Increased macrophage colony-stimulating factor levels in patients with Graves’ disease

Previous studies have found markedly elevated serum concentrations of proinflammatory cytokines in patients with Graves’ disease (GD). We investigated the role of macrophage colony-stimulating factor (M-CSF) in GD. We assayed concentrations of M-CSF in sera from 32 patients with GD (25 untreated; 7 receiving thiamazole therapy). We also studied 32 age-matched healthy subjects as controls. Relationships between serum M-CSF and both thyroid state and serum lipids were examined. Moreover, to examine the effect of thyroid hormone alone on serum M-CSF, T3 was administered orally to normal subjects. Serum concentrations of M-CSF in GD patients who were hyperthyroid were significantly increased compared with GD patients who were euthyroid (P < 0.05) and control subjects (P < 0.0001). Serum M-CSF concentrations correlated closely with T3 levels in patients (r = 0.51, P < 0.005). Serial measurement of five individual patients revealed that serum concentrations of M-CSF were significantly decreased (P < 0.05), reaching normal control values upon attainment of euthyroidism. Furthermore, oral T3 administered to 15 volunteers for 7 days produced significant increases in serum levels of M-CSF (P < 0.05). The close correlation between serum M-CSF and serum thyroid hormone levels suggests that high circulating levels of thyroid hormones may directly or indirectly potentiate the production of M-CSF in patients with GD.     

Clinicopathology of pancreaticobiliary maljunction: relationship between alterations in background biliary epithelium and neoplastic development

Background/Purpose

Between 1988 and 2003, 38 patients underwent biliary resection for pancreaticobiliary maljunction (PBM). We reviewed the histopathologic findings for the surgically resected specimens to compare the clinical and pathologic features and assess the relationship between changes in the background biliary epithelium and the development of neoplasms.

Methods

Papillary hyperplasia (PHP) seen in the biliary epithelium of patients with PBM, was classified into grades 0–III in the gallbladder and grades 0–II in the extrahepatic bile duct, according to the extent, and was assessed for links with tumors in the same specimens.

Results

The incidence of gallbladder carcinoma was 13/21 in grades I–II, versus 0/16 in grade III, while the incidence of bile duct carcinoma was 4/20 in grade I versus 0/5 in grade II. Furthermore, these incidences for patients below age 50 years and age 50 or older were 1/18 versus 12/20, and 0/14 versus 6/17, respectively.

Conclusions

PHP of the biliary epithelium in PBM patients is an important precursor lesion, especially for gallbladder cancer, and the risk becomes greater with age, regardless of the type of pancreatobiliary junction (PBJ) and its location in the biliary tract.     

Pain in patients with fibromyalgia syndrome

Chronic diffuse pain and hyperalgesia are two cardinal features of pain in fibromyalgia syndrome (FMS). Advancement in understanding the pathophysiology and treatment efficacy often depends on pain that is defined and measured. Pain is a subjective phenomenon that we can measure only by indirect methods. In this article, we provide methodological guidelines for pain assessment and review recent developments in understanding pain mechanisms and evaluating treatments in FMS. Finally, we demonstrate the heterogeneity of the FMS population and suggest the need for matching treatments to patient characteristics in order to improve clinical outcomes.     

The efficacy and safety of bucillamine as a second-line DMARD in the treatment of rheumatoid arthritis: a retrospective cohort study

We investigated the efficacy and safety of bucillamine administered as a second-line DMARD compared to administration as a first-line DMARD in the treatment of rheumatoid arthritis (RA). We conducted a retrospective cohort study and reviewed medical records of 86 patients with active RA who began to receive bucillamine at Yokohama Minami Kyosai Hospital between January 1998 and July 2004. The efficacy of treatments was compared based on rates of achievement of 20, 50, and 70% improvement in ACR core set 6 months after initiation of the therapy. In the group administered bucillamine as a first-line DMARD (18 patients), 44.4, 22.2, and 11.1% of patients achieved ACR 20, 50, 70, respectively, while 56.5, 34.1, and 19.5% achieved ACR 20, 50, 70, respectively, in the group administered bucillamine following switching from MTX (46 patients), and 53.3, 33.3, and 13.3% achieved ACR 20, 50, and 70, respectively, in the group administered bucillamine following switching from Sulfasalazine (SSZ) (15 patients). The rates of achievements of ACR 20, 50, 70 did not differ statistically between the three groups and there was no increase in risk of serious adverse effects related to previous DMARDs. The usefulness of bucillamine as a second-line DMARD was demonstrated.     

Innate control of adaptive immunity via remodeling of lymph node feed arteriole

The adaptive immune system relies on rare cognate lymphocytes to detect pathogen-derived antigens. Na?ve lymphocytes recirculate through secondary lymphoid organs in search of cognate antigen. Here, we show that the na?ve-lymphocyte recirculation pattern is controlled at the level of innate immune recognition, independent of antigen-specific stimulation. We demonstrate that inflammation-induced lymphocyte recruitment to the lymph node is mediated by the remodeling of the primary feed arteriole, and that its physiological role is to increase the efficiency of screening for rare antigen-specific lymphocytes. Our data reveal a mechanism of innate control of adaptive immunity: by increasing the pool of na?ve lymphocytes for detection of foreign antigens via regulation of vascular input to the local lymph node.     

Prognostic value of pacing-induced mechanical alternans in patients with mild-to-moderate idiopathic dilated cardiomyopathy in sinus rhythm.

OBJECTIVES: The relation between the occurrence of pacing-induced mechanical alternans and prognosis in patients with mild-to-moderate idiopathic dilated cardiomyopathy (IDCM) in sinus rhythm was investigated prospectively. The myocardial expression of genes for Ca2+-handling proteins in such patients was also examined. BACKGROUND: Mechanical alternans occurs in some patients with severe heart failure, but the relation between the occurrence of mechanical alternans and prognosis in patients with IDCM has remained unknown. METHODS: Left ventricular (LV) pressure was measured during atrial pacing, and LV endomyocardial biopsy specimens were collected in 36 IDCM patients and 8 controls. Idiopathic dilated cardiomyopathy patients were divided into two groups consisting of 22 individuals who did not develop mechanical alternans at heart rates up to 140 beats/min (group A) and of 14 individuals who did (group B). The patients were followed up for a mean of 3.7 years. RESULTS: There was no significant difference in LV ejection fraction or the plasma concentration of brain natriuretic peptide between groups A and B. The myocardial abundance of ryanodine receptor 2 messenger ribonucleic acid (mRNA) was significantly lower in groups A and B than in controls, whereas that of sarcoplasmic reticulum Ca2+-ATPase mRNA was significantly lower in group B than in group A or controls. Stepwise multivariate analysis identified pacing-induced mechanical alternans as the strongest predictor of cardiac events. Event-free survival in group A was significantly greater than that in group B. CONCLUSIONS: The occurrence of pacing-induced mechanical alternans is a potentially useful indicator of poor prognosis in patients with mild-to-moderate IDCM in sinus rhythm.