Chronic cholesterol crystal embolism with a spontaneous onset

A 74-year-old man was referred to our hospital because of hypertension, blue toe syndrome and an elevation of serum creatinine from 0.8 to 1.4 mg/dl for eleven months. He had no history of invasive vascular procedures. Atherosclerosis was initially suspected, but renal impairment was accelerated following anticoagulant therapy. A renal biopsy established the diagnosis of cholesterol crystal embolism. Withdrawal of anticoagulants and the combination therapy with LDL apheresis and corticosteroids led to stabilization of the renal function. In patients with risk factors for atherosclerosis, cholesterol crystal embolism should be included in the differential diagnosis of chronic kidney disease.     

Insulin Autoimmune Syndrome possibly caused by alpha lipoic acid

Insulin Autoimmune Syndrome (IAS) is a rare disease characterized by hypoglycemia and autoantibodies to insulin without prior insulin administration. Here, we report a case of IAS associated with alpha lipoic acid (ALA). The patient is a 55-year-old man. He began to complain of hypoglycemic symptoms after taking ALA. He lost consciousness in the late postprandial period and blood glucose was found to be 27 mg/dl. A high insulin level and high titers of insulin antibodies were detected. His HLA genotype contains DRB1* 0406. As ALA comes to be used widely, the incidence of IAS due to ALA might increase.     

Histological characteristics of plaque with ultrasonic attenuation: a comparison between intravascular ultrasound and histology

OBJECTIVES: Intermediate echogenic plaque without acoustic shadow on intravascular ultrasound (IVUS) imaging has been recognized as fibrous plaque. Such echogenic plaque with ultrasonic attenuation may have higher risk for distal flow disturbance (slow flow/no-reflow) during percutaneous coronary intervention. However, histological evaluation of plaque with ultrasonic attenuation has not been performed. This study evaluated the histological characteristics of plaque with ultrasonic attenuation assessed by IVUS. METHODS: By using IVUS, 36 samples of human cadaveric coronary arterial echogenic plaque (percentage plaque area > 40%) without calcium were selected, and classified into the attenuation group; plaque with ultrasonic attenuation, and the non-attenuation group; plaque without attenuation. These plaques were classified for fibrous, fibrofatty, calcium, and necrotic core areas by histological examination. RESULTS: True fibrous plaque was found in 91.7% of the non-attenuation group, but only 68.0% of the attenuation group (p < 0.01) . On the other hand, the percentage fibrofatty and necrotic core plaque areas in the attenuation group were significant larger than those in the non-attenuation group (fibrofatty: 16.3 +/- 13.8% vs. 2.7 +/- 3.1%, p < 0.01; necrotic core: 13.0 +/- 19.4% vs. 3.9 +/- 8.0%, p = 0.03). CONCLUSIONS. Plaque with ultrasonic attenuation contains more fibrofatty tissue and necrotic core compared to fibrous plaque without attenuation.     

Biological roles of estrogen and progesterone in human endometrial carcinoma--new developments in potential endocrine therapy for endometrial cancer

Endometrial carcinoma is one of the most common female pelvic malignancies. It is well known that uterine endometrial cell proliferation is under the control of both estrogen and progesterone. In this review, results of the recent studies on the biosynthesis and action of estrogen and progestin in normal endometrium and its disorders will be summarized and the new aspects of hormonal therapies in the patients with endometrial carcinoma will be discussed including its future prospectives. We reported that the enzymes responsible for intratumoral estrogen metabolism and biosynthesis are markedly different between human breast and endometrial carcinoma, although both of them are considered "estrogen-dependent malignancies". In addition, the biological significance of Progesterone receptor (PR) isoforms is considered to differ between endometrial and breast carcinomas. Clinical data concerning Hormone replacement therapy (HRT) and estrogen-dependent cancer risk also support these findings. These basic and clinical findings help to understand the biology and provide the new knowledge for prevention, diagnosis and treatment of human endomerial carcinoma. Specific endocrine treatment of endometrial carcinoma should be explored in future, although aromatase inhibitors are the most effective endocrine treatments of estrogen-responsive breast carcinoma. Retinoid, metabolities of vitamin A, and synthetic peroxisome proliferator-activated receptor (PPAR) gamma ligands, which have been used for the treatment of insulin resistance in type II diabetes mellitus, may be the important candidates as drugs not only for prevention but also for possible endocrine treatment of endometrial carcinoma.     

Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa

High serum level of GH in the presence of low plasma level of insulin-like growth factor-I (IGF-I) is one of the endocrinological features of anorexia nervosa (AN). Whether the amount of endogenous GH is not enough to increase IGF-I is not certain. We studied the effect of recombinant human growth hormone (rhGH) on the GH-IGF-I axis and on malnutrition-related disorders in this syndrome. Twenty patients with AN were divided into two groups; one (N = 13) was given rhGH (0.33 mg/day), and the other (N = 7) was given placebo for 6 or 12 months, respectively. During each treatment, levels of serum GH, plasma IGF-I, serum thyroid hormones, serum cholesterol, fasting plasma glucose and cardiac function were monitored. Changes in body mass index (BMI) and calorie taken were also evaluated. Plasma IGF-I level increased from 74.4 +/- 41.9 to 269.0 +/- 31.2 microg/L (P<0.001) during administration of rhGH, which associated with a decrease in serum GH level from 17.0 +/- 15.0 to 1.6 +/- 0.8 microg/L (P<0.001). Administration of rhGH increased BMI, body temperature, fasting plasma glucose level, and food intake. Serum level of triiodothyronine, but not thyroxine, increased during treatment with rhGH. The treatment decreased serum levels of both total and HDL-cholesterol. Studies with echocardiography showed an increase in cardiac output during the treatment with rhGH. These improvements were not observed in patients treated with placebo. Administration of rhGH is recommended as one of the methods of managing the patients with AN.     

Adiponectin inversely correlates with high sensitive C-reactive protein and triglycerides, but not with insulin sensitivity, in apparently healthy Japanese men

Adiponectin, an antiatherogenic peptide, has diverse biological actions on insulin sensitivity, inflammation and lipid metabolism. To explore physiological and pathophysiological significance of adiponectin in the Japanese general population, we systematically analyzed the relationship between adiponectin and high sensitive CRP (hsCRP), lipids, insulin sensitivity, and anthropometric parameters in 166 consecutive adult male health examinees. By univariate analysis, serum adiponectin was positively correlated with age and HDL-cholesterol, and inversely correlated with fasting plasma glucose, fasting insulin, homeostasis model assessment insulin-resistance, waist, body mass index, triglycerides and hsCRP. However, multivariate analysis revealed that adiponectin independently correlated with triglycerides (r = -0.243, P = 0.0033) and hsCRP (r = -0.262, P = 0.0015) but not with all other variables. Adiponectin was lower and hsCRP higher in the subjects with metabolic syndrome (n = 22) than in those without it (n = 144) (adiponectin, 5.4 +/- 2.8 vs 7.5 +/- 4.2 microg/ml, p = 0.002; hsCRP, 832 +/- 605 vs 470 +/- 524 ng/ml, p = 0.0004). Current findings suggest that relative importance of hypertriglyceridemia and enhanced inflammation, rather than insulin resistance, as the downstream events of hypoadiponectinemia leading to atherosclerosis in the Japanese general population.     

A Prospective Study of Cyclosporine A Treatment of Patients with Low-Risk Myelodysplastic Syndrome: Presence of CD55−CD59− Blood Cells Predicts Platelet Response

Although immunosuppressive therapy using antithymocyte globulin or cyclosporine A (CSA) is effective in selected patients with low-risk myelodysplastic syndrome, the response rates reported so far are inconsistent, and the indication of immunosuppressive therapy for myelodysplastic syndrome has not been clearly defined. We treated 20 myelodysplastic syndrome patients (17 refractory anemia cases [RA], 2 RA with excess blasts, and one RA with ringed sideroblasts) with 4 mg/kg per day of CSA for 24 weeks. Among the 19 patients evaluated, 10 showed hematologic improvement; 8 patients showed an erythroid response, 6 showed a platelet response, and one showed a neutrophil response. Most patients with hematologic improvement continued CSA thereafter, and the progressive response was observed until the latest follow-up (median, 30 months). Most toxicities associated with CSA usage were manageable, and no patient had developed acute leukemia up to this point. Short duration of illness, refractory anemia with minimal dysplasia determined by bone marrow morphology, and the presence of paroxysmal nocturnal hemoglobinuria-type cells were significantly associated with the platelet response. A minority of RA patients who did not possess such predictive variables achieved an isolated erythroid response. In conclusion, CSA may be a therapeutic option for patients with RA who do not have adverse prognostic factors.     

Successful All-<Emphasis Type="Italic">trans</Emphasis> Retinoic Acid Treatment of Acute Promyelocytic Leukemia in a Patient with <Emphasis Type="Italic">NPM/RAR</Emphasis> Fusion

Acute promyelocytic leukemia (APL) is characterized by a reciprocal chromosomal translocation involving the gene for retinoic acid receptor alpha(RAR). Most APL patients have a t(15;17) translocation that generates the PML-RAR fusion gene, and such patients respond well to treatment with all-trans retinoic acid (ATRA). Some APL cases also involve rearrangements that fuse RAR to partner genes other than PML, including nucleophosmin (NPM), promyelocytic leukemia zinc finger (PLZF), nuclear mitotic apparatus (NUMA), and Stat5b, but the clinical characteristics of APL without PML-RAR have not been fully clarified. We describe a 64-year-old man with NPM-RAR-positive APL who was receiving hemodialysis therapy for chronic uremia. Complete remission was achieved with ATRA monotherapy and was maintained for 18 months with consolidation chemotherapy. These findings suggest that ATRA can be used to treat APL patients with NPM/RAR as well as APL with PML/RAR.