• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.95-103
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• 1996

Reverse redistribution(RRD) refers to a perfusion defect that develops or becomes more evident on rest imaging compared with the stress imaging. This phenomenon was not uncommonly noted on myocardial perfusion single photon emission computed tomography (SPECT). However, the clinical significance and pathophysiological mechanism of RRD were unclear. The aim of this study was to evaluate the incidence and clinical significance of RRD on either dipyridamole T1-201 or Tc-99m MIBI myocardial perfusion SPECT. RRD was defined as ${\geq}10%$ decrease in relative T1-201 and Tc-99m MIBI uptakes on rest images compared to the stress images or as an appearance of new perfusion defects on rest images. It was observed in both T1-201 (44/463, 9.5%) and Tc-99m MIBI (124/999, 12.4%) myocardial SPECTs similarly, with an overall incidence of 11.5%(168/1462). Many apparent)y unrelated disease groups showed the finding: post-revascularization(53.9%), coronary artery disease(24.6%), myocardial infarction(12.3%), and those with normal coro-nary arteries (9.2%). Clinical and angiographic characteristics of 65 consecutive patients who underwent coronary arteriography in 168 patients who had RRD on myocardial perfusion SPECT were reviewed. Tc-99m MIBI was used in 44 patients, and T1-201 was used in 21 patients. Of the 81 myocardial segments analyzed which showed RRD, 32 segments(39.5%) were in septum, 24(29.5%) in inferior wallL, 12(14.8%) in anterior wall, 7(8.7%) in apex and 6(7.4%) in lateral wall. There was no clear association between RRD and coronary arterial stenosis or Presence of collateral circulations. Ventriculographical wall motion was evaluated in 27 regions with RRD; it was normal in 12 regions, hypokinetic in 12 regions and dyskinetic in 3 regions. In 14 of 21 patients who showed RRD on T1-201 myocardial SPECT, T1-201 reinjection was performed immediately after the 3-4 hour redistribution studies. Ten of 14 (71.4%) showed enhanced T1-201 activity(${\geq}10%$ increased) after reinjection. We conclude that RRD is not related to mode of stress or radiopharmaceuticals. RRD might represent many inhomogeneous pathophysiological processes.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.153-168
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• 1998

Background: The existing data indicate that obstructive sleep apnea syndrome contributes to the development of cardiovascular dysfunction such as systemic hypertension and cardiac arrhythmias, and the cardiovascular dysfunction has a major effect on high long-term mortality rate in obstructive sleep apnea syndrome patients. To a large extent the various studies have helped to clarify the pathophysiology of obstructive sleep apnea, but many basic questions still remain unanswered. Methods: In this study, the influence of obstructive sleep apnea on systemic blood pressure, cardiac rhythm and urinary catecholamines concentration was evaluated. Over-night polysomnography, 24-hour ambulatory blood pressure and ECG monitoring, and measurement of urinary catecholamines, norepinephrine (UNE) and epinephrine (UEP), during waking and sleep were undertaken in obstructive sleep apnea syndrome patients group (OSAS, n=29) and control group (Control, n=25). Results: 1) In OSAS and Control, UNE and UEP concentrations during sleep were significantly lower than during waking (P<0.01). In UNE concentrations during sleep, OSAS showed higher levels compare to Control (P<0.05). 2) In OSAS, there was a increasing tendency of the number of non-dipper of nocturnal blood pressure compare to Control (P=0.089). 3) In both group (n=54), mean systolic blood pressure during waking and sleep showed significant correlation with polysomnographic data including apnea index (AI), apnea-hypopnea index (AHI), arterial oxygen saturation nadir ($SaO_2$ nadir) and degree of oxygen desaturation (DOD). And UNE concentrations during sleep were correlated with AI, AHI, $SaO_2$ nadir, DOD and mean diastolic blood pressure during sleep. 4) In OSAS with AI>20 (n==14), there was a significant difference of heart rates before, during and after apneic events (P<0.01), and these changes of heart rates were correlated with the duration of apnea (P<0.01). The difference of heart rates between apneic and postapneic period (${\Delta}HR$) was significantly correlated with the difference of arterial oxygen saturation between before and after apneic event (${\Delta}SaO_2$) (r=0.223, P<0.001). 5) There was no significant difference in the incidence of cardiac arrhythmias between OSAS and Control In Control, the incidence of ventricular ectopy during sleep was significantly lower than during waking. But in OSAS, there was no difference between during waking and sleep. Conclusion : These results suggested that recurrent hypoxia and arousals from sleep in patients with obstructive sleep apnea syndrome may increase sympathetic nervous system activity, and recurrent hypoxia and increased sympathetic nervous system activity could contribute to the development of cardiovascular dysfunction including the changes of systemic blood pressure and cardiac function.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.147-158
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• 1996

Background : Endobronchial tuberculosis(ET) is known to affect frequently young female and serious complication like bronchial stenosis would occur if early diagnosis and treatment for ET is not performed immediately. But ET shows normal chest roentgenogram in about 10% of patients, and is often confused with bronchial asthma because ET presents clinical features like cough, dyspnea, wheezing in history and physical examination. The pulmonary function test(PFT) feature of ET is not well known, but when we consider the fact that ET is pathophysiologically different from bronchial asthma, if there is any feature of PFT in ET, and we know it, PFT will be very helpful for diagnosis and follow up of ET. Methods : We performed both PFT and bronchoscopy in 68 ET patients who visited Boramae hospital, and were confirmed as ET by bronchoscopic biopsy and were followed prospectively from November 1991 to March 1995. After history taking and physical examination, we performed chest roentgenogram, complete blood count, sputum AFB stain and culture, and also performed PFT before anti-tuberculosis chemotherapy. PFT was classified as restrictive, if only PVC was reduced below 80%, and obstructive, if only FEV1 was reduced below 75%. In the case of both FVC and FEV1 were reduced, PFT was classified as restrictive if FEY1/FVC was greater than 75%, and mixed if FEV1/FVC was reduced below 75%. We repeated the PFT and bronchoscopy for 68 ET patients who were proven by biopsy in the first month and sixth month after starting anti-tuberculosis chemotherapy, and studied the feature and change of PFT of the ET and the relation between PFT and the bronchoscopic finding, and obtained following results. Results: 1) Number of male patients was 12, and that of female patient was 56, and mean age was $35.4{\pm}17yr$.(17-74yr). Clinical symptom was in the order of cough(86.8%), dyspnea(63.2%), fever(17.6%) and hemoptysis (10.3%), and the wheezing and stridor were audible among the 40 patients(58.4%) in the physical examination. 2) Hemoglobin level was below 12g/dl among 25 patients (36.8%), and WBC level was above $10,000/mm^3$ among 9 patients(13.2%) and ESR was above 20 among 46 patients (67.6%) and AFB stain and culture were positive among 50 patients(73.5%). 3) The dominant roentgenographic finding of ET was fibronodular feature in 35 patients(51.5%), pneumonic feature in 14 patients (20.6%), collapse in 11 patients(16.2%), mass-like lesion in 3 patients(4.4%), cavitary lesion in 2 patients(2.9%), and normal in 3 patients(4.4%). 4) PFT feature at the time of diagnosis of ET was normal in 16 patients(23.5%), restrictive pattern in 32 patients (47%), obstructive in 4 patients(5.8%), and mixed in 14 patients(23.5%). So restrictive pattern was the dominate feature of ET. 5) The PFT feature was little correlated with the gross finding of bronchoscopy, but the change of PFT during treatment of ET showed relatively good correlation with the change of bronchoscopic finding. 6) FVC(2.30L vs. 2.61L) and FEV1(1.74L vs. 2.06L) increased significantly (p < 0.01), but FEV1/FVC(82% vs. 83%) and PEF(3.45L/sec vs. 3.95L/sec) did not change significantly after 1 month of treatment (p > 0.01), and there was no significant change among all parameters during first and sixth month of treatment(p > 0.01). Conclusion : PFT may be useful in the diagnosis and treatment follow up of ET but further study would be needed to confirm it.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.822-835
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• 1997

Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1236-1251
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• 1998

Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.