Identification of tissue-dependent proteins in knee OA synovial fluid.

OBJECTIVE: For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis. DESIGN: Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation. RESULTS: Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid revealed 70 proteins with a relatively higher abundance and 264 proteins with a relatively lower abundance in osteoarthritic synovial fluid. Of the 70 higher abundance proteins, 23 were amongst the most highly expressed in the secretomes of a specific intra-articular tissue measured. Tissue-dependent release was validated for SLPI, C8, CLU, FN1, RARRES2, MATN3, MMP3 and TNC. Abundance in synovial fluid of tissue-dependent proteins was validated for IGF2, AHSG, FN1, CFB, KNG and C8. CONCLUSIONS: We identified proteins with a tissue-dependent release from intra-articular human knee OA tissues. A number of these proteins also had an osteoarthritis-specific abundance in knee synovial fluid. These proteins may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis.

Determining predictive metabolomic biomarkers of meniscal injury in dogs with cranial cruciate ligament rupture.

OBJECTIVES: This study used hydrogen nuclear magnetic resonance spectroscopy for the first time to examine differences in the metabolomic profile of stifle joint synovial fluid from dogs with cranial cruciate ligament rupture with and without meniscal injuries, in order to identify biomarkers of meniscal injury. Identifying a biomarker of meniscal injury could then ultimately be used to design a minimally invasive diagnostic test for meniscal injuries in dogs. MATERIALS AND METHODS: Stifle joint synovial fluid was collected from dogs undergoing stifle joint surgery or arthrocentesis for lameness investigations. We used multi-variate statistical analysis using principal component analysis and univariate statistical analysis using one-way analysis of variance and analysis of co-variance to identify differences in the metabolomic profile between dogs with cranial cruciate ligament rupture and meniscal injury, cranial cruciate ligament rupture without meniscal injury, and neither cranial cruciate ligament rupture nor meniscal injury, taking into consideration clinical variables. RESULTS: A total of 154 samples of canine synovial fluid were included in the study. Sixty-four metabolites were annotated to the hydrogen nuclear magnetic resonance spectroscopy spectra. Six spectral regions were found to be significantly altered (false discovery rate adjusted P-value <0.05) between groups with cranial cruciate ligament rupture with and without meniscal injury, including three attributed to nuclear magnetic resonance mobile lipids [mobile lipid -CH3 (P=0.016), mobile lipid -n(CH3 )3 (P=0.017), mobile unsaturated lipid (P=0.031)]. CLINICAL SIGNIFICANCE: We identified an increase in nuclear magnetic resonance mobile lipids in the synovial fluid of dogs with meniscal injury which are of interest as potential biomarkers of meniscal injury.

Characterization of the public transit air microbiome and resistome reveals geographical specificity.

BACKGROUND: The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized. RESULTS: City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes. CONCLUSIONS: Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.

PM2.5 on the London Underground.

INTRODUCTION: Despite the London Underground (LU) handling on average 2.8 million passenger journeys per day, the characteristics and potential health effects of the elevated concentrations of metal-rich PM2.5 found in this subway system are not well understood. METHODS: Spatial monitoring campaigns were carried out to characterise the health-relevant chemical and physical properties of PM2.5 across the LU network, including diurnal and day-to-day variability and spatial distribution (above ground, depth below ground and subway line). Population-weighted station PM2.5 rankings were produced to understand the relative importance of concentrations at different stations and on different lines. RESULTS: The PM2.5 mass in the LU (mean 88 µg m-3, median 28 µg m-3) was greater than at ambient background locations (mean 19 µg m-3, median 14 µg m-3) and roadside environments in central London (mean 22 µg m-3, median 14 µg m-3). Concentrations varied between lines and locations, with the deepest and shallowest submerged lines being the District (median 4 µg m-3) and Victoria (median 361 µg m-3 but up to 885 µg m-3). Broadly in agreement with other subway systems around the world, sampled LU PM2.5 comprised 47% iron oxide, 7% elemental carbon, 11% organic carbon, and 14% metallic and mineral oxides. Although a relationship between line depth and air quality inside the tube trains was evident, there were clear influences relating to the distance from cleaner outside air and the exchange with cabin air when the doors open. The passenger population-weighted exposure analysis demonstrated a method to identify stations that should be prioritised for remediation to improve air quality. CONCLUSION: PM2.5 concentrations in the LU are many times higher than in other London transport Environments. Failure to include this environment in epidemiological studies of the relationship between PM2.5 and health in London is therefore likely to lead to a large exposure misclassification error. Given the significant contribution of underground PM2.5 to daily exposure, and the differences in composition compared to urban PM2.5, there is a clear need for well-designed studies to better understand the health effects of underground exposure.

Repair of DNA alkylation induced in L1210 leukemia and murine bone marrow by three chloroethylnitrosoureas.

The removal of DNA adducts is an essential step of DNA repair following exposure to chloroethylnitrosoureas. Adduct removal was evaluated in both L1210 and murine bone marrow DNA for lesions induced by three chloroethylnitrosoureas. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea, a marrow-toxic agent with high carbamoylating activity, was not removed in either system for at least 6 to 12 hr. These results were compared with those obtained with two glucose-linked chloroethylnitrosoureas, chlorozotocin and 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea. Both of these agents have low marrow toxicity at therapeutic doses. Chlorozotocin, which has very low chemical carbamoylating activity, was found to permit approximately 40% removal of drug-derived DNA adducts in both systems within the first 6 hr and approximately 50% by 18 hr. The second glucose-linked analog, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea, has relatively high carbamoylating activity and was found to inhibit early removal of DNA adducts as effectively as does 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. It would thus appear that the selective marrow-sparing property of the sugar-linked chloroethylnitrosoureas is not dependent upon carbamoylation-mediated differences in the rate and extent of DNA adduct removal. In view of the comparable therapeutic activity of the three drugs for L1210 leukemia, therapeutic efficacy does not appear to be impaired by the increased rate of adduct removal observed with chlorozotocin in this system.

Delayed pericardial disease after radiotherapy.

Delayed chronic constrictive pericarditis developed in seven patients 51 to 268 (mean 116) months after radiotherapy. Six of the seven complained of exertional dyspnea that was initially believed to be caused by mediastinal fibrosis. All patients had raised jugular venous pressure, although in two patients this finding was not appreciated by the primary physician. There were no consistent noninvasively identifiable features to allow prediction of constrictive pericarditis other than consideration of its existence and careful examination of the cardiovascular system. All patients had constrictive pericarditis proved at cardiac catheterization. Of the five patients who underwent pericardiectomy, two had an excellent functional result, one has residual pericardial constriction and two died of unrelated causes. Recommendations for the treatment of radiation-induced pericardial disease are given.

Value of anterior mediastinotomy in bronchogenic carcinoma of the left upper lobe.

Neoplasms of the left upper lobe may spread directly to the anterior mediastinal group of nodes without involving the inferior tracheobronchial, superior tracheobronchial, or paratracheal nodal chain. Routine cervical mediastinoscopy does not sample the anterior mediastinal node group. Parasternal anterior mediastinotomy was performed in 28 patients with left upper lobe carcinoma and normal findings from cervical mediastinoscopy. Despite the normal findings at cervical mediastinoscopy, 10 of the 28 patients were deemed to have inoperable disease because of spread of the neoplasm to the anterior nodal group or because of direct neoplastic involvement of the aorta or main pulmonary artery. All patients in whom results of anterior mediastinotomy were normal had resectable lesions at thoracotomy. Fourteen of the 16 patients who came to thoracotomy had normal hilar nodes. Parasternal anterior mediastinotomy, introduced by Chamberlain, should be performed in addition to standard cervical mediastinoscopy if the nodal drainage of left upper lobe neoplasms is to be more completely evaluated. Combining these two procedures samples all major drainage pathways except the posterior mediastinal nodal chain.

Echocardiography in Lutembacher's syndrome.

The findings in a patient with surgically proven Lutembacher's syndrome (coexisting mitral stenosis and atrial septal defect) are presented. In addition to a typical pattern of mitral stenosis, the preoperative echocardiogram revealed paradoxical septal motion, thereby providing, prior to cardiac catheterization, a basis for the suspicion of an associated lesion due to diastolic overload of the right ventricle.

Dipyridamole-aspirin as thromboembolic prophylaxis in patients with aortic valve prosthesis. Prospective study with the Model 2320 Starr-Edwards prosthesis.

In a prospective study, the efficacy of a dipyridamole-aspirin regimen in prevention of thromboembolism was evaluated in 50 patients having isolated aortic valve replacement with the Model 2320 Starr-Edwards prosthesis. These operations were performed between February, 1972, and October, 1974. In 1,380 patient-months of follow-up, there was a 20% incidence of thromboembolism with a rate of 8.7/100 patient-years and a 19% probability of an embolic episode occurring by 3 years. Seven patients had transient episodes, two had permanent neurologic residua, and one patient died. Comparison is made to a similar group of patients having solitary aortic valve replacement but receiving no medication, studied by Starr and associates. There was no statistical difference in the incidence of thromboembolism between the two groups. In November, 1975, all patients were converted to a regimen of warfarin therapy. Since conversion to anticoagulation, there have been two thromboembolic episodes in 2,132 patient-months of follow-up for a rate of 1.1/100 patient-years. We conclude that the use of antiplatelet therapy in the form of dipyridamole-aspirin is inadequate for routine thromboembolic prophylaxis following SE 2320 aortic valve replacement.

Giant coronary pseudoaneurysm. Five-year follow-up after bypass grafting.

A roentgenogram of the shoulder in a 25-year-old man with an athletic injury revealed a large mass along the left heart border. Evaluation with coronary arteriography established the diagnosis of a massive aneurysm of the left anterior descending coronary artery. The aneurysm was excised and a saphenous vein bypass graft was placed into the distal artery. Histologic examination revealed that the excised segment was a false aneurysm. Five years postoperatively, the patient is asymptomatic and the graft remains widely patent.

Use of a zipper in cardiac surgical operations.

A simplified technique to gain repeated access to the median sternotomy incision is presented. The technique involves the use of a sterile polyester zipper attached to the skin edge. The sternum remains open. Unzipping the zipper allows for repeated relief of cardiac tamponade and viewing of cardiac action. Other advantages include prevention of cardiac compression or kinking of assist device cannulas from sternal closure, ease in changing of dressings, and quick removal of ventricular assist devices without reopening the sternum.

Secundum atrial septal defect and cleft mitral valve.

The association of a secundum atrial septal defect and mitral insufficiency is not uncommon. Five patients with this combination of lesions are presented and the pathological anatomy of the mitral valve is discussed. All 5 patients demonstrated a similar cleft mitral valve; 2 had cleft valves when only mitral valve prolapse was suspected preoperatively. The surgical implication of these lesions is discussed.

Thoracic traction for median sternotomy dehiscence.

Standard management of median sternotomy dehiscence sometimes fails to achieve lasting reduction and fixation of the sternal halves. An effective method of external thoracic traction that augments internal fixation of the sternal fracture is presented.

Pulmonary sequestration. A broad spectrum of bronchopulmonary foregut abnormalities.

We believe the broad clinical, embryological, and radiological spectrum of pulmonary sequestration has not been adequately emphasized. In order to gain clearer understanding of these foregut abnormalities, all cases from the files of three Army Medical Centers were reviewed. Thirty-two patients, the largest single series in the literature, met the criteria for a diagnosis of bronchopulmonary sequestration. Clinical manifestations varied from no symptoms to recurrent pulmonary infection, hemoptysis, and intrapleural hemorrhage. The presence of symptoms strongly correlated (23/32) with air-containing cystic sequestrations. The embryological and radiological spectra as well as appropriate operative therapy are reviewed.

Surgical management of lung cancer with solitary cerebral metastasis.

Between 1964 and 1986, 19 patients underwent resection of both a primary lung cancer and the associated brain metastasis. One patient underwent resection of 2 separate primary lung cancers and the associated metastases. The 12 men and 7 women ranged in age from 42 to 67 years (mean, 54.6 years). The cell type was adenocarcinoma in 12 tumors, squamous or adenosquamous cell in 5, large cell undifferentiated or anaplastic in 2, and malignant carcinoid in 1 tumor. The types of resection were as follows: lobectomy for 12 neoplasms, pneumonectomy for 5, bilobectomy for 2, and wedge resection for 1 neoplasm. Radiotherapy to the brain was given in connection with sixteen of the twenty craniotomies. The patient with 2 separate primary neoplasms survived 19 years before dying 5 months after the second craniotomy. The mean survival is 8.0 +/- 2.1 years (+/- the standard error), and the median survival is 1.67 years. Survival at 1 year was 65 +/- 10.7% and at 5 years, 45 +/- 11.1%. On univariate analysis, the following factors were found to correlate significantly with longer survival: a lung tumor in Stage I or II; negative mediastinal nodes; curative rather than palliative resection of the lung tumor; and age younger than 55 years. However, on multivariate analysis, only curative resection was a significant factor (p less than 0.01). We believe these results justify continued application of this combined surgical approach to patients having limited-stage lung cancer with a solitary brain metastasis.

Management of penetrating cardiac injuries: the role of emergency room thoracotomy.

Sixty-four consecutive patients with penetrating cardiac injuries were treated between January, 1977, and January, 1983, at the University of Maryland Hospital. Twenty-eight patients had major associated injuries of other organs. The patients were divided into groups according to their clinical status on arrival. An aggressive approach was utilized including early emergency room (ER) thoracotomy for "lifeless" or deteriorating patients. Three patients required immediate cardiopulmonary bypass for repair of their injuries. Twenty-one (57%) of the 37 patients undergoing ER thoracotomy survived; most of the deaths occurred in patients arriving "lifeless" from gunshot wounds. Twenty-four (89%) of the 27 patients who were in stable enough condition to undergo initial repair in the operating room (OR) survived. Overall survival was 45 patients (70%). Though superficial wound infections developed in 18 patients, there were no deep or systemic infections. None of the survivors sustained severe neurological sequelae. Five patients underwent late reoperations for closure of a ventricular septal defect (2), mitral valve replacement (1), and pericardiectomy (2) with no deaths. Though repair of penetrating cardiac injuries should preferably be carried out in the OR, immediate thoracotomy for "lifeless" or deteriorating patients can be performed in the ER with a low incidence of direct surgical complications and with high patient survival.

An in vivo canine model for testing treatment effects in laryngeal hyperadduction disorders.

Adductor spastic dysphonia is a voice disorder characterized by a strained, squeezed, effortful voice produced by true and false cord hyperadduction. An in vivo canine model has been developed to simulate hyperadduction of the true cords. Using this model, the thyroarytenoid muscle was found to have a greater effect on intraglottic and subglottic pressure than cricothyroid muscle contraction. The intraglottic and subglottic pressure was reduced after simulated recurrent laryngeal paralysis. This model can be used in future studies to compare laryngeal treatment modalities for disorders that have a component of vocal cord hyperadduction, such as spastic dysphonia.

Physiologic motion after vocal cord reinnervation: a preliminary study.

This study attempted to reestablish physiologic vocal cord motion, rather than synkinesis, to a reinnervated vocal cord. One mongrel dog underwent a division and reanastomosis of the anterior branch of the right recurrent laryngeal nerve and simultaneous separation and reimplantation of a posterior division nerve-muscle pedicle into the posterior cricoarytenoid muscle. After 21 weeks, spontaneous physiologic vocal cord movement and electromyographic (EMG) activity were recorded during respiratory obstruction and laryngeal mechanical stimulation. Acoustic measures and histologic data are also presented from the reinnervated and normal vocalis muscle and from the recurrent laryngeal nerve. This study demonstrated that physiologic vocal cord motion can be achieved after laryngeal reinnervation using this technique.

How contraceptive use patterns differ by pregnancy intention: implications for counseling.

To increase awareness of issues to include in contraceptive counseling-the objectives of this study were to evaluate: 1) how contraceptive use patterns (eg, non-use), level of effectiveness of contraceptive method, and sociodemographic characteristics may be associated with the occurrence of unintended pregnancy; 2) patterns of health care use for women with intended and unintended pregnancy; and 3) the association between contraceptive use patterns and sociodemographic characteristics. In-person interviews were conducted with 279 women enrolled in a Medicaid managed care health plan who had been pregnant in the last 5 years. Self-reported measures of pregnancy intention, contraceptive use, and health care use were collected. The relationships of pregnancy intention with contraceptive use patterns, level of effectiveness of contraceptive method used, and patterns of recent health care use were assessed. Differences in contraceptive use patterns by sociodemographic groups were assessed. Seventy-eight percent of women reported an unintended pregnancy. Non-use of birth control the month before conception was reported by 57% of women with unintended pregnancies and 84% of women with intended pregnancies. Use of birth control of low effectiveness was reported by 20% of women with unintended pregnancies and 8% of women with intended pregnancies. Non-use or use of contraceptive methods of low effectiveness did not differ for women in different sociodemographic groups regardless of pregnancy intention status. A majority of women reported recent health care use. Health care providers should be aware that women who have no intention for pregnancy may not be using an effective contraceptive method NOR have an effective pattern of contraceptive use.