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Biomedical subjects

J G Lee

Publications and source records attributed to J G Lee.

At least 19 recordsLinked to original sources
PubMed1995

Microsatellite instability and K-ras mutations associated with pancreatic adenocarcinoma and pancreatitis.

ras oncogene mutations and microsatellite instability (MIN) have been described in pancreatic cancer studies from paraffin blocks and fresh frozen tissue. We sought to determine whether they could be detected in endoscopic retrograde cholangiopancreatography-derived pancreatic juice. ras mutations were detected in the pancreatic juice of 40% (2 of 5) of patients with pancreatic cancer and 2 of 5 patients with pancreatitis. MIN was detected at a single locus in the pancreatic juice of 40% of pancreatic cancer patients and at > or = 2 loci of 100% of pancreatitis patients. The finding of MIN in pancreatitis specimens was verified in studies performed on paraffin blocks. MIN was not detected in normal pancreas controls. All of the cancer patients who had ras mutations in their pancreatic juice also had evidence of MIN at one or more loci (P < or = 0.05), suggesting that MIN is associated with the development of a ras mutation. More importantly, the finding of MIN in pancreatitis specimens suggests that MIN can occur in nonneoplastic conditions of the pancreas and may represent the saturation of an intact mismatch repair system.

Adenocarcinoma↗
PubMed1995

Periprocedural myocardial ischemia in patients with severe symptomatic coronary artery disease undergoing endoscopy: prevalence and risk factors.

PURPOSE: To determine the prevalence of and risk factors for periprocedural myocardial ischemia associated with gastrointestinal endoscopy in patients with severe symptomatic coronary artery disease. PATIENTS AND METHODS: In this prospective observational study, myocardial ischemia (ST segment change > 100 microV in any 2 leads or > 200 microV in any 1 lead, lasting > 60 seconds) was assessed using a continuous 12-lead digital electrocardiographic monitor before, during, and after gastrointestinal endoscopy. RESULTS: Between June 1992 and May 1993, 1,084 esophagogastroduodenoscopies and 588 colonoscopies were performed during 1,438 consecutive endoscopies on patients admitted to a university hospital. Seventy (18%) of 252 patients with prior angiography had significant coronary artery disease. Fifty-two (74%) were successfully enrolled, and satisfactory electrocardiographic recordings were obtained from 49 (median age 65 years, interquartile range 58 to 74). Thirty-six were men, 12 had myocardial infarctions within the 6 weeks (median 12.5 days, interquartile range 8 to 18), and 25 had unstable angina. The coronary artery disease involved 1 vessel in 14 subjects, 2 vessels in 21, and 3 vessels in 14. Nineteen episodes of ischemia (4 pre-, 6 intra-, 9 postprocedure) were detected in 8 patients (16%; 95% confidence interval, 6% to 26%) during the recording period (median duration 322 min, interquartile range 227 to 429). One patient became symptomatic with a myocardial infarction. Multivariable logistic regression showed that women experienced more periprocedural ischemia compared to men (31% versus 11%; P = 0.058). CONCLUSIONS: Myocardial ischemia occurs during the periprocedural period in 16% of hospitalized patients with severe coronary artery disease undergoing gastrointestinal endoscopy. Endoscopy is safe in hemodynamically stable patients with recent myocardial infarction and/or unstable angina. Women appear to be at greater risk for periprocedural ischemia associated with endoscopy.

Aged↗
PubMed1995

Laser-Doppler measurement of the effects of halothane and isoflurane on the cerebrovascular CO2 response in the rat.

We used laser-Doppler flowmetry to compare the effects of the volatile anesthetics, isoflurane and halothane, on the cerebrovascular response to CO2 inhalation in male Sprague-Dawley rats. The effects of 0.5 and 1.5 minimum alveolar anesthetic concentrations (MAC) of halothane and isoflurane on the microcirculatory response to CO2 were compared at 22, 36, and 66 mm Hg end-tidal partial pressure of carbon dioxide (ETCO2). An additional group of animals was anesthetized by continuous barbiturate infusion (10-20 mg.kg-1.h-1). Arterial blood pressure was maintained at control levels throughout the experiment using an infusion of phenylephrine (0.5-5 micrograms.kg-1.min-1). Laser-Doppler flow (LDF) was greater at 1.5 MAC than at 0.5 MAC at each ETCO2 for both anesthetics. The CO2 reactivity (percent LDF change/mm Hg change ETCO2) from hypocapnia to normocapnia was similar to that from normocapnia to hypercapnia. CO2 reactivity with barbiturate infusion and 0.5 MAC isoflurane were 1.78 +/- 0.19 and 2.28 +/- 0.22 (no difference), respectively, both being greater than that with 0.5 MAC halothane at 1.19 +/- 0.14 (P < 0.05). A similar difference was suggested at 1.5 MAC halothane and 1.5 MAC isoflurane (1.99 +/- 0.25 and 2.67 +/- 0.35, respectively). The CO2 reactivity was greater at 1.5 MAC halothane compared to 0.5 MAC halothane. The results of this study suggest that an increase in arterial CO2 may increase cerebrocortical red cell flow more with isoflurane than with halothane, at least at moderate anesthetic concentrations.

Anesthesia↗
PubMed1995

Halothane and isoflurane decrease the open state probability of K+ channels in dog cerebral arterial muscle cells.

BACKGROUND: Both halothane and isoflurane evoke cerebral vasodilation. One of the potential mechanisms for arterial vasodilation is enhanced K+ efflux resulting from an increased opening frequency of membrane K+ channels. The current study was designed to determine the effects of volatile anesthetics on K+ channel current in single vascular smooth muscle cells isolated from dog cerebral arteries. METHODS: Patch clamp recording techniques were used to investigate the effects of volatile anesthetics on macroscopic and microscopic K+ channel currents. RESULTS: In the whole-cell patch-clamp mode, in cells dialyzed with pipette solution containing 2.5 mM EGTA and 1.8 mM CaCl2, depolarizing pulses from -60 to +60 mV elicited an outward K+ current that was blocked 65 +/- 5% by 3 mM tetraethylammonium (TEA). Halothane (0.4 and 0.9 mM) depressed the amplitude of this current by 18 +/- 4% and 34 +/- 6%, respectively. When 10 mM EGTA was used in the pipette solution to strongly buffer intracellular free Ca2+, an outward K+ current insensitive to 3 mM TEA was elicited. This K+ current, which was reduced 51 +/- 4% by 1 mM 4-aminopyridine, was also depressed by 17 +/- 5% and 29 +/- 7% with application of 0.4 and 0.9 mM halothane, respectively. In cell-attached patches using 145 mM KCl in the pipette solution and 5.2 mM KCl in the bath, the unitary conductance of the predominant channel type detected was 99 pS. External application of TEA (0.1 to 3 mM) reduced the unitary current amplitude of the 99 pS K+ channel in a concentration-dependent manner. The open state probability of this 99 pS K+ channel was increased by 1 microM Ca2+ ionophore (A23187). These findings indicate that the 99 pS channel measured in cell-attached patches was a TEA-sensitive, Ca(2+)-activated K+ channel. Halothane and isoflurane reversibly decreased the open state probability (NPo), mean open time, and frequency of opening of this 99 pS K+ channel without affecting single channel amplitude or the slope of the current-voltage relationship. CONCLUSIONS: Halothane and isoflurane suppress the activity of K+ channels in canine cerebral arterial cells. These results suggest that mechanisms other than K+ channel opening likely mediate volatile anesthetic-induced vasodilation.

Animals↗
PubMed1995

Modification of cerebral laser-Doppler flow oscillations by halothane, PCO2, and nitric oxide synthase blockade.

We investigated whether nitric oxide (NO) played a role in the generation of cerebrocortical flow oscillations and their modification by hypocapnia, hypercapnia, and halothane administration. Parietal cortical laser-Doppler flow (LDF) was monitored transcranially in anesthetized (barbiturate + 0-1.0% halothane), artificially ventilated, adult male Sprague-Dawley rats. Thirty minutes after infusion of N omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) mean arterial pressure (MAP) increased from 105 +/- 10 to 132 +/- 15 mmHg (P < 0.02), while mean LDF decreased from 159 +/- 36 to 135 +/- 30 perfusion units (PU, P < 0.05). Oscillations in LDF at a frequency of 6.3-7.8 cycles/min and amplitude of 10% were induced or augmented by L-NAME but not by D-NAME or indomethacin (2 mg/kg i.p.). L-arginine (200 mg/kg) abolished the oscillations post-L-NAME at constant MAP. Sodium nitroprusside infusion (10(-5) M, 5-50 microliters/min) reversed the L-NAME-induced increase in MAP and decrease in mean LDF but did not attenuate the flow oscillations. Hypocapnia post-L-NAME decreased LDF to 110 +/- 20 PU (P < 0.001) and augmented the flow oscillations (amplitude: 11-31%). Hypercapnia (5% CO2) or halothane (0.4-1.0%) suspended the oscillations in the presence of L-NAME. The results suggest that NO synthase activity inhibits cerebrocortical flow oscillations, and NO is not an obligatory mediator of the effects of halothane, hypocapnia, and hypercapnia on oscillatory activity.

Amino Acid Oxidoreductases↗
PubMed1995

Effects of the peptide leukotriene receptor antagonist ICI 198,615 on the in vivo and in vitro changes in guinea pig bladder function which occur after sensitization with ovalbumin.

PURPOSE: The present studies were designed to determine the effects of in vivo and in vitro administration of ICI 198,615 (ICI), a leukotriene receptor antagonist, on the inflammatory changes that occur in the bladder after sensitization with ovalbumin. MATERIALS AND METHODS: The effect of intravenous administration of ICI on urodynamic changes after instillation of ovalbumin to sensitized guinea pigs was evaluated by in vivo cystometry. Responses of in vitro bladder muscle strips to contractile stimuli and ovalbumin were also evaluated in the presence of ICI. RESULTS: In sensitized guinea pigs, in vivo cystometry with ovalbumin induced a marked decrease in bladder capacity and increase in intravesical pressure. Pretreatment with ICI prior to cystometry prevented the ovalbumin-induced changes in capacity and intravesical pressure. There were no significant differences between control and sensitized animals in the responses of in vitro bladder muscle strips to field stimulation or bethanechol. However, maximal contractile responses to ovalbumin were significantly greater in the strips from sensitized animals than in controls. Preincubation with ICI, indomethacin, or pyrilamine alone was unable to inhibit the contractile responses to ovalbumin. However, combined administration of ICI, indomethacin and pyrilamine completely blocked the responses. CONCLUSIONS: In vivo administration of the leukotriene receptor antagonist ICI 198,615 reversed the urodynamic changes induced by ovalbumin challenge in sensitized guinea pigs. These results indicate that leukotrienes are primarily responsible for the changes in in vivo bladder function associated with sensitization.

Animals↗
PubMed1995

Benign, dysplastic, or malignant--making sense of endoscopic bile duct brush cytology: results in 149 consecutive patients.

OBJECTIVES: To determine the efficacy of endoscopic bile duct brush cytology for diagnosis of pancreaticobiliary malignancies and to provide guidelines for interpretation of dysplastic cytology. METHODS: Consecutive endoscopic bile duct brush cytology specimens were classified by an independent cytopathologist as benign, low- or high-grade dysplasia, or cancer. A final diagnosis was established in a blinded fashion by histopathology, radiographic evidence of metastatic disease, or independent clinical follow-up. Sensitivity and specificity were adjusted for dysplastic cytology, and likelihood ratios were determined for each diagnosis and used for calculation of posttest probability of malignancy. RESULTS: Dysplasia was found in 23% of 168 consecutive bile duct brushings performed in 149 patients. Sensitivity of brush cytology was 37% and specificity 100%; its likelihood ratio for malignancy ranged from 3.4 for high-grade dysplasia, to 1.1 for low-grade dysplasia, to 0.6 for benign. For a patient with a 50% pretest probability of malignancy, finding of high-grade dysplasia changed the posttest probability to 77%, low-grade dysplasia to 52%, and benign to 38%. CONCLUSION: Cytological dysplasia occurs frequently, with high-grade dysplasia being strongly suggestive of malignancy. Presented likelihood ratios can be used to calculate the posttest probability of malignancy for any diagnosis.

Aged↗
PubMed1995

Endoscopic therapy of sclerosing cholangitis.

The efficacy of endoscopic treatment in primary sclerosing cholangitis has not been clearly established. This report presents endoscopic intervention in 53 consecutive patients with this disorder. Pertinent data were abstracted from the GI-TRAC database, medical records, and cholangiograms, and clinical follow-up was obtained by telephone interview of the subjects. Assessed treatment outcomes were clinical symptom, liver function test, and cholangiographic appearance. Between 1986 and 1993, 85 patients with primary sclerosing cholangitis underwent successful ERCP, of which 36 men and 17 women underwent 100 therapeutic endoscopic procedures. Forty-three of 50 dilations, 37 of 38 stentings, 8 of 8 nasobiliary tube placements, and 11 of 17 stone extractions were technically successful. These treatments were complicated by cholangitis or pancreatitis in 15 patients. Clinical follow-up was obtained in 50 of 53 patients who had undergone 85 procedures (median follow-up of 31 months): 28 patients felt better, 21 felt the same, and 1 felt worse. Liver function tests obtained within 3 months of the endoscopic treatment were significantly improved compared with pretreatment values (P < .001). Cholangiograms showed improvement in 36% of the patients, no change in 51%, and the effect of therapy could not be assessed in 13%. Overall, 41 of 53 patients (77%) had improvements of their clinical symptoms, liver function tests, or cholangiograms.

Adult↗
PubMed1994

Comparative studies on the ontogeny and autonomic responses of the fetal calf bladder at different stages of development: involvement of nitric oxide on field stimulated relaxation.

This initial study correlates the passive length-tension relationship, contractile and relaxant responses to field stimulation and contractile responses to specific autonomic agonists and antagonists with gestational age. Fetal bovine bladders were separated into three groups based on the head-rump length (FL): 30 to 45 cm. (early gestation), 50 to 65 cm. (middle gestation) and 70 to 85 cm. (late gestation). Each bladder was separated into upper and lower bladder segments; longitudinal strips of smooth muscle were isolated and placed in individual muscle baths. Passive length-tension studies demonstrated that compliance was greatest in the bladder of late gestation and lowest in the bladder of early gestation period. Field stimulation (FS) elicited frequency-dependent contractile responses in all strips. In the upper bladder, the maximal response and maximal rate of tension generation to FS was lowest in the youngest fetuses and increased in proportion to the gestational age. In the lower bladders, there were no gestational age-related differences in the maximal response or maximal rate of tension generation in response to field stimulation. The maximal response of the upper bladder to bethanechol increased significantly from the youngest gestational age to mid-gestation, with no further changes between mid- and late gestation. The maximal response to field stimulation and bethanechol were equal between upper and lower bladder segments for the youngest gestational bladders, whereas for the oldest gestational ages, the maximal response of the upper bladder to FS and bethanechol were significantly greater than the responses of the lower bladder. In the presence of maximal precontraction with bethanechol, FS induced a rapid and marked decrease in tension. The magnitude of the relaxation was substantially greater for the strips of lower bladder than for the strips of upper bladder at late gestation. In lower bladders, the magnitude of the field stimulated relaxation was greater in the strips from the older fetuses than in the strips from younger fetuses. In all strips, field stimulated relaxations were completely inhibited by pretreatment with L-NAME (an inhibitor of nitric oxide synthesis), indicating that the FS-induced relaxation was due to nitric oxide. In addition to nitric oxide-induced relaxation, beta adrenergic stimulation also induced a significant relaxation of the isolated strips. In summary, these data suggest that, in the tubular shaped fetal bovine bladder, there were distinct differences in the autonomic responses between the upper bladder segment and the lower bladder segment in the late gestation period.

Adenosine Triphosphate↗
PubMed1994

Gastrointestinal manifestations of amyloidosis.

We reviewed gastrointestinal manifestations in 40 patients with amyloidosis. Gastrointestinal symptoms included anorexia, macroglossia, intestinal pseudo-obstruction, and altered bowel habits. Hepatomegaly was detected in eight patients, but none had clinically significant infiltrative liver disease. Mucosal friability and erosions were common endoscopic findings. Barium enema was noncontributory in the diagnosis of amyloidosis, since colonoscopy disclosed mucosal abnormalities in three of six patients with normal radiographic findings. Rectal biopsy had the highest diagnostic yield, followed by duodenal, gastric, and colonic biopsies.

Adult↗
PubMed1994

Hydrogen peroxide effects on rat mast cell function.

Oxidant exposure of the airway mucosa may play a significant role in the pathophysiology of asthma and allergic rhinitis. Mast cells play an important role in asthma, and oxidant exposure has been reported to cause direct mast cell degranulation as well as augment immunoglobulin E (IgE)-mediated responses in vivo. H2O2 is an oxidant generated by inflammatory cells and by the interaction of ozone with lipids or aqueous solutions. In this study, the RBL-2H3 mast cell line was used to investigate the ability of H2O2 to induce mast cell responses as well as to effect mast cell responses to IgE and the calcium ionophore A23187. Although cytotoxicity of RBL-2H3 cells at the membrane level was not observed with any concentration of H2O2, DNA damage resulted from exposure to 0.2 and 2.0 mM H2O2, and cell proliferation was inhibited by 0.075-0.2 mM H2O2. RBL cell prostaglandin D2 generation was enhanced after 60- and 120-min exposure to 0.2-20 mM H2O2. Direct serotonin release required 120-min exposures to 2.0 mM and 60-min exposures to 20 mM H2O2. However, degranulation responses induced by either IgE or A23178 were diminished after exposure to 0.2-2.0 mM H2O2. Lesser amounts (0.005-0.02 mM) had no effect on mast cell function. In summary, H2O2-induced responses of RBL cells, as well as modification of responses to IgE and A23187, occurred only at high concentrations of H2O2, which also induced both intracellular damage and inhibition of cell proliferation. Concentrations of H2O2 more likely to be physiologically relevant had no effect on mast cell responses or cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Comparative pharmacology of the male and female rabbit bladder neck and urethra: involvement of nitric oxide.

The present study compared the contractile and relaxant responses of male and female rabbit bladder neck and urethra to field stimulation (FS) and various contractile and relaxant agents, with special attention paid to the involvement of nitric oxide (NO) in the mediation of field-stimulated relaxation. FS at basal tension elicited a frequency-dependent contractile response in all preparations. The maximal response to high frequency FS was significantly greater in the bladder neck strips isolated from male rabbits than in those from female rabbits. There were no significant differences in the response to bethanechol or phenylephrine between strips isolated from males and females. Field-stimulated responses of the strips from male bladder neck and urethra were greater than the response to phenylephrine. The responses of all strips to FS were greater than those to bethanechol. In addition, the response to phenylephrine was generally greater than that to bethanechol. Phentolamine was a significantly more effective inhibitor of the response of the female bladder neck and urethral strips to FS than of the response of the male strips. The contractile response of all strips to phenylephrine was generally greater than that to bethanechol for both sexes and for both bladder neck and urethral strips. NG-nitro-L-arginine methylester (L-NAME) inhibited totally the field-stimulated relaxation of all strips. Isoproterenol stimulated a slowly developing but significant inhibition of phenylephrine prestimulated contractions. In conclusion, significant differences exist in the magnitude of field-stimulated relaxation between the bladder neck and urethra of both male and female rabbits, and, for all tissues, field-stimulated relaxation could be completely inhibited by pretreatment with L-NAME, an NO synthesis inhibitor.

Animals↗
PubMed1994

The effects of halothane and isoflurane on cerebrocortical microcirculation and autoregulation as assessed by laser-Doppler flowmetry.

The effects of volatile anesthetics on red blood cell flow in the cerebral microcirculation have not been compared. We used laser-Doppler flowmetry, which measures red blood cell flow in the microcirculation to compare the effects of differing concentrations of isoflurane and halothane on cerebrocortical microcirculation. Sprague-Dawley rats were anesthetized with pentobarbital (65 mg/kg intraperitoneally). The animals were tracheotomized, paralyzed, and artificially ventilated. In the first protocol laser-Doppler flow (LDF) was recorded at 0.5, 1, 1.5, and 2 minimum alveolar anesthetic concentration (MAC) halothane or isoflurane, with blood pressure controlled by intravenous phenylephrine infusion (0.5-5 micrograms.kg-1.min-1). In the second protocol the effects of 0.5 and 1.5 MAC halothane and isoflurane on LDF changes in response to changes in mean arterial blood pressure (MABP) were compared. MABP was increased by phenylephrine infusion and decreased by hemorrhage. LDF increased with each 0.5 MAC increase in halothane and isoflurane concentration (P < 0.05). LDF was greater at 1.5 and 2 MAC isoflurane than at equi-MAC halothane (P < 0.01). Autoregulation of LDF was present but attenuated at MABP of 60-140 mm Hg at low halothane and isoflurane concentrations. LDF was increased at 1.5 MAC vs 0.5 MAC for both drugs (P < 0.01). The autoregulation coefficients (percent LDF change/mm Hg MABP change) were 0.41 +/- 0.10, 0.42 +/- 0.07, 0.27 +/- 0.04, and 0.20 +/- 0.05 at 0.5 MAC halothane, 0.5 MAC isoflurane, 1.5 MAC halothane, and 1.5 MAC isoflurane, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Clues to patient dissatisfaction with conscious sedation for colonoscopy.

OBJECTIVES: Most colonoscopy is performed using conscious sedation to facilitate the procedure. However, little is known about which patients are dissatisfied with sedation and why. The goal of this study was to examine whether certain patient- and procedure-specific variables are associated with patient dissatisfaction. METHODS: A total of 403 consecutive outpatients underwent colonoscopy during a 4-month study period. Of 342 patients who met entrance criteria, 328 completed the initial questionnaire and were enrolled. Subjects received standard conscious sedation; after colonoscopy, the primary endoscopist and nurse recorded the level of sedation as adequate or inadequate. Twenty-four to 72 hr after the procedure, an independent observer contacted the subjects by telephone and asked whether they were satisfied with the level of sedation achieved during the colonoscopy. A number of patient- (age, gender, anxiety level, and educational background) and procedure-specific variables (waiting time and procedure type, difficulty, and duration) were analyzed to determine their association with patient dissatisfaction. RESULTS: Forty-eight patients (15%) were dissatisfied with sedation. Univariable analysis showed that females, anxiety, higher education (at least 1 yr of college), procedure duration > or = 60 min, and procedure difficulty were all associated with the dissatisfaction with sedation (p < 0.05). Multivariable analysis revealed that only higher education (p = 0.009) and longer procedure duration (p = 0.018) were associated with patient dissatisfaction. CONCLUSIONS: Highly educated patients and those who underwent longer procedures were more likely to be dissatisfied with conscious sedation used for colonoscopy. A thorough discussion of expectations and/or patient-controlled sedation might improve satisfaction with colonoscopy in educated patients. Regular supplementation of sedation, termination of a lengthy procedure with the offer of a further attempt at a later date, and referral to a more experienced endoscopist when appropriate might all improve patient satisfaction with colonoscopy.

Anxiety↗
PubMed1993

Distribution and function of the adrenergic and cholinergic receptors in the fetal calf bladder during mid-gestational age.

Previous studies on the developing fetal bovine bladder demonstrate that compliance is low during early stages of fetal development and increases with fetal age. In addition, the pharmacological response of isolated fetal bovine bladder smooth muscle strips to field stimulation and bethanechol increased in proportion with the gestational age. In the adult bladder (rabbit), the contractile response to autonomic receptor stimulation and the autonomic receptor density showed a parallel gradation in the the bladder between bladder dome and the urethra. The present studies were designed to determine the distribution of the cholinergic and adrenergic receptors in the urinary bladder of the fetal calf at mid-gestational age, and to correlate the receptor density with the magnitude of the response to receptor stimulation. Each bladder body was separated into upper, middle, and lower segments. For the functional studies, circular and longitudinal strips were cut from each bladder segment and stimulated with field stimulation (FS), bethanechol, methoxamine, isoproterenol, and KCl. Autonomic receptor assays were performed using 3H-QNB (muscarinic cholinergic), 3H-DHE (alpha adrenergic), and 3H-DHA (beta adrenergic) as ligands. In general, there were no significant differences in receptor density among the three bladder segments. However, the density of muscarinic receptors was significantly greater than the density of alpha- or beta-adrenergic receptors for all bladder segments. The receptor densities correlated very well with the functional response of isolated bladder strips to the specific autonomic agonists. The contractile response of isolated bladder strips to the specific autonomic agonists. The contractile responses of the strips to FS, bethanechol, and methoxamine were not significantly different among the three different bladder segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗