Tibolone and estradiol plus norethisterone acetate similarly influence endothelium-dependent vasodilatation in healthy postmenopausal women

In healthy postmenopausal women, E(2) plus norethisterone acetate (1 mg + 0.5 mg) or tibolone (2.5 mg) similarly modify flow-mediated endothelium-dependent vasodilatation. The effect is dependent on baseline vasodilator reserve, with low values being augmented by either treatment.     

Randomized study on removable PGE2 vaginal insert versus PGE2 cervical gel for cervical priming and labor induction in low-Bishop-score pregnancy

BACKGROUND: Dinoprostone vaginal insert has been compared to Dinoprostone cervical gel in few studies, whose cases presented different Bishop scores and gestational ages at admission, and various treatment strategies in control arms. The present study compares the vaginal insert to the cervical gel in patients with low Bishop score at term. METHODS: Prospective multicenter randomized trial, with parity-based randomization. Admission criteria: single pregnancy with Bishop score of 0-4, gestational age of 37-41 weeks, intact membranes, no previous cesarean section, no bleeding or abnormal cardiotocography at admission. RESULTS: Vaginal prostaglandins were required as a second-line induction procedure in 25% of study patients versus 47.1% of controls (p < 0.03, chi2). Study patients experienced shorter induction-to-delivery time (920 +/- 428 versus 1,266 +/- 740 min, p <0,01), with a mean difference of 5 h and 46 min between the groups. Even though patients that received vaginal insert showed a trend of increased incidence of abnormal cardiotocography during labor (12% versus 6.3%) and hyperkinetic labor (11.8% versus 2.1%), the incidence of cesarean sections (21.4% versus 21.6%), cesareans for fetal distress (12.5% versus 11.8%), and umbilical artery pH <7.10 (4.9% versus 2.5%) was comparable between the two groups. CONCLUSIONS: Dinoprostone vaginal insert is more efficient than cervical gel in promoting cervical priming and labor induction in low-Bishop-score patients at term. The vaginal insert placement seems to be safe for the mother and the newborn, although larger studies are required to investigate uterine hyperstimulation incidence.     

Modification of 24-h ambulatory blood pressure and heart rate during contraception with the vaginal ring: a prospective study

Background

Hypertension is recognized as a major risk factor for coronary, cerebral and renal vascular disease. Hormonal methods of contraception may increase the risk for cardiovascular events. We evaluated whether the combined hormonal contraceptive vaginal ring that releases 15-mcg ethinylestradiol and 120 mcg of etonogestrel each day influences 24-h ambulatory blood pressure.

Study Design

At baseline, ambulatory blood pressure was automatically monitored every 30 min for 41 h in 18 normotensive healthy women during their follicular phase (Days 3–6). Each subject was immediately treated with the vaginal ring for six cycles. Monitoring of ambulatory blood pressure was repeated in the last days of the sixth cycle of treatment.

Results

During the vaginal ring, a significant increase was observed for 24-h diastolic (2.75±5.13 mmHg; p=.03) and mean (2.69±5.35 mmHg; p=.048) blood pressure and for daytime diastolic (3.04±6.36 mmHg; p=.05) blood pressure. No variation was found in nighttime blood pressure. Heart rate increased in the 24-h period (3.39±5.85 beats/min; p=.025) and in the daytime (3.38±6.25 beats/min; p=.034) measurements.

Conclusions

In normotensive women, the vaginal ring slightly increases 24-h blood pressure and heart rate. The underlying mechanisms and the clinical impact of these slight modifications require further evaluation.     

CACNA1A-p.Thr501Met mutation associated with familial hemiplegic migraine: a family report

Background and aimsHemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe.We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation.MethodsWe screened for mutations in CACNA1A gene 15 patients belonging to the same family. The exonic sequences of CACNA1A were analyzed using a Tru-seq® Custom Amplicon (TSCA) (Illumina Inc., San Diego, CA) targeted capture and paired end library kit. Sanger sequencing was used to confirm CACNA1A variants and segregation analysis.ResultsCACNA1A-p.Thr501Met mutation was found in 12 of the 15 patients screened, which was compatible with the diagnosis of FHM1.Attacks of hemiplegic migraine were reported by 10 of the 12 subjects (83.33%). Only one subject developed persistent mild cerebellar symptoms and none of the subjects developed cerebellar atrophy.DiscussionThe variant p.Thr501Met was described previously in association with episodic ataxia and rarely with FHM related to cerebellar symptoms. FHM1 has a broad clinical spectrum and about half of the families have cerebellar involvement. In our study, only one patient developed persistent cerebellar deficits.These data suggest that CACNA1A-p.Thr501Met mutation can occur prevalently as hemiplegic migraine.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01297-5.     

Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin

Purpose The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy. Methods Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m² i.v. only on day 1, with leucovorin 100 mg/m² i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m²/day and a 22-h infusion of 5-FU 600 mg/m²/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion. Results The percentage of patients presenting with grade ≥2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade ≥2 neurotoxicity in group A (6.1%) than in group B (18.5%) (P < 0.001). Conclusions This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.