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Biomedical subjects

C McKinley

Publications and source records attributed to C McKinley.

At least 19 recordsLinked to original sources

The role of telementoring and telerobotic assistance in the provision of laparoscopic colorectal surgery in rural areas.

PURPOSE: The aim of this study was to assess whether telementoring and telerobotic assistance would improve the range and quality of laparoscopic colorectal surgery being performed by community surgeons. METHODS: We present a series of 18 patients who underwent telementored or telerobotically assisted laparoscopic colorectal surgery in two community hospitals between December 2002 and December 2003. Four community surgeons with no formal advanced laparoscopic fellowship were remotely mentored and assisted by an expert surgeon from a tertiary care center. Telementoring was achieved with real-time two-way audio-video communications over bandwidths of 384 kbps-1.2 mbps and included one redo ileocolic resection, two right hemicolectomies, two sigmoid resections, three low anterior resections, one subtotal colectomy, one reversal of a Hartmann operation, and one abdominoperineal resection. A Zeus TS microjoint system (Computer Motion Inc, Santa Barbara CA) was used to provide telepresence for the telerobotically assisted laparoscopic procedures, which included three right hemicolectomies, three sigmoid resections, and one low anterior resection. RESULTS: There were no major intraoperative complications. There were two minor intraoperative complications involving serosal tears of the colon from the robotic graspers. In the telementored cases, there were two postoperative complications requiring reoperation (intra-abdominal bleeding and small bowel obstruction). Two telementored procedures were converted because of the mentee's inability to find the appropriate planes of dissection. One telerobotically assisted procedure was completed laparoscopically by the local surgeon with aid of telementoring because of inadequate robotic arm position. The median length of hospital stay for this series was 4 days. The surgeons considered telementoring useful in all cases (median score 4 out of 5). The use of remote telerobotic assistance was also considered a significant enabling tool. CONCLUSIONS: Telementoring and remote telerobotic assistance are excellent tools for supporting community surgeons and providing patients better access to advanced surgical care.

Abdomen↗

Differences in antigen recognition and cytolytic activity of CD8(+) and CD8(-) T cells that express the same antigen-specific receptor.

CD8(+) and CD8(-) T cell lines expressing the same antigen-specific receptor [the 2C T cell receptor (TCR)] were compared for ability to bind soluble peptide-MHC and to lyse target cells. The 2C TCR on CD8(-) cells bound a syngeneic MHC (K(b+))-peptide complex 10-100 times less well than the same TCR on CD8(+) cells, and the CD8(-) 2C cells lysed target cells presenting this complex very poorly. Surprisingly, however, the CD8(-) cells differed little from CD8(+) cells in ability to bind an allogeneic MHC (L(d+))-peptide complex and to lyse target cells presenting this complex. The CD8(+)/CD8(-) difference provided an opportunity to estimate how long TCR engagements with peptide-MHC have to persist to initiate the cytolytic T cell response.

Animals↗

Comparison of nicardipine versus placebo to control hemodynamic responses during emergence and extubation.

OBJECTIVE: To compare 2 different doses of intravenous nicardipine versus placebo to control heart rate and blood pressure responses to emergence and extubation. DESIGN: Prospective, randomized, double-blind, placebo-controlled. SETTING: University hospital, single-institutional. PARTICIPANTS: Forty-five American Society of Anesthesiologists (ASA) class I through III adult patients. INTERVENTIONS: General endotracheal anesthesia was with oxygen and isoflurane and muscle relaxation. At the end of surgery, with at least 2 twitches present by nerve stimulator and end-tidal isoflurane <0.4%, reversal was accomplished with neostigmine and glycopyrrolate. Two minutes post-reversal, the study drug (nicardipine, 0.015 mg/kg; nicardipine, 0.03 mg/kg; or a saline placebo) was given. Heart rate and blood pressure were measured for every minute up to 10 minutes and at 15 minutes postreversal. MEASUREMENTS AND MAIN RESULTS: There were no significant differences among groups in age, gender, ASA class, weight, or heart rate. The nicardipine groups, 0.015 and 0.03 mg/kg, had lower blood pressure values than the placebo group. There was a significant difference in blood pressure among groups, with greater and more consistent attenuation of blood pressure occurring with the larger nicardipine dose. There were no episodes of hypotension or adverse events. CONCLUSIONS: Compared with placebo, both nicardipine doses attenuated blood pressure but not heart rate responses during emergence and extubation. Greater blood pressure control occurred with the larger nicardipine dose of 0.03 mg/kg.

Adult↗

Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss.

OBJECTIVES: Orlistat, an intestinal lipase inhibitor, has recently been approved by the US Food and Drug Administration for treatment of obesity. The effects of orlistat on hepatobiliary function have not been previously defined. A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet. METHODS: A total of 23 obese (BMI 30-41 kg/m2) subjects were randomized to a double blind t.i.d. treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet (1200-1500 kcal/day). The study was designed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat. Cholesterol saturation, bile composition, and gallbladder motility were measured. RESULTS: At the end of the treatment period, mean weight loss of 3.8 kg was achieved in the orlistat group (vs 2.3 kg with placebo, p = NS). Total bile acid concentration decreased significantly with placebo (-18.57 +/- 6.99 mmol/L; 95% CI = -32.26 to -4.87), but not with orlistat. Biliary phospholipid concentration decreased significantly with placebo (-4.38 +/- 1.91 mmol/L; 95% CI = -8.13 to -0.64) but not with orlistat. Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups. Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group. CONCLUSIONS: Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids. Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function. We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat.

Adult↗

Postmenopausal estrogen therapy selectively stimulates hepatic enlargement in women with autosomal dominant polycystic kidney disease.

The goal of this study was to determine whether use of postmenopausal estrogen (Premarin, Wyeth-Ayerst, Philadelphia, PA) in women with autosomal dominant polycystic kidney disease (ADPKD) increases liver, hepatic cyst, or kidney volume. We also determined whether clinical symptoms correlated with the volume of either the liver or kidneys. Eight women off estrogen (control, C) and 11 others on estrogen (Premarin, E) were studied basally and after 1 year. The two groups were similar in age, weight, age at menarche, and gravida. Volumes of total liver, hepatic cysts, hepatic parenchyma, and total kidney were measured by a validated computed tomography (CT) technique. Estrogen treatment was associated with a selective increase in total liver volume (E vs. C: delta = 7% +/- 12% vs. -2% +/- 8%, P < .03) and no change in kidney volume (E vs. C: delta = 0% +/- 6% vs. -2% +/- 6%, P = NS). Symptoms were common, regardless of estrogen treatment (abdominal pain 60%, shortness of breath 40%, or both 35%). Patients with symptoms of abdominal pain and shortness of breath had significantly increased hepatic volumes (P < .03) but similar kidney volume compared with patients without symptoms. We conclude that estrogen treatment of postmenopausal ADPKD women is associated with selective liver enlargement and that abdominal symptoms in ADPKD patients may be because of extensive hepatic cystic disease.

Antipyrine↗

Quantitative liver function tests define the functional severity of liver disease in early-stage cirrhosis.

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.

Administration, Oral↗

Possible idiopathic thrombocytopenic purpura associated with natural alpha interferon therapy for chronic hepatitis C infection.

We report the case of a 41-yr-old male with chronic hepatitis C who developed severe thrombocytopenia on interferon alfa-n3 therapy. The patient was enrolled in a multi-center trial of interferon alfa-n3 in the treatment of chronic hepatitis C. In the 10th wk of therapy, he presented with gingival bleeding and a petechial rash. Complete blood count demonstrated WBC 5,800/mm3. Hgb 16.3 g/dl, Hct 45.5%, and platelet count 6,000/mm3. Interferon was withdrawn, and he was admitted to intensive care and was treated with platelet transfusion, intravenous steroids, and intravenous immunoglobulin. His platelet counts returned to 157,000/mm3 in 7 days and remained normal on a tapering dose of prednisone. Bone marrow biopsy/aspirate demonstrated numerous megakaryocytes. Stored plasma was negative for development of specific high-titer anti-platelet antibody. We suggest that the clinical findings and response to therapy are consistent with interferon-induced idiopathic thrombocytopenic purpura.

Adult↗

The effect of dose of mifepristone and gestation on the efficacy of medical abortion with mifepristone and misoprostol.

Although it has been demonstrated that a combination of mifepristone and a prostaglandin is an effective method of inducing abortion in early pregnancy, the optimum dose of the antigestogen is unknown. Women (n = 220) requesting abortion in early pregnancy (< or = 63 days amenorrhoea) were randomized to receive a single dose of either 600 or 200 mg mifepristone followed 48 h later by a single dose of 600 micrograms misoprostol by mouth. The percentage of women who had a complete abortion (93.6% confidence interval 90.4-95.5%) was identical in the two groups. There was no significant difference in the number of women who passed the fetus within 4 h of receiving the prostaglandin (64 versus 74%), the days of bleeding (14.6 +/- 1.1 versus 15.3 +/- 0.9) nor in the onset of the next period (39.7 +/- 1.3 versus 36.7 +/- 1.3) respectively between the groups receiving 200 or 600 mg mifepristone. However, the complete abortion rate was significantly higher in women < or = 49 days compared to women 50-63 days amenorrhoea (97.5 versus 89.1% respectively; P < 0.02). There was no difference in any of the other parameters at different weeks of gestation. We conclude: (i) that the recommended dose of mifepristone could be reduced from 600 to 200 mg without loss of clinical efficacy, (ii) that the combination of mifepristone and 600 micrograms misoprostol is a highly effective alternative to vacuum aspiration for inducing abortion in women < 50 days amenorrhoea and (iii) at gestation > 56 days, this combination may result in too many incomplete abortions to be clinically acceptable.

Abortion, Induced↗

Accelerated gallstone dissolution in methyl tert-butyl ether by sonication. An in vitro study.

OBJECTIVES: The authors tested the effect of 195 KHz therapeutic ultrasound energy on gallstone dissolution in concert with methyl tert-butyl ether (MTBE) in vitro. METHODS: Sixteen sets of three gallstones matched for weight and appearance were selected from 16 surgically resected human gallbladders. One stone from each set was analyzed for its density pattern by computed tomography (CT) and biochemically for cholesterol content. Based on CT appearance, the stones were classified into eight noncalcified, four partially calcified, and four heavily calcified sets. The three stones were subjected to dissolution with MTBE: one with simultaneous sonication via an experimental ultrasound unit, one with manual stirring, and one acted as control without added treatment. RESULTS: Sonication reduced the dissolution time of noncalcified stones by 96% (range, 94%-98%; standard deviation [SD], 2%) relative to controls, and it was three to four times more effective than manual stirring. It was similarly effective in helping to dissolve partially calcified stones, but not heavily calcified stones. CONCLUSIONS: This study demonstrates the positive effect of sonication in accelerating gallstone dissolution with MTBE in vitro for stones without heavy calcification.

Cholelithiasis↗

Effects of psyllium hydrophilic mucilloid on LDL-cholesterol and bile acid synthesis in hypercholesterolemic men.

The goal of the current study was to determine the mechanism of the hypocholesterolemic effect of psyllium using a randomized, double-blind, crossover design. Twenty males (age 44 +/- 4 yr, weight 79 +/- 10 kg) with moderate hypercholesterolemia (total 265 +/- 17 mg/dl, low density lipoprotein (LDL) 184 +/- 15 mg/dl) were studied at baseline (B) and after randomization to receive a 40-day course of 15 g/day of either psyllium (Ps) or placebo (Pl) (cellulose). After a washout period (11 +/- 2 days), subjects were crossed over to the other fiber treatment for an additional 40 days and restudied. Intestinal cholesterol absorption, cholesterol synthesis in isolated peripheral blood mononuclear cells, bile acid kinetics, gallbladder motility, and intestinal transit were measured at each study period. Psyllium lowered LDL cholesterol (x:184 (B), 169 (Ps), and 179 (Pl) mg/dl; Ps vs. B,Pl: P less than 0.004, P less than 0.02), decreased relative cholesterol absorption (x:51 (B), 45 (Ps), and 49 (Pl) %; Ps vs. B,Pl: P less than 0.03, P less than 0.03), did not alter absolute cholesterol absorption, and increased the fractional turnover of both chenodeoxycholic acid (x:0.176 (B), 0.203 (Ps), and 0.170 (Pl) day-1; Ps vs. B,Pl: P less than 0.0001, P less than 0.01) and cholic acid (x:0.303 (B), 0.411 (Ps), and 0.301 (Pl) d-1; Ps vs. B, Pl: P less than 0.006, P less than 0.002). Bile acid synthesis increased in subjects whose LDL cholesterol was lowered by more than 10% (Ps vs. B: 1304 +/- 489 vs 992 +/- 307 mumol/day, P less than 0.006; Ps vs. PI: 1304 +/- 489 vs. 914 +/- 321 mumol/day, P less than 0.0002). We conclude that psyllium lowers LDL cholesterol primarily via stimulation of bile acid synthesis.

Adult↗

Mechanisms of gallstone formation in women. Effects of exogenous estrogen (Premarin) and dietary cholesterol on hepatic lipid metabolism.

Our aim was to define mechanisms whereby conjugated estrogens (Premarin, exogenous estrogen; Ayerst Laboratories, New York) increase the risk of developing cholesterol gallstones and to determine the role, if any, of dietary cholesterol. We studied gallbladder motor function, biliary lipid composition and secretion, cholesterol absorption, cholesterol synthesis and esterification by peripheral blood mononuclear cells, the clearance of chylomicron remnants, and bile acid kinetics in 29 anovulatory women. 13 were studied on both a low (443 +/- 119 mumol/d) and high (2,021 +/- 262 mumol/d) cholesterol diet. Premarin increased the lithogenic index of bile (P less than 0.05), increased biliary cholesterol secretion (P less than 0.005), lowered chenodeoxycholate (CDCA) pool (P less than 0.001) and synthesis (P less than 0.05), altered biliary bile acid composition [( CA + DCA]/CDCA increases, P less than 0.005), stimulated cholesterol esterification (P less than 0.03), and enhanced the clearance of chylomicron remnants (P = 0.07). Increases in dietary cholesterol stimulated the biliary secretion of cholesterol (P = 0.07), bile acid (P less than 0.05), phospholipid (P = 0.07), and as a result, did not alter lithogenic index. The reduction in CDCA pool and synthesis by Premarin was reversed by increasing dietary cholesterol. Off Premarin, only 24% of the increase in cholesterol entering the body in the diet was recovered as biliary cholesterol or newly synthesized bile acid. On Premarin, 68% of this increase in cholesterol was recovered as these biliary lipids. We conclude that Premarin increases biliary cholesterol by enhancing hepatic lipoprotein uptake and inhibiting bile acid synthesis. These actions of Premarin divert dietary cholesterol into bile.

Adult↗

Blood-borne collagenous debris complexes with plasma fibronectin after thermal injury.

Plasma fibronectin augments the clearance of blood-borne foreign and effete complexes by mononuclear phagocytes. The release of a "gelatin-like" ligand into plasma after thermal injury has been reported. We quantified the release of this collagenous debris from thermally injured skin, and its potential interaction with soluble fibronectin in plasma using anesthetized rats. Collagen-like material debris in the plasma was detected by assay of hydroxyproline. Fibronectin was measured by a double antibody enzyme-linked immunosorbent assay (ELISA) technique. Over a 24-hour postburn interval, plasma hydroxyproline increased from 6.7 +/- 0.6 micrograms/mL to a maximum of 19.0 +/- 3.3 micrograms/mL at 60 minutes postburn, and normalized by 6 hours. A direct correlation existed between the magnitude of burn injury and the increase in plasma hydroxyproline. In parallel, plasma fibronectin declined over a 15-minute to 2-hour period postburn, and normalized by 3 to 4 hours with rebound hyperfibronectinemia observed at 24 hours. The elevation in total plasma hydroxyproline was not due to an increase in plasma Clq (zero time, 26.2 +/- 1.4 micrograms/mL; 60 minutes, 23.9 +/- 1.1 micrograms/mL). Tracer studies with 125I-fibronectin showed that the acute decline of plasma fibronectin was due to its uptake by the liver and binding to sites of tissue injury. Total hydroxyproline in extracts of burn skin, used as an index of soluble collagenous material, rose from 15 +/- 3.3 micrograms/g skin at zero time to 129.3 +/- 43.7 micrograms/g skin by 5 minutes postburn, with a decline to 38 +/- 22 micrograms/g skin by 24 hours. The formation of circulating fibronectin-gelatin complexes in vivo was documented by cross-immunoelectrophoresis coupled with autoradiography using 125I-gelatin as a model ligand. Thus, collagenous tissue debris from burned skin may enter the plasma after thermal injury and directly complexes with soluble fibronectin before hepatic phagocytic clearance.

Animals↗

A tri-institutional comparison of tissue and mechanical values using a patient-oriented definition of "treatment failure".

Selection of valve type for predominant usage is obscured by limiting the analysis to prosthesis-related rather than patient-oriented failure modes. In this report, "treatment failure" is defined as a valve-related death or permanent patient disability; successful reoperations are excluded, and emboli with permanent residua are included. Results with the Starr-Edwards Silastic ball valve (Oregon) and the Hancock (Stanford) and Carpentier-Edwards (Vancouver) porcine valves are compared using this new definition of treatment failure. Evaluated according to structural failure, the mechanical valve is superior to the tissue valve, and using the Stanford definition of valve failure, it becomes so between 5 and 10 years. Using treatment failure, tissue valves are superior at 5 years; at 10 years in the aortic position, the results are comparable; and in the mitral position at 8 to 10 years, tissue valves show a continued but small advantage.

Aortic Valve↗

Gallbladder and small intestinal regulation of biliary lipid secretion during intraduodenal infusion of standard stimuli.

The gallbladder and small intestine are reservoirs for the bile acid pool during its enterohepatic circulation and, as such, may regulate biliary secretion of bile acid. During studies of biliary bile acid secretion, a stimulus to gallbladder contraction is continuously infused into the duodenum. Under these conditions, it is assumed that the gallbladder is tonically contracted and that the rate of bile acid secretion into the duodenum equals the hepatic bile acid secretion rate. However, secretion rates vary by as much as 100%, depending upon which of two standard stimuli is used. Therefore, we studied the role of gallbladder emptying and small intestinal transit in determining biliary lipid secretion rate and composition during infusion of these stimuli in five healthy subjects. Each subject was studied with a liquid formula containing 40% of calories as fat, and with an amino acid solution for 10 h. Bile acid, phospholipid, cholesterol, and markers were measured in duodenal bile and hourly secretion rates were calculated by marker dilution technique. Real-time gallbladder sonographs and serum pancreatic polypeptide levels were obtained every 30 min. Small bowel transit time was estimated levels were obtained every 30 min. Small bowel transit time was estimated by the breath hydrogen response after giving lactulose intraduodenally.During liquid formula infusion, gallbladder emptying was more complete, small intestinal transit was faster, and pancreatic polypeptide levels were higher. Secretion rates of all lipids were greater and molar percent cholesterol was lower. For the combined data from both infusions, the secretory relationships of cholesterol to bile acid, cholesterol to phospholipid, and phospholipid to bile acid were curvilinear. We conclude that more complete gallbladder emptying and faster intestinal transit increase the enterohepatic cycling of bile acids and lower the molar percent cholesterol of bile. Some of the fluctuation observed in biliary lipid secretion rates, especially during amino acid infusion, is due to gallbladder refilling and emptying.

Adult↗

Gallbladder function in the human female: effect of the ovulatory cycle, pregnancy, and contraceptive steroids.

We have previously shown that in pregnancy fasting gallbladder volume is increased and emptying after a small volume liquid meal is incomplete. In this study we measured gallbladder volume throughout day and night in healthy women ingesting regular meals. Pregnant women, postpartum women, contraceptive-steroid users, and controls in both phases of the ovulatory cycle were studied. After an overnight fast gallbladder volume was measured by realtime ultrasonography in the fasting state and every 5-10 min for 90 min after breakfast. Residual volume was the lowest volume achieved and the rate constant of gallbladder emptying was calculated from the ln/linear regression of gallbladder volume vs. time. Gallbladder volume was also measured hourly from 11 AM to midnight while subjects ate regular, standard meals, allowing the determination of an average hourly volume. There was no effect of phase of the ovulatory cycle on any measure of gallbladder function. Fasting, residual, and average hourly volume were increased in all trimesters of pregnancy, but tended to return to normal in the postpartum period. Women taking contraceptive steroids had an increased fasting volume. Two distinct rates of emptying after breakfast, an early and a late one, were identified. The early rate was the same in all groups. Pregnant women had a slower late rate of emptying, but women taking contraceptive steroids had emptying rates similar to controls. Retention of bile in the gallbladder may be one reason for the increased risk of cholesterol cholelithiasis in pregnant women and in those taking contraceptive steroids.

Adult↗

Biliary lipids, bile acids, and gallbladder function in the human female: effects of contraceptive steroids.

Individuals who take contraceptive steroids or estrogens are at increased risk of developing cholesterol gallstones. The mechanisms of the increased stone formation are incompletely understood. In this study we report biliary lipid composition and secretion, bile acid composition and kinetics, and gallbladder function in a group of healthy, nonobese women taking a contraceptive steroid preparation. A comparable group of healthy women served as controls. Bile-rich duodenal fluid was obtained after stimulation of gallbladder contraction; bile acid, phospholipid, and cholesterol concentrations were determined. Biliary lipid secretion rate was measured by the marker perfusion technique. Bile acid distribution was determined by gas-liquid chromatography. The pool size, FTR, and synthesis rate of each bile acid were measured by using CA and CDCA labeled with the stable isotope of carbon, 13C. In some of the subjects gallbladder storage and emptying were measured during the kinetic study, by real-time ultrasonography. Contraceptive steroid use was associated with a significant increase in biliary cholesterol saturation and in the lithogenic index of bile. The rate of cholesterol secretion in the contraceptive steroid group was 50% greater than in the control (p much less than 0.001) and the rate of bile acid secretion was reduced (p less than 0.02). The total bile acid pool size was significantly increased by contraceptive steroids. The major increase occurred in the CA pool (p less than 0.04). The daily rate of enterohepatic cycles of the bile acid pool was decreased by contraceptive steroids from 6.6 to 4.3 (p less than 0.01). The only effect of contraceptive steroids on gallbladder function was a slower emptying rate in response to intraduodenal amino acid infusion. No index of gallbladder function correlated significantly with any parameter of bile acid kinetics in this small group of subjects. The findings confirm the lithogenic effect of contraceptive steroids and indicate that its causes are an increase in cholesterol secretion and a decrease in bile acid secretion.

Bile↗