Prognostic value of C-reactive protein,fibrinogen, interleukin-6, and macrophage colony stimulating factor in severe unstable angina

BACKGROUND: Inflammatory process plays an important role in the pathogenesis of acute coronary syndromes. HYPOTHESIS: The study was undertaken to evaluate whether admission levels of C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6). and macrophage colony stimulating factor (MCSF) can predict short-term prognosis in patients with unstable angina. METHODS: C-reactive protein, fibrinogen, IL-6, and MCSF were measured on admission in 141 consecutive patients, aged 59 +/- 10 years, with unstable angina (Braunwald class IIIb). Patients were divided into two groups according to their in-hospital outcome: Group 1 comprised 77 patients with a complicated course (2 died, 15 developed nonfatal myocardial infarction, and 60 had recurrence of angina), and Group 2 comprised 64 patients with an uneventful course. RESULTS: Admission median levels of CRP (8.8 vs. 3.1 mg/l, p = 0.0002). fibrinogen (392 vs. 340 mg/dl, p = 0.008), IL-6 (8.8 vs. 4.5 pg/ml, p = 0.03), and MCSF (434 vs. 307 pg/ml, p = 0.0001) were higher in Group I than in Group 2. The MCSF levels were an independent risk factor for in-hospital events, with an adjusted odds ratio for eventful in-hospital outcome of 3.3 (95% confidence interval 1-10.9, p = 0.04), and correlated with levels of IL-6 (r(s) = 0.52, p = 0.0001), CRP (r(s) = 0.43, p = 0.0001), and fibrinogen (r(s) = 0.25, p = 0.004). CONCLUSIONS: These findings suggest that among the studied inflammatory indices only increased admission levels of MCSF are strongly and independently related with adverse short-term prognosis in patients with severe unstable angina.     

Thyroid function in humans with morbid obesity.

Morbidly obese subjects may present with abnormal thyroid function tests but the reported data are scarce. Therefore, we studied the thyroid parameters in 144 morbidly obese patients, 110 females and 34 males, to assess the prevalence of hypothyroidism. Eleven percent (11.8%) carried the diagnosis of hypothyroidism and were undergoing levothyroxine (LT4) replacement therapy, 7.7% had newly diagnosed subclinical hypothyroidism, 0.7% had subclinical hyperthyroidism and 7.7% were euthyroid with positive antibodies (anti-thyroid peroxidase antibodies [TPOAb]). From the 144 subjects, we selected a cohort of 78 euthyroid subjects with negative TPOAb, who did not receive LT4 replacement or suppression therapy (the experimental group) and compared them to 77 normal-weight euthyroid subjects, TPOA-negative, matched for age and gender who served as controls. The experimental group had higher serum levels of triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), and thyrotropin (TSH) compared to the control group. Serum TSH concentration was associated with fasting serum insulin levels and insulin resistance but not with serum leptin levels, body mass index (BMI), fat mass, and lean body mass. In conclusion, in morbidly obese individuals, the prevalence of overt and subclinical hypothyroidism was high (19.5%). The morbidly obese subjects have higher levels of T3, FT3, T4, and TSH, probably the result of the reset of their central thyrostat at higher level.     

The prolyl‐hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia

EGLN1 and EGLN3 are members of the egg‐laying‐defective 9 (EglN) prolyl‐hydroxylases which during normoxia catalyse hydroxylation of the hypoxia‐inducible factor (HIF)‐1α, thereby promoting its ubiquitination by a complex containing the von Hippel–Lindau (VHL) tumour suppressor. EGLN3 also has pro‐apoptotic activity in some cell types. Analyses of a well‐characterised series of cases of plasma cell dyscrasias, including multiple myeloma (MM), Waldenström’s macroglobulinaemia (WM) and monoclonal gammopathy of undetermined significance (MGUS) surprisingly demonstrated that the CpG island of EGLN3, and not EGLN1, is frequently methylated in these disorders. Multiple myeloma patients with a methylated EGLN3 promoter showed trends towards an increased risk of death, bone lytic lesions, anaemia, advanced stage of disease and the presence of extramedullary disease. Those individuals with methylation in the EGLN3 CpG island also had significantly lower albumin levels. These data suggest that the prolyl‐hydroxylases may be a novel class of potential tumour suppressors in plasma cell neoplasia that warrant further investigation with regard to their potential utility as biomarkers. Moreover, we observed that EGLN3 is also methylated at high frequency in B‐cell lymphoma subtypes, implying that loss of EGLN3 is an important epigenetic event not only in plasma cell neoplasias but also in B‐cell neoplasias.     

Phantom cytomegalovirus infection in vasculitis patients: what it means and what to do

We report our experience and hypothesis on the diagnosis and treatment of patients with vasculitis who are simultaneously diagnosed with serum-positive cytomegalovirus (CMV) immunoglobulin (Ig)M antibodies and negative CMV DNA polymerase chain reaction (PCR). It remains unknown how to treat this kind of phantom CMV infection. In a patient diagnosed with Henoch-Schönlein vasculitis, CMV IgM titers were increased while angiitis and renal function deteriorated. Empiric treatment of phantom CMV infection with ganciclovir in this CMV IgM-positive and PCR-negative patient resulted in complete vasculitis remission, serum CMV antibody seroconversion, and renal function improvement. These results imply something more than coincidence.     

High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas

Objectives Previous studies based on standard endocrine testing have shown a variable incidence of autonomous cortisol secretion (ACS) or autonomous aldosterone secretion (AAS) in patients with single adrenal adenomas (SAA). We tested whether the use of appropriate controls and modification of standard testing, aiming at eliminating interference from endogenous ACTH, reveals previously undetected subtle ACS and AAS by SAA. Design Case control study. Patients We investigated 151 patients with SAA and 72 matched controls with normal adrenal computerized tomography. Measurements All participants had arterial blood pressure recorded, and serum cortisol and aldosterone measured before and after intravenous administration of 250 μg of ACTH, and following dexamethasone administration. Eighty‐three patients and all the controls had serum aldosterone and renin measured before and after saline infusion, and after a second saline infusion following dexamethasone administration. Results Using the mean + 2 SD values obtained from controls after dexamethasone administration and saline infusion following dexamethasone administration, normal cut‐off values for cortisol (30·11 nm ), aldosterone (67·59 pm ), and aldosterone/renin ratio (9·74 pm /mU/l) were developed. Using these cut‐off values, the estimated incidence of ACS and AAS in patients with SAA was 56·63% and 24·10%, respectively, whereas 12·05% had autonomous secretion of both cortisol and aldosterone. Systolic and diastolic arterial blood pressure correlated significantly with the aldosterone/renin ratio following ΑCTH stimulation (P < 0·0002 and P < 0·001, respectively), and after saline infusion following dexamethasone administration (P < 0·003 and P < 0·002, respectively). Conclusions By applying new cut‐offs, ACS and AAS in patients with a SAA is very common, and aldosterone secretion correlates with arterial blood pressure.