Acute myocardial infarction and pulmonary embolism in a young man with pernicious anemia-induced severe hyperhomocysteinemia

A 27 year-old man who presented to the hospital with progressive lower extremity weakness, developed an acute ST elevation myocardial infarction on his second hospital day. Primary angioplasty to the left anterior descending coronary artery was performed. Due to persistent dyspnea, the patient underwent a diagnostic chest computed tomography which confirmed multiple small pulmonary emboli. Laboratory analysis revealed a megaloblastic anemia with a reduced vitamin B12 level and positive titers for antibodies against intrinsic factor, establishing a diagnosis of pernicious anemia. Screening for hypercoaguable markers documented an isolated severely elevated homocysteine levels (105 μmol/l). No other significant risk factors for coronary artery disease including a family history of premature atherosclerosis were identified. This case illustrates the importance of testing for hyperhomocysteinemia as part of a workup for atherothrombotic disease, especially in patients without other significant risk factors. The severity of hyperhomocysteinemia found in our patient is unusual for patients with vitamin B12 malabsorption and raises the question of whether the widely practiced folic acid fortification in the United States may mask or even worsen vitamin B12 deficiency over time, leading to more severe cases of vitamin B12 deficiency and hyperhomocysteinemia than seen in the past

Clinical impact of a new cardiac magnetic resonance imaging program: a single center US experience

While establishing a Cardiac Magnetic Resonance (CMR) program at an academic institution in the United States, we sought to evaluate indications and direct clinical impact of CMR on patient management and decision- making

Household Perceptions and Patterns of Crop Loss by Wild Pigs in North India

Loss to cultivated crops by wild pigs (Sus scrofa) is widespread and can jeopardize low-income farmers. In India, although there is lot of political interest in the problem, efforts to understand the patterns, correlates, and underlying reasons for wild pig conflict continue to be minimal. We quantified loss of wheat (Triticum aestivum) to wild pigs and assessed the spatial patterns of damage in a forest settlement of Van Gujjar (Haridwar, India), which is a dairy-based pastoralist community. We chose a 4-km2 cultivated area comprising 400 farmlands (each measuring 0.8 ha and belonging to a family) and assessed crop damage by wild pigs through field surveys during the harvest season. We interviewed 159 respondents who manage 219 of the total 400 farmlands in the study area to compare actual crop loss with perceived losses. Wild pigs damaged 2.29 tonnes (2,290 kg) of wheat, which was about 2.6% of the potential yield in the study area. A total of 39 farmlands (9.5%), managed by 28 respondents, suffered losses during the survey period at an average loss of about 58.8 kg (SD ± 89.5, range = 0.7–388 kg). During interviews, 81 respondents managing 155 farmlands (70.7%) reported having suffered wild pig-related crop loss during the survey period. They also perceived losing about 23.4% of the potential yield of wheat due to wild pigs. The perceived losses were much higher than actual losses. Actual losses measured through field surveys underscore the dichotomy between actual and perceived crop loss due to wild pigs. About 81% of recorded wild pig-related damage to wheat occurred within 200 m from the forest edge. The crop protection measures aimed at stopping wild pigs from entering the fields were mostly reactive. Although overall crop losses due to wild pigs seem low at the settlement level, for affected individual families, the losses were financially significant. Such recurrent crop losses can cause families to go into debt, trigger animosity toward conservation, and lead to retaliation measures, which may be indiscriminate and have the potential to affect other endangered mammals in conservation priority landscapes. Because crop losses by wild pigs are severe along the narrow band of fields along the edge of the forest, channeling monetary benefits through insurance-based compensation schemes can help assuage losses to farmers. Further, because crop damage by wild pigs is seasonal, experimenting with mobile fences that can be dismantled and packed away after use would be beneficial

Immediate 3-dimensional ridge augmentation after extraction of periodontally hopeless tooth using chinblock graft

Background: The aim of the present study was to evaluate clinically and radiographically, the efficacy of immediate ridge augmentation to reconstruct the vertical and horizontal dimensions at extraction sites of periodontally hopeless tooth using an autogenous chin block graft. Material and Methods: A total of 11 patients (7 male & 4 female) with localized advanced bone loss around single rooted teeth having hopeless prognosis and indicated for extraction were selected for the study. The teeth were atraumatically extracted and deficient sites were augmented using autogenous chin block graft. Parameters like clinically soft tissue height - width and also radiographic ridge height -width were measured before and 6 months after augmentation. Obtained results were tabulated and analysed statistically. Results: After 6 months of immediate ridge augmentation, the mean gain in radiographic vertical height and horizontal width was 7.64 + 1.47 mm ( P = 0.005) and 5.28 + 0.46 mm ( P = 0.007) respectively which was found to be statistically significant ( P < 0.05). Mean change of width gain of 0.40mm and height loss of 0.40mm of soft tissue parameters, from the baseline till completion of the study at 6 months was observed. Conclusions: The present study showed predictable immediate ridge augmentation with autogenous chin block graft at periodontally compromised extraction site. It can provide adequate hard and soft tissue foundation for perfect 3-Dimensional prosthetic positioning of implant in severely deficient ridges

Complex I dysfunction underlies the glycolytic switch in pulmonary hypertensive smooth muscle cells.

ATP is essential for cellular function and is usually produced through oxidative phosphorylation. However, mitochondrial dysfunction is now being recognized as an important contributing factor in the development cardiovascular diseases, such as pulmonary hypertension (PH). In PH there is a metabolic change from oxidative phosphorylation to mainly glycolysis for energy production. However, the mechanisms underlying this glycolytic switch are only poorly understood. In particular the role of the respiratory Complexes in the mitochondrial dysfunction associated with PH is unresolved and was the focus of our investigations. We report that smooth muscle cells isolated from the pulmonary vessels of rats with PH (PH-PASMC), induced by a single injection of monocrotaline, have attenuated mitochondrial function and enhanced glycolysis. Further, utilizing a novel live cell assay, we were able to demonstrate that the mitochondrial dysfunction in PH-PASMC correlates with deficiencies in the activities of Complexes I-III. Further, we observed that there was an increase in mitochondrial reactive oxygen species generation and mitochondrial membrane potential in the PASMC isolated from rats with PH. We further found that the defect in Complex I activity was due to a loss of Complex I assembly, although the assembly of Complexes II and III were both maintained. Thus, we conclude that loss of Complex I assembly may be involved in the switch of energy metabolism in smooth muscle cells to glycolysis and that maintaining Complex I activity may be a potential therapeutic target for the treatment of PH

Metabolic Changes Precede the Development of Pulmonary Hypertension in the Monocrotaline Exposed Rat Lung.

There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH

Correction: Impact of cardiovascular magnetic resonance on management and clinical decision-making in heart failure patients

Background: Cardiovascular magnetic resonance (CMR) can provide important diagnostic and prognostic information in patients with heart failure. However, in the current health care environment, use of a new imaging modality like CMR requires evidence for direct additive impact on clinical management. We sought to evaluate the impact of CMR on clinical management and diagnosis in patients with heart failure. Methods: We prospectively studied 150 consecutive patients with heart failure and an ejection fraction ≤50% referred for CMR. Definitions for “significant clinical impact” of CMR were pre-defined and collected directly from medical records and/or from patients. Categories of significant clinical impact included: new diagnosis, medication change, hospital admission/discharge, as well as performance or avoidance of invasive procedures (angiography, revascularization, device therapy or biopsy). Results: Overall, CMR had a significant clinical impact in 65% of patients. This included an entirely new diagnosis in 30% of cases and a change in management in 52%. CMR results directly led to angiography in 9% and to the performance of percutaneous coronary intervention in 7%. In a multivariable model that included clinical and imaging parameters, presence of late gadolinium enhancement (LGE) was the only independent predictor of “significant clinical impact” (OR 6.72, 95% CI 2.56-17.60, p=0.0001). Conclusions: CMR made a significant additive clinical impact on management, decision-making and diagnosis in 65% of heart failure patients. This additive impact was seen despite universal use of prior echocardiography in this patient group. The presence of LGE was the best independent predictor of significant clinical impact following CMR

Pathogenic Role of mTORC1 and mTORC2 in Pulmonary Hypertension.

Concentric lung vascular wall thickening due to enhanced proliferation of pulmonary arterial smooth muscle cells is an important pathological cause for the elevated pulmonary vascular resistance reported in patients with pulmonary arterial hypertension. We identified a differential role of mammalian target of rapamycin (mTOR) complex 1 and complex 2, two functionally distinct mTOR complexes, in the development of pulmonary hypertension (PH). Inhibition of mTOR complex 1 attenuated the development of PH; however, inhibition of mTOR complex 2 caused spontaneous PH, potentially due to up-regulation of platelet-derived growth factor receptors in pulmonary arterial smooth muscle cells, and compromised the therapeutic effect of the mTOR inhibitors on PH. In addition, we describe a promising therapeutic strategy using combination treatment with the mTOR inhibitors and the platelet-derived growth factor receptor inhibitors on PH and right ventricular hypertrophy. The data from this study provide an important mechanism-based perspective for developing novel therapies for patients with pulmonary arterial hypertension and right heart failure

Comparison of Echocardiographic Measures in a Hispanic/Latino Population With the 2005 and 2015 American Society of Echocardiography Reference Limits (The Echocardiographic Study of Latinos)CLINICAL PERSPECTIVE

BACKGROUND: Reference limits for echocardiographic quantification of cardiac chambers in Hispanics are not well studied. METHODS AND RESULTS: We examined the reference values of left atrium and left ventricle (LV) structure in a large ethnically diverse Hispanic cohort. Two-dimensional transthoracic echocardiography was performed in 1818 participants of the Echocardiographic Study of Latinos (ECHO-SOL). Individuals with body mass index ≥30 kg/m(2), hypertension, diabetes mellitus, coronary artery disease, and atrial fibrillation were excluded leaving 525 participants defined as healthy reference cohort. We estimated 95th weighted percentiles of LV end systolic volume, LV end diastolic volume, relative wall and septal thickness, LV mass, and left atrial volume. We then used upper reference limits of the 2005 and 2015 American Society of Echocardiography (ASE) and 95th percentile of reference cohort to classify the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) target population into abnormal and normal. Reference limits were also calculated for each of 6 Hispanic origins. Using ASE 2015 defined reference values, we categorized 7%, 21%, 57%, and 17% of men and 18%, 29%, 60%, and 26% of women as having abnormal LV mass index, relative, septal, and posterior wall thickness, respectively. Conversely, 10% and 11% of men and 4% and 2% of women were classified as having abnormal end-diastolic volume and internal diameter by ASE 2015 cutoffs, respectively. Similar differences were found when we used 2005 ASE cutoffs. Several differences were noted in distribution of cardiac structure and volumes among various Hispanic/Latino origins. Cubans had highest values of echocardiographic measures, and Central Americans had the lowest. CONCLUSIONS: This is the first large study that provides normal reference values for cardiac structure. It further demonstrates that a considerable segment of Hispanic/Latinos residing in the United States may be classified as having abnormal measures of cardiac chambers when 2015 and 2005 ASE reference cutoffs are used