High-dose methylprednisolone with chemotherapy for invasive thymoma: a case report.

A case of invasive thymoma that responded well to the administration of a high-dose methylpredonisolone with cisplatin and adriamycin is reported. A 63-year-old woman was admitted to our hospital because of dyspnea, chest oppression and edema of the face. Chest CT revealed a large mass in the anterior mediastinum with the opacification of superior vena cava. Biopsy specimens from the mass revealed a spindle cell thymoma, consisting of epithelial cells and lymphoid cells. A diagnosis of invasive thymoma was made and the patient was intravenously treated with a high-dose of methylprednisolone (1000 mg on days 1-5 and 500 mg on days 6 and 7), cisplatin (80 mg/m2 on day 1) and adriamycin (40 mg/m2 on day 1). The treatment with three courses of this combined chemotherapy resulted in the improvement and regression of all clinical signs and symptoms. This case demonstrated that a high-dose methylprednisolone with cisplatin and adriamycin might be potentially effective for invasive thymoma.

Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-alpha therapy: possible etiology of HCV-associated immune thrombocytopenia.

We evaluated the relationship between the severity of thrombocytopenia and the serum hepatitis C virus (HCV) RNA level to investigate the mechanism of thrombocytopenia in patients with HCV infection. Patients who had chronic hepatitis without splenomegaly were divided into two groups according to the platelet count, which were 18 patients with a platelet count < or =150 x 10(9)/L and 22 patients with a platelet count >150 x 10(9)/L. HCV RNA, platelet-associated immunoglobulin G (PAIgG), rheumatoid factor (RF), and other immunological parameters were measured and correlations were investigated. Patients in the low platelet group had higher levels of PAIgG, Th1 cells, thrombopoietin (TPO), and RF than those in the normal platelet group (textitP < 0.05). Twenty-two patients completed 6 months of IFN therapy and were followed for more than 1 yr afterwards. Twelve patients who responded to IFN therapy with clearance of HCV showed an increase of the platelet count, whereas the 10 patients who did not respond to IFN showed a decrease of the platelet count. The improvement of thrombocytopenia after interferon therapy suggests a contribution of HCV infection to this condition.

Successful treatment of hypertrophic osteoarthropathy by gefitinib in a case with lung adenocarcinoma.

Hypertrophic osteoarthropathy is an important manifestation of lung carcinoma, particularly in a non-small cell tumor, and hampers quality of life. Although removal of the primary tumor usually resolves this syndrome, effective treatment in patients with advanced lung carcinoma has not been established. Recently, an orally active, selective epidermal growth factor receptor tyrosine kinase (EGFR) inhibitor ("Gefitinib") provided clinical anti-tumor activity. We describe a 71-year-old male smoker with cough, who presented with clubbed fingers. A transbronchial lung biopsy (stage T2N3M1-IV) on a cavity lesion in the left lower lobe showed the features of adenocarcinoma, while bone scintigram revealed bilaterally symmetrical abnormal uptakes in the lower extremities, suggesting secondary hypertrophic osteoarthropathy. The serum level of growth hormone was increased to 1.42 ng/ml. Chemotherapy (cisplatin, vinorelbine) was not effective. Gefitinib, as a second-line therapy, induced disappearance of the abnormal accumulation on bone scintigraphy and decrease of the cavity in the lung and of serum growth hormone. The presented case suggests that the EGFR inhibitor might be a promising option for the treatment of hypertrophic osteoarthropathy with advanced lung adenocarcinoma.

Weekly variation of home and ambulatory blood pressure and relation between arterial stiffness and blood pressure measurements in community-dwelling hypertensives.

Although blood pressure (BP) is a major determinant of pulse wave velocity (PWV), some treatments have independent effects on BP and arterial stiffness. Although both ambulatory BP (ABP) and self-measured BP at home (HBP) have become important measures for the diagnosis and management of hypertension, single day recordings may be insufficient for a proper diagnosis of hypertension or the evaluation of treatment efficacy. To evaluate weekly variations in BP using 7-day HBP and 7-day ABP monitoring and to determine the relation between arterial stiffness and BP measurements in community-dwelling patients with hypertension. We enrolled 68 community-dwelling hypertensive subjects in this study. Significant weekly variations in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found in the awake ABP data (p < .01, respectively), while no significant weekly variations in the asleep ABP or the morning and evening HBP data were observed. In untreated subjects, significant correlations were obtained between the brachial-ankle PWV and the average awake SBP, the average asleep SBP and the average SBP measured by HBP in the evening. In treated subjects, only the average SBP measured by HBP in the morning was significantly correlated with the baPWV. Differences in the weekly variations in BP were observed between HBP and ABP monitoring. In addition, the morning systolic HBP was not correlated with arterial stiffness in untreated subjects with hypertension but was correlated in treated subjects. Relations between the morning HBP and arterial stiffness might be attributed to morning surges in BP and/or trough levels of antihypertensive drugs.

Repeated ambulatory monitoring reveals a Monday morning surge in blood pressure in a community-dwelling population.

BACKGROUND: Although weekly variations with a peak on Monday have been reported in the incidence of cardiovascular events, few studies have investigated weekly variations in blood pressure (BP). METHODS: One hundred and thirty-five community-dwelling subjects had 24-h ambulatory BP monitoring for 7 days. We calculated the mean awake, asleep, morning (during the first 3 h after awaking) BP, and morning BP surge (mean morning systolic BP minus mean asleep systolic BP) for each day. RESULTS: Monday surge in BP was found in the awake and morning BP (awake BP: 128.8 +/- 15.4/79.1 +/- 9.2 v 131.5 +/- 16.3/80.7 +/- 10.0 mm Hg, P < 0.01, respectively; morning BP: 127.3 +/- 17.8/78.8 +/- 11.4 v 132.5 +/- 18.2/81.2 +/- 10.0 mm Hg, P < 0.01, respectively) but was not found in the asleep BP (112.7 +/- 18.3/68.4 +/- 10.7 v 113.1 +/- 17.6/68.7 +/- 10.5 mm Hg, P = NS, respectively). The morning BP surge on Monday was higher than on the other days of the week except for Tuesday (Monday: 19.7 +/- 13.3 mm Hg v Friday: 16.4 +/- 12.9 mm Hg, P < 0.05; v Saturday: 14.7 +/- 13.3 mm Hg, P < 0.01 v Sunday: 13.7 +/- 12.0 mm Hg, P < 0.01; v Wednesday: 15.5 +/- 14.3 mm Hg, P < 0.01). CONCLUSION: Morning BP surge was the greatest on Monday in a community-dwelling population. This may be in accord with clinical evidence that cardiovascular events more frequently occur in the morning on Monday.

Lewy bodies in the sinoatrial nodal ganglion: clinicopathological studies.

Lewy bodies (LB) are characteristic pathological findings for idiopathic Parkinson disease, and extracranial organs have also been known to exhibit these structures. Clinically, the possible involvement of LB in cardiac dysfunction has attracted attention based on the findings of studies using [123I] metaiodobenzyl guanidine (MIBG) scintigraphy. The purpose of the present study was to investigate the possible involvement of LB in heart disease. A total of 40 autopsy cases consisting of Lewy body disease and Parkinson syndrome were examined. The former were cases with intracranial LB regardless of clinical symptoms, and the latter were cases with parkinsonism but without intracranial LB. The presence of heart disease or an atrial arrhythmia and the results of an MIBG scintigraphy study were clinically examined. The sinoatrial node was examined microscopically and immunohistochemically. The results showed that heart disease and atrial arrhythmia complications were more frequent in cases with Lewy body disease than in cases with Parkinson syndrome and that LB were frequently found in extracranial organs, especially in the sinoatrial nodal ganglion, in cases with Lewy body disease. In the current report, we hypothesized that neuronal changes involving LB in the sinoatrial nodal ganglion may cause arrhythmia and ischemic heart disease as a result of vasoconstriction.

Tuberculous liver abscess not associated with lung involvement.

Hepatic tuberculosis is one of the uncommon forms of extrapulmonary tuberculosis. We report a 78-year-old woman who developed tuberculous liver abscesses with splenic abscess not associated with pulmonary foci. Ultrasonography and computed tomography of the abdomen showed the low-density lesions in the liver and spleen. Histopathology of specimens obtained by percutaneous needle biopsy revealed coagulation necrosis and epithelioid cells but not tumor cells, suggesting tuberculosis infection in the liver and spleen. Systemic chemotherapy with anti-tuberculous agents led to the improvement of the lesions in the liver as well as spleen. Although tuberculous liver abscess is a very rare case, it should be included in the differential diagnosis of unknown hepatic mass lesions.

Toward chronocardiologic and chronomic insights: dynamics of heart rate associated with head-up tilting.

As a step towards investigating the chronome (i.e. the inferential endpoints of chaos, trends and rhythms) of heart rate (HR) variability (HRV), we investigated whether the fractality or complexity of HRV is affected by a head-up tilting (HUT) test in the morning after an overnight fast. Spectral and non-linear analyses of HR were performed on data gathered during an 80 degrees passive HUT test in 15 men and 28 women 32.8 +/- 11.5 years of age. The non-linear endpoints included the scaling exponents alpha1 (<11 beats) and alpha2 (>11 beats), which indicate fractal properties, calculated with detrended fluctuation analysis, and the approximate entropy (ApEn), a measure of overall complexity. Passive HUT increased alpha1 (from 0.986 +/- 0.217 to 1.370 +/- 0.185; P = 0.0001), but did not alter alpha2 (from 0.925 +/- 0.110 to 0.958 +/- 0.130; P = 0.19). A slight but statistically significant decrease in ApEn was seen during HUT (from 1.114 +/- 0.131 to 1.013 +/- 0.197; P = 0.002). In the tilt-up position, there was a statistically significant negative correlation between alpha1 and ApEn (r = -0.490; P < 0.05). In both the supine and the tilt-up position, alpha1 was correlated weakly with HF (r = -0.343 and r = -0.322, respectively), and strongly with LF/HF (r = 0.557 and r = 0.795), respectively. There was also a negative correlation between ApEn and LF/HF (r = -0.406 and r = -0.357, respectively). alpha2 did not correlate with any spectral or non-linear measures of HRV. Short-term fractal properties and complexity of HR were lowered with orthostatic stress. Alterations of the autonomic activities could be partly responsible for these changes and await extension of such studies to assess the broad spectral element of HRV, that includes, with components of approximately 3.6 and approximately 10.5 s, cycles with very much lower frequencies, along the scales of hours and even years, that critically modulate the mislabeled (only relatively high- and low-frequency) components in the range of seconds or minutes.

[A case of Lemierre syndrome].

We present a case of Lemierre syndrome characterized by thrombophlebitis of the internal jugular vein with multiple metastatic foci after acute otopharyngeal infection in a 30-year-old woman. Despite treatment with tonsillectomy leading to a diagnosis of peritonsillar abscess, her condition worsened and she was admitted with high fever. Chest radiograph and CT scan of the thorax revealed multiple pulmonary cavities and pleural effusion on the right side. On neck CT, a thrombus was detected in the left internal jugular vein. She received with intravenous clindamycin (CLDM) and cefepime (CFPM) and progressively improved. Although Lemierre syndrome is a relatively uncommon disease with the potentially life-threatening complication of acute pharyngotonsillitis, this syndrome should be considered in cases of severe tonsillitis or pharyngitis.

Involvement of Akt kinase in the action of STI571 on chronic myelogenous leukemia cells.

To elucidate the role of mitogen-activated protein kinases (MAPKs) and Akt kinase in leukemogenesis caused by the breakpoint cluster region (BCR)-Abelson (ABL) tyrosine kinase oncoprotein, we examined the activities of MAPKs and Akt kinase and their roles in the action of STI571, a specific inhibitor of BCR-ABL tyrosine kinase, in chronic myelogenous leukemia (CML) cells. We found that extracellular signal-regulated kinase (ERK) 1/2 and Akt kinase are constitutively active in the chronic phase of CML, blast crisis of CML, and the CML-derived K562 cell line. Both interferon-alpha and STI571 suppressed ERK1/2 activity in K562 cells. In contrast, Akt kinase activity was inhibited only by STI571. K562 cell proliferation was markedly suppressed by LY294002, a specific inhibitor of PI3K/Akt kinase, and STI571 but not by PD98059, a specific inhibitor of MEK1/2. In addition, caspase-3 was activated by treatment of cells with STI571 and LY294002 but not with PD98059. These data indicate that Akt kinase may play a role in the proliferation of CML leukemia cells and the action of STI571. Primary leukemia cells from patients with CML blast crisis did not show inhibition of ERK1/2 or Akt kinase activity and were resistant to caspase-3-associated apoptosis after treatment with STI571. These findings suggest that STI571 does not effectively block signaling molecules downstream of the BCR-ABL tyrosine kinase in some cases of CML blast crisis.

Type C chronic hepatitis with the discovery of a small hepatocellular carcinoma 7 years after successful interferon therapy.

The patient, a 61-year-old man, had sustained injuries in a traffic accident at the age of 26, for which he received a blood transfusion. Since 1988 (age, 49 years), abnormal hepatic function had been detected, and, because of the presence of hepatitis C virus antibodies, he was diagnosed as having type C chronic hepatitis. Based on a liver biopsy that was conducted in July 1992 (age, 53), a histological diagnosis of chronic active hepatitis (F(1)/A(2)) was made. Over a period of 6 months, starting in 1992, the patient was treated with interferon (IFNalpha-2a; total dosage, 720 MU). At the end of this regimen, the alanine aminotransferase level was normalized and serum hepatitis C virus-ribonucleic acid was negative. This condition was maintained until August 1996 (age, 57), after which the patient stopped reporting to our hospital. In June 2000 (age, 61) when he was hospitalized for an adhesive ileus, a small hepatocellular carcinoma (a solitary lesion measuring 18 mm in diameter) at S(8) was found, and it was extirpated by a segmental excision in July. The case is introduced to call attention to the need for longterm follow-up observation, even after effective IFN therapy.

[Successful use of etoposide in an elderly patient with chronic recurrent hemophagocytic syndrome].

A 66-year-old man was admitted to our hospital for fever on January 19, 1998. He began showing periodic high fever in June 1997 and an increased serum LDH in August 1997. His history included surgery for esophageal cancer in 1993. On admission, the patient's body temperature was 38.5 degrees C. Physical examination was negative for lymphadenopathy, hepatosplenomegaly, and skin rash. Peripheral blood revealed a hemoglobin level of 8.6 g/dl and a platelet count of 7.9 x 10(4)/microliter. Bone marrow examination showed hypocellularity with marked histiocytic hemophagocytosis. The various bacterial cultures were negative. Serum LDH was elevated to 1,606 IU/l, and ferritin was greater than 3,000 ng/ml. Antinuclear antibodies were negative. No significant elevation of viral antibody titers including that to Epstein-Barr virus was found. Hemophagocytic syndrome (HPS) was diagnosed, but no underlying diseases was identified. The patient's condition was complicated by interstitial pneumonia and pleural effusion. gamma-globulin and pulse methylprednisolone both proved ineffective for the HPS; however, complete remission was achieved with cyclic intravenous administration of etoposide (VP-16, 150 mg/day). Interestingly, the interstitial pneumonia resolved promptly with etoposide therapy. The patient relapsed, in July 2001, exhibiting high fever, cytopenia, and marrow hemophagocytosis. His condition was ameliorated by administration of etoposide. This was a rare case of chronic and recurrent HPS of unknown etiology accompanied by interstitial pneumonia. Etoposide should be considered as a primary therapy for HPS and its complications in cases such as our patients.

[An autopsied case with a bicuspid aortic valve who had progressive angina pectoris and heart failure during follow-up of 27 years].

A Japanese man who died at age 85 had been followed since the age of 59, when he first presented. He had hypertension of 162/102 mmHg and a loud systolic murmur on his first visit. He had had an active daily life without any medication for the next 10 years. At the age of 72 he complained of mild chest discomfort on exercise. Although electrocardiography showed no abnormalities, echocardiogram showed calcified bicuspid aortic valve with mild stenosis. At the age of 81 the dyspnea and chest oppression were exacerbated, associated with marked ST depression on exercise electrocardiogram and restriction of aortic valve opening on echocardiograms. In the following years a gradual increase in QRS voltage and ST depression with T wave inversion were recorded on resting electrocardiograms and sharp increases in both left ventricular end-diastolic diameter and flow velocity at the aortic root were observed on echocardiograms. At the age of 85 he died of intractable heart failure with massive pleural effusion. Autopsy revealed marked hypertrophy and moderate dilatation of the heart (weight: 580 g). The bicuspid aortic valve had anterior-posterior cusps with a raphe on the anterior cusp. The mobility of the cusps was almost lost because of severe calcification and thickening. Severe stenosis was found near the orifice of the right coronary artery, but there were no significant ischemic myocardial lesions.