The Janus face of maternal serum relaxin: a facilitator of birth,might it also induce preterm birth?

Objective: Preterm birth is a major cause of neonatal morbidity and mortality in the developed world. In order to better understand the pathophysiological pathway of this condition, the role of genetic factors and/or inflammation-associated molecules, as well as of socioeconomic parameters, is therefore under intense investigation. The purpose of this review study was to examine the potential role of maternal serum relaxin levels in the etiology of preterm birth.

Methods: Electronic databases (Pubmed, Embase, Cochrane Library) were searched for previously published research studies that investigated the biological role of relaxin and the mechanisms in which this hormone is involved during pregnancy and labor.

Results: It is evident that while relaxin is an essential endometrial/decidual angiogentic factor playing a vital role in maternal accommodation of pregnancy, elevated levels of this hormone could well be associated with preterm birth.

Conclusions: There are strong indications that maternal serum hyperrelaxinemia correlates with an increased risk of preterm birth.     

Results from an international multicentre double-blind randomized controlled trial on the perioperative efficacy and safety of bipolar vs monopolar transurethral resection of the prostate

Study Type – Therapy (RCT) Level of Evidence 1b What’s known on the subject? and What does the study add? Short‐term efficacy is similar but B‐TURP is preferable due to a more favourable safety. a) first multicentre RCT, b) adequate quality, c) experience with a new bipolar device, d) morbidity standardize using the modified Clavien classification system.

OBJECTIVE

? To compare the perioperative efficacy and safety of bipolar (B‐) and monopolar transurethral resection of the prostate (M‐TURP) in an international multicentre double‐blind randomized controlled trial using the bipolar system AUTOCON® II 400 ESU for the first time.

PATIENTS AND METHODS

? From July 2006 to June 2009, consecutive transurethral resection of the prostate (TURP) candidates with benign prostatic obstruction were prospectively recruited in four academic urological centres, randomized 1:1 into an M‐TURP or B‐TURP arm and followed up for 6 weeks after surgery. ? A total of 295 eligible patients were enrolled. ? Of these, 279 patients received treatment (M‐TURP, n= 138; B‐TURP, n= 141) and were analysed for immediate postoperative outcomes and perioperative safety. In all, 268 patients (M‐TURP, n= 129; B‐TURP, n= 139) were analysed for efficacy, which was quantified using changes in maximum urinary flow rate, postvoid residual urine volume and International Prostate Symptom Score at 6 weeks compared with baseline. Safety was estimated using sodium and haemoglobin level changes immediately after surgery and perioperative complication occurrence graded according to the modified Clavien classification system. ? Secondary outcomes included operation‐resection time, resection rate, capsular perforation and catheterization time.

RESULTS

? No significant differences were detected between each study arm except that postoperative decreases in sodium levels favoured B‐TURP (–0.8 vs –2.5 mmol/L, for B‐TURP and M‐TURP, respectively; P= 0.003). The lowest values were 131 mmol/L (B‐TURP) and 106 mmol/L (M‐TURP). Nine patients ranged between 125 and 130 mmol/L and the values for three patients were <125 mmol/L after M‐TURP. The greatest decrease was 9 mmol/L after B‐TURP (two patients). In nine patients (M‐TURP) the decrease was between 9 and 34 mmol/L. ? These results were not translated into a significant difference in TUR‐syndrome rates (1/138: 0.7% vs 0/141: 0.0%, for M‐TURP and B‐TURP, respectively; P= 0.495).

CONCLUSIONS

? In contrast to the previous available evidence, no clinical advantage for B‐TURP was shown. Perioperative efficacy, safety and secondary outcomes were comparable between study arms. ? The potentially improved safety of B‐TURP that is attributed to the elimination of dilutional hyponatraemia risk, a risk still present with M‐TURP, did not translate into a significant clinical benefit in experienced hands.     

Immunotherapy against invasive mold infections

Invasive infections due to filamentous fungi, such as Aspergillus spp., Zygomycetes, Scedosporium and Fusarium spp., cause significant morbidity and mortality in immunocompromised patients with hematological malignancies, recipients of hematopoietic stem cell transplants and those with chronic granulomatous disease. Despite antifungal therapy, the outcome is often unfavorable in these patients; immune restoration is considered as the cornerstone of successful treatment. Important aspects of human immune response against fungi include effective innate immune response expressed as effective phagocytic functions and a balance between proinflammatory and regulatory adaptive immune responses. A number of immunomodulatory approaches, including the administration of enhancing cytokines, adoptive transfer of pathogen-specific T lymphocytes and granulocyte transfusions have been investigated as adjunctive treatments against serious mold infections. Despite encouraging in vitro and in vivo data, current clinical evidence is not sufficient to allow firm recommendations on the use of these immunomodulatory modalities in serious mold infections.     

Unilateral lymphocytic pleuritis as a manifestation of familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disease affecting predominantly populations surrounding the Mediterranean basin. It is the most prevalent hereditary periodic fever syndrome characterized mainly by recurrent and short attacks of fever and serositis (pleuritis, arthritis, peritonitis). Unilateral polymorphonuclear exudative pleuritis associated with fever has been reported as the solitary manifestation of the first FMF attack, in < 10% of patients. This case study describes a 30-year-old Greek man with recurrent episodes of lymphocytic exudative pleuritis associated with fever. After a thorough workup (clinical criteria and molecular genetic testing identifying homozygosity polymorphisms of the FMF gene), the diagnosis of FMF was established. Treatment with colchicine, 2 mg/d, eliminated FMF attacks. To our knowledge, this is the first well-documented case report of a patient with FMF presenting with a lymphocytic exudative pleural effusion.     

Effects of dexamethasone and vitamin D3 on cartilage differentiation in a clonal chondrogenic cell population

We have investigated the regulation of chondroblast/chondrocyte differentiation using a unique clonal cell population, designated RCJ 3.1C5 (C5), which differentiates into discrete three-dimensional cartilage nodules when grown in the presence of 15% fetal calf serum. Histologically, the nodules resembled hyaline cartilage; they contained large rounded chondrocytes surrounded by a refractile matrix which stained intensely with Alcian blue, exhibited metachromasia after Toluidine blue staining, and stained with an antibody against type II collagen. The cartilage nodules that formed did not mineralize, despite the presence of organic phosphate in the culture medium. The synthetic glucocorticoid dexamethasone (DEX) increased the number of cartilage nodules formed in a dose-dependent manner (ED50, approximately 10(-9) M), with a maximal stimulatory dose of 10(-8) M. DEX had no effect on the population doubling time and saturation density. The effects of DEX on the number of cartilage nodules were similar whether it was added from the beginning of the culture period (starting during exponential growth) or at confluence. In contrast, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited cartilage nodule formation in a dose-dependent manner (IC50, approximately 5 x 10(-10) M), with maximum inhibition at 10(-7) M. In addition, 1,25-(OH)2D3 decreased cell proliferation and saturation density. Equimolar doses of the vitamin D3 metabolites 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 had no effect. C5 cells treated with 1,25-(OH)2D3 in the absence of DEX during the exponential growth phase exhibited a reduced capacity to form cartilage nodules upon subsequent exposure to DEX. At confluence, before cartilage nodules had formed, C5 cells responded to PTH and prostaglandin-E2 with increases in intracellular cAMP of about 10- and 95-fold respectively. After cartilage nodules were present, prostaglandin-E2 responsiveness decreased to about 25-fold, whereas there was no significant change in PTH responsiveness. DEX decreased the population alkaline phosphatase levels at all times measured, whereas 1,25-(OH)2D3 had a biphasic effect: an increase at 5 days in culture, followed by a decrease at later times in culture. These data indicate that the clonal cell line RCJ 3.1C5 is a useful model system in which to investigate cartilage differentiation.