The ocular findings related to oral bisphosphonate use.

OBJECTIVE: We aimed to investigate ocular involvement findings in female osteoporosis patients using oral bisphosphonate (BP). METHODS: A total of 51 female osteoporosis patients aged 50-75 years using oral BP for at least one year for the study group and 64 age-matched non-osteoporosis female patients for the control group were included in the study. The BP type and exposure time were noted. The ophthalmic examination findings and measurements of the flare of the patients who received oral BP due to osteoporosis and the controls were evaluated. RESULTS: The mean duration of BP use was 3.96 years. In the study group, it was detected four of 51 patients were diagnosed with meibomian gland dysfunction (MGD) (7.8%), seven of 102 eyes had erythematous, irregular, thickened lid margin or telangiectasia around the glandular orifices. There were no pathological findings on fundus examination. The mean value of measurements of the flare (ph/ms) was 7.90±7.96 in the study group, and 5.02±0.81 in the control group. When the mean values were compared, there was a significant difference between the two groups (P=.001). A significant difference was found in the mean value of measurements of the flare between the patients using alendronate, and ibandronate with the control group (P=.001; P=.005, respectively). CONCLUSION: Our study showed that the flare in the anterior chamber associated with chronic ocular inflammation can be seen higher rate in patients using oral alendronate, and ibandronate compared to those who do not. Morever it can be said that oral BPs may cause similar ocular side effects like as intravascular BPs.

Psoriasis and coronary heart disease-not as severe as predicted.

BACKGROUND: Psoriasis is a systemic disorder involved in several disease processes, including cancer, metabolic syndrome and cardiovascular disease (CVD). Previous studies showed that psoriasis is most likely an independent risk factor for CVD, yet the extent of its impact on CVD and the extent of coronary artery disease (CAD) remains unclear. We investigated the correlation of psoriasis to the severity of CAD in age and gender-matched patients with CAD with and without psoriasis. METHODS: This is a retrospective, case-control study of 59 patients with psoriasis who underwent coronary angiography were matched using a computer software to 59 patients without psoriasis according to age, gender, smoking status, hyperlipidemia, hypertension and diabetes. CAD severity was defined according to number of affected vessels (single vs. multiple) and location of lesions (proximal vs. distal). RESULTS: CAD severity was significantly higher in the control group compared to the psoriasis group (P = 0.038). Among patients with psoriasis, 20.3% were disease free or with low severity (42.4%), while only 37.3% had severe CAD. Among patients without psoriasis, the majority had severe CAD (57.6%), followed by low severity (30.5%) or disease free (11.9%). We did not find an association of prior treatment with anti-inflammatory medications and the severity of CAD. CONCLUSIONS: Our results show that although psoriasis may be a risk factor for CAD, psoriatic patients have a less severe CAD compared to the general population. The use of anti-inflammatory medications does not explain this finding.

Particle size dynamics and risk implication of atmospheric aerosols in South-Asian subcontinent.

Presented here are size-resolved aerosol measurements conducted using cascade impactor set at breathing zone in indoor-outdoor residential microenvironments. PM2.5 contributed about 64-80% of PM10 in which over 29% of mass was shared by PM0.25. Total PM concentration varied from 261 ± 22 µg/m3 (indoors) to 256 ± 64 µg/m3 (outdoors) annually; whilst summer and monsoon demonstrated 1.2- and 1.9- times lower concentration than winters. The measured metals ranged between 9% (in PM2.5-10) to 18% (in PM1-2.5) of aerosol concentration; whereby crustal elements dominated coarse fractions with relatively higher proportion of toxic elements (Ba, Cd, Co, Cr, Cu, Ni) in ultrafine range. Considering lognormal particle size distribution (PSD), accumulation mode represented the main surface area during entire monitoring period (Mass Median Aerodynamic Diameter (MMAD) < 1). PSD of metal species reflected their different emission sources with respect to season integrated samples. High air exchange conditions permitted the shift of indoor PSD pattern closer to that of outdoor air while low ventilation in winters reflected modal shift of metals (Pb, Mg. K) towards larger size particles. Relative surge towards smaller diameter size of soluble metal fraction relative to the total concentration of toxic elements was noted on an annual basis with high infiltration capacity of smaller size particulates (Finf =1.36 for ultrafine particles in summers) identified through indoor-outdoor regression analysis. Principal Component Analysis identified sources such as vehicular traffic, combustion, crustal emission with activities viz. smoking and those involving use of electric appliances.

A novel rat model for tracheal mucosal damage assessment of following long term intubation.

OBJECTIVE: Tracheal mucosal damage is a well-known complication of endo-tracheal intubation and animal models are essential for studying the underlying cellular injury cascade. The novel rat model described here is based on retrograde intubation via tracheotomy and suture fixation of the tube. It aims to simulate the common clinical scenario of tube-related airway damage due to long term intubation. STUDY DESIGN: Prospective randomized control pilot study. METHODS: Male Sprague-Dawley were randomly assigned into two groups: control (no intubation, n = 10), one week of intubation (n = 13). The animals were then euthanized and the trachea was sent for histological analysis. Epithelial damage, mucosal thickness, mucosal gland hypertrophy and fibrosis were reviewed. RESULTS: Intubation procedure survival rate was 84.6% (11/13) and 100% in the control (10/10). The damaged ciliary mechanism was a common finding in the intubated group compared to the preserved normal ciliary architecture in almost all control rats. Average tracheal mucosal thickness was 119.0 ±â€¯21.8 µm for the control group and 254.6 ±â€¯22.8 µm for the intubated group, (p < 0.001). The ciliary damage score was 1.00 ±â€¯0.02 in the intubated group, and 0 ±â€¯0.02 in the control group. (p < 0.001). The (objective) average total tracheal mucosal gland area was 19,530 ±â€¯24,606 in the intubated group and 10,031 ±â€¯23,461 in the control group (p < 0,05). Collagen deposition seems higher in the intubated trachea compared to the control. CONCLUSIONS: We describe a novel rat-based animal model for simulating tracheal mucosal damage following long term intubation. This animal model is easy to carry out, reproducible and involves containable animal mortality rates. LEVEL OF EVIDENCE: I.

A novel rat model for assessment of laryngotracheal injury following transoral intubation.

OBJECTIVE: Laryngotracheal damage is a well-described complication of endotracheal intubation and animal models are essential for studying the underlying cellular injury cascade. This novel rat model is based on transoral intubation and aims to simulate the common clinical scenario of tube-related airway damage. METHODS: Prospective randomized control pilot study. 28 male Sprague-Dawley were randomly assigned into three groups: control, 3-h' intubation and 6-h' intubation. The animals were then euthanized and their laryngotracheal complexes sent for histological analysis. Epithelial damage, mucosal thickness and mucosal gland hypertrophy were reviewed. RESULTS: Total of 13 control animals and 15 intubated animals. 10 intubated animals survived the study protocol. Loss of epithelial surface architecture including damage to the microscopic ciliary mechanism was a common feature amongst all intubated animals. Average mucosal thickness of the larynx (including vocal cords and subglottic area) was 143 ±â€¯88 µm for control rats, 315 ±â€¯101 µm for rats intubated 3 h and 574 ±â€¯174 µm for rats intubated 6 h .This was a statistically significant difference. Average mucosal gland hypertrophy in the laryngeal subsite was 0.41 ±â€¯0.5 in control rats, 1.4 ±â€¯0.5 in rats intubated 3 h and 2.0 ±â€¯0.0 for rats intubated 6 h (statistically significant difference). There was a clear difference between three and 6 h of intubation with poorer mucosal injury parameters for longer intubation. CONCLUSIONS: We describe a novel rat-based animal model for simulating airway mucosal damage following transoral intubation. This animal model is easy to carry out, reproducible and involves containable animal mortality rates.

Anterior parasternal approach for creation of a pericardial window.

INTRODUCTION: The optimal method for creation of a pericardial window (PW) is still controversial and it remains a surgical challenge, mainly in obese patients. The aim of this study was to evaluate the efficacy and safety of a novel approach that has not been described previously, for creation of a PW in patients with symptomatic, chronic, large pericardial effusion. METHODS: We retrospectively analysed the records of 30 patients (14 men, 16 women) who underwent a PW procedure between 2001 and 2011. The mean age was 63 years (standard deviation [SD]: 17 years, median: 60 years, range: 27-90 years) and the mean body mass index was 34 kg/m(2) (SD: 2 kg/m(2)). The operation was performed through a curvilinear parasternal approach, 6-8 cm in length, followed by a mini-thoracotomy between ribs 4 and 5. Discharged patients were followed up clinically. RESULTS: The mean operative time was 73 minutes (SD: 21 minutes) and a median of 658 ml (range: 300-1,500 ml) of fluid was evacuated. The main aetiologies were idiopathic in 17 patients (57%) and malignant in 9 (30%). Seven patients (23%) died in hospital owing to underlying malignancy. Postoperative complications included mild renal failure (20%), respiratory failure (20%), pneumonia (13%), atrial fibrillation (10%) and atelectasis (6%). There were no wound infections. The median length of stay following the procedure was 8 days. In a median follow-up period of 3.8 years, 16 patients with non-malignant effusion were free of recurrence of pericardial effusion. CONCLUSIONS: The anterior parasternal approach for creation of a PW is simple, safe and efficacious, and results in long-term symptomatic improvement, specifically in patients with non-malignant effusions. This approach may be more appealing in obese patients.

Etiology and characteristics of large symptomatic pericardial effusion in a community hospital in the contemporary era.

BACKGROUND: The etiology and laboratory characteristics of large symptomatic pericardial effusion (LSPE) in the Western world have evolved over the years, and vary between regions, community and tertiary hospitals. METHODS: We reviewed data of 86 consecutive patients who underwent pericardiocentesis or pericardial window due to LSPE in a community hospital from 2001 to 2010. The characteristics of the PE including chemistry, hematology, bacteriology, serology and cytology have been analyzed. We correlated the etiologies of PE with age, gender and clinical presentation. RESULTS: The most frequent etiology of LSPE was idiopathic [36% (77% with a clinical diagnosis of pericarditis)], followed by malignancy (31.4%), ischemic heart disease (16.3%), renal failure (4.6%), trauma (4.6%) and autoimmune disease (4.6%). The average age of all the etiological groups excluding trauma was over 50 years. Laboratory tests did not modify the pre-procedure diagnosis in any of the patients. The most frequent presenting symptom was dyspnea (76.6%). Chest pain was mostly common in patients with idiopathic etiology (58.06%). The most frequent medical condition associated with LSPE was the use of anticoagulant or antiplatelet drugs (31.40%), especially aspirin, and in those, the PE tended to be bloody (73%, P = 0.11). Most of the effusions were exudates (70.9%). PE due to renal failure was the largest (1467 ± 1387 ml). CONCLUSION: The spectrum of etiologies of LSPE in a community hospital in the Western world in the contemporary era is continuously evolving. The most frequent etiology is now idiopathic, followed by malignancy. Routine laboratory testing still rarely modifies the pre-procedure diagnosis.

Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases.

The aim of this study is to understand intracellular regulatory mechanisms in peripheral blood mononuclear cells (PBMCs), which are either common to many autoimmune diseases or specific to some of them. We incorporated large-scale data such as protein-protein interactions, gene expression and demographical information of hundreds of patients and healthy subjects, related to six autoimmune diseases with available large-scale gene expression measurements: multiple sclerosis (MS), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), Crohn's disease (CD), ulcerative colitis (UC) and type 1 diabetes (T1D). These data were analyzed concurrently by statistical and systems biology approaches tailored for this purpose. We found that chemokines such as CXCL1-3, 5, 6 and the interleukin (IL) IL8 tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In addition, the anti-apoptotic gene BCL3, interferon-γ (IFNG), and the vitamin D receptor (VDR) gene physically interact with significantly many genes that tend to be differentially expressed in PBMCs of patients with the analyzed autoimmune diseases. In general, similar cellular processes tend to be differentially expressed in PBMC in the analyzed autoimmune diseases. Specifically, the cellular processes related to cell proliferation (for example, epidermal growth factor, platelet-derived growth factor, nuclear factor-κB, Wnt/ß-catenin signaling, stress-activated protein kinase c-Jun NH2-terminal kinase), inflammatory response (for example, interleukins IL2 and IL6, the cytokine granulocyte-macrophage colony-stimulating factor and the B-cell receptor), general signaling cascades (for example, mitogen-activated protein kinase, extracellular signal-regulated kinase, p38 and TRK) and apoptosis are activated in most of the analyzed autoimmune diseases. However, our results suggest that in each of the analyzed diseases, apoptosis and chemotaxis are activated via different subsignaling pathways. Analyses of the expression levels of dozens of genes and the protein-protein interactions among them demonstrated that CD and UC have relatively similar gene expression signatures, whereas the gene expression signatures of T1D and JRA relatively differ from the signatures of the other autoimmune diseases. These diseases are the only ones activated via the Fcɛ pathway. The relevant genes and pathways reported in this study are discussed at length, and may be helpful in the diagnoses and understanding of autoimmunity and/or specific autoimmune diseases.

Mitral annular calcification: a marker of severe coronary artery disease in patients under 65 years old.

BACKGROUND: Mitral annular calcification has been associated with various systemic and cardiac diseases, with a higher prevalence in women and patients over 70. A possible association between mitral annular calcification and coronary artery disease has recently been suggested. OBJECTIVE: To determine the prevalence of severe coronary artery disease in younger patients with mitral annular calcification. METHODS: Consecutive patients aged or= 70% stenosis of at least one major epicardial coronary artery. PATIENTS: 17 735 patients were screened. Of these, 6207 (35%) had mitral annular calcification and 885 (5%) were also

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age < or =65 years old.

OBJECTIVES: We examined the hypothesis that mitral annulus calcification (MAC), aortic valve sclerosis (AVS) and aortic root calcification (ARC) are associated with coronary artery disease (CAD) in subjects age < or =65 years. BACKGROUND: Mitral annulus calcification, AVS and ARC frequently coexist and are associated with coronary risk factors and CAD in the elderly. METHODS: We studied 338 subjects age < or =65 years who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography (SPECT) and a two-dimensional transthoracic echocardiogram for other indications. The association of MAC, AVS and ARC with abnormal SPECT was evaluated by using chi-square analyses and logistic regression analyses. RESULTS: Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (> or =2) calcium (or sclerosis) deposits with diabetes or multiple (> or =2) coronary risk factors were significantly associated with abnormal SPECT in women age < or =55 years old (odds ratio [OR], 20.00), in women age >55 years old (OR, 10.00) and in men age < or =55 years old (OR, 5.55). Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age < or =55 years (p < 0.05) and the total group of subjects (p < 0.01). CONCLUSIONS: When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men < or =55 years old and women.

Augmentation of in-vitro clot dissolution by low frequency high-intensity ultrasound combined with antiplatelet and antithrombotic drugs.

BACKGROUND: Glycoprotein IIb/IIIa antagonists and heparin are increasingly used for treatment of acute coronary syndromes. There is no data on the effect of these drugs on clot dissolution when combined with low frequency high-intensity ultrasonic energy. We examined a possible additive effect of low frequency high-intensity ultrasound with an antithrombotic, an antiplatelet and a fibrinolytic agent alone or in combinations for in vitro blood clot dissolution. METHODS: Human blood clots were incubated for 10', 15' and 30' in normal saline containing commonly used concentrations of heparin, tirofiban, t-PA and Optison (echocardiographic contrast agent) alone and in combinations. Clots were then randomly exposed to low frequency high-intensity ultrasound (27[emsp3 ]kHz) for 5 minutes. The percent difference in clot weight and the incremental effect of ultrasound energy were calculated. RESULTS: The most significant additive effect of ultrasound energy was detected with the combination of tirofiban and heparin (39+/-2% augmentation after 10' of incubation, p<0.0001). The greatest magnitude of percent clot weight reduction was observed with ultrasound energy combined with either t-PA alone (72+/-1% after 30' incubation, p=0.0016) or with the combination of t-PA, tirofiban, heparin and Optison (68+/-4% after 30' incubation, p=0.015). CONCLUSIONS: Application of low frequency high-intensity ultrasound has an additive effect to antiplatelet, antithrombotic and fibrinolytic drugs, specifically with the combination of tirofiban and heparin or with t-PA; this effect is observed after a short incubation period.

Noninvasive transthoracic low frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction--evaluation of the extent of ST-segment resolution.

BACKGROUND: Recently it has been demonstrated that transcutaneous delivery of ultrasound combined with tissue plasminogen activator (tPA) is more effective than tPA alone in recanalizing acutely thrombosed canine coronary arteries. In the present study, we investigated the incidence of partial (> or =50%) and complete (> or =70%) ST-segment elevation resolution in the precordial leads of dogs with experimental acute myocardial infarction that were treated with tissue plasminogen activator (tPA) alone or in combination with noninvasive transcutaneous delivery of high-intensity low frequency (27[emsp3 ]kHz) ultrasound. METHODS: Thrombotic coronary occlusions were induced in the midportion of left anterior descending (LAD) coronary artery by electrical injury in 24 dogs. All dogs were given intravenous heparin and tPA. Dogs were randomized to tPA alone (n=12) or combined tPA and adjunctive transcutaneous ultrasound (US) delivery (n=12). Electrocardiograms were recorded at 1) baseline, 2) after coronary occlusion just before initiation of therapy, 3) when coronary angiography showed recanalization of the coronary artery (or at 90 minutes after initiation of therapy if reperfusion did not occur before then) and 4) 90 minutes later. ST amplitude was measured in all 6 precordial leads. RESULTS: ST-segment amplitude at baseline was comparable between the tPA and the US group. Before initiation of therapy, sum of ST-segment elevation tended to be higher in the US group. At reperfusion and 90 minutes thereafter, sum of ST-segment amplitude tended to be smaller for the US group than in the tPA group (p<0.001 for the time effect; p=0.118 for the time x group interaction). Up to 90 minutes after initiation of therapy >/=50% resolution of the sum of precordial ST elevation was detected in 7 out of 11 dogs (63.6%) in the tPA group versus 10 out of 11 dogs (90.9%) in the US group. Ninety minutes thereafter, 3 out of 7 dogs in the tPA group (42.9%) versus 9 of 11 dogs in the US group (81.8%) had >/=50% resolution of the sum of precordial ST elevation. CONCLUSIONS: The combination of tPA with noninvasive transcutaneous delivery of low frequency high-intensity ultrasound resulted in greater resolution of ST-segment elevation when reperfusion occurs and 90 minutes thereafter, as well as a higher rate of epicardial coronary artery reperfusion.

Arterial thrombus dissolution in vivo using a transducer-tipped, high-frequency ultrasound catheter and local low-dose urokinase delivery.

PURPOSE: To examine the hypothesis that a transducer-tipped high-frequency ultrasound drug-delivery catheter may augment the thrombolytic effects of locally delivered low-dose urokinase and result in improved recanalization rates and reduced residual thrombotic burden. METHODS: Thrombi were induced in situ bilaterally in 5- to 6-cm-long segments of the superficial femoral arteries in 9 dogs by intraluminal thermal damage and injection of thrombin. A transducer-tipped high-frequency local drug-delivery catheter was applied at 1.1 MHz and 0.6 W for 60 minutes to one superficial femoral artery segment, and an identical catheter with an inactivated ultrasound transducer was used to treat the contralateral control segment. Urokinase (5000 IU/kg) was delivered bilaterally into the thrombi during the treatment interval. RESULTS: Angiography documented TIMI grade 2 or 3 flow in 9 (100%) segments in the ultrasound-treated group versus 6 (67%) of the controls (no ultrasound) (p = 0.058). Angiographically detected distal embolization was found in 2 ultrasound-treated segments compared with 5 controls (p = 0.02). Protruding or occlusive thrombi were seen angioscopically in 8 (89%) control segments but in only 1 (11%) of the ultrasound-treated arteries (p < 0.001). By histopathology, 7 (78%) segments in the control group had occlusive thrombi, whereas only 3 nonocclusive thrombi were found in the ultrasound-treatment group (p < 0.001). CONCLUSIONS: Catheter-delivered high-frequency ultrasound and local low-dose urokinase infusion is efficacious for the treatment of acute thrombotic occlusions as evaluated by angiography, angioscopy, and histopathology.

The use of transducer-tipped ultrasound catheter for recanalization of thrombotic arterial occlusions.

Ultrasound energy is currently being used and intensively investigated for recanalization of thrombotically occluded arteries. The ultrasonic energy is mainly applied either by a transcutaneous approach or by a percutaneous approach through a catheter with an external ultrasound transducer. Catheter-delivered transducer-tipped ultrasound thrombolysis is a new and innovative method. In this article we summarize the current available data on the use of this new type of catheter and discuss future directions and clinical applications.

Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in peripheral and coronary arteries.

Previous studies have shown that external ultrasound with low frequencies and high intensities can enhance thrombolytic drug-induced clot dissolution during in vitro experiments. In this series of studies, we evaluated the efficacy of peripheral and coronary thrombolysis in vivo in animals by using noninvasive transcutaneous ultrasound combined with thrombolytic drugs (streptokinase and tPA) and/or microbubbles agents (dodecafluoropentane [DDFP] and perfluorocarbon-exposed sonicated dextrose albumin [PESDA]). Thrombotic occlusions were induced in 74 rabbit iliofemoral arteries and 24 canine left anterior descending (LAD) coronary arteries in this in vivo study. By using the combination of transcutaneous ultrasound and streptokinase, the angiographic patency rate in rabbit iliofemoral arteries was higher (56%-100%) than with ultrasound (6%; P < or = 0.0036) and streptokinase alone (6%; P < or = 0.0012). Also, with transcutaneous ultrasound and microbubbles, the angiographic patency rates were 76%-100% as compared with ultrasound alone (0%, P < or = 0.0003) or microbubbles alone (9%, P < or = 0.0001). In the canine study of acute myocardial infarction, thrombolysis in myocardial infarction (TIMI) grade flow at 90 minutes in the tPA alone group was 0.92 +/- 1.4 as compared with 2.42 +/- 1.9 in the tPA plus transthoracic ultrasound group (P = 0.006). There was much improved reperfusion with tPA plus ultrasound as compared with tPA alone. In vivo animal studies demonstrate that noninvasive transcutaneous ultrasound can greatly enhance the effect of clot dissolution with thrombolytic drugs and/or microbubbles, and has the potential for clinical application as an adjunctive method to improve arterial thrombolysis.

Pacing stress echocardiography: an alternative to pharmacologic stress testing.

OBJECTIVES: We sought to evaluate the diagnostic accuracy and feasibility of bedside pacing stress echocardiography (PASE) as a potential substitute for pharmacologic stress echocardiography in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris. BACKGROUND: Accurate and rapid noninvasive identification and evaluation of the extent of coronary artery disease (CAD) is essential for optimal management of these patients. METHODS: Bedside transthoracic stress echocardiography was performed in 54 consecutive patients admitted to a community hospital with new-onset chest pain, after acute myocardial infarction had been excluded. We used 10F transesophageal pacing catheters and a rapid and modified pacing protocol. The PASE results were validated in all patients by coronary angiography performed within 24 h of the test. Significant CAD was defined as > or =75% stenosis in at least one major epicardial coronary artery. RESULTS: The sensitivity of PASE for identifying patients with significant CAD was 95%, specificity was 87% and accuracy was 92%. The extent of significant CAD (single- or multivessel disease) was highly concordant with coronary angiography (kappa = 0.73, p<0.001). Pacing stress echocardiography was well tolerated, and only 4% of the patients had minor adverse events. The mean rate-pressure product at peak pacing was 22,313+/-5,357 beats/min per mm Hg, and heart rate >85% of the age-predicted target was achieved in 94% of patients. The average duration of the bedside PASE test, including image interpretation, was 38+/-6 min. CONCLUSIONS: Bedside PASE is rapid, tolerable and accurate for identification of significant CAD in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris.