Enhanced TLR2 responses in multiple sclerosis.

The roles of the microbiome and innate immunity in the pathogenesis of multiple sclerosis (MS) remain unclear. We have previously documented abnormally low levels of a microbiome-derived Toll-like receptor (TLR)2-stimulating bacterial lipid in the blood of MS patients and postulated that this is indicative of a deficiency in the innate immune regulating function of the microbiome in MS. We postulated further that the resulting enhanced TLR2 responsiveness plays a critical role in the pathogenesis of MS. As proof-of-concept, we reported that decreasing systemic TLR2 responsiveness by administering very low-dose TLR2 ligands attenuated significantly the mouse model of MS, experimental autoimmune encephalomyelitis. Studies of Toll-like receptor responses in patients with MS have been conflicting. Importantly, most of these investigations have focused on the response to TLR4 ligation and few have characterized TLR2 responses in MS. In the present study, our goal was to characterize TLR2 responses of MS patients using multiple approaches. Studying a total of 26 MS patients and 32 healthy controls, we now document for the first time that a large fraction of MS patients (50%) demonstrate enhanced responsiveness to TLR2 stimulation. Interestingly, the enhanced TLR2 responders include a significant fraction of those with progressive forms of MS, a subset of patients considered unresponsive to adaptive immune system-targeting therapies. Our results suggest the presence of a pathologically relevant TLR2 related innate immune abnormality in patients with both relapsing-remitting and progressive MS. These findings may have significant implications for understanding the role of innate immunity in the pathogenesis of MS.

A Single-Institution Experience in Percutaneous Image-Guided Biopsy of Malignant Pleural Mesothelioma.

PURPOSE: Mesothelioma has been considered a difficult pathologic diagnosis to achieve via image-guided core needle biopsy. The purpose of this study was to assess the diagnostic sensitivity of percutaneous image-guided biopsy for diagnosis of pleural mesothelioma. MATERIALS AND METHODS: Retrospective review was performed to identify patients with a confirmed diagnosis of pleural mesothelioma and who underwent image-guided needle biopsy between January 1, 2002, and January 1, 2016. Thirty-two patients with pleural mesothelioma were identified and included for analysis in 33 image-guided biopsy procedures. Patient, procedural, and pathologic characteristics were recorded. Complications were characterized via standardized nomenclature [Common Terminology for Clinically Adverse Events (CTCAE)]. RESULTS: Percutaneous image-guided biopsy was associated with an overall sensitivity of 81%. No CTCAE clinically significant complications were observed. No image-guided procedures were complicated by pneumothorax or necessitated chest tube placement. No patients had tumor seeding of the biopsy tract. CONCLUSION: Percutaneous image-guided biopsy can achieve high sensitivity for pathologic diagnosis of pleural mesothelioma with a low procedural complication rate, potentially obviating need for surgical biopsy.

Utility of endoscopic therapy in the management of Boerhaave syndrome.

Background/aims: The optimal intervention for Boerhaave perforation has not been determined. Options include surgical repair with/without a pedicled muscle flap, T tube placement, esophageal resection or diversion, or an endoscopic approach. All management strategies require adequate drainage and nutritional support. Our aim was to evaluate outcomes following Boerhaave perforation treated with surgery, endoscopic therapy, or both. Patients and methods: We performed a 10-year review of our prospectively maintained databases of adult patients with Boerhaave perforations. We documented clinical presentation, extent of injury, primary intervention, "salvage" treatment (any treatment for persistent leak), and outcome. Results were analyzed using the Fisher's exact and Kruskal - Wallis tests. Results: Between October 2004 and October 2014, 235 patients presented with esophageal leak/fistula with 17 Boerhaave perforations. Median age was 68 years. Median length of perforation was 1.25 cm (range 0.8 - 5 cm). Four patients presented with systemic sepsis (two treated with palliative stent and two surgically). Primary endotherapy was performed for eight (50 %) and primary surgery for eight (50 %) patients. Two endotherapy patients required multiple stents. Median stent duration was 61 days (range 56 - 76). "Salvage" intervention was required in 2/8 (25 %) endotherapy patients and 1/8 (13 %) surgery patient (stent). All patients healed without resection/reconstruction. There were no deaths in the surgically treated group and two in the endotherapy group (stented with palliative intent due to poor systemic condition). Readmission within 30 days occurred in 3/6 of alive endotherapy patients (50 %) and 0/8 surgery patients. Re-intervention within 30 days was required for one endotherapy patient. Conclusion: Endoscopic repair of Boerhaave perforations can be useful in carefully selected patients without evidence of systemic sepsis. Endoscopic therapy such as stenting is particularly valuable as a "salvage" intervention. The benefits of endoscopic therapy and esophageal preservation are offset against an increased risk of readmission in patients primarily treated endoscopically.

Impact of endoscopic ultrasonography and physician specialty on the management of patients with esophagus cancer.

While endoscopic ultrasonography (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) are the most accurate techniques for locoregional staging of esophageal cancer, little evidence exists that these innovations impact on clinical care. The objective on this study was to determine the frequency with which EUS and EUS-FNA alter the management of patients with localized esophageal cancer, and assess practice variation among specialists at a tertiary care center. Three gastroenterologists, three medical oncologists, three radiation oncologists and four thoracic surgeons were asked to independently report their management recommendations as the anonymized staging information of 50 prospectively enrolled patients from another study were sequentially disclosed on-line. Compared to initial management recommendations, that were based upon history, physical examination, upper endoscopy and CT scan results, EUS prompted a change in management 24% (95% CI: 12-36%) of the time; usually to a more resource-intensive approach (71%), for example from recommending palliation to recommending neoadjuvant chemoradiation therapy. EUS-FNA plus cytology results altered management an additional 8% (95% CI: 6-15%) of the time. Agreement between specialists ranged from fair (intraclass correlation [ICC=0.32) to substantial (ICC=0.65); improving with additional information. Among specialists, agreement was greatest for patients with stage I disease. EUS and EUS-FNA changed patient management the most for patients with stages IIA, IIB or III disease. EUS, with or without FNA, significantly impacts the management of patients with localized esophageal cancer. With respect to the optimal treatment for each patient, agreement among physicians incrementally increases with endoscopic ultrasound results. Specialty training appears to influence therapeutic decision-making behavior.

Porphyromonas gingivalis dihydroceramides induce apoptosis in endothelial cells.

Porphyromonas gingivalis dihydroceramides are found in extracts of calculus-contaminated root surfaces, diseased gingival tissue, and atherosclerotic plaques. These ceramides have been shown to promote inflammatory secretory responses in gingival fibroblasts. Little is known about their effects on the vascular system. We tested the hypothesis that P. gingivalis lipids induce apoptosis of human endothelial cells, and investigated the effects of extracted and purified P. gingivalis lipids on human umbilical vein endothelial cells. P. gingivalis phosphoglycerol dihydroceramides induced apoptosis, but not necrosis, in endothelial cells. Early apoptotic cells showed exposure of phosphatidylserine on the cell surface, followed by the cleavage of procaspases 3, 6, and 9. The release of apoptosis-inducing factor was increased, suggesting mitochondrial involvement. Different caspase inhibitors and cAMP elevation blocked DNA fragmentation. Moreover, N-acetylcysteine significantly reduced apoptosis, suggesting a role for reactive oxygen species in this process. Analysis of these data indicates that dihydroceramides may be important virulence factors of P. gingivalis.

The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial.

BACKGROUND: Transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) can identify intracranial atherosclerosis but have not been rigorously validated against the gold standard, catheter angiography. The WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) required performance of angiography to verify the presence of intracranial stenosis, allowing for prospective evaluation of TCD and MRA. The aims of Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial were to define abnormalities on TCD/MRA to see how well they identify 50 to 99% intracranial stenosis of large proximal arteries on catheter angiography. STUDY DESIGN: SONIA standardized the performance and interpretation of TCD, MRA, and angiography. Study-wide cutpoints defining positive TCD/MRA were used. Hard copy TCD/MRA were centrally read, blind to the results of angiography. RESULTS: SONIA enrolled 407 patients at 46 sites in the United States. For prospectively tested noninvasive test cutpoints, positive predictive values (PPVs) and negative predictive values (NPVs) were TCD, PPV 36% (95% CI: 27 to 46); NPV, 86% (95% CI: 81 to 89); MRA, PPV 59% (95% CI: 54 to 65); NPV, 91% (95% CI: 89 to 93). For cutpoints modified to maximize PPV, they were TCD, PPV 50% (95% CI: 36 to 64), NPV 85% (95% CI: 81 to 88); MRA PPV 66% (95% CI: 58 to 73), NPV 87% (95% CI: 85 to 89). For each test, a characteristic performance curve showing how the predictive values vary with a changing test cutpoint was obtained. CONCLUSIONS: Both transcranial Doppler ultrasound and magnetic resonance angiography noninvasively identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial methods allow transcranial Doppler ultrasound and magnetic resonance angiography to reliably exclude the presence of intracranial stenosis. Abnormal findings on transcranial Doppler ultrasound or magnetic resonance angiography require a confirmatory test such as angiography to reliably identify stenosis.

Transcranial Doppler ultrasonography in adults with sickle cell disease.

BACKGROUND: Transcranial Doppler (TCD) is used to select children with sickle cell disease (SCD) for primary stroke prevention using regular blood transfusion. Whether it can also identify high stroke risk in adults with SCD is not known. METHODS: The authors examined 112 adult patients from two convenience population samples with SCD and 53 healthy control subjects to compare velocities in adults to those reported in children with SCD and to evaluate the influence of age and hematocrit on TCD. RESULTS: Adults with SCD had a higher mean time-averaged maximum mean velocity (110.9 +/- 25.7 cm/s) compared with healthy controls (71.1 +/- 12.0 cm/s), and the difference is approximately proportional to their anemia. No cases with velocities >/=200 cm/s (the threshold used in children for prophylactic treatment) were found in this sample. CONCLUSIONS: Transcranial Doppler velocities in adults with sickle cell disease (SCD) are lower than those in children with SCD. Velocity criteria used in children cannot be used to stratify risk of stroke in adults.

Percutaneous endoscopic gastrostomy risks rendering the gastric conduit unusable for esophagectomy.

Surgical treatment for cancer of the esophagus most often involves replacement of the esophagus with a gastric conduit. This gastric tube relies upon the continuity of the gastroepiploic artery for its blood supply. This case report involves a patient whose gastroepiploic artery became thrombosed by a percutaneous endoscopic gastrostomy, rendering his gastric conduit unusable.

Porphyromonas gingivalis lipids and diseased dental tissues.

BACKGROUND/AIM: Porphyromonas gingivalis synthesizes several classes of dihydroceramides and at least one of these lipid classes promotes proinflammatory secretory reactions in gingival fibroblasts as well as alters fibroblast morphology in culture. The purpose of this investigation was to determine whether the dihydroceramide lipids of P. gingivalis are recovered in lipid extracts of subgingival plaque, diseased teeth, and diseased gingival tissue samples. METHODS: Lipids were extracted from P. gingivalis, subgingival plaque, subgingival calculus, teeth laden with gross accumulations of subgingival calculus, and gingival tissue samples obtained from chronic severe periodontitis sites. Lipid samples were analyzed by gas chromatography-mass spectrometry as trimethylsilyl derivatives or by electrospray-mass spectrometry as underivatized products. High-performance liquid chromatography fractions of P. gingivalis lipids and gingival tissue lipids were also analyzed by electrospray-mass spectrometry analysis. RESULTS: P. gingivalis phosphorylated dihydroceramides were recovered in lipid extracts of subgingival plaque, subgingival calculus, calculus contaminated teeth, and diseased gingival tissue samples. However, the distribution of phosphorylated dihydroceramides varied between these samples. CONCLUSION: Subgingival plaque, subgingival calculus, diseased teeth, and gingival tissue are contaminated with phosphorylated dihydroceramides produced by P. gingivalis. The previously reported biological activity of these substances together with the recovery of these lipids at periodontal disease sites argues strongly for their classification as virulence factors in promoting chronic inflammatory periodontal disease.

Lobar torsion after pulmonary resection: presentation and outcome.

OBJECTIVE: We reviewed our experience on postoperative lobar torsion. METHODS: Between January 1972 and January 1998, 7887 patients underwent pulmonary resection at our institution. Seven (0.089%; 4 women and 3 men; median age, 68 years) patients required surgical reintervention for lobar torsion. RESULTS: The indications for pulmonary resection were non-small cell carcinoma in 5 patients, lymphoma in 1 patient, and metastatic prostate carcinoma in 1 patient. The right upper lobe was resected in 3 patients, the left lower lobe in 2 patients, and the right middle and right lower lobe in 1 patient each. Postoperative radiographs demonstrated pulmonary infiltrates and volume loss in 5 patients and complete opacification in 2 patients. The median white blood cell count was 10.6 x 10(9) cells/L (range, 9.3-14.9 x 10(9) cells/L), and the median peak temperature was 38.4 degrees C (range, 37.8 degrees C-40.2 degrees C) during the first 48 hours postoperatively. The diagnosis of lobar torsion was made a median of 10 days (range, 2-14 days) after the initial operation; 4 patients underwent completion pneumonectomy, and 3 had lobectomy. Median hospitalization was 24 days and ranged from 10 to 56 days. There were no postoperative deaths. Complications after reoperation included respiratory failure in 2 patients, atrial arrhythmia in 2 patients, and empyema, urinary tract infection, and a transient ischemic attack in 1 patient each. CONCLUSIONS: Lobar torsion represents a difficult diagnostic dilemma in the early postoperative period after pulmonary resection. A high index of suspicion is necessary to avoid a delay in treatment. Late diagnosis results in further pulmonary resection and prolonged hospitalization in the majority of cases.

Stroke prevention in sickle cell disease (STOP) study guidelines for transcranial Doppler testing.

The Stroke Prevention in Sickle Cell Disease (STOP) trial used transcranial Doppler (TCD) to screen children with sickle cell disease with no history of stroke. Children (who consented) who had time-averaged mean of the maximum (TAMM) velocities in the middle cerebral artery and/or distal internal carotid artery were randomized to transfusion or standard. Over a slightly more than 20-month average follow-up, there were 11 strokes in the standard care arm and 1 stroke in the transfusion arm. This study has caused a great deal of interest in using TCD to screen children with sickle cell disease. For the STOP TCD data to be applied appropriately, it is necessary for users of TCD to understand how the STOP TCD examinations were performed, how the TCD velocities were measured, and which velocities were used. This article will review the STOP TCD scanning protocol and the reading protocol and review the TAMM velocity and how it differs from other velocity measurements.

Laparoscopic repair of large paraesophageal hiatal hernia.

BACKGROUND: The objective of this study was to analyze our initial results after laparoscopic repair of large paraesophageal hiatal hernias. METHODS: Between October 1997 and May 2000, 37 patients (23 women, 14 men) underwent laparoscopic repair of a large type II (pure paraesophageal) or type III (combined sliding and paraesophageal) hiatal hernia with more than 50% of the stomach herniated into the chest. Median age was 72 years (range 52 to 92 years). Data related to patient demographics, esophageal function, operative techniques, postoperative symptomatology, and complications were analyzed. RESULTS: Laparoscopic hernia repair and Nissen fundoplication was possible in 35 of 37 patients (95.0%). Median hospitalization was 4 days (range 2 to 20 days). Intraoperative complications occurred in 6 patients (16.2%) and included pneumothorax in 3 patients, splenic injury in 2, and crural tear in 1. Early postoperative complications occurred in 5 patients (13.5%) and included esophageal leak in 2, severe bloating in 2, and a small bowel obstruction in 1. Two patients died within 30 days (5.4%), 1 from delayed splenic bleeding and 1 from adult respiratory distress syndrome secondary to a recurrent strangulated hiatal hernia. Follow-up was complete in 31 patients (94.0%) and ranged from 3 to 34 months (median 15 months). Twenty-seven patients (87.1%) were improved. Four patients (12.9%) required early postoperative dilatation. Recurrent paraesophageal hiatal hernia occurred in 4 patients (12.9%). Functional results were classified as excellent in 17 patients (54.9%), good in 9 (29.0%), fair in 1 (3.2%), and poor in 4 (12.9%). CONCLUSIONS: Laparoscopic repair of large paraesophageal hiatal hernias is a challenging operation associated with significant morbidity and mortality. More experience, longer follow-up, and further refinement of the operative technique is indicated before it can be recommended as the standard approach.

Comparison of transcranial color Doppler imaging (TCDI) and transcranial Doppler (TCD) in children with sickle-cell anemia.

BACKGROUND: Transcranial Doppler (TCD) has been demonstrated to identify those at highest risk of stroke among children with sickle-cell disease. Based on a randomized clinical trial [Stroke Prevention in Sickle-Cell Anemia Trial (STOP)], which ended in 1997, the National Heart Lung and Blood Division of NIH has recommended TCD screening and chronic blood transfusion based on Nicolet TC 2000 dedicated Doppler (TCD). Studies performed using TCD imaging modalities need to be correlated to that used in the clinical trial to provide information for treatment decisions when screening with TCDI. OBJECTIVE: To correlate transcranial arterial time-averaged mean velocities obtained from an Acuson Transcranial Doppler Imaging to those obtained using the TCD as the gold standard for treatment decisions based on STOP. MATERIALS AND METHODS: A total of 29 children with sickle-cell disease, age 3-16 years, were studied at one of two scanning sessions using both techniques and a scanning protocol based on that used in STOP performed and read independently. The average difference in the measured velocities for each arterial segment was tested to determine difference from zero. Differences were compared before and after modifications to the TCDI technique were made to mimic the STOP protocol more closely. RESULTS: TCDI velocities were generally lower than TCD velocities for the same segment, but the difference was reduced (from 15 % to 10% for the middle cerebral artery) by modifications to the TCDI protocol. CONCLUSIONS: Measurements using the Acuson system are modestly lower than those obtained with dedicated Doppler using the Nicolet TCD.

The chemical and physical stability of a 1:1 mixture of propofol and methohexital.

Anesthetic drugs are frequently mixed or coadministered to optimize anesthetic effects while minimizing adverse effects. Methohexital advantages include its low cost and rapid onset, while propofol provides improved airway anesthesia and extremely rapid clearance from the plasma. Therefore, a mixture of these agents might well be superior to either drug given alone. We wished to determine whether a mixture of methohexital and propofol is chemically and physically stable. A 1:1 mixture of propofol 10 mg/ml and methohexital was prepared. At times varying from 0 to 48 hours, mixtures with an internal standard of thymol kept at room temperature were thrice extracted with a 2:1 v/v mixture of diethyl ether:pentane, dried under nitrogen, and treated overnight with bis-trimethylsilyl-trifluoroacetamide. The resultant derivatives were transferred to microsample vials and analyzed by GC-MS. Drug stability was quantified by electronic integration of peak areas representing characteristic ions for each drug. For each sample, the peak area of the methohexital ion (m/z 239) or propofol ion (m/z 235) relative to the corresponding thymol ion (m/z 207) served as an index of the concentration of the drug in the sample. At times varying from 0 to 48 hours, mixtures without thymol were used to determine mean droplet size of the particles. This was accomplished using both an Accusizer and a Nicomp 370 Particle Sizer. One way ANOVA tested for significant changes in drug concentrations and mean particle size as a function of time. There was no significant breakdown of propofol or methohexital when combined in a 1:1 mixture and allowed to stand for 48 hours, nor was there an increase in particle size suggestive of emulsion instability. We concluded that a 1:1 mixture of propofol and methohexital was stable up to 48 hours after mixing.

Empyema and bronchopleural fistula after pneumonectomy: factors affecting incidence.

BACKGROUND: Factors affecting the incidence of empyema and bronchopleural fistula (BPF) after pneumonectomy were analyzed. METHODS: All patients who underwent pneumonectomy at the Mayo Clinic in Rochester, Minnesota, from January 1985 to September 1998 were reviewed. There were 713 patients (514 males and 199 females). Ages ranged from 12 to 86 years (median 64 years). Indication for resection was primary malignancy in 607 patients (85.1%), metastatic disease in 32 (4.5%), and benign disease in 74 (10.4%). One hundred fifteen patients (16.1%) underwent completion pneumonectomy. Factors affecting the incidence of postoperative empyema and BPF were analyzed using univariate and multivariate analysis. RESULTS: Empyema was documented in 53 patients (7.5%; 95% confidence interval [CI], 5.7% to 9.7%) and a BPF in 32 (4.5%; 95% CI, 3.1% to 6.3%). Univariate analysis demonstrated that the development of empyema was adversely affected by benign disease (p = 0.0001), lower preoperative forced expiratory volume in 1 second (FEV1; p < 0.01) and diffusion capacity of lung to carbon monoxide (DLCO; p = 0.0001), lower preoperative serum hemoglobin (p = 0.05), right pneumonectomy (p = 0.0109), bronchial stump reinforcement (p = 0.007), completion pneumonectomy (p < 0.01), timing of chest tube removal (p = 0.01), and the amount of blood transfusions (p < 0.01). Similarly, the development of BPF was significantly associated with benign disease (p = 0.03), lower preoperative FEV1 (p = 0.03) and DLCO (p = 0.01), right pneumonectomy (p < 0.0001), bronchial stump reinforcement (p = 0.03), timing of chest tube removal (p = 0.004), increased intravenous fluid in the first 12 hours (p = 0.04), and blood transfusions (p = 0.04). Bronchial stump closure with staples had a protective effect against BPF compared with suture closure (p = 0.009). No risk factors were identified as being jointly significant in multivariate analysis. CONCLUSIONS: Multiple perioperative factors were associated with an increased incidence of empyema and BPF after pneumonectomy. Prophylactic reinforcement of the bronchial stump with viable tissue may be indicated in those patients suspected at higher risk for either empyema or BPF.

Prostaglandin E2 secretion from gingival fibroblasts treated with interleukin-1beta: effects of lipid extracts from Porphyromonas gingivalis or calculus.

Complex lipids of Porphyromonas gingivalis have been identified in lipid extracts from calculus-contaminated root surfaces and in diseased gingival tissues. However, little is known about the biological effects of these complex lipids on host cells. The purpose of this study was to evaluate the effects of P. gingivalis or calculus lipids on prostaglandin secretion from gingival fibroblasts. Lipids were extracted from paired subgingival plaque and teeth samples, and calculus-contaminated root surfaces before and after scaling and root planing, in order to determine the relevant levels of lipid extracts for the treatment of gingival fibroblasts in culture. Primary cultures of gingival fibroblasts were exposed to lipid extracts from either P. gingivalis or calculus/teeth for a period of 7 days. Control and lipid-treated cultures were exposed to human recombinant interleukin-1beta for 48 h and prostaglandin secretion from interleukin-1beta-treated fibroblasts was compared with control and lipid-treated fibroblasts without interleukin-1beta treatment. These experiments demonstrated that P. gingivalis lipids or calculus-tooth lipids potentiate interleukin-1beta-mediated prostaglandin secretory responses from gingival fibroblasts. Additionally, P. gingivalis or calculus-tooth lipid extracts were readily taken up by gingival fibroblasts as measured by bacterial fatty acid recovery in lipid extracts of cultured fibroblasts. These results indicate that bacterial lipid penetration into gingival tissues in combination with a chronic inflammatory response may substantially potentiate prostaglandin secretion from gingival fibroblasts, thereby promoting tissue destructive processes associated with adult periodontitis.

Management of postpneumonectomy empyema and bronchopleural fistula.

Empyema after pneumonectomy is often associated with a bronchopleural fistula (BDF) and has a significant mortality. Management options include systemic antibiotics and observation, adequate pleural drainage, appropriate parenteral antibiotics, removal of necrotic tissue, and obliteration of residual pleural space. We prefer to treat the empyema with the procedure originally described by Clagett and Geraci in 1963. They demonstrated that postpneumonectomy empyema could be successfully treated by open pleural drainage, frequent wet-to-dry dressing changes, and when the thorax was clean, secondary chest wall closure with obliteration of the pleural cavity with an antibiotic solution. Failure was most often caused by a persistent or recurrent fistula. Because of this, when a BPF is present, the original Clagett technique was modified to include transposition of a well-vascularized muscle to cover the stump at the time of open drainage to prevent further ischemia and necrosis. Our preference is intrathoracic transposition of extrathoracic skeletal muscle. The goals of therapy for postpneumonectomy empyema remain a healthy patient with a a healed chest wall and no evidence of drainage or infection. Excellent results can be obtained in more than 80% of patients by using the Clagett procedure and intrathoracic muscle transposition when a BPF is present.

Recruiting problem-based learning (PBL) tutors for a PBL-based curriculum: the Flinders University experience.

OBJECTIVES: To examine the contribution made to problem-based learning (PBL) by individual teachers and by departments in years 1 and 2 of a new graduate-entry medical programme (GEMP) with a PBL-based curriculum. METHODS: We compiled a database on all PBL tutoring undertaken in years 1 and 2 during the first 3 years in which the GEMP was delivered. This allowed us to quantify and analyse the contribution made by individuals and by departments. RESULTS: At 3 years following introduction of the GEMP, 136 (25.9%) of the school's 525 staff had trained as PBL tutors and 98 (18.7%) had tutored. Both individuals and departments differed greatly in the amount of time devoted to PBL tutoring. Staff who tutored once tended to tutor again in subsequent years. Compared with staff in clinical departments, those in non-clinical departments (who constituted 12% of the total) made a greater relative contribution though a smaller absolute contribution to tutoring. CONCLUSIONS: These findings prompted us to develop a formula that distributes the PBL tutoring load more evenly across departments. This was successfully introduced in 1999. It recognizes the fact that only a minority of staff will volunteer to become PBL tutors. Strategies that might encourage more staff to tutor are briefly discussed.