Return of fertility following discontinuation of an injectable contraceptive — Norethisterone oenanthate (NET EN) 200mg dose

The return of fertility following discontinuation of norethisterone oenanthate (NET EN) 200 mg injectable contraceptive after use for a minimum period of six months or more was studied in 69 women who discontinued the method for planning pregnancy. Former users of copper intra-uterine device (CuT 200) were enrolled as a control group. Another 161 women who had discontinued NET EN due to other reasons (e.g. amenorrhoea, excessive bleeding or personal reasons) were also studied for return of fertility after ensuring that they were not using any other method of contraception and were exposed to the risk of pregnancy. The subjects from both groups were followed for a period of one year. The cumulative conception rates at one year were 72.5 and 83.6 per 100 subjects for ex-NET EN and ex-CuT 200 users who had discontinued the method for planning pregnancy and this difference was not statistically significant (P > 0.05). The median time for conception for ex-NET EN users was 7.8 months as compared to 3.7 months in ex-CuT 200 users but the cumulative conception rates at the end of one year show that future return of fertility in NET EN users does not appear to be adversely affected.

In 51 subjects who had discontinued NET EN due to amenorrhoea, the return of fertility was predictably slower and less. The return of fertility in subjects who discontinued NET EN for other reasons (e.g. excessive bleeding and other personal reasons) was similar to ex-NET EN and ex-CuT 200 users.     

The glycosaminoglycans of the gubernaculum during testicular descent in the fetus

Tissues were obtained from 387 male pig fetuses ranging from 60 to 120 days of gestation. The relative wet mass and water content of the gubernaculum increased during and decreased after the period of testicular descent. The extracellular glycosaminoglycans (GAG) were assayed to determine whether these polyanionic macromolecules are responsible for the increased water content of the gubernaculum. The total GAG/wet tissue mass in the gubernaculum decreased during and increased after descent, while the total GAG/dry mass decreased during and after descent, indicating an accumulation of water during descent, with a loss of water and an increase in less hydrated tissue components after descent. The major GAG fraction in the gubernaculum was dermatan sulfate, but the percentage hyaluronate in the gubernaculum was two times higher than in striated muscle or umbilical cord, indicating that this GAG fraction may be responsible for the increased water content of the gubernaculum, which probably serves to dilate the inguinal canal and scrotum, thus facilitating descent.     

Photodynamic therapy inhibits transforming growth factor β activity associated with vascular smooth muscle cell injury

Purpose: The multifunctional cytokine, transforming growth factor β1 (TGF-β), plays an important role in the development of injury-associated intimal hyperplasia (IH). Strategies to suppress local TGF-β activity may have a clinical potential to prevent restenosis caused by IH. Photodynamic therapy (PDT) involves the local generation of cytotoxic free radicals by light activation of photosensitizer dyes and has been shown to inhibit experimental IH. This study investigated whether PDT-generated free radicals can affect TGF-β activity in a biologic system using vascular smooth muscle cells (SMCs).Methods: The release and activation of TGF-β by injured SMCs in culture was compared between mechanical injury and PDT. Mechanical injury was induced with a rubber policeman, and PDT was performed with the photosensitizer chloroaluminum sulfonated phthalocyanine (5 μg/ml) and 675 nm laser light at subtherapeutic 10 J/cm² and the in vivo therapeutic dose of 100 J/cm². Cell viability was assessed by the tetrazolium salt conversion assay, and active and total (active + latent) TGF-β was determined by enzyme-linked immunosorbent assay in the conditioned media of SMCs 24 hours after treatment. Functional TGF-β activity was assessed by inhibition of endothelial cell mitogenesis.Results: Both forms of injury severely reduced (p < 0.0005) SMC viability to less than 15%. In untreated SMC conditioned media, only 14.5% of the total TGF-β was active (27.7 ± 8.7 pg per 1 × 10⁵ cells). However, after mechanical injury and PDT with 10 J/cm², there was a significant increase (p < 0.02) in active TGF-β (60.1 ± 10.1 pg and 48.6 ± 21.0 pg, respectively), despite a total reduction of approximately 50%. In contrast to this result, PDT with 100 J/cm² did not result in increased levels of active TGF-β (8.1 ± 3.5 pg), despite having similar levels of total TGF-β. Consequently, the conditioned media of SMCs that had 100 J/cm² PDT did not inhibit endothelial cell mitogenesis as compared with the conditioned media of SMCs with mechanical injury and 10 J/cm² PDT (p < 0.0002).Conclusions: This report describes two novel findings: (1) injury to SMCs in vitro induces the conversion of biologically latent TGF-β to active TGF-β; and (2) the therapeutic PDT dose interferes with this injury activation process. This study substantiates the concept of local cytokine inhibition by PDT in a biologic system and provides new insights into the mechanisms of PDT-mediated inhibition of experimental IH. (J Vasc Surg 1997;25:1033-43.)     

Hyperplasia and hypertrophy of the gubernaculum during testicular descent in the fetus

The role of the gubernaculum during testicular descent was investigated in 115 male pig fetuses ranging from 68 to 109 days of gestation. Descent of the testis through the inguinal canal occurred between 77 and 94 days. There was a marked increase in the total and relative wet mass as well as the wet/dry mass ratio of the gubernaculum, denoting an increase in the water content of this structure during descent of the testis. Similar changes were not seen in other fetal tissues. Asymmetrical descent of the testes occurred in seven of the 40 fetuses between 81 and 92 days of gestation. Descended testes had gubernacula with a greater relative wet mass than the gubernacula of undescended testes. These findings indicate that the increase in mass of the gubernaculum plays an important part in testicular descent. An increase in both the DNA content (hyperplasia) and the RNA/DNA ratio (hypertrophy) was noted in the gubernaculum during descent of the testis. Hyperplasia in the gubernaculum occurred at a rapid rate initially and ceased after the completion of descent. Hyperplasia was also seen in the testis and epididymis, but occurred at a slower rate initially, with a rapid acceleration after the completion of descent. Cellular hypertrophy was not noted in the testis and epididymis, but did occur in umbilical cord tissue. If gonadotropins acting via androgen secretion by the testis provide the stimulus for these changes, the observed difference in response between the gubernaculum and testis could be due to a difference in end-organ sensitivity. However, it is also possible that some unidentified non-androgenic gubernaculotropin, possibly secreted by the fetal testis, provides the stimulus for gubernacular growth.     

Waiting times for radiotherapy: consequences of volume increase for the TCP in oropharyngeal carcinoma.

BACKGROUND AND PURPOSE: Waiting lists for radiotherapy have become longer over the past years. Apart from the psychological distress for the patient we are concerned about tumour growth during this waiting time, which may worsen prognosis. The purpose of this pilot study was to investigate tumour growth in the waiting time and to obtain an indication of its clinical consequences for patients with oropharyngeal carcinoma. A tumour control probability (TCP) model was applied to evaluate consequences for outcome. METHODS AND MATERIALS: Increase in tumour volume was measured for 13 patients with oropharyngeal carcinoma by outlining the tumour on the diagnostic as well as on the treatment planning CT scan. Waiting time was defined as time between histopathological diagnosis and start of radiotherapy. For each tumour we calculated the increase in tumour volume and the tumour doubling time. The potential increase in TCP was calculated for each tumour for the situation without treatment delay. RESULTS: The mean increase in tumour volume was 70%. The mean waiting time was 56 days. Expected TCP with incorporation of delay was 47%, without delay it might have been 63-66%. CONCLUSION: This study shows tumour progression during the time between the diagnostic CT scan and the treatment planning CT scan in oropharyngeal cancer. As a consequence of waiting time, which allows tumour volume increase, there may be an average control loss of 16-19 % for these tumours during the total waiting time before radiotherapy.     

Recombinant follicle stimulating hormone: development of the first biotechnology product for the treatment of infertility. Recombinant Human FSH Product Development Group

Genes encoding the common gonadotrophin subunit and folliclestimulating hormone (FSH)-specific ß subunit wereisolated from a DNA library derived from human fetal liver cells,and inserted into separate expression vectors containing a selectable/amplifiablegene. These vectors were inserted into the genome of the Chinesehamster ovary cell line, resulting in expression of large amountsof biologically active human (h)FSH. This cell line was culturedon microcarrier beads in a large-scale bioreactor. hFSH in thecell culture supernatant was purified to homogeneity by a multistepprocess. The mature ß subunit had seven fewer aminoacid residues than reported in the literature and three otherdifferences were found in the sequence. Similar oligosaccharidestructures were present on recombinant (r)-hFSH and a purifiedurinary (u)-hFSH preparation. In-vitro and in-vivo, the biologicalactivities of u- and r-hFSH were indistinguishable, r-hFSH wasformulated in ampoules containing 75 IU FSH activity ( 7.5 µgFSH), which accounts for >99% of the protein content of thepreparation. Studies in non-human primates and human volunteersshowed the pharmacokinetics of u- and r-hFSH to be similar.In healthy volunteers, r-hFSH stimulated follicular developmentand induced significant increases in serum oestradiol and inhibin.Clinical experience with r-hFSH has shown it is more effectiveat stimulating ovarian follicle growth than urinary gonadotrophins.It is also effective at initiating spermatogenesis when giventogether with human chorionic gonadotrophin.     

Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network

BACKGROUND: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. METHODS: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. RESULTS: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. CONCLUSIONS: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.     

人格特征与防御方式的相关研究

目的 :尝试用防御机制解释EPQ各维度的特征。方法 :采用EPQ人格问卷、DSQ防御方式问卷、16PF中的G量表对 2 2 0例成人进行测试。结果 :本样本中EPQ各维度与成熟防御方式均无显著相关 (P >0 .0 5 ) ,N维度和P维度均与不成熟防御方式、中间型防御方式有显著正相关 (P <0 .0 0 1)。结论 :本研究显示 ,可以用防御机制解释EPQ各维度的某些特征。