A case of mixed connective tissue disease successfully treated for hemophagocytic syndrome with intermittent intravenous injection of cyclophosphamide]

A 52 year-old woman noticed general fatigue, polyarthralgia, and muscle weakness of lower extremities in October 2001. In December, she felt difficulty in walking due to muscle weakness. In January 2002, she admitted another hospital because of dyspnea on exertion and edema of lower extremities. Laboratory test revealed leukocytopenia, the elevation of creatine kinase and positive anti-U1-RNP antibodies. Her chest computed tomography (CT) showed severe interstitial pneumonia. Cardiac echogram revealed that she had pericardial effusion and pulmonary hypertension. Then she was transferred to Keio University Hospital and she was diagnosed as having mixed connective tissue disease (MCTD) manifestating myositis, interstitial pneumonia, pulmonary hypertension and pericarditis. Prednisolone (PSL) 60mg daily following to methylprednisolone (mPSL) pulse therapy was begun and her symptoms were gradually improved. In middle of February, she complained of high fever over 39.0 degrees C. Bacterial culture tests were negative and laboratory data indicated pancytopenia and a high level of serum ferritin. Bone marrow aspiration revealed hemophagocytosis in bone marrow specimens and she was diagnosed as having hemophagocytic syndrome associated with MCTD. mPSL pulse therapy was not effective and intermittent cyclophosphamide pulse therapy (IV-CY) was performed resulting in improvement of the symptoms. This case suggested the effectiveness of IV-CY therapy in patients with corticosteroid-resistant HPS associated with connective tissue diseases.     

Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats.

PURPOSE: This study investigated the effect of parathyroid hormone (1-34) [PTH(1-34)] on bone reactions after tibial placement of titanium screw implants into ovariectomized rats. MATERIALS AND METHODS: Twelve-week-old female Wistar rats were divided into 3 groups of 24. The first group (Sham group) was sham-operated; the second group (OVX group) was ovariectomized only; and the third group (PTH group) was subcutaneously administered 30 microg/kg PTH in the dorsal region 3 days per week starting the fourth week after ovariectomy until the end of the experiment. Titanium screw implants were placed in the proximal metaphysis of the tibia of all 3 groups at 168 days after surgery. The animals were killed 7, 14, 28, and 56 days after implantation. Undecalcified sections were prepared and evaluated by light microscopy. Histomorphometric measurements were obtained using a computer-based image analyzer to quantify the unit bone mass around the implant and the rate of implant-bone contact. RESULTS: When PTH administration was started 21 days after ovariectomy, the volume density of bone around implants in the PTH group was almost the same as that of the Sham group throughout the entire observation period. This finding suggests that not only can intermittent human PTH(1-34) administration prevent resorption of newly generated trabeculae around an implant but also it can aid in the recovery of bone volume lost due to ovariectomy. CONCLUSION: When dental implants are applied to jaw bone showing trabecular bone loss, it may be possible to increase bone density around an implant by intermittent human PTH(1-34) administration and thereby improve clinical results.     

A case of autoimmune pancreatitis complicated with immune thrombocytopenia]

A 80-year old man was referred to our hospital because of an elevation of serum amylase level. Diffuse enlargement of the pancreas was detected by abdominal computed tomography, and also diffuse narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. The serum level of IgG was elevated to 3450mg/dl. Besides, on the 10th hospital day, petechia developed and the platelet level decreased to 1.5 x 10(4)/microl. The platelet-associated IgG, antiplatelet antibody and antinuclear antibody in serum were positive. The levels of serum complements were low. From all these findings the patient was diagnosed as autoimmune pancreatitis complicated with immune thrombocytopenia. The treatment with prednisolone was started, which was effective on each disease. The medication was suspended a year ago, and so far there is no data suggesting the recurrence of autoimmune pancreatitis or immune thrombocytopenia.     

A Case of Pelvic Osteomyelitis

A patient presenting with osteomyelitis of the pelvis is described. In this case it was difficult to establish a correct diagnosis by use of scintigraphic scanning, in spite of clear roentgenographic evidence of osteomyelitis.     

Glucose as regulator of glucose transport activity and glucose-transporter mRNA in hamster beta-cell line.

To investigate the role of glucose in regulating glucose transporters in pancreatic beta-cells, we studied the hamster clonal beta-cell line HIT-T15, which retains responsiveness to glucose. Northern blot analysis demonstrates that GLUT2 and GLUT1 mRNA are abundant in HIT cells. After a 24-h culture with various concentrations of glucose (0-22.2 mM [0-400 mg/dl]), the GLUT2 mRNA level in HIT cells increased by 40% at 22.2 mM (400 mg/dl) glucose compared with 11.1 mM (200 mg/dl) without a change in mRNA stability. It also decreased proportionally to the reduction of glucose concentration. Glucose deprivation resulted in a decrease of GLUT2 mRNA to an almost undetectable level, with a marked increase in the degradation rate of mRNA. In contrast, the GLUT1 mRNA was not affected by glucose. We show that glucose uptake is highest in HIT cells incubated at 2.8-5.5 mM (50-99 mg/dl) glucose for 24 h, and that levels in cells cultured at 0 mM (0 mg/dl) and 22.2 mM (400 mg/dl) glucose decrease to approximately 20% of the maximum level. This decrease is consistent with the effects of glucose on glucose-stimulated insulin secretion in HIT cells. Our results indicate that glucose is involved in regulating GLUT2 mRNA and glucose uptake activity and that the glucose responsiveness of the insulin secretion correlates with the glucose-induced change in glucose uptake activity in HIT cells.     

Choroidal dye filling velocity in patients with Vogt–Koyanagi–Harada disease

Purpose To evaluate quantitative choroidal dye filling velocity in patients with Vogt-Koyanagi-Harada disease (VKH) before and after corticosteroid treatment using indocyanine green (ICG) angiography.Methods ICG angiography was performed in seven VKH patients before and after systemic corticosteroid treatment. Choroidal dye curves were obtained by image analysis software and analyzed using an exponential model. The model’s time constant (τ) was used to evaluate choroidal dye filling velocity.Results Compared with controls, acute phase choroidal τ values in VKH patients were significantly longer, suggesting choroidal circulation disturbance. During the recovery phase, choroidal τ values were significantly shortened, suggesting choroidal circulatory disturbance improvement.Conclusion Choroidal dye filling velocity may be useful for VKH diagnosis and verification of corticosteroid treatment effectiveness.     

Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Serial diffusion-weighted MRI (DWI) in a patient with sporadic Creuztfeldt-Jakob disease]

Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease.