Search PubMed⌕ Search

Biomedical subjects

D Grimaud

Publications and source records attributed to D Grimaud.

At least 19 recordsLinked to original sources
PubMed2003

[Metformin-associated lactic acidosis remains a serious complication of metformin therapy].

We report 4 cases of lactic acidosis in diabetic patients usually treated with metformin. For the first 3 patients, the clinical history was similar because lactic acidosis was precipitated by gastro-intestinal disorders whereas all of them were simultaneously treated with several nephrotoxic drugs. These 3 patients presented with acute renal failure on arrival at hospital. Their issue was fatal whereas any obvious cause of overproduction of lactate was found. The fourth case, which was due to a voluntary intoxication, was the only one presenting with a favourable evolution. The metformin plasma and red blood cell levels were performed for 2 of 4 patients and confirmed the overdose. These observations remind that metformin-associated lactic acidosis remains a serious complication, and that medical doctors must respect strictly contra-indications and guidelines for withdrawing metformin.

Acidosis, Lactic↗
PubMed2002

[Severe metabolic alkalosis and beer drinking].

We describe a case report with moderately low plasma sodium level and predominant metabolic alkalosis. Others have reported acid-base balance disorders, although no clear pathophysiological explanation has been put forward. We hypothesize that, combine with poor protein intake, mild hyperosmolar beer leads to a water intoxication syndrome, whereas strong hyperosmolar beer intake more likely induces hypochloremic metabolic alkalosis.

Adult↗
PubMed2002

[Rapid sequence intubation in emergency: is there any place for fentanyl?].

OBJECTIVES: Rapid sequence intubation (RSI) with the association of etomidate and succinylcholine is the French "Gold standard" for urgent "full stomach" endotracheal intubations. The aim of this study is to assess the fentanyl as a co-induction agent to take over the sedation between the RSI and the keeping of sedation, which is a critical period in which harmful neuro-vegetatives events, and awakening signs are frequently seen. STUDY DESIGN: Randomized, double blind controlled prospective study, after acceptation by the local ethical committee. PATIENTS AND METHODS: Three groups of patients undergoing RSI in the intensive care unit and by the out-of-hospital medical team were compared: group A patients received fentanyl 3 micrograms kg-1 during RSI, before paralysis was induced. Group B patients received the same dose of fentanyl immediately after endotracheal intubation. Group C patients did not received fentanyl (control group). Outcome measures were awakening signs arrival (respiratory movements, eyes opening, spontaneous limb movements), Ramsay score assessment, and haemody namics. Attempt at intubation and vomiting incident were also measured. Discrete data were compared by chi-2 analysis, continuous data were compared with two-way analysis of variance. A p value < 0.05 was the significant threshold. RESULTS: Thirty-six patients were enrolled and completed the study. All the included patients presented awakening signs. The use of fentanyl did not prevent the recourse of other sedative medications. Ten minutes after endotracheal intubation, significant differences has been noticed for the awakening signs arrival between fentanyl groups (A: 42% and B: 36%) and control group (C: 77%). The Ramsay score evolution follows the same variation. All the patients were intubated on the first attempt, there was no vomiting incident noticed. CONCLUSION: The use of fentanyl, as a co-induction agent with etomidate and succinylcholine during RSI, allows a significant delay of the awakening signs arrival and attenuate the neurovegetative response during the minutes after endotracheal intubation after RSI, without deleterious haemodynamic effects.

Anesthesia, Intravenous↗
PubMed2002

Comparison of the effects of sevoflurane and propofol on cortical somatosensory evoked potentials.

BACKGROUND: Propofol (P) and sevoflurane (S) are potential anaesthetic agents if electrophysiological monitoring is required during spinal surgery. They allow rapid recovery and do not depress cortical somatosensory evoked potentials (SSEP) as much as other agents. The effects of these agents on SSEP have not been compared before. METHODS: Twenty-four patients were allocated randomly to receive either S (n = 12) or P (n = 12). SSEP evoked by electrical stimulation of the posterior tibial nerve at the ankle were recorded before anaesthesia. The cortical potential P40 was recorded (latency P40 and amplitudes N29P40 and P40N50). The anaesthetic concentration was adjusted gradually to obtain three predetermined ranges of values of bispectral index (BIS): 45-55, 35-45 and 25-35. For each range, a stable state was maintained for 10 min and SSEP were recorded. RESULTS: For the BIS 45-55 range, compared with preoperative values, P40 latency increased during S [mean change +2 (SD 0.6) ms] but not during P [+0.4 (0.2) ms (P = 0.12)] and both amplitudes (N29P40 and P40N50) decreased with S. Increasing S concentration caused a dose-dependent depression of SSEP. P did not have a statistically significant effect on the recordings and the signals remained stable in each BIS range. CONCLUSION: Sevoflurane affected SSEP recordings in a dose-dependent fashion. Propofol had a minimal effect on SSEP recordings.

Adult↗
PubMed2002

Tapia's syndrome following shoulder surgery.

Multiple cranial palsy occurred after shoulder surgery in the sitting position. Compression by the tracheal tube, caused by displacement of the head, may have caused the injury.

Adult↗
PubMed2002

[Impact of the development of anesthesia protocols on the incidence of peri-anesthetic anaphylactoid reactions].

INTRODUCTION: What impact does the use of new drugs and latex gloves it have on the frequency and the severity of peri-anaesthetic anaphylactoid reactions? Does the evolution of in vitro techniques does represent a progress in the imputability of the substances at the origin of the shock? THE METHODS: They include the letter from the anaesthetic doctor, the questioning by the allergologist, skin tests (Pricks, IDR) with the anaesthetic substances and the latex according to the GERAP protocol and the biologic tests (Human Basophilic Degranulation test (TDBH), Radio ImmunoAssay (RIA), leukotrienes E4 assay (LTC4), Flow Cytometry (CMF)). THE RESULTS: 386 patients were explored (289 women and 88 men, mean age 41.5 years). The muscle relaxants are the first cause of anaphylaxis 77%. Muscle relaxants cross allergy is found in 55.1%. The Latex, tested since 1989 with Allerbio and Stallergenes extracts, is responsible for 25 shocks with one death and 15 with grade III or IV. Preventive antibiotherapy, since consensus meeting of 1992, seems responsible of 17 accidents. 116 TDBH, 216 RIA, 17LTC4 and 47CMF. TDBH are made concordant with skin tests in 48.2% against, 71.2% for the RIA. CONCLUSION: The experience of 17 years of allergo-anaesthetic consultation confirms the first row for the muscles relaxants for the target of anaphylactic shock, but the imputability of Vecuronium and Rocuronium increases to the detriment of the Suxamethonium. The Latex is in the second row, but the target questioning, the systematic use of Prick tests and "latex free" surgery room limit its increase which should change down. The antibiotherapy occupies the third row and might increase. 54 accidents have remained unexplained.

Adult↗
PubMed2001

Improvement of 'dynamic analgesia' does not decrease atelectasis after thoracotomy.

There is still controversy concerning the beneficial aspects of 'dynamic analgesia' (i.e. pain while coughing or moving) on the reduction of postoperative atelectasis. In this study, we tested the hypothesis that thoracic epidural analgesia (TEA) prevents these abnormalities as opposed to multimodal analgesia with i.v. patient controlled analgesia (i.v. PCA) after thoracotomy. Fifty-four patients undergoing thoracotomy (lung cancer) were randomly assigned to one of the two groups. Clinical respiratory characteristics, arterial blood gas, and pulmonary function tests (forced vital capacity and forced expiratory volume in 1 s) were obtained before surgery and on the next 3 postoperative days. Atelectasis was compared between the two groups by performing computed tomography (CT) scan of the chest at day 3. Postoperative respiratory function and arterial blood gas values were reduced compared with preoperative values (mean (SD) FEV1 day 0: 1.1 (0.3) litre; 1.3 (0.4) litre) but there was no significant difference between groups at any time. PCA and TEA provided a good level of analgesia at rest (VAS day 0: 21 (15/100); 8 (9/100)), but TEA was more effective for analgesia during mobilization (VAS day 0: 52 (3/100); 25 (17/100)). CT scans revealed comparable amounts of atelectasis (expressed as a percentage of total lung volume) in the TEA (7.1 (2.8)%) and in the i.v. PCA group (6.71 (3.2)%). There was no statistical difference in the number of patients presenting with at least one atelectasis of various types (lamellar, plate, segmental, lobar).

Aged↗
PubMed2001

An evaluation of the brachial plexus block at the humeral canal using a neurostimulator (1417 patients): the efficacy, safety, and predictive criteria of failure.

UNLABELLED: To evaluate the efficacy and safety of the multiple peripheral nerve block technique at the humeral canal (humeral block) with the use of a neurostimulator, we prospectively studied 1417 patients undergoing upper limb surgery with a brachial plexus block at the humeral canal (1468 blocks). The success rate (defined as sensory block [in all nerve distributions] and/or the absence of another anesthetic technique required to allow surgery) was 95%. The threshold of minimal stimulation used to locate each nerve before injecting the anesthetic solution was the unique predictive factor for identified failure. For the median nerve, the threshold was 0.8 mA with a relative risk of failure (RRf: relative risk evaluated by series of Taylor with a 95% confidence interval) = 1.49 (P = 0.04), for the radial nerve the threshold was 0.6 mA (RRf 1.3, P = 0.02), and 0.7 mA for the ulnar nerve (RRf 1.36, P = 0.04). For any equal or higher stimulation level, the risk of failure of the humeral block increased. For the musculocutaneous nerve, we did not observe a significant stimulation threshold for the risk of failure; although beyond 0.7 mA, the RRf was always more than 1.3. Adverse events occurred in 7% of all cases and were usually minor (nausea/vomiting, anxiety, local pain). Our study provides supplementary information on the efficacy and safety of this technique. Stimulation thresholds are clinically identified for the first time as the main factor linked to the failure of a technique using a neurostimulator. We conclude that the humeral block is a reliable peripheral block allowing good success rates results with minor complications, which can be used as an alternative to the axillary block. IMPLICATIONS: We prospectively evaluated the feasibility and the factors causing failure of a peripheral nerve block technique (humeral block) using neurostimulation in a large number of patients. The importance of the level of stimulation for the success of the block was evaluated for the first time.

Adolescent↗
PubMed2001

Initial effect of sodium bicarbonate on intracellular pH depends on the extracellular nonbicarbonate buffering capacity.

OBJECTIVE: The effect of sodium bicarbonate on intracellular pH under conditions close to those in vivo, with both bicarbonate and nonbicarbonate buffering systems, is unknown. We postulated that this effect depends on the nonbicarbonate buffering capacity because the alkali-induced back-titration of these buffers results in a concentration-dependent release of CO2 in the extracellular space, leading to a decrease in intracellular pH. DESIGN: The study was conducted in two stages. First, human hepatocytes were perfused with pH 7 bicarbonate-buffered medium (5 mM HCO3-, 20 torr Pco2) containing no nonbicarbonate buffer or small amounts (5 mM 4-[2-hydroxyethyl]-1-piperazineethanesulfonic acid [HEPES]) or large amounts (20 mM HEPES) of nonbicarbonate buffer. Second, the changes in intracellular pH of hepatocytes placed in acidotic human blood (pH 7, 5 mM HCO3-, 20 torr Pco2) at three hematocrits (40%, 20%, and 5%) were measured. SETTING: Research laboratory at a medical university. SUBJECTS: Cryopreserved human hepatocytes thawed the day before the experiments. INTERVENTIONS: Sodium bicarbonate was infused for 10 mins to increase the HCO3- concentration from 5 to 30 mM. In the second part, 20 mM sodium bicarbonate was added directly to the blood bathing the cells. MEASUREMENTS AND MAIN RESULTS: The intracellular pH was measured with the pH-sensitive fluorescent dye bis-carboxyethyl carboxy-fluorescein in its esterified form, acetoxy-methyl ester, by using a single-cell imaging technique. Gas analyses were performed before and during the sodium bicarbonate load. Sodium bicarbonate caused a decrease in intracellular pH with all media except the artificial medium containing no HEPES. This decrease was small in media with low nonbicarbonate buffering capacity (5 mM HEPES and 5% hematocrit blood) and large in media with high nonbicarbonate buffering capacity (20 mM HEPES and 40% hematocrit blood). The change in intracellular pH was linked closely to the change in Pco2 caused by the sodium bicarbonate. CONCLUSIONS: The effect of sodium bicarbonate on intracellular pH depends on changes in Pco2 in the medium bathing the cells. The increase in Pco2 is correlated with the extracellular nonbicarbonate buffering capacity because of the release of H+ ions coming from the back-titration of these buffers. We conclude that sodium bicarbonate may exacerbate cell acidosis under buffering conditions close to those in vivo and that the initial changes in cell pH caused by sodium bicarbonate depend on the extracellular nonbicarbonate buffering capacity.

Blood↗
PubMed2001

Acute postoperative metabolic complications of diabetes.

Because of several factors, including a change in the hormonal behavior, the postoperative period is at high risk for the diabetic patient to present a metabolic complication. On the other hand, a diabetic metabolic disorder may be secondary and reveal a severe underlying complication (sepsis...). Ketoacidosis is the consequence of an absolute or relative lack of insulin and occurs mainly in insulin dependent diabetic patients. Its incidence should be very low during the postoperative period since insulin protocols are systematically used. The main clinical and biological signs are a polypnea, signs of dehydration, an hyperglycemia associated with a high anion gap metabolic acidosis and the presence of ketoacids in the urine. Its treatment is mainly based on an active rehydration and an insulin and potassium supply. Sodium bicarbonate should not be used systematically any more, even during severe acidosis. Hyperosmolar non ketotic states affects insulin nondependent and older diabetic patients for the most part and occurs under similar conditions than ketoacidosis, revealing most of the time a severe underlying complication. Clinical and biological manifestations include a severe dehydration, alterations in consciousness and a major hyperglycemia associated to a moderate or mild metabolic acidosis. Its main treatment is an active rehydration and insulin plus potassium in a second time. Hypoglycemia is usually the consequence of a mistake in the diabetes care and in the insulin management. Every sickness or consciousness disorder occurring in a diabetic patient treated with insulin should lead to perform a blood glucose measurement. In case of severe manifestations, glucose should be administered in emergency, orally if the patient is conscious or intravenously if he is not. Lactic acidosis occurring during the postoperative period in a diabetic patient is usually non specific of diabetic disease and reflects the existence of an underlying complication (sepsis, hemorrhage, hypoxia,...), as it would in an non diabetic patient. Lactic acidosis due to a treatment with metformin is now very rare and occurs almost only in patients having a contraindication to the use of metformin.

Acidosis, Lactic↗
PubMed2000

The increase in CO2 production induced by NaHCO3 depends on blood albumin and hemoglobin concentrations.

OBJECTIVE: To evaluate the origin of H+ ions participating in the generation of CO2 coming from sodium bicarbonate infusion during metabolic acidosis. We hypothesized that these H+ ions come from a back-titration of the main non-bicarbonate buffers present in the blood, i. e. the hemoglobin and the albumin, and thus postulated that the rate of CO2 release from a bicarbonate load is dependent on the concentration of these buffers. DESIGN: Prospective clinical and experimental study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS AND MATERIAL: (1) Sixteen stable sedated and artificially ventilated critically ill patients with a mild base deficit. (2) Acidotic human blood (bicarbonate 5 mM, pH 7.0) of hematocrit 5, 10, 20 and 40% regenerated from a mixture of frozen fresh plasma and packed red blood cells. INTERVENTIONS PATIENTS: infusion of 1.5 mmol/kg sodium bicarbonate over 5 min. Regenerated blood: 25 mM sodium bicarbonate load. MEASUREMENTS AND RESULTS PATIENTS: continuous measurement of CO2 production (VCO2) on the expired gas using a metabolic monitor and arterial blood gas analysis before (T0), at the end (T5) and at 10, 30 and 60 min after the beginning of the bicarbonate infusion. The increase in VCO2 was 18 +/- 7% leading to a rise in PaCO2 from 39.6 +/- 2.3 at T0 to 46.2 +/- 2.7 mmHg at T5. The increases in VCO2 and in PaCO2 were significantly correlated to the albumin (r = 0.73, p < 0.005 and r = 0.70, p < 0.005, respectively) and to the hemoglobin (r = 0.51, p < 0.05 and r = 0.65, p < 0.01, respectively) concentrations. Regenerated blood: gas analysis 1 min after the bicarbonate load. The increase in PCO2 was closely related to the hematocrit (Ht) of the blood as it was 15.9 +/- 7.5 mmHg for Ht 5%, 29.0 +/- 9.6 for Ht 10%, 44.2 +/- 5.9 for Ht 20% and 71.0 +/- 3.5 for Ht 40% (n = 5 for each, p < 0.001). CONCLUSIONS: The importance of the release of CO2 from a bicarbonate load is dependent on the concentration of the blood non-bicarbonate buffers. It is therefore likely that the adverse effects of bicarbonate therapy linked to the CO2 generation are more important in patients with high blood albumin and hemoglobin concentrations.

Acidosis↗
PubMed2000

Comparison of the renal effects of low to high doses of dopamine and dobutamine in critically ill patients: a single-blind randomized study.

OBJECTIVE: The renal effects of dopamine in critically ill patients remain controversial. Low-dose dobutamine has been reported to improve renal function. We compared the effects of various doses of dopamine and dobutamine on renal function in critically ill patients. DESIGN: Prospective, single-blind, randomized study. SETTING: University hospital, 19-bed multidisciplinary intensive care unit. PATIENTS: Twelve hemodynamically stable patients with mild nonoliguric renal impairment. INTERVENTIONS: Each patient randomly received four different doses of dopamine and dobutamine (placebo, 3, 7, and 12 microg/kg/min). Each infusion lasted for 4 hrs. Cardiac output and systemic hemodynamic variables were measured using a pulmonary arterial catheter at the beginning (HO) and the end (H4) of each infusion. The bladder was emptied at HO and H4 to determine urine volume and to collect samples. MEASUREMENTS AND MAIN RESULTS: The cardiac index increased significantly with both dopamine and dobutamine (p < .001). Mean arterial pressure (MAP) increased, with the maximum effect of 20% seen with 12-microg/kg/min dopamine infusion (p < .01). No change in MAP was seen with dobutamine. Dobutamine infusions did not change any renal variables. Conversely, all dopamine infusions significantly increased diuresis, creatinine clearance, and the fractional excretion of sodium (p < .01). Creatinine clearance increased from 61+/-16.9 (SD) mL/min to a maximum of 85.7+/-30 mL/min at the 7-microg/kg/min dose; fractional excretion of sodium increased from 0.26%+/-0.28% to a maximum of 0.62%+/-0.51% at the 12-microg/kg/min dose (p < .01). During dopamine infusions, there was a significant relationship between MAP and creatinine clearance (p = .018). CONCLUSIONS: At all doses studied, 4-hr infusions of dopamine significantly increased creatinine clearance, diuresis, and the fractional excretion of sodium in stable critically ill patients. Conversely, dobutamine did not modify these variables. Although the level of MAP might partially contribute to the improvement in renal variables, it is more likely that the activation of renal dopamine receptors played a prominent role.

Adrenergic beta-Agonists↗
PubMed2000

Prolonged low-dose dopamine infusion induces a transient improvement in renal function in hemodynamically stable, critically ill patients: a single-blind, prospective, controlled study.

OBJECTIVE: To evaluate the length of the effects of long-term (48 hrs), low-dose dopamine infusion on both renal function and systemic hemodynamic variables in stable nonoliguric critically ill patients. DESIGN: Prospective, single-blind, controlled clinical study. SETTING: University hospital, 19-bed multidisciplinary intensive care unit. PATIENTS: Eight hemodynamically stable, critically ill patients with a mild nonoliguric renal impairment (creatinine clearance between 30 and 80 mL/min). INTERVENTIONS: Each patient consecutively received 4 hrs of placebo, followed by a 3 microg/kg/min dopamine infusion during 48 hrs, then a new 4-hr placebo period. We measured cardiac output and other hemodynamic variables by using a pulmonary artery catheter. The bladder was emptied to determine urine volume and to collect urine samples. Measurements were performed at six times: after the initial control of 4 hrs of placebo (C1); after 4 hrs (H4), 8 hrs (H8), 24 hrs (H24), and 48 hrs (H48) of dopamine infusion; and after the second control of 4 hrs of placebo (C2). MEASUREMENTS AND MAIN RESULTS: We saw no significant change in systemic hemodynamic variables with dopamine at all times of infusion. Diuresis, creatinine clearance, and the fractional excretion of sodium (FENa) at C1 and C2 were not different. Urine flow, creatinine clearance, and FENa increased significantly 4 hrs after starting dopamine (for all these changes, p < .01 vs. C1 and C2). The maximum changes were obtained at H8, with an increase of 50% for diuresis, 37% for creatinine clearance, and 85% for FENa (for all these changes, p < .01 vs. C1 and C2). But these effects waned progressively from H24, and both creatinine clearance and FENa at H48 did not differ from control values. CONCLUSIONS: In stable critically ill patients, preventive low-dose dopamine increased creatinine clearance, diuresis, and the fractional excretion of sodium without concomitant hemodynamic change. These effects reached a maximum during 8 hrs of dopamine infusion. But despite a slight persistent increase in diuresis, improvement in creatinine clearance and FENa disappeared after 48 hrs. According to these data, it is likely that tolerance develops to dopamine-receptor agonists in critically ill patients at risk of developing acute renal failure.

APACHE↗
PubMed1998

Hypocapnia does not alter hepatic blood flow or oxygen consumption in patients with head injury.

OBJECTIVE: To evaluate the effects of hypocapnia on the systemic and hepatic circulations and oxygenation values in patients with head injury. DESIGN: Open-label, prospective study. SETTING: University hospital, department of anesthesiology and intensive care unit. PATIENTS: Eleven mechanically ventilated patients with isolated head trauma and stable hemodynamic status. INTERVENTIONS: At the beginning of the study, each patient presented with normocapnic ventilation. Mechanical hyperventilation was then adjusted to obtain stable hypocapnia over an interval of 24 hrs. Cardiac output and other systemic hemodynamic parameters were measured, using a pulmonary artery catheter. Hepatic parameters were measured via a catheter inserted into the hepatic vein. Total hepatic blood flow was determined by the Fick principle using a continuous infusion of indocyanine green. Arterial and hepatic venous blood gases were sampled to determine systemic and hepatic-splanchnic oxygenation. Measurements were done at the end of the four phases: a) 30 mins of normocapnia (N); b) 30 mins of hypocapnia (H0); c) 3 hrs of hypocapnia (H3); and d) 24 hrs of hypocapnia (H24). Intracranial pressure and cerebral perfusion pressure were hourly monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in systemic hemodynamic parameters. The hepatic blood flow index did not differ from normocapnia (N 1.8 +/- 0.4 L/min/m2) to hypocapnia (H0 1.6 +/- 0.3 L/min/m2; H3 1.7 +/- 0.4 L/min/m2; H24 1.7 +/- 0.4 L/min/m2). The ratio of hepatic blood flow index to cardiac index remained stable throughout the study. Hypocapnia did not affect hepatic-splanchnic oxygen delivery and consumption. CONCLUSIONS: Hypocapnic hyperventilation does not alter hepatic hemodynamic parameters in patients with head injury. This result may be related to the lack of changes in cardiac output or in the hepatic vasoreactivity. Moreover, hypocapnia does not modify hepatic-splanchnic oxygenation. Thus, in case of intracranial hypertension, hypocapnia might be used without undesirable effect on the hepatic-splanchnic perfusion.

Adult↗
PubMed1998

Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction.

A prospective study was conducted on 34 stable septic patients to determine whether mild hyperlactatemia is a marker of lactate overproduction or an indicator of lactate underutilization during sepsis. Plasma lactate clearance and lactate production were evaluated by modeling the lactate kinetic induced by an infusion of 1 mmol/kg L-lactate over 15 min. The patients were divided in two groups depending on their blood lactate: < or = 1.5 mmol/L (n = 20, lactate = 1.2+/-0.2 mmol/L) or > or = 2 mmol/L (n = 10, lactate = 2.6+/-0.6 mmol/L). The hyperlactatemic patients had a lower lactate clearance (473+/-102 ml/kg/h) than those with normal blood lactate (1,002+/-284 ml/kg/h, p < 0.001), whereas lactate production in the two groups was similar (1,194+/-230 and 1,181+/-325 micromol/kg/h, p = 0.90). A second analysis including all the patients confirmed that the blood lactate concentration was closely linked to the reciprocal of lactate clearance (r2 = 0.73, p < 0.001) but not to lactate production (r2 = 0.03, p = 0.29). We conclude that a mild hyperlactatemia occurring in a stable septic patient is mainly due to a defect in lactate utilization.

Adult↗