Solitary fibrous tumor of the pleura causing recurrent hypoglycemia by secretion of insulin-like growth factor II

A case of malignant solitary fibrous tumor (SFT) is reported, occurring in a 61-year-old man with frequent hypoglycemia. Endocrinological analyses showed high serum levels of insulin-like growth factor II (IGF-II) and suppressed secretion of insulin. After the removal of a pleural tumor, which weighed 3150g, serum IGF-II levels returned to normal and hypoglycemic attacks ceased. The tumor was composed of uniform spindle cells arranged in bundles, and fascicles with varying amounts of collagen and retlculin fibers. Mitotlc figures at the rate of 6/10 high-power fields, and frequent foct of necrosis and hemorrhage were seen. Almost all of the tumor cells were Immunohlstochemically positive for vimentin and CD34. Electron microscopy revealed the immature mesenchymal or myofibroblastic nature of the tumor cells. These findings are consistent with malignant SFT of the pleura. Moreover, the tumor produced IGF-II mRNA as demonstrated by northern blot analysis. Thus, hypoglycemia of this patient was induced by SFT through the production and secretion of IGF-II.     

Why is biologic therapy useful in spondyloarthritis? Knowledge from synovial immunopathologic studies of spondyloarthritis

The pathogenesis of most rheumatic diseases remains unknown. It is believed that both genetic and environmental factors play a pivotal role in the development of synovial inflammation in rheumatoid arthritis (RA), spondyloarthritis (SpA) and osteoarthritis (OA). In the last two decades, there have been many immunopathologic studies on RA, SpA and OA, and the findings revealed different types of arthritis may also present different pathologic patterns. These included higher vascularity and increased infiltration with CD163 macrophages and neutrophils, but relatively low values for lining cell (LL) hyperplasia in SpA synovium. However, the increased LL hyperplasia, as well as CD1a+ cells and the presence of intracellular citrullinated protein were more prominent in RA than in SpA synovitis. Anti‐tumor necrosis factor alpha (anti‐TNFα) therapy can significantly reduce synovial LL hyperplasia, vascularity and mononuclear cells infiltration in the majority of RA or SpA patients. This may explain why clinically, arthritis patients can get significant improvement after TNFα blocker treatment.     

Reactive hyperemia following coronary balloon angioplasty, but not dipyridamole-induced hyperemia, predicts resolution of exercise-induced ST-segment depression

OBJECTIVES: To characterize delayed restoration of coronary blood flow following successful percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Delayed restoration of coronary blood flow following successful PTCA is common and likely the result of multiple factors. Temporary myocardial ischemia and dipyridamole administration both result in increased coronary blood flow, but by different mechanisms. The relationship between these phenomena and exercise-induced ST-segment depression after PTCA was investigated to determine if any correlation existed. METHODS: Forty consecutive patients with single-vessel coronary artery disease underwent treadmill exercise testing before and after PTCA. The percentage change in coronary blood flow before and after 90 s balloon inflation was assessed. After a new steady state had been reached, dipyridamole was infused and changes in coronary blood flow were again determined. The relationship between changes in coronary blood flow and the presence of ST-segment depression during exercise testing after PTCA was determined. RESULTS: Peak coronary blood flow induced by reactive hyperemia was significantly greater than that in the steady state after balloon inflation (48.5+/-38.8 compared with 15.1+/-13.2 ml/min, P<0.0001). Dipyridamole administration also resulted in significant increases in coronary blood flow (15.1+/-13.2 ml/min compared with 31.0+/-24.9 ml/min, P<0.0001). ST-segment depression after PTCA was significantly less than before (0.10+/-0.07 mV compared with 0.19+/-0.08 mV, P<0.001). Further, reactive hyperemia, but not dipyridamole-induced hyperemia, correlated with attenuation of exercise-induced ST-segment depression after PTCA (r=0.62, P<0.0001). CONCLUSIONS: Reactive hyperemia following temporary coronary occlusion recreates local conditions associated with delayed resolution of myocardial ischemia following successful PTCA. Further, this phenomenon appears to be distinct from changes in coronary blood flow induced by dipyridamole.     

Case of a Patient with Progressive Adult T-Cell Leukemia/Lymphoma Treated Successfully by Reduced-Intensity Conditioning Stem Cell Transplantation from an HLA-Incompatible Related Donor

A 61-year-old man with progressive adult T-cell leukemia/lymphoma (ATLL) successfully received reduced-intensity conditioning stem cell transplantation (RIST) without T-cell depletion (TCD) from his HLA-incompatible son, who had negative results for human T-lymphotropic virus type 1 (HTLV-1) (1-locus, 1-allele mismatch in the graft-versus-host [GVH] direction; 2-loci, 1-allele mismatch in the host-versus-graft direction). The preparatory regimen consisted of fludarabine, busulfan, and rabbit antithymocyte globulin. GVH disease (GVHD) prophylaxis consisted of short-term administration of methotrexate, tacrolimus, and methylprednisolone. The patient achieved complete donor chimerism on day 30 after transplantation. On approximately day 50 the patient started to experience steroid-refractory skin GVHD (grade IV), which was successfully managed with basiliximab (anti-CD25 monoclonal antibody) and mycophenolate mofetil (MMF). Serial analysis of HTLV-1 proviral load by quantitative polymerase chain reaction analysis using whole peripheral blood demonstrated undetectable levels from day 90. At the time of this writing the patient had been in complete remission for more than 16 months. The results in this case suggest the potential of non-TCD RIST from an HLA-incompatible relative donor as an alternative source of hematopoietic stem cells even for an elderly patient with advanced ATLL. In addition, basiliximab combined with MMF may be effective for the treatment of steroid-refractory skin GVHD without deteriorating the graft-versus-ATL effect.     

Brainstem thyrotropin-releasing hormone regulates food intake through vagal-dependent cholinergic stimulation of ghrelin secretion

The brainstem is essential for mediating energetic response to starvation. Brain stem TRH is synthesized in caudal raphe nuclei innervating brainstem and spinal vagal and sympathetic motor neurons. Intracisternal injection (ic) of a stable TRH analog RX77368 (7.5-25 ng) dose-dependently stimulated solid food intake by 2.4- to 3-fold in freely fed rats, an effect that lasted for 3 h. By contrast, RX77368 at 25 ng injected into the lateral ventricle induced a delayed and insignificant orexigenic effect only in the first hour. In pentobarbital-anesthetized rats, RX77368 (50 ng) ic induced a significant bipeak increase in serum total ghrelin levels from the basal of 8.7+/-1.7 ng/ml to 13.4+/-2.4 ng/ml at 30 min and 14.5+/-2.0 ng/ml at 90 min, which was prevented by either bilateral vagotomy (-60 min) or atropine pretreatment (2 mg/kg, -30 min) but magnified by bilateral adrenalectomy (-60 min). TRH analog ic-induced food intake in freely fed rats was abolished by either peripheral atropine or ghrelin receptor antagonist (D-Lys-3)-GHRP-6 (10 micromol/kg) or ic Y1 receptor antagonist 122PU91 (10 nmol/5 microl). Brain stem TRH mRNA and TRH receptor 1 mRNA increased by 57-58 and 33-35% in 24- and 48-h fasted rats and returned to the fed levels after a 3-h refeeding. Natural food intake in overnight fasted rats was significantly reduced by ic TRH antibody, ic Y1 antagonist, and peripheral atropine. These data establish a physiological role of brainstem TRH in vagal-ghrelin-mediated stimulation of food intake, which involves interaction with brainstem Y1 receptors.     

Beneficial effect of preinfarction angina on in-hospital outcome is preserved in elderly patients undergoing coronary intervention for anterior acute myocardial infarction.

BACKGROUND: Preinfarction angina improves survival after acute myocardial infarction (AMI) in nonelderly but not elderly patients in the thrombolytic era. However, it remains unclear whether preinfarction angina has a beneficial effect on clinical outcome in elderly patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: The study group comprised 484 anterior AMI patients who were admitted within 24 h of onset and underwent emergency PCI. Patients were divided into 2 groups: those aged < 70 years (nonelderly patients, n = 290) and those aged > or = 70 years (elderly patients, n = 194). Angina within 24 h before AMI was present in 42% of nonelderly patients and in 37% of elderly patients. In nonelderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (1% vs 7%, p = 0.02). Similarly, in elderly patients, preinfarction angina was associated with a lower in-hospital mortality rate (6% vs 16%, p = 0.03). Multivariate analysis showed that the absence of preinfarction angina was an independent predictor of in-hospital mortality in both nonelderly (odds ratio 4.20; 95% confidence interval (CI) 1.20-10.6; p = 0.04) and elderly patients (odds ratio 3.04; 95%CI 1.06-18.1; p = 0.04). CONCLUSIONS: Angina within the 24 h before AMI is associated with better in-hospital outcomes in elderly and nonelderly patients.     

Oncogenic osteomalacia in a case with a maxillary sinus mesenchymal tumor

We herein describe the rare case of a 41-year-old woman with oncogenic osteomalacia due to a tumor in the maxillary sinus who presented with chronic general pain that had been gradually deteriorating. The patient's laboratory findings revealed hypophosphatemia due to renal phosphate wasting, an inappropriately low serum 1 alpha,25-dihydroxyvitamin D3 level for hypophosphatemia and an unusually high serum level of fibroblast growth factor 23 (FGF23). The causative tumor was surgically removed, resulting in a rapid resolution of the patient's biochemical abnormalities. An improvement of the abnormal multiple deposits on (99)Technetium-methylene diphosphonate bone scintigraphy and an increase in the bone metabolism markers suggested the development of bone remodeling within 49 days after the operation. The pathologic diagnosis of the tumor was a "phosphaturic mesenchymal tumor, mixed with a connective tissue variant." The expression of FGF23 was demonstrated in the tumor by the immunohistochemical techniques and a Western analysis.     

Thyrotropin-producing pituitary adenoma associated with Graves' disease

OBJECTIVES: The examination of potential associations between Graves' disease and thyrotropin-producing pituitary adenoma (TSHoma) after treatment using octreotide, and of the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). DESIGN AND METHODS: A specimen of resected TSHoma tissue from our case was immunohistochemically examined for expression of somatostatin receptor 2A (SSTR2A) and PPAR gamma. Specimens of thyroid tissue from two cases with Hashimoto's thyroiditis were immunohistochemically examined for expression of SSTR2A. RESULTS: Expression of SSTR2A and PPAR gamma was identified in TSHoma cells. SSTR2A was also expressed in lymphocytes that had infiltrated thyroid tissue in Hashimoto's thyroiditis. In previous reports, three of four patients with TSHoma displayed Graves' disease after tumor resection, and TSH is also known to play a major role in regulating immunomodulatory gene expression in thyrocytes. CONCLUSIONS: Both the immunomodulatory effects of octreotide on intrathyroidal lymphocytes and rapid reductions in TSH may contribute to the onset of Graves' disease. Patients with TSHoma-associated autoimmune thyroiditis should undergo careful follow-up for development of Graves' disease after treatment. Both octreotide and the PPAR gamma receptor-activating ligands, thiazolidinediones, may be effective for patients with TSHoma.     

Adult T-cell leukemia with anti-HTLV-I antibody but no HTLV-I DNA in tumor cells.

Adult T-cell leukemia (ATL) is usually defined as a malignant disease of T cells infected by human T-lymphotropic virus type I (HTLV-I). In the present study, we describe a 49-year-old woman with an acute type ATL, whose leukemic cells do not contain the HTLV-I genome. Laboratory tests revealed an increase in abnormal lymphocytes with convoluted nuclei, elevated serum lactate dehydrogenase levels, increased thymidine kinase activity and soluble interleukin-2 receptor-alpha levels. Serum examination demonstrated positive anti-HTLV-I antibody, but Southern blot analysis using the whole HTLV-I genome as a probe did not detect any integration of the viral genome. In contrast, PCR detected the HTLV-I pX region in the same DNA samples as used for Southern blot analysis. These findings suggest two possibilities. One possibility is that ATL in this patient is generated by other pathogens than HTLV-I virus. She is also an HTLV-I carrier. The other possibility is that her leukemic T cell clone derived its malignant phenotype from HTLV-I infection, and once this malignant phenotype was obtained, partial deletions of viral genome repeated until the whole viral genome was deleted. Although there is no direct evidence, the former possibility is more likely in the present case.