Immunoglobulin G4-related aortitis mimicking an intramural hematoma.

Immunoglobulin G4-related systemic disease is a rare entity with various presenting symptoms. We report the case of a 34-year-old Chinese male who presented with immunoglobulin G4-related aortitis and the unusual symptom of hoarseness of voice. He underwent distal ascending aorta and total aortic arch replacement.

CD166(pos) subpopulation from differentiated human ES and iPS cells support repair of acute lung injury.

Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient's own iPS cells to prevent immune rejection which arise from allogenic transplantation.

Relation between combining evidence-based medications on mortality following myocardial infarction in patients with and without renal impairment.

BACKGROUND: Antiplatelet agents, beta-blockers, statins and ACE inhibitors have been shown to reduce mortality in patients following myocardial infarction (MI). However, it is uncertain if the combination of these agents has a similar impact on mortality following MI in patients with renal dysfunction. METHODS: We studied 5529 consecutive patients with confirmed MI between January 2000 and December 2003. Data on baseline demographics, co-morbidities and in-hospital management were collected prospectively. Glomerular filtration rate (GFR) was estimated using the 4-component Modification of Diet in Renal Disease equation. Based on discharge use of evidence-based medications, the patients were divided into those using 0, 1, 2, 3 or 4 medications. The impact of medication use on 1-year mortality was then assessed for patients with GFR > or =60 ml/min/1.73 m2 (group I) and GFR < 60 ml/min/1.73 m2 (group 2). RESULTS: Mean age was 63 +/- 13 years with 71% men.The prevalence of reduced GFR was 35% and the adjusted odds ratio for I-year mortality of patients in group 2 compared to those in group I was 1.86 (95% CI 1.54-2.25, P < 0.001). Compared with patients with no medication, the adjusted odds ratio for 1-year mortality was lower in patients with 1, 2, 3 and 4 medications in both groups. There was no significant interaction between the number of medications used and GFR. CONCLUSION: Increased use of combined evidence-based medications was independently associated with a lower 1-year post MI mortality. Such therapies offer similar survival benefit in patients with and without renal dysfunction.

Comparison of mini-cardiopulmonary bypass system with air-purge device to conventional bypass system.

BACKGROUND: Although mini-cardiopulmonary bypass systems reduce inflammation, hemodilution, and transfusion requirements, the problem of air entrainment and embolization into the system has limited its use. Newer systems incorporate an air purge to address this problem. We compared the benefits and possible risks in using the newer mini-cardiopulmonary bypass system with those for conventional cardiopulmonary bypass. METHODS: Data of 60 patients who underwent cardiac surgery with a newer mini-cardiopulmonary bypass system incorporating an air purge from August 2005 to July 2006 (group A) were retrospectively collected and compared with that of 60 matched patients who underwent cardiac surgery with conventional cardiopulmonary bypass during the same period (group B). Matching criteria were prebypass hematocrit, body surface area, age, and surgical procedure. RESULTS: Demographic and background data were similar for both groups. There were no detectable episodes of air embolism. Patients in group A had higher initial and nadir hematocrits during cardiopulmonary bypass and received fewer transfusions. However, postoperative blood loss and transfusion requirements were similar in both groups. Episodes of low indexed flows during cardiopulmonary bypass commonly occurred in group A, and this was associated with a greater than 50% decrease in urine output and lower mixed venous oxygen saturations (58% +/- 6% versus 68% +/- 5%) as compared with group B. There were no differences in clinical outcomes. CONCLUSIONS: The newer mini-cardiopulmonary bypass system addressed the problem of air embolization. It preserved hematocrit and reduced transfusion during cardiopulmonary bypass, but did not improve outcomes postoperatively. It is unclear whether these benefits outweigh the potential risk of hypoperfusion associated with its use.

Contractile and vasorelaxant effects of hydrogen sulfide and its biosynthesis in the human internal mammary artery.

This study aimed to test these hypotheses: cystathionine gamma-lyase (CSE) is expressed in a human artery, it generates hydrogen sulfide (H(2)S), and H(2)S relaxes a human artery. H(2)S is produced endogenously in rat arteries from cysteine by CSE. Endogenously produced H(2)S dilates rat resistance arteries. Although CSE is expressed in rat arteries, its presence in human blood vessels has not been described. In this study, we showed that both CSE mRNA, determined by reverse transcription-polymerase chain reaction, and CSE protein, determined by Western blotting, apparently occur in the human internal mammary artery (internal thoracic artery). Artery homogenates converted cysteine to H(2)S, and the H(2)S production was inhibited by dl-propargylglycine, an inhibitor of CSE. We also showed that H(2)S relaxes phenylephrine-precontracted human internal mammary artery at higher concentrations but produces contraction at low concentrations. The latter contractions are stronger in acetylcholine-prerelaxed arteries, suggesting inhibition of nitric oxide action. The relaxation is partially blocked by glibenclamide, an inhibitor of K(ATP) channels. The present results indicate that CSE protein is expressed in human arteries, that human arteries synthesize H(2)S, and that higher concentrations of H(2)S relax human arteries, in part by opening K(ATP) channels. Low concentrations of H(2)S contract the human internal mammary artery, possibly by reacting with nitric oxide to form an inactive nitrosothiol. The possibility that CSE, and the H(2)S it generates, together play a physiological role in regulating the diameter of arteries in humans, as has been demonstrated in rats, should be considered.

Should non-expert clinician examiners be used in objective structured assessment of communication skills among final year medical undergraduates?

BACKGROUND: Adoption of the objective structured clinical examination may be hindered by shortages of clinicians within a specialty. Clinicians from other specialties should be considered as alternative, non-expert examiners. AIMS: We assessed the inter-rater agreement between expert and non-expert clinician examiners in an integrated objective structured clinical examination for final year medical undergraduates. METHODS: Pairs of expert and non-expert clinician examiners used a rating checklist to assess students in 8 oral communication stations, representing commonly encountered scenarios from medicine, paediatrics, and surgery. These included breaking bad news, managing an angry relative, taking consent for lumbar puncture; and advising a mother on asthma and febrile fits, and an adult on medication use, lifestyle changes and post-suture care of a wound. 439 students participated in the OSCE (206 in 2005, 233 in 2006). RESULTS: There was good to very good agreement (intraclass coefficient: 0.57-0.79) between expert and non-expert clinician examiners, with 5 out of 8 stations having intraclass coefficients > or =0.70. Variation between paired examiners within stations contributed the lowest variance to student scores. CONCLUSION: These findings support the use of clinicians from other specialties, as 'non-expert' examiners, to assess communication skills, using a standardized checklist, thereby reducing the demand on clinicians' time.

An alternative approach to determining therapeutic choices in advanced non-small cell lung carcinoma (NSCLC): maximizing the diagnostic procedure and the use of low-volume lung biopsies.

BACKGROUND: Accurate mutational analysis, especially epidermal growth factor receptor (EGFR) mutations, of diagnostic biopsies from all Asian NSCLC patients is crucial to their clinical management, but faces problems. Here, we explore, within usual hospital constraints, the practicalities of incorporating mutational analysis in every newly diagnosed case of NSCLC, namely, maximizing tissue acquisition during the diagnostic procedure and determining the maximum quantity and quality of DNA sequence data available from these biopsies. METHODS: Sixty-eight Chinese patients were enrolled. Thirty-five underwent surgical resections for early-stage tumors. Thirty-three underwent diagnostic procedures, i.e., needle aspirates under bronchoscopic or computed tomographic/fluoroscopic guidance, or forceps biopsies via bronchoscopy. Separate samples for research purposes were obtained from these 33 patients during the diagnostic procedure. All samples were analyzed for mutations in EGFR exons 18 to 21, p53 exons 4 to 9, and Kras exon 2. RESULTS: No deaths occurred in this study. Success rates in obtaining sequence data from surgical samples versus low-volume samples for EGFR, p53, and Kras were 100% versus 85%, 100% versus 82%, and 100% versus 85%, respectively. Sequencing nine polymerase chain reaction products from each low-volume sample resulted in the exhaustion of all extracted DNA from three samples. CONCLUSIONS: Acquiring a separate low-volume lung biopsy sample for mutational analysis in lung cancer patients during the diagnostic procedure is feasible and may be a valuable complement to the usual diagnostic workflow in future.

Combined open and endovascular repair of acute type A aortic dissection.

A 62-year-old man with an acute Stanford type A dissection underwent successful emergent replacement of the ascending aorta. The patient was readmitted with a left pleural effusion and complex dissection in the arch and descending thoracic aorta. A hybrid surgical procedure was performed involving complete arch transposition, followed by arch and descending aortic stenting, with a good result. The surgical management and techniques are reviewed.

Surgical coronary revascularization in severe left ventricular dysfunction.

Surgical revascularization in patients with coronary artery disease and severe left ventricular dysfunction is a common practice and poses a surgical challenge. From September 2002 to May 2004, 50 patients (47 men and 3 women; mean age, 59 +/- 9 years) with a mean preoperative ejection fraction of 19.7% +/- 3.2% underwent surgical revascularization. The mean EuroSCORE was 7.2 +/- 3.4. Indications for surgery were congestive heart failure in 8 patients (16%), angina in 20 (40%), ventricular arrhythmias in 4 (8%), and critical left main stem disease in 12 (24%). Twenty-two patients (44%) had emergency surgery for critical anatomy and unstable symptoms. The number of grafts per patient was 3.7 +/- 0.8. Seventeen patients (34%) required intra-aortic balloon pump support, 16 (32%) needed pacing, and 48 (96%) had inotropic support postoperatively. Morbidity included re-operation for bleeding (2%), acute renal failure (10%), hemodialysis (4%), and fatal multiorgan failure (4%). Postoperative (4.9 +/- 3.7 months) 2-dimentional echocardiography was available in 18 patients of whom 11 (61%) showed improved left ventricular function (range, 5% to 45%). Thirty-day hospital mortality was 8%. These data indicate that surgical revascularization can be performed safely with acceptable hospital mortality in high-risk patients with severe left ventricular dysfunction.

Expression of neuronal nitric oxide synthase in the internal thoracic artery and saphenous vein.

OBJECTIVES: Endothelial nitric oxide synthase (type III) generates nitric oxide, which dilates blood vessels. Recently, it was discovered that arterial smooth muscle cells express neuronal nitric oxide synthase (type I). The purpose of this study was to determine the relative amounts of neuronal nitric oxide synthase in the human internal thoracic artery and saphenous vein. METHODS: Remainder segments of internal thoracic arteries and saphenous veins were obtained from 45 patients during coronary artery bypass grafting. Western blotting used specific antibodies against the 3 isoforms of human nitric oxide synthase and beta-actin (for normalization) to measure the relative amounts of the 3 isoforms of nitric oxide synthase proteins in vessel specimens. Immunohistochemistry was used to localize the 3 proteins in specific cells. RESULTS: Western blotting detected all 3 isoforms of nitric oxide synthase in the human internal thoracic artery. The band density (normalized to beta-actin) of neuronal nitric oxide synthase was not significantly different from the band density of endothelial nitric oxide synthase. The amounts of neuronal nitric oxide synthase in arteries and veins were equal. Immunohistochemistry showed that the highest expression of endothelial nitric oxide synthase was in endothelial cells, but some expression was also seen in smooth muscle cells. Most of the neuronal nitric oxide synthase was in smooth muscle cells. The location and relative amounts of inducible nitric oxide synthase were variable. CONCLUSIONS: Neuronal nitric oxide synthase is expressed in the vascular smooth muscle of patients undergoing bypass, and the amount in the internal thoracic artery is the same as in the saphenous vein.

A randomized, double-blind, placebo-controlled trial of a COX-2 inhibitor (Rofecoxib) in patients undergoing coronary artery bypass surgery.

The endothelium of patients with coronary artery disease shows increased expression of cyclooxygenase-2 (COX-2) during coronary artery bypass graft surgery (CABG) using cardiopulmonary bypass. This, together with serotonin, may lead to coronary microvessel spasm, which potentially, can contribute to myocardial ischemia and injury after surgery. We performed a randomized, double-blind, placebo-controlled trial in patients undergoing isolated CABG to determine whether short-term treatment with a selective COX-2 inhibitor, Rofecoxib (25 mg), given preoperatively and for 5 days after operation, can offer better myocardial protection in patients undergoing CABG by measuring serial cardiac troponin T (cTnT) levels. The study was powered to recruit 150 consecutive patients undergoing isolated CABG but the study was terminated prematurely by the worldwide withdrawal of rofecoxib. There were highly statistically significant (P<0.001) increases in cTnT in both groups at each time point (1, 6, 24 and 48 h after onset of cardiopulmonary bypass) compared to preoperative levels. cTnT levels were similar at all post-operative time points between the 2 groups. There is no evidence that short-term treatment with rofecoxib has a myocardial protective effect in patients undergoing CABG. There is also no evidence that its effect is deleterious to the myocardium in patients undergoing CABG.

Combined blunt aortic and bronchial injury.

We report the case of a 29-year-old man with left blunt chest trauma resulting in an intimal tear of the proximal descending aorta, for which he underwent successful thoracic endovascular graft stenting. He subsequently developed progressive left lung collapse, and bronchoscopy revealed left bronchial disruption. A left thoracotomy with end-to-end anastomosis of the left bronchus was performed successfully. The literature from 6 other similar cases of concomitant aortic and bronchial injuries was reviewed.

Posterior mediastinal goiter.

Most mediastinal goiters are retrosternally situated in the anterior mediastinal compartment. Posterior mediastinal goiters, either retrotracheal or retroesophageal, are rare. We herein describe a case involving a retrotracheal goiter in the right posterior mediastinum, which was excised using a combined cervico-partial sternotomy and right thoracotomy approach.