Biomedical subjects

M Mancini

Publications and source records attributed to M Mancini.

At least 271 records · Page 15Linked to original sources

PubMed1990

Serum lipoproteins, apolipoproteins and very low density lipoprotein subfractions during 6-month fibrate treatment in primary hypertriglyceridaemia.

Serum lipoproteins and apolipoproteins were studied in 14 hypertriglyceridaemic (HTG) patients during a 24-week period of treatment with gemfibrozil, and after a 6-week washout period. A marked decrease in very low density lipoprotein (VLDL) cholesterol and triglyceride was observed. There was an increase in high density lipoprotein (HDL) cholesterol, particularly the HDL3 component. A slight increase in low density lipoprotein (LDL) cholesterol was observed after 12 weeks, but this had almost disappeared after 24 weeks. The treatment resulted in an increase in serum apolipoprotein A-II levels and a reduction in serum apo C-III and apo E. VLDL subfractionation by density gradient centrifugation in four subfractions of decreasing size (A, B, C and D) showed a predominant reduction of the large subfractions A, B and C, while the decrease in VLDL-D was less marked. Percentage changes from the baseline level of VLDL-A and VLDL-D cholesterol were found to be inversely correlated with percentage changes in HDL and LDL cholesterol, respectively. This might reflect a transfer of cholesterol from VLDL-A to HDL, and from VLDL-D to LDL. The above data suggest fibrate-induced stimulation of lipoprotein lipase, and indicate that the enhanced transfer of cholesterol from VLDL to LDL, induced by fibrates in HTG patients, is less pronounced after a prolonged period of treatment.

Apolipoproteins↗

PubMed1990

A technique for intraoperative arrhythmia induction during automatic implantable defibrillator placement.

In 14 patients (12 men, 2 women, mean age 51 +/- 4 years) we evaluated a new technique for intraoperative arrhythmia induction during Ventak 1550 automatic implantable cardioverter defibrillator (AICD), pulse generator placement. At the time of surgery (nine new implants, five pulse generator replacements), when the AICD pulse generator is in its final configuration with the rate sensing and patch electrodes leads inserted into the header, a #2 hex wrench was inserted into each of the rate sensing lead set screw sites. The alligator clips of a temporary pacing cable were placed on each of the hex wrenches and the remainder of the cable passed off field for attachment to a programmed stimulator or AC fibrillator. In all 14 patients, the clinical arrhythmia was induced at least twice (ventricular tachycardia in eight patients, ventricular fibrillation in six patients). No difficulties with arrhythmia induction or AICD sensing as discharge were encountered. We conclude that this technique is both a safe and effective means of intraoperative arrhythmia induction during placement or replacement in the Ventak AICD 1550 and 1600 series pulse generators.

Cardiac Pacing, Artificial↗

PubMed1990

Interferon alpha-2b as therapy for patients with Ph'-positive chronic myelogenous leukemia.

We treated 114 Ph'+ chronic myeloid leukemia (CML) patients, 105 of whom were in chronic phase (CP) and 9 in accelerated phase (AP), with interferon alpha-2b (IFN alpha-2b) at intermittent or daily doses of 2-5 MU/m2. Of 35 previously untreated CP patients, 22 (63%) showed complete hematological response (CHR). This was significantly influenced by initial risk status. In 19 of the 22 CHR patients the median of Ph'+ cells decreased from 100% to 58%. Of 36 patients pretreated for less than 12 months, 19 (53%) achieved CHR. CHR rate was significantly related to IFN dose. Cytogenetic improvement was observed in 15 of the 19 patients, the median of Ph'+ cells dropping from 100% to 76%, with complete suppression of the Ph' chromosome in 1 case. Of the 34 patients pretreated for greater than 12 months, 21 (62%) obtained CHR. Cytogenetic improvement was observed in 10 cases, the median of Ph'+ cells declining from 100% to 66%. 1 of 9 AP patients obtained CHR. After a median follow-up of 32 months for the 63 CHR patients, 49 (78%) are still in disease control: 34 on IFN therapy, 15 after bone marrow transplantation (BMT) (13 autologous and 2 allogeneic). Blastic transformation (BT) occurred in 9 of 63 (14%) CHR patients and in 24 of 51 (47%) patients with less than CHR. IFN alpha-2b has proved to be an effective treatment for CML. Its combination with other treatment modalities represents an interesting and promising approach for future studies.

Humans↗

PubMed1990

T- and B-lymphocyte responses to human immunodeficiency virus (HIV) type 1 in macaques immunized with hybrid HIV/hepatitis B surface antigen particles.

Recombinant human immunodeficiency virus (HIV)/hepatitis B surface antigen (HBsAg) subviral particles of dual antigenicity and immunogenicity were obtained by fusing 84 amino acids of the HIV type 1 external envelope glycoprotein within the pre-S2 part of the hepatitis B middle protein (M.-L. Michel, M. Mancini, E. Sobczak, V. Favier, D. Guétard, E.-M. Bahraoui, and P. Tiollais, Proc. Natl. Acad. Sci. USA 85:7957-7961, 1988). We now describe the humoral and cellular immune response of rhesus monkeys immunized with these hybrid particles. Macaque antisera raised by subcutaneous injections of the HIV/HBsAg particles were shown to be specific for HIV in peptide-binding assays. Moreover, we were able to generate in these vaccinated animals a T-cell-proliferative response to both parts of the hybrid particle, i.e., HIV and HBsAg. These results establish the presence of a T-cell epitope in this HIV segment, which has been shown previously (L.A. Lasky, G. Nakamura, D. H. Smith, C. Fennie, C. Shimasaki, E. Patzer, P. Berman, T. Gregory, and D. J. Capon, Cell 50:975-985, 1987) to be an important domain involved in the binding of the virus to its cellular receptor, the CD4 molecule. This work demonstrates the feasibility of using the HBsAg subviral particle as a carrier protein for the presentation of foreign immunogenic epitopes to the immune system.

Animals↗

PubMed1990

Hemodynamic changes in the peripheral circulation after repeat low density lipoprotein apheresis in familial hypercholesterolemia.

Repeat low density lipoprotein (LDL) apheresis and blood flow determinations in the forearm and leg were performed in 10 patients (age range, 13-49 years; four male, six female) with familial hypercholesterolemia (eight homozygous, two heterozygous). To perform LDL apheresis, plasma was first separated by a polysulphone hollow fiber filter; then, LDL was selectively removed from plasma by dextran sulphate cellulose beads packed in columns. Blood flows in the forearm and leg were determined at rest and during a reactive hyperemia test (peak flow). This test was performed noninvasively by a strain-gauge plethysmograph with semicontinuous registration of arterial blood flow variables before the first apheresis and 3 weeks after the last of six procedures for apheresis. Resting arterial blood flows in the forearm and leg were slightly increased after repeat LDL apheresis (p less than 0.05). Peak blood flow in the leg significantly increased (+34%, p less than 0.01). No change in peak blood flow in the forearm was observed. Systolic blood pressures were slightly but significantly reduced (p less than 0.05); forearm peripheral resistances were also reduced (p less than 0.05). Flow response was not related to LDL receptor status. Blood and plasma viscosities were determined before and 7 days after the last apheresis. Blood viscosity was significantly reduced after LDL apheresis at shear rates of 11.25-450 sec-1. Plasma viscosity did not change.

Adolescent↗

PubMed1990

Influence of dietary intake of energy and carbohydrate on the proportion of saturated and monounsaturated fatty acids in adipose tissue of middle aged men.

The fatty acid composition of subcutaneous tissue has been determined in a population sample of apparently healthy middle aged men from Southern Italy. Dietary appraisal has been carried out by evaluating the usual pattern of food consumption during the year preceding the interview. The whole population sample was subdivided into three tertiles on the basis of the energy intake by the different individuals. The proportion of adipose tissue polyunsaturated fatty acids was relatively low in the high energy tertile III and high in the low energy tertile reflecting parallel differences in the intake of polyunsaturated fatty acids. The percentage of monounsaturated fatty acids (mainly oleic acid) was relatively high (p less than 0.01) and that of saturated fatty acids (mainly palmitic acid) relatively low (p less than 0.05) in the high energy tertile (III) as compared to the low energy tertile (I); these differences were independent of the amount and type of dietary fatty acids. Total energy was positively correlated (r = .87, p less than 0.01) to carbohydrate intake (g/day). Dietary carbohydrates (g/day) were inversely related to adipose tissue saturated fatty acids (r = -.40, p less than 0.001) and directly correlated to adipose tissue monounsaturated fatty acids (p = .40, p less than 0.001). Carbohydrate intake was related to adipose tissue monounsaturated and saturated fatty acids independently of daily energy intake. On the other hand when the influence of dietary carbohydrates was eliminated, no correlation was detectable any longer between energy intake and adipose tissue fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1990

Plasma antioxidants and coronary heart disease: vitamins C and E, and selenium.

The possibility of a relation between plasma antioxidants such as vitamins C and E and selenium, and mortality from coronary heart disease (CHD) was examined. A cross-sectional survey was undertaken of random population samples of apparently healthy middle-aged men in four European regions with differing mortalities from CHD [rate/100,000 for men aged 40-49]: north Karelia (eastern Finland) (n = 99) [212/100,000]; south-west Finland (n = 85) [146/100,000]; Scotland (n = 131) [140/100,000]; and south Italy (n = 80) [43/100,000]. Median (5th-95th percentile) plasma vitamin C concentrations were lower in Scotland: 18.2 (5.7-61.3) microM than in other regions: north Karelia 28.4 (6.2-85.2); south-west Finland 33.5 (5.7-76.6); south Italy 38.0 (10.2-69.8) microM (P less than 0.001). The median levels in the four areas did not however reflect the regional CHD mortality rates. Regional differences in plasma vitamin E levels were also observed: Scottish levels were low 20.0 (12.1-29.3) microM (P less than 0.001) and did not differ between the other areas: 23.0 (16.7-35.1), 22.5 (13.7-31.6) and 23.9 (15.6-41.3) microM respectively. The vitamin E gradient could be explained in part by differences in serum cholesterol. However, cholesterol-adjusted vitamin E levels were low in the three high CHD areas: Scotland 3.41 (2.41-4.62); north Karelia 3.53 (2.67-5.18); south-west Finland 3.53 (2.58-4.92); Italy 4.81 (3.25-5.99) mumol/mmol cholesterol (P less than 0.001). Cholesterol-adjusted vitamin E was not lower in north Karelia, the higher CHD mortality area in Finland. Serum selenium values also varied with the area examined and reported low levels in Finland were confirmed. Nevertheless, selenium levels did not correlate with the reported mortality rates of CHD. Thus in our small cross-cultural study the evidence did not support our hypothesis that plasma antioxidants explain regional differences in CHD mortality.

Adipose Tissue↗

PubMed1990

Cytogenetic follow-up after allogeneic bone-marrow transplantation for Ph1-positive chronic myelogenous leukemia.

Serial cytogenetic studies were carried out on 36 patients with Ph1-positive chronic myelogenous leukemia treated with allogeneic bone-marrow transplantation from unlike sex (21 patients) or like sex (15 patients) donors. Fourteen of the 21 sex-mismatched and 12 of the 15 sex-matched donor marrows were T cell depleted. Disease relapse was documented in 19 of the 26 patients who received T cell-depleted marrow, and in none of the 10 patients who received non-T cell-depleted marrow. In the group of patients with unlike sex donor, a triple donor/normal recipient/Ph1-positive recipient or a double donor/Ph1-positive recipient chimerism was documented during the subsequent months, while on alpha-interferon treatment for relapse. Two of these patients subsequently showed a complete disappearance of the Ph1 chromosome. Unstable and/or stable, clonal or non-clonal chromosome changes were detected in Ph1-positive cells from 12 of the 19 patients who relapsed. Analysis of the identified stable changes showed a non-random distribution of breakpoints with clustering to chromosome nos. 1, 4, 7 and 12.

Adolescent↗

PubMed1990

Cerebral blood flow in patients with chronic cerebrovascular disease: effect of acetyl L-carnitine.

The effect of acetyl-L-carnitine on cerebral blood flow was evaluated in ten patients with cerebrovascular disease, who suffered an ischaemic stroke at least six months before the study. All patients performed a computerized tomograph scan and were investigated by Xenon 133 using a brain dedicated Single Photon Emission Computerized Tomography. Acetyl-L-carnitine was administered intravenously (i.v.) at a dosage of 1.5 g. Cerebral blood flow (ml/min. 100 g) was evaluated before and 45 min after the injection. Cerebral blood flow improved in both the ispilateral and controlateral hemisphere of the ischaemic area, but not in the stroke corresponding zone. It is concluded that acetyl-L-carnitine at a dosage of 1.5 g i.v. improves cerebral blood flow in patients with cerebrovascular disease.

Acetylcarnitine↗

PubMed1989

Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects.

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.

Adipose Tissue↗

PubMed1989

Effect of nicardipine on insulin secretion, glucose and lipid metabolism in hypertensive, non-insulin dependent diabetics.

Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d. The glucose and insulin responses to the i.v.GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl.90 min on placebo, 33.1 mg/dl.90 min acutely and 31.4 mg/dl.90 min on chronic administration of nicardipine; insulin 2.08 microU/ml.90 min on placebo, 1.87 microU/ml.90 min acutely and 1.93 microU/ml.90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v.GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%.min-1 with chronic nicardipine. Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.

Adult↗

PubMed1989

Calcium-channel blockers and sodium intake: a controlled study in patients with essential hypertension.

Thirteen patients with mild to moderate essential hypertension and whose average supine blood pressure with no treatment was 165/104 mmHg were studied as inpatients for 3 consecutive one-week periods on different sodium intakes. On the last day of each dietary period, they received a single, 20-mg nitrendipine tablet and blood pressure was monitored every 10 minutes for 2 hours after drug administration. Nitrendipine significantly lowered blood pressure independently of the level of sodium intake, and the maximum blood-pressure lowering effect was achieved approximately 1 hour after the dose. The blood-pressure lowering effect of nitrendipine was greater on high sodium intake as compared to low sodium intake (p less than 0.02), and it was also greater with higher initial blood pressures. However, the sodium-related effect on blood pressure was, at least in part, independent of the pretreatment blood pressure. These results suggest that calcium antagonists, such as nitrendipine, are effective in reducing blood pressure in patients with essential hypertension and could be drugs of choice in those who are unable to restrict their salt intake.

Adult↗

PubMed1989

Plasma vitamin E, apolipoprotein B and HDL-cholesterol in middle-aged men from southern Italy.

Plasma vitamin E, HDL-cholesterol, apolipoprotein B and triglycerides were measured in an apparently healthy, male, random population sample (n = 74) from Southern Italy. Plasma vitamin E concentration was positively correlated to that of serum cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B (all P less than 0.001). The results of partial correlation analysis showed that apo B, the apolipoprotein constituent of LDL, was related to vitamin E independently of serum triglycerides, a fairly accurate marker of VLDL. On the other hand, triglycerides were related to vitamin E independently of apo B. Both correlations were much weaker if an adjustment was performed for non-HDL-cholesterol. No independent relationship was demonstrated between plasma vitamin E and HDL-cholesterol.

Adult↗

PubMed1989

Plasma lipids and geriatric assessment in a very aged population of south Italy.

A very old population of a rural area of Southern Italy with a mean age of 87 years was investigated in order to evaluate serum lipid levels and their possible association with health conditions, such as mental status, social behaviour and physical autonomy. Among 101 subjects with ages above 82 years, 73 were investigated (participation rate 72%, 31 men and 42 women). Mean +/- SD serum cholesterol level was 199 +/- 36 and 210 +/- 40 mg/dl and mean serum triglyceride level was 107 +/- 43 and 148 +/- 74 mg/dl (P less than 0.05) in men and women, respectively. Mean high density lipoprotein (HDL)-cholesterol level was 49 mg/dl in both sexes. All subjects were investigated by means of geriatric and neuropsychometric scales such as Sandoz Clinical Assessment Geriatric Scale (SCAGS), Hachinski Dementia Scale (HDS), Plutchik Geriatric Rating Scale (PGRS) and Indexes of Activity of Daily Living (ADL). When subjects were divided into 3 groups according to levels of serum lipids, HDL-cholesterol appeared to be better related to clinical conditions than total serum cholesterol: the group with the higher HDL-cholesterol level presented better scores at all the administered assessment scales when compared to the groups with lower and modal levels (P range between less than 0.05 and less than 0.001). Subjects in the higher serum cholesterol group presented better scores at PGRS only (P less than 0.01). No relation was observed between serum total triglyceride levels and geriatric assessment scores.

Activities of Daily Living↗

PubMed1989

Effects of bezafibrate on insulin secretion and peripheral insulin sensitivity in hyperlipidemic patients with and without diabetes.

Although it has been reported that bezafibrate influences carbohydrate metabolism, this possibility has never been properly evaluated in a controlled clinical trial. In this study we attempted to evaluate the effects of bezafibrate on plasma lipoproteins, glucose tolerance, insulin secretion and peripheral insulin sensitivity in a group of hypertriglyceridemic patients with and without diabetes. Sixteen hyperlipidemic patients (10 males and 6 females) participated in the study. Eight had type IIB and 8 type IV hyperlipoproteinemia; 6 of them also had non-insulin dependent diabetes mellitus. The study was performed according to a double blind, crossover design: after 1 month wash-out period in which patients were on diet alone, they underwent, in a random order, a period of placebo therapy and another period in which they received a single daily dose of a long-acting bezafibrate preparation (400 mg) administered in the evening. Each treatment lasted 2 months. Total plasma and VLDL triglyceride concentrations were consistently reduced by bezafibrate (-46%, P less than 0.001; and -50%, P less than 0.001). Total and VLDL-cholesterol were also reduced by bezafibrate. The effects of bezafibrate on lipoproteins were similar in diabetic and non-diabetic subjects. Bezafibrate treatment did not influence fasting blood glucose concentration, glucose tolerance, peripheral insulin sensitivity or insulin secretion. In conclusion, the results of this controlled trial clearly indicate that bezafibrate can be successfully employed to lower plasma lipid levels in patients with non-insulin dependent diabetes mellitus and hyperlipidemia.

Adult↗

PubMed1989

Different localization of early arterial lesions in insulin-dependent diabetes mellitus and in familial hypercholesterolemia.

Ultrasound methods have been used for the vascular examination of middle-aged patients with insulin-dependent diabetes mellitus (IDDM, n = 44) or heterozygous familial hypercholesterolemia (FH, n = 37); they were compared with 50 healthy controls. To define the localization of the early arterial lesions in these two conditions, the determination of ankle pressure by Doppler ultrasound and the detection of flow disturbances in the iliac arteries by echo-Doppler technique have been combined in a single vascular investigation. There were no major differences in mean age, degree of overweight, sex distribution, blood pressure, or smoking habits among the three groups. Total serum cholesterol in patients with FH was almost double compared with diabetics and controls. Triglyceride, HDL cholesterol, and blood pressure values did not differ. Nine of 88 limbs of patients with IDDM had an abnormally low ankle-arm pressure ratio (less than 0.97), and there were three cases of low ratio of 100 limbs in the control subjects (P less than .02). The corresponding figure for heterozygous FH was of three of 74 limbs (not different from controls). Echo-Doppler abnormalities suggesting lesions in the iliac arteries were significantly increased (P less than .01) in FH patients (13 limbs with lesions of 74) compared with controls (four of 100 limbs). The proportion of echo-Doppler abnormalities in IDDM (four of 88 limbs) was practically the same as compared to the controls.

Adult↗

PubMed1989

Altered kinetics of an intravenous calcium load in idiopathic hypercalciuria.

Increased gut calcium absorption or reduced renal tubular calcium reabsorption have been alternatively reported in idiopathic hypercalciuria with kidney calculi. The present study aimed to investigate the handling of an exogenous calcium load in hypercalciuric stone formers to detect possible differences with regard to tissue calcium metabolism in vivo. A constant rate intravenous calcium infusion (0.2 mmol kg bodyweight per two hours) was carried out on six absorptives and six renals, defined according to the reported criteria, as well as on normal controls from clinical staff. Serum ionized calcium concentration were determined at regular intervals during the infusion and in the four hours after the end of calcium load. Over the same period, urinary calcium excretion was evaluated in timed urine collections. Absorptive and renal hypercalciurics had lower serum ionized calcium levels compared with normal controls at all experimental times, a finding that suggests a faster disappearance of calcium from the circulation. The total body calcium clearance calculated from the area under the curve of the serum calcium concentrations was enhanced in hypercalciuric patients (P less than .001). Although renal calcium excretion was higher in hypercalciurics, renal calcium clearance accounted for only a minor fraction of the total body clearance, suggesting that the reduced serum calcium levels found in the hypercalciurics could not be explained by the renal calcium leak. The enhanced total body calcium clearance found in hypercalciuric subjects is therefore due to an increased tissue calcium uptake. This finding provides indirect evidence of altered cell calcium handling in idiopathic hypercalciura with no difference between the so-called absorptives and renals in terms of the pathophysiologic mechanism.

Adult↗

PubMed1989

Short-term effects of moderate alcohol consumption on lipid metabolism and energy balance in normal men.

The short-term effects of moderate alcohol consumption on energy balance, serum lipids, and lipoproteins were studied in eight healthy middle-aged men (age 30 to 47 years and body mass index 23.1 to 27.7 w/h2). A crossover dietary trial included two isocaloric periods without (20% protein, 50% carbohydrate, 30% fat) or with alcohol (12% protein, 29% carbohydrate, 25% fat, 75 g of alcohol as red wine). Each period lasted 2 weeks. The body weight of the subjects remained stable over the study. Fasting blood glucose, serum insulin, total cholesterol, and LDL cholesterol were similar at the end of both dietary periods. Mean values of serum total triglyceride (108 +/- 18 v 85 +/- 24 mg/dL, P less than 0.05), VLDL-Tg (88 +/- 24 v 73 +/- 16 mg/dL, NS), and total HDL cholesterol (49.4 +/- 6.0 v 43.4 +/- 5.5 mg/dL, P less than 0.05) were higher after the diet with alcohol than without alcohol. The increase of HDL cholesterol was primarily due to that of HDL2 cholesterol (10.4 +/- 5.1 v 5.7 +/- 3.9 mg/dL, P less than 0.05). The concentration of apoprotein A-I, A-II, and B averaged 104 +/- 17 v 89 +/- 16 mg/dL, 33 +/- 4 v 28 +/- 8 mg/dL, P less than 0.02, and 111 +/- 24 v 105 +/- 33 mg/dL after the diets with and without alcohol, respectively. Adipose tissue LPL activity increased in six of the eight volunteers during the diet with alcohol. Resting metabolic rate, postprandial energy expenditure, and postprandial responses of blood glucose, serum insulin, triglyceride, and plasma FFA were similar after the both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗