Long-term experience of spironolactone in essential hypertension.
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Blood Pressure↗
Biomedical subjects
G Chatellier
Publications and source records attributed to G Chatellier.
[Localization of primary hyperaldosteronism].
After diagnosis of primary aldosteronism on the basis of biochemical evidence, the detection of the tumour is of crucial importance in the management of the disease. We reviewed the efficacy of CT-Scan, Iodo-Cholesterol Scintigraphy, digitalized phlebography, adrenal vein sampling for steroid measurements (AVS), and Nuclear Magnetic Resonance (NMR) in 160 hypertensive patients with primary aldosteronism. Diagnosis of Conn's adenoma (n = 96) or Adrenal Hyperplasia (n = 40) was confirmed by surgery or at least two concordant tumour localization tests. Scintigraphy gave a correct diagnosis in 53% of the 51 exams, CT-Scan in 82% of the 85 exams, and phlebography in 79% of 61 exams. Plasma Aldosterone/Cortisol ratio was 5 times higher on the side of adenoma in 55% of the 47 cases but this ratio was also present in 23% of 22 patients with adrenal hyperplasia. Each procedure exhibited few false positive and false negative cases. NMR performed in 15 patients with Conn's adenoma identified all the cases. But tumours displayed a signal close to the liver signal and identical to the normal adrenal. These results and the risk of invasive procedure (failure of catheterization of the right adrenal vein (n = 6) and adrenal haematoma (n = 2) lead us to propose a schema of exploration of patients with primary aldosteronism. The CT-Scan could be performed at the first step once the biological diagnosis confirmed. Phlebography and AVS will be performed only if tumour was less than 1 cm at the CT-Scan despite important biological abnormalities. This schema requires to be validated by a prospective evaluation.
Adenoma↗
[Detection, diagnosis and localization of pheochromocytoma. 77 cases in a population of 21,420 hypertensive patients].
Phaeochromocytoma was diagnosed in 77 (0.36%) of 21,420 hypertensive patients examined in the hypertension units of the Broussais and Saint-Joseph hospitals, Paris, between 1976 and 1986. Our diagnostic strategy is to reserve biochemical examinations to cases with suspected phaeochromocytoma and to explore only those patients who have positive laboratory results. Patients suspected of harbouring a phaeochromocytoma are those who complain of headaches, palpitations and sweating (these 3 symptoms together having a 90.9% sensitivity and a 99.9% exclusion value), those who have a family history of phaeochromocytoma or who present with medullary thyroid carcinoma or phakomatosis, or those who do not respond to anti-hypertensive treatments. Altogether, these patients account for less than 10% of all cases of hypertension. The most sensitive test in this group is measurement of urinary metanephrines. Among 30 patients with phaeochromocytoma in whom urinary metanephrines and plasma noradrenaline were measured on the same day, none had urinary metanephrine values lower than 3.69 mumol/24 h (0.7 mg/24 h) while 6, who had normal blood pressure at the time of sampling, had noradrenaline levels below 3.53 nmol/l (600 pg/ml). Prior to surgery, the tumour was correctly located by urography (69% of 58 n = tumours), ultrasounds (74%, n = 38), arteriography (83%, n = 23), radioisotope scanning (91%, n = 32), computed tomography (95%, n = 40) and nuclear magnetic resonance imaging (12/12). In 28 patients who had both radioisotope scanning and computed tomography the sensitivities of these examinations were 90% and 100% respectively. A stage by stage approach to the diagnosis of phaeochromocytoma, using detection criteria followed by biochemistry then location methods, is an economical strategy with the best yield from diagnostic and imaging techniques.
Adrenal Gland Neoplasms↗
[Ambulatory blood pressure in normotensive subjects. Definition of reference values as a function of age by the Spacelabs instrument].
For a finer assessment, by repeated blood pressure (BP) measurements, of the cardiovascular risk associated with BP levels, new instruments have been developed which provide multiple reading during periods of activity. However, the lack of epidemiological studies makes it necessary to determine reference ambulatory BP levels by another method. Twelve-hour recordings were taken with the Spacelabs instrument in 130 volunteers (45% males) aged from 20 to 90 years during their various activities. Mean systolic and diastolic BP values +/- SD were calculated per age-groups of 10 years each. That this sample was representative of the general population was confirmed by the fact that BP fluctuations and variations according to age and sex in these 130 subjects were identical with those observed in the population of an entire town (Framingham). The concept of hypertension, as defined by ambulatory BP recordings, is discussed. This study provides, for the first time, reference ambulatory BP values according to age and sex, measured in normotensive subjects with the Spacelabs instrument. These values constitute a preliminary step indispensable to evaluate this technique in hypertensive patients.
Adult↗
Efficacy and tolerance of spironolactone in essential hypertension.
The long-term efficacy and tolerance of spironolactone in essential hypertension was evaluated among 20,812 patients referred to the Broussais and St. Joseph systemic hypertension clinics between 1976 and 1985 by using information prospectively collected in the computerized ARTEMIS data bank. In 182 patients (51 men, 131 women) treated with spironolactone alone during a mean follow-up period of 23 months, a mean dose of 96.5 mg decreased systolic and diastolic blood pressure (BP) by 18 and 10 mm Hg, respectively, below pretherapeutic levels. The BP decrease was greater with doses of 75 to 100 mg (12.4% and 12.2%) than with doses of 25 to 50 mg (5.3 and 6.5%, p less than 0.001), but no additional decrease was found with doses above 150 mg. Plasma creatinine level increased modestly (8.3 mumol/liters), as did plasma potassium level (0.6 mmol/liters) (both p less than 0.001); uric acid level increased, but not significantly (10.5 mumol/liter). Fasting blood glucose and total cholesterol levels did not change, triglyceride levels increased slightly (0.1 mmol/liter, p less than 0.05). These changes were similar in both sexes and were not influenced by length of follow-up. Among the 699 men prescribed spironolactone alone or in association with another antihypertensive treatment, 91 cases of gynecomastia developed (13%). Gynecomastia was reversible and dose-related; at doses of 50 mg or less the incidence was 6.9%, but 52.2% for doses of 150 mg or higher. Despite limitations inherent in the interpretation of data banks, it is concluded that spironolactone administered in daily practice reduced BP without inducing adverse metabolic adverse effects and that in patients with essential hypertension, doses should be kept below 100 mg.
Aged↗
Treatment of mild to moderate hypertension with or without the converting enzyme inhibitor enalapril. Results of a six-month double-blind trial.
A group of 205 patients with mild to moderate essential uncomplicated hypertension was chosen from 3,183 hypertensive patients referred to a hypertension clinic for the first time, and was asked to participate in a six-month double-blind parallel trial. A single physician was in charge of all the patients. After a two-week single-blind placebo period, the patients were randomly assigned to regimens of either enalapril (20 mg per day) or placebo. Both groups were then followed up every two weeks, and increasing doses of hydrochlorothiazide (25 and 50 mg), oxprenolol (160 and 320 mg), and dihydralazine (50 and 100 mg) were added until the diastolic blood pressure was lower than 90 mm Hg. After a six-month follow-up, the enalapril group showed lower systolic and diastolic blood pressures than the control group (129/82 +/- 12/6 mg Hg versus 135/86 +/- 10/5 mm Hg; p less than 0.001). The number of daily tablets of active drugs was 2.7 +/- 1.8 in the enalapril group and 4.4 +/- 2.4 in the control group (p less than 0.01). The mean plasma potassium level was 4.16 +/- 0.4 mmol/liter in the enalapril group versus 3.92 +/- 0.4 mmol/liter in the control group (p less than 0.001), despite more frequent use of amiloride (p less than 0.001). This difference is explained by the lower dose of hydrochlorothiazide used in the enalapril group by comparison to the control group, and a lower excretion of urinary aldosterone in the enalapril group than in the control group (11.6 +/- 7.4 versus 19.8 +/- 11.8 micrograms per 24 hours, p less than 0.001). Drug withdrawal was necessary in eight patients in the enalapril group and in 16 patients in the control group (p less than 0.05). These results show that first-step treatment of mild to moderate uncomplicated essential hypertension with enalapril permits better blood pressure control than the standard treatment, requires fewer tablets to be taken daily, and involves a smaller risk of hypokalemia.
Adult↗
Isolated clinical syndrome of primary aldosteronism in four patients with adrenocortical carcinoma.
Adrenocortical carcinoma is a rare disorder that can be revealed by an isolated syndrome of mineralocorticoid excess. In a retrospective study of 137 patients referred to our hypertension clinic in the past 10 years for primary aldosteronism, four cases of adrenocortical carcinoma were identified. The clinical presentation of these patients was similar to that of patients with Conn's adenoma, but preoperatively, malignant tumoral primary aldosteronism was suspected because of profound hypokalemia, marked elevation in plasma aldosterone levels, and enlarged size and weight of an heterogenous adrenal tumor with internal calcifications. Malignancy was confirmed by the histologic features. No prognostic criteria could be established and two patients died despite specific surgery, which was performed in all cases. More recent developments in the use of mitotane led to the addition of adrenocorticolytic therapy in the remaining two patients, who are still alive at the time of this report.
Adolescent↗
Evaluation of slow release nicardipine in essential hypertension by casual and ambulatory blood pressure measurements. Effects of acute versus chronic administration.
We conducted a randomized placebo-controlled double-blind study in 40 hypertensive subjects to assess the antihypertensive effect of a new galenic form of nicardipine administered at a dosage of 50 mg twice daily for 3 weeks. Regardless of whether blood pressure was measured by standard mercury sphygmomanometer, non-ambulatory automatic oscillometry or a Remler ambulatory blood pressure recorder, it dropped by a significantly larger amount in the nicardipine group than in the placebo group. In the control group, a placebo effect was observed with the ambulatory diastolic blood pressure recording, whereas it was not observed with hospital blood pressure measurements, especially when using the serial measurements performed for 30 min by an automatic recorder. The fall in blood pressure measured with the Remler recorder was correlated with the fall measured 10-20 min during one acute intravenous nicardipine perfusion before the trial, although the correlation coefficients do not suggest clinically relevant predictability of nicardipine efficacy at the individual level. The present findings support the need for controlled double-blind trials with careful office blood pressure measurements.
Administration, Sublingual↗
Efficacy and influence on quality of life of enalapril as a first step treatment of hypertension.
205 patients with mild to moderate uncomplicated hypertension participated in a six-month double-blind parallel study performed in a unique center. After a two-week single-blind placebo period, the patients were randomly allocated to receive either Enalapril 20 mg once-a-day or placebo as the first step treatment. They were then followed-up every two weeks and successive doses of hydrochlorothiazide, oxprenolol, and dihydralazine were added until the diastolic pressure was lower than 90 mmHg. After six months, the systolic and diastolic blood pressures were lower in the Enalapril than in the control group (129/82 +/- 12/6 mmHg versus 136/86 +/- 10/5 mmHg; p less than 0.001). Drug withdrawal was necessary for 8 patients in the Enalapril group and for 16 patients in the control group (p less than 0.05). The number of daily tablets was 2.7 +/- 1.8 in the Enalapril group and 4.4 +/- 2.4 in the control group (p less than 0.01). Therefore, a stepped-care program based on Enalapril appears significantly more effective than a stepped-care program based on a diuretic.
Adult↗
[Definition and consequences of blocking the renin-angiotensin system by converting enzyme inhibition].
46 patients (39 males), mean age 51 years (range 33-66), were randomly allocated to two different groups of treatment if their diastolic blood pressure was superior to 90 mmHg after a one-month treatment by 20 mg of enalapril. In the first group (ENA), 23 patients were given higher dosages of enalapril (40 and, if necessary 60 mg once-a-day). In the second group (HCTZ) 23 patients were given enalapril 20 mg and hydrochlorothiazide 25 and, if necessary, 50 mg once-a-day. Dosages were eventually increased after 2 weeks and evaluation of the results was performed after 4 weeks on treatment. Blood pressure was monitored in the supine position, at 3 minutes interval for thirty minutes, by an automatic device based on oscillometric method. Two successive measurements with a standard sphygmomanometer were performed by the physician at the end of the recording. No patient withdrew from the study nor was lost to follow-up. At the end of the study, 14 patients in the ENA group were receiving enalapril 60 mg once-a-day and 8 patients in the HCTZ group were receiving 50 mg of hydrochlorothiazide. Blood pressure was significantly lower in teh HCTZ group with the automatic device (130 +/- 9/80 +/- 8 vs 141 +/- 5/86 +/- 8 mmHg, p less than 0.01/p less than 0.05) and with the sphygmomanometer (134 +/- 10/89 +/- 6 vs 149 +/- 16/94 +/- 5 mmHg, p less than 0.001/p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Comparison of the effect of captopril and minoxidil on left ventricular mass. Results of a 6-month comparative double-blind test].
A randomised double blind study was performed in order to compare the cardiac effects of captopril and minoxidil in a subset of patients with severe primitive hypertension, uncontrolled (diastolic BP greater than 100 mmHg) by Metroprolol 200 mg/d and Furosemide 80 mg/d. 25 male pts completed the six month study, 33 pts having been excluded before randomisation (22 inadequate echoes) and 20 after randomisation (7 ambiguities on wall measurement). Average captopril dosage was 265 mg/d (150-300 mg), average minoxidil dosage was 19.6 mg/d (7.5-30 mg), dosages of Furosemide, Spironolactone and Metroprolol were similar in the two groups. Blood pressure decreased dramatically with both regimens (208/130 to 148/96 with captopril, 194/115 to 154/100 with minoxidil). Sokolow index was at the upper range of normal and decreased with both drugs. Cardiothoracic ratio decreased only with captopril. Echocardiograms were performed and read blindly at the end of the study. LV mass was measured according to Devereux, method. All patients had severe LVH. After 6 months posterior wall thickness decreased from 14.8 to 13.8 mm with captopril, remained stable from 14.1 to 14.9 mm with minoxidil, septal thickness decreased from 17.2 to 15.7 mm with captopril and remained stable (14.8 to 15.2 mm) with minoxidil. LV mass and mass index respectively decreased from 456 g and 232 g/m2 to 372 g and 190 g/m2 with captopril, and remained unchanged from 413 g and 215 g/m2 to 420 g and 218 g/m2 with minoxidil. Fractional shortening remained normal in both groups. Intra patients reproducibility was suboptimal because of difficulties in precise delineation of the endocardium in the severely hypertrophied ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[The decision to treat moderate hypertension: repetition of office visits or ambulatory monitoring of arterial pressure?].
World Health Organization (WHO) recommends antihypertensive therapy for mild to moderate hypertensive patients after 3 or more visits. We tested the hypothesis that an ambulatory blood pressure recording could also help to decide which patient need therapy. Blood pressure was measured in 89 essential, uncomplicated, hypertensive patients (diastolic (DBP): 90-110 mmHg, mean age: 41 +/- 13 years), with a mercury sphygmomanometer at 3 visits and with an ambulatory blood pressure recorder (Spacelabs) during 12 hours. According to WHO recommendations, patients were classified "WHO+" if they need a treatment (n = 44) and "WHO-" if they did not. The mean ambulatory DBP of each subject was compared to the arbitrary limit defined as the mean +2 standard deviations of the ambulatory DBP of a population of normotensive subjects in the same decade and same sex: patients with ambulatory DBP above this limit were defined "AMB+" (n = 27), the others were "AMB-". Ten patients were "WHO- AMB+" and 24 were "WHO+ AMB-". These discordances were independent of age, body weight, duration of hypertension, variability of ambulatory systolic and diastolic blood pressure defined by the standard deviation. By contrast, the difference between the measurements of the simultaneous blood pressure measurements performed with the two methods (mercury sphyngmomanometer and Spacelabs) 2 times by each patient could explain in part these discrepancies. The Spacelabs underestimates DBP measured with the mercury sphyngmomanometer in patients "AMB-" but not in patient "AMB+".(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure Determination↗
[Predictive factors of resistance to antihypertensive treatment].
Results of antihypertensive treatment were analyzed in a group of 5,209 hypertensive patients referred in two hypertension Clinics in Paris from 1976 to 1985. Patients were included in the study if they fulfilled the following criteria: 1) at least four visits in the clinic, 2) follow-up period greater than 6 months, 3) initial diastolic blood pressure greater than or equal to 90 mmHg and/or presence of an antihypertensive treatment. After a mean follow-up period of 43 months, blood pressure was reduced from 177/105 mmHg to 148/89 mmHg. However, in spite of at least two antihypertensive drugs, 16.7 p. 100 of these patients had a diastolic blood pressure above 95 mmHg at the end of the follow-up period and were defined as uncontrolled hypertensives (UH). By comparison with controlled hypertensives (CH), UH patients were more frequently males (67.9 vs 56.6 p. 100, p less than 0.001), had a greater known duration of hypertension (11.6 vs 8.7 years, p less than 0.001), and presented at the first visit with higher blood pressures (188/113 vs 174/103 mmHg, p less than 0.001/p less than 0.001), despite a higher rate of antihypertensive treatment (66.6 vs 53.8 p. cent, p less than 0.001), a higher ponderal index (26.3 vs 25.3/kg/m2, p less than 0.01) and a higher prevalence of end-organ damage (23.2 vs 16.3 p. 100, p less than 0.001). Sokolov index, serum creatinine and uric acid levels were higher among UH than among CH patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure↗
[Measurement of platelet catecholamine content for the diagnosis of pheochromocytoma with intermittent hypertension].
We have compared platelet and plasma catecholamines (radioenzymatic assay with catechol-O-methyl transferase) and urinary metanephrines (high performance liquid chromatography) in 16 patients with phaeochromocytoma, 12 essential hypertensives, and 15 normotensive volunteers. Hypertensive patients with or without phaeochromocytoma had labile or paroxysmal hypertension with normal or borderline blood pressures between paroxysms. Catecholamine concentrations in platelets and plasma did not differ in essential hypertensives and controls, but were higher in patients with phaeochromocytoma than in subjects without tumour, with values overlapping between groups. Metanephrine excretion was markedly higher in phaeochromocytoma than in essential hypertension, with no intergroup overlap. Platelet adrenaline plus noradrenaline content was highly correlated to urinary metanephrines (r' = 0.830, n = 28 p less than 0.01). Using as a cut-off point the highest values measured in essential hypertensives, the sensitivity of each measurement was 1.00 for metanephrines, 0.87 for platelet catecholamines and 0.50 or less for plasma catecholamines. Measurement of platelet catecholamine content is a sensitive test and an appropriate alternative to metanephrine measurement in the difficult cases of suspected phaeochromocytoma with intermittent hypertension.
Adrenal Gland Neoplasms↗
[Double-blind evaluation of slow-release nicardipine using different methods of blood pressure measurement. Predictive value of the acute response to intravenous nicardipine].
Forty hypertensive patients (diastolic greater than 95 mmHg) were included after 15 days of a single blind placebo period in a randomized placebo controlled double-blind study to assess the antihypertensive effect of a new galenic form of nicardipine (N) administered 50 mg b.i.d. for 3 weeks. They comprised 27 men and 13 women aged from 27 to 72 years (mean: 53 +/- 10). Blood pressure (BP) was measured in hospital before morning drug intake by an automatic recorder (Sentron) in supine position for 30 minutes (min) and by a mercury sphygmomanometer. Ambulatory BP was assessed by a portable patient activated recorder (Remler 2000). Mercury sphygmomanometer supine BP under N fell from 160 +/- 21/104 +/- 6 mmHg to 151 +/- 14/98 +/- 8 mmHg (n = 20; p less than 0.01/p less than 0.01) whereas BP under placebo (P) was respectively 158 +/- 14/103 +/- 6 mmHg and 156 +/- 20/102 +/- 9 mmHg (NS). Sentron BP under N fell from 158 +/- 17/96 +/- 8 mmHg to 148 +/- 13/90 +/- 7 mmHg (p less than 0.001/p less than 0.01) with no BP change under P (152 +/- 12/93 +/- 7 mmHg to 151 +/- 14/93 +/- 8 mmHg NS). BP recorder every 30 min for 12 hours revealed a decrease under N (160 +/- 18/105 +/- 10 mmHg to 142 +/- 16/94 +/- 10 mmHg; p less than 0.001/p less than 0.001) with a placebo effect in the control group on the diastolic BP (160 +/- 15/103 +/- 7 mmHg to 156 +/- 16/100 +/- 8 mmHg/NS/p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Decentralization of the ARTEMIS system in a nephrology service in a general hospital].
"ARTEMIS" is a standardized and computerized medical file which is intended for improving the follow-up of hypertensive patients, the efficacy of treatment and for realising national-wide surveys. The software "LIED" of data base for "ARTEMIS" is nowadays transposable on mini-computer. In Nephrology Unit of General Hospital from Colmar, the system has been working since September 1985 with MICRO-MEGA E 32 (Thomson). The administrative and medical data are directly acquired by the doctors and secretaries of the Unit on a conversational mode from six terminals. There is no writing collecting of data. An evaluation of the system was realized with the 113 first hypertensive patients. The results were compared to those obtained from patients of Paris area.
Follow-Up Studies↗
[Does hypertension have fewer complications in pregnancy in obese patients?].
In order to study the relationships between hypertension, obesity and perinatal morbidity and mortality, we have studied a group of 264 women included in a cooperative prospective study with respect to obesity arbitrarily defined as a body mass index greater than or equal to 27 kg/m2. The obese and normal-weight groups comprised respectively 55 and 209 women of similar age (29.1 +/- 5.5 vs 30.2 +/- 5.3 years, NS). Obese women were less often primiparous than women with a normal weight (29.1 vs 50.2 p. 100, p less than 0.01). Hypertension before pregnancy was similarly frequent in both groups (41.8 vs 31.6 p. 100). Hypertension begun sooner during the pregnancy in the obese than in the normal group (17.1 +/- 11 vs 22 +/- 11 weeks of amenorrhea, p less than 0.01), the first abnormal blood pressure being comparable in both groups (156 +/- 15/96 +/- 14 vs 152 +/- 15/95 +/- 10 mmHg, NS). Indicators of perinatal risk were less often observed in the obese group: hypertension begins less often during the second trimester of the pregnancy (7.4 vs 21.7 p. 100, p less than 0.05), proteinuria greater than or equal to 2+ is more rare (13.0 vs 25.1 p. 100, p = 0.07), plasma urates are lower (maximum recorded value: 272 +/- 63 vs 322 +/- 96 mumol/l, p less than 0.001). No perinatal death occured in the obese group, as compared with 15 in the normal group (p less than 0.05). The weight of surviving babies was higher in the obese than in the normal group (3,294 +/- 596 vs 2,947 +/- 702 g, p less than 0.001), despite a comparable gestational age (38.3 +/- 2.3 vs 38.9 +/- 1.8 weeks, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Results of the surgical treatment of Conn's adenomas].
During the last 10 years we operated on 69 Conn's adenomas of which 59 were followed up for a mean period of 16 months (range: 3-96 months). Surgery cured the hypertension (blood pressure less than 140/90) in 47 p. 100 of the patients. Improved blood pressure (systolic: mean = 46 mmHg; range 0-135 mmHg and diastolic: mean = 25 mmHg; range 0-66 mmHg) was noted in another 47 p. 100 of patients whereas no blood pressure change was noted in 3 patients. Biological primary aldosteronism was found post-operatively in 2 of these 3 patients and also in one whose hypertension was improved. In this last patient plus the three unimproved by surgery, small tumours (less than 10 mm) were found and co-existnt multifocal hyperplasia was found in the 2 patients who had had an adrenalectomy. Fifty-one patients were treated pre-operatively by spironolactone (SP) alone (3.2 +/- 1.3 mg/kg) for a mean period of 6.8 weeks (range: 3 to 20 weeks). Only 2 of the 24 patients controlled by SP were not cured by surgery and one of them had persistnt primary aldosteronism. Conversely, 3 of the 27 uncontrolled by SP were cured post-operatively, and these exceptions could be due to the weak dose of SP (n = 2) and an observance problem (n = 1). Patients cured by surgery had shorter duration of hypertension (4.3 +/- 3.0 years vs 10.1 +/- 8.1; p less than 0.01) and lower diastolic pressure (111 +/- 14 mmHg vs 121 +/- 12; p less than 0.01) than uncured patients. No significant difference between these two groups was observed with respect to systolic pressure, age, sex, plasma potassium, plasma renin activity and plasma aldosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗