Acute exacerbation of interstitial pneumonia associated with active systemic lupus erythematosus in a patient with rheumatoid arthritis]

A 36-year-old woman with rheumatoid arthritis was admitted to our hospital for evaluation of newly developed active systemic lupus erythematosus (SLE). After hospitalization, she showed progressive respiratory failure. Chest CT revealed exacerbation of interstitial pneumonia, showing acute development of air-space consolidation and ground-glass opacity in addition to intensified reticular shadows. Administration of high-dose corticosteroids and cyclosporine A resulted in recovery from respiratory failure, accompanied by obvious improvement in the chest radiographs and CT, as demonstrated by the disappearance of air-space consolidation and ground-glass opacity. Clinically, the exacerbation of her interstitial pneumonia was compatible with acute lupus pneumonitis, a rare complication with active SLE.     

Liver sarcoidosis that presented with dysphagia

We report a case of liver sarcoidosis with dysphagia. Although akinesia of the soft palate, disappearance of the palatal reflex, and pyramidal signs indicated brainstem lesions, brain magnetic resonance imaging showed no lesion and the focus was obscure. Iritis, parotiditis, and hilar lymphadenopathy supported the diagnosis of sarcoidosis. However, lung biopsy was normal. Finally, sarcoidosis was diagnosed by liver biopsy. We speculated that microgranulomas in the brainstem that did not exhibit imaging abnormalities causing the neurological symptoms and that liver biopsy can be an effective diagnostic tool even for cases that presented with neurological signs, but no gastrointestinal symptom.     

Disruption of tumor necrosis factor-alpha gene diminishes the development of atherosclerosis in ApoE-deficient mice

Inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) have been implicated in atherogenesis. However, the precise role of TNF-alpha in atherogenesis is still unclear. To examine the effect of TNF-alpha on atherogenesis, we generated compound-deficient mice in apolipoprotein E (apoE) and TNF-alpha (apoE-/-/TNF-alpha-/-) and compared them with apoE-/- mice. Although serum total cholesterol levels were markedly elevated in both apoE-/-/TNF-alpha-/- and apoE-/- mice compared to wild-type mice, no differences were observed between apoE-/-/TNF-alpha-/- and apoE-/- mice. The atherosclerotic plaque area in the aortic luminal surface of apoE-/-/TNF-alpha-/- mice (n=8, 3.1+/-0.4%) was significantly smaller than that of apoE-/- mice (n=7, 4.7+/-0.4%, p<0.001) despite the lack of difference in serum cholesterol levels. The atherosclerotic lesion size in the aortic sinus of apoE-/-/TNF-alpha-/- mice (n=10, 5.1+/-0.3 x 10(5)microm(2)) was also significantly smaller than that of apoE-/- mice (n=11, 7.0+/-0.3 x 10(5)microm(2), p<0.0001). RT-PCR analysis indicated that the expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in apoE-/- than apoE-/-/TNF-alpha-/- mice. Macrophages from apoE(-/-) mice showed higher uptake level of oxidized LDL and increased expression level of scavenger receptor class A (SRA) compared to those from apoE-/-/TNF-alpha-/- mice. These results indicate that TNF-alpha plays an atherogenic role by upregulating the expressions of ICAM-1, VCAM-1 and MCP-1 in the vascular wall, and by inducing SRA expression and oxidized LDL uptake in macrophages.     

Impacts of nicorandil on infarct myocardium in comparison with nitrate: assessed by cardiac magnetic resonance imaging

In this pilot study, we compared the infarct and edema size in acute myocardial infarction (MI) patients treated by nicorandil with those treated by nitrate, using cardiac magnetic resonance (CMR) imaging. Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention (PCI) were enrolled, and were assigned to receive nicorandil or nitrate at random just before reperfusion. For the assessment of infarct and edema areas, short-axis delayed enhancement (DE) and T2-weight (T2w) CMR images were acquired 6.1 ± 2.4 days after the onset of MI. A significant correlation was observed between the peak creatinine kinase (CK) level and the infarct size on DE CMR (r = 0.62, p < 0.05), as well as the edema size on T2w CMR (r = 0.70, p < 0.05) in patients treated by nicorandil (28 patients). A similar correlation was seen between the peak CK level and the infarct size on DE CMR (r = 0.84, p < 0.05), as well as the edema size on T2w CMR (r = 0.84, p < 0.05) in patients treated by nitrate (24 patients). The maximum CK level was significantly lower in patients treated by nicorandil rather than nitrate (1991 ± 1402, 2785 ± 2121 IU/L, respectively, p = 0.03). Both the edema size on T2w CMR and the infarct size on DE CMR were significantly smaller in patients treated by nicorandil rather than nitrate (17.7 ± 9.9, 21.9 ± 13.7 %; p = 0.03, 10.3 ± 6.0, 12.7 ± 6.9 %, p = 0.03, respectively). The presence and amount of microvascular obstruction were significantly smaller in patients treated by nicorandil rather than nitrate (39.2, 64.7 %; p = 0.03; 2.2 ± 1.3, 3.4 ± 1.5 cm²; p = 0.02, respectively). Using CMR imaging, we demonstrated that the complementary use of intravenously and intracoronary administered nicorandil during PCI favorably acts more on the damaged myocardium after MI than nitrate. We need a further powered prospective study on the use of nicorandil.     

Accelerated telomere length shortening in granulocytes: a diagnostic marker for myeloproliferative diseases

OBJECTIVE: The telomere in mature myeloid cells derived from abnormal progenitor cells of myeloproliferative diseases (MPDs) may shorten more rapidly than that in T lymphocytes, which are considered to be derived from normal clones. To test this hypothesis, we measured telomere lengths in granulocytes and T lymphocytes from patients with MPDs and compared them with those from normal individuals. MATERIALS AND METHODS: Granulocytes and T lymphocytes were separated from the peripheral blood of 65 patients with MPDs (25 chronic myelogenous leukemia [CML], 16 polycythemia vera, 19 essential thrombocythemia, 5 chronic idiopathic myelofibrosis) and 35 normal individuals. Genomic DNA from each cell fraction was subjected to Southern blot hybridization to determine the mean telomere length. RESULTS: Telomere lengths in granulocytes from patients with MPDs were significantly shorter than those from normal individuals (vs CML, p = 0.002; vs other MPDs, p < 0.0001). However, there was no statistical difference in telomere length in T lymphocytes between MPD patients and normal individuals (vs CML, p = 0.35; vs other MPDs, p = 0.85). DeltaTRF (terminal restriction fragment) in patients with MPDs, which is defined as the difference in telomere length between granulocytes and T lymphocytes, was significantly longer than that in normal individuals. CONCLUSIONS: The results support the disease theory that MPDs result from extensive proliferation of myeloid progenitor cells, leading to accelerated telomere length shortening in mature granulocytes. An increase in DeltaTRF over the standard value (>1.74 kb) may be useful for discriminating leukocytosis due to MPDs from reactive leukocytosis.     

Analysis of cardiopulmonary stress during endoscopy: Is unsedated transnasal esophagogastroduodenoscopy appropriate for elderly patients?

BACKGROUND:

Transnasal esophagogastroduodenoscopy (EGD) without sedation has been reported to be safe and tolerable. It has recently been used widely in Japan for the detection of upper gastrointestinal disease. Alternatively, transoral examination using a thin endoscope has also been reported to be highly tolerable.

OBJECTIVE:

To examine the cardiocirculatory effects of transoral versus transnasal EGD in an attempt to determine the most suitable endoscopic methods for patients ≥75 years of age.

METHODS:

Subjects who underwent monitoring of respiratory and circulatory dynamics without sedation during endoscopic screening examinations were enrolled at the New Ooe Hospital (Kyoto, Japan) between April 2008 and March 2009. A total of 165 patients (age ≥75 years) provided written informed consent and were investigated in the present study. Patients were randomly divided into three subgroups: UO group – thin endoscope; SO group – standard endoscope; and UT group – transnasal EGD. Percutaneous arterial blood oxygen saturation, heart rate and blood pressure were evaluated just before EGD and at five time points during EGD. After transnasal EGD, patients who had previously been examined using transoral EGD with a standard endoscope were asked about preferences for their next examination.

RESULTS:

There were no statistical differences in the characteristics among the groups. Percutaneous oxygen saturation in the UT group showed a transient drop compared with the SO and UO groups at the beginning of the endoscopic procedure. Heart rate showed no significant differences among the SO, UO and UT groups; Systolic blood pressure in the UO group was lower immediately after insertion compared with the SO and UT groups. The rate pressure product in the UO group was comparable with that in the UT group during endoscopy, and the SO group showed a continuously higher level than the UO and UT groups. More than one-half (54.4%) of patients were ‘willing to choose transnasal EGD for next examination’.

CONCLUSIONS:

For elderly patients, unsedated transnasal EGD failed to show an advantage over unsedated standard endoscopy. Transoral thin EGD was estimated to be safe and tolerable.     

Limited value of the international staging system for predicting long-term outcome of transplant-ineligible,newly diagnosed,symptomatic multiple myeloma in the era of novel agents

We retrospectively investigated clinical outcomes and prognostic factors of 131 patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) who received melphalan and prednisolone (MP) as first-line therapy from 2006 to 2013. Eighty-one patients received salvage therapies incorporating bortezomib, lenalidomide, and/or thalidomide. The overall response rate to MP was 54.2 %, including 9.2 % of better than very good partial response. With a median follow-up period of 30.2 months, median overall survival (OS) and median time to next treatment (TNT) were 54.4 and 19.0 months, respectively. Univariate analysis revealed that performance status and serum calcium level significantly associated with both OS and TNT, and multivariate analysis revealed that the higher serum calcium level had a significantly unfavorable impact on OS and TNT. Importantly, staging informed by the international staging system (ISS) was not predictive for OS or TNT in the analyzed cohort. Our study revealed that, in the context of first-line MP therapy for NDMM, the salvage therapy incorporating novel agents produced a survival period of >30 months after the initiation of second-line therapy, suggesting that the predictive value of ISS for OS and TNT may be limited in the era of novel agents.     

Cerebral Infarction with Pulmonary Thromboembolism Due to Immobilization

Arterial and venous thrombi can coexist without preexisting conditions, such as malignant disease, thrombotic predisposition, or arteriovenous shunt. We herein report a case of acute cerebral infarction and pulmonary thromboembolism in the absence of underlying disease. A 71-year-old woman presented with left hemiplegia. On an examination, her oxygen saturation was 91% on ambient air despite the absence of chest symptoms and clear lung fields on a chest radiograph. The patient was finally diagnosed with acute cerebral infarction caused by large artery atherosclerosis and acute pulmonary thromboembolism due to deep vein thrombosis, consequent to immobilization for three days after the onset of cerebral infarction.