Ferring Pharmaceuticals (Finland)

BACKGROUNDOvarian hyperstimulation syndrome (OHSS) seems to be induced by the ovarian release of vascular endothelial growth factor (VEGF), which increases vascular permeability. Dopamine agonists inhibit VEGF receptor phosphorylation and thereby decrease vascular permeability.METHODSA randomized, double-blind, placebo-controlled, multicentre study assessing three oral doses (50, 100, 200 µg/day) of the non-ergot derived dopamine agonist quinagolide started on the day of human chorionic gonadotrophin (hCG) and continued for 17–21 days without dose-titration in comparison to placebo in preventing moderate/severe early OHSS (onset ≤9 days after hCG administration) in 182 IVF patients with ≥20 but less than 30 follicles ≥10 mm.RESULTSThe incidence of moderate/severe early OHSS was 23% (12/53) in the placebo group and 12% (6/51), 13% (7/52) and 4% (1/26) in the quinagolide 50, 100 and 200 µg/day groups, respectively. The moderate/severe early OHSS rate was significantly lower with all quinagolide groups combined compared with placebo [P = 0.019; OR = 0.28 (0.09–0.81)]. The incidence of ultrasound evidence of ascites among patients with no clinical pregnancy was significantly reduced from 31% (8/26) with placebo to 11% (8/70) with all quinagolide groups combined [P = 0.033; OR = 0.29 (0.10–0.88)], although there was no difference for those with clinical pregnancy. Quinagolide did not have a detrimental effect on pregnancy or live birth rates. The incidence of gastrointestinal and central nervous system adverse events increased with increasing doses of quinagolide.CONCLUSIONSQuinagolide appears to prevent moderate/severe early OHSS while not affecting treatment outcome. The effect is more marked in patients who did not achieve a clinical pregnancy. Quinagolide administered in high doses without dose-titration is associated with poor tolerability.ClinicalTrials.gov Identifier: NCT00329693.

To evaluate the accuracy of total serum calcium (CaT) and albumin-adjusted total calcium (CaA) determinations in the assessment of calcaemic status in the elderly, serum ionized calcium (CaI), CaT and serum albumin (Alb) concentrations were measured in 558 geriatric hospital patients. As expected, CaT was correlated with Alb (r = 0.316, p less than 0.001) and CaI with serum pH (r = -0.351, p less than 0.001) and they were closely interrelated (r = 0.746, p less than 0.001). Various albumin-adjustment formulas from the literature decreased the correlation of CaT and CaI. Using conventional reference limits for CaT only 12% and 72% of patients with CaI above or below the reference limits for CaI, respectively, were found. This study demonstrates the low sensitivity of total and albumin-adjusted calcium in the detection of slightly or moderately abnormal calcaemic states.

Clinical, pathophysiological, pharmacological, and biochemical evidence support the concept that the prostanoid system may be involved in migraine. As a local defence system prostaglandins may best be linked with hyperalgesia and vascular events. The response to potent inhibitors of PG-synthesis like tolfenamic acid further supports the involvement of prostaglandins in the “inflammatory-like” aspects of migraine pain. The prostanoid system may be closely coupled with the monoaminergic mechanism; e.g. in stress reactions plasma thromboxane correlates with adrenaline levels. The possible participation of leukotrienes in migraine is only speculative. However, in cerebral hypoxia lipid peroxidation is increased and leukotrienes might participate in the cerebrovascular reactions. Prostaglandins may inhibit the formation of free radicals, antagonize some actions of leukotrienes and protect the tissues. The interplay between leukotrienes and prostaglandins may give new aspects to some cerebrovascular abnormalities in migraine.