Multiscale wavelet p-leader based heart rate variability analysis for survival probability assessment in CHF patients.

A priori discrimination of high mortality risk amongst congestive heart failure patients constitutes an important clinical stake in cardiology and involves challenging analyses of the temporal dynamics of heart rate variability (HRV). The present contribution investigates the potential of a new multifractal formalism, constructed on wavelet p-leader coefficients, to help discrimination between survivor and non survivor patients. The formalism, applied to a high quality database of 108 patients collected in a Japanese hospital, enables to assess the existence of multifractal properties amongst congestive heart failure patients and to reveal significant differences in the multiscale properties of HRV between survivor and non survivor patients, for scales ranging from approximately 60 to 250 beats.

Population pharmacokinetics of fluconazole after administration of fosfluconazole and fluconazole in critically ill patients.

WHAT IS KNOWN AND OBJECTIVE: Fluconazole is an antifungal agent that is commonly used to treat patients with serious systemic fungal infections in intensive care units. Fosfluconazole is a phosphate prodrug of fluconazole, which was developed to reduce the volume of fluid required to administer fluconazole by intravenous injection. The objective of this study was to characterize the pharmacokinetics of the antifungal fluconazole after the intravenous administration of the prodrug fosfluconazole or fluconazole in critically ill patients with serious systemic fungal infections, by population pharmacokinetic analysis using the nonmem software package. METHODS: Clinical biochemical data including serum fluconazole levels were obtained from 57 patients treated in the intensive care unit along with two naïve pooled patients gleaned from previous reports. The pharmacokinetic model of fluconazole was estimated using a one-compartment model. The probability that the area under the concentration-time curve is higher than 800 µg h/mL was determined by simulation. RESULTS: It was assumed that all the administered fosfluconazole was converted to fluconazole with an estimated fosfluconazole-fluconazole conversion rate constant of 2·05/h. The significant covariates for clearance for fluconazole (CL) and volume of distribution for fluconazole (Vd) were resulted in creatinine clearance (CLcr) and body weight (BW), respectively, in the final pharmacokinetic model equations: CL (L/h) = 0·799 × [CLcr (mL/min)/92·7](0·685) and Vd (L) = 48·1 × [BW (kg)/65](1·40) , where the interpatient variabilities in CL and Vd and the intrapatient variability were 44·8%, 79·7% and 19·8%, respectively. On the basis of the results of the Monte Carlo simulation, the probabilities of target attainment were 60%, 26% and 11% for 400 mg/day administration as fluconazole equivalent at CLcr values of 40, 70 and 100 mL/min, respectively. WHAT IS NEW AND CONCLUSION: The present population pharmacokinetic analysis strongly indicates that fosfluconazole (and fluconazole) dosage should be optimized in terms of CLcr in critically ill patients.

Early assessment of therapeutic response using FDG PET in small cell lung cancer.

PURPOSE: We evaluated the ability of 2-deoxy-2-(18)F-fluoro-D-glucose (FDG) positron emission tomography (PET) in the early assessment of therapeutic response in patients with small cell lung cancer (SCLC). PROCEDURES: FDG PET studies were performed before (baseline PET), after the first cycle of chemotherapy (early PET), and after completion of therapy (final PET) in 12 patients with SCLC. The standardized uptake value (SUVmax) was measured. Metabolic response was defined as a reduction in SUVmax of more than 20% on the early PET, compared with the baseline PET. Tumor response after completion of therapy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Eleven patients were classified as metabolic responders and had a mean (+/-SD) reduction in SUVmax of 57.9 +/- 10.3%. The remaining one patient was classified as a metabolic nonresponder with a reduction in SUVmax of 13.5%. In all patients, metabolic response after the first cycle of chemotherapy was associated with subsequent response according to RECIST. CONCLUSIONS: FDG PET has the potential to identify the therapeutic response in patients with SCLC as early as after the first cycle of chemotherapy.

Reliability of recalled self-report on headache intensity: investigation using ecological momentary assessment technique.

Recalled evaluation of headache intensity is often affected by several factors. Recently, computerized ecological momentary assessment (EMA) has been developed to avoid such problems as recall bias. Here, we compared recalled headache intensity with momentary headache intensity using EMA in tension-type headache (TTH). Forty patients with TTH wore watch-type computers for 1 week to record momentary headache intensity and also rated their headache intensities by recall. We calculated intraclass correlation coefficients between recalled headache intensity and indices from EMA recordings in the whole study population and in two subgroups divided by variability of momentary headache intensity. The results showed that consistency and agreement of momentary and recalled headache intensity were low, and this was especially marked in the subjects whose headache varied widely. These observations suggested that variability of headache intensity may affect recall of headache intensity and this should be taken into consideration in both clinical and research settings.

99mTc galactosyl human serum albumin liver dynamic SPET for pre-operative assessment of hepatectomy in relation to percutaneous transhepatic portal embolization.

We have devised an original predictive residual index (PRI) using 99mTc diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA) liver dynamic SPET for the pre-operative assessment of hepatectomy, including the prediction of residual liver function before hepatectomy. The aim of this study was to evaluate the usefulness of the PRI by using 99mTc-GSA liver dynamic SPET before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe, and to compare the results with the prognosis after hepatectomy. The subjects included eight patients with cholangiocellular carcinoma, five with gallbladder cancer, four with hepatocellular carcinoma and three with metastatic liver cancer. 99mTc-GSA liver dynamic SPET was performed immediately before and 2 weeks after PTPE. Dynamic SPET with 35 continuous rotations was performed to obtain the k-value according to the accumulation curve in each voxel (0.54 cm x 0.54 cm x 1.08 cm) of the liver immediately after a bolus injection of 185 MBq 99mTc-GSA. Each rotation consisted of 180 degrees turn in 64 steps in a 64 x 64 matrix. The acquisition time of each rotation was 35 s. We devised an original PRI by combining the k-value with functional liver volume which were measured by liver dynamic SPET. Hepatectomy was performed following the second SPET. The correlation between the PRI and post-operative patient prognosis was investigated retrospectively. The functional liver volume of the remnant lobe and the PRI significantly increased after PTPE compared with respective values before PTPE (P<0.005 and P<0.0001, respectively). Regarding the relationship between the PRI and the clinical course following surgery, post-operative complications were observed in only two patients. The PRI values of these two patients were 0.323 and 0.394. When the PRI was above 0.400, no patient had symptoms of hepatic failure. The results of this study suggest that, when the PRI value is above 0.400, there is a low probability of hepatic failure after hepatectomy. We conclude that the PRI devised in this study is useful in the pre-operative assessment of hepatectomy after PTPE.

Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine.

Although nicotine is thought to be one of the major immunomodulatory components of cigarette smoking, how nicotine alters the host defense of the lung and, in particular, immune responses of alveolar macrophages, which are critical effector cells in the lung defense to infection, is poorly understood. Nicotinic acetylcholine receptors (nAChRs) are the receptor for nicotine and may be involved in the modulation of macrophage function by nicotine. In this study, therefore, nicotine-induced suppression of antimicrobial activity and cytokine responses of alveolar macrophages mediated by nAChRs to Legionella pneumophila, a causative agent for pneumonia, were examined. The murine MH-S alveolar macrophage cell line cells expressed the messages for alpha4 and beta2 subunits of nAChRs, but not alpha7 subunits, determined by RT-PCR. The nicotine treatment of MH-S alveolar macrophages after infection with L. pneumophila significantly enhanced the replication of bacteria in the macrophages and selectively down-regulated the production of IL-6, IL-12, and TNF-alpha, but not IL-10, induced by infection. These effects were completely blocked by a nonselective antagonist, d-tubocurarine, for nAChRs, but not by a selective antagonist, alpha-bungarotoxin, for alpha7-nAChRs. Furthermore, the stimulation of nAChRs with another agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, showed the same effects, which were blocked by the antagonist d-tubocurarine, on the bacterial replication and cytokine regulation with that of nicotine. Thus, the results revealed that nAChRs, the major exogenous ligands of which are nicotine, are involved in the regulation of macrophage immune function by nicotine and may contribute to the cigarette-induced risk factors for respiratory infections in smokers.

CT assessment of subtypes of pulmonary emphysema in smokers.

OBJECTIVE: To determine the incidence of subtypes of pulmonary emphysema (PE) identified by CT imaging in male patients who have a significant smoking history. PATIENTS AND SETTING: We reviewed 945 subjects (619 men and 326 women) who had undergone CT scanning. However, only the data for male subjects were analyzed due to there being too few female subjects. The male subjects were divided into the following two age groups: group A (age, 50 years). There were two subtypes of PE found: centrilobular emphysema (CLE) and paraseptal emphysema (PSE). Based on these subtypes, PE was divided into the following three categories: I (CLE or CLE-predominant); II (CLE and PSE of equal extent); and III (PSE or PSE-predominant). RESULTS: PE was found in 270 of 516 male smokers (10 of 38 female smokers had PE). Among male subjects, in age group A there were 53 subjects with some degree of PE (category I, 12 subjects [22.6%]; category II, 7 subjects [13.2%]; and category III, 34 subjects [64.2%]). Among men in age group B, there were 217 subjects with some degree of PE (category I, 109 subjects [50.2%]; category II, 23 subjects [10.6%]; and category III, 85 subjects [39.2%]). CONCLUSION: In age group A, men < 50 years of age who were in category III (PSE or PSE-predominant PE) predominated (34 of 53 subjects; 64.2%). In age group B, men > 50 years of age who were in category I (CLE or CLE-predominant PE) predominated (109 of 217 subjects; 50.2%).

Alveolar macrophage cell line MH-S is valuable as an in vitro model for Legionella pneumophila infection.

Alveolar macrophages are the preferential site for growth of Legionella pneumophila (Lp) during infection. However, the study of Lp infection in alveolar macrophages is difficult due to the limitation of available primary alveolar macrophages. In the present study, we established an in vitro Lp infection model in alveolar macrophages using a continuous cell line of murine alveolar macrophages designated MH-S. Infection of both MH-S cells and primary mouse alveolar macrophages obtained by alveolar lavage with virulent L. pneumophila (Lp-V) showed vigorous growth of the bacteria, but infection with avirulent L. pneumophila (Lp-Av) resulted in only minimum growth. Cytokine message expression determination in the MH-S cells after infection showed strong induction of interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha messages induced by Lp-V but minimal induction of these cytokines by Lp-Av infection. IL-1 alpha protein secretion and the message levels for IL-1 alpha were also analyzed, and remarkable induction of IL-1 alpha was evident in both macrophage types when infected with Lp-V. Analysis of IL-12 p40 responses of both macrophage types to Lp-V infection assessed by reverse transcriptase/polymerase chain reaction revealed induction of increased message levels, but significant levels were induced only slowly. Determination of IL-12 protein secretion by enzyme-linked immunosorbent assay of culture supernatants from both macrophage types infected with either Lp-V or Lp-Av showed only minimum production. Thus, MH-S alveolar macrophages showed a similar response to Lp infection compared with primary alveolar macrophages and can be a useful in vitro model system to study Lp infection. The study also revealed the restricted IL-12 protein secretion of alveolar macrophages by Lp infection.

Assessment of the primary effect of aging on heart rate variability in humans.

Beat-to-beat heart rate variability (HRV), reflecting cardiac autonomic control mechanisms, is known to change with age. However, the degree to which this change is mediated by aging per se or by physiologic changes characteristic of normative aging is still unclear. This study was designed to examine the association of aerobic fitness, body habitus or obesity, and blood pressure with age-related changes in HRV. Resting HRV data was recorded from 373 healthy subjects (124 men, 249 women; age range, 16-69 y) and analyzed by coarse-graining spectral analysis to decompose the total spectral power into its harmonic and fractal components. The low- and high-frequency (LF, 0.0-0.15 Hz; HF, >0.15 Hz) harmonic components were calculated from the former, whereas the latter was used to calculate the integrated power (FR) and the spectral exponent , beta, which were, in turn, used to evaluate the overall complexity of HRV. Factor analysis was performed to test whether potentially age-related changes in the components of HRV might be observed secondarily through other variables affecting HRV. Significant (p <0.05) age-related changes in the harmonic (HF and LF) and fractal (FR and beta) components of HRV were generally consistent with those described in the literature. In addition, factor analysis showed that there was a unique common factor that primarily explained correlations among age, HF, and beta (p <0.05) without the contributions from LF, FR, aerobic fitness, body habitus or obesity, and blood pressure. It was concluded that, in this population-based sample, age-related changes in HF and beta, both of which reflect vagal modulation of heart rate, were primarily mediated by aging per se and not by physiologic changes characteristic of normative aging.

Cost analysis between stent and conventional balloon angioplasty.

The present study evaluated the cost of coronary stenting compared with conventional balloon angioplasty in Japan. Procedural cost was estimated as the sum of the procedural fee and the cost of devices such as angioplasty balloon and stent. The data such as the number of balloon catheters and stents used, and the rate of crossovers that was shown by the Stent Restenosis Study (STRESS) were applied to calculate the costs of stenting and conventional balloon angioplasty. For the estimation of hospital room and nursing costs, the length of the in-hospital stay was estimated at 7 days. The costs of procedures such as laboratory and radiological tests were determined based on routine coronary intervention at Chiba University Hospital. The rates of target lesion revascularization in the STRESS trial (conventional balloon angioplasty: 21%, stenting: 15%) were used to calculate the cost during follow up. The in-hospital costs of conventional balloon angioplasty and stenting were estimated to be Yens 982,300 and Yens 1,416,893, respectively. The overall costs, including follow-up cost, of conventional balloon angioplasty and stenting were estimated to be Yens 1,188,583 and Yens 1,564,238, respectively. The in-hospital cost of stenting is higher compared with conventional balloon angioplasty because of greater balloon use and direct stent cost. Lower target lesion revascularization reduces the cost difference between conventional balloon angioplasty and stenting, but the higher initial cost of stenting is not fully offset.

[Capsules containing contrast medium for the assessment of gastric emptying in functional dyspepsia patients].

Usefulness of No. 00 capsules containing contrast medium tests for functional dyspepsia was evaluated in 13 healthy volunteers and 22 patients with dysmotility-like symptoms. Each subject swallowed 15 No. 00 capsules with Okunosu A (200 Kcal; Horika Canned Food Co., Niigata, Japan), and at 0, 15, 30, 45, 60, 90, 120 min, the capsule movement and size were monitored fluoroscopically and radiograms were obtained. And more, we tried to examine 5 healthy volunteers using 15 No. 3 capsules or 20 sitzmarks with Okunos A. In addition, they were examined by using 15 No. 00 capsules and sitzmarks meal. As a result, visualized capsule movement from the proximal to distal stomach up to 90 min was faster in the patients. The number of capsules remaining in the distal stomach from 30 min up to 120 min was significantly larger in the patients (p < 0.05). This test method was evaluated as being useful in monitoring solid emptying and we recognized that the way of the examination using No. 00 capsules and Okunos A could be an aptitude for evaluating functional dyspepsia up to date.

[Consultation and survey for drug interaction in outpatients taking the medicines potentially interact with St. John's Wort].

Ministry Health Welfare of Japan announced the caution for drug interaction of St. John's Wort (SJW), a herbal supplement occasionally used for depression, on May, 2000. Immediately after the announcement, we conducted drug consultation for outpatients prescribed the medicines potentially interacting with SJW. We provided information concerning possible drug interaction with SJW for 741 outpatients (except for pediatrics) during the period of May 22-June 16, 2000. The potential drugs prescribed frequently were warfarin (28.0%), theophylline (19.7%), digitalis (18.4%), carbamazepine (7.2%), disopyramide (6.9%) and cyclosporin (6.3%). Of the patients, 401 subjects were surveyed by collecting the questionnaires to clarify the background of SJW drug interaction. Twenty-two subjects (5.5%) have known commercially available SJW products, 5 subjects (1.2%) have ever taken SJW products before and 2 subjects (0.5%) have taken SJW products concomitant with prescribed medicines. Gender difference was observed in paying attention to SJW products; female subjects (8.6%) tended to have more interest in SJW products than male subjects (2.8%). Two subjects taking SJW have realized for the first time that the supplements they took were SJW products when their package photographs were shown at the consultation. Showing the package photographs might be helpful for making the patients easy to identify the SJW products, because most patients do not pay attention to whether the supplements contain SJW or not. It is recommended that drug consultation should be provided to avoid serious drug interaction with SJW while the outpatients are taking potential medicines prescribed.

Sulfamethizole capsules containing contrast medium for assessment of gastric emptying in functional dyspepsia patients.

The usefulness of sulfamethizole capsules containing contrast medium in gastric emptying tests for functional dyspepsia was evaluated in five healthy volunteers and nine patients with dysmotility-like symptoms. Each subject swallowed 15 capsules with a liquid, food, and at 0, 15, 30, 45, 60, 90, and 120 min, the capsule position and size were monitored fluoroscopically for 30 sec and radiograms were obtained. Blood sulfamethizole concentrations were also measured at the same time. Visualized capsule movement from the proximal to distal stomach up to 60 min was faster in the patients, whereas in the later digestion period, proximal stomach emptying in the patients was delayed significantly (P < 0.05), and the number of capsules remaining in the distal stomach at 120 min was significantly larger in the patients (P < 0.05). This test method was evaluated as being useful in monitoring solid emptying in normal and pathophysiologic conditions.

Easy assessment of ES cell clone potency for chimeric development and germ-line competency by an optimized aggregation method.

Production of germ-line competent chimeric mice from embryonic stem (ES) cells is an inevitable step in establishing gene-manipulated mouse lineages. A common method used for creating chimeric mice is the injection of ES cells into the blastocoelic cavity (blastocyst injection). The aggregation method is an alternative way to introduce ES cells to the host embryo which is less difficult than blastocyst injection. Here we re-examined the condition of embryo-ES cell coculture on the aggregation method and found improvement of germ-line competent chimeric production by a simple modification of the coculture medium. Moreover, R1 ES cell and its 10 gene-manipulated subclones were tested by this method. Although all ES cell clones showed good morphology and a normal karyotype, the efficiency of chimeric development and germ-line transmission varied among clones and were classified into three grades according to germ-line competency. In the first group (class A), both the incidence of chimera with high ES cell contribution and the rate of germ-line transmission were fairly high. Germ-line competent chimeras were obtained but with rather low efficiency in the second group (class B), while another group (class C) showed an absence of high ES cell-contributed chimeras and no germ-line transmission. These results suggest the usefulness of this modified aggregation method to predict the potency of ES cell clones for germ-line competency.

Protein-nutritive assessment of sake lees obtained by brewing from liquefied rice.

Sake lees obtained by brewing from liquefied rice were deprived of water and alcohol by lyophilization, and then examined for nutritional availability with the aid of proximate food analysis, amino acid analysis and animal experiment. Freeze-dried sake lees powder was comprised of 44.6% protein, 37.4% carbohydrate, 2.5% fat, 6.7% fiber, 1.8% ash and 7.2% moisture (alcohol < 0.1%), of which the nutritive value (amino acid score) was estimated as 89.6 when compared with the amino acid requirements for preschool children (FAO/WHO/UNU, 1985). Sake lees protein had been, however, appreciably improved in the limiting amino acid "lysine" relative to polished rice protein. As a result of an animal experiment, the rats fed a 50% sake lees powder diet proved to be equal in growth to those fed a 20% casein (control) diet, although the former diet had to be supplemented with vitamins and minerals, which were in shortage as compared to the control diet. On the other hand, the feeding of sake lees powder was effective in lowering the serum triacylglycerol concentration. Accordingly, sake lees powder can be assessed as a favorable candidate for not only protein-rich but also hypolipidemic provisions.

Assessment of technetium-99m Technegas scintigraphy for ventilatory impairment in pulmonary emphysema: comparison of planar and SPECT images.

Pulmonary emphysema can be diagnosed easily by X-ray CT (CT) as a low attenuation area. Recently Tc-99m-Technegas (Technegas) has been used for ventilation scintigraphy. The present study was undertaken to assess the usefulness of planar and SPECT images by using Technegas scintigraphy in patients with pulmonary emphysema. Technegas scintigraphy, CT and pulmonary function tests were performed in 20 patients (males, age 32-78 years). We classified the findings of Technegas images into 4 grades. Comparing planar and SPECT images of Technegas, more detailed findings were shown by SPECT than by planar images in mild cases (6 cases, 30%). In more severe cases, findings of SPECT and planar images were equivalent (14 cases, 70%). The degree of abnormal findings obtained by SPECT was equivalent to that obtained by CT in severe cases (6 cases, 30%). SPECT should be excluded in advanced stages as indicated by planar images.

Estimation of daily minimum energy expenditure in free-moving rats and mice.

In this paper, we presented a new procedure to determine daily minimum energy expenditure (MEE) in free-moving rats and mice kept in a chamber. Energy expenditure was measured for 23 h period and averaged every 10 min. Data were sorted in ascending order. MEE was estimated from the regression line with the smallest slope and the biggest intercept among the regression lines calculated between the sorted energy expenditure and the data ranking. Among three duplicate measurements in individual animals, MEE gave the smallest coefficient of variation (2.2%) as compared with actual measured-values: either the single lowest value (4.0%) or the average of the 6 lowest values (2.5%). Judging from diurnal patterns of energy expenditure and locomotor activity and from video tape observation of the rat's performance, it was confirmed that MEE represented an energy expenditure at rest. MEE decreased with fasting from days 1 to 5. MEE per body weight also declined with age, but stayed around 71-72 kcal/day/kg3/4 at 18 and 34 weeks of age in male Wistar rats. MEE in mice increased at lower ambient temperatures between 16 and 32 degrees C, but stayed fairly constant at the same temperature in repeated experiments. Thus, MEE estimated by the present regression procedure was highly reproducible and valid to determine the fundamental value of daily energy expenditure under free-moving conditions.

[Assessment of osteoporosis in the local population by means of a portable dual energy X-ray absorptiometry unit].

We assessed bone mineral density (BMD) in the local population by means of a portable dual energy X-ray absorptiometry (DXA) unit. BMD was measured by DXA in 197 women (62 premenopausal and 135 postmenopausal) in Shiunji town. Age, height, weight, body mass index (BMI), menstrual history, obstetric history, habits, symptoms and hormonal cytology (eosinophilic index (EI), karyopyknotic index (KPI) and maturation value (MV)) were investigated. A negative correlation (r = -0.645, p < 0.01) was found between BMD and age. Low BMD (BMD < 0.8g/cm2) was found at a rate of 3.2% in premenopausal women and 51.1% in postmenopausal women. The low BMD group of postmenopausal women had significantly lower BMI and higher age at first delivery than the normal BMD group (BMD > or = 0.8g/cm2). There were no differences between the 2 groups in other factors. We found a positive correlation between BMD and hormonal cytology (KPI and MV). These findings suggest that the rate of osteopenia in postmenopausal women is high than expectation and it is difficult to predict bone loss by symptoms, history and habits. The portable DXA unit is useful for screening osteopenia in local populations.

Assessment of bromodeoxyuridine-labeled S-phase cells in experimentally induced precancerous lesions in the rat's tongue.

Precancerous lesions and early invasive carcinomas were produced in the tongues of rats by oral administration of 0.001% 4-nitroquinoline 1-oxide in drinking water. The distribution and densities of S-phase cells were then studied in an attempt to clarify the mechanism of carcinogenesis from the viewpoint of cell cycle. Bromodeoxyuridine (BrdU)-labeled S-phase cells were demonstrated by an indirect peroxidase method, using anti-BrdU monoclonal antibody, and their percentage was determined as the labeling index (LI). The average BrdU LI was significantly higher in the precancerous lesions than in the normal epithelium. There was a wide range of LI found in cells showing such changes as hyperplasia, hyperparakeratosis, dysplasia and papilloma, but the differences among them were not significant. These findings also showed that there could be considerable differences in proliferative activity among lesions of the same grade, while the difference in histology did not mean a difference in proliferative activity. Additionally, many BrdU-labeled cells were seen in a few layers over the basement membranes of non-cancerous lesions immediately adjacent to early invasive carcinoma, suggesting that these layers had a higher possibility for advancing to early invasive carcinoma.

Trimethadione tolerance tests for the assessment of feasible size of hepatic resection in patients with hepatocellular carcinoma.

Pre-operative evaluation of the quantity of functional remnant hepatic parenchyma after hepatectomy was carried out to predict the optimal amount of hepatic resection using the trimethadione (TMO) tolerance test. This test is an estimate based on serum diamethadione (DMO)/TMO ratio (DMO is the only metabolite of TMO) 4 h after oral administration of TMO, and computed tomography (CT) scans of the liver in patients with hepatocellular carcinoma (HCC). The percentage of remnant hepatic parenchyma was calculated pre-operatively from the remaining non-cancerous portion and the whole hepatic parenchyma, excluding the HCC portion, using the CT scans. Presumptive remnant DMO/TMO ratio was calculated by multiplying the percentage of remnant hepatic parenchyma and pre-operative serum DMO/TMO ratio in 45 patients with HCC undergoing resection. The presumptive remnant DMO/TMO ratios were 0.31 +/- 0.10 (mean +/- s.d.) in 42 patients who survived hepatectomy and 0.13 +/- 0.02 (below 0.15) in the three patients who died from postoperative hepatic failure. Of these surviving patients, two patients who had the presumptive remnant DMO/TMO ratios under 0.15 developed postoperative severe complications. Thus, hepatectomy may not be indicated in patients where presumptive remnant DMO/TMO ratio is 0.15 and lower. These findings suggest that pre-operative measurement of presumptive remnant DMO/TMO ratio, when obtained with the CT of the liver and TMO tolerance test, is useful for prediction of the quantity of functional remnant hepatic parenchyma after hepatectomy in patients with chronic liver disease.