Angiotensin-converting enzyme inhibition with enalapril slows progressive intima-media thickening of the common carotid artery in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND AND PURPOSE: Whether angiotensin-converting enzyme (ACE) inhibitors have any clinically significant antiatherogenic effects in humans remains unproven. We undertook a prospective randomized clinical trial of 98 patients with non-insulin-dependent diabetes mellitus (NIDDM) to examine the efficacy of ACE inhibition with enalapril for preventing intima-media (IM) thickening of the carotid wall as measured ultrasonographically. METHODS: Ninety-eight NIDDM patients were randomly assigned either to enalapril at 10 mg/d (n=48) or to a control group (n=50); the planned duration of the trial was 2 years. All patients were seen at baseline (study entry) and 2 subsequent formal annual evaluations, in addition to standard clinical management for NIDDM. IM thickening and vascular lumen diameters were determined for all patients on the basis of baseline and 2 subsequent annual evaluations with carotid ultrasonography. We performed an intent-to-treat analysis to assess changes in IM thickening over the course of the study. RESULTS: Annual IM thickening measurements of the right and left common carotid arteries were 0.01+/-0.02 and 0.01+/-0.02 mm/y in the enalapril-treated group and 0.02+/-0.03 and 0.02+/-0.02 mm/y in the control group, respectively (P<0.05). From regression analysis, annual IM thickening was found to be predicted by enalapril use, sex, and insulin use (F(3,94)=3.86, P=0.012). When we controlled for these other variables, enalapril use reduced annual IM thickening of right and left common carotid arteries by 0.01+/-0.004 mm/y relative to the control group over the course of this study. CONCLUSIONS: Long-term treatment with an ACE inhibitor (enalapril) slows progressive IM thickening of the common carotid artery in NIDDM patients.

Induced hypertension treatment to improve cerebral ischemic injury after transient forebrain ischemia.

The effect of induced hypertension treatment on cerebral ischemia is still controversial. We investigated the preferred blood pressure manipulation level and pressor agent required to reduce cerebral ischemic injury following transient forebrain ischemia induced by bilateral occlusion of the common carotid arteries in anesthetized gerbils. Following 60-min cerebral ischemia, we evaluated the preferred blood pressure manipulation level and pressor agent required to treat cerebral ischemic injury after reperfusion by examining the effects of different levels of mean arterial blood pressure (MABP), increased with phenylephrine or angiotensin II or decreased by blood withdrawal, on cerebral blood flow (CBF), survival ratio, cerebral edema, and brain energy metabolism following transient forebrain ischemia in gerbils. Mild phenylephrine-induced hypertension treatment (21+/-4 mmHg) during post-cerebral ischemia-reperfusion improved the survival ratio and reduced cerebral edema, which was also associated with an increase in local CBF and a recovery of brain energy metabolism. However, intense phenylephrine-induced hypertension, angiotensin II-induced hypertension, or hypotension worsen the survival rate and produced extra cerebral edema, that were also associated with deterioration of brain energy metabolism. These results demonstrate that a mild induced hypertension with phenylephrine (21+/-4 mmHg above the baseline level) results in reduction of the cerebral edema and improves the survival ratio and brain energy metabolism. Furthermore, angiotensin II may have neurotoxic effect to use as the pressor agent for induced hypertension after cerebral ischemia.

Effect of olprinone, a phosphodiesterase III inhibitor, on arterial wall distensibility: differentiation between aorta and common carotid artery.

Although the effects of phosphodiesterase III (PDE III) inhibitors as vasorelaxants have been well documented, there are only few data on the wall response of different arteries. We evaluated the artery-specific effect of olprinone (OP), one of the PDE III inhibitors, on the major branches of human arteries and peripheral circulation. In 14 healthy subjects (average age: 57.5 +/- 21.2 years), systolic and diastolic diameters (Ds and Dd, respectively) and the time velocity integral (VI) of flow velocity patterns were measured by M-mode and Doppler echocardiography in the carotid artery (CA), the ascending aorta (asAo), the abdominal aorta (abAo), and the left ventricular outflow tract. Blood pressure (BP) was simultaneously measured using a cuff sphygmomanometer. Measurements were taken before and 20min after a bolus injection of OP (0.2 microg/kg). Distensibility (Ds - Dd), stiffness parameter beta (In(systolic BP/diastolic BP)/(Ds/Dd - 1)), cardiac output (CO: (Flow Area) x VI x HR at left ventricular outflow), selective flow volume (FV: (Flow Area) x VI x HR at CA or abAo), and vascular resistance (VR: mean BP/(CO or FV)) were then calculated. The distensibility increased significantly after OP administration (P = 0.0015), but that of the asAo or abAo did not change. Although there was a significant increase in CO (P = 0.001) and a significant decrease in systemic VR (P = 0.001) following OP administration, the FV and VR of both CA and abAo did not change significantly. The selectiveness of the effect of OP was demonstrated in terms of the CA wall distensibility. This was thought to be attributable to the differences in the structural components or the reactivity of smooth muscle cells to OP.

Effects of mannitol and glycerol on cerebral energy metabolism in gerbils.

OBJECTIVES: To evaluate the effects of infusion with hyperosmolar solutions, mannitol and glycerol on the recovery of cerebral energy metabolism during ischemia and reperfusion in the gerbil brain. MATERIALS AND METHODS: Sequential changes in cerebral energy metabolism following 90-min ischemia and up to 8 h after reperfusion were measured in 15 gerbils using 31P nuclear magnetic resonance (NMR) spectroscopy after 60-min infusion of 10% glycerol (0.5 g/kg; n=5), or 20% mannitol (1.0 g/kg; n=5), and compared with those gerbils receiving with saline (n=5). Gerbils were anesthetized by intraperitoneal injection of pentobarbital. Forebrain ischemia was induced by clipping of bilateral common carotid arteries for 90 min and reperfused. NMR spectroscopy was measured by a 6.34-Tesla JEOL spectrometer, before administration, 2, 4, 6, and 8 h after 90-min ischemia and reperfusion. Areas of inorganic phosphate (Pi), phosphocreatine (PCr), and beta-ATP peaks were measured to calculate parameters of cerebral energy metabolism, i.e., PCr/Pi and beta-ATP/Pi ratios. Intracellular pH (pHi) was calculated from chemical shifts of Pi relative to PCr. RESULTS: PHi was higher in the mannitol group than in the glycerol and saline groups (P<0.05) 2 h after reperfusion. PCr/Pi ratio was higher 2, 4, and 8 h after reperfusion (P<0.01, P<0.05, P<0.01) in the mannitol group; and 6 h after reperfusion (P<0.05) in the glycerol group; than in the saline group. Beta-ATP/Pi ratio was higher 2 and 8 h after reperfusion (P<0.05) in the glycerol group; and 2 h after reperfusion (P<0.01) in the mannitol group, than in the saline group. CONCLUSIONS: The mannitol group had improved pHi higher than the glycerol group 2 h after reperfusion (P<0.05), while the glycerol group had improved beta-ATP/Pi ratio higher than the mannitol group 6 h after reperfusion (P<0.05). Both mannitol and glycerol groups had improved parameters of cerebral energy metabolism during ischemia and up to 8 h after reperfusion in the gerbil brain.

Chronic hemorheological effects of the calcium antagonist nilvadipine in essential hypertension.

Because blood viscosity is significantly raised in patients with essential hypertension (EH), the hemorheological effects of a 4-month chronic treatment with the calcium antagonist nilvadipine (FK 235, 5-isopropyl-3-methyl-2-cyano-1,4-dihydro-6-methyl-4- (m-nitrophenyl)-3,5-pyridinedicarboxylate, CAS 75530-68-6) on elevated blood viscosity was investigated prospectively in patients with EH, and compared with those in normotensive individuals of similar age. Hemorheological parameters were measured in 13 patients with EH (mean 63.7 years), before and 16.3 weeks (mean) after treatment with 8 mg nilvadipine, twice a day, following a 2-week placebo period, and in 14 normotensive individuals (mean 65.8 years). Whole blood viscosity of 45.0-562.5 s-1 shear rates and corrected blood viscosity of low (45.0 s-1) and high (225.0 s-1) shear rates at standardised hematocrit (Ht) of 45%, plasma viscosity, Ht, serum albumin, and plasma fibrinogen were measured before and after drug treatment and compared with those in normotensive individuals. Whole-blood and plasma viscosities were measured by cone-plate viscometer. Systolic and mean blood pressures (BPs), whole blood viscosities (at low and middle shear rates), corrected blood viscosity (Ht 45% at a low shear rate), and plasma viscosity were higher in patients with EH than in normotensive individuals before medication (p < 0.001 to p < 0.01). All these parameters decreased significantly after nilvadipine (p < 0.004 to p < 0.05). On the other hand, serum albumin and plasma fibrinogen were not altered significantly after nilvadipine. Ht decreased but not significantly after nilvadipine. Mean BP correlated with corrected blood viscosities at 112.5 s-1 and 225.0 s-1 (r = 0.491 p < 0.01 and r = 0.537 p < 0.005), while systolic BP did not correlate, before and after nilvadipine. Chronic treatment with calcium antagonist nilvadipine brought about significant reductions in BPs and rheological parameters of whole-blood viscosities at low and middle shear rates, corrected blood viscosity (Ht 45%) at a low shear rate, and plasma viscosity without changes in serum albumin and plasma fibrinogen levels, as compared with normotensive individuals. Significant linear correlations between values of mean BP and corrected blood viscosities before and after milvadipine show improved hemorheology in association with BP reduction in EH. Vasodilative effects of nilvadipine may have improved the blood rheology in patients with EH.

Volume of infarction and blood flow in cerebral embolism.

The value of measuring asymmetry of cerebral perfusion semiquantitatively by single-photon emission computed tomography (SPECT) correlated with measuring the volume of infarction on computed tomography (CT) was evaluated in cerebral embolism. Eighteen patients with acute cerebral embolism (mean age: sixty-nine years) were evaluated. Ten were diagnosed as having middle cerebral artery (MCA) occlusion, 3 as having MCA branch occlusion, and 4 as having unilateral and 1 as having bilateral internal carotid occlusion. The infarct volume was measured, summing up the area of infarction on CT, at 8.5 days, mean time after onset. Outcomes of the patients were classified into three groups: good, fair, or dead, judged by the consequences one month after onset. Regional cerebral blood flow (rCBF) was measured in 9 of 10 surviving patients at one month, mean time after onset, by 123[iodine N-isopropyl-p-iodoamphetamine (IMP) SPECT. Semiquantitative rCBF index of asymmetry (AI) was evaluated from four regions of brain cortex. Eleven patients with < 300 mL infarct and 7 with > or = 300 mL infarct showed a significant difference of outcome with infarct volumes (P < 0.01). The mean AI value in patients with < 150 mL infarct was 31% while it was 52% with > or = 150 mL infarct (P < 0.039). There were significant linear correlations between mean AI values and the volumes of infarction or infarct/brain volume ratios (P < 0.034 or P < 0.018). The significant correlations of the AI values with the volumes of infarction suggest that the measured asymmetry of perfusion evaluated by SPECT could reflect the ultimate tissue damage and residual intact brain volume after cerebral embolism.

Hemorheologic profiles of plasma fibrinogen and blood viscosity from silent to acute and chronic cerebral infarctions.

Hemorheologic changes from silent to acute and chronic cerebral infarction have seldom been reported. We evaluated hemorheologic profiles of the whole blood viscosity, plasma viscosity and fibrinogen level in stroke at-risk patients with silent cerebral infarction, patients with acute or chronic cerebral lacunar infarction, and subjects at low risk for stroke. Hemorheologic profiles were measured in 88 subjects: (1) 36 patients with silent cerebral infarction (mean 64.7 years), who provided no clinical history of having had definitive stroke but showing > 5 mm lesions of cerebral infarction or periventricular hyperintensity (PVH) observed in magnetic resonance imaging (MRI) T2-weighted images; (2) 12 patients with acute cerebral lacunar infarction (mean 69.1 years), measured within 3 days and repeated 1 month after onset; (3) 25 patients with chronic cerebral lacunar infarction (mean 66.2 years), measured 12.5 months after onset; and (4) 15 subjects at low risk for stroke (mean 65.8 years) without cardiovascular risk factors or lesions on MRI. Patients with silent cerebral infarction were subdivided into two groups of less advanced and more advanced grades, based on the number of infarctions or the grade of PVH. Whole blood viscosity (shear rates: 22.5-225.0 s-1), corrected blood viscosity for 45% standard hematocrit (Hct), plasma viscosity, fibrinogen, serum total protein, albumin, and Hct were measured. Plasma fibrinogen levels were lower in silent cerebral infarctions than in chronic cerebral infarctions (P < 0.01), and patients with more advanced grades of silent cerebral infarction showed higher levels of plasma fibrinogen than those with less advanced grades (P < 0.01 and P < 0.05). Whole blood viscosity, corrected blood viscosity (Hct 45%), plasma viscosity and fibrinogen levels in acute cerebral infarction within 3 days after onset were higher significantly than those in subjects at low risk for stroke. Plasma fibrinogen level persisted to be elevated up to 1 month after onset, which continued as well in patients with chronic cerebral infarction. Advanced grades of silent cerebral infarction in stroke at-risk patients are accompanied by elevations of plasma fibrinogen level, which increases further after onset of cerebral infarction; such abnormalities persist up to the chronic stage. Elevated plasma fibrinogen level might reflect progression of atherogenesis in patients with advanced grades of silent cerebral infarction, resulted in an increased probability as to be a risk factor for cerebral infarction.

Nimodipine improves brain energy metabolism and blood rheology during ischemia and reperfusion in the gerbil brain.

Whether nimodipine improves cerebral blood flow (CBF) and metabolism in cerebral ischemia remains a controversial issue. We investigated the effect of nimodipine on CBF, brain energy metabolism, using a laser-Doppler flowmeter and in vivo 31phosphorus nuclear magnetic resonance (31P NMR) spectroscopy, and blood rheology during forebrain ischemia and reperfusion in gerbils. Eighty-three adult gerbils received nimodipine (1 micrograms/kg/min), or an equal volume of the vehicle, or saline, over 60 min prior to a transient forebrain ischemia for 60 min. We measured sequential changes in phosphocreatine (PCr) / inorganic phosphate (Pi) ratio, beta-ATP/Pi ratio, and intracellular pH (pHi) during ischemia and reperfusion by 31P NMR spectroscopy, and the measurement of whole blood viscosity (WBV) at 60 min after reperfusion. CBF was measured continuously throughout the study by a laser-Doppler flowmeter. During forebrain ischemia, PCr/Pi and beta-ATP/Pi ratios were higher significantly in the nimodipine-treated group (p < 0.05 and 0.01) than in the vehicle- or saline-treated groups. During reperfusion, PCr/Pi and beta-ATP/Pi ratios recovered significantly only in the nimodipine-treated group (p < 0.05 and 0.01). The WBV at high shear rate (562.5 s-1) lowered significantly in the nimodipine-treated group (p < 0.05) compared with the vehicle- or saline-treated group. CBF was higher significantly only during administration of nimodipine in the nimodipine-treated group (p < 0.01) than other groups. Nimodipine improved brain energy metabolism and blood rheology during forebrain ischemia and reperfusion in the gerbil brain.

Duration threshold of induced hypertension on cerebral blood flow, energy metabolism, and edema after transient forebrain ischemia in gerbils.

We have investigated whether there is a duration threshold for the effects of phenylephrine-induced hypertension on CBF, brain energy metabolism, and cerebral parenchymal specific gravity (SG) following transient forebrain ischemia in gerbils. Sixty gerbils were randomly assigned to one of the four treatment groups: one control group and three groups subjected to an increase of 25 mm Hg in MABP induced by treatment, 30 min after reperfusion, with phenylephrine for 15 min, 30 min, or 60 min. The local CBF was measured continuously, and the SG was evaluated 120 min after reperfusion. Sequential changes in brain energy metabolism, as shown by the ratio of phosphocreatine to inorganic phosphate (Pi), the beta-ATP/Pi ratio, and intracellular pH, were also measured. The 15-min induced hypertension regimen was most suited to the recovery of brain energy metabolism, which was associated with an increase in local CBF and a decrease in cerebral edema. These results demonstrate that a suitable duration can be chosen to optimize the beneficial effects of phenylephrine-induced hypertension on ischemic brain injury following transient forebrain ischemia.

Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia.

Elevated plasma fibrinogen level is known to progress atherosclerosis and to be one of the risk factors for the occurrence of cardiovascular diseases. The objective of this study is to evaluate the changes in plasma fibrinogen level and blood rheology in patients with type II hyperlipoproteinemia before and after random administrations of HMG-CoA (3-hydroxy-e-methylglutaryl-cocarboxylase-A) reductase inhibitors, pravastatin sodium and simvastatin, and compare with results in normal subjects. Of a total of 28 patients with type II primary hyperlipoproteinemia with > 230 mg/dl fasting total plasma cholesterol, 16 patients (mean, 59.7 years old) were administered 10-15 mg/day of pravastatin sodium for an average of 10.2 weeks, and 12 patients (mean, 62.0 years old) were administered 5-10 mg/day of simvastatin for an average of 13.9 weeks. Patients were evaluated before and after drug administration and results were compared with those of 16 normal subjects of similar age (mean, 56.9 years old). Blood viscosities were measured using a cone-plate viscometer (Biorheolizer, BRL-1000, Japan). The following were measured before and after drug administration: whole blood viscosity at shear rates of 75-375 s-1, corrected blood viscosity at low (112.5 s-1) and high (225.0 s-1) shear rates for the standard hematocrit of 45%, plasma viscosity, hematocrit, total protein, serum albumin, and plasma fibrinogen. Total cholesterol level was significantly decreased (from 270 to 225, mg/dl, mean values; P < 0.0007) an average of 10.2 weeks after start of pravastatin sodium administration. In addition to the reductions of whole blood viscosity, at every shear rate examined, corrected blood viscosity, and plasma viscosity, plasma fibrinogen levels were significantly decreased (from 354 to 309 mg/dl, mean values; P < 0.0007) after start of pravastatin sodium administration. Fibrinogen level and blood rheology were not significantly changed after start of simvastatin administration despite similar significant reductions in total cholesterol level (from 260 to 207 mg/dl, mean values; P < 0.0001) to those in the case of pravastatin sodium. From the results, we conclude that administration of pravastatin sodium, but not simvastatin, reduced the plasma fibrinogen level and blood viscosities to normal levels in type II hyperlipoproteinemic patients while both drugs reduced total cholesterol level. The hydrophilicity and a small binding capacity with plasma protein of pravastatin sodium may be responsible in part for the beneficial hemorheologic effects observed in the patients with type II hyperlipoproteinemia. Further investigations should be conducted to confirm the findings observed.

Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia.

Pravastatin sodium, a newly developed potent synthesis inhibitor of HMG-CoA (beta-hydroxy-beta-methylglutaryl-cocarboxylase-A) reductase (Sankyo Co., Ltd., Japan) was medicated, 10 approximately 15 mg/day (mean: 11.1 mg/day) for 10.2 weeks in mean, in 14 patients with primary hyperlipoproteinemia of more than 230 mg/dl of serum cholesterol levels (mean age: 56.9 y.o.). The values of serum cholesterol decreased (from 242 +/- 12 to 207 +/- 22; mg/dl), and of high density lipoprotein (HDL) increased (from 42.3 +/- 8.8 to 45.3 +/- 9.2; mg/dl) significantly (p < 0.05, respectively) 10.2 weeks in mean after medication with pravastatin sodium. The whole blood viscosity, at every shear rate examined, corrected blood viscosity, for the standard hematocrit level of 45%, and plasma fibrinogen decreased significantly (p < 0.05, respectively) at the same time, without showing significant differences any more 10.2 weeks in mean after medication with those in 14 elderly normal subjects (mean age: 56.7 y.o.), which suggested that the hemorheological parameters in patients with primary hyperlipoproteinemia had improved significantly by medication with pravastatin sodium.

Photodynamic therapy of rat liver cancer: protection of the normal liver by indocyanine green.

The application of photodynamic therapy (PDT) to hepatocellular carcinoma (HCC) has been difficult because hematoporphyrin derivatives (HpD) accumulate not only in cancer cells but also in normal hepatocytes and, hence, laser irradiation causes injuries in both tissues. Protection of the normal liver tissue from laser phototoxicity was demonstrated using indocyanine green (ICG) as a protective agent. In vitro, argon laser irradiation decolored the green tint of ICG much faster in solutions containing HpD than those without, suggesting that ICG captured singlet oxygen from HpD. Degeneration of Change hepatocytes induced by HpD and laser irradiation was prevented by an addition of ICG into the medium. In vivo, laser irradiation of the rat liver surface caused hyperemia when HpD was injected two days before, while the hyperemia was much milder in rats additionally receiving ICG injection 10 minutes before the irradiation. ICG injected into rat HCC accumulated only in the normal liver tissue. Laser irradiation of rat HCC preinjected with both HpD and ICG destroyed only the cancer tissue, while the surrounding liver tissue was preserved. Both in vitro and in vivo results suggest that ICG has a scavenger effect against excited oxygen and it might be used as a protective agent in PDT of HCC.

Injurious effects of ethanol on rat Kupffer cells.

The effects of ethanol on rat Kupffer cells were studied functionally and morphologically. Eight g ethanol per kg body weight per day was intragastrically administered to rats for 7 days. An isocaloric glucose solution was administered to control rats. The phagocytic activity of the reticuloendothelial system was measured by the carbon clearance method (57 mg carbon particles per kg body weight) on the 7th day. Kupffer cells having phagocytized carbon particles were counted under the light microscope. Kupffer cells were also observed by scanning electron microscopy. Both the carbon clearance and Kupffer cell number were lower in ethanol-administered rats (32 +/- 8 X 10(-4) mg/ml; 0.6 +/- 0.3/0.01 mm2 liver lobule) as compared to control rats (63 +/- 15; 3.1 +/- 1.0). Microvilli and filopodia of Kupffer cells were fewer in ethanol-administered rats than in control rats. Carbon clearance correlated with Kupffer cell number per 0.01 mm2 liver lobule and liver weight. These results suggest that the decrease in carbon clearance induced by ethanol is due mainly to the decrease in Kupffer cell number and partly to the decrease in Kupffer cell activity as demonstrated by the disappearance of microvilli and filopodia.

Comparison of estimation methods of liver maximum removal rate of indocyanine green.

Three linear plots by which the liver's maximum removal rate (Rmax) of indocyanine green (ICG) and the Michaelis constant (Km) can be calculated were compared in a microcomputer simulation study. The widely-used Lineweaver-Burk plot (1/V vs. 1/S; V, ICG initial removal rate (mg/kg/min); S, ICG loading dose (mg/kg] presented the greatest bias and variance. There was no remarkable difference in bias between the S/V vs. S plot and the V vs. V/S plot, but the latter possessed a smaller variance. Therefore, the V vs. V/S plot was considered the best for estimating Rmax. The best combination of three ICG loading doses was 0.5, 2, and 5 mg/kg. This combination was selected by comparison of the Rmax estimated from three points with that estimated from six points (0.5, 1, 2, 3, 4 and 5 mg/kg).

Peritoneoscopy of alcoholic liver cirrhosis in comparison with non-alcoholic liver cirrhosis.

Peritoneoscopic findings of 39 patients with alcoholic liver cirrhosis (ALC) were compared with those of 95 patients with non-alcoholic liver cirrhosis (NALC). They were selected from 245 patients with liver cirrhosis subjected to peritoneoscopy in the 7 year period from 1975 to 1981. Out of the 95 NALC patients, 24 had hepatitis B surface antigen. The ALC patients had nodules which varied in size (61%), large depressions (69%), and a markedly rounded edge of the liver (33%) more often than NALC patients (18, 43 and 3%, respectively). Nodularity differed between the right and left lobes in ALC (41%) more often than in NALC (16%). Interstitial reddish markings and patchy nodules were, however, more frequent in NALC (51 and 28%, respectively) than in ALC (8 and 5%, respectively). Lymphatic vesicles were observed both in ALC (85%) and NALC (78%). In conclusion, the peritoneoscopic features which suggested ALC were the coexistence of nodules of various sizes, large depressions and a markedly dull edge of the liver. Interstitial reddish markings and patchy nodules were more indicative of NALC than ALC.

Comparative diagnosis of alcoholic liver diseases by multivariate and histological analysis.

Sixty-seven cases of alcoholic liver disease were histologically classified into 4 groups: alcoholic liver cirrhosis (ALC), alcoholic hepatitis (AH), alcoholic liver fibrosis (ALF) and alcoholic fatty liver (AFL). They were statistically reclassified by the likelihood method using age, total alcohol intake, hepatomegaly and 12 liver function tests. A score table for likely diagnosis was constructed from the incidences of each range. The cases were re-evaluated using the score table, with an overall correct diagnosis rate of 73%. The best combination of 5 parameters included the indocyanine green plasma disappearance rate, total alcohol intake, cholesterol, choline esterase and glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio. A correct diagnosis rate of 75% was attained using these 5 parameters, and 94% of patients were correctly diagnosed by the first or the second likelihood diagnosis. Differential diagnosis of alcoholic liver diseases was easily and confidently obtained with the likelihood score table.

Effects of sake and bourbon on liver histopathology and function in rats.

Sake or bourbon (8g ethanol/kg body weight) was intragastrically administered to rats for 12 days. An equal dose of ethanol in water or an isocaloric glucose solution was administered to control groups. Food was withheld, but water freely provided. Neither mortality nor liver and body weights were different between the alcohol-treated groups. Glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were more elevated in the sake group than in the other groups. Additionally, liver fibrosis was more pronounced, and vacuole formation or steatosis was less in this group. These results suggest that sake is more fibrogenic. Some components other than ethanol, such as long-alkyl chain alcohols, may have been responsible for the differential histopathology.

Diagnosis of hepatocellular carcinoma in patients with liver cirrhosis using liver function assays.

Sex, age and 21 routine liver function assays were analyzed by stepwise selection and the best-of-all-possible-combinations method to identify a small group of assays valuable in establishing which liver cirrhosis (LC) patients have a high risk of hepatocellular carcinoma (HCC), when alpha-fetoprotein (AFP) is not elevated. Data was obtained from 115 HCC and 122 LC patients on admission. Tumor size correlated with AFP (0.73), alkaline phosphatase (ALP, 0.47), leucine aminopeptidase (LAP, 0.42), lactic dehydrogenase (LDH, 0.42), and the glutamic oxaloacetic transaminase (GOT)/glutamic pyruvic transaminase (GPT) ratio (GOT/GPT, 0.41). The mean of the correct diagnosis rates (CDR) of HCC and LC utilizing AFP as the sole parameter (89%) was markedly higher than those of the other parameters. The best-of-all-possible-combinations method presented a more powerful combination than stepwise selection. The best combination of 7 parameters (LAP, GOT/GPT, choline esterase, one-hour erythrocyte sedimentation rate, age, albumin/globulin ratio, and total bilirubin) presented a mean CDR of 80%, HCC CDR of 77%, and false positive rate of 18%. LC patients statistically diagnosed as having HCC by these 7 parameters are proposed as high risk patients. Fourteen (78%) of 18 HCC patients who were AFP-negative were statistically diagnosed. This analysis can be applied to LC patients to distinguish those that should be followed closely by imaging diagnostic techniques.

Scanning electron microscopy of Ito's fat-storing cells in the rat liver.

The whole body including extended processes of Ito's fat-storing cells was observed by scanning electron microscopy in rat liver injured with lithocholic acid (LCA). Necrotic foci developed in the midlobular zone 48 h after LCA administration. Demonstration of Ito cell bodies around the foci was probably facilitated by easy detachment of hepatocytes from Ito cells. The body and the processes were located mainly between the sinusoidal endothelium and hepatocytes; sometimes they were between hepatocytes. Ito cells often were proximate to collagen fiber bundles and sometimes were attached to them. The cell body was flatly round or elliptic, 7 to 12 micron in diameter. Its surface was finely undulated with microvillous projections about 0.1 micron in length. Branching patterns of the processes resembled a fern-leaf mantling the sinusoidal endothelium. The trunks of the processes were about 2 micron in diameter and 20-30 micron in length. These processes tapered, branching into thinner processes, with the most peripheral being 0.1 micron in diameter. Ito cells and their branching processes likely strengthen sinusoidal walls and control blood flow in the sinusoids.