Expectant management versus IUI in unexplained subfertility and a poor pregnancy prognosis (EXIUI study): a randomized controlled trial.

STUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births? SUMMARY ANSWER: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births. WHAT IS KNOWN ALREADY: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain. STUDY DESIGN, SIZE, DURATION: We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: -30% to -9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD -24%, 90% CI -36% to -13%) in line with inferiority of EM. LIMITATIONS, REASONS FOR CAUTION: Our trial did not reach the planned sample size, therefore the results are limited by the number of participants. WIDER IMPLICATIONS OF THE FINDINGS: This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS. STUDY FUNDING/COMPETING INTEREST(S): The trial was supported by a grant of the SEENEZ healthcare initiative. The subsidizing parties were The Dutch Organisation for Health Research and Development (ZonMW 837004023, www.zonmw.nl) and the umbrella organization of 10 health insurers in The Netherlands. E.R.G. receives personal fees from Titus Health care outside the submitted work. M.G. declares unrestricted research and educational grants from Guerbet, Merck and Ferring not related to the presented work, paid to their institution VU medical centre. A.B.H. reports receiving travel and speakers fees from Nordic Pharma and Merck and he is member of the Nordic Pharma ANGEL group and of the Safety Monitoring Board of Womed. C.B.L. reports speakers fee from Inmed and Yingming, and his department receives research grants from Ferring, Merck and Guerbet paid to VU medical centre. B.W.J.M. is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy for ObsEva and Merck. M.v.W. received a grant from the Netherlands Organisation for Health Research and Development ZonMW (80-8520098-91072). F.M. received two grants from the Netherlands Organisation for Health Research and Development ZonMW (NTR 5599 and NTR 6590). The other authors report no competing interest. TRIAL REGISTRATION NUMBER: Dutch Trial register NL5455 (NTR5599). TRIAL REGISTRATION DATE: 18 December 2015. DATE OF FIRST PATIENT'S ENROLMENT: 26 January 2017.

Gonadotrophins or clomiphene citrate in women with normogonadotropic anovulation and CC failure: does the endometrium matter?

STUDY QUESTION: Is endometrial thickness (EMT) a biomarker to select between women who should switch to gonadotropins and those who could continue clomiphene citrate (CC) after six failed ovulatory cycles? SUMMARY ANSWER: Using a cut-off of 7 mm for EMT, we can distinguish between women who are better off switching to gonadotropins and those who could continue CC after six earlier failed ovulatory CC cycles. WHAT IS ALREADY KNOWN: For women with normogonadotropic anovulation, CC has been a long-standing first-line treatment in conjunction with intercourse or intrauterine insemination (IUI). We recently showed that a switch to gonadotropins increases the chance of live birth by 11% in these women over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth. It is unclear whether EMT can be used to identify women who can continue on CC with similar live birth rates without the extra costs of gonadotropins. STUDY DESIGN, SIZE, DURATION: Between 8 December 2008 and 16 December 2015, 666 women with CC failure were randomly assigned to receive an additional six cycles with a change to gonadotropins (n = 331) or an additional six cycles continuing with CC (n = 335), both in conjunction with intercourse or IUI. The primary outcome was conception leading to live birth within 8 months after randomisation. EMT was measured mid-cycle before randomisation during their sixth ovulatory CC cycle. The EMT was available in 380 women, of whom 190 were allocated to gonadotropins and 190 were allocated to CC. PARTICIPANTS/MATERIALS, SETTING, METHODS: EMT was determined in the sixth CC cycle prior to randomisation. We tested for interaction of EMT with the treatment effect using logistic regression. We performed a spline analysis to evaluate the association of EMT with chance to pregnancy leading to a live birth in the next cycles and to determine the best cut-off point. On the basis of the resulting cut-off point, we calculated the relative risk and 95% CI of live birth for gonadotropins versus CC at EMT values below and above this cut-off point. Finally, we calculated incremental cost-effectiveness ratios (ICER). MAIN RESULTS AND THE ROLE OF CHANCE: Mid-cycle EMT in the sixth cycle interacted with treatment effect (P < 0.01). Spline analyses showed a cut-off point of 7 mm. There were 162 women (45%) who had an EMT ≤ 7 mm in the sixth ovulatory cycle and 218 women (55%) who had an EMT > 7 mm. Among the women with EMT ≤ 7 mm, gonadotropins resulted in a live birth in 44 of 79 women (56%), while CC resulted in a live birth in 28 of 83 women (34%) (RR 1.57, 95% CI 1.13-2.19). Per additional live birth with gonadotropins, the ICER was €9709 (95% CI: €5117 to €25 302). Among the women with EMT > 7 mm, gonadotropins resulted in a live birth in 53 of 111 women (48%) while CC resulted in a live birth in 52 of 107 women (49%) (RR 0.98, 95% CI 0.75-1.29). LIMITATIONS, REASONS FOR CAUTION: This was a post hoc analysis of a randomised controlled trial (RCT) and therefore mid-cycle EMT measurements before randomisation during their sixth ovulatory CC cycle were not available for all included women. WIDER IMPLICATIONS OF THE FINDINGS: In women with six failed ovulatory cycles on CC and an EMT ≤ 7 mm in the sixth cycle, we advise switching to gonadotropins, since it improves live birth rate over continuing treatment with CC at an extra cost of €9709 to achieve one additional live birth. If the EMT > 7 mm, we advise to continue treatment with CC, since live birth rates are similar to those with gonadotropins, without the extra costs. STUDY FUNDING/COMPETING INTEREST(S): The original MOVIN trial received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). C.B.L.A. reports unrestricted grant support from Merck and Ferring. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva, IGENOMIX and Guerbet. All other authors have nothing to declare. TRIAL REGISTRATION NUMBER: Netherlands Trial Register, number NTR1449.

The capacity of transvaginal hydrolaparoscopy versus hysterosalpingography to diagnose tubal pathology in the work-up of subfertile women, a randomised clinical trial.

OBJECTIVE: To assess the capacity of transvaginal hydrolaparoscopy (THL) versus hysterosalpingography (HSG) as a primary tool to diagnose tubal pathology. STUDY DESIGN: We performed a multicenter RCT (NTR3462) in 4 teaching hospitals in the Netherlands, comparing THL and HSG as first line tubal test in subfertile women. The primary outcome of the trial was cumulative live birth rate at 24 months. Here, we present the secondary outcomes, the diagnostic findings of both THL and HSG as well as performance defined as failures, complications and pain- and acceptability scores. RESULTS: Between May 2013 and October 2016, we allocated 149 women to THL and 151 to HSG, of which 17 women in the THL group (11.4%) and 12 in the HSG group (7.9%) conceived naturally before the scheduled procedure, while 13 HSGs and 5 THLs were not performed for other reasons (withdrawal of informed consent, not willing to undergo tubal testing and protocol violations). A total of 119 THLs and 134 HSGs were carried out. Failures were seen more in the THL group (n = 8, 5.6%) than in the HSG group (n = 1, 0.7%) (p = 0.014). Complications did not differ significantly between the groups (THL n = 4; 2.8% vs HSG n = 1; 0.7%) (p = 0.20). Bilateral tubal occlusion was detected in one versus three women (0.9% versus 2.2%) of the THL group and HSG group, while unilateral tubal occlusion was detected in seven (6.2%) versus eight (5.9%) women, respectively. Normal findings were seen in 96 (79.3%) women randomised to THL and in 119 (87.5%) in women randomised for HSG (RR 0.91 95%CI 0.81-1.01, p = 0.08). The pain score was significantly less for THL (VAS 4.7 (SD: 2.5)) than for HSG (VAS 5.4 (SD:2.5)) (p 0.038). The acceptability rate of THL and was high and comparable. CONCLUSION: THL and HSG have a comparable capacity in diagnosing tubal pathology with comparable performance in safety, pain and acceptability.

Comparison of inter- and intra-cycle variability of anti-Mullerian hormone and antral follicle counts.

BACKGROUND: The antral follicle count (AFC) and anti-Müllerian hormone (AMH) both represent age-related follicular decline quite accurately, although long-term follow-up studies are still lacking. The best ovarian reserve test would need only a single, cycle-independent measurement to be representative. METHODS: To compare the inter- and intra-cycle stability of AFC and AMH, we used age-adjusted intra-class correlation coefficients (ICCs). To measure inter-cycle stability across a number of up to four menstrual cycles, we used data, prospectively collected for the purpose of an other study, from 77 regularly cycling, infertile women aged 24-40 years. AMH and AFC values were measured on cycle day 3. To study intra-cycle variability, we used data from a prospective cohort study of 44 regularly cycling volunteers, aged 25-46 years and measured AMH and assessed the AFC (2-10 mm) every 1-3 cycle days. RESULTS: Between menstrual cycles, AFC and AMH varied between 0 and 25 follicles (median 10), and 0.3 and 27.1 ng/ml (median 4.64). The difference in age-adjusted ICC between AMH [ICC, 0.89 (95% CI, 0.84-0.94)] and AFC [ICC, 0.71 (95% CI, 0.63-0.77)] was 0.18 (95% CI, 0.12-0.27). For the intra-cycle variation, 0-43 antral follicles (median 7) were counted per volunteer. The difference in age-adjusted ICC between AMH [ICC, 0.87 (95% CI, 0.82-0.91)] and AFC [ICC, 0.69 (95% CI, 0.46-0.82)] was 0.18 (95% CI, 0.034-0.42). CONCLUSIONS: Serum AMH demonstrated less individual intra- and inter-cycle variation than AFCs and may therefore be considered a more reliable and robust means of assessing ovarian reserve in subfertile women.

Patient satisfaction with switching to esomeprazole from existing proton pump inhibitor therapy for gastro-oesophageal reflux disease: an observational, multicentre study.

OBJECTIVE: To determine treatment satisfaction in patients with gastro-oesophageal reflux disease (GORD) when switched to esomeprazole. METHODS: This observational, multicentre study conducted in the Netherlands included primary-care patients being treated with a proton pump inhibitor (PPI) [omeprazole, pantoprazole, rabeprazole or lansoprazole] for GORD who were switched to esomeprazole by their physician. After a median of 28 days' esomeprazole therapy, patients' satisfaction was assessed using a questionnaire. Patients self-rated whether they were 'more satisfied', felt there was 'no difference' or were 'less satisfied' with esomeprazole compared with previous PPI therapy. Symptom control, concomitant medication use and tolerability were also assessed. RESULTS: Overall, 4929 patients were included in this study; of these, only 21.9% were satisfied with PPI treatment at consultation (i.e. prior to switching to esomeprazole). Following switching to esomeprazole therapy, 88.0% of patients were satisfied with therapy and only 26.9% of patients were still experiencing symptoms (vs 84.0% at consultation); 71.3% were more satisfied with esomeprazole than with their previous PPI, most frequently because they had fewer or no symptoms. Among patients who had been using concomitant therapy to control GORD symptoms, 62.0% were no longer using any such medication. Of the 1069 patients who had been satisfied with their previous PPI therapy, 39.4% were even more satisfied with esomeprazole. Esomeprazole was well tolerated; the most commonly reported adverse events were nausea/vomiting and headache, and no treatment-related serious adverse events occurred. CONCLUSION: Among primary-care patients receiving PPI therapy for GORD, switching to esomeprazole therapy impacts positively on treatment satisfaction and symptom control.

A systematic review of tests predicting ovarian reserve and IVF outcome.

The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.

Intercycle variability of ovarian reserve tests: results of a prospective randomized study.

BACKGROUND: This study was designed to assess prospectively the intercycle variability (ICV) of basal FSH (bFSH), clomiphene citrate challenge test (CCCT) (analysis of the CCCT was performed by the parameter: sum bFSH + sFSH) and exogenous FSH ovarian reserve test (EFORT) (analysis of the EFORT included the following parameters: estradiol (E(2)) increment and inhibin B increment 24 h after administration of FSH), and secondarily to assess the influence of the variability of these ovarian reserve tests. METHODS: Eighty-five regularly menstruating patients, aged 18-39 years, participated in this prospective study, randomized, by a computer-designed four-blocks system into two groups. Forty-three patients underwent a CCCT, and 42 patients underwent an EFORT. Each test was performed 1-4 times in subsequent cycles, one test per cycle. During the first three cycles, patients were treated with intrauterine insemination (IUI). Follicle number and oocyte yield during IVF ovarian stimulation in the fourth cycle were taken as measures for ovarian reserve. RESULTS: The per cycle variance of bFSH ranged from 1.8 to 4.4 (maximum to minimum ratio of 2.44, P < 0.0001), while that of CCCT ranged from 21.3 to 70.6 (3.31, P < 0.0001). No significant change in per cycle variance was found for the E(2) increment (1.25, P > 0.2) and inhibin B increment (1.31, P > 0.2), which were the EFORT parameters. A large ICV of CCCT and bFSH test results was strongly associated with lower ovarian reserve. CONCLUSIONS: Our study shows that the ICV of the inhibin B increment and the E(2) increment in the EFORT is stable in consecutive cycles, which indicates that this reproducible test is a more reliable tool for determination of ovarian reserve than bFSH and CCCT. Women with limited ovarian reserve show a strong ICV of bFSH and FSH response to clomiphene citrate.

Comparison of endocrine tests with respect to their predictive value on the outcome of ovarian hyperstimulation in IVF treatment: results of a prospective randomized study.

BACKGROUND: This study was designed to compare endocrine tests [clomiphene citrate challenge test (CCT), exogenous FSH ovarian reserve test (EFORT) and basal FSH, basal estradiol (E(2)) and basal inhibin B as an integral part of all CCT and EFORT], with respect to their ability to estimate the stimulable cohort of follicles in the ovaries (ovarian capacity) and to analyse which test or combination of tests would give the best prediction of ovarian capacity. METHODS: A total of 110 regularly menstruating patients, aged 18-39 years, participated in this prospective study, randomized by a computer-designed 4-block system study into two groups. Fifty-six patients underwent a CCT, and 54 patients underwent an EFORT. In all patients, the test was followed by an IVF treatment. The result of ovarian hyperstimulation during IVF treatment, expressed by the total number of follicles, was used as gold standard. RESULTS: Univariate linear regression analysis showed that the best correlation with the number of follicles after ovarian hyperstimulation (Y) is found by the inhibin B increment (InhB incr.) in the EFORT (Y = 3.957 + 0.081 x InhB incr. (95% CI 0.061-0.101); r = 0.751; P < 0.001). Multiple linear regression analysis showed a significant contributing value of the variables basal FSH, E(2) increment of the EFORT and inhibin B increment to the basic model with the variable age. The best prediction of ovarian capacity (Y) was seen when E(2) increment and inhibin B increment were used simultaneously in a stepforward multiple regression prediction model [Y = 2.659 + 0.052 x InhB incr. (0.026-0.078) + 0.027 x E(2) incr. (95% CI 0.012-0.054); r = 0.796; P < 0.001]. The CCT could not be used in a prediction model. CONCLUSIONS: The EFORT is the endocrine test which gives the best prediction of ovarian capacity.

The rise of estradiol and inhibin B after acute stimulation with follicle-stimulating hormone predict the follicle cohort size in women with polycystic ovary syndrome, regularly menstruating women with polycystic ovaries, and regularly menstruating women with normal ovaries.

Polycystic ovaries contain a larger number of antral follicles than control ovaries. The aim of this study was to test whether the increase in estradiol (E(2)) and inhibin B after stimulation with 300 IU recombinant FSH in the early follicular phase and the ovarian volume can predict the size of the follicle cohort in polycystic ovary syndrome (PCOS) patients (n = 10), patients with polycystic ovaries detected by ultrasound but with regular menstrual cycles (PCO; n = 10), and regularly menstruating patients with normal ovaries (n = 10). The follicle cohort size was measured as the FSH-sensitive follicles growing during a standardized in vitro fertilization stimulation. Linear regression analysis showed that the slopes of the regression lines of the E(2) increment and the inhibin B increment in relation to the number of follicles were not significantly different among the three groups, meaning that an increased sensitivity for FSH of the granulosa cells of polycystic ovaries was not found. For the total group (n = 30) we calculated that an E(2) increment of 100 pmol/L predicts 5.5 follicles (95% confidence interval, 2.8--8.2; r = 0.617; P < 0.001), and an inhibin B increment of 100 ng/L predicts 6.2 follicles (95% confidence interval, 3.5--9.0; r = 0.665; P < 0.001). The ovarian volume could not be used in a prediction model because the association with the number of follicles was different in the PCO group compared with the PCOS and the control group. Women with PCO and women with PCOS both had a follicle cohort twice as big as the cohort in control women (P < 0.01). The differences in menstrual cycle pattern between the PCO and PCOS groups cannot be explained by differences in cohort size.

Cell proliferation induced by 8-oxoguanosine and 8-methylguanosine, two adducts produced by free radical attack on ribonucleosides and RNA.

The ability of C8-substituted guanine (Gua) ribonucleosides to induce B cell proliferation has been well documented in the literature. These compounds are analogues of adducts formed from free radical attack on ribonucleosides and RNA. Here we examined the proliferative properties of two of these radical adducts, 8-methylguanosine (8-MeG) and 8-oxo-7,8-dihydroguanosine (8-OxoG) and compared them with those of the well studied B cell mitogen, 8-bromoguanosine (8-BrG). 8-MeG and 8-OxoG were synthesized in the considerable yields of 28, and 55%, respectively, and were characterized by UV, NMR and CG-MS. Their effects upon [3H]thymidine uptake into DNA by Swiss mouse splenocytes, mouse embryo 3T3 fibroblasts (A31) and mouse B16F10 melanoma were examined. Both guanosine (G) radical adducts were shown to increase [3H]thymidine uptake by mouse splenocytes but displayed selectivity in respect to continuous cell lines. 8-MeG acted upon 3T3 fibroblasts whereas 8-OxoG acted upon B16F10 melanoma. The non-physiological analogue 8-BrG acted upon all tested cells. Parallel experiments of cell counting, cytotoxicity,and cell sorting indicated that DNA synthesis induced by the C8-substituted G's reflected cell growth. It is proposed that the compounds act intracellularly because their proliferative effects were blocked in the presence of a nucleoside transport inhibitor but were not inhibited by an antagonist of the A2 purine receptor. The present results, taken together with data from the literature, suggest that in the case of 3T3 fibroblasts and mouse splenocytes the proliferative effects of the compounds are not dependent on metabolism through purine salvage pathways. In the case of melanoma, however, the compounds are likely to become part of the purine nucleoside pool. The demonstration that adducts produced by free radical attack on ribonucleosides and RNA are able to induce cell proliferation opens new perspectives for the understanding of free radical mediated carcinogenesis.

Leishmanicidal activity of peroxynitrite.

Nitric oxide reacts with superoxide to produce peroxynitrite which has been reported to be highly microbicidal to Trypanosoma cruzi in phosphate buffer but ineffective against Leishmania major in culture medium. This contradiction and the potential importance of peroxynitrite as a cytotoxic effector molecule of both macrophages and neutrophils led us to re-examine its leishmanicidal effects. Our results demonstrate that peroxynitrite inhibits growth of Leishmania amazonensis promastigotes in a concentration-dependent manner both in phosphate buffer and culture medium (DMEM containing 20% fetal calf serum). In the latter, 43% growth inhibition was observed with 4 mM peroxynitrite whereas in buffer a 70% inhibition was already observed with 0.5 mM peroxynitrite. Treated parasites presented reduced motility and became round in shape further confirming the leishmanicidal activity of peroxynitrite. The latter was attenuated by reduced glutathione supporting the view that peroxynitrite-mediated oxidation of critical thiol groups is a major mechanism accounting for its trypanocidal activity.

Lowered superoxide dismutase in highly metastatic B16 melanoma cells.

Superoxide dismutases (SOD), which are enzymes scavenging the superoxide radical, were studied in two variant lines of the B16 melanoma: B16F1 with low metastatic potential and B16F10 with high metastatic potential. SOD activity was measured by a method utilizing reduction in the chemiluminescence of luminol. Using cell free extracts it was shown that the highly metastatic B16F10 cell line has a SOD activity lower (20.70 +/- 3.07) units/mg protein, n = 8, than that of the less metastatic B16F1 cell line (81.38 +/- 6.78) units/mg protein, n = 8. Acrylamide gel electrophoresis suggested that Mn-SOD activity is higher in B16F1 cells.

Sarcoma metastatic to the central nervous system parenchyma: a review of the literature.

Sarcoma metastatic to cerebral parenchyma, although rare, occurs more frequently than generally recognized. With increased duration of survival due to multi-modal therapy, more CNS metastases are being found. A literature search occasioned by a patient with metastatic sarcoma has produced some interesting results.