Decreased bone mineral density in pre-menopause women with prolactinoma

Tumoral hyperprolactinemia and consequent hypogonadism have been associated with osteoporosis. Bone mineral density (BMD) was measured by dual-energy RX absorptiometry in 24 patients with prolactinoma (15 macro and 9 micro adenomas; age range = 18 to 49 years). Student unpaired t or Mann-Whitney tests were used to compare groups, and Spearman test studied correlations. Lumbar spine (LS) was the most affected, as LS Z-score was < -2 SD in 20.83% of the patients. No difference was found in densitometric parameters for the comparison between macro and microprolactinoma, or those with normal prolactin versus hyperprolactinemia. LS BMD and LS Z-score were higher in the patients with > 8 menstrual cycles in the preceding year then in those with oligoamenorrhea (p = 0.030). The number of cycles was correlated to LS BMD (r = 0.515, p = 0.017) and body mass index to femoral neck BMD (r = 0.563, p = 0.006) and total femur BMD (r = 0.529, p = 0.011). CONCLUSIONS: Decreased bone mineral density was detected in 20.83% of our young patients with prolactinoma. The great involvement of trabecular bone skeletal regions, such as vertebrae, suggests the participation of hypogonadism in the pathogenesis of bone disease. Irrespective of prolactin levels, return to normal menses seems the best index of good control.     

Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma

Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P < or = .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P < or = .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95% confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.     

Targeted treatment using monoclonal antibodies and tyrosine-kinase inhibitors in pregnancy

An expanding knowledge of the signalling pathways involved in the cell cycle has led to great improvements in the understanding of the molecular events involved in carcinogenesis. The past decade has seen substantial advances with the introduction of several classes of targeted therapeutics for the treatment of various cancers and autoimmune disorders. However, the question arises as to whether pregnant women can take advantage of these new treatments in view of the potential risks to the fetus. Published work suggests that biological agents, like traditional treatments, have the potential to affect the fetus, and should, therefore, be used with caution during pregnancy. However, when targeted treatment is clearly indicated the magnitude of the risk to the fetus might not reach that of standard chemotherapy. In circumstances where better alternative treatments do not exist, or where failure to use targeted treatments would result in suboptimum patient care or survival, the risk-benefit analysis might favour the use of potentially effective molecular treatment during pregnancy.     

Urolithiasis in pregnancy

The presentation of urolithiasis is often dramatic, but rarely is it more anxiety provoking than during pregnancy. The evaluation and the intervention are often approached with trepidation as the health of the mother and the fetus must be taken into account. The typical diagnostic course and surgical management used in the nonpregnant population must be reevaluated in the expectant mother. Failure to promptly diagnose and manage urolithiasis during pregnancy may have adverse consequences for mother and child. The authors present a review of the relevant anatomic and physiologic changes of pregnancy as they affect stone disease and outline options for radiologic evaluation and surgical management.     

The kinesin Eg5 inhibitor K858 exerts antiproliferative and proapoptotic effects and attenuates the invasive potential of head and neck squamous carcinoma cells

Investigational New Drugs - Our group recently demonstrated that K858, an inhibitor of motor kinesin Eg5, has important antiproliferative and apoptotic effects on breast cancer, prostatic cancer,...     

Safety of Efalizumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: Review of Clinical Data. Part II

Background

The efficacy and safety of efalizumab have been evaluated in multiple clinical trials.

Objective

The purpose of this review is to provide an overview of the safety profile of efalizumab during the clinical trials.

Methods

Twelve-week data from four placebo-controlled trials were pooled and analyzed. Data from patients receiving 13–60 weeks of efalizumab therapy were pooled to evaluate longer-term safety.

Results

The most common adverse events were mild to moderate, self-limiting, flu-like symptoms that were most frequent following the first two efalizumab doses; by the third dose the incidence was comparable to placebo. Serious adverse events were observed in 2.2% and 1.7% of efalizumab- and placebo-treated patients, respectively. Nonserious adverse events leading to withdrawal were infrequent and similar to placebo (2.8% vs 1.8%). There does not appear to be increased risk of end-organ toxicity, infection, or malignancy in efalizumab-treated patients.

Conclusion

Efalizumab was well tolerated, with a favorable safety profile.