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PubMed2002

Gap junction remodeling in heart failure.

Gap junctions, clusters of transmembrane channels that link adjoining cells, mediate myocyte-to-myocyte electrical coupling and communication. The component proteins of gap junction channels are termed connexins, and gap-junctional channels composed of different connexin types exhibit different biophysical properties. In common with other tissues, the heart expresses multiple connexin isotypes. Spatially defined patterns of expression of 3 connexin isotypes-connexin43, connexin40, and connexin45-form specific cell-to-cell conduction pathways for the spread of current flow that governs the normal cardiac rhythm. Remodeling of gap junction organization and connexin expression is a conspicuous feature of human congestive heart failure and other cardiac conditions in which there is an arrhythmic tendency. This remodeling may take the form of disturbances in the distribution of gap junctions, in which the normal ordered pathways for cell-to-cell conduction are disrupted, or quantitative alterations in connexin expression, notably reduced connexin43 levels, which may contribute to slowing of conduction. Recent evidence from studies in experimental animals strengthens the case that gap junction remodeling is a key determinant of the proarrhythmic substrate in the diseased heart.

Connexins↗
PubMed1992

Developmental changes in tolerance to ischaemia in the rabbit heart: disparity between interpretations of structural, enzymatic and functional indices of injury.

The vulnerability of the heart to injury during ischaemia and reperfusion and its responsiveness to various protective and pharmacological interventions are age-dependent. Using three independent indices of tissue injury (cardiac structure, contractile function and creatine kinase leakage), we compared the response of adult (60-90 days old) and neonatal (7 days old) isolated perfused rabbit hearts to global ischaemia and reperfusion. Prior to ischaemia, heart rate was significantly higher in neonatal hearts, as were control values for coronary flow, aortic flow and cardiac output when expressed on a dry wt basis. In experiments in which adult and neonatal hearts (n = 8 per group) were subjected to 2 min of cardioplegia and 45 min of ischaemia, the post-ischaemic recovery of all indices of cardiac function (when expressed as a percentage of pre-ischaemic control) was significantly higher in neonatal than in adult hearts. Thus, cardiac output recovered to 82.9 +/- 3.6% in the neonate but to only 57.9 +/- 6.7% in the adult (P < 0.05). The functional evidence of a greater resistance to ischaemia in the neonate was, however, contradicted by the levels of creatine kinase leakage which tended to be greater in the neonatal than in the adult heart (32.0 +/- 4.7 vs 20.0 +/- 3.1 IU/15 min/g dry wt). Morphological studies indicated that injury was comparable (moderate-to-severe in degree) in both groups. To assess further the relationship between the three indices, additional experiments were undertaken in which the duration of ischaemia in the neonate was extended to 60 min so that the post-ischaemic recovery of function was reduced to a level similar to that seen in the adult after 45 min of ischaemia. Under these conditions cardiac output recovered to 55.6 +/- 4.8% in the neonatal heart (P = NS when compared with the adult) and creatine kinase leakage increased to 88.2 +/- 13.9 IU/15 min/g dry wt--a value over four times greater than that measured in adult hearts with a comparable degree of functional injury. Morphological examination of tissue obtained after 15 min of reperfusion revealed a remarkable recovery of structure in both age groups. In conclusion, in functional terms the neonatal heart was more resistant to ischaemia than the adult; enzymic leakage, however, indicated the opposite and structural assessment revealed no differences. Thus, in comparing injury during ischaemia and reperfusion between different age groups, it is clearly important to employ several independent indices.

Age Factors↗
PubMed1998

Antiarrhythmic drug therapy in pregnancy and lactation.

Antiarrhythmic agents commonly used in clinical practice are reviewed with respect to their potential for teratogenic or other adverse fetal effects. Although most experience with antiarrhythmic drug therapy during pregnancy has accrued with digoxin, quinidine, and propranolol, other antiarrhythmic agents may also be used in the pregnant patient if indicated. The choice of antiarrhythmic drug depends on the specific arrhythmia being treated, the cardiac condition of the patient or fetus, and the known or anticipated actions of the antiarrhythmic drug being considered. The management of specific arrhythmias encountered in pregnant women are also discussed. For benign arrhythmias, a conservative approach starting first with preventive measures is appropriate. For more severe or symptomatic arrhythmias, pharmacologic therapy should be instituted using drugs with proven safety to the fetus, if possible. Electrical cardioversion of the patient may be performed with relative safety in more emergent situations.

Anti-Arrhythmia Agents↗
PubMedDate not supplied

Temporal electrical heterogeneity for detecting coronary artery disease: results in a heterogeneous cardiac population.

BACKGROUND: A new 22-lead electrocardiographic test has been advocated as a screening tool for coronary artery disease and has been shown to have accuracy similar to stress electrocardiography in specific patient populations. OBJECTIVE: To determine the accuracy of this test for detecting coronary artery disease in patients undergoing coronary angiography for a variety of cardiac conditions. METHODS: We prospectively determined the temporal electrical heterogeneity (TEH) index at rest in 70 patients who had no angina or Q waves on the resting 12-lead electrocardiogram before they underwent coronary angiography. RESULTS: Twenty-six of the 70 patients had significant coronary artery disease, defined as 70% stenosis or greater in at least one major epicardial coronary artery. A TEH index of 80 or more had a sensitivity of 58%, a specificity of 75%, and a positive predictive value of 58%. The group with significant coronary disease had a mean TEH index of 77.2, and the group without coronary disease had a mean index of 65.5 (P = .02), despite similar clinical characteristics and indications for angiography. CONCLUSION: The TEH index shows promise as a screening tool for coronary artery disease in a heterogeneous cardiac population. However, larger studies are needed before it can be endorsed for widespread clinical use.

Aged↗
PubMed1992

The complications of infective endocarditis. A reappraisal in the 1980s.

BACKGROUND: The frequency of complications of infective endocarditis and their influence on the outcome of the patients changed in the antibiotic era. Therefore, we evaluated the complications in a recent large series of patients with infective endocarditis. METHODS: We studied 300 episodes of endocarditis in 287 patients in a tertiary cardiology referral center. Predisposing cardiac conditions were valvular heart disease in 147 episodes, congenital heart disease in 37, other heart diseases in five, and prosthetic heart valves in 69. In 69 episodes, there was no previous heart disease. The infecting microorganisms were streptococci in 147 episodes, Staphylococcus aureus in 59, Staphylococcus epidermidis in 14, gram-negative bacteria in 16, other gram-positive bacteria in eight, and fungi in four. In 52 episodes, blood cultures were negative. Seventy-eight patients (26%) died. Complications were defined as any clinically unfavorable event occurring during treatment. RESULTS: A total of 386 complications occurred in 223 episodes (74%); one complication occurred in 128 episodes (57%), two in 57 (26%), three in 18 (8%), four in 13 (6%), five in three (1%), and six or more in three (1%). The complications were as follows: cardiac, 100 occurrences; neurological, 72; septic, 46; associated with medical treatment, 41; renal, 27; extracranial systemic arterial embolism, 16; septic pulmonary embolism, 26; complications related to surgical treatment, 11; acute prosthetic heart valve insufficiency, six; splenic infarction or abscess, three; cardiac rhythm disturbances, three; and other, 19. The distribution of the complications relative to outcome of the patients revealed that fatality exceeded survival rates for neurologic and septic complications. CONCLUSIONS: Complications may be common in patients with infective endocarditis. Cardiac complications were the most common ones, but fatality rates were higher for neurologic and septic complications. Hence, heart failure was replaced by neurologic and septic complications as the leading causes of death in patients with infective endocarditis.

Adolescent↗
PubMed2003

New surgical therapies for heart failure.

A growing number of patients present with heart failure. Some of them may qualify for surgical correction of their cardiac condition. Since heart transplantation will always be available to only a small number of patients, several new surgical techniques have been developed for approval in heart failure patients. Classic interventions such as revascularization, valve repair, or valve replacement have been improved and modified to meet the need of heart failure patients. Several of these techniques are currently under investigation in large clinical trials. These trials will definitely have an impact on the development of surgical treatment of patients with heart failure.

Cardiac Surgical Procedures↗
PubMed1996

Thyroid hormone abnormalities in heart failure: possibilities for therapy.

Though thyroid hormone abnormalities have been identified in many cardiac conditions, the role of thyroid hormones in congestive heart failure has not been well defined. In a population of patients with advanced heart failure, a reduction in triiodothyronine (T3) with an increase in reverse T3 was identified in many patients, with an abnormally low ratio of T3/reverse T3 being the strongest predictor of mortality. Normalization of thyroid indices appeared to be necessary for prolonged survival to occur. To address the concern of T3 administration possibility exacerbating a hypermetabolic state, basal metabolic rate was measured in a group of advanced heart failure patients and was found to be generally within the normal range. A preliminary safety study of short-term intravenous T3 administration (bolus +/- 6 h infusion, total dose 0.15-2.7 micrograms/kg) was then performed in 23 patients under hemodynamic and electrocardiographic monitoring. There were neither adverse events nor substantial hemodynamic changes, but some patients had an increase in cardiac output, consistent with a peripheral vasodilatory effect. With this foundation, further investigation into the possible role of T3 and its analogs in congestive heart failure therapy may be pursued.

Heart Failure↗
PubMed2000

[Maternal cardiac arrhythmias in pregnancy].

During pregnancy an increased incidence of maternal cardiac arrhythmias is observed. These include a wide spectrum, from clinically irrelevant isolated premature beats to debilitating supraventricular and ventricular tachycardias. In principle, management of arrhythmias during pregnancy is similar to that in non-pregnant patients. However, special consideration should be given to foetal age and potential teratogenic and haemodynamic adverse drug effects on the foetus. Therapeutic strategy should be guided by interdisciplinary consulting (i.e. cardiology, obstetrics, neonatology). Diagnostic evaluation must rule out underlying cardiovascular, pulmonary, endocrine or metabolic diseases. Additionally, precipitating factors such as excessive caffeine and/or alcohol ingestion and cigarette smoking should be avoided. For benign arrhythmias a conservative approach is appropriate. Antiarrhythmic drug selection depends on the specific arrhythmia being treated and the cardiac condition of the mother and the foetus. Some antiarrhythmic agents, such as propranolol, metoprolol, digoxin and quinidine, have been extensively tested during pregnancy and have proven to be safe; they should therefore, whenever possible, be used as firstline. For supraventricular tachycardia, intravenous adenosine may be used to terminate the arrhythmia if vagal manoeuvres fail. In emergency situations cardioversion may be performed with relative safety. Implantable cardioverter defibrillators as a preventive measure for life-threatening arrhythmias in pregnant patients do not seem to increase the risk of major complications.

Adult↗
PubMed2006

Perioperative management of chronic heart failure.

Heart failure (HF) is one of the few cardiac conditions that is increasing. Despite a better understanding of how hormones and other signaling systems underlie the pathophysiology, and despite improved outcomes from pharmacologic therapy, many HF patients receive no effective treatment. Patients with HF commonly require medical diagnosis and management in operating rooms and critical care units; thus anesthesiologists are obliged to remain up-to-date both with advances in outpatient (chronic) medical management and with inpatient treatments for acute exacerbations of HF. Accordingly, we reviewed angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-adrenergic receptor blockers, and aldosterone antagonists because these drugs prolong life and are included in current clinical practice guidelines for treating patients with chronic HF. We also reviewed the implications of chronic HF for patients undergoing surgery and anesthesia and discuss how best to provide intensive treatment for acute exacerbations of symptoms, such as might be caused by excessive intravascular volume, inappropriate drug "holidays," or worsening of the underlying cardiac disease.

Adrenergic beta-Antagonists↗
PubMed2005

Association between particulate matter and emergency room visits, hospital admissions and mortality in Spokane, Washington.

There is conflicting evidence regarding the association between different size fractions of particulate matter (PM) and cardiac and respiratory morbidity and mortality. We investigated the short-term associations of four size fractions of particulate matter (PM(1), PM(2.5), PM(10), and PM(10-2.5)) and carbon monoxide with hospital admissions and emergency room (ER) visits for respiratory and cardiac conditions and mortality in Spokane, Washington. We used a log-linear generalized linear model to compare daily averages of PM and carbon monoxide with daily counts of the morbidity and mortality outcomes from January 1995 to June 2001. We examined pollution lags ranging from 0 to 3 days and compared our results to a similar log-linear generalized additive model. Effect estimates tended to be smaller and have larger standard errors for the generalized linear model. Overall, we saw no association with respiratory ER visits and any size fraction of PM. However, there was a suggestion of greater respiratory effect from fine PM when compared to coarse fraction. Carbon monoxide was associated with both all respiratory ER visits and visits for asthma at the 3-day lag. We feel that carbon monoxide may be serving as a marker for combustion-derived pollutants, which is one large component of the diverse air pollutant mixture. We also found no association with any size fraction of PM or CO with cardiac hospital admissions or mortality at the 0- to 3-day lag. We found no consistent associations between any size fraction of PM and cardiac or respiratory ER visits or hospital admissions.

Air Pollutants↗
PubMed2001

Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial.

BACKGROUND: Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis. METHODS AND RESULTS: This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis. CONCLUSIONS: IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months.

Acute Disease↗
PubMed2005

Antibiotic prophylaxis for endocarditis: time to reconsider.

Some cardiac conditions require antibiotic prophylaxis for some types of dental treatment to reduce the risk of infective endocarditis (IE). All medical and dental practitioners are familiar with this practice but tend to use different regimens in apparently similar circumstances. Generally, the trend has been to prescribe antibiotics if in doubt. This review explores the evidence for antibiotic prophylaxis to prevent IE: does it work and is it safe? The changing nature of IE, the role of bacteraemia of oral origin and the safety of antibiotics are also reviewed. Most developed countries have national guidelines and their points of similarity and difference are discussed. One can only agree with the authority who describes antibiotic guidelines for endocarditis as being 'like the Dead Sea Scrolls, they are fragmentary, imperfect, capable of various interpretations and (mainly) missing!' Clinical case-controlled studies show that the more widely antibiotics are used, the greater the risk of adverse reactions exceeding the risk of IE. However, the consensus is that antibiotic prophylaxis is mandatory for a small number of high-risk cardiac and high-risk dental procedures. There are a large number of low-risk cardiac and dental procedures in which the risk of adverse reactions to the antibiotics exceeds the risk of IE, where prophylaxis should not be provided. There is an intermediate group of cardiac and dental procedures for which careful individual evaluation should be made to determine whether IE or antibiotics pose the greater risk. These categories are presented. All medical and dental practitioners need to reconsider their approach in light of these current findings.

Antibiotic Prophylaxis↗
PubMed1994

The pediatric cardiac care consortium--revisited.

BACKGROUND: The Pediatric Cardiac Care Consortium (PCCC) is a collaborative, voluntary effort of pediatric cardiologists to gather and analyze data regarding operative results. METHODS: PCCC collects information on each child who undergoes cardiac catheterization, electrophysiologic study, or a cardiac operation, or dies with a cardiac malformation. The data are analyzed annually and individual reports are created for each center. Also, representatives from the centers meet annually, and data-on the major operative procedures, including risk factors, patient profiles, and variations in adjusted mortality-are presented. RESULTS: Since PCCC's founding in 1982, overall operative mortality has decreased from 14% to 4.1% in 1991 (22% to 8.2% for infants). In one center, for example, in which overall and infant operative mortality dropped in seven years from 15% and 28% to 8% and 15%, respectively, the cardiologists and surgeon used the PCCC data to identify areas of weakness and adopt new diagnostic and treatment methods for particular cardiac conditions. They now opt for safer initial operative approaches. Another center reduced its operative mortality for coarctation of the aorta in infants after data review led to a decision to be more aggressive in early referral of infants for operations and for changes in perioperative management. DISCUSSION: Use of the study group model, in which key members work with their institution to use and interpret the data, has been an effective strategy for data dissemination. The PCCC is exploring the concept of "model centers," which would probably be procedure specific. With additional funding, the database could be expanded to include morbidity measures, functional outcome, and long-term follow-up.

Cardiac Care Facilities↗
PubMed1978

Late hemodynamic and angiographic findings after ascending aorta--pulmonary artery anastomosis.

Ascending aorta-pulmonary artery (Waterston) anastomosis was performed in 75 children, 51 of whom were younger than 1 month of age and 36 younger than 1 week of age at the time of operation. There were 21 operative and eight late deaths. Operative deaths occurred more frequently in infants with complex cardiac conditions and severe hypoxemia and acidosis preoperatively. The postoperative status of the pulmonary arteries or arterioles could not be correlate with the degree of cardiomegaly, the pulmonary vascular markings, or characteristics of the shunt murmur. Sixty-four percent of the patients catheterized had one or more postoperative structural abnormalities of the pulmonary arteries following the operation, most frequently kinking or narrowing of a pulmonary artery. Occlusion of a pulmonary artery occurred in five of 33 patients studied by angiography. Pulmonary vascular disease may also develop. Therefore, patients should be catheterized 1 year postoperatively to evaluate the level of pulmonary vascular resistance and the pulmonary arteries.

Aorta↗
PubMed2004

American Heart Association scientific sessions.

The Annual Scientific Sessions of the American Heart Association is the leading scientific conference in the cardiovascular field, both for basic and clinical research in cardiology and related disclipines. This report covers the outcome of major clinical trials that were presented in the 'late-breaking' clinical trial sessions. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) investigated the angiotensin receptor blocker valsartan, the angiotensin-converting enzyme inhibitor captopril, and their combination in 14,703 survivors of an acute myocardial infarction with a reduced left ventricular ejection fraction on clinical outcome. The study demonstrated that valsartan and captopril where equally effective, whereas the combination was associated with an increased risk of side effects without further benefit. VALIANT is a landmark trial because it was the first large study that compared the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor in the setting of acute myocardial infarction. Other trials that will be summarised in this report are the Na + /H + Exchange Inhibition to Prevent Coronary Events in Acute Cardiac Conditions Trial (EXPEDITION; cariporide in coronary artery bypass graft surgery), the Reversal of Atherosclerosis with Aggressive Lipid Lowering Trial (REVERSAL; atorvastatin and pravastatin for atherosclerosis reversal), the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation V (SPORTIF V; ximelagatran and warfarin for stroke prevention in atrial fibrillation), the Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularisation (PAPABEAR; amiodarone for the prevention of postoperative atrial fibrillation), the Acute and Chronic Therapeutic Impact of a Vasopressin 2 Antagonist in Congestive Heart Failure (ACTIV in CHF; vasopressin 2 antagonist tolvaptan in congestive heart failure) and Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT; fosinopril and pravastatin in microalbuminuric subjects without hypertension or hypercholesterolemia).

American Heart Association↗
PubMed2003

Maternal arrhythmias during pregnancy.

INTRODUCTION: An increased incidence of maternal cardiac arrhythmias is observed during pregnancy and they can range from clinically irrelevant isolated premature beats to debilitating supraventricular and ventricular tachycardias. DISCUSSION: Management of arrhythmias during pregnancy is similar to that in non-pregnant patients. However, the presence of the foetus and the risk of teratogenicity, the haemodynamic changes, the effect of therapy on labour, delivery and lactation must be evaluated. Antiarrhythmic drug selection depends on the specific arrhythmia being treated and the cardiac condition of the mother. Although no drug is completely safe, most are well tolerated and can be given with relatively low risk. Some antiarrhythmic agents, such as propranolol, metoprolol, digoxin and quinidine, have been extensively tested during pregnancy and have proved to be safe; they should therefore, whenever possible, be used as a first-line. For supraventricular tachycardia, intravenous adenosine may be used to terminate the arrhythmia if vagal manoeuvres fail. If possible, drug therapy should be avoided during the first trimester of pregnancy. When drug treatment fails or is not indicated because of the haemodynamic instability of the patient, direct current cardioversion can be used. CONCLUSION: Most patients with arrhythmias during pregnancy can be treated with an excellent result.

Anti-Arrhythmia Agents↗
PubMed2006

Operating characteristics of the Finapress system to predict elevated left ventricular filling pressure.

BACKGROUND: Dyspnea is a common symptom and can be caused by many different conditions. The detection of congestive heart failure (CHF) is sometimes difficult. HYPOTHESIS: The pulse amplitude ratio (PAR) measured by the Finapress procedure during a Valsalva maneuver can detect elevated left ventricular end-diastolic pressure (LVEDP) accurately over a wide range of values. METHODS: Comparison of the estimated LVEDP by PAR with the invasively measured LVEDP before and after ventriculography during coronography was made in 101 consecutive stable patients referred for chest pain and/or chronic dyspnea. RESULTS: A significant correlation was found between the catheter-measured LVEDP (range 3-40 mmHg) and the PAR (R2 = 0.70, p < 0.001). The receiver operator characteristics (ROC) of the PAR to detect an LVEDP > 15 mmHg can be considered to be excellent, with an area under the ROC curve achieving 0.92 (95% confidence interval [CI] 0.87-0.96; p < 0.001). A PAR of > 0.675 predicted the presence of an LVEDP > 15 mmHg with a sensitivity of 0.865 (95% CI 0.780-0.926) and a specificity of 0.847 (95% CI 0.730-0.928). The positive and negative LRs were 5.70 and 0.16, respectively. CONCLUSIONS: The observed likelihood ratios confirm that the PAR determined by the Finapress procedure may be a useful bedside diagnostic tool in patients with cardiac conditions.

Adult↗
PubMed1990

Early and late results after repair of tetralogy of Fallot.

Between January 1, 1975, and December 31, 1988, 233 patients were operated on for correction of tetralogy of Fallot (TOF). Mean follow-up was 13.9 years (median 7.65 years) and was 99.6% complete. Actuarial survival was 84 +/- 3%. The risk of death decreased gradually to a constant rate of 0.00034 deaths/month by the 6th postoperative month. There were 22 early deaths, due mostly to Low Output Syndrome. The principal incremental risk factor was the postrepair ventricular pressure ratio (PRV/LV) (P less than 0.0001). Other factors were: patent ductus arteriosus (PDA; P = 0.02), other associated anomalies (P = 0.005), higher preoperative hemoglobin levels (P = 0.06) and use of transannular patches (P = 0.02). The operative risk was significantly reduced by a recent operative date (P = 0.01) and by an older age at operation (P = 0.12). Among 8 late deaths, 2 were unrelated to the cardiac condition, 2 occurred suddenly, 3 were due to congestive heart failure and the last was due to reoperation for patch endocarditis. The risk of late death was significantly higher in patients operated on at an older age (P = 0.04). There were 10 open heart reoperations: 5 for patch dehiscence, 4 for residual pulmonary stenosis and 1 for residual atrial septal defect. The reoperation-free actuarial survival was 82 +/- 3%. With the present operative standards, the parametric operative risk of an average patient with simple TOF (hemoglobin = 12 g, PRV/LV = 0.5) is 0.7%. Where the TOF is severely cyanotic (hemoglobin = 25 g) and the pulmonary arteries are severely restricted, the average mortality is 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗