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Biomedical subjects

M Höher

Publications and source records attributed to M Höher.

At least 37 records · Page 2Linked to original sources

Quantification of mitral and tricuspid regurgitation by the proximal flow convergence method using two-dimensional colour Doppler and colour Doppler M-mode: influence of the mechanism of regurgitation.

In patients with mitral (n=77: organic=49, functional=28) and tricuspid regurgitation (n=55: functional=54) quantified by angiography, the temporal variation of the proximal flow convergence region throughout systole was assessed by colour Doppler M-Mode, and peak and mean radius of the proximal isovelocity surface area for 28 cm/s blood flow velocity were measured. Additionally, the peak radius derived from two-dimensional colour Doppler was obtained. About 50% of the patients with mitral and tricuspid regurgitation showed a typical temporal variation of the flow convergence region related to the mechanism of regurgitation. The different proximal isovelocity surface area radii were similarly correlated to the angiographic grade in mitral and tricuspid regurgitation (rank correlation coefficients 0.55-0.89) and they differentiated mild to moderate (grade < or =II) from severe (grade > or =III) mitral and tricuspid regurgitation with comparable accuracy (82-96%). However, moderate mitral regurgitation due to leaflet prolapse in two patients was correctly classified by the mean M-mode radius and overestimated by both peak radii. Only half of the patients showed a typical variation of the flow convergence region related to the mechanism of regurgitation. The different proximal isovelocity surface area radii were suitable to quantify mitral and tricuspid regurgitation in most patients. However, in mitral regurgitation due to leaflet prolapse the use of the mean M-mode radius may avoid overestimation.

Adult↗

A remark on the high-conductance calcium-activated potassium channel in human endothelial cells.

The patch-clamp technique was used to examine the presence of large conductance calcium-activated potassium channels (BKCa) in human endothelial cells and to characterize their properties in terms of voltage dependence, ion conduction and blockade by iberiotoxin (IbTX). Experiments were performed using cell-attached and outside-out configurations on human umbilical vein endothelial cells (HUVEC). For the experiments HUVECs, which were passaged 6-19 times, were used. In early passages channel activities were absent suggesting the appearance of BKCa depending on cell culture time. The inverse logarithmic voltage sensitivity was 10.17 mV (median) for cell-attached recordings and 12.10 mV (median) for outside-out patches (membrane voltage range: 60-120 mV, symmetrical 140 mM K+ solutions). The I/V relationship was quasilinear in the range of 0-80 mV and exhibited a nonlinear behaviour under further depolarization suggesting some kind of saturation mechanism. Using a sigmoid function to fit the data, channel conductance was calculated as 172.9 pS (median) for cell-attached patches and as 262.1 pS (median) for outside-out patches. IbTX, known as one of the most selective blockers of BKCa was perfused to outside-out patches. In two out of three experiments there was complete block of the ion channel after 1 min.

Cells, Cultured↗

Comparison of the proximal flow convergence method and the jet area method for the assessment of the severity of tricuspid regurgitation.

AIMS: To compare the value of the proximal flow convergence method and the jet area method for the determination of the severity of tricuspid regurgitation. METHODS AND RESULTS: The proximal isovelocity surface area radius and the jet area/length were measured in 71 consecutive patients with angiographically graded (grade 0/I-III) tricuspid regurgitation. Rank correlation coefficients with the angiographic grade were 0.71 (P < 0.001) for the proximal isovelocity surface area radius (aliasing border of 28 cm.s-1), 0.66 (P < 0.001) for the jet area, and 0.63 (P < 0.001) for the jet length. The proximal isovelocity surface area radius was significantly correlated with the jet area/length (correlation coefficients 0.82/0.77, P < 0.001). Correct differentiation between mild to moderate (grade I-II) and severe (grade III) tricuspid regurgitation was achieved in 62 of 71 patients (87%) by means of the proximal isovelocity surface area radius, in 61 of 71 (86%) by the jet area, and in 62 of 71 (87%) by the jet length. Grade III tricuspid regurgitation was not identified in five of 21 patients (24%) by means of the proximal isovelocity surface area radius, in six of 21 (29%) by the jet area, and in seven of 21 (33%) by the jet length. CONCLUSION: The flow convergence method and the jet area method are of similar value for the determination of the severity of tricuspid regurgitation. Both methods differentiated mild to moderate from severe tricuspid regurgitation in most patients. However, underestimation of severe tricuspid regurgitation in 20-30% of the cases represents a serious limitation of both methods.

Adult↗

[Clinical and economic cost-benefit relations in treatment of patients with coronary heart disease].

Economic evaluation of medical treatment in terms of costs and utility has gained increasing interest within the medical community and in political discussions. In particular this applies for highly prevalent diseases such as coronary artery disease, still the most common cause of death in the western world. Health economy studies can be performed from different perspectives (e.g., hospital, insurance company, society) and with various approaches (e.g., cost-utility analysis, cost minimization). Those will be discussed for the primary prevention of myocardial infarction, coronary stent implantation, and for rehabilitation programs after myocardial infarction, serving as examples. Health-economical analyses provide data to compare treatment strategies beyond a certain speciality. However, economic evaluation is only one step within the medical assessment process and does not per se imply the political allocation of financial resources.

Angioplasty, Balloon, Coronary↗

Signal-averaged electrocardiogram in patients with insulin-dependent (type 1) diabetes mellitus with and without diabetic neuropathy.

The purpose of this study was to investigate the presence of ventricular late potentials derived from signal-averaged ECG in patients with IDDM with and without diabetic neuropathy. Eighty patients with IDDM but without evidence of cardiac disease and 80 age-matched healthy control subjects were investigated. The corrected QT interval was measured from the standard surface electrocardiogram. Ventricular late potentials were derived from signal-averaged electrocardiogram. Out of the 80 diabetic patients, 20 had an autonomic neuropathy, 20 had an isolated peripheral neuropathy, and 40 had no symptoms of neuropathy. The corrected QT interval was significantly prolonged in patients with an autonomic neuropathy as compared with the control group (436 +/- 23 ms(x 5) vs 384 +/- 23 ms(x 5), p < 0.001). In the other patient groups there was no significant prolongation of the corrected QT interval. Ventricular late potentials were present in 3 diabetic patients with an isolated peripheral neuropathy and in 1 control subject (NS). No diabetic patient with an autonomic neuropathy had ventricular late potentials. Our data did not indicate an increased incidence of ventricular late potentials derived from signal-averaged electrocardiogram in diabetic patients independent of a coexisting diabetic neuropathy or a prolonged corrected QT interval.

Adolescent↗

Felodipine and amlodipine in stable angina pectoris: results of a randomized double-blind crossover trial.

A randomized, double-blind, crossover study tested the antiischemic and antianginal efficacy of felodipine, extended-release 5-10 mg, versus amlodipine, 5-10 mg once daily. Fifty-two patients with documented exercise-induced angina pectoris and myocardial ischemia during 24-h electrocardiographic monitoring were included in the study. Forty-seven patients completed the 8-week treatment period, whereas five patients withdrew from the study. The mean number of ischemic episodes/24 h was reduced from 19.9 at baseline to 2.3 during amlodipine and to 2.4 during felodipine; the total duration of ischemic episodes decreased from 69.8 min/24 h to 15.2 min and 15.5 min during amlodipine and felodipine, respectively (for both variables, p = 0.83 and p = 0.53 between treatments, and for both treatments, p < 0.001 compared with baseline). Eighteen (38%) patients receiving amlodipine and 19 (40%) patients receiving felodipine showed no ST-segment depression during treatment. Maximal ST-depression was reduced from an average of 2.1 mm to 1.1 and 1.2 mm on amlodipine and felodipine, respectively (p = 0.68 between treatments and p < 0.001 compared with baseline). Mean heart rate remained unchanged compared with baseline. Anginal attacks were reduced from 16.4/week at baseline to 4.7/week with amlodipine and to 4.3/week with felodipine (p = 0.26 between treatments, and p < 0.001 vs. baseline). Accordingly, nitrate consumption was reduced from 14.7 capsules per week to 4.0 and 3.8 with amlodipine and felodipine, respectively (p = 0.40 between treatments, and p < 0.001 compared with baseline). Adverse reactions were infrequent and distributed similarly between the two treatments. It is concluded that both drugs effectively reduced ischemic episodes and anginal attacks and were well tolerated in patients with stable angina pectoris. There was no evidence that the two regimens were different in their antiischemic and antianginal properties.

Adult↗

[Whole body distribution of Tc-99m-sestamibi after pharmacological stress with arbutamine and dipyridamole compared with resting conditions].

AIM: Arbutamine is a new catecholamine that has been developed as a pharmacologic stress agent for the diagnosis of coronary artery disease. Optionally, it can be used in myocardial scintigraphy. The pharmacologic effect compared to dipyridamole was assessed looking at the whole body distribution of Tc-99m-Sestamibi. METHODS: 9 patients were investigated after injection of Tc-99m-Sestamibi during rest, after infusion of arbutamine, and after vasodilatation with dipyridamole. RESULTS: Infusion of arbutamine results in a measurable diminished radiotracer deposition in the lower limb as compared to dipyridamole. The amount of myocardial activity of Tc-99m-sestamibi, however, is also reduced as shown by the percentage of myocardial activity compared to the whole body distribution (2.5% +/- 0.4% for arbutamine vs. 2.8% = 0.5% for dipyridamole) in addition, the heart/lung ratio is lower after application of arbutamine (12.1% +/- 0.5% vs. 2.4% +/- 0.4%). CONCLUSION: After infusion of arbutamine the percentage of myocardial activity as well as the contrast of the myocardium to the surrounding lungs is decreased as compared to dipyridamole. Further studies should reveal whether this difference is relevant in diagnosing coronary artery disease.

Adrenergic beta-Agonists↗

Increased endothelin release by cultured human smooth muscle cells from atherosclerotic coronary arteries.

OBJECTIVES: Endothelin, a 21-amino acid peptide initially purified from the medium of cultured endothelial cells, is a potent vasoconstrictor exerting its effects predominantly in a paracrine or autocrine manner. Recent data indicate that endothelin is also synthesized by cultured vascular smooth muscle cells and that endothelin is an effective stimulator of smooth muscle cell proliferation. This study aimed to investigate the endothelin release of cultured human smooth muscle cells, isolated from coronary plaques and from normal coronary tunica media, and to determine circulating endothelin concentrations in patients with coronary artery disease compared to control subjects. METHODS: Coronary plaque material was extracted by thrombendarterectomy during aorto-coronary bypass grafting (n = 19). Segments of normal coronary arteries were obtained at autopsy (n = 33). Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells with antibodies against smooth muscle alpha-actin. Venous blood samples were drawn from patients with coronary artery disease undergoing cardiac catheterization (n = 32) and from control subjects (n = 38). Endothelin concentrations in culture medium and in plasma samples were measured by radioimmunoassay after Sep Pak C18 extraction. RESULTS: Cultured smooth muscle cells, isolated from coronary plaques, released a significantly (P < 0.001) higher amount of immunoreactive endothelin into the culture medium (39.2 +/- 3.9 pg/10(4) cells, mean +/- s.e.m., 31 supernatant samples) than smooth muscle cells from normal coronary tunica media (3.9 +/- 0.8 pg/10(4) cells, 28 samples). Circulating endothelin concentrations were slightly elevated (P < 0.01) in patients with coronary artery disease (3.8 +/- 0.2 pg/ml) compared to control subjects (3.0 +/- 0.2 pg/ml). CONCLUSIONS: These data suggest that the endothelin production is markedly increased in smooth muscle cells of coronary atherosclerotic plaques. The enhanced endothelin release may stimulate smooth muscle cell proliferation in a paracrine or autocrine manner and thus may contribute to the development or progression of coronary artery disease.

Cells, Cultured↗

Influence of the mechanism of regurgitation on the quantification of mitral regurgitation by the proximal flow convergence method and the jet area method.

In 84 patients mitral regurgitation was quantified by angiography. The mechanism of regurgitation was determined by echocardiography (organic, n = 54, functional, n = 30). The radii of the proximal isovelocity surface areas in the flow convergence region for 28 and 41 cm.s-1 blood flow velocity and the area and length of the regurgitant jet were measured using colour flow Doppler imaging. The radii of the proximal isovelocity surface areas correlated more closely with the angiographic grade than the jet parameters irrespective of the mechanism of regurgitation. In more than 90% of the patients, grades I-II mitral regurgitation were correctly differentiated from grades III-IV by means of the radii of the proximal isovelocity surface areas. Using the jet parameters, the differentiation was correct in 50-90% of the patients depending on the mechanism of regurgitation. The jet area method particularly failed to identify grades III-IV organic mitral regurgitation due to a high prevalence of eccentric jets in these patients. It is concluded that the proximal flow convergence method was suitable for the quantification of mitral regurgitation irrespective of the mechanism of mitral regurgitation. On the other hand, the value of the jet area method depended largely on the regurgitation mechanism.

Adult↗

Quantification of mitral regurgitation--comparison of the proximal flow convergence method and the jet area method.

A total of 92 patients with mitral regurgitation (age 63 +/- 13 years, 51 men, 41 women), quantified by angiography, were studied using color-flow Doppler imaging of isovelocity surface areas in the flow convergence region proximal to the regurgitant orifice (PISAs) and of the regurgitant jet in the left atrium. The PISA radii for the flow velocities (aliasing borders) of 28 and 41 cm/s, jet area, jet length, and relation of jet area to left atrial area were measured. A proximal flow convergence region was imaged in 98% (85%) of all patients for a flow velocity of 28 (41) cm/s. A regurgitant jet could be visualized in all patients. The PISA radii for both flow velocities correlated more closely with the angiographic grade (rSp = 0.79 for both flow velocities) than the jet area (rSp = 0.43), jet length (rSp = 0.39), and relation of jet area to left atrial area (rSp = 0.37). A correct differentiation of grade I-II from grade III-IV mitral regurgitation was provided in 95% of the patients by the proximal flow convergence method for both flow velocities and in up to 78% of the patients by the jet area method using the uncorrected jet area. The PISA radii correlated weakly with the parameters from the regurgitant jet (r = 0.5-0.58). It can be concluded that the proximal flow convergence method and the jet area method reach comparable sensitivity for the detection of mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A prescreening system for potential antiproliferative agents: implications for local treatment strategies of postangioplasty restenosis.

BACKGROUND: Recent advances in the understanding of the biology of restenosis indicate that it is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. The aim of this study was to investigate the in vitro effect of five potential antiproliferative agents on smooth muscle cells from human atherosclerotic femoral arteries. METHODS AND RESULTS: Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. Dalteparin sodium (0.001-100 anti-Xa units/ml), cyclosporine A (0.005-500 micrograms/ml), colchicine (0.00004-4 pg/ml), etoposide (0.002-200 micrograms/ml), and doxorubicin (0.0005-50 micrograms/ml) were added to the cultures. Six days after seeding, cells were trypsinized and cell number was measured by a cell counter. All five agents tested exhibited a significant inhibition of smooth muscle cell proliferation (P < 0.001). After an incubation time of 48 h, the cytoskeletal components, alpha-actin, vimentin, and microtubules were investigated. At peak concentrations, all five tested agents except dalteparin sodium caused severe damage to the cytoskeleton. CONCLUSIONS: All five potential antiproliferative agents exhibited a significant inhibition of smooth muscle cell proliferation. The development of new intravascular delivery systems may open the way for local antiproliferative treatment strategies in interventional cardiology.

Actins↗

A coronary porcine organ culture system for studies of postangioplasty cell proliferation.

BACKGROUND: Restenosis after angioplasty is generally considered to be caused mainly by an increased proliferation of smooth muscle cells, but recently this theory has been questioned. METHODS: Fresh hearts of 25 pigs were obtained and the left anterior descending coronary arteries carefully prepared, cut into segments and treated with a 3 mm standard balloon catheter for 60 s with 3, 6, 9 and 12 bar. Immediately after angioplasty the specimens were cultured in a mixture of WM/F-12, supplemented with 15% fetal calf serum. RESULTS: After staining with a modified Verhoeff-van Gieson technique, intimal wall thickening was analysed with a computerized morphometric system. After 14 days in culture, angioplasty with 6, 9 and 12 bar resulted in a significant (P < 0.05) increase of neointimal thickening. After 21 days, a significant increase of neointimal thickening was seen after ballooning with 3, 9 or 12 bar (P < 0.05). After 28 days angioplasty with 3 or 6 bar showed a dose-dependent increase of neointima, which was not further increased after ballooning with 9 or 12 bar. Significance was reached after ballooning with 6, 9 and 12 bar (P < 0.05). Smooth muscle cells were identified with a monoclonal antibody against smooth muscle alpha-actin. Endothelial cells were identified using an anti-human von Willebrand factor. To determine the number of cells undergoing DNA synthesis, bromodeoxyuridine, a thymidine analogue, was added to the culture media 18 h before fixation. It was detected with a monoclonal antibody, with a biotinylated horse-anti-mouse antibody as secondary antibody. After 4 and 7 days in culture bromodeoxyuridine-positive cells were observed, indicating an early proliferative response after angioplasty. CONCLUSIONS: The coronary organ culture model offers opportunities for investigations of complex cellular events that are considered important in the development of restenosis. The data reported emphasize the importance of an early proliferative response of smooth muscle cells after coronary angioplasty, resulting in a significant neointimal thickening.

Angioplasty, Balloon↗

[Assessment of severity of mitral insufficiency--value of various color Doppler echocardiographic methods].

A total of 79 patients with mitral regurgitation (age 62 +/- 11 years, 45 men, 34 women) quantified by angiography was studied using color-Doppler imaging of isovelocity surface areas in the flow convergence region proximal to the regurgitant orifice (PISAs), of the jet cross-section at the level of the regurgitant orifice and of the regurgitant jet in the left atrium. The PISA-radii for the flow velocities (aliasing borders) of 28 and 41 cm/s, the cross-sectional jet area and the jet length, and relation of jet area to left atrial area were measured. The sensitivity for the detection of mitral regurgitation was at least 97% for the color-Doppler methods investigated in these patients in which a sufficient imaging was obtained. However, a sufficient imaging of the flow convergence region and the jet cross-section was not possible in about 5% of all patients. The PISA-radii for both flow velocities and the cross-sectional jet area correlated more closely with the angiographic grade (rSp = 0.79-0.80, p < 0.001) than the jet area (rSp = 0.39, p < 0.001), jet length (rSp = 0.37, p < 0.001), and relation of jet area to left atrial area (rSp = 0.31, p < 0.01) did. A correct differentiation of grades I to II from grades III to IV mitral regurgitation was provided in 93-95% of patients by the proximal flow convergence and by the cross-sectional jet area method and, at most, in 76% of the patients by the jet area method using the uncorrected jet area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Recurrent stenosis following coronary angioplasty. Clinical, cell biological and molecular aspects].

Percutaneous transluminal coronary angioplasty by balloon dilatation (PTCA) has proved to be the standard procedure for non-operative removal of coronary artery stenoses. Since the initial description and application by Andreas Grüntzig, the results of this procedure are excellent with an acute success rate of 90-96%, a rate of severe acute complications of 1% and less, and a procedure-related death rate below 1%, mainly due to considerable technical improvements and greater experience of the interventional cardiologists. On the other hand, the restenosis rate following PTCA could not be significantly lowered. In recent years a number of alternative angioplasty devices has been developed aimed at-among other indications-reducing the restenosis rate following PTCA by a "less traumatic" vessel angioplasty. These include radiofrequency angioplasty (RFCA), high frequency rotational angioplasty (HFRCA), excimer-laser angioplasty (ELCA), directional atherectomy (DCA), as well as implantation of intravascular stents. Based on more or less extensive experiences from the literature, the aim at lowering the recurrency rate by the latter procedures has been missed, despite the fact that particularly ELCA and HFRCA were used to reduce stenoses in lesions unsuitable for balloon catheter dilatation. There is a trend of lowering the recurrence rate with the implantation of coronary stents. The benefit of this procedure, however, is at the expense of an increased rate of acute stent thrombosis and by local acute bleeding problems quite often requiring surgical repair. The cellular biological mechanisms following balloon angioplasty are only partially understood. Among these are a number of interactive processes like cell adhesion, coagulation, vascular contraction, cell migration, cell proliferation, and synthesis of extracellular matrix. In this respect, migration and proliferation of smooth muscle cells represent a key process for the development of restenosis. In addition, endothelial denudation represents a stimulus for migration and proliferation of smooth muscle cells. Rapid and efficient reendothelialization may counteract this process. Recent progress of modern biology has provided new concepts and methodological tools for the molecular analysis of vascular remodeling. It has been shown that specialized cellular functions such as proliferation, migration, and production of extracellular matrix can be mediated by growth factors such as platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) or transforming growth factor-beta (TGF-beta).(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary↗

[Three AV-nodal pathways in a patient with atypical AV-nodal reentry tachycardia].

In a female patient with paroxysmal AV nodal reentrant tachycardias the electrophysiological study revealed three AV nodal pathways. During atrial extrastimulation a sudden AH interval prolongation of more than 50 ms ("break" phenomenon) was observed twice at one basic cycle length. During ventricular extrastimulation a sudden prolongation of the AH interval of the anterograde AV nodal conduction of the induced echo beats was recorded. Three AV nodal pathways were thus present. The atypical form of AV nodal reentrant tachycardia was induced, showing a varying cycle length (290-340 ms). After radiofrequency catheter ablation of the fast conducting beta-pathway, another tachycardia was initiated, now showing a constant cycle length, using the two remaining, more slowly conducting alpha-pathways. One of these was eliminated in another ablation procedure.

Adult↗

Corticosteroid agents inhibit proliferation of smooth muscle cells from human atherosclerotic arteries in vitro.

We studied the in vitro effect of steroid agents on smooth muscle cells from human atherosclerotic arteries. Recent advances in the understanding of the biology of restenosis indicate that restenosis is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. The steroid agents prednisolone (0.0075-750 micrograms/ml), hydrocortisone (0.0125-1250 micrograms/ml), and dexamethasone (0.0004-40 micrograms/ml) were added to the cultures. Six days after seeding the cells were trypsinized and the cell number was measured by a cell counter. All three steroid agents exhibited a significant antiproliferative effect on smooth muscle cell proliferation. At high concentrations of hydrocortisone, cytoskeletal elements of smooth muscle cells such as actin, microtubules, and vimentin, were largely altered. Our data indicate that the proliferation of smooth muscle cells from human atherosclerotic arteries in vitro can be inhibited by steroid agents and thus may open the way for local post-angioplasty treatment strategies.

Actins↗

[Long-term electrocardiography in the idiopathic QT syndrome].

The value of long-term electrocardiographic (ECG) monitoring was assessed in 14 patients (8 males, 6 females; mean age 21 [17-30] years) with the idiopathic long QT syndrome (LQTS), 14 healthy subjects of the same age serving as controls. Twelve patients had the typical history of syncopes or sudden cardiac death among family members; seven patients had a history of syncope, while four patients had been successfully resuscitated. None had associated cardiac disease. Among the group with LQTS the rate-corrected QT interval at rest was 498 + 56 ms, in the control group 412 +/- 30 ms (P < 0.005). Resting and maximal heart rates on exercise were similar in the two groups. The rate-corrected QT interval on exercise was significantly longer in the LQTS patients (P < 0.001). In the control group the maximal heart rate in the long-term ECG was significantly higher (144 +/- 28/min) than in the LQTS patients (128 +/- 17/min; P < 0.01). The long-term ECG recorded abnormal findings in five patients: torsade-de-pointes tachycardia in two, T-wave alternans in two, and bradycardia resulting from intermittent sinoatrial block in one. No abnormal findings were recorded in the control group (P < 0.03).

Adolescent↗