list. DESIGN: Inpatient and outpatient charges were obtained from the hospital billing service and home health agencies. Quality-adjusted life year scores (QALYs) were computed from the following: (1) utility scores obtained through standard gamble interviews, and (2) published survival data from an international lung transplant registry and from studies of patients on lung transplant waiting lists. RESULTS: Transplantation charges averaged $164,989 (median, $152,071). Average monthly charges posttransplant were $11,917 in year 1 and $4,525 thereafter, vs $3,395 for waiting-list patients. Posttransplant utility scores were significantly higher than waiting-list scores (0.80 vs 0.68; p < 0.001). Life expectancy was not greater for lung transplant vs waiting-list patients (5.89 vs 5.32 years; p > 0.05), although quality-adjusted life expectancy did improve significantly. After converting charges to costs, the incremental cost per QALY gained for posttransplant compared with waiting-list patients was $176,817. CONCLUSIONS: Lung transplantation is very expensive, although it can substantially improve quality of life. Two-thirds of care costs are incurred after transplantation. The principal barriers to cost-effectiveness at present are the high cost of postrecovery care and marginal gains in life expectancy compared with conservative care.

Underestimation of mortality following lung volume reduction surgery resulting from incomplete follow-up.

STUDY OBJECTIVES: Incomplete follow-up can bias interpretation of data that are collected in longitudinal studies. We noted that many patients failed to return for follow-up in a study of effect of lung volume reduction surgery (LVRS) on quality of life (QOL). Accordingly, we designed this investigation to determine the reasons patients dropped out, and to assess differences between those who continued in the study (attendees) and those who did not (nonattendees). DESIGN: Telephone survey. SUBJECTS: Patients with advanced emphysema who had undergone LVRS and had previously agreed to participate in a longitudinal QOL study. RESULTS: No differences were found with regard to age, gender, preoperative pulmonary function, or oxygen use between attendees and nonattendees. Long-term mortality in nonattendees (27%) was considerably greater than that seen in attendees (3%, p < 0.05). Distance from the hospital, financial burden, and living out of the region were the most common reasons cited by surviving nonattendees for their failure to return for follow-up. CONCLUSIONS: Studies reporting the long-term mortality after LVRS can be biased in the direction of underestimating the true value if they are compromised by incomplete follow-up.

Successful lung transplantation in spite of cystic fibrosis-associated liver disease: a case series.

Lung transplantation has recently offered hope for prolonged survival in patients with cystic fibrosis. Patients with cystic fibrosis have a 7% prevalence of associated liver disease and portal hypertension. These patients have been previously excluded from consideration for lung transplantation. The natural history of cystic fibrosis-associated liver disease suggests a benign and protracted course in most cases. At the University of Washington, 14 of 53 patients (26%) have undergone lung transplantation for cystic fibrosis-related respiratory failure. We report the outcome of double lung transplantation in four of these 14 patients who also had cystic fibrosis-associated liver disease and portal hypertension, all of whom were symptom free from their liver disease. All four patients are alive and well without complications 4 to 31 months after transplantation. We conclude that the presence of cystic fibrosis-associated liver disease with portal hypertension, in the setting of good synthetic function (albumin > 3.0 gm/L and normal prothrombin time), normal serum bilirubin, minimal varices, without ascites or encephalopathy, should not be an absolute contraindication to lung transplantation. We recommend that other transplantation centers also include this patient population in consideration for lung transplantation.

Proficiency testing in parasitology. An educational tool to improve laboratory performance.

In 1977, the Laboratory Proficiency Testing Program began testing laboratories that examine samples for gastrointestinal parasites and operated with little change in the subsequent 17 years. Four surveys, each containing four samples, are distributed each year to every currently licensed medical laboratory in Ontario. Participation is mandatory. Survey results indicate a remarkable improvement in laboratory performance during this period. Improvement is believed to result from a combination of the voluntary withdrawal from testing by laboratories with poor performance and the improved performance of the others. The extensive educational services devised and carried out by the Parasitology Committee is believed to have been a significant factor leading to this improvement.