The potential of volatile organic compound analysis in cervicovaginal mucus to predict estrus and ovulation in estrus-synchronized heifers.

Cervicovaginal mucus is a mixture of mucins, ions, salts, and water, the proportions of which change during the reproductive cycle. It is suspected that this mucus emits an important volatile signal indicative of the reproductive state of the female. The objective of this study was to identify volatile organic compounds (VOC) in bovine cervicovaginal mucus that are modulated during the estrous cycle and could potentially be used as biomarkers of estrus and ovulation. Cervicovaginal mucus was collected from crossbred beef heifers (n = 8), which were synchronized using an 8-d controlled internal drug release (CIDR) protocol and in which onset of estrus and time of ovulation were determined by visual observation and ultrasonography, respectively. Mucus samples were collected between 0 and 96 h after CIDR removal (estrus onset occurred at 49.1 ± 3.3 h after CIDR removal). A validation study was performed on an independent group of 15 heifers from which cervicovaginal mucus samples were collected every 8 h from 40 to 80 h after CIDR removal. The VOC in mucus were identified using gas chromatography-mass spectrometry and selected compounds were quantified using selected-ion flow-tube mass spectrometry. The presence of 47 VOC was detected in mucus samples by gas chromatography-mass spectrometry with those exhibiting highest abundance including 2-butanone, acetone, 2-pentanone, 4-methyl-2-pentanone, 1-(1-methylethoxy)-2-propanone, ethanol, 2-methyl-2-propanol, and 2-butanol. All VOC peaked between 24 to 47 h after the onset of estrus (ovulation occurred 26.6 ± 5.6 h after estrus onset). Two VOC, 2-pentanone and 4-methyl-2-pentanone, exhibited a significant increase at the onset of estrus, whereas concentration of 2-butanone increased significantly just after estrus onset, indicating that these VOC may be used as putative biomarkers of estrus. The results of our study may contribute to the development of a sensor device based on VOC to aid the detection of estrus and ovulation in cattle, with particular relevance for the dairy industry where the majority of females are bred by artificial insemination.

Outcomes of intragastric balloon placements in a private practice setting.

BACKGROUND AND STUDY AIM: Intragastric balloons are used as a treatment for obesity. Much of the data collected on balloons has been in the context of clinical trials in academic medical centers or as a bridge to bariatric surgery in obesity centers. The aim of this study was to investigate the efficacy and safety of balloon treatment in private practice. PATIENTS AND METHODS: This was a retrospective analysis of 6-month weight loss data and balloon-related complications of patients referred to three private centers for obesity treatment. RESULTS: A total of 815 patients (131 males) were referred for balloon treatment (mean age 36.5 years, mean body weight 111.7 kg, mean body mass index [BMI] 38.1 kg/m(2)). The 6-month weight loss data were available for 672 patients. Mean weight loss was 20.9 kg (7.2 BMI units). A total of 372 patients visited the center only once following balloon placement (i. e. for balloon removal), but these patients still achieved a mean weight loss of 19.4 kg (6.6 BMI units). Successful weight loss (i. e. ≥ 10 %) was achieved in 85.0 %. Severe complications consisted of dehydration requiring hospital admission (n = 2; 0.2 %), and intestinal obstruction caused by balloon deflation, which required surgery (n = 2; 0.2 %). A total of 35 deflated balloons (4.3 %) were passed rectally without any adverse events. Severe esophagitis following balloon placement was diagnosed in 12 patients (1.5 %). A total of 53 patients (6.5 %) requested balloon removal during the first month. Nine balloons (1.1 %) were removed for medical reasons. CONCLUSION: In the private practice setting, intragastric balloons on their own, without an intensive lifestyle program and supportive consultations, resulted in safe and substantial weight losses, and may fill the therapeutic gap between pharmacotherapy and surgery.

Bleeding in a Jehovah's Witness patient undergoing a redo aortic valve replacement controlled with cryoprecipitate and a prothrombin complex concentrate.

PURPOSE: This is a case report involving a middle-aged Jehovah's Witness patient who underwent a redo aortic valve replacement, coronary artery bypass graft, and Maze procedure facilitated by cardiopulmonary bypass. The consent process included a discussion of the management of bleeding and hemostasis in the perioperative period in the context of the patients' religious choice and the possible consequences of avoiding transfusion in massive bleeding. The medical team agreed to abide by the patient's wishes with respect to the blood and blood products deemed unacceptable by the patient irrespective of the consequences. The consent included a discussion of manufactured hemostatic agents that are designated by the Hospital Liaison Committee Network for Jehovah's Witnesses as subject to personal decision. There was also a discussion of recombinant agents available, all of which are acceptable to Jehovah's Witness patients. The patient accepted the use of cryoprecipitate, prothrombin complex concentrate, and recombinant factor VIIa. CLINICAL FEATURES: After separation from cardiopulmonary bypass and protamine administration, blood loss was 350 mL over a ten-minute period. The international normalized ratio (INR) was 3.5 at that time. Cryoprecipitate 15 U, 1-deamino-8-D-arginine vasopressin 16 U, and a prothrombin complex concentrate, Octaplex®, 60 mL were administered. Blood loss improved significantly. The INR in the cardiac surgical intensive care unit was 1.3. The sample was taken approximately one hour following the administration of the hemostatic agents. The patient's chest was closed, and chest tube drainage was 310 mL over the next 12 hr. CONCLUSION: This is a novel case involving the use of prothrombin complex concentrate in the setting of a Jehovah's Witness patient undergoing a complex operative procedure.

Urgent replacement of a mechanical mitral prosthesis in an anticoagulated patient with Bombay red blood cell phenotype.

PURPOSE: Bombay red blood cell phenotype is an extremely rare blood type for which patients can receive only autologous or Bombay phenotype red blood cells. We report a case of urgent repeat sternotomy for replacement of a mechanical mitral prosthesis in a patient with Bombay phenotype anticoagulated with warfarin, to emphasize the transfusion challenges in such patients. CLINICAL FEATURES: A male of Indian descent presented to hospital with New York Heart Association IV symptoms. His medical history revealed previous mitral valve replacement with a mechanical prosthesis in 2005 and Bombay phenotype blood. Preoperative transthoracic echocardiography demonstrated thrombus obstruction of the mitral prosthesis despite anticoagulation with warfarin. Right ventricular systolic pressure was >100 mmHg with 3+ tricuspid regurgitation. The patient's condition was temporized with diuretics, bronchodilators, and bi-level positive airway pressure ventilation while transfusion medicine and cardiac surgery were consulted for urgent surgery. The patient received vitamin K and prothrombin complex concentrate prior to repeat sternotomy and successful mitral prosthesis replacement. After cardiopulmonary bypass, heparinization was corrected with protamine and followed by a second dose of prothrombin complex concentrate and recombinant activated factor VIIa. Postoperatively, the patient received four units of packed red blood cells, two autologous units and two units of Bombay specific red blood cells. Right ventricular pressures stabilized at 40 mmHg following surgery. The patient recovered following several days of inotropic support with milrinone, diuretics, and bronchodilators. CONCLUSION: Patients with Bombay phenotype red blood cells present as type O, but they are unable to receive red blood cells from any phenotype other than Bombay phenotype. They are able to receive all other blood products, including fresh frozen plasma, cryoprecipitate, platelets, prothrombin complex concentrate, and recombinant activated factor VIIa. Coordination between Canadian Blood Services, transfusion medicine, surgery, and anesthesia is important in managing these patients.

Breaking the diffraction barrier outside of the optical near-field with bright, collimated light from nanometric apertures.

The optical diffraction limit has been the dominant barrier to achieving higher optical resolution in the fields of microscopy, photolithography, and optical data storage. We present here an approach toward imaging below the diffraction barrier. Through the exposure of photosensitive films placed a finite and known distance away from nanoscale, zero-mode apertures in thin metallic films, we show convincing, physical evidence that the propagating component of light emerging from these apertures shows a very strong degree of collimation well past the maximum extent of the near-field (lambda(0)/4n-lambda(0)/2n). Up to at least 2.5 wavelengths away from the apertures, the transmitted light exhibits subdiffraction limit irradiance patterns. These unexpected results are not explained by standard diffraction theory or nanohole-based "beaming" rationalizations. This method overcomes the diffraction barrier and makes super-resolution fluorescence imaging practical.

Functional improvement of jeopardized myocardium following intracoronary streptokinase infusion in acute myocardial infarction.

The effect of reperfusion on regional left ventricular performance following acute myocardial infarction in man was determined. Intracoronary streptokinase was administered in 24 patients within 6 h of the onset of symptoms. 15 patients (62%) were successfully recanalized during the initial study. Mean percent radial shortening (%RS) in both the jeopardized and compensatory regions were determined using 23 radii from the centroid of diastolic and systolic angiographic silhouettes. Sequential measurements were obtained during repeat cardiac catheterization studies at 24 h in 19 patients and before discharge from the hospital (16 +/- 11 d) in 15 patients. At the time of the predischarge study, each acutely reperfused patient showed improvement in %RS in the jeopardized region (P = 0.01) with 56% returning to the normal range. Despite the uniform improvement in the contractile function of the jeopardized region in each reperfused patient, the global ejection fraction showed no improvement or a decrease at the time of the chronic study in 44%. This was due to a decrease in the compensatory wall motion in the uninvolved segments between the acute and chronic study in each case. Neither the %RS nor the ejection fraction changed significantly at the time of the chronic study in the patients who could not be acutely recanalized. These data indicate (a) significant salvage of jeopardized myocardium associated with recovery of contractile function in patients reperfused during the first 6 h of chest pain following acute myocardial infarction; (b) no improvement in regional or global left ventricular performance in patients who could not be reperfused acutely; and (c) the ejection fraction is strongly influenced by changes in the compensatory wall motion of the uninvolved segments and does not accurately reflect changes in the contractile function of the jeopardized myocardium.

Prospective analysis of possible myocardial damage or hemolysis occurring as a result of prolonged autoperfusion angioplasty in humans.

OBJECTIVES: The purpose of this study was to further explore the procedural safety of prolonged (15-min) dilation using an autoperfusion coronary angioplasty balloon by assessing the degree of myocardial damage or hemolysis, if any, occurring as a result of the procedure. BACKGROUND: Prolonged balloon inflation periods may be beneficial during percutaneous transluminal coronary angioplasty. The duration of standard balloon angioplasty is often limited by the occurrence of myocardial ischemia due to loss of anterograde blood flow. Autoperfusion angioplasty allows continued myocardial perfusion during balloon inflation and has previously been shown to reduce but not totally eliminate acute myocardial ischemia during prolonged (up to 15 min) balloon inflation. The risk of intravascular hemolysis as a result of autoperfusion angioplasty has not yet been fully delineated. METHODS: Sixty-two consecutive patients (76% men; mean age 58 years) undergoing elective percutaneous transluminal coronary angioplasty of a single lesion were studied. Serial electrocardiographic and creatine kinase MB isoenzyme data were examined to detect evidence of myocardial damage. Tests for hemolysis (plasma free hemoglobin, serum haptoglobin and serum lactate dehydrogenase) were obtained in the 1st 24 consecutive patients. RESULTS: Inflation time was 14 +/- 4 min (mean +/- SD) and the procedure was successful (less than or equal to 50% residual lesion stenosis) in 59 patients (95%). Electrocardiographic evidence of myocardial infarction (greater than 1 mm persistent ST segment depression, greater than 1 mm ST segment elevation or new Q waves) was not observed in any patient. Cardiac enzyme assays were within the normal range in all patients. No evidence of hemolysis was found in the 24 consecutive patients studied. CONCLUSIONS: We conclude that prolonged autoperfusion angioplasty can be performed in patients without clinical evidence of myocardial damage or hemolysis.

Late restenosis after emergent coronary angioplasty for acute myocardial infarction: comparison with elective coronary angioplasty.

The late restenosis rate after emergent percutaneous transluminal coronary angioplasty for acute myocardial infarction was assessed by performing outpatient follow-up cardiac catheterization in 79 (87%) of 91 consecutive patients who had been discharged from the hospital with a successful coronary angioplasty. The majority of patients (90%) received high dose intravenous thrombolytic therapy with streptokinase in addition to angioplasty. Similar follow-up data were obtained in 206 (90%) of 228 consecutive patients who had successful elective angioplasty during the same period. The interval from angioplasty to follow-up was 28 +/- 9 weeks for the myocardial infarction group and 30 +/- 11 weeks for the elective group. Baseline clinical variables were similar for both the myocardial infarction and elective groups except for a higher percentage of men in the infarction group (81 versus 63%, p = 0.001). The number of coronary lesions undergoing angioplasty and the incidence of intimal dissection were similar, but multivessel angioplasty was more common in the elective group (13 versus 4%, p = 0.02). The rate of in-hospital reocclusion was higher in the patients receiving angioplasty for myocardial infarction (13 versus 2%, p = 0.0001). At the time of late follow-up after hospital discharge, the patients with myocardial infarction were more often asymptomatic (79 versus 55%, p = 0.0001), and the rate of angiographic coronary restenosis was lower for the infarction group both overall (19 versus 35%, p = 0.006) and when multivessel angioplasty patients were excluded (19 versus 33%, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Emerging tools for real-time label-free detection of interactions on functional protein microarrays.

The availability of extensive genomic information and content has spawned an era of high-throughput screening that is generating large sets of functional genomic data. In particular, the need to understand the biochemical wiring within a cell has introduced novel approaches to map the intricate networks of biological interactions arising from the interactions of proteins. The current technologies for assaying protein interactions--yeast two-hybrid and immunoprecipitation with mass spectrometric detection--have met with considerable success. However, the parallel use of these approaches has identified only a small fraction of physiologically relevant interactions among proteins, neglecting all nonprotein interactions, such as with metabolites, lipids, DNA and small molecules. This highlights the need for further development of proteome scale technologies that enable the study of protein function. Here we discuss recent advances in high-throughput technologies for displaying proteins on functional protein microarrays and the real-time label-free detection of interactions using probes of the local index of refraction, carbon nanotubes and nanowires, or microelectromechanical systems cantilevers. The combination of these technologies will facilitate the large-scale study of protein interactions with proteins as well as with other biomolecules.

Cell differentiation by mechanical stress.

Growth factors, hormones, and other regulatory molecules are traditionally required in tissue engineering studies to direct the differentiation of progenitor cells along specific lineages. We demonstrate that mechanical stimulation in vitro, without ligament-selective exogenous growth and differentiation factors, induces the differentiation of mesenchymal progenitor cells from the bone marrow into a ligament cell lineage in preference to alternative paths (i.e., bone or cartilage cell lineages). A bioreactor was designed to permit the controlled application of ligament-like multidimensional mechanical strains (translational and rotational strain) to the undifferentiated cells embedded in a collagen gel. The application of mechanical stress over a period of 21 days up-regulated ligament fibroblast markers, including collagen types I and III and tenascin-C, fostered statistically significant cell alignment and density and resulted in the formation of oriented collagen fibers, all features characteristic of ligament cells. At the same time, no up-regulation of bone or cartilage-specific cell markers was observed.

Hemodynamics at rest and during exercise after oral hydralazine in patients with cor pulmonale.

Oral hydralazine has been shown to be effective in decreasing pulmonary arteriolar resistance and increasing cardiac output in some patients with primary pulmonary hypertension. To determine whether a similar response could be observed in patients with chronic cor pulmonale, the hemodynamic status before and after the oral administration of hydralazine (25 mg, then 50 mg every 6 hours for 48 hours) were evaluated in 12 patients at rest and in 8 during upright exercise. After hydralazine, there was an increase in cardiac output at rest, from 4.3 to 6.3 liters/min (p < 0.001), and reductions in arteriovenous oxygen difference, from 8.1 to 6.1 volume percent (p < 0.001), mean pulmonary arterial pressure, from 52 to 44 mm Hg (p < 0.01), and pulmonary arteriolar resistance, from 11.2 to 6.2 units (p < 0.0005). Similar hemodynamic changes occurred during exercise, including an increase in pulmonary arterial saturation from 27 to 39 percent (p < 0.001) and a decrease in total pulmonary resistance from 12.7 to 8.9 units (p < 0.01). Results of pulmonary function tests performed before and after hydralazine did not change with drug administration. These findings indicate that the lung vascular bed in some patients with cor pulmonale is capable of responding to hydralazine with a reduction in pulmonary resistance and an increase in cardiac output both at rest and during exercise.

Left bundle branch block: angiographic segmental wall motion abnormalities.

Ventricular wall motion as studied with contrast ventriculography has been judged normal in the few previously reported cases of patients with left bundle branch block who have neither coronary artery disease nor diffuse cardiomyopathy. However, recent echocardiographic studies have demonstrated a high frequency of segmental asynergy of the septal wall in such patients. In this study left ventricular wall motion was analyzed in 15 patients with left bundle branch block and without significant coronary artery disease or diffuse cardiomyopathy. Biplane cineangiograms from these patients were compared with those from 100 consecutive patients with normal intraventricular conduction and without coronary artery disease or cardiomyopathy using two techniques: qualitative visual inspection and a computer-assisted quantitative method. By qualitative review, 6 of 15 patients with left bundle branch block had regional akinesia or dyskinesia as compared with none of 100 patients with normal intraventricular conduction (chi square = 42.3; P less than 0.001). By quantitative review, 10 of 12 patients with left bundle branch block had abnormal wall motion along at least one hemiaxis. It is concluded that angiographic regional wall motion abnormalities are common in patients with left bundle branch block, even in the absence of coronary artery disease or diffuse cardiomyopathy. The abnormalities may result from the abnormal sequence of ventricular activation rather than from myocardial fibrosis.

Ventricular aneurysm with ventricular tachycardia. Report of a case with epicardial mapping and successful resection.

A case of ventricular aneurysm with refractory ventricular tachycardia is presented. Epicardial mapping was used to localize the site of earliest epicardial activity to the margin of the aneurysm, and subsequent resection of this area abolished the rhythm disturbance.

Aortocoronary bypass surgery: Correlation of angiographic symptomatic and functional improvement at 1 year.

Angiographic changes in the coronary circulation were evaluated in 60 patients 1 year after aortocoronary bypass surgery, and their relation to the postoperative clinical status was examined. Of 124 grafts implanted, 26 were closed, 7 stenotic and 91 (74 percent) patent at 1 year. Progression of occlusive disease occurred in 21 of 57 (37 percent) nongrafted and 78 of 123 (63 percent) grafted vessels. On the basis of location and severity of progression, significant lesions bypassed and patency of grafts, postoperative coronary perfusion was considered optimal in 16 patients (Group I), better in 24 (Group III). Complete freedom from chest pain or lessening of pain (improvement by two New York Heart Association functional classes) occurred in 88 and 79 percent of patients in Group III. Positive preoperative treadmill stress tests became negative after surgery in five of six patients in Group I, five of eight in Grojp II and three of eight in Group III. This study demonstrates that when progression of disease, graft patency and extent of revasculariztion are considered in combination, the postoperative angiographic status of the coronary circulation correlates well with clinical improvement at 1 year. These findings support the hypothesis that improved blood supply to ischemic myocardium is a major factor contributing to relief of angina pectoris after saphenous vein bypass surgery.

Intracoronary ultrasound evaluation of interventional technologies.

The feasibility and applicability of intravascular ultrasound (IVUS) of the coronary arteries were evaluated in 65 patients undergoing 70 coronary interventional procedures. Morphologic and quantitative analyses were performed with a mechanically rotated IVUS catheter (4.8Fr, 20 MHz) and with orthogonal view cineangiography. A semiautomated edge-detection algorithm was used for cineangiographic quantification. Coronary interventions included 45 percutaneous transluminal coronary angioplasties, 9 excimer lasers, 11 directional coronary atherectomies, 3 rotational atherectomies and 2 stents. Most lesions consisted of a mixture of plaque composition (hard, n = 30; soft, n = 64). Other unique morphologic data by IVUS were plaque topography (eccentric, n = 34; concentric, n = 36) and vessel dissection (IVUS [n = 29] versus angiography [n = 14], p less than 0.05). Postprocedure minimal lumen diameter and cross-sectional area measured by IVUS were larger and poorly correlated with angiography (r = 0.28, standard error of the estimate = 0.52 mm; r = 0.08, standard error of the estimate = 1.0 cm2, respectively). IVUS is more sensitive than angiography when assessing postintervention lesion characteristics including vessel dissection and plaque morphology. Catheter-based ultrasound appears to be a useful adjunct to contrast angiography when evaluating and comparing the therapeutic impact of conventional percutaneous transluminal coronary angioplasty with new technologies.

Outcomes following interventions in small coronary arteries with the use of hand-crimped Palmaz-Schatz stents.

Although coronary stenting has been shown to be effective, retrospective studies have suggested that stents do not provide better results than angioplasty in small coronary arteries. We sought to examine procedural, in-hospital, and long-term outcomes of patients undergoing small-vessel stenting with Palmaz-Schatz stents hand-crimped on a balloon catheter <3 mm in diameter. We retrospectively analyzed the outcomes of 117 patients who underwent this type of coronary stent implantation at Duke University Medical Center between January 1, 1997 and May 30, 1998. The clinical indications for percutaneous revascularization included unstable angina in 67.5% of patients, acute myocardial infarction in 4.3%, postinfarct angina in 3.4%, silent ischemia in 3.4%, and stable angina in 1% of patients. Quantitative angiographic analysis was performed immediately before angioplasty and after stent implantation. Stents were used for elective indications in 24%, for suboptimal angiographic result in 61.5%, and for abrupt and/or threatened closure in 14.5% of patients. Reference vessel diameter was similar before and after the procedure. Minimum luminal diameter increased from 0.63 to 2.35 mm, an acute gain of 1.72+/-0.43 mm. Percent stenosis decreased from 74.2% to 4.7%. The clinical composite of death (n = 1, 1%), nonfatal myocardial infarction (n = 6, 5.1%), and revascularization (n = 1, 1%) occurred in-hospital in only 8 patients (6.8%), resulting in clinical procedure success in 109 patients (93%). Our data suggest that stents designed for vessels >3.0 mm can be deployed in small vessels, with a low in-hospital event rate. However, target lesion revascularization in small vessels remains high. Development of antiproliferative strategies could improve long-term outcomes for small-vessel interventions.

Arteriosclerotic heart disease following correction of tetralogy of Fallot.

An increasing number of people who have undergone surgical repair of tetralogy of Fallot are living long lives. Several late sequelae of corrected tetralogy of Fallot have been found, including residual ventricular septal defect, restenosis of the pulmonary outflow tract, ventricular tachycardia, and right ventricular failure from pulmonary insufficiency. A long-term survivor of corrected tetralogy of Fallot is reported with acquired coronary artery disease unrelated to the congenital anomaly or its correction as an additional cause of late morbidity in this select but growing population of patients.

Cor pulmonale caused by recurrent pulmonary emboli.

A 53-year-old black man developed femoral thrombophlebitis in 1983 following a Harrington nail implantation in his first lumbar vertebral region. There was evidence of pulmonary embolization at that time and recurrently until he developed ventricular fibrillation and died in 1987. The terminal event followed a hypotensive episode during the course of a right ventricular catheterization. Autopsy confirmed the clinical impression that he had multiple recurrent thromboemboli to his lungs. After several years of embolization, the pulmonary arterial circulation was sufficiently occluded to result in pulmonary hypertension. Cor pulmonale was produced, with congestive heart failure leading to a progressively downhill course in the 4 months before his death.

Delayed presentation of a mitral annular perforation complicating Staphylococcus aureus infective endocarditis.

This report describes a patient who presented with congestive heart failure secondary to a mitral annular-left atrial fistula. There was a remote history of Staphylococcus aureus endocarditis involving the mitral valve which was treated medically 30 years previously. The sterile fistula was managed surgically with an annuloplasty.

Right ventricular obstruction secondary to intracardiac metastatic osteosarcoma.

A 30-year-old female with a history of surgically treated osteosarcoma 2 years prior to admission presented with progressive dyspnea and cyanosis. Physical examination was otherwise negative. Cardiac catheterization demonstrated a right ventricular mass lesion. At surgery, a metastatic osteosarcoma filling the entire right ventricle and extending from the pulmonary valve across the tricuspid valve and into the right atrial cavity was partially excised. Despite marked improvement postoperatively, she did 33 d after surgery. Postmortem findings were unusual in that the heart represented the sole site of metastasis. The diagnostic approach to cardiac symptoms from malignancy is discussed in relation to this patient.