Lower limb perfusion during robotic-assisted laparoscopic radical prostatectomy evaluated by near-infrared spectroscopy: an observational prospective study.

BACKGROUND: Decreased perfusion in the lower extremities is one of the several adverse effects of placing patients in a lithotomy or Trendelenburg position during surgery. This study aimed to evaluate the effects of patient positioning in lower limb perfusion patients undergoing robotic-assisted laparoscopic radical prostatectomy (RARP) using near-infrared spectroscopy (NIRS). METHODS: This observation study comprised 30 consenting males with American Society of Anaesthesiologists physical status classes I and II (age range, ≥20 to < 80 years). Regional saturation of oxygen measurements was obtained using an INVOS™ oximeter (Somanetics, Troy, MI, USA). A NIRS sensor was positioned on the surface of the skin at the mid-diaphyseal region of the calf muscles (the gastrocnemius and soleus), over the posterior compartment, in the right lower leg. Regional saturation of oxygen (rSO2) was sampled during the following time points: before and 5 min after induction of anaesthesia (T0,T1); 5 min after establishment of pneumoperitoneum in a 0° lithotomy position (T2); 5 min after a 25° Trendelenburg position (T3); 30, 60, 90 and 120 min after pneumoperitoneum in a Trendelenburg position (T4, T5, T6 and T7, respectively); after desufflation in a supine position (T8); and after tracheal extubation (T9). RESULTS: Lower limb perfusion evaluated by NIRS was increased after induction of anaesthesia and maintained during steep Trendelenburg positions in RARP patients with no risk for lower limb compartment syndrome (LLCS) (T0:65 ± 7.2%, T1:69 ± 6.1%, T2:70±:6.1%, T3:68 ± 6.7%, T4:66 ± 7.5%, T5:67 ± 6.9%, T6:68 ± 7.2%, T8:73 ± 7.2%, T9:71 ± 7.9%, respectively). CONCLUSIONS: Lower limb perfusion evaluated by NIRS was maintained during the RARP procedure. Correct patient positioning and careful assessment of risk factors such as vascular morbidity could be important for the prevention of LLCS during RARP.

Rapid Aggravation of Rhabdomyolysis Caused by Daptomycin After Aortic Arch Replacement: A Case Report.

Although rare, rhabdomyolysis is a serious complication of cardiothoracic surgery. Daptomycin is a polypeptide antimicrobial agent used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections of the soft tissues. Daptomycin is associated with elevations in serum creatine kinase (CK). A 50-year-old man with acute Stanford A-type aortic dissection was performed Bentall procedure and total arch replacement with frozen elephant trunk. The CK level was 6,573 U/L on the first postoperative day (POD), suggesting rhabdomyolysis associated with lower limb ischemia. The CK level increased to 11,934 U/L on POD 2 and started to decrease thereafter. On POD 5, the patient had a suspected surgical site infection. Antibiotics were changed to empiric therapy of daptomycin and meropenem to address soft tissue MRSA infection. The CK level at the start of daptomycin administration was 4,122 U/L. However, the CK level rose to 21,813 U/L on POD 6. None of the findings suggested new-onset lower limb ischemia. Assuming that the rhabdomyolysis was induced by daptomycin, it was discontinued. The CK level peaked at 26,123 U/L on POD 8, after which it started to decrease and normalized on POD 16. Daptomycin should be used with extreme caution in patients recovering from rhabdomyolysis.

Fluoride-treated rare earth-free magnesium alloy ZK30: An inert and bioresorbable material for bone fracture treatment devices.

Bone fractures represent a common health problem, particularly in an increasingly aging population. Bioresorbable magnesium (Mg) alloy-based implants offer promising alternatives to traditional metallic implants for the treatment of bone fractures because they eliminate the need for implant removal after healing. The Mg-Y-rare-earth (RE)-Zr alloy WE43, designed for orthopedic implants, has received European Conformity mark approval. However, currently, WE43 is not clinically used in certain countries possibly because of concerns related to RE metals. In this study, we investigated the use of a RE-free alloy, namely, Mg-Zn-Zr alloy (ZK30), as an implant for bone fractures. Hydrofluoric acid (HF) treatment was performed to improve the corrosion resistance of ZK30. HF-treated ZK30 (HF-ZK30) exhibited lower corrosion rate and higher biocompatibility than those of WE43 in in vitro experiments. After implanting a rod of HF-ZK30 into the fractured femoral bones of mice, HF-ZK30 held the bones and healed the fracture without deformation. Treatment results of HF-ZK30 were comparable to those of WE43, indicating the potential of HF-ZK30 as a bioresorbable and safe implant for bone repair.

A Case of General Anaesthesia Using an I-gel Airway for MRI of an Adult Patient With Athetoid Cerebral Palsy.

Patients with athetoid cerebral palsy may develop cervical myelopathy owing to repetitive involuntary motion. In these patients, MRI evaluation is required; involuntary motion is problematic, and general anaesthesia and immobilisation may be necessary. However, MRI studies requiring muscle relaxation and general anesthesia in adults are rare. A 65-year-old man with a history of athetoid cerebral palsy required an MRI of the cervical spine under general anaesthesia. General anaesthesia was administered with 5 mg of midazolam and 50 mg of rocuronium in a room adjacent to the MRI room. The airway was secured using an i-gel airway, and the patient was ventilated using a Jackson-Rees circuit. As the only MRI-compatible monitoring method available at our institution was SpO2 monitoring, blood pressure was monitored by palpation of the dorsal pedal artery, and ventilation was monitored visually by an anaesthesiologist in the MRI room. The MRI was uneventful. After scanning, the patient awoke promptly and was returned to the ward. An MRI scan under general anaesthesia requires monitoring of the patient, securing of the airway and ventilation, and careful selection of suitable anaesthetic agents. Although MRI scans requiring general anaesthesia are rare, anaesthesiologists should be prepared for this eventuality.

Anesthetic Management of a Cesarean Section for Preeclampsia in a Parturient With Stickler Syndrome: A Case Report.

Stickler syndrome is a connective tissue disease with the pathogenic involvement of procollagen genes. It is characterized by ocular and joint abnormalities, hearing loss, and midfacial hypoplasia. In Stickler syndrome, the Pierre Robin sequence is a possible complication. A 30-year-old female was admitted at 33 weeks of gestation. She had a genetic diagnosis of Stickler syndrome type 1. The parturient was diagnosed with preeclampsia, and a decision was made to terminate the pregnancy via cesarean section. Combined spinal epidural anesthesia was planned. Pediatricians were included in the operating room in case of neonatal resuscitation. The mother's perioperative course was stable. The neonate needed directional positive airway pressure. He was strongly suspected of having Stickler syndrome. For those with Stickler syndrome undergoing cesarean sections, the risk of a difficult airway must be considered for both the parturient and the neonate. Adequate staffing and collaboration among anesthesiologists, obstetricians, and pediatricians are crucial.

One-lung ventilation using a laryngeal mask airway and bronchial blocker in a patient with vocal cord cancer: a case report.

BACKGROUND: One-lung ventilation is a standard technique for thoracic anesthesia. Usually, one-lung ventilation requires a large-bore tracheal tube. Therefore, in patients with vocal cord morbidity, it is challenging to achieve one-lung ventilation while preventing the damage of vocal cord lesions. CASE PRESENTATION: A 77-year-old man was diagnosed with vocal cord cancer and lung tumor. One-lung ventilation with a combination of a laryngeal mask airway and bronchial blocker was planned to avoid unexpected vocal cord injury. After securing the airway with a laryngeal mask airway, a bronchial blocker was placed under fiberscope guidance. The bronchial blocker passed through a position far enough from the vocal cord lesion. The bronchial blocker provided a clear view of the operative field. The patient's perioperative course was uneventful. CONCLUSIONS: When one-lung ventilation is required for patients with vocal cord lesions, a combination of a laryngeal mask airway and bronchial blocker is considered a good option.

Development of a Simple Fabrication Method for Magnetic Micro Stir Bars and Induction of Rotational Motion in Chlamydomonas reinhardtii.

A magnetic micro stirrer bar (MMSB) is used in the mixing operation of microfluidic devices. We have established a low-cost and easy method to make MMSBs using magnetic (neodymium magnets, magnet sheets) or non-magnetic powders (SUS304) as materials. We demonstrated three kinds of MMSB have respective advantages. To confirm the practical use of this MMSB, a cell suspension of the motile unicellular green alga Chlamydomonas reinhardtii was stirred in microwells. As a result, the number of rotating cells increased with only one of the two flagella mechanically removed by the shear force of the rotating bar, which facilitates the kinetic analysis of the flagellar motion of the cell. The rotational motion of the monoflagellate cell was modeled as translational (orbital) + spinning motion of a sphere in a viscous fluid and the driving force per flagellum was confirmed to be consistent with previous literature. Since the present method does not use genetic manipulations or chemicals to remove a flagellum, it is possible to obtain cells in a more naturally viable state quickly and easily than before. However, since the components eluted from the powder material harm the health of cells, it was suggested that MMSB coated with resin for long-term use would be suitable for more diverse applications.

Effect of Parylene C on the Corrosion Resistance of Bioresorbable Cardiovascular Stents Made of Magnesium Alloy 'Original ZM10'.

Magnesium (Mg) alloy has attracted significant attention as a bioresorbable scaffold for use as a next-generation stent because of its mechanical properties and biocompatibility. However, Mg alloy quickly degrades in the physiological environment. In this study, we investigated whether applying a parylene C coating can improve the corrosion resistance of a Mg alloy stent, which is made of 'Original ZM10', free of aluminum and rare earth elements. The coating exhibited a smooth surface with no large cracks, even after balloon expansion of the stent, and improved the corrosion resistance of the stent in cell culture medium. In particular, the parylene C coating of a hydrofluoric acid-treated Mg alloy stent led to excellent corrosion resistance. In addition, the parylene C coating did not affect a polymer layer consisting of poly(ε-caprolactone) and poly(D,L-lactic acid) applied as an additional coating for the drug release to suppress restenosis. Parylene C is a promising surface coating for bioresorbable Mg alloy stents for clinical applications.

Delayed Ventricular Tachycardia After Prophylactic Doses of Droperidol in Patients With Mild QT Interval Prolongation Due to Preoperative Medication.

Prophylactic doses of droperidol are effective in preventing postoperative nausea and vomiting (PONV). However, due to concerns of QT interval prolongation and ventricular arrhythmias, the safety of droperidol for PONV prophylaxis has been debated. A 70-year-old woman was scheduled for total knee arthroplasty. She had a history of aortic valve replacement. Oral aprindine (40 mg/day) was prescribed. Preoperative electrocardiogram showed mild QT interval prolongation (QTc = 475 ms). Anesthesia was induced using propofol, remifentanil, and rocuronium, and maintained using desflurane, remifentanil, and a bolus dose of rocuronium. The surgery was uneventful. At the time of skin closure, droperidol (1.25 mg) was administered intravenously for PONV prophylaxis. Twenty-three minutes after administration of droperidol, a sudden onset of premature cardiac contraction was observed, which progressed directly to ventricular tachycardia and atrioventricular block. Arrhythmia due to droperidol-induced QT interval prolongation was strongly suspected. Intravenous magnesium sulfate (2 g) and atropine (0.5 mg) were administered immediately. The ventricular tachycardia resolved quickly after the magnesium injection. Following the resolution of the arrhythmia, the patient was extubated. The patient experienced ventricular tachycardia after a prophylactic dose of droperidol that resulted from QT interval prolongation due to the preoperative medication. It may be prudent to avoid even low-dose droperidol in the background of already present QT prolongation, especially when multiple putative QT-prolonging drugs are used.

Laparoscopic image of carbon dioxide embolism during laparoscopic hepatectomy: a case report.

BACKGROUND: Carbon dioxide embolism is a life-threatening complication of laparoscopic hepatectomy. CASE PRESENTATION: A 59-year-old man was admitted for laparoscopic hepatectomy. Approximately 5 h after commencing the operation, we observed a gradual decline in the SpO2 from 100 to 94%, reduction in the ETCO2 from 44 to 19 mmHg, reduction in the systolic blood pressure from 100 to 82 mmHg, and elevation of the heart rate from 82 to 120 beats/min. Intraoperatively, the image displayed on the laparoscopic monitor revealed a small tear in the vein. The inspired O2 fraction was raised to 1.0, intravenous phenylephrine (0.1 mg bolus) was administered, and the respiratory rate was increased. After the patient was stabilized, the injured vein was cut and sealed. After the embolic event, the entire operation was completed without complications. CONCLUSIONS: Careful observation of the laparoscopic monitor is important, particularly during establishment of pneumoperitoneum in patients undergoing laparoscopic hepatectomy.

Opposing effects of estradiol and progesterone on the oxidative stress-induced production of chemokine and proinflammatory cytokines in murine peritoneal macrophages.

In inflammatory and oxidative liver injury, virus proteins and reactive oxygen species are involved in the regulation of proinflammatory cytokine production by macrophages. This study investigated the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stress-stimulated production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, macrophage inflammatory protein (MIP)-2, and macrophage chemotactic protein (MCP)-1 by peritoneal macrophages isolated from male and female mice. E2 inhibited the cytokine production of TNF-alpha, IL-1beta, MIP-2, and MCP-1 by the unstimulated macrophages from males and females, which was then further stimulated by progesterone. The exposure to hydrogen peroxide in the macrophages from both sexes induced the production of cytokine. The hydrogen peroxide-stimulated cytokine production was suppressed by E2 and enhanced by progesterone. The sex hormone effects on the unstimulated and stimulated macrophages were blocked by their receptor antagonists and showed no significant difference between male and female subjects. These findings suggest that E2 may play a favorable role in the course of persistent liver injury, by inhibiting proinflammatory cytokine production, which, in addition, progesterone may counteract the favorable E2 effects through their receptors.

Effects of estradiol and progesterone on the proinflammatory cytokine production by mononuclear cells from patients with chronic hepatitis C.

AIM: To investigate the effects of estradiol (E2) and progesterone on the unstimulated and oxidative stress-stimulated production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-8, and macrophage chemotactic protein (MCP)-1 by peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis C and healthy controls. METHODS: The PBMCs were separated from age-matched 72 males and 71 females with and without chronic hepatitis C, who were divided into two groups based on a mean menopausal age of 50 years. Oxidative stress was induced by hydrogen peroxide in the cells incubated in serum-free media. Cytokines in the culture supernatant were measured by an enzyme-linked immunosorbent assay. RESULTS: The highest levels of the spontaneous production of TNF-alpha, IL-1beta, IL-8, and MCP-1 by the unstimulated PBMCs were in the older male patients with chronic hepatitis C and the lowest levels were in the pre-menopausal female healthy controls. E2 inhibited the cytokine production by the unstimulated PBMCs from the older male and post-menopausal female patients, which was further stimulated by progesterone. The exposure to hydrogen peroxide in the PBMCs from the younger male and pre-menopausal female healthy subjects induced the production of cytokines. The change rates of the hydrogen peroxide-stimulated cytokine production were suppressed by E2 and enhanced by progesterone. CONCLUSION: These findings suggest that E2 may play a favorable role in the course of persistent liver injury by preventing the accumulation of monocytes-macrophages and by inhibiting proinflammatory cytokine production, whereas progesterone may counteract the favorable E2 effects.

Reducing effect of feeding powdered nacre of Pinctada maxima on the visceral fat of rats.

An abdominal fat accumulation complicated by high blood triglycerides is regarded as a risk factor of metabolic syndrome. Feeding powdered nacre, mother of pearl, from Pinctada maxima, resulted in reduced body weight, visceral fat amount, and blood triglyceride level without influencing the food intake, body length, or amount of muscular tissue, suggesting that nacre powder specifically could decrease visceral fat.

The immunoregulatory roles of natural killer T cells in cyclophosphamide-induced tolerance.

BACKGROUND: Recent studies have indicated that natural killer T (NKT) cells are essential for the establishment of transplantation tolerance. In the present study, we have elucidated the role of recipient and donor NKT cells in cyclophosphamide (CP)-induced tolerance. METHOD: DBA/2 (DBA; H-2) mice were used as donors and BALB/c (BALB; H-2) wild-type (WT) or Valpha14 NKT-knockout (KO, BALB/c background) mice were used as recipients. Recipients were treated with CP-induced tolerance regimen, which consists of donor spleen cells (SC) on day 0 and CP on day 2. In some experiments, NKT KO mice, which received NKT cells from either WT, inferon-gamma KO, or interleukin-4 KO mice, were treated with tolerant regimen. To deplete Ly49 inhibitory receptors on NKT cells in the recipient mice, anti-Ly49 monoclonal antibody cocktails were injected on day -1 when indicated. RESULTS: Donor skin graft was permanently accepted in recipient BALB WT mice with induction of donor mixed chimerism. On the contrary, donor DBA skin allografts were chronically rejected in NKT KO recipient. Lower levels of mixed chimerism were observed in NKT KO recipients comparing to the WT recipients. The production of interferon-gamma or interleukin-4 from NKT cells did not affect the induction of tolerance. Depletion of Ly49 positive NKT cells abrogated the induction of skin graft tolerance. CONCLUSION: Recipient NKT cells, but not donor NKT cells, were dominantly required for the induction of allograft tolerance. Our results indicated that the single cytokine produced by NKT cells did not mediate the regulatory function in the induction of allograft tolerance.

Double radiofrequency ablation is more extensive with a spherical zone shape compared to single ablation in a pig liver model.

OBJECTIVE: We compared the duration of ablation and the area of coagulation necrosis between a single ablation method (SAM) and a double ablation method (DAM) with a 'multitined expandable' electrode (LeVeen 2 cm) for radiofrequency ablation (RFA) using pig liver. METHOD: In the SAM group, ablation was completed after the first roll-off. In the DAM group, an additional ablation was performed to achieve a second roll-off. The comparison was made of the time required for roll-off and the extent of coagulation necrosis between the both groups. The Ellipticity index (EI) quantitatively describes the shape of the general RF ablation zone in the axial plane. RESULTS: There was no statistically significant difference in the interval until the first roll-off between both groups (SAM group: 100.7+/-24.7 seconds vs DAM group: 103.2+/-37.7 seconds, P=0.43). In the DAM group, the interval from the start of the additional ablation until the second roll-off was 154.0+/-86.9 seconds, longer than the interval for the first roll-off (P=0.023). The extent of coagulation necrosis was significantly more extensive in the DAM group (axial diameter, mean+/-SD, 26.2+/-2.8mm) x (maximal diameter: 29.3+/-1.6mm) x (minimal diameter: 26.5+/-3.6mm) compared to the SAM group with (23.0+/-3.3mm) x (23.7+/-3.1mm) x (20.0+/-2.5mm), respectively. Although there was no statistically significant difference in the EI between both groups, macroscopically, the shape of coagulation necrosis tended to be non-spherical in the SAM group and spherical in the DAM group. CONCLUSIONS: The DAM with a 'multitined expandable' electrode was more extensive with a spherical zone shape compared to the SAM.

Influence of an artificial pleural effusion technique on cardio-pulmonary function and autonomic activity.

OBJECTIVE: Percutaneous treatment of hepatocellular carcinoma (HCC) located directly under the diaphragm is problematic because ultrasonic imaging is difficult, and the lung may be injured during the procedure. It has been reported that an infusion of 5% glucose solution into the thoracic cavity enables percutaneous treatment in such cases. However, the safety aspects of this have not been investigated. In this study, variations in heart rate and changes in circulatory and respiratory dynamics were examined during the infusion of artificial pleural effusion directly under the diaphragm in patients with HCC. METHOD: The subjects were 13 patients with an HCC directly under the diaphragm. About 500 ml of a 5% glucose solution was infused into the thoracic cavity, and mean blood pressure, heart rate, and oxygen saturation were measured. Holter electrocardiography was simultaneously recorded to evaluate autonomic nerve function. To analyze variations in heart rate, the low-frequency waves (LF: 0.04-0.15 Hz), high-frequency waves (HF: 0.15-0.40 Hz, an index of parasympathetic nerve activity), and the LF/HF ratio (index of sympathetic nerve activity) were examined. The above parameters were measured before, during (when infusion of the half the planned volume was complete), and after infusion were compared. RESULTS: No significant changes in the mean blood pressure or heart rate were found. Oxygen saturation was significantly decreased during and after the infusion. The HF value was slightly higher after infusion and the LF value was significantly increased during infusion. The LF/HF ratio was significantly increased during infusion, and this increase persisted after infusion. CONCLUSIONS: The infusion of artificial pleural effusion had no effect on circulatory dynamics, but transiently affected respiratory functions. It was also revealed that infusion stimulated the parasympathetic nerves.

Gastric mucosal levels of prostaglandins and leukotrienes in patients with gastric ulcer after treatment with rabeprazole in comparison to treatment with ranitidine.

AIM: Prostaglandins (PGs) and leukotrienes (LTs) are major factors involved in the defense of the gastric mucosa against ulcer formation. However, little is still known about the gastromucosa-protecting action of proton pump inhibitors (PPIs) and histamine H(2) receptor antagonists (H(2) blockers) in patients with gastric ulcer. We therefore examined the effectiveness of a PPI in protecting the gastric mucosa. METHODS: We compared the PGE(2) and LTB(4) levels and the expression levels of cyclooxygenase (COX)-1 and COX-2 mRNA in the gastric mucosa in gastric ulcer patients between the group treated for 8 weeks with a PPI, rabeprazole (PPI group; n=5), and the group treated for 8 weeks with an H(2) blocker, ranitidine (H(2) blocker group; n=6), as well as in nonulcer subjects (control group; n=5). RESULTS: The mucosal levels of PGE(2) and COX-2 mRNA expression were significantly lower in the ulcer patients than those in the nonulcer patients, whereas the LTB(4) level was significantly higher in the ulcer patients than that in the nonulcer patients, and it was also significantly lower in the ulcerated mucosa than that in the nonulcerated mucosa. The PPI group had a significantly increased PGE(2) and decreased LTB(4) levels in comparison to the H(2) blocker group during the ulcer-healing stage. The COX-1 mRNA expression showed no difference among the PPI and H(2) blocker groups or between before and after the treatment. However, the COX-2 mRNA expression increased in the PPI group more than that in the H(2) blocker group during the ulcer-healing stage. CONCLUSION: These findings demonstrated the significant gastric-mucosa-protecting effect of PPI by increasing the PGE(2) production and reducing the LTB(4) production.

Historical changes of hospitalization in patients with hepatocellular carcinoma considering for clinical path preparation.

We examined the hospitalization time in 346 patients with hepatocellular carcinoma who were treated between January 1991 and March 2002 (486 admissions). A newly introduced IVR CT system and an advanced catheter shortened the mean time from 65.0 (1991) to 35.6 (2001) days in patients who underwent transcatheter arterial embolization (TAE). For patients having TAE combined with percutaneous ethanol infusion (PEI), the mean time was shortened from 156.5 to 48.7 days. In those who underwent PEI, the values were 56.0 and 36.8 days, respectively. In those who underwent radio frequency ablation (RFA), the mean time in 2001 was 25.3 days. Overall, the mean time was shortened from 60.5 to 38.0 days. In particular, the mean time (41.0 days) after 1999, when the IVR CT system and RFA were introduced, was significantly shorter than that before their introduction (58.9 days). Advances in instruments and procedures for TAE have greatly shortened the hospitalization period. In patients who underwent PEI, the rate of decrease in the mean time was small and it is difficult decrease their length of hospital stay; therefore, RFA may be frequently employed in the future.

Protection of estrogens against the progression of chronic liver disease.

Hepatitis C virus infections are recognized as a major causative factor of chronic liver disease. A characteristic feature of chronic hepatitis C, alcoholic liver disease and non-alcoholic fatty liver disease is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory and oxidative stimuli, and to produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. Estradiol is a potent endogenous antioxidant. Hepatic steatosis was reported to become evident in an aromatase-deficient mouse and was diminished in animals after treatment with estradiol. Our previous studies showed that estradiol suppressed hepatic fibrosis in animal models, and attenuated HSC activation by suppressing the generation of reactive oxygen species in primary cultures. Variant estrogen receptors were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. A better understanding of the basic mechanisms underlying the gender-associated differences observed in the progression of chronic liver disease would provide valuable information relative to the search for effective antifibrogenic therapies.