Thrombotic microangiopathy due to malignant hypertension following corticosteroid therapy for microscopic polyangitis

A 78-year-old woman was treated with 40 mg of prednisolone for microscopic polyangitis, and favorable effects were observed. However, her blood pressure increased and she developed severe thrombocytopenia. Thrombotic microangiopathy (TMA) due to malignant hypertension was suspected and she was treated with an angiotensin-converting enzyme inhibitor; her platelet count then rose. She showed a close temporal relationship between initiation of corticosteroid therapy and the onset of TMA. Corticosteroid therapy should be used with caution in patients with underlying vascular endothelial damage.     

Serologically HLA-DR—Mismatched Unrelated Donors Might Provide a Valuable Alternative in Allogeneic Transplantation: Experience from a Single Japanese Institution

To clarify the clinical significance of a serologic HLA-DR mismatch after unrelated-donor transplantation, we evaluated for hematologic malignancies 123 cases of unrelated bone marrow transplantation carried out in a single institution between 1995 and 2004. Of the patients in these cases, 12 were serologically mismatched at the single HLA-DR locus. Eighty-two patients who received HLA-matched transplantations were used as controls. Conditioning consisted of a conventional total body irradiation-based regimen or a fludarabine-based reduced-intensity regimen. Prophylaxis for graft-versus-host disease (GVHD) consisted of tacrolimus plus short-term methotrexate. Graft failure did not develop. With a median follow-up of 42 months (range, 11-99 months), rates of overall survival, nonrelapse mortality, and relapse at 4 years were 63%, 38%, and 0%, respectively, all of which were comparable with those after HLA-matched transplantation. The frequency of acute GVHD of grades II to IV was 75%, significantly higher than after HLA-matched transplantation (42%, P = .046), and there was a trend toward an increased incidence of acute GVHD of grades III to IV after serologically HLA-DR-mismatched unrelated transplantation (27% versus 10%, P = .093). Chronic GVHD developed in 4 of 11 evaluable patients, an incidence comparable with that after HLA-matched transplantation. In summary, serologically HLA-DR-mismatched unrelated transplantation is feasible and might be an acceptable alternative for the Japanese population, although the higher incidence of acute GVHD is notable.     

Role of endogenous androgen against insulin resistance and athero- sclerosis in men with type 2 diabetes

Age-related decline in serum testosterone and dehydroepiandrosterone sulfate concentrations occur in men. Low concentrations of these endogenous androgens have been linked with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, hypertension, or hyperlipidemia, and increased cardiovascular risk. Moreover, men with diabetes have significantly less circulating androgen than nondiabetic men. Here, we summarize how androgen affects insulin resistance and atherosclerosis in men with type 2 diabetes. Low serum concentrations of endogenous androgens are associated with visceral fat accumulation. Androgen deprivation by castration to treat prostate cancer increases insulin resistance, while testosterone administration in type 2 diabetic men with androgen deficiency improves glucose homeostasis and decreases visceral fat, in addition to alleviating symptoms of androgen deficiency including erectile dysfunction. Androgen correlates inversely with severity of atherosclerosis and has beneficial effects upon vascular reactivity, inflammatory cytokine, adhesion molecules, insulin resistance, serum lipids, and hemostatic factors. Because men with type 2 diabetes have relative hypogonadism, testosterone supplementation could decrease both insulin resistance and atherosclerosis.     

Pitching biomechanics as a pitcher approaches muscular fatigue during a simulated baseball game

BACKGROUND: The effects of approaching muscular fatigue on pitching biomechanics are currently unknown. As a pitcher fatigues, pitching mechanics may change, leading to a decrease in performance and an increased risk of injury. HYPOTHESIS: As a pitcher approaches muscular fatigue, select pitching biomechanical variables will be significantly different than they were before muscular fatigue. STUDY DESIGN: Controlled laboratory study. METHODS: Ten collegiate baseball pitchers threw 15 pitches per inning for 7 to 9 innings off an indoor throwing mound during a simulated baseball game. A pitching session ended when each pitcher felt he could no longer continue owing to a subjective perception of muscular fatigue. A 6-camera 3D automatic digitizing system collected 200-Hz video data. Twenty kinematic and 11 kinetic variables were calculated throughout 4 phases of the pitch. A repeated-measure analysis of variance (P < .01) was used to compare biomechanical variables between innings. RESULTS: Compared with the initial 2 innings, as a pitcher approached muscular fatigue during the final 2 innings he was able to pitch, there was a significant decrease in ball velocity, and the trunk was significantly closer to a vertical position. There were no other significant differences in kinematics or kinetics variables. CONCLUSION: The relatively few differences observed imply that pitching biomechanics remained remarkably similar between collegiate starting pitchers who threw between 105 and 135 pitches for 7 to 9 innings and approached muscular fatigue. CLINICAL RELEVANCE: This study did not support the idea that there is an increase in shoulder and elbow forces and torques as muscular fatigue is approached. It is possible that if a pitcher remained in a fatigued state for a longer period of time, additional changes in pitching mechanics may occur and the risk of injury may increase.     

F-18 FDG PET demonstration of a thyroid metastasis in a patient with colon cancer

A 51-year-old man with a history of surgical removal of sigmoid colon cancer underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to search for distant metastases and/or local recurrence because the carcinoembryonic antigen level was elevated. F-18 FDG PET images showed increased focal FDG uptake in the left lobe of the thyroid. Computed tomography images showed thyroid tumor in the left lobe as well as F-18 FDG PET images. Thereafter he underwent thyroidectomy and the resected specimen was histopathlogically shown to have thyroid metastasis from colon cancer. F-18 FDG PET was useful to detect thyroid metastasis from colon cancer as well as the most frequently seen metastatic sites such as liver, lungs, and lymph nodes.     

Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent patients with primary CNS lymphoma

Purpose The purpose of this study was to investigate the accumulation of FDG in immunocompetent patients with primary central nervous system (CNS) lymphoma using qualitative and quantitative PET images and to compare baseline with follow-up PET after therapy. Methods Twelve immunocompetent patients with CNS lymphoma were examined. Dynamic emission data were acquired for 60 min immediately following injection of FDG. In seven patients, repeated PET studies were performed after treatment. Applying a three-compartment five-parameter model, K ₁, k ₂, k ₃, k ₄, vascular fraction (V _B ) and cerebral metabolic rate of glucose (CMR_Glc) were obtained. We evaluated the FDG uptake visually using qualitative and parametric images and quantitatively using parametric images. Results A total of 12 lesions were identified in ten patients with newly diagnosed CNS lymphoma. On visual analysis, ten lesions showed an increase on qualitative images, eight showed an increase on K ₁ images, 12 showed an increase on k ₃ images and ten showed an increase on CMR_Glc images. On quantitative analysis, k ₂, k ₃ and CMR_Glc values of the lesion were significantly different from those of the normal grey matter (p<0.02–0.0005). A total of three lesions were identified in two patients with recurrent tumour. All three lesions showed an increase on qualitative, k ₃ and CMR_Glc images. The K ₁, k ₂, k ₃ and CMR_Glc values after treatment were significantly different from those obtained before treatment (p<0.04–0.008). Conclusion Kinetic analysis, especially with respect to k ₃, using dynamic FDG PET might be helpful for diagnosis of CNS lymphoma and for monitoring therapeutic assessment.     

Central hypotensive effect involving neurotransmitters of long-term administration of taurine to stroke-prone spontaneously hypertensive rat

BACKGROUND: Taurine is an inhibitory neurotransmitter or neuromodulator that reduces blood pressure when systemically or centrally administered. We studied the central hypotensive effects of long-term oral taurine administration. METHODS: Arterial blood pressure was measured after delivering an intracisternal injection of 100 mg x 20 microl(-1) or 200 microg x 20microl(-1) of taurine in normal saline, or 20 micro1 normal saline to anesthetized Sprague-Dawley rats. Drinking water containing 3% taurine was administered to stroke-prone spontaneously hypertensive rats (SHRSP) from the age of 4 weeks. Amino acids and monoamine neurotransmitters in the cerebrospinal fluid were measured at 8, 12, 16, 18 weeks of age in taurine treated SHRSP and normotensive Wistar Kyoto rats (WKY) and in untreated SHRSP using high performance liquid chromatography. RESULTS: Intracisternal injections of taurine caused a dose dependent decrease in arterial blood pressure. Although concentrations of taurine decreased in treated SHRSP rats in an age-related manner, the drug persistently suppressed the development of hypertension. The values of excitatory amino acids and GABA, norepinephrine, NMN, dopamine metabolites, serotonin and its metabolite were lower in taurine-treated SHRSP than those in untreated SHRSP. CONCLUSIONS: Taurine reduces blood pressure through not only direct inhibition of the cardiovascular center in the medulla, but also by reducing brain monoamine concentrations.