[Radiomics nomogram of MR: a prediction of cervical lymph node metastasis in laryngeal cancer].

Objective: To establish and validate a radiomics nomogram based on MR for predicting cervical lymph node metastasis in laryngeal cancer. Methods: One hundred and seventeen patients with laryngeal cancer who underwent MR examinations and received open surgery and neck dissection between January 2016 and December 2019 were included in this study. All patients were randomly divided into a training cohort (n=89) and test cohort (n=28) using computer-generated random numbers. Clinical characteristics and MR were collected. Radiological features were extracted from the MR images. Enhanced T1 and T2WI were selected for radiomics analysis, and the volume of interest was manually segmented from the Huiyihuiying radiomics cloud platform. The variance analysis (ANOVA) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to reduce the dimensionality of the radiomics features in the training cohort. Then, a radiomic signature was established. The clinical risk factors were screened by using ANOVA and multivariate logistic regression. A nomogram was generated using clinical risk factors and the radiomic signature. The calibration curve and receiver operator characteristic (ROC) curve were used to confirm the nomogram's performance in the training and test sets. The clinical usefulness of the nomogram was evaluated by decision curve analysis (DCA). Furthermore, a testing cohort was used to validate the model. Results: The radiomics signature consisted of 21 features, and the nomogram model included the radiomics signature and the MR-reported lymph node status. The model showed good calibration and discrimination. The model yielded areas under the ROC curve (AUC) in the training cohort, specificity, and sensitivity of 0.930, 0.930 and 0.875. In the test cohort, the model yielded AUC, specificity and sensitivity of 0.883, 0.889 and 0.800. DCA indicated that the nomogram model was clinically useful. Conclusion: The MR-based radiomics nomogram model may be used to predict cervical lymph node metastasis of laryngeal cancer preoperatively. MR-based radiomics could serve as a potential tool to help clinicians make an optimal clinical decision.

Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway.

BACKGROUND: Ketamine is widely used as an i.v. anaesthetic agent and as a drug of abuse. Hepatocytes contribute to the metabolism of endogenous and exogenous substances. This study evaluated the toxic effects of S-(+)-ketamine and possible mechanisms using human hepatoma HepG2 cells as the experimental model. METHODS: HepG2 cells were exposed to S-(+)-ketamine. Cell viability and the release of lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GPT) were measured to determine the toxicity of S-(+)-ketamine to HepG2 cells. Cell morphology, DNA fragmentation, and apoptotic cells were analysed to evaluate the mechanism of S-(+)-ketamine-induced cell death. Amounts of Bax, an apoptotic protein, and cytochrome c in the cytoplasm or mitochondria were quantified by immunoblotting. Cellular adenosine triphosphate levels were analysed using a bioluminescence assay. Caspases-3, -9, and -6 were measured fluorometrically. RESULTS: Exposure of HepG2 cells to S-(+)-ketamine increased the release of LDH and GPT, but decreased cell viability (all P<0.01). S-(+)-Ketamine time-dependently caused shrinkage of HepG2 cells. Exposure to S-(+)-ketamine led to significant DNA fragmentation and cell apoptosis (P=0.003 and 0.002). S-(+)-Ketamine increased translocation of Bax from the cytoplasm to mitochondria, but decreased the mitochondrial membrane potential and cellular adenosine triphosphate levels (all P<0.01). Sequentially, cytosolic cytochrome c levels and activities of caspases-9, -3, and -6 were augmented after S-(+)-ketamine administration (all P<0.001). Z-VEID-FMK, an inhibitor of caspase-6, alleviated the S-(+)-ketamine-induced augmentation of caspase-6 activity, DNA fragmentation, and cell apoptosis (all P<0.001). CONCLUSIONS: This study shows that S-(+)-ketamine can induce apoptotic insults to human HepG2 cells via a Bax-mitochondria-caspase protease pathway. Thus, we suggest that S-(+)-ketamine at a clinically relevant or an abused concentration may induce liver dysfunction possibly due to its toxicity to hepatocytes.

Preparation and characterization of polyoxometalate-modified poly(vinyl alcohol)/polyethyleneimine hybrids as a chemical and biological self-detoxifying material.

Nanohybrid membranes based on the Keggin-type polyoxometalate (POM) H5PV2Mo10O40 and a poly(vinyl alcohol)/polyethyleneimine (PVA/PEI) blend were prepared as a chemical and biological protective material. The objective of the study was to develop and evaluate permeable membranes (PVA/PEI) impregnated with reactive nanoparticulates (POM) that can protect against simulants of chemical and biological warfare agents. The physical properties of the PVA/PEI-POM hybrids were examined using SEM, TEM, TGA, and UV-Vis spectroscopy, the results of which indicated that the POM was incorporated in the PVA/PEI matrix after impregnation. The redox properties against 2-chloroethyl-ethyl sulfide (CEES) were investigated based on significant color changes and UV absorption in the POM upon reduction by CEES. The antibacterial effects of the PVA/PEI-POM hybrids were assessed by the zone of inhibition, minimum inhibitory concentration (MIC), and plate-counting methods. The results of this study showed that PVA/PEI-POM hybrids that act against simulants of chemical and biological weapons while retaining their ability to transmit moisture vapor could be obtained.

Differential regulation of renal phospholipase C isoforms by catecholamines.

Dopamine and D1 agonists and NE all increase phosphatidyl inositol-specific phospholipase C (PLC) activity, but whereas dopamine produces a natriuresis, NE has an antinatriuretic effect. To determine if catecholamines differentially regulate the expression of PLC isoforms, we infused fenoldopam, a D1 agonist, or pramipexole, a D1/D2 agonist, intravenously or infused fenoldopam or NE into the renal artery of anesthetized rats. After 3-4 h of infusion, when the expected natriuresis (fenoldopam or pramipexole) or antinatriuresis (NE) occurred, the kidneys were removed for analysis of PLC isoform protein expression activity. Western blot analysis revealed that in renal cortical membranes, fenoldopam and pramipexole increased expression of PLC beta 1 and decreased expression of PLC gamma 1; PLC delta was unchanged. In the cytosol, pramipexole and fenoldopam increased expression of both PLC beta 1 and PLC gamma 1. No effects were noted in the medulla. A preferential D1 antagonist, SKF 83742, which by itself had no effect, blocked the effects of pramipexole, thus confirming the involvement of the D1 receptor. In contrast, NE also increased PLC beta 1 but did not affect PLC gamma 1 protein expression in membranes. The changes in PLC isoform expression were accompanied by similar changes in PLC isoform activity. These studies demonstrate for the first time differential regulation of PLC isoforms by catecholamines.

Dopamine D1 receptor and protein kinase C isoforms in spontaneously hypertensive rats.

-Dopamine, via D1-like receptors, stimulates the activity of both protein kinase A (PKA) and protein kinase C (PKC), which results in inhibition of renal sodium transport. Since D1-like receptors differentially regulate sodium transport in normotensive and hypertensive rats, they may also differentially regulate PKC expression in these rat strains. Thus, 2 different D1-like agonists (fenoldopam or SKF 38393) were infused into the renal artery of anesthetized normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (n=5 to 6/drug/strain). Ten or 60 minutes after starting the D1-like agonist infusion, both the infused kidney and the noninfused kidney that served as control were prepared for analysis. The D1-like agonists produced a greater diuresis and natriuresis and inhibited Na+,K+-ATPase activity in proximal tubule (PT) and medullary thick ascending limb (mTAL) to a greater extent in WKY (Delta20+/-1%) than in SHR (Delta7+/-1%, P<0.001). D1-like agonists had no effect on PKC-alpha or PKC-lambda expression in either membrane or cytosol but increased PKC-theta expression in PT in both WKY and SHR at 10 minutes but not at 60 minutes. However, membranous PKC-delta expression in PT and mTAL decreased in WKY but increased in SHR with either 10 or 60 minutes of D1-like agonist infusion. D1-like agonists also decreased membranous PKC-zeta expression in PT and mTAL in WKY but increased it in PT but not in mTAL in SHR. We conclude that there is differential regulation of PKC isoform expression by D1-like agonists that inhibits membranous PKC-delta and PKC-zeta in WKY but stimulates them in SHR; this effect in SHR is similar to the stimulatory effect of norepinephrine and angiotensin II and may be a mechanism for their differential effects on sodium transport.

Dopamine-1 receptor coupling defect in renal proximal tubule cells in hypertension.

The ability of the dopamine-1 (D1)-like receptor to stimulate adenylyl cyclase (AC) and phospholipase C (PLC), inhibit sodium transport in the renal proximal tubule (RPT), and produce natriuresis is attenuated in several rat models of hypertension. Since the inhibitory effect of D1-like receptors on RPT sodium transport is also reduced in some patients with essential hypertension, we measured D1-like receptor coupling to AC and PLC in cultures of human RPT cells from normotensive (NT) and hypertensive (HT) subjects. Basal cAMP concentrations were the same in NT (n=6) and HT (n=4). However, the D1-like receptor agonist fenoldopam increased cAMP production to a greater extent in NT (maximum response=67+/-1%) than in HT (maximum response=17+/-5%), with a potency ratio of 105. Dopamine also increased cAMP production to a greater extent in NT (32+/-3%) than in HT (14+/-3%). The fenoldopam-mediated increase in cAMP production was blocked by SCH23390 (a D1-like receptor antagonist) and by antisense D1 oligonucleotides in both HT and NT, indicating action at the D1 receptor. The stimulatory effects of forskolin and parathyroid hormone-related protein of cAMP accumulation were not statistically different in NT and HT, indicating receptor specificity and an intact G-protein/AC pathway. The fenoldopam-stimulated PLC activity was not impaired in HT, and the primary sequence and expression of the D1 receptor were the same in NT and HT. However, D1 receptor serine phosphorylation in the basal state was greater in HT than in NT and was not responsive to fenoldopam stimulation in HT. These studies demonstrate the expression of D1 receptors in human RPT cells in culture. The uncoupling of the D1 receptor in both rats (previously described) and humans (described here) suggests that this mechanism may be involved in the pathogenesis of hypertension; the uncoupling may be due to ligand-independent phosphorylation of the D1 receptor in hypertension.

Dopamine D1 receptor regulation of phospholipase C.

Dopamine is an endogenous catecholamine which exerts its actions by occupancy of specific receptors. Dopamine receptors are classified into two main groups: the two cloned D1-like receptors (D1A and D1B in rats; D1B is also known as D5 in humans) are linked to stimulation of adenylyl cyclase, while the three cloned D2-like receptors (D2 or D2A, D3 or D2B, D4 or D2C) are linked to inhibition of adenylyl cyclase. All these dopamine receptors originally cloned from the brain are expressed in tissues outside the central nervous system including the kidney. Dopamine regulates many cellular activities, including transmembrane ion transport. Activation of D1-like receptor decreases sodium transport by cAMP dependent and cAMP independent mechanisms. Dopamine, via D1-like receptors, may inhibit Na+/H+ exchange activity in renal brush border membranes by a cAMP independent/Gs alpha-linked mechanism. Another cAMP independent pathway of sodium transport inhibition is mediated by phospholipase C, which has several isoforms (PLC beta, PLC gamma, and PLC delta with several members in each). Catecholamines stimulate expression and activity of phospholipase C isoforms in a concentration, time, and receptor-dependent as well as regional and subcellular compartmental-specific manner. In renal cortical membranes, intrarenal administration of norepinephrine for 3-4 h increases PLC beta expression and activity but has no effect on PLC gamma activity. In contrast, intrarenal administration of a D1 agonist for 3-4 h increases PLC beta 1 but decreases PLC gamma expression and activity.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical experience of laryngeal mask airway combined with continuous intravenous propofol infusion during general anesthesia].

BACKGROUND: Propofol's greatest attributes are its pharmacokinetic properties which result in a rapid, clear emergency and lack of cumulative effects even after prolonged administration. It is a drug of popular choice for the maintenance of general anesthesia. The laryngeal mask airway (LMA), originally described by Dr. Brain is now a good alternative as the airway management technique. Because of its high success rate in securing a clinically acceptable airway in anesthetized patients, LMA has been proposed as a practical airway and conveyer for general anesthesia. This study was designed to observe and evaluate the feasibility of propofol infusion combined with N2O for maintenance of anesthesia, with a LMA as airway and conveyer during general anesthesia. METHODS: Sixty patients, ASA class I-II, aged 15-59 years, were selected for this study. They were scheduled for upper-limb orthopedic surgeries in supine position. No patient was premedicated. Intraoperative monitoring included electrocardiography, pulse oximetry, end-tidal carbon dioxide and automatic non-invasive blood pressure. The agents for induction of anesthesia included atropine 0.01 mg/kg, atracurium 5 mg, fentanyl 2-3 micrograms/kg, 2% lidocaine 1.5-2 mg/kg, propofol 2 mg/kg, and succinylcholine 1-1.5 mg/kg, all of which were given intravenously in sequence. After that laryngeal mask airway (LMA) was inserted. The position of LMA was confirmed by even undulation of chest wall and breathing sound. Anesthesia was then maintained with nitrous oxide in 40% oxygen and continuous propofol infusion. The pumping rate was set to start at 6 mg/kg/h. Muscle relaxation was achieved by intravenous tracrium given intermittently. All patients were mechanically ventilated with a ventilator incorporated to the anesthesia machine. The ventilator was set to give a tidal volume of 8 ml/kg at a rate of 12-14/min. At the end of the operation, the propofol infusion and nitrous oxide were simultaneously discontinued. The effect of muscle relaxant was antagonized by atropine 1.0 mg and neostigmine 2.5 mg intravenously. The LMA was removed while the patient was awake and able to open mouth at request. They were followed 24 h postoperatively for inquiring intraoperative awareness and other complaints. RESULTS: No patient was noted to experience awareness during the intraoperative period. Regarding LMA insertion, success in the first attempt was seen in 55 patients (90.2%). Success in the second attempt was seen in 5 patients (8.2%). Failure was encountered in one patient (1.6%). The average time of emergence was 92 +/- 3.4 min. The average rate of speed of propofol infusion was 6.29 +/- 0.97 mg/kg/h. CONCLUSIONS: The combination of propofol infusion and N2O with laryngeal mask as airway and recovery was a good alternative in administration of general anesthesia.

Magnetic resonance angiographic inflow-sensitive inversion recovery technique for vascular evaluation before liver transplantation.

BACKGROUND: The recipient's hepatic vascular anatomy is essential in living-donor liver transplantation (LDLT). Magnetic resonance angiographic inflow-sensitive inversion recovery (IFIR-MRA) is a new noncontrast technology for vascular evaluation, particularly for those patients with renal function impairment. The purpose of this study was to improve the image quality with different blood suppression inversion time (BSP TI) settings. METHODS: From October 2012 to March 2013, 21 recipient candidates underwent IFIR-MRA with the use of the GE 1.5T-Discovery 450 for LDLT preoperation evaluation with different BSP TI settings. Subjective visualized image quality and depiction of hepatic arteries, portal veins, and inferior vena cava (IVC) were all evaluated on a vessel-to-vessel basis. A paired t test analysis was used to assess the difference in grading scales between the different BSP TI settings in IFIR-MRA. RESULTS: The 21 recipients (4 female, 17 male) had a mean age of 53.43 ± 11.07 years. A significant difference (P < .001) existed in the arterial depiction scores between BSP TI 1,000 ms (3.10 ± 0.70) and BSP TI 1,400 ms (3.57 ± 0.7). There were no significant differences of quality scores in artery (3.71 ± 0.56 vs 3.48 ± 0.60), portal vein (3.57 ± 0.60 vs 3.48 ± 0.51), and IVC (2.71 ± 1.19 vs 2.76 ± 1.09), and no significant differences of depiction scores in portal vein (2.29 ± 0.46 vs 2.48 ± 0.51) and IVC (1.57 ± 0.68 vs 1.62 ± 0.15). CONCLUSIONS: The images with BSP TI 1,400 ms were the most optimal for IFIR noncontrast MRA imaging in LDLT. This new technology can replace traditional contrast-enhanced MRA, especially for patients with renal function impairment.

[Development of visible-light cured FRP denture].

Acrylic denture may be fractured easily because it has a relatively poor resistance to stresses of impact, and the thick acrylic denture base also uncomforted to denture wearers. In this study, for improvement of the mechanical properties, the FRP is applied to the denture base, and try to make a thin denture base. Using the visible light-curing system, the laboratory fabrication time is saved dramatically. To develop the visible light-cured FRP denture base, with various combination of matrix resins and reinforcements, the physical properties of FRP plates were investigated first. From the results of the bending test, hardness test, and manipulation considering, the sateen weave's glasscloth was choose as the reinforcement of the prepreg. The matrix resin of Bis-GMA/UDMA/3G at 48/48/4 wt% was determined. The 3 plies glasscloth included FRP plate is 0.8 mm thickness has the maximum bending strength about 50 kgf/mm2, which is about 5 times larger than that of acrylic resin. Succeeding the study of above, the FRP denture base was fabricated by using the 0.8 mm thickness 3 plies included prepreg. This repreg is manufactured in sheet form beforehand, which is ease to manipulate at laboratory. By using the visible light curing system, it is only taken 10 min. to make a FRP denture base. The following procedures of fabricating a FRP denture is the same as metalplate denture. The visible-light cured FRP denture has some advantages such as accuracy of fit, ease of fabrication and manipulation, and only 0.8 mm thickness but has superior strength.

A comparative study of patient-controlled epidural fentanyl and single dose epidural morphine for post-caesarean analgesia.

In a prospective, randomized, double-blinded study, 23 patients who had undergone Caesarean delivery under epidural anaesthesia were assessed to evaluate the effectiveness of patient-controlled epidural analgesia (PCEA) with fentanyl compared with a single dose of epidural morphine for postoperative analgesia. Group A (n = 11) received epidural fentanyl 100 micrograms intraoperatively then self-administered a maximum of two epidural fentanyl boluses 50 micrograms (10 micrograms.ml-1) with a lockout period of five minutes for a maximum of two doses per hour. Group B (n = 11) received a single bolus of epidural morphine 3 mg (0.5 mg.ml-1) intraoperatively and received the same instructions as Group A but had their PCA devices filled with 0.9% NaCl. Patients were assessed up to 24 hr for pain, satisfaction with pain relief, nausea and pruritus using visual analogue scales (VAS). The treatments for inadequate analgesia, nausea and pruritus as well as time to first independent ambulation were recorded. The ventilatory response to carbon dioxide challenge was measured at four and eight hours. Pain relief, satisfaction with pain relief, and the use of supplemental analgesics were similar in both groups. The mean 24 hr dose of epidural fentanyl used by group A patients was 680 micrograms. Pruritus was less common in Group A patients at the 8 and 24 hr observation periods (P < 0.0125). Both groups experienced the same degree of nausea and clinically unimportant respiratory depression. We conclude that PCEA with fentanyl provides analgesia equal to a single dose of epidural morphine and may be suitable for patients who have experienced considerable pruritus after epidural morphine administration.

Pulmonary artery pressures with tension pneumothorax.

Five hours following an uneventful coronary artery bypass graft operation, an otherwise healthy 54-yr-old man developed a pneumothorax while his lungs were being ventilated in the recovery room. Neither arterial blood gas analysis, ventilatory variables, nor clinical examination had suggested this diagnosis, which was made subsequent to a chest radiograph taken as part of the assessment of hypotension. At the same time, the waveform of the pressure tracing from his pulmonary artery catheter changed inexplicably while attempting balloon inflation as part of the assessment of the hypotensive episode. In retrospect, the changes in the pressure tracing most likely were due to alterations in the pulmonary vasculature associated with the pneumothorax. These changes can be explained in terms of a well-known physiological model. If such changes are encountered in similar circumstances, a tension pneumothorax should be suspected.

Rates of removal and degradation of chylomicron remnants by isolated perfused rat liver.

Chylomicron remnants are removed intact by isolated perfused rat livers and their lipid components are metabolized by the liver (Biochim. Biophys. Acta 488: 464, 1977). The present study provides quantitative information regarding these processes. When the lipoprotein concentration of the perfusate was constant, the removal of chylomicron remnants increases lineraly for 17 min. The rate of remnant removal was a hyperbolic function of the perfusate's remnant concentration. The removal rate had aV max of 28microgram cholesterol per g liver per min and an apparent Km of 64 microgram cholesterol per ml perfusate. Feeding the liver donors a diet containing 1% cholesterol or 4% cholesterol and 1% cholic acid failed to alter the hepatic removal rate. The cholesteryl ester removed from the remnants was hydrolyzed at a rate that was a small fraction of the removal rate (about 0.5% of removed cholesteryl ester per min). The rate of cholesteryl ester hydrolysis did not appear to approach saturation in the range studied. Studies of the lysosomal cholesteryl ester hydrolase suggested that this enzyme was not responsible for limiting the initial rate of hydrolysis, raising the possibility that the degradation rate is determined by the movement of the removed remnant to the site of hydrolysis.

[Development of denture base resin. 2. Manufacturing of visible-light cured prepreg and physical properties of FRP].

To develop the visible light-cured FRP denture base, we investigated the physical properties and the warp of FRP plate by using various combinations of matrix resin and reinforcement. From the results of the bending test, hardness test and manipulation processing, the matrix resin of Bis-GMA/UDMA/3 G at 48/48/4 wt% was determined. The sateen weave's glasscloth as the reinforcement of the prepreg was used. The maximum plies included FRP of 0.5 mm, 0.8 and 1.0 mm thickness have the same maximum bending strengths of 45 kgf/mm2, which is about 5 times larger than that of conventional acrylic resin. The warp of these FRP plates were not found.

An in vitro model of fibroblast activity and adhesion formation during flexor tendon healing.

We studied fibroblast activity during tendon healing with an in vitro tendon culture model. Tendons were embedded in a translucent collagen gel matrix whose porous nature permitted free nutrient diffusion, fibroblast migration out of the tendon, and microphotographic documentation of fibroblast activity. Experiments were performed using one or more tendons cultured in the same collagen gel. We identified three zones of fibroblast activity in the gel. Zone I was an area of randomly dispersed cells directly adjacent to the tendon where collagen synthesis and remodeling were probably taking place. In zone II, spindle-shaped fibroblasts were aligned pointing away from the cut tendon end forming a sunburst-like aggregate of cells. Zone II fibroblasts were responsible for formation of migration trails by exerting a mechanical force on the collagen matrix, which was evident as a local gel contraction. Zone III was the leading edge of the sunburst populated by the fastest moving fibroblasts, which responded to guidance by other cut tendon ends. We speculate that the collagen gel used in the culture system may help maintain a chemotactic concentration gradient that allows fibroblasts to locate other distal cut tendon surfaces also embedded in the collagen gel.

Effect of varying doses of chenodeoxycholic acid on bile lipid and biliary bile acid composition in gallstone patients: a dose-response study.

In a dose-response study, a formulation of chenodeoxycholic acid (chenic acid) with complete bioavailability was fed at doses of 0, 250, 500, 750 mg for randomized 6-week periods to 13 patients with radiolucent gallstones. The proportion of chenic acid in biliary bile acids increased in direct relation to dose. Lithocholic acid also increased, but ursodeoxycholic acid showed no significant change. Bile saturation decreased with increasing dose, but response was variable and achieved significance only at 750 mg/day. Cholesterol saturation was negatively correlated with the proportion of chenic acid in biliary bile acids: When biliary bile acids contained greater than 70% chenic acid (and ursodeoxycholic acid), bile became unsaturated, on the average. The data suggest that a dose of at least 10-15 mg/kg may be necessary to obtain desaturation in many gallstone patients.

A facile hydrolysis-solvolysis procedure for conjugated bile acid sulfates.

Methods for hydrolyzing and solvolyzing conjugated bile acid sulfates were compared on reference mixtures of conjugated and unconjugated bile acid sulfates gas-liquid chromatography to assess recovery, and thin-layer chromatography and zonal scanning to define the products occurring after hydrolysis. Conventional methods in which solvolysis preceded vigorous alkaline saponification gave incomplete recoveries. However, essentially complete recovery of primary and secondary bile acid sulfates was obtained with a mild alkaline saponification procedure followed by acidification and extraction into ether, in shich complete solvolysis was shown to occur within 12 hours. Based on these findings, we developed and validated a simple hydrolysis-solvolysis procedure; the method features mild alkaline hydrolysis, acidification to pH 1, and extraction with ether followed by a 1-hour incubation.

Lithocholate metabolism during chenotherapy for gallstone dissolution. 1. Serum levels of sulphated and unsulphated lithocholates.

Serum levels of total sulphated and total unsulphated lithocholates were each measured by a specific radioimmunoassay in 66 patients ingesting chenodeoxycholic (chenic) acid for gallstone dissoultion and in 35 gallstone patients ingesting either cholic acid or placebo. No changes occurred in serum lithocholate levels in the control groups. In patients ingesting chenic acid, there was a twofold increase in serum levels of total lithocholate, but the percent sulphation (greater than 75%) remained unchanged during chenotherapy. There was no correlation in the chenic acid treated group between serum lithocholate levels and the proportion of lithocholate in biliary bile acids or changes in serum SGOT. The data suggest that there is effective sulphation of lithocholate in such patients; this may explain the lack of hepatotoxicity observed during ingestion of chenic acid.

Chenotherapy for gallstone dissolution. II. Induced changes in bile composition and gallstone response.

Changes in bile saturation and biliary bile acid composition in patients with gallstones who received chenodeoxycholic ("chenic") acid, cholic acid, or placebo were measured. Chenodeoxycholic induced bile desaturation; this effect was attributable solely to a decrease in the proportion of cholesterol. By gas chromatography, chenodeoxycholic acid increased substantially in the biliary bile acids of patients receiving it, and by mass spectrometry, no unusual bile acids were detected in appreciable amounts. Changes in bile saturation and biliary bile acid composition were then related to chenodeoxycholic acid dosage, and all of these variables were, in turn, related to gallstone response. In general, patients whose gallstones dissolved ingested a higher dose of chenodeoxycholic acid or had bile that contained a higher proportion of this acid and it was more unsaturated, but there were many exceptions, casting doubt on the value of a single analysis of fasting-state bile for predicting gallstone dissolutions. The major factor influencing response, provided dosage is adequate, appears to be gallstone type. Nonetheless, the proportion of chenodeoxycholic acid in biliary bile acids can probably be used to infer patient compliance.