Antitumor effects of TRAIL-expressing mesenchymal stromal cells in a mouse xenograft model of human mesothelioma.

Malignant mesothelioma (MM) remains a highly deadly malignancy with poor treatment option. The MM cells further promote a highly inflammatory microenvironment, which contributes to tumor initiation, development, severity and propagation. We reasoned that the anti-inflammatory actions of mesenchymal stromal cells (MSCs) and further antitumor effects of MSCs engineered to overexpress tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein (MSC-TRAIL) would effectively inhibit mesothelioma growth. Using a mouse xenograft model of intraperitoneal human mesothelioma, native mouse (mMSCs) or human (hMSC) MSCs were administered either systemically (intravenously or intraperitoneally) at various times following tumor inoculation. Both mMSCs and hMSCs localized at the sites of MM tumor growth in vivo and decreased local inflammation. Further, a trend towards decrease in tumor burden was observed. Parallel studies of in vitro exposure of nine primary human mesothelioma cell lines to mMSCs or hMSCs demonstrated reduced tumor cell migration. MSC-TRAIL exposure induced apoptosis of TRAIL-sensitive MM cells in vitro, and both mouse and human MSC-TRAIL significantly reduced the inflammatory tumor environment in vivo. Moreover, human MSC-TRAIL administration significantly reduced peritoneal tumor burden in vivo and increased tumor cell apoptosis. These proof-of-concept studies suggest that TRAIL-expressing MSCs may be useful against malignant mesothelioma.

Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women.

1. A randomized controlled trial of the effect of oral hormone replacement therapy plus calcium compared with calcium alone on balance, muscle performance and falls was conducted over 48 weeks in 116 post-menopausal women (aged 45-70 years), all of whom had suffered a distal radial fracture during the previous 3 months. Treatment was with Prempak C or Premarin 0.625 mg in the test group with 1 g calcium daily (Sandocal) in both groups. Measurements were made of balance, assessed as sway, leg extensor power and self-paced walking speed, at 12-week intervals over 24 weeks. Hand grip strength was measured every 12 weeks for 48 weeks, and falls in the preceding 12 weeks were recorded at each visit. 2. There was no relation between initial levels of oestradiol and any other variable assessed, except body mass. Levels of follicle-stimulating hormone in the test group were in the premenopausal range. There was no significant change attributable to hormone replacement therapy at any time point in any of the outcome variables. The only significant difference was an increase of 4.2% (95% confidence interval 0.7-7.6%) in leg extensor power in the control group (calcium alone) compared with the group treated with hormone replacement therapy. 3. Of the total group, 37% fell again during the year, with three patients suffering a further fracture. Frequent fallers swayed significantly more often than the others, but there was no evidence that their muscle strength was poorer or that the group treated with hormone replacement therapy fell less frequently. 4. Hormone replacement therapy did not increase muscle performance, improve balance or reduce falls over a year in middle-aged women.

Hormone replacement therapy acceptability to Nottingham post-menopausal women with a risk factor for osteoporosis.

In Nottingham we have assessed the acceptability of oral hormone replacement therapy (HRT) for an at risk group of post-menopausal women for osteoporosis. One hundred post-menopausal women between the ages of 50 and 70 years who had sustained a distal radial fracture were offered oral HRT. There was a 36% overall uptake of HRT with 9% of patients unable to take HRT because they had medical contraindications. The uptake in the 50-55 year age group was 54%. We conclude that in prospective studies of HRT for osteoporosis up to 50% of patients may not wish to take HRT and therefore study design should allow for this level of uptake.

A comparison of Lamicel and prostaglandin E2 vaginal gel for cervical ripening before induction of labor.

The efficiency and safety of Lamicel, a new synthetic cervical ripening agent, were compared with those of intravaginal prostaglandin E2 gel in a group of 80 primigravid women about to undergo induction of labor. Lamicel caused less uterine activity and fetal distress than prostaglandin gel, although the induction-delivery intervals were similar in both groups. More normal deliveries occurred in the Lamicel group than in the prostaglandin group. It is suggested that Lamicel is a useful, efficient preinduction ripening agent that is safer than intravaginal prostaglandin gel.

A force sensor and peak-reading recorder for measurement of cervical dilatation force.

Earlier dilatation force-sensing transducers, when subjected to side loads, suffered frictional losses which affected their accuracy. This new instrument incorporates a thermal-writing chart recorder and a digital readout of the peak force during dilatation of the cervix.

Midtrimester amniocentesis: is it safe? A single centre controlled prospective study of 517 consecutive amniocenteses.

The outcome of pregnancy following amniocentesis was studied prospectively in 517 consecutive patients undergoing amniocentesis in a single centre. The outcome in 289 of these pregnancies was compared with that in 289 control patients strictly matched for social class, age and parity. There were no significant differences in fetal loss, perinatal mortality or vaginal bleeding between the amniocentesis and control groups. There were significantly more congenital abnormalities in the amniocentesis group (P less than 0.01). These appear to be associated with the amniocentesis procedure and not with the occurrence of raised maternal serum alpha-fetoprotein levels. Although there was an increased risk of preterm delivery (P less than 0.02) there was no significant difference in the distribution of birthweights by centiles for gestational age between amniocentesis and control groups. There was a significant association between intrauterine growth retardation and raised serum alpha-fetoprotein (P less than 0.005). It is concluded that where the indications are strong, amniocentesis continues to be justified.

Lamicel: a new technique for cervical dilatation before first trimester abortion.

Mechanical dilation of the cervix can be both difficult and dangerous and has potentially serious complications. Lamicel, a synthetic hydrophilic polymer, was inserted into the cervix between 2 and 24 h before termination by vacuum aspiration in the first trimester in 48 nulliparae. A control group of 12 nulliparae were not treated with Lamicel. The force needed to dilate the cervix, accurately measured with a specifically designed force-measuring instrument, was found to be significantly reduced in all treated groups. The greatest rate of dilatation occurred within the first 2 h after insertion.

PIP: The study objective was to investigate the effectiveness of a synthetic hydrophilic polymer used as a cervical osmotic dilator before vacuum aspiration in 1st trimester abortion. Lamicel is a polyvinyl alcohol polymer sponge impregnated with magnesium sulphate and compressed to form a thin cylindrical tent. When inserted into the endocervical canal and left in position the Lamicel absorbs and retains fluid from the cervical tissue because of its hygroscopic properties. In the process the Lamicel swells to 4 times its original diameter and is converted from a hard rigid tent into a soft sponge. 60 nullipara who were having vacuum termination of pregnancy in the 1st trimester at the Queen's Medical Center and City Hospital, Nottingham, UK, were recruited into the study. The patients were randomly allocated to 1 of 5 groups each composed of 12 patients. 4 of the groups were treated with Lamicel for various periods before abortion; the 5th group was not treated with Lamicel and constituted a control group. In the 4 treated groups the Lamicel was left in position for periods of 2, 6, 12, or 24 hours in groups 2, 3, 4, and 5, respectively, before abortion. In the control group (group 1) lamicel was not inserted. After insertion the patients were monitored for evidence of discomfort, uterine cramps, sepsis, syncope, or bleeding. These observations were continued for 24 hours after the operation. The patients ranged in age from 14-28 years and gestation at termination ranged from 10-13 weeks. A comparison of the pressure recordings of the control group with each of the treated groups showed a highly significant difference. The reduction of cervical resistance occurred mainly in the first 2 hours after insertion of the Lamicel. There was further reduction in resistance up to 6 hours, but the difference between groups 1 (2 hours) and 2 (6 hours) was not statistically significant, and there were no significant differences between any of the treated groups. Insertion of 5mm Lamicel was achieved without difficulty in 43 (90%) of the patients. A 3mm Lamicel was chosen for the remaining 5 patients because of cervical resistance encountered at the internal os. During insertion 16 patients (33%) experienced mild discomfort. This resolved spontaneously within 5 minutes. There were no problems associated with the removal of the tents and no other side effects were noted. There were no differences in the amount of blood lost during the operation or in the incidence of postoperative pain and bleeding between the 5 groups.