Lupus Nephritis with Thymoma Managed by Thoracoscopic Surgery and Prednisolone.

A 48-year-old woman was admitted to our hospital to undergo evaluation for fatigue, severe weight loss, and nephrotic range proteinuria. Light microscopy of a renal biopsy specimen revealed class III (A) lupus nephritis, while immunofluorescence and electron microscopy only showed sparse immune deposits with findings that were not typical of lupus nephritis. Computed tomography revealed a mass in the anterior mediastinum, which was resected. The examination of the surgical specimen revealed type A noninvasive thymoma. In combination with thymomectomy, postoperative steroid therapy achieved the prompt remission of lupus nephritis. In this patient, thymoma-related autoimmunity may have contributed to the exacerbation of lupus nephritis.

Two cases with solitary pulmonary nodule due to non-tuberculous mycobacterial infection showing intense 18F-fluorodeoxyglucose uptake on positron emission tomography scan.

We report an 81-year-old man and a 65-year-old woman with a solitary pulmonary nodule (SPN) due to infection with non-tuberculous mycobacteria (NTM). In each case, the nodule showed a high (18)F-fluorodeoxyglucose (FDG) uptake with the maximum standardized uptake values (SUV) of 13.2 and 4.8 on positron emission tomography (PET) imaging, respectively. Both cases required partial lung resection for confirmation of the histological diagnosis. A review of six reported patients with SPN due to NTM infections showed that the SUV of FDG was more than 4.0 in the nodules of all cases. Positive results on FDG-PET should be interpreted cautiously when evaluating SPN, especially in patients having predisposing factors for NTM infections.

Evaluation of pancreatic exocrine secretion using 13C-dipeptide (benzoyl-L-tyrosyl-[1-(13)C]alanine) breath test: focusing on pancreatoduodenectomy cases.

OBJECTIVES: We investigated whether a breath test using benzoyl-L-tyrosyl-[1-(13)C]alanine (Bz-Tyr-Ala) allows assessment of pancreatic exocrine function. METHODS: Benzoyl-L-tyrosyl-[1-(13)C]alanine was orally administered, and changes in (13)CO2 were expressed as delta per thousand. 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 delta per thousand was lower in the chronic pancreatitis patients than in healthy subjects. In the postoperative patients, the delta per thousand was higher at tube insertion than at tube removal. The correlations of the delta per thousand 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 delta per thousand 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.

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

OBJECTIVE: (13)C-breath tests have been investigated in order to assess pancreatic exocrine function using various (13)C-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 (13)C-compound that would make a rapid (13)C-breath test for assessing exocrine pancreatic function possible. MATERIAL AND METHODS: N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was synthesized, and the characteristics of its cleavage in duodenal juice and in the duodenum of rats were examined. Thereafter, a (13)C-breath test was carried out in which N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was given orally to pancreatic exocrine-insufficient and normal control rats. RESULTS: N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was readily cleaved and liberated 1-(13)C-L-alanine in the duodenal juice. Carboxypeptidase was a major contributor to the cleavage. When N-benzoyl-L-tyrosyl-1-(13)C-L-alanine was injected into the duodenum and orally administered to the rats, the (13)C atom% of CO(2) in breath increased rapidly. This indicated that N-benzoyl-L-tyrosyl-1-(13)C-L-alanine in the duodenum liberated (13)C-Ala on cleavage. (13)C-Ala is absorbed and metabolized to liberate (13)CO(2), which is exhaled. It was shown that the Delta(13)CO(2) ( per thousand) in the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test in the pancreatic exocrine-insufficient rats, in whom the absorption and metabolism of (13)C-Ala was unimpaired, was significantly lower than that in the control rats. CONCLUSIONS: The rate of increase in the Delta(13)CO(2) ( per thousand) in the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test is expected to be proportional to the rate of N-benzoyl-L-tyrosyl-1-(13)C-L-alanine cleavage by pancreatic proteases in the duodenum. We propose the N-benzoyl-L-tyrosyl-1-(13)C-L-alanine breath test as a rapid test for assessing pancreatic exocrine function.

Measurement of extra-pancreatic secretory function by 13C-dipeptide breath test.

A simple breath test was developed for assessment of exocrine pancreatic function employing 13C-dipeptide [ie, benzoyl-L-tyrosyl-[1-(13)C]alanine (Bz-Tyr-Ala)], and this test was examined to determine whether it can be used to diagnose exocrine pancreatic insufficiency in patients with chronic pancreatitis. The subjects, 24 patients with chronic pancreatitis and 16 healthy adult controls, underwent the Bz-Tyr-Ala breath test, in which breath samples were collected every 10 min up to 90 min after oral administration of an aqueous solution of 5-mg/kg Bz-Tyr-Ala (7 mM). They also underwent a breath test with [1-(13)C]alanine equimolar to that contained in Bz-Tyr-Ala and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test. Delta13CO2 values at 10-60 min for the Bz-Tyr-Ala breath test were significantly lower in chronic pancreatitis patients than in normal controls. However, the [1-(13)C]alanine breath test results did not differ between patients and normal controls. The correlation coefficient between the Bz-Tyr-Ala breath test Delta13CO2 value at 20 min, and the results of the BT-PABA test were r=0.726 (r2=0.527, P<0.0001). The results suggest that this newly developed Bz-Tyr-Ala breath test can quickly and noninvasively diagnose the exocrine pancreatic dysfunction.

Usefulness of rectally administering [1-(13)C]-butyrate for breath test in patients with active and quiescent ulcerative colitis.

OBJECTIVE: Impaired butyrate metabolism plays a part in ulcerative colitis (UC). To assess the usefulness of measuring butyrate metabolism as an indication of inflammatory activity, we investigated the rate of butyrate metabolism by breath test after administering [1-(13)C]-butyrate rectally to patients with UC. MATERIAL AND METHODS: Thirty-eight UC patients (22 active, 16 quiescent) and 15 healthy controls were given [1-(13)C]-butyrate enemas. The (13)CO2 production rate was measured by breath test using an infrared spectrometric analyzer. RESULTS: The quantity of expired (13)CO2 was significantly lower in the active than in the quiescent UC and control groups. Cumulative (13)CO2 production at 240 min showed significant negative correlations with the clinical activity index (r=-0.65, p<0.0001), endoscopic activity index (r=-0.63, p=0.0001) and histology (r=-0.71, p<0.0001) in the active UC group. The (13)CO2 production rate was significantly increased in the quiescent stage as compared with the active stage in six UC patients, in whom clinical remission was achieved, in accordance with improvements in the clinical activity index, the endoscopic activity index, histology and fecal butyrate concentrations. Significant inverse correlations between the cumulative (13)CO2 production rate and these three parameters were seen in these six UC patients assessed in both the active and quiescent stages. CONCLUSIONS: Measurement of expired (13)CO2 after rectally administering [1-(13)C]-butyrate in active and quiescent UC appears to be a promising and reliable method for evaluating disease activity and metabolic changes associated with amelioration of inflammation.

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

Compared to healthy subjects, patients with severe liver cirrhosis (LC) are reported to show lower values in the L-[1-(13)C] 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 (%(13)C dose h(-1)) and %(13)C 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 %(13)C dose h(-1) and %(13)C cumulative excretion decreased during his clinical course. We confirmed that PBT was useful for following the course of LC.

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.

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

OBJECT: The purpose of this study was to perform L-[1-13C] 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-[1-13C] 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 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 < 0.05). The results of PBT %13C 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 < 0.0001). %13C 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.

Recovery of liver function in two-third partial hepatectomized rats evaluated by L-[1-13C]phenylalanine breath test.

BACKGROUND: We have previously reported that by means of a breath test with intravenously administered L-[1-13C] phenylalanine (13Cphe), hepatopathy could be quantitatively evaluated by measuring expiratory 13CO2 levels in a short period. It is known that phenylalanine hydroxylase activity (PAHA) plays an important role in phenylalanine metabolism. We examined the relationship between changes in PAHA and the results of the 13Cphe breath test during hepatic regeneration in a rat model of 70% hepatectomy, to assess their usefulness for evaluating hepatic regeneration. METHODS: Male Wistar rats (Shizvoka Laboratory Animal Center, Hamamatsu, Japan) weighing 230 to 290 g were subjected to 70% hepatectomy under anesthesia with sodium pentobarbital. One, 2, 3, 5, 7, and 14 days postoperatively, 30 mg/kg 13Cphe was intravenously injected into the femoral vein, and the increase in exhaled 13CO2 (Delta 13CO2) was measured for 15 minutes. Simple laparotomy was performed in control rats. After the breath test, the regenerated liver was removed and weighed. The amount of DNA, amount of hepatic tissue total protein (TP), and PAHA were determined. RESULTS: The r between liver weight/body weight and PAHA, between DNA and PAHA, and between TP and PAHA were 0.832, 0.720, and 0.758, respectively. Breath test graphs revealed that liver weight/body weight, DNA, and TP showed the best correlations with the peak value of Delta 13CO2 (liver weight/body weight percentage, r = 0.801; DNA, r = 0.660; TP, r = 0.706), and r between PAHA and peak value was 0.638. CONCLUSIONS: These results suggest that measurement of PAHA in regenerated liver is an effective method for following up liver function after hepatic resection. Moreover, the 13Cphe breath test may also be useful to evaluate liver function after partial hepatectomy.

l-[1-(13)C]Alanine is a useful substance for the evaluation of liver function.

BACKGROUND: Using a rat model of hepatectomy, we investigated whether the severity of hepatopathy could be quantitatively measured from changes in expiratory (13)CO(2) levels after intravenous administration of l-[1-(13)C]alanine. MATERIALS AND METHODS: Under nembutal anesthesia, 20 mg/kg l-[1-(13)C]alanine was administered to rats via the femoral vein, and expiratory (13)CO(2) levels were measured for 15 min. Then, 30, 70, or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. A breath test was conducted 20 min after laparotomy. We examined the correlation of total (13)CO(2) output (S) or single point (13)CO(2) level (SP) every 1 min for 15 min with liver weight/body weight (LW/BW) (%). RESULTS: In the control group, the breath test graph showed a specific peak level about 3 min after administration, but in all groups undergoing hepatectomy, it did not show any peak level during measurement. The correlation coefficient between S(12--15) after l-[1-(13)C]alanine administration and LW/BW was 0.902 (P < 0.0001). The correlation coefficient between SP(7) after l-[1-(13)C]alanine administration and LW/BW was highest, 0.908 (P < 0.0001). The severity of hepatopathy could also be evaluated, with significant differences in S(12-14) compared to control when the volume of resected liver was 30% or greater, but there was no significant difference between the groups undergoing 70 and 90% hepatectomy. However, the severity of hepatopathy could be evaluated, with significant differences in S(15) and SP(7) in all comparisons between groups. CONCLUSION: In the breath test with intravenously administered l-[1-(13)C]alanine, the severity of hepatopathy could be quantitatively evaluated in a short period by measuring S(15) and SP(7).