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Biomedical subjects

Yutaka Imai

Publications and source records attributed to Yutaka Imai.

At least 19 recordsLinked to original sources

Circadian variation of the myocardial ischemic threshold in patients with ischemic heart disease.

PURPOSE: Circadian variation of the heart rate (HR) at the myocardial ischemic threshold was compared with that of the HR at the sympathetic tone threshold in 16 cases of effort angina pectoris. METHODS: The high (0.15-0.40 Hz, Hf) and low (0.03-0.15 Hz, Lf) frequency spectral components were extracted every twenty seconds, using frequency domain analysis of the RR interval recorded by a 24-hour Holter ECG with an accelerometer. HR-Hf data collected every five minutes were plotted as the X-Y coordinates, and a two-compartment analysis was performed. The HR at the autonomic tone threshold was then determined at the intersection point of the lines. A loop of the HR-ST segment was drawn during walking to determine the ischemic threshold at which heart rate ischemic ST segment depression began and circadian variation was observed. RESULTS: The circadian rhythm at the sympathetic tone threshold and the HR at the ischemic threshold were high during the day and low at night. The HR at the ischemic threshold was 15-20% higher than that at the sympathetic tone threshold at night but only 9-13% higher during the day. Also, there was a period during which there was no significant difference between the HR at the two thresholds. CONCLUSION: In comparing circadian variation between HR at the sympathetic tone threshold and HR at the ischemic threshold, there was a period during which there was no significant difference between the HRs. This might suggest a period in which a high incidence of cardiac ischemic attack is likely. This information could provide a feasible indicator for appropriate exercise training for patients with ischemic heart disease.

Activities of Daily Living↗

Progress report on The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study: status at February 2004.

The Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) Study is the first large-scale intervention trial in Japan using a PROBE design to determine an optimal target blood pressure (BP) level on the basis of self-measured BP at home and optimal initial antihypertensive medication. The registered patients are randomized to one of two different BP levels and to initial antihypertensive regimens (i.e., calcium antagonist [Ca-A], angiotensin-converting enzyme inhibitor [ACE-I], or angiotensin II receptor antagonist [ARB]). At the end of February 2004, 2729, 1687, and 971 patients were recruited, randomized, and followed-up for 12 months or more. Among the 971 patients, mean systolic/diastolic BP levels at randomization in the Ca-A, ACE-I, and ARB groups were 150/90, 152/89, and 151/89 mmHg, respectively. These values reduced after six months of Ca-A-, ACE-I-, and ARB-based treatment (133/81 mmHg, 135/80 mmHg, and 134/79 mmHg, respectively) and further reduced after 12 months (131/80 mmHg, 134/79 mmHg, and 132/79 mmHg, respectively) without any significant differences among groups. In more intensive and less intensive BP-lowering groups, mean systolic/diastolic BP levels at randomization were 151/90 and 150/89 mmHg, respectively. Although BP levels reduced after 6-month (135/80 mmHg and 133/80 mmHg, respectively) and 12-month treatment (133/79 mmHg and 132/80 mmHg, respectively) in each target group, no significant difference in BP values was observed between groups. These results indicate the necessity of additional interventional strategies to improve the achievement of target BP levels, especially in the more intensive BP-lowering group.

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Detection of carotid atherosclerosis in individuals with masked hypertension and white-coat hypertension by self-measured blood pressure at home: the Ohasama study.

OBJECTIVE: To investigate carotid atherosclerosis in individuals with masked hypertension (MHT) and white-coat hypertension (WCHT) in a general population. METHODS: Self-measurement of blood pressure at home (HBP) and casual blood pressure (CBP) measurements were recorded in 812 individuals aged at least 55 years (mean 66.4 years) from the general Japanese population. The intima-media thickness (IMT) of the near and far wall of both common carotid arteries was measured and averaged. The relationships between carotid atherosclerosis (IMT and plaque) and the four blood pressure groups (sustained normal blood pressure: HBP < 135/85 mmHg, CBP < 140/90 mmHg; WCHT: HBP < 135/85 mmHg, CBP >or= 140/90 mmHg; MHT: HBP >or= 135/85 mmHg, CBP < 140/90 mmHg; sustained hypertension: HBP >or= 135/85 mmHg, CBP >or= 140/90 mmHg) were examined using multivariate analysis adjusted for possible confounding factors. RESULTS: Adjusted IMT in individuals with sustained hypertension [0.77 mm; 95% confidence interval (CI) 0.75 to 0.79 mm] and MHT (0.77 mm; 95% CI 0.73 to 0.80 mm) was significantly greater than in those with sustained normal blood pressure (0.71 mm; 95% CI 0.69 to 0.72 mm) and WCHT (0.72 mm; 95% CI 0.71 to 0.74 mm) (P < 0.0001). The odds ratios for the presence of plaques in all four groups were similar to the trends in IMT. CONCLUSIONS: Our findings imply that CBP measurements alone are insufficient to distinguish individuals at high risk of carotid atherosclerosis from those at low risk. However, these individuals do have distinct HBP measurements, suggesting that HBP measurement could become a valuable tool for predicting carotid atherosclerosis.

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Amlodipine versus angiotensin II receptor blocker; control of blood pressure evaluation trial in diabetics (ADVANCED-J).

BACKGROUND: The coexistence of type 2 diabetes mellitus and hypertension increases the risk of cardiovascular diseases. The U.K. Prospective Diabetes Study has shown that blood pressure control as well as blood glucose control is efficient for prevention of complications in hypertensive patients with diabetes mellitus. However, some reports have shown that it is difficult to control the blood pressure and the concomitant use of a plurality of drugs is needed in hypertensive patients with diabetes mellitus. In recent years renin-angiotensin system depressants are increasingly used for the blood pressure control in diabetic patients. Particularly in Japan, angiotensin II (A II) antagonists are increasingly used. However, there is no definite evidence of the point of which is efficient for the control, the increase in dose of A II antagonist or the concomitant use of another drug, in hypertensive patients whose blood pressure levels are inadequately controlled with A II antagonist. METHODS/DESIGN: Hypertensive patients of age 20 years or over with type 2 diabetes mellitus who have been treated by the single use of AII antagonist at usual doses for at least 8 weeks or patients who have been treated by the concomitant use of AII antagonist and an antihypertensive drug other than calcium channel blockers and ACE inhibitors at usual doses for at least 8 weeks are included. DISCUSSION: We designed a multi-center, prospective, randomized, open label, blinded-endpoint trial, ADVANCED-J, to compare the increases in dose of A II antagonist and the concomitant use of a Ca-channel blocker (amlodipine) and A II antagonist in hypertensive patients with diabetes mellitus, whose blood pressure levels were inadequately controlled with A II antagonist. This study is different from the usual previous studies in that home blood pressures are assessed as indicators of evaluation of blood pressure. The ADVANCED-J study may have much influence on selection of antihypertensive drugs for treatment in hypertensive patients with diabetes mellitus. It is expected to give an important hint for considering the validity of selection of antihypertensive drugs from the aspects not only of the antihypertensive effect but medical cost-effectiveness.

Adult↗

Predicting stroke using 4 ambulatory blood pressure monitoring-derived blood pressure indices: the Ohasama Study.

We investigated the association between stroke and blood pressure (BP) indices (systolic BP [SBP], diastolic BP [DBP], mean BP [MBP], and pulse pressure [PP]) determined by ambulatory BP monitoring. The predictive power for stroke of these indices was compared in the general Japanese population. We obtained ambulatory BP data in 1271 subjects (40% men) aged > or = 40 (mean: 61) years. During a mean follow-up of 11 years, 113 strokes were observed. The multivariate adjusted relative hazard and likelihood ratio for a 1-SD increase for each BP index was determined by Cox proportional hazard regression. Comparison of the likelihood ratio between Cox models including 2 indices and those including 1 index indicated that PP was significantly less informative than other indices (P<0.01 when adding MBP, SBP, or DBP to the PP model; P>0.09 when adding PP to the model including another index). However, after removing age from covariates, PP became more informative than DBP and MBP (P<0.0001 when adding PP to the MBP or DBP model, whereas SBP was more informative than PP even after removing age; P<0.05 when adding SBP to the PP model). In conclusion, PP was the weakest predictor of stroke. Exclusion of age from covariates increased the predictive power of PP, suggesting that the stroke risk associated with PP reflected the risk of aging per se.

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Prediction of stroke by home "morning" versus "evening" blood pressure values: the Ohasama study.

Predictive power of self-measured blood pressure at home (home BP) for cardiovascular disease risk has been reported to be higher than casual-screening BP. However, the differential prognostic significance of home BP in the morning (morning BP) and in the evening (evening BP), respectively, has not been elucidated. In the Ohasama study, 1766 subjects (>or=40 years) were followed up for an average of 11 years. The predictive power for stroke incidence of evening BP was compared with that of morning BP as continuous variables. The Cox regression model demonstrated that evening BP and morning BP predicted future stroke risk equally. Subjects were also assigned to 1 of 4 categories based on home BP. In this analysis, stroke risk in morning hypertension ([HT] morning BP >or=135/85 mm Hg and evening BP <135/85 mm Hg; relative hazard (RH): 2.66; 95% CI:1.64 to 4.33) and that in sustained HT(morning BP and evening BP >or=135/85 mm Hg; RH: 2.38; 95% CI: 1.65 to 3.45) was significantly higher than that in normotension (morning BP and evening BP <135/85 mm Hg). The risk in morning HT was more remarkable in subjects taking antihypertensive medication (RH: 3.55; 95% CI: 1.70 to 7.38). Although the risk in evening HT (morning BP <135/85 mm Hg and evening BP >or=135/85 mm Hg) was higher than that in normotension, the differences were not significant. In conclusion, morning BP and evening BP provide equally useful information for stroke risk, whereas morning HT, which indicates HT specifically observed in the morning, might be a good predictor of stroke, particularly among individuals using anti-HT medication.

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Potential effect on cellular response to cadmium of a single-nucleotide A --> G polymorphism in the promoter of the human gene for metallothionein IIA.

Most people generally ingest cadmium in their food. Cadmium that has accumulated in tissues induces the synthesis of metallothioneins (MTs) which are metal-binding proteins that bind tightly to cadmium to inhibit its renal toxicity. Individuals whose ability to induce the synthesis of MTs is low seem likely to be particularly susceptible to the toxic effects of cadmium. In this study, we analyzed the polymorphism of the promoter region of the gene for MT-IIA, the major species of MT in humans, in 119 adult Japanese subjects. We found that about 18% of the subjects had an A --> G single-nucleotide polymorphism in the core region of the promoter near the TATA box. A reporter-gene assay using HEK293 cells showed that replacement of A by G at position -5 reduced the efficiency of the cadmium-induced transcription of the gene for MT-IIA. This single-nucleotide polymorphism inhibited the binding of nuclear proteins to the core promoter region of the gene for MT-IIA. When the promoter region upstream of the TATA box was replaced by a sequence that contained three dioxin-responsive elements, the reporter-gene assay demonstrated that the A --> G single-nucleotide polymorphism resulted in a marked reduction in the rate of dioxin-induced transcription. These results suggest that the A --> G single-nucleotide polymorphism reduces the efficiency of those aspects of the transcription of the gene for MT-IIA that are controlled by general transcription factors.

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The current status of home and office blood pressure control among hypertensive patients with diabetes mellitus: the Japan Home Versus Office Blood Pressure Measurement Evaluation (J-HOME) study.

Although self-measured blood pressure (BP) at home (HBP) has become popular in clinical practice, little information is available regarding the proportion of diabetic patients with properly controlled HBP. We evaluated the status of HBP control in diabetic hypertensives. HBP control status was cross-sectionally evaluated among 3400 essential hypertensives taking antihypertensive treatment. Of these, 466 (14%) had diabetes. Physicians evaluated the subjects' HBP control as "poor", "fairly good", or "excellent" using a self-administered questionnaire. When the HBP threshold in diabetic patients was set tentatively at 130/80 mmHg or 135/85 mmHg, HBP was properly controlled in 18% or 30% of diabetic patients, respectively. The same trend was observed in office BP. The average number of drugs prescribed for diabetic patients was 2.0 drugs. In the majority of diabetic patients with uncontrolled BP, the BP control status in two-thirds of those was evaluated as "excellent" or "fairly good" by their physicians. In Japan, HBP and office BP were not adequately controlled in most diabetic hypertensives. The main reason for this would appear to be a lack of intensive treatment and a lack of recognition by physicians that their patients' BP was insufficiently controlled.

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Enhanced radial late systolic pressure augmentation in hypertensive patients with left ventricular hypertrophy.

BACKGROUND: Wave reflection augments central blood pressure (BP) in late systole, thus increasing cardiac afterload. We examined the relationship between late systolic pressure augmentation in the peripheral radial artery pulse wave and the existence of left ventricular hypertrophy (LVH) in hypertension. METHODS: Brachial BP, radial augmentation index (AI(r)), and carotid-femoral pulse wave velocity (PWV(cf)) were determined in 77 untreated hypertensive patients aged 56 +/- 10 years. Cardiac structure and function were assessed by ultrasound, and LVH was defined based on the LV mass index (LVMI). Using multivariate analysis, patient characteristics were compared between those with (+) and without (-) LVH. RESULTS: The LVMI was correlated independently and positively with AI(r) (beta = 0.33, P = .004) and the brachial mean arterial pressure (MAP; beta = 0.25, P = .03). The ratio of early to atrial peak velocities (E/A ratio) of the diastolic transmitral flow tended to be correlated negatively with the AI(r). The LVH (+) group had a significantly higher AI(r) than the LVH (-) group [LVH (+), 97% v LVH (-), 89%, P = .003]; this difference remained significant even after adjustment for age, gender, MAP, and heart rate. The adjusted relative risk of LVH was 1.99 for each 10% AI(r) increase (P = .005). In contrast, LVMI was not correlated with the PWV(cf), and the PWV(cf) was not different between the LVH (+) and LVH (-) groups. Moreover, there was no significant correlation between PWV(cf) and AI(r). CONCLUSIONS: These results suggest that the peripheral AI(r) measurement is clinically useful in predicting LVH. Enhanced wave reflection may be related to the development of LVH in hypertensive patients.

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Electrocardiographic left ventricular hypertrophy and arterial stiffness: the Ohasama study.

BACKGROUND: Whether arterial stiffness per se contributes to left ventricular hypertrophy (LVH) independently of blood pressure (BP) remains unknown. We examined the relationship between pulse wave velocity (PWV) and LVH in a large population. METHODS: The PWV was measured between the brachial and ankle regions (baPWV) of 798 individuals. We diagnosed LVH using electrocardiographic criteria: Cornell voltage-duration product >2440 mm x msec or Sokolow-Lyon voltage >38 mm. The participants were initially separated into those with and without LVH [LVH(+) and LVH(-) groups, respectively]. To determine theoretical baPWV, we first constructed a nomogram for the LVH(-) group, calculated the PWV index (measured baPWV - theoretical baPWV) for each individual and then compared the two groups. We also examined the factors associated with LVH(+) using multivariate analyses. RESULTS: Linear regression analysis revealed that the theoretical baPWV (m/sec) = 0.20 x age (years) + 0.13 x Mean arterial pressure (MAP) (mm Hg) + 0.05 x Heart rate (beats/min) - 11.74 (R(2) = 0.56). The PWV index was greater in the LVH(+) than in the LVH(-) group (P = .025). The baPWV was independently related to LVH(+) along with MAP, medication for hypertension, and for diabetes; a 1 SD (4.3 m/sec) increase in baPWV was associated with a 26% increase in the risk of LVH(+) (P = .022). When LVH(+) risk factors were defined as hypertension, diabetes, and high baPWV (> or =14.6 m/sec), the prevalence of LVH(+) linearly increased with the number of concomitant LVH(+) risk factors (P < .001). CONCLUSIONS: Arterial stiffness is independently related to electrocardiographically determined LVH in the general population.

Adult↗

Characteristics of resistant hypertension determined by self-measured blood pressure at home and office blood pressure measurements: the J-HOME study.

OBJECTIVES: To diagnose resistant hypertension using self-measured blood pressure (BP) at home and office BP, and to evaluate the characteristics of resistant hypertensive patients. METHODS: The subjects were 528 hypertensive patients taking at least three or more different antihypertensive drugs. Subjects were classified into four groups (controlled hypertension, isolated office resistant hypertension, isolated home resistant hypertension and sustained resistant hypertension) on the basis of the cut-off values of home BP (135/85 mmHg) and office BP (140/90 mmHg). The relationship between each resistant hypertension group and various factors was analysed using univariate and multivariate analyses. RESULTS: Of the 528 patients, 17.8% were classified with controlled hypertension, 16.1% with isolated office resistant hypertension, 23.5% with isolated home resistant hypertension and 42.6% with sustained resistant hypertension. The presence of hypercholesterolemia was found to have a significant and independent association with isolated office resistant hypertension. Higher office systolic blood pressure (SBP), a past history of ischaemic heart disease, and a lower prescription rate of potassium-sparing diuretics were found to have a significant and independent association with isolated home resistant hypertension. Patients with sustained resistant hypertension had a significantly lower prescription rate of potassium-sparing diuretics than those with controlled hypertension. CONCLUSIONS: The present study demonstrated that resistant hypertension is mediated at least partly by the white-coat effect. Home BP measurements and other relevant factors associated with resistant hypertension, such as relatively higher office SBP, type of drugs prescribed, and cardiovascular complications, should be taken into account for the diagnosis and treatment of resistant hypertension.

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Prognostic significance of night-time, early morning, and daytime blood pressures on the risk of cerebrovascular and cardiovascular mortality: the Ohasama Study.

OBJECTIVE: To clarify whether high blood pressure (BP) at a particular time of day is associated with cerebrovascular and cardiovascular mortality risk. METHODS: Cerebrovascular and cardiovascular mortality in 1360 individuals aged 40 years and older in Ohasama, Japan, was followed for an average of 10.6 years. We used 2-h moving averages of the BP (a total of 24 average BP measurements for two consecutive hours based on four BP readings taken every 30 min) to compare the predictive power of BP taken during a 24-h period given the same number of measurements. The associations between cerebrovascular and cardiovascular mortality risk and the 2-h moving averages of systolic blood pressure (2 h-SBP) recorded over 24 h were analysed using a Cox proportional hazards model after adjusting for possible confounding factors. RESULTS: The total cerebrovascular and cardiovascular mortality risk was significantly associated with elevated 2 h-SBP recorded during the night and early morning periods. Haemorrhagic stroke mortality was significantly associated with elevated daytime 2 h-SBP. Cerebral infarction mortality and heart disease mortality were significantly associated with elevated night-time 2 h-SBP. CONCLUSION: High BP at different times of day were associated with different subtypes of cerebrovascular and cardiovascular mortality risk.

Adult↗

Introversion associated with large differences between screening blood pressure and home blood pressure measurement: The Ohasama study.

OBJECTIVE: To explore the effect of personality on screening blood pressures measured in clinical settings and home blood pressure measurements. METHODS: From 1997 to 1999, 699 participants underwent screening and home blood pressure measurements and completed the Japanese version of the short-form Eysenck personality questionnaire. An increased screening blood pressure was defined as screening blood pressure > or = 140/90 mmHg and an increased home blood pressure was defined as home blood pressure > or = 135/85 mmHg. RESULTS: Participants with lower extroversion scores (i.e., introversion) showed a greater difference between screening and home systolic blood pressure. The association between introversion and differences was statistically significant, even after adjustment for other possible factors (younger age, female, wide screening pulse pressure, never smoked, and no antihypertensive medication). The adjusted means of SBP differences were 7.3 and 4.4 mmHg among the lowest and highest extroversion quartiles, respectively (P for trend = 0.02). Other personality scores (psychoticism or neuroticism) were not associated with screening and home blood pressure differences. The incorporation of an extroversion score in the basic model consisting of the above factors that affected the difference between screening and home blood pressure slightly improved the prediction of a high home blood pressure. The area under the receiver operating characteristic curve increased by 0.037 among participants with high screening blood pressure and 0.006 for those with normal screening blood pressure compared with the basic model. CONCLUSION: Physicians may need to be aware of 'introverted' patients who have high blood pressure in clinic settings, because they have the potential for 'white-coat' hypertension.

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The economic impact of the introduction of home blood pressure measurement for the diagnosis and treatment of hypertension.

OBJECTIVES: To investigate the economic consequences resulting from introduction of home blood pressure measurement in diagnosis of hypertension instead of casual clinic blood pressure measurement. METHODS: We constructed a decision tree model using data from the Ohasama study and a Japanese national database. The Ohasama study provided the prognostic value of home blood pressure as compared with clinic blood pressure measurement. RESULTS: It is predicted that the use of home blood pressure for hypertension diagnosis results in a saving of 9.30 billion US dollars (1013.6 billion yen) in hypertension-related medical costs in Japan. Most of this was attributable to medical costs saved by avoiding the start of treatment for untreated individuals who were diagnosed as hypertensive by clinic blood pressure but whose blood pressures were in the normal range when based on home blood pressure; that is, the so called white-coat hypertension. Furthermore, it could be expected that adequate blood pressure control mediated by the change in the diagnostic method from clinic to home blood pressure measurement would improve the prognosis for hypertension. We estimated that the prevention of hypertensive complications resulted in a reduction of annual medical costs by 28 million US dollars (3.0 billion yen). In addition, stroke prevention due to adequate blood pressure control based on home blood pressure measurement reduced annual long-term care costs by 39 million US dollars (4.2 billion yen). A per-person break-even cost for introducing home blood pressure monitoring was calculated as 409 US dollars (44,580 yen). CONCLUSIONS: The introduction of home blood pressure measurement for the diagnosis and treatment of hypertension would be very effective to save costs.

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The value of self-measured home blood pressure in predicting stroke.

Home blood pressure measurements more accurately and reliably reflect target organ damage and the prognosis of cardiovascular disease than conventional blood pressure measurements. All evidence of the value of home blood pressure measurement in predicting stroke is currently derived from a population-based prospective study in Japan (the Ohasama study). The authors demonstrated that home blood pressure measurement provides more useful prognostic information on stroke than conventional blood pressure measurements. The predictive value of home blood pressure measurement increased progressively with the number of measurements. Even the initial-first home blood pressure values (one measurement) showed a significantly greater relation with stroke risk than conventional blood pressure values (mean of two measurements). Home blood pressure measurement increased the predictive power of categorizations of guidelines compared with conventional blood pressure measurement. Home blood pressure measurement is a useful tool to predict future risk of stroke.

Blood Pressure↗

Differentiation-inducing therapy for solid tumors.

Treating malignant tumor through the induction of cell differentiation has been an attractive concept, but clinical development of differentiation-inducing agents to treat malignant tumor, especially for solid tumors has been limited to date. Nerve growth factor, all trans retinoic acid, dimethyl sulfoxide, active form vitamin D(3), peroxisome proliferator-activated receptorgamma, 12-0-tetradecanoylphorbol 13-acetate, hexamethylene-bis-acetamide, transforming growth factor-beta, butyric acid, cAMP, and vesnarinone are known to have a differentiation-inducing capability on solid tumors in vitro and/or in vivo. Moreover some of the differentiation-inducing agents have been used for treating patients with solid tumor, but the therapeutic effect of the differentiation-inducing agents on solid tumor is not strong when compared with that of conventional chemotherapeutic agents. However, because most of the differentiation-inducing agents can potentiate the effect of conventional chemotherapy or radiation therapy, combination of differentiation-inducing therapy with conventional chemotherapy or radiation therapy might be used as a second- or third-line therapy in patients with advanced cancer. Furthermore, analysis of the molecular mechanisms of the tumor differentiation therapy might provide selective and targeted molecules for novel cancer therapy.

Animals↗

[A case of tuberculous lymphadenitis found as an abdominal mass penetrating the duodenum].

A 42-year-old woman who complained of epigastralgia was referred to our hospital because of an abdominal mass found by ultrasonography. CT and MRI scans revealed that the abdominal mass, 4 cm in diameter, located on the left side of the right kidney. Gastroduodenoscopy detected a deep ulcerative lesion covered with a yellowish coat in the second portion of duodenum. A sonolucent area at the bottom of the ulcerative lesion seemed to expand to the abdominal mass on ultrasonic endoscopy. Tuberculosis was one possible differential diagnosis. Pathological examination including Ziehl-Neelsen staining using biopsy specimens taken from the bottom of the ulcerative lesion did not show tuberculosis infection. However, polymerase chain reaction analysis using the biopsy specimens revealed that gene expression of tuberculosis was positive. We determined that tuberculous lymphadenitis penetrated the duodenum forming an ulcerative lesion in the duodenum. The administration of anti-tubercular medicine for 6 months male the abdominal mass disappeared and the duodenal ulcerative lesion formed an ulcer scar. We report here a case of tuberculous lymphadenitis penetrating the duodenum which was successfully treated by conservative therapy without surgical treatment.

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