First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma.

BACKGROUND: Bone involvement is frequently observed in multiple myeloma (MM) patients both at diagnosis and during the course of the disease. The evaluation of biochemical markers of bone turnover could allow a dynamic evaluation of the effects of a given therapy on bone metabolism. METHODS: In the present study, markers of bone resorption [urinary free pyridinoline (PYD), deoxypyridinoline (DPYD), N-terminal telopeptide of collagen I (NTX) and C-terminal telopeptide (serum crosslaps)] and of bone formation [bone alkaline phosphatase (BAP) and osteocalcin] were evaluated at diagnosis and after induction therapy in 40 patients (23M, 17F, median age = 53.5 yr) enrolled in the 'Bologna 2002' clinical trial. By study design, all patients received 4 months of combined thalidomide (100 mg/d for 2 wk then 200 mg/d), dexamethasone (40 mg/d on days 1-4, 9-12, 17-20/28 on odd cycles and on days 1-4 on even cycles) and zoledronic acid (4 mg/28 d). RESULTS: At diagnosis, although bone resorption markers were increased in more than 40% of the patients, only NTX (P = 0.029) and crosslaps (P = 0.000) were significantly related to the extent of skeletal lesions, as assessed by X-ray. After 4 months of therapy, a significant decrease in mean (+/-SE) urinary NTX (52.7 +/-6.9 nmol/mmol creatinine +/-6.9 vs. 14 +/- 1.42 nmol/mmol creatinine, P = 0.000) and serum crosslaps (6242.4 +/-945 pmol/L vs. 1414.9 +/- 173.8 pmol/L, P = 0.000) was observed in patients obtaining > or =partial response, at variance to what has been detected in patients showing

Effects of weight loss and risk factor treatment in subjects with elevated serum C3, an inflammatory predictor of myocardial infarction.

BACKGROUND: Serum C3 is an inflammatory predictor of myocardial infarction and a covariate of fasting insulin and several endogenous risk factors. This study was performed to ascertain whether risk factor control may reduce elevated C3 concentrations. METHODS: After traditional risk factor and C3 assessment in 1100 unselected men aged 55-64 years, 238 men with persistently elevated C3 levels (>=1.19 g/l, high tertile) were randomised into 2 groups: 43 controls, who were referred to their general practitioner, and 195 subjects who were intensively treated with diet, and anti-hypertensive or antidiabetic drugs according to specific indications, without anti-dyslipidemic drugs. RESULTS: After three months in the treated subjects significant decrements of body weight, blood pressure, blood glucose and serum lipids were obtained, with stable C3 levels (while in controls a 3.3% increase occurred, P=0.02). The factors associated with a C3 decrement >5% were a high baseline C3 level, a recent acute inflammation, physical activity, belonging to the treated group, and a significant reduction in body weight, triglycerides or blood glucose. However, in multivariate analysis only an elevated baseline C3 (P<0.0001), a weight loss >2% (P=0.0009) and physical activity (P=0.02) remained independently associated with a C3 decrement >5% (R(2)=0.14). CONCLUSIONS: Only weight loss and physical activity, but not traditional risk factor lowering, could independently induce a significant C3 decrease. Thus, C3 elevation is associated with, but probably not caused by, traditional risk factors.

Maternal serum levels of pro-inflammatory cytokines in missed and threatened abortion.

PROBLEM: A study of association between pro-inflammatory cytokines, and missed and threatened abortions with good outcome has been performed. METHOD OF STUDY: The presence of pro-inflammatory cytokines, namely interleukin (IL)-8 and IL-12 and the soluble interleukin-2 receptor (SIL-2R) was investigated in maternal serum of 12 patients with threatened abortion twice (at admission and discharge), 14 patients with missed abortion, 14 women with healthy first-trimester pregnancy, and 14 normal non-pregnant women, using specific enzyme-linked immunosorbent assays. RESULTS: SIL-2R and, in particular, IL-12 was detected with significantly higher levels in missed abortion group compared with all other groups. IL-8 was detected with no significant difference among all the groups studied. CONCLUSIONS: In spite of caution due to the small sizes of the subject samples, these results support a role of the immune system in the first trimester pregnancy and hypothesize that missed abortion may be associated with an enhanced Th1 reactivity, whereas threatened abortion with good outcome resembles the normal pregnancy with a non-enhanced Th1 reactivity.

T-helper 2-cytokine levels in women with threatened abortion.

OBJECTIVE: Considering that successful embryo development has been immunologically attributed to a T-helper 2 phenomenon and that threatened abortion is a very frequent but pathogenetically not well-defined clinical entity, our purpose was to investigate serum levels of the main T-helper 2-type cytokines during the evolution of this condition. STUDY DESIGN: Three T-helper 2-type cytokines (interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-13 (IL-13)) were measured by an enzyme-linked immunosorbent assay (ELISA) in serum of 12 women with threatened abortion both at hospital admission and discharge time. Fourteen women with missed abortion, 14 normal pregnant women and 14 normal non-pregnant women represent study control groups. RESULTS: Serum concentrations of the selected T-helper 2-type cytokines showed no significant differences in women with threatened abortion with those of normal pregnant and non-pregnant women, whereas showed significantly lower values in women with missed abortion. CONCLUSION: Our data (a) confirm the concept that first-trimester normal pregnancy is a T-helper 2 phenomenon, (b) show that threatened abortion, when T-helper 2-biased, may tend to a positive evolution of the condition, (c) display that interleukin-10, particularly, may represent a useful diagnostic and prognostic marker for predicting the normal continuance of the pregnancy in threatened abortion, (d) confirm the existence of a T-helper 2-type pattern deficiency in missed abortion, and finally (e) may open the way to new T-helper 2-biased immune therapies in case of difficult first-trimester pregnancies.