Asuka Ito

L-[1-13C] phenylalanine breath test reflects histological changes in the liver

OBJECTIVE Compared with healthy individuals, patients with chronic liver disease reportedly have lower L-[1-13C] phenylalanine breath test (PBT) values. However, there is no report detailing the relationship between the results of PBT and pathological data in liver disease patients. This study was designed to investigate the degree of histological changes in the liver that induce PBT changes and the time of measurement that reflects the histological change. MATERIALS AND METHODS PBT was performed in 47 patients (10 with a normal liver, and 37 with chronic hepatitis C). After administering 10 mg/kg L-[1-13C] phenylalanine, 300 mL of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (%13C dose h(-1)) at each time point was calculated from the amount of 13CO(2) in the exhaled air, assuming a CO(2) production rate of 300 mmol m(-2) body surface area per hour. Subsequently, we examined the relationship between the results of PBT and METAVIR pathological scoring. RESULTS The highest correlation coefficients between the fibrosis score and %13C dose h(-1) and between the fibrosis score and %13C cumulative excretion were obtained at 45 min (r = -0.779, R(2) = 0.607; P < 0.0001) and 75 min (r = -0.768, R(2) = 0.590; P < 0.0001), respectively. CONCLUSION PBT is a useful adjunct for detecting histological changes in the liver. The %13C dose h(-1) value at 45 min and the %13C cumulative excretion value at 75 min of PBT are useful for detecting hepatic histological change.

Gender Differences in Stroke Risk Among the Elderly After Coronary Artery Surgery

BACKGROUND: Previous studies have shown that women are at higher risk than men for stroke after coronary artery bypass graft (CABG) surgery, but gender differences in systemic atherosclerosis have not been studied adequately. We investigated gender differences in the incidence of craniocervical and ascending aortic atherosclerosis and other risk factors for stroke in elderly patients (age ≥60 yr) undergoing CABG surgery. METHODS: Data were prospectively collected on 720 patients (31.8% women) undergoing CABG surgery. All patients underwent preoperative brain magnetic resonance imaging and angiography to assess for prior cerebral infarctions, carotid artery stenosis, and intracranial arterial stenosis. Epiaortic ultrasound was performed at the time of surgery to assess for atherosclerosis of the ascending aorta. Cognitive status was measured using the Hasegawa-dementia score in all patients before surgery and on the seventh postoperative day. RESULTS: Women were older and had more hypertension and intracranial arterial stenosis than did men. Men had significantly higher rates of hyperlipidemia, peripheral vascular disease, abdominal aortic aneurysm, smoking history, severe carotid artery stenosis, and severe aortic atherosclerosis than did women. Although there were no differences in prior cerebral infarction or preoperative cognitive impairment, the rate of perioperative stroke was marginally higher in men than in women (3.9% vs 1.3%, P = 0.066). Univariate predictors of perioperative stroke were prior cerebral infarctions, ascending aortic atherosclerosis, preexisting cognitive impairment, and peripheral vascular disease. Stepwise logistic regression analysis demonstrated that significant independent predictors of perioperative stroke were prior cerebral infarctions and aortic atherosclerosis. CONCLUSIONS: These data suggest that men are more likely than women to have risk factors for stroke, including severe carotid artery stenosis, severe aortic atherosclerosis, and peripheral vascular disease. The rates of prior cerebral infarction and preoperative cognitive impairment were similar between genders.

Early neuropsychological dysfunction in elderly high-risk patients after on-pump and off-pump coronary bypass surgery

PurposeAdvanced age is associated with systemic atherosclerosis and is a risk factor for neurological dysfunction after coronary artery bypass grafting (CABG). However, few studies have investigated early neurological dysfunction after off-pump CABG in elderly patients.MethodsData were collected prospectively on 218 patients (≥60 years) who underwent elective off-pump (n = 89) or on-pump CABG (n = 129). Four cognitive tests were performed preoperatively and 1 week postoperatively. Neuropsychological (NP) dysfunction was defined as a decrease in an individuals performance in more than two tests of at least 20% from baseline. We compared the incidence of NP dysfunction, stroke, graft patency grading, and systemic atherosclerosis between patients who underwent off-pump and on-pump CABG.ResultsOff-pump patients were more likely to have a history of cerebrovascular disease, peripheral vascular disease, smoking, multiple cerebral infarctions, and severe aortic atherosclerosis. None of the off-pump and three on-pump patients suffered intraoperative strokes (P = 0.27). The incidence of NP dysfunction was 11.2% in the off-pump group and 22.5% in the on-pump group, (P = 0.02). Multivariate analysis revealed that NP dysfunction was associated with cardiopulmonary bypass (CPB) and multiple cerebral infarctions. The off-pump group had fewer vessels grafted (2.4 vs 3.4; P < 0.01), and a higher rate of stenosis (>50%) and occlusion of the grafted vessels (13.0% vs 7.4%; P = 0.01) than the on-pump group.ConclusionOff-pump CABG reduced postoperative NP dysfunction in elderly patients with severe systemic atherosclerosis compared to on-pump CABG.

High Correlation between Results of the [1-13C]-Phenylalanine Breath Test and Phenylalanine Hydroxylase (EC 1.14.16.1) Activity of the Liver in Rats

Background:¹³CO₂ is decreased in patients with end-stage liver disease by the [1-¹³C]-phenylalanine breath test. Decreased ¹³CO₂ is supposed to be caused by the decreased ability of the liver to oxidize phenylalanine. However, no direct evidence has been reported. Methods: The [1-¹³C]-phenylalanine breath test was performed in galactosamine hepatitis rats (n = 14) and control rats (n = 8). Plasma phenylalanine concentration before intravenous administration of [1-¹³C]-phenylalanine, the elimination rate of phenylalanine and the phenylalanine hydroxylase (PAH; EC 1.14.16.1) activity of the whole liver were examined. Results: Increase of ¹³CO₂ in the breath [Δ¹³CO₂ (‰)] of galactosamine hepatitis rats 2 min after administration of [1-¹³C]-phenylalanine was only 1/5 of that in control rats. The concentration of plasma phenylalanine and the elimination rate of plasma phenylalanine in hepatitis rats did not show significant differences compared to control rats. On the other hand, a clear difference in the activity of PAH was observed between hepatitis rats and control rats. Δ¹³CO₂ (‰) 2 min after administration of [1-¹³C]-phenylalanine was highly correlated to the PAH activity of the whole liver (r = 0.917). Conclusion: It was strongly indicated that decreased Δ¹³CO₂ in hepatitis rats was the result of decreased activity of PAH.

A comparison of postoperative sore throat after use of laryngeal mask airway and tracheal tube

PurposeWe compared the degree of postoperative sore throat (PST) after use of a laryngeal mask airway (LMA; by two insertion techniques) and a tracheal tube (TT) in adult patients.MethodsEighty-six adult patients undergoing surgery of an extremity were randomized into three groups. The LMAs (size 4 for men, 3 for women) and TTs were lubricated with 2% lidocaine gel. After the induction of anesthesia, an LMA with the cuff deflated was inserted and then the cuff was inflated in group A, an LMA with the cuff inflated was inserted in group B, and the trachea was intubated using vecuronium in group C; staff anesthesiologists performed all these methods. LMA cuffs were inflated with the maximum recommended volume of air. TT cuffs were inflated with the minimum volume of air without gas leakage at 20 cmH2O pressure. The mode of ventilation depended on the individual anesthesiologists. Blood traces on the devices were examined after their removal. PST was rated immediately after anesthesia and on the first postoperative day, using a three-point score and a 100-mm visual analog scale, respectively.ResultsMost of the patients receiving an LMA breathed spontaneously and those receiving a TT underwent controlled ventilation. The ratio of positive blood traces on devices, as well as the degree of PST immediately after anesthesia, was similar in the three groups; however, on the first postoperative day, the severity of PST was greater in the LMA groups than in the TT group (P = 0.016). The severity of PST was similar with the two LMA insertion techniques.ConclusionIn the conditions of our study, LMAs inserted with the cuff either fully inflated or deflated worsened PST compared with TTs.

Evaluation of Pancreatic Exocrine Secretion Using 13C-Dipeptide (Benzoyl-L-Tyrosyl-[1-13C]Alanine) Breath Test: Focusing on Pancreatoduodenectomy Cases

Objectives: We investigated whether a breath test using benzoyl-L-tyrosyl-[1-13C]alanine (Bz-Tyr-Ala) allows assessment of pancreatic exocrine function. Methods: Benzoyl-L-tyrosyl-[1-13C]alanine was orally administered, and changes in 13CO2 were expressed as Δ‰. The breath test was performed in chronic pancreatitis patients and healthy subjects in a preliminary study and, subsequently, in 17 pancreatoduodenectomy patients, to examine the difference between the results obtained at the times of pancreatic tube insertion and removal, the relationship between breath test results after tube removal and the volume of pancreatic juice drained, and the difference in results between the presence versus the absence of histological changes of chronic pancreatitis. Results: The Δ‰ was lower in the chronic pancreatitis patients than in healthy subjects. In the postoperative patients, the Δ‰ was higher at tube insertion than at tube removal. The correlations of the Δ‰ with the maximum volume of pancreatic juice, its mean volume, and pancreatic juice amylase levels were 0.865, 0.757, and 0.853, respectively. The Δ‰ was lower in 11 patients with that in 6 patients without histological changes of chronic pancreatitis. Conclusions: These results suggest that the Bz-Tyr-Ala breath test can measure pancreatic exocrine function.Abbreviations: Bz-Tyr-Ala - benzoyl-L-tyrosyl-[1-13C]alanine, BT-PABA - N-benzoyl-L-tyrosyl-p-aminobenzoic acid, ABT - L-[1-13C]alanine breath test, ChP - chronic pancreatitis, DPC - duodenal papillary carcinoma, PC - pancreatic head cancer

L-[1-13C] phenylalanine breath test reflects phenylalanine hydroxylase activity of the whole liver.

Abstract Object The purpose of this study was to perform L-[1- 13 C] phenylalanine breath test (PBT), measure phenylalanine hydroxylase (PAH) activity in liver tissue biopsies from patients, analyze the relationship between PBT results and PAH activity, and determine the time point at which measurements best reflect PAH activity in liver tissue. Methods PBT was performed in 25 patients (10 with normal liver and 15 with liver cirrhosis). After administering 10 mg/kg L-[1- 13 C] phenylalanine, 300 ml of expired air was collected over 90 min at 15-min intervals. The rate of hepatic phenylalanine oxidation (% 13 C dose h −1 ) at each time point was calculated from the amount of 13 CO 2 in the breath, assuming a CO 2 production rate of 300 mmol m −2 body surface area per hour. Subsequently, we examined the relationship between the results of PBT and PAH activity. Results PAH activity of the whole liver was significantly decreased in hepatic cirrhosis patients ( P 13 C dose h −1 correlated with the PAH activity/liver, with correlation coefficients at 30, 45, and 60 min of more than 0.7, and the maximum correlation was at 30 min ( r = 0.821, P 13 C cumulative excretion correlated with the PAH activity/liver with correlation coefficients of more than 0.7 after 45 min. The maximum correlation was at 90 min ( r = 0.770, P = 0.001). Conclusion PBT values reflect PAH activity in the whole liver and, in particular, the % dose h −1 at 30 min after oral administration highly correlates with PAH activity, providing an important indicator for monitoring changes in whole liver PAH activity.

Patients with severe liver cirrhosis followed up by L-[1-13C] phenylalanine breath test

Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-13C] phenylalanine breath test (PBT). We performed this test several times during the clinical course in two patients with severe liver cirrhosis (LC). Patient 1 was a 67-year-old woman with non-B, non-C LC and hepatocellular carcinoma (HCC) in the lateral hepatic segment. Because the patient wanted to receive nonsurgical treatment for HCC, intraarterial administration of zinostatin stimalamer was performed. The patient was hospitalized four times before her death from liver failure on December 20, 2000. During her clinical course, PBT was performed four times. Values for both the rate of hepatic phenylalanine oxidation (%13C dose h−1) and %13C cumulative excretion gradually decreased during her clinical course. Patient 2 was a 57-year-old man with hepatitis C virus (HCV)-positive LC. He was hospitalized seven times between December 1998 and his death on May 24, 2001. During his clinical course, PBT was performed four times. Values for both %13C dose h−1 and %13C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.

Ethanol and acetaldehyde differentially alter extracellular dopamine and serotonin in Aldh2-knockout mouse dorsal striatum: A reverse microdialysis study.

Dopamine (DA) and serotonin (5-HT) seem to be involved in several of the effects of ethanol (EtOH). Acetaldehyde (AcH), especially in the brain, induces effects that mimic those of EtOH. The purpose of this study was to investigate the effects of local perfusion of EtOH and AcH on extracellular DA and 5-HT in the dorsal striatum of Aldh2-knockout (Aldh2-KO) and wild-type (WT) mice. Aldh2-KO mice were used as a model of aldehyde dehydrogenase 2 deficiency in humans to examine the effects of AcH. Mice were perfused with Ringers solution (control), EtOH (100, 200, or 500mM) and AcH (100, 200, or 500μM) into the dorsal striatum. Dialysate samples were collected every 5min, and then analyzed with HPLC coupled to an ECD. We found that local perfusion with 500mM EtOH increased extracellular levels of DA (p<0.05) in both Aldh2-KO and WT mice, while 5-HT levels remain unchanged. EtOH at a dose of 200mM also increased DA in WT mice, but this was limited to a 30-40-min time-point. In contrast, perfusion with 200 and 500μM AcH decreased both DA and 5-HT (p<0.05) in Aldh2-KO mice, but this decrease was not found in WT mice at any AcH dose, indicating an effect of AcH on DA and 5-HT levels. There were no genotype effects on the basal levels of DA and 5-HT. These results indicate that high EtOH can stimulate DA, whereas high AcH can depress both DA and 5-HT in the dorsal striatum of mice.

Synthetic 13C-dipeptide breath test for the rapid assessment of pancreatic exocrine insufficiency in rats

Objective. 13C-breath tests have been investigated in order to assess pancreatic exocrine function using various 13C-compounds, but they have not been accepted for routine clinical use. One of the barriers to their acceptance is that these tests are time-consuming and require up to several hours for breath collection. The purpose of this study was to design a novel 13C-compound that would make a rapid 13C-breath test for assessing exocrine pancreatic function possible. Material and methods. N-benzoyl-L-tyrosyl-1-13C-L-alanine was synthesized, and the characteristics of its cleavage in duodenal juice and in the duodenum of rats were examined. Thereafter, a 13C-breath test was carried out in which N-benzoyl-L-tyrosyl-1-13C-L-alanine was given orally to pancreatic exocrine-insufficient and normal control rats. Results. N-benzoyl-L-tyrosyl-1-13C-L-alanine was readily cleaved and liberated 1-13C-L-alanine in the duodenal juice. Carboxypeptidase was a major contributor to the cleavage. When N-benzoyl-L-tyrosyl-1-13C-L-alanine was injected into the duodenum and orally administered to the rats, the 13C atom% of CO2 in breath increased rapidly. This indicated that N-benzoyl-L-tyrosyl-1-13C-L-alanine in the duodenum liberated 13C-Ala on cleavage. 13C-Ala is absorbed and metabolized to liberate 13CO2, which is exhaled. It was shown that the Δ13CO2 (‰) in the N-benzoyl-L-tyrosyl-1-13C-L-alanine breath test in the pancreatic exocrine-insufficient rats, in whom the absorption and metabolism of 13C-Ala was unimpaired, was significantly lower than that in the control rats. Conclusions. The rate of increase in the Δ13CO2 (‰) in the N-benzoyl-L-tyrosyl-1-13C-L-alanine breath test is expected to be proportional to the rate of N-benzoyl-L-tyrosyl-1-13C-L-alanine cleavage by pancreatic proteases in the duodenum. We propose the N-benzoyl-L-tyrosyl-1-13C-L-alanine breath test as a rapid test for assessing pancreatic exocrine function.