Surgical resection of a massive primary mediastinal liposarcoma with cervical extension.

A 73-year-old man was referred for surgical excision of a massive mediastinal and cervical liposarcoma following neoadjuvant chemotherapy. Surgery was performed via a cervical incision, sternotomy and right posterolateral thoracotomy. The tumour arose from the oesophagus, which underwent extensive dissection and was oversewn with pleura after tumour resection. Histology confirmed a completely excised grade 2 de-differentiated liposarcoma with complete macroscopic excision. The patient made an excellent recovery. Oesophageal liposarcomas are rare and, unlike in this case, often extend intraluminally, necessitating oesophagectomy. To our knowledge, this is the largest such tumour found in the literature.

Oral and topical boswellic acid attenuates mouse osteoarthritis.

OBJECTIVE: Boswellic acid is a plant-derived molecule with putative anti-inflammatory effects. This study was performed to determine whether oral or topical administration of boswellic acid can attenuate joint damage in a mouse model of osteoarthritis (OA). METHODS: Levels of boswellic acid were measured in the blood and synovium of mice treated with oral or topical boswellic acid. OA was generated by surgical destabilization of the medial meniscus (DMM). Therapy with oral or topical boswellic acid was initiated one day after surgery and continued for 12 weeks, when knees were harvested and scored histologically for degree of cartilage loss, osteophyte formation, and synovitis. Microdissected OA synovium was stimulated with IL-1ß or lipopolysaccharide (LPS) in the presence or absence of boswellic acid and cytokine production by quantitative polymerase chain reaction (PCR) or multiplex enzyme linked immunoabsorbant assay (ELISA). RESULTS: Topical treatment resulted in synovial concentrations of boswellic acid 2-6-fold higher than that measured in plasma. Cartilage loss was significantly reduced in mice treated with oral or topical boswellic acid compared with vehicle control (P < 0.01 for both oral and topical therapies). Likewise, treatment with either oral boswellic acid or boswellic acid ointment reduced of synovitis (P = 0.006 and 0.025, respectively) and osteophyte formation (P = 0.009 and 0.030, respectively). In vitro, boswellic acid was able to inhibit IL-1ß and TLR4 mediated induction of several inflammatory mediators from OA synovial explant tissue. CONCLUSIONS: Significant synovial concentration and therapeutic efficacy can be achieved with topical boswellic acid treatment. These findings suggest that boswellic acid has potential as a disease-modifying agent in OA.

Idiopathic pulmonary arteriovenous malformations: clinical and imaging characteristics.

Pulmonary arteriovenous malformations (PAVMs) can cause stroke, brain abscess or life-threatening haemorrhage. Most PAVMs are associated with hereditary haemorrhagic telangiectasia (HHT). The aim of the present study was to describe the clinical presentation and treatment outcomes of those with idiopathic PAVMs, which has not previously been described in the literature. Patients with idiopathic PAVMs were identified at our HHT centre. Retrospective review of charts and imaging were performed. 20 patients were identified with idiopathic PAVMs. The most common symptoms reported were dyspnoea and migraines (50 and 30% of patients, respectively). Previous complications of PAVMs included haemoptysis (20%), stroke (20%) and brain abscess (5%). A total of 28 focal PAVMs were identified. Most patients (80%) had a solitary PAVM. 13 out of 28 PAVMs (46%) were located in the lower lobes. Most were simple and fistulous rather than complex and plexiform. Transcatheter embolotherapy was performed in 17 patients and was successful in improving oxygenation in all cases. The clinical manifestations and complications of idiopathic PAVMs are similar to those associated with HHT. Idiopathic PAVMs are anatomically similar to HHT-related PAVMs except for a greater number of solitary PAVMs and a lack of lower lobe predominance. Transcatheter embolotherapy is a safe and effective method for treating idiopathic PAVMs.

Targeted therapies for pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a devastating malignancy and a leading cause of cancer mortality. Furthermore, early diagnosis represents a serious hurdle for clinicians, as symptoms are non-specific and usually manifest in advanced, treatment-resistant stages of the disease. SOURCES OF DATA: Here, we review the rationale and progress of targeted therapies currently under investigation. AREAS OF AGREEMENT: At present, chemoradiation regimes are administered palliatively, and produce only marginal survival benefits, underscoring a desperate need for more effective treatment modalities. AREAS OF CONTROVERSY: Questions have been raised as to whether erlotinib, the only targeted therapy to attain a statistically significant increase in median survival, is cost-effective. GROWING POINTS: The last decade of research has provided us with a wealth of information regarding the molecular nature of pancreatic cancer, leading to the identification of signalling pathways and their respective components which are critical for the maintenance of the malignant phenotype. AREAS TIMELY FOR DEVELOPING RESEARCH: These proteins thus represent ideal targets for novel molecular therapies which embody an urgently needed novel treatment strategy.

Pediatric transplantation in the United States, 1995-2004.

This article reviews trends in pediatric solid organ transplantation over the last decade, as reflected in OPTN/SRTR data. In 2004, children younger than 18 years made up nearly 3% of the 86,378 candidates for organ transplantation and nearly 7% of the 27,031 organ transplant recipients. Children accounted for nearly 14% of the 7152 deceased organ donors. The transplant community recognizes important differences between pediatric and adult organ transplant recipients, including different etiologies of organ failure, surgical procedures that are more complex or technically challenging, effects of development on the pharmacokinetic properties of common immunosuppressants, unique immunological aspects of transplant in the developing immune system and increased susceptibility to posttransplant complications, particularly infectious diseases. For these reasons, and because of the impact of end-stage organ failure on growth and development, the transplant community has generally provided pediatric candidates with special consideration in the allocation of deceased donor organs. Outcomes following kidney, liver and heart transplantation in children often rank among the best. This article emphasizes that the prospects for solid organ transplantation in children, especially those aged 1-10 years are excellent. It also identifies themes warranting further consideration, including organ availability, adolescent survival and challenges facing pediatric transplant clinical research.

SRTR center-specific reporting tools: Posttransplant outcomes.

Measuring and monitoring performance--be it waiting list and posttransplant outcomes by a transplant center, or organ donation success by an organ procurement organization and its partnering hospitals--is an important component of ensuring good care for people with end-stage organ failure. Many parties have an interest in examining these outcomes, from patients and their families to payers such as insurance companies or the Centers for Medicare and Medicaid Services; from primary caregivers providing patient counseling to government agencies charged with protecting patients. The Scientific Registry of Transplant Recipients produces regular, public reports on the performance of transplant centers and organ procurement organizations. This article explains the statistical tools used to prepare these reports, with a focus on graft survival and patient survival rates of transplant centers--especially the methods used to fairly and usefully compare outcomes of centers that serve different populations. The article concludes with a practical application of these statistics--their use in screening transplant center performance to identify centers that may need remedial action by the OPTN/UNOS Membership and Professional Standards Committee.

Structural changes to airway smooth muscle in cystic fibrosis.

BACKGROUND: Chronic airway obstruction is characteristic of cystic fibrosis (CF) but there are few studies of airway smooth muscle remodelling in CF. METHODS: Airway smooth muscle content and mean airway smooth muscle cell size were measured by applying design-based stereology to bronchoscopic biopsy specimens obtained from seven subjects with CF and 15 healthy controls. RESULTS: The smooth muscle content increased by 63% in subjects with CF (mean (SD) 0.173 (0.08) v 0.106 (0.042) mm(3) smooth muscle/mm(3) submucosa, mean difference -0.067; 95% CI -0.12 to -0.013, p = 0.017) but there was no increase in mean cell size (2705 (351) v 2654 (757) microm(3), mean difference -51; 95% CI -687 to 585, p = 0.87). CONCLUSIONS: These findings indicate hyperplasia of airway smooth muscle cells without hypertrophy and suggest that accumulation of airway smooth muscle cells may contribute to airway narrowing and bronchial hyperresponsiveness in CF.

Allergen challenge causes inflammation but not goblet cell degranulation in asthmatic subjects.

BACKGROUND: An allergen challenge to the airways of sensitized mice causes eosinophilic airway inflammation and degranulation of goblet cells, which lead to airway obstruction. However, whether allergen challenge causes a similar pattern of airway inflammation and goblet cell degranulation in human beings is unknown. OBJECTIVE: The purpose of this study was to determine whether allergen challenge increases airway inflammatory cells and causes goblet cell degranulation in human subjects with asthma. METHODS: In bronchial biopsy specimens taken from 8 asthmatic subjects at 1 and 24 hours after allergen challenge, we measured eosinophil and neutrophil numbers as indicators of inflammation. We also measured goblet cell mucin stores and the amounts of secreted mucin in bronchial lavage as indicators of goblet cell degranulation. RESULTS: Airway eosinophil numbers at both 1 and 24 hours after allergen challenge were twice as high as those after diluent challenge. Changes in neutrophil numbers were smaller and statistically insignificant. Goblet cell mucin stores measured in tissue stained with alcian blue/periodic acid-Schiff did not decrease significantly from baseline to 1 hour and actually tended to increase at 24 hours. This increase was significant in the subgroup of subjects with normal stored mucin levels at baseline. Mucin-like glycoprotein concentrations in bronchial lavage did not change significantly at either time point. CONCLUSION: Although allergen challenge in asthmatic subjects increases airway eosinophil numbers as early as 1 hour after challenge, this inflammatory response does not cause goblet cell degranulation. In fact, in subjects with normal baseline mucin stores, allergen challenge increases goblet cell mucin stores.

Abdominal wall abscess secondary to spilled gallstones: late complication of laparoscopic cholecystectomy and preventive measures.

Spilled gallstones left in the abdominal cavity or trapped at trocar sites may cause considerable morbidity. We saw a patient with an abdominal wall abscess 2 years after laparoscopic cholecystectomy secondary to spilled stones. After we reviewed the operative procedure in addition to the accumulated experience in laparoscopic surgery, we believe that retrieval of specimens and their contents is of paramount importance, especially when the gallbladder is infected, contains several stones, or may harbor malignancy. Therefore, we made use of a simple surgical glove with a long pursestring suture surrounding the opening to collect the specimen. This method proved to be simple and quite convenient, with the needed materials readily available. It can collect the spilled stones within the abdominal cavity as well as the gallbladder and can transport these stones out of the abdominal cavity with ease and safety. It also protects the specimen in contact with the wound and cuts short the operating time. The technique and advantages are described.

Mild and moderate asthma is associated with airway goblet cell hyperplasia and abnormalities in mucin gene expression.

Excessive airway mucus is an important cause of morbidity and mortality in asthma, but the relationship between accumulation of mucus and goblet cell size, number, and function is incompletely understood. To address these questions, stored mucin in the epithelium and goblet cell size and number were measured morphometrically, and mucin gene expression was measured by polymerase chain reaction and immunohistochemistry in endobronchial biopsies from 13 subjects with mild and moderate asthma and from 12 healthy control subjects. Secreted mucin was measured in induced sputum. We found that stored mucin in the airway epithelium was three times higher than normal in the subjects with asthma (p < 0.005). Goblet cell size was similar in both groups, but goblet cell number was significantly higher in the subjects with asthma (93,043 +/- 15,824 versus 41,959 +/- 9,230/mm3, p < 0.05). In mild asthma (FEV1 > or = 80% pred, n = 7), the level of stored mucin was as high as in moderate asthma (FEV1 < 80% pred, n = 6), but the level of secreted mucin was significantly lower (28.4 +/- 6.3 versus 73.5 +/- 47.5 microg/ml, p < 0.05). Secreted mucin was inversely correlated with stored mucin for the whole asthma group (rs = -0.78, p = 0.007). MUC5AC was the predominant mucin gene expressed in healthy subjects and subjects with asthma, and MUC5AC protein was increased in the subjects with asthma. We conclude that even mild asthma is associated with goblet cell hyperplasia and increased stored mucin in the airway epithelium, whereas moderate asthma is associated with increased stored mucin and secreted mucin. These findings suggest that acute degranulation of hyperplastic goblet cells may represent a mechanism for asthma exacerbations in mild and moderate asthma and that chronic degranulation of goblet cells may contribute to chronic airway narrowing in moderate asthma.

Migration of endoclip into duodenum. A rare complication after laparoscopic cholecystectomy.

The long-term effect of spilled clips within the abdominal cavity after laparoscopic cholecystectomy is unknown. However, most surgeons agree that the migration of clips has limited clinical consequences. A few cases have been reported of clips that have migrated into the common bile duct, causing stone formation and/or obstructions. We present a case of gallstone pancreatitis treated with laparoscopic cholecystectomy that was complicated by bile leakage from the cystic duct stump 1 day after the procedure. Although the leaking stump sealed itself spontaneously after the placement of a biliary stent, a clip had migrated directly to the superior wall of the first portion of the duodenum. Herein the details of the patient's history are presented. We also discuss the possible mechanisms of clip migration and describe some preventive measures.

Epithelial desquamation in asthma: artifact or pathology?

To determine whether the denudation of the bronchial epithelium observed in endobronchial biopsies from asthmatic subjects is a true pathologic feature or an artifact of tissue sampling, we analyzed epithelial integrity in bronchial biopsies from 14 subjects with mild and moderate asthma and 12 healthy subjects. In each subject, 4 to 8 bronchial biopsies were taken from large airways during bronchoscopy, fixed in 4% paraformaldehyde, embedded in glycomethacrylate, cut into 2-microM sections, and stained with toluidine blue. A x4 image of each biopsy was copied to a computer file using a video camera, and lines were drawn and measured along the basement membrane underlying areas completely denuded of overlying epithelium, areas covered by a single layer of basal cells, and areas of intact epithelium. We found that the percentage of basement membrane that was denuded of epithelium was similar in the healthy and asthmatic subjects (14.8 +/- 11.8 versus 11.4 +/- 9.8% respectively, p = 0.38); the percentage of basement membrane that was covered by a single layer of basal cells was also similar in the two groups (46.4 +/- 11.0 versus 54.5 +/- 9.8%, respectively, p = 0. 11). In the asthmatic subjects, we found no significant correlation between the percentage of basement membrane covered by denuded epithelium or by a single layer of basal cells and the FEV(1) percentage of predicted or the PC(20) methacholine. We conclude that denudation of bronchial epithelium in endobronchial biopsies from asthmatic subjects with stable mild and moderate disease is an artifact of tissue sampling and is not a true pathologic feature of the disease, and that the extent of airway epithelial denudation is not correlated with the severity of airway narrowing or the severity of bronchial hyperresponsiveness.

Laparosopic removal of large gastric phytobezoars.

Large gastric bezoars are difficult to remove endoscopically. A 78-year-old man presenting with abdominal pain and loss of appetite for 4 months was admitted and evaluated. Gastroscopy disclosed two large phytobezoars within the stomach. Laparoscopic removal was undertaken. The bezoars were removed via a gastrotomy using the three-trocar technique. They were successfully retrieved from the abdominal cavity using an improvised "endobag" made from a simple surgical glove. Such an endobag presents several advantages; they are easy to make, sterile, economical, readily available, disposable, there is ample space to manipulate the specimen within, and there is minimal risk of contamination throughout the procedure. The authors recommend this approach for the treatment of patients with large gastric bezoars in whom laparotomy is indicated.

Liberal use of a bag made from a surgical glove during laparoscopic surgery for specimens retrieval.

Laparoscopic surgery has been gaining wide acceptance in recent years. Tissue removal from the abdominal cavity becomes a paramount issue, especially when the specimen is infected, contains several fragments, or potentially contains a malignancy. Several sophisticated instruments and devices have been designed for this purpose. However, most of these are expensive, difficult to handle, and come in a fixed size. Condoms, glove fingers, and zipper-type plastic bags have been tried also, but with limited success. The authors report use of a simple bag made from a surgical glove to collect specimens; a long purse-string suture surrounds the opening or the base of the glove finger to secure material during retrieval. This method has been found to be simple and convenient, and necessary construction material is readily available. The bag not only protects the specimen from contact with the wound but also cuts short the operating time. The technique and advantages are described.

Predictors of late asthmatic response. Logistic regression and classification tree analyses.

To identify predictors of the late asthmatic response (LAR), we reviewed data from 60 asthmatic subjects who had undergone allergen challenge over the past 5 yr (33 females, age 31.4 +/- 6.7 yr [mean +/- SD], FEV(1) 90% +/- 14% predicted). Variables considered likely predictors of LAR included baseline FEV(1), PC(20) methacholine (PC(20)), sputum eosinophil percent, and the decrease in FEV(1) within 20 min of allergen challenge. A LAR (FEV(1) >/= 15% fall between 3 and 7 h after challenge) was documented in 57% of subjects. A variety of logistic regression methods revealed a significant inverse association between LAR and PC(20) (odds ratio [OR] = 0.14 [95% CI = 0.03-0.66]) and a positive association between LAR and the decrease in FEV(1) at 20 min (OR = 1.18 [1.04 -1.33]). Classification tree analysis revealed that a threshold of 0.25 mg/ml for PC(20) was most predictive of LAR; LAR developed in 87% of those with PC(20) 0.25 mg/ml (n = 37). Notably, in subjects with PC(20) > 0.25 mg/ml, the incidence of LAR increased from 38% to 57% if the allergen-induced decline in FEV(1) at 20 min was >/= 27%. Surprisingly, baseline FEV(1) and percent eosinophils in induced sputum were not significantly associated with LAR. We conclude that a threshold value of 0.25 mg/ml for PC(20) methacholine is a good predictor of LAR. Measuring the PC(20) methacholine may be useful as a screening method to improve the efficiency of identifying asthmatic subjects with a LAR.

Production of medium-chain-length polyhydroxyalkanoates by high-cell-density cultivation of Pseudomonas putida under phosphorus limitation.

High-cell-density fed-batch cultures of Pseudomonas putida were carried out for the production of medium-chain-length polyhydroxyalkanoates (PHAs) using oleic acid as a carbon source. By employing an optimal feeding strategy without the limitation of any nutrient, a high cell concentration of 173 g/L was achieved, but the PHA concentration and PHA content were only 32.3 g/L and 18.7 wt%, respectively. To increase the PHA concentration and content, phosphorus limitation was applied during fed-bath culture by reducing the initial KH(2)PO(4) concentration. When the initial KH(2)PO(4) concentration was reduced to 4 g/L, cell concentration, PHA concentration, and PHA content obtained in 38 h were 141 g/L, 72. 6 g/L, and 51.4 wt%, respectively, resulting in a high productivity of 1.91 g PHA/L per hour.

Low- and high-dose fluticasone propionate in asthma; effects during and after treatment.

The dose dependency of the effects of inhaled corticosteroids on markers of asthmatic airway inflammation have not been well studied. There is a need to study the dose/response effects on this inflammation. In order to determine the dose/response effects of fluticasone propionate (FP), 24 asthmatic subjects were randomized to low- (100 microg x day(-1)) or high-dose (1,000 microg x day(-1)) FP for six weeks followed by placebo for 3 weeks. During treatment, the median increase in forced expiratory volume in one second (FEV1)was 12% in the high-dose group (p<0.05) and 10% in the low-dose group (p<0.05) (p>0.05 between groups); the median decrease in the percentage of sputum eosinophils was 93% in the high-dose group (p<0.05) and 46% in the low-dose group (p<0.05) (p>0.05 between groups). Symptoms, salbutamol use, morning peak flow, provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophil cationic protein concentration and tryptase activity improved significantly in both groups (p<0.05), but only the improvement in salbutamol use was greater in the high-dose group (p<0.05). During the run-out, the improvements in FEV1 and PC20 were rapidly reversed in both groups, but the improvements in peak flow and tryptase activity persisted; the improvement in sputum eosinophil concentration persisted only in the high-dose group (p<0.05). It was concluded that dose/response effects for FP are not easily demonstrable because low-dose FP is quite effective. For most outcomes, the effects of high- and low-dose FP are relatively short-lived after treatment is stopped. This finding raises questions about the extent to which inhaled corticosteroids are disease-modifying in asthma.

Effect of aerosolized anti-IgE (E25) on airway responses to inhaled allergen in asthmatic subjects.

Intravenous administration of a humanized monoclonal antibody of IgE (E25) attenuates the early and late phase response to inhaled allergen in allergic asthmatic subjects. To test whether direct delivery of E25 to the airway might have the same effect, we conducted a randomized, double-blind, three group study in 33 subjects with mild allergic asthma (20 to 46 yr of age, 21 men, FEV(1) > 70% predicted). The airway responses to aerosolized allergen were determined at baseline, after 2 and 8 wk of once daily treatment with aerosolized placebo (n = 11), aerosolized E25 1 mg (n = 12), or aerosolized E25 10 mg (n = 10), and after 4 wk of treatment withdrawal. We found that E25 was detectable in the serum during aerosol treatment, although serum IgE did not change significantly in any of the three groups during treatment. In addition, both doses of E25 were no more effective than placebo in attenuating the early phase responses to allergen at both times during treatment. Although aerosolized E25 was generally well tolerated, one subject receiving aerosolized E25 10 mg daily was found to have serum IgG and IgA antibodies to E25. We conclude that aerosol administration of an anti-IgE monoclonal antibody does not inhibit the airway responses to inhaled allergen in allergic asthmatic subjects. We speculate that the observed lack of efficacy may be due to the inability of aerosol route of delivery to result in high enough concentrations of E25 in the tissue compartments surrounding IgE effector cells to neutralize IgE arising from local airway and pulmonary sources and IgE arising from the vascular space. Additionally, the aerosol route of delivery of monoclonal antibodies may be more immunogenic than the parenteral route.

Fractional analysis of sequential induced sputum samples during sputum induction: evidence that different lung compartments are sampled at different time points.

BACKGROUND: The effect of the duration of sputum induction on markers of inflammation in induced sputum is unknown, and the optimal duration of sputum induction for research purposes in airway disease is uncertain. OBJECTIVE: We sought to determine whether the duration of sputum induction influences the cellular or biochemical characteristics of induced sputum. METHODS: Induced sputum was collected sequentially at 4-minute intervals during a 20-minute sputum induction in 12 subjects with mild and moderate asthma. Each 4-minute sample was collected and analyzed separately for total and differential cell counts and for levels of eosinophil cationic protein, fibrinogen, mucin-like glycoprotein, and surfactant protein SP-A. RESULTS: The percentages of eosinophils and neutrophils were significantly higher at the beginning of the 20-minute sputum induction than at the end, whereas the percentage of macrophages was significantly lower at the beginning than at the end. In addition, the levels of eosinophil cationic protein and mucin-like glycoprotein were significantly higher at the beginning of the 20-minute induction than at the end, whereas the level of surfactant protein SP-A was significantly lower. CONCLUSIONS: The duration of sputum induction significantly affects the cellular and biochemical composition of induced sputum in a manner suggesting that large airways are sampled at the beginning of sputum induction, whereas peripheral airways and alveoli are sampled at later time periods. Our data demonstrate the importance of standardizing the duration of sputum induction in clinical research studies, and on the basis of these data, we have chosen 12 minutes as the optimal duration for sputum induction in asthmatic subjects.

Recent advances in polyhydroxyalkanoate production by bacterial fermentation: mini-review.

Poly(3-hydroxybutyrate) [P(3HB)] and other polyhydroxyalkanoates (PHAs) have been drawing much attention as biodegradable substitutes for conventional nondegradable plastics. For the economical production of P(3HB), various bacterial strains, either wild-type or recombinant, and new fermentation strategies were developed for the production of P(3HB) with high concentration and productivity. To reduce the cost of carbon substrate, several processes for P(3HB) production from cheap carbon sources were also developed. P(3HB) can now be produced to a content of 80% of cell dry weight with the productivity greater than 4 g/l per h. Fermentation strategy was also developed for the efficient production of medium chain length PHA by high cell density culture. With all these advances, P(3HB) and PHAs can be produced by bacterial fermentation at a cost (ca. $2/kg) similar to that of other biodegradable polymers under development.