Importance of gated CT acquisition for the quantitative improvement of the gated PET/CT in moving phantom.

OBJECTIVE: The aim of this study was to investigate the utility of gated PET/CT and CT attenuation correction (AC) for the quantitation of radioactivity. METHODS: An ellipse phantom containing six spheres, ranging from 10 to 37 mm in diameter, was filled with 36.7 kBq/mL of F-18. The respiratory motion was simulated by a motor-driven plastic platform to move the phantom with a displacement of 2 cm in the craniocaudal direction at a frequency of 15/min. With the phantom at rest, PET/CT data were acquired and used as a standard (nonmotion). With the phantom in motion, PET data were acquired in both the static and gated modes (sPET and gPET, respectively). Helical CT (HCT), slow CT (SCT), average CT (ACT), and four-dimensional CT (4DCT) were acquired and used to correct attenuation. On both PET and CT images, the maximum radioactivity, dimensions, and CT numbers were measured on the central slices. RESULTS: In nonmotion, recovery coefficients whose spheres were 22 mm or smaller gradually decreased. Regarding motion, the PET counts of the spheres in the static acquisition were lower than those acquired in nonmotion with either type of CTAC (sPET-HCT: -43.8%, sPET-SCT: -51.4%, sPET-ACT: -49.5%). Gated acquisition of PET significantly improved the PET counts (gPET-HCT: -30.1%) (p < 0.05), while additional gated acquisition of CT significantly improved them further (gPET-4DCT: -15.2%) (p < 0.01). The dimensions of sPET were overestimated, but those of gPET were close to the standard values. The SCT significantly overestimated the dimensions, and the water density area decreased (p < 0.01). The 4DCT images were similar to the HCT images. CONCLUSIONS: In respiratory motion, PET acquisition in the static mode underestimated the radioactivity and overestimated the dimensions. Neither SCT nor ACT improved these errors. Although PET acquisition in the gated mode improved the quantification of PET/CT images, the additional gated CT acquisition using 4DCT is required for further improvement.

Molecular characterization of Anisakis pegreffii larvae in Pacific cod in Japan.

It is now recognized that the morphospecies Anisakis simplex is not a single species but a complex composed of three sibling species, A. simplex sensu stricto, A. pegreffii and A. simplex C. In Japan, A. simplex-like larvae have been isolated from a variety of fish and humans, but the larvae collected have been identified as A. simplex by only light microscopy. Therefore, the epidemiology of the A. simplex complex, composed of three sibling species, is still unclear in Japan. In the present study, 26 A. simplex-like larval isolates were obtained from two Pacific cod landed in Hokkaido, Japan, and examined genetically by PCR-RFLP and direct sequencing of the ITS region of rDNA. Among the 26 isolates, 24 were identified as A. simplex sensu stricto, the other two as A. pegreffii. The present study is the first to confirm the distribution of A. pegreffii in Japan, and to detect A. pegreffii larvae in Pacific cod.

Inducible nitric oxide synthase expression and nuclear factor-kappaB activation in alveolar type II cells in lung injury.

Alveolar type II cells (type II cells) play a crucial role in the progression and repair of lung inflammation and injury. We investigated whether inducible nitric oxide synthase (iNOS) was expressed and nuclear factor-kappaB (NF-kappaB) was activated in type II cells in lung injury. After injecting lipopolysaccharide (LPS) or saline in the rat, the lungs were excised and type II cells were isolated. iNOS and its mRNA were expressed both in lung tissue and isolated type II cells in response to LPS. The lungs from saline-treated rats showed only minimal expression of iNOS. Electrophoretic mobility shift assay revealed that expression of NF-kappaB in the nuclear extracts was augmented by LPS, and p5O/NFkappaB was expressed in type II cells in LPS-treated rats. Intraperitoneal dexamethasone almost completely inhibited the iNOS expression and attenuated the activation of NF-kappaB in the LPS-treated lung. These findings suggest that type II cells can be a source of NO production in lung injury,and that the effects of corticosteroids may be in part through inhibition of both iNOS expression and NF-kappaB activation.

Effects of hypoxia on alveolar fluid transport capacity in rat lungs.

There is little information regarding the effect of hypoxia on alveolar fluid clearance capacity. We measured alveolar fluid clearance, lung water volume, plasma catecholamine concentrations, and serum osmolality in rats exposed to 10% oxygen for up to 120 h and explored the mechanisms responsible for the increase in alveolar fluid clearance. The principal results were 1) alveolar fluid clearance did not change for 48 h and then increased between 72 and 120 h of exposure to hypoxia; 2) although nutritional impairment during hypoxia decreased basal alveolar fluid clearance, endogenous norepinephrine increased net alveolar fluid clearance; 3) the changes of lung water volume and serum osmolality were not associated with those of alveolar fluid clearance; 4) an administration of beta-adrenergic agonists further increased alveolar fluid clearance; and 5) alveolar fluid clearance returned to normal within 24 h of reoxygenation after hypoxia. In conclusion, alveolar epithelial fluid transport capacity increases in rats exposed to hypoxia. It is likely that a combination of endogenous norepinephrine and nutritional impairment regulates alveolar fluid clearance under hypoxic conditions.

Beta1-adrenoceptor stimulation by high-dose terbutaline downregulates terbutaline-stimulated alveolar fluid clearance in ex vivo rat lung.

Because high-dose terbutaline and isoproterenol (10(-3) M), beta2-adrenergic agonists, failed to increase alveolar fluid clearance, the mechanisms responsible for this effect were examined in ex vivo rat lungs. An isosmolar 5% albumin solution with Evans blue dye was instilled into the distal airspaces in isolated rat lungs that were then inflated with 100% oxygen at an airway pressure of 8 cm H2O in a 37 degrees C incubator. Alveolar fluid clearance was measured by the progressive increase in dye concentrations over 1 hour. The results indicated that: (1) although 10(-5) M terbutaline or isoproterenol increased alveolar fluid clearance, 10(-3) M terbutaline or isoproterenol did not; (2) both concentrations of terbutaline (10(-5), 10(-3) M) increased intracellular adenosine 3',5'-cyclic monophosphate in cultured type II alveolar epithelial cells; (3) instillation of atenolol, a selective beta1-adrenergic antagonist, in the presence of either 10(-3) M terbutaline or isoproterenol was associated with an increase in alveolar fluid clearance. These results suggested that beta1-adrenoceptor stimulation prevented the normal response to a beta2-adrenergic agonist. To further test this hypothesis, a selective beta1-adrenergic agonist, denopamine, was administered; these results showed that (4) 10(-3) M denopamine, a selective beta1-adrenergic agonist, inhibited the increase in alveolar fluid clearance in the presence of 10(-5) M terbutaline; (5) hypoxia for 2 hours did not alter the effects of terbutaline on alveolar fluid clearance. The mechanism for the inability of the alveolar epithelium to respond to high-dose terbutaline or isoproterenol with the normal upregulation of alveolar fluid clearance in ex vivo rats lungs appears to be mediated by beta1-adrenoceptor stimulation that subsequently suppresses the beta2-adrenergic response.

Expression and localization of a novel Rab small G protein (Rab38) in the rat lung.

The Rab small G protein family participates in intracellular vesicle transport, including exocytosis and endocytosis. The cDNA encoding a novel Rab-related small G protein (Rab38) has been cloned from rat lung cDNA library and recorded in GenBank (accession no. M94043). However, the expression and localization of the protein in the lung remains primarily unknown. We produced polyhistidine-tagged recombinant Rab38 and a polyclonal antibody with a synthetic peptide. Immunohistochemistry demonstrated that the protein is specifically localized in alveolar type II cells and in bronchial epithelial cells. In situ hybridization using a digoxygenin-labeled RNA riboprobe clearly showed that the mRNA of the protein is localized in alveolar type II cells and bronchial epithelial cells, especially terminal airway epithelial cells. Western blot and reverse transcriptase-polymerase chain reaction showed distinct expression of the protein and mRNA in isolated alveolar type II cells, but not in alveolar macrophages. The native protein was predominantly hydrophobic and was enriched in a high-density vesicle fraction but was barely detectable in nuclear and lamellar body fractions in alveolar type II cells. Immunofluorescence cytochemistry performed on cultured alveolar type II cells showed that Rab38 distributed extensively in the cytoplasm with a distribution pattern similar to endoplasmic reticulum rather than other subcellular organelles. These results suggest that this novel rab small G protein (Rab38) mediates vesicular transport in terminal airway epithelium.

Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs.

Because it was still uncertain whether a stimulation of beta1-adrenoceptors accelerated alveolar fluid clearance in hyperoxic lung injury, the effect of denopamine, a selective beta1-adrenergic agonist, on alveolar fluid clearance was determined in rats exposed to 93% oxygen for 48 and 56 h. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue labeled albumin instilled into the alveolar spaces over 1 h at 37 degrees C in isolated rat lungs. The principle results were as follows: 1) Although lung water volume increased in rats exposed to hyperoxia for 48 and 56 h, basal alveolar fluid clearance did not change for up to 56 h; 2) Denopamine increased alveolar fluid clearance in rats exposed to hyperoxia as well as in rats without exposure to hyperoxia; 3) Denopamine primarily increased amiloride-insensitive alveolar fluid clearance in rats exposed to hyperoxia; 4) The potency of denopmaine was similar to that of terbutaline, a selective beta2-adrenergic agonist. In summary, denopamine is a potent stimulator of alveolar fluid clearance in rats exposed to hyperoxia.

Sensorineural hearing loss as the initial manifestation of polyarteritis nodosa.

A 74-year-old male was referred for the sudden onset of bilateral sudden deafness. The patient had no history of any disease or trauma to the head. Pure tone audiometry revealed bilateral moderate, to severe, sensorineural hearing loss. Auditory brain stem responses (ABRs) showed normal peak and interpeak latencies. These audiological findings suggested that his hearing loss could be attributed to inner ear lesions. However, we felt an alternative explanation for this sudden deafness was likely to exist because the patient also had a month-long fever of unknown origin (FUO) and weight loss of 5 kg/month. Using the criteria of The American College of Rheumatology, we made the diagnosis of polyarteritis nodosa (PAN). Serum MPO-ANCA was positive (x 661). For treatment, the patient was begun on prednisolone and cyclophosphamide. Nine months later, fever, hypertension, nephritis, pneumonitis, and arthritis had completely resolved, the MPO-ANCA became negative (MPO-ANCA < x 10). Furthermore, his hearing improved.

Denopamine, a beta(1)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs.

The effect of denopamine, a selective beta(1)-adrenergic agonist, on alveolar fluid clearance was determined in both ex vivo rat and guinea pig lungs. Alveolar fluid clearance was measured by the progressive increase in the concentration of Evans blue-labeled albumin over 1 h at 37 degrees C. Denopamine (10(-6) to 10(-3) M) increased alveolar fluid clearance in a dose-dependent manner in ex vivo rat lungs. Denopamine also stimulated alveolar fluid clearance in guinea pig lungs. Atenolol, a selective beta(1)-adrenergic antagonist, and amiloride, a sodium channel inhibitor, inhibited denopamine-stimulated alveolar fluid clearance. The potency of denopamine was similar to that of similar doses of isoproterenol or terbutaline. Short-term hypoxia (100% nitrogen for 1-2 h) did not alter the stimulatory effect of denopamine. Denopamine (10(-4), 10(-3) M) increased intracellular adenosine 3',5'-cyclic monophosphate levels in cultured rat alveolar type II cells. In summary, denopamine, a selective beta(1)-adrenergic agonist, stimulates alveolar fluid clearance in both ex vivo rat and guinea pig lungs.

[Acoustic reflection technique].

Acoustic reflection technique has been employed to assess the pharyngeal cross-sectional area in sleep apnea patients. It has the advantage of being noninvasive and quick, and it also allows for continuous evaluation of the patency of these regions. The technique, however, has never been used during sleep because of its restrictions. This issue overlook the recent progress of the technique, i.e., the newly developed nasal acoustic reflection technique which enabled us to assess the pharyngeal cross-sectional area during sleep. Application of this technique includes a method of determining the site of pharyngeal occlusion, a method of evaluating the efficiency of various therapeutic methods of sleep apnea, and a method of measuring the upper airway collapsibility during sleep.

Lung deflation impairs alveolar epithelial fluid transport in ischemic rabbit and rat lungs.

BACKGROUND: Because the fluid transport capacity of the alveolar epithelium after lung ischemia with and without lung deflation has not been well studied, we carried out experimental studies to determine the effect of lung deflation on alveolar fluid clearance. METHODS: After 1 or 2 hr of ischemia, we measured alveolar fluid clearance using 125I-albumin and Evans blue-labeled albumin concentrations in in vivo rabbit lungs in the presence of pulmonary blood flow and in ex vivo rat lungs in the absence of any pulmonary perfusion, respectively. RESULTS: The principal results were: (1) lung deflation decreased alveolar fluid clearance while inflation of the lungs during ischemia preserved alveolar fluid clearance in both in vivo and ex vivo studies; (2) alveolar fluid clearance was normal in the rat lungs inflated with nitrogen (thus, alveolar gas composition did not affect alveolar fluid clearance); (3) amiloride-dependent alveolar fluid clearance was preserved when the lungs were inflated during ischemia; (4) terbutaline-simulated alveolar fluid clearance was preserved in the hypoxic rat lungs inflated with nitrogen; (5) lecithinized superoxide dismutase, a scavenger of superoxide anion, and N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide, preserved normal alveolar fluid clearance in the deflated rat lungs. CONCLUSION: Lung deflation decreases alveolar fluid clearance by superoxide anion- and nitric oxide-dependent mechanisms.

A new nasal acoustic reflection technique to estimate pharyngeal cross-sectional area during sleep.

The conventional acoustic reflection technique in which acoustic waves are launched through the mouth cannot be applied during sleep, nor can it be applied to the nasopharynx, which is the major site of occlusion in patients with obstructive sleep apnea syndrome. We propose a new technique of nasal acoustic reflection to measure pharyngeal cross-sectional areas including the nasopharynx. The acoustic waves are introduced simultaneously to both nostrils during spontaneous nasal breathing. A new algorithm takes into account the nasal septum with asymmetric nasal cavities on both sides and assumes prior knowledge of the cross-sectional area of the nasal cavities and the position of the nasal septum. This method was tested on an airway model with a septum and on healthy human subjects. The conventional technique gave inaccurate measurements for pharyngeal cross-sectional areas for an airway model with asymmetric branching, whereas the new technique measured them almost perfectly. The oro- and hypopharyngeal cross-sectional area measurements acquired by the new method were not different from those obtained by the conventional method in normal subjects. This new method can be used as a monitor of upper airway dimensions in nocturnal polysomnography.

[Multiple renal infarction associated with lupus anticoagulant in a patient with systemic lupus erythematosus].

We report a rare case with multiple renal infarction associated with lupus anticoagulant and SLE. A 20-year old woman presented with remitent fever, butterfly rash and, abdominal pain. Laboratory findings showed leukopenia, positive antinuclear and anti-DNA antibodies, and biological false positive for syphilis. Despite a therapy with prednisolone 25 mg/day, the patient showed hypocomplementemia, high titer of anti-DNA antibody and a development of proteinuria and an elevation of serum creatinine. Renal biopsy revealed no abnormalities. She presented abdominal pain with an elevation of serum LDH. Abdominal dynamic computed tomography demonstrated multiple perfusion defects in both kidneys indicating multiple renal infarction. Brain MRI showed multiple micro infarction in the anterior lobes. She was treated with 80 mg of aspirin and have been in remission for two years. Although there have been reported 18 cases with renal infarction associated with antiphospholipid syndrome, this is the first report in Japan. Renal infarction should be differentiated from renal involvement in patients with SLE who have antiphospholipid antibodies.

[Pulmonary metastatic malignant phyllodes tumor showing multiple thin walled cavities].

A 52-year-old woman who had undergone a partial mastectomy 1 year earlier because of benign phyllodes tumor was admitted because of dry cough and abnormal chest radiograph findings. Chest computed tomograms demonstrated multiple thin-walled cavities and nodules. Clinical examinations and transbronchial biopsy specimens failed to provide a conclusive diagnosis. However, the pulmonary thin-walled cavities enlarged, and a nodular shadow revealed cavitary formation. An open lung biopsy was performed to diagnose the pulmonary lesions. Although biopsy specimens disclosed the infiltration of poorly differentiated adenocarcinoma cells in pleura and pulmonary parenchyma, no primary site was detected. The patient did not respond to systemic chemotherapy (CDDP and VP-16), and died of respiratory failure due to advanced pulmonary metastasis. Autopsy demonstrated marked tumor invasion of the lungs, myocardium, and bone. We analyzed malignant cells in lung tissues at autopsy by immunohistochemistry, and found identical malignant cells in surgical samples obtained during the patients earlier mastectomy. A diagnosis of pulmonary metastasis from malignant phyllodes tumor of the breast was made. Thin walled cavitary lesions from malignant phyllodes tumor are rare; however, pulmonary metastasis of malignant phyllodes tumor should be considered one disease that exhibits thin-walled cavities as a radiographic manifestation.

Serum KL-6, a novel mucin-like glycoprotein, as an indicator of interstitial pneumonitis following lobectomy.

Serum KL-6 has been shown to be a useful marker of active interstitial pneumonitis in patients who have not undergone lobectomy. Considering that KL-6 is produced mainly in the distal airway epithelium, the present study was conducted to determine whether resected lung volume influenced the postoperative KL-6 levels, and also to evaluate whether it is a useful parameter in patients who have undergone lobectomy. The serum KL-6 levels decreased by 36% 1 week after lobectomy, but returned to the preoperative levels by 2 months postoperatively. Although the KL-6 levels increased by 100% 3 to 4 months after lobectomy, the levels were significantly lower than those in interstitial pneumonitis (P < 0.05). The decrease in the KL-6 levels correlated with the number of resected lung segments, but not with the changes in white blood cell count, lactate dehydrogenase level, or C-reactive protein level. In comparison with the lobectomy patients, the serum KL-6 levels decreased by half in patients who had undergone partial resection (P < 0.05). The results of this study suggest that the serum KL-6 level may be a useful indicator of interstitial pneumonitis after lobectomy. Serum KL-6 levels are influenced by the volume of the resected lung, and probably also by the upregulation of KL-6 production.

Ischemia-reperfusion lung injury in rabbits: mechanisms of injury and protection.

To study the mechanisms responsible for ischemia-reperfusion lung injury, we developed an anesthetized rabbit model in which the effects of lung deflation, lung inflation, alveolar gas composition, hypothermia, and neutrophils on reperfusion pulmonary edema could be studied. Rabbits were anesthetized and ventilated, and the left pulmonary hilum was clamped for either 2 or 4 h. Next, the left lung was reperfused and ventilated with 100% oxygen. As indexes of lung injury, we measured arterial oxygenation, extravascular lung water, and the influx of a vascular protein (131I-labeled albumin) into the extravascular space of the lungs. The principal results were that 1) all rabbits with the deflation of the lung during ischemia for 4 h died of fulminant pulmonary edema within 1 h of reperfusion; 2) inflation of the ischemic lung with either 100% oxygen, air, or 100% nitrogen prevented the reperfusion lung injury; 3) hypothermia at 6-8 degreesC also prevented the reperfusion lung injury; 4) although circulating neutrophils declined during reperfusion lung injury, there was no increase in interleukin-8 levels in the plasma or the pulmonary edema fluid, and, furthermore, neutrophil depletion did not prevent the reperfusion injury; and 5) ultrastructural studies demonstrated injury to both the lung endothelium and the alveolar epithelium after reperfusion in deflated lungs, whereas the inflated lungs had no detectable injury. In summary, ischemia-reperfusion injury to the rabbit lung can be prevented by either hypothermia or lung inflation with either air, oxygen, or nitrogen.

[Relapsing polychondritis developing in a patient with Graves' disease: a possible association with propylthiouracil].

A 31-year-old woman presented 1993 with fever, painful swelling of cartilaginous portions of the ears and the bridge of nose, polyarthralgia including costochondroral pains, and episcleritis. She has been taking propylthiouracil since 1991 when she was diagnosed as Graves' disease. Laboratory evaluations revealed an elevated erythrocyte sedimentation rate (ESR) of 133 mm/h, a high CRP level of 13.2 mg/dl and positive antinuclear antibodies and anti-type II collagen antibodies. Histopathological findings of the biopsy specimen from the auricular cartilage included chondrocyte degeneration, matrix destruction and inflammatory cell infiltration. She was diagnosed as RP and treatment with 30 mg/day of prednisolone dramatically improved all symptoms and signs, accompanied by a fall in ESR, CRP and autoantibodies. When prednisolone was tapered to 5 mg/day, a clinical relapse occurred. After discontinuation of propylthiouracil, she has been well without prednisolone. Propylthiouracil-induced SLE-like syndrome or antineutrophil cytoplasmic antibodies (ANCA) related angitis has been reported previously. In addition, recent studies demonstrated that about 20% of sera from patients with relapsing polychondritis are P-ANCA positive. This is the first report suggesting a possible association between the development of relapsing polychondritis and propylthiouracil.

Bronchial arterial angio-CT: evaluation of intradural and oesophageal enhancement before bronchial arterial infusion.

Ultrafast CT combined with bronchial angiography (BA angio-CT) demonstrated a supply from the bronchial arteries to the oesophagus and spinal cord which is not identified on conventional bronchial arteriography using a digital subtraction technique. 20 patients with bronchial carcinoma and one with lung metastasis were examined using BA angio-CT, before bronchial artery infusion. 20 ml of non-ionic iodinated contrast medium (300 mgI ml-1) was injected into the bronchial artery, and ultrafast CT of the whole mediastinum was commenced when 10 ml had been injected. The 6 mm single slice mode was used and 40 images were obtained. Intradural and oesophageal enhancement was evaluated on BA angio-CT, and compared with the findings on digital subtraction angiography (DSA) of the bronchial arteries. BA angio-CT clearly showed intradural enhancement in eight patients. Marked spinal cord enhancement was demonstrated in three, and a coaxial catheter technique was used to avoid infusing the intercostal branch of the intercostobronchial trunk. Oesophageal enhancement was demonstrated in 18 patients on BA angio-CT. In contrast, no enhancement of these structures was seen on bronchial arterial DSA. In conclusion, BA angio-CT enabled precise evaluation of intradural and oesophageal enhancement.