The Effects of Laser Marking and Symbol Etching on the Fatigue Life of Medical Devices.

This paper examines the question;" does permanent laser marking affect the mechanical performance of a metallic medical component?" The literature review revealed the surprising fact that very little has been presented or studied even though intuition suggests that its effect could be detrimental to a component's fatigue life. A brief investigation of laser marking suggests that defects greater than 25 µm are possible. A theoretical investigation further suggests that this is unlikely to cause issues with relation to fast fracture but is highly likely to cause fatigue life issues. An experimental investigation confirmed that laser marking reduced the fatigue life of a component. This combination of lines of evidence suggests, strongly, that positioning of laser marking is highly critical and should not be left to chance. It is further suggested that medical device designers, especially those related to orthopaedic implants, should consider the position of laser marking in the design process. They should ensure that it is in an area of low stress amplitude. They should also ensure that they investigate worst-case scenarios when considering the stress environment; this, however, may not be straightforward.

The value of sex hormone binding globulin (SHBG) in predicting treatment response in polycystic ovary syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterised by chronic anovulation, hyperandrogenism and polycystic ovaries on ultrasound. Patients commonly show features of the metabolic syndrome and insulin resistance. It has been shown that treatment with the insulin sensitising agent metformin can lead to improvements in symptoms in some but not all patients. The aim of the study was to assess whether sex hormone binding globulin (SHBG) (a surrogate marker of insulin resistance) could predict a positive response to metformin treatment in women with PCOS. METHODS: Medical notes of patients who presented to the gynaecology clinic at Southmead Hospital, Bristol with suspected PCOS were reviewed. Data collected included clinical symptoms and signs of hyperandrogenism, markers of PCOS in the family and obstetric history, biochemical markers and outcome of any treatment. RESULTS: A total of 66 patients were included in the study; 45 were classified as PCOS positive. In this group, patients who responded to metformin treatment had significantly lower SHBG levels compared to those who did not (median SHBG 37.5 nmol/L compared to 56.0 nmol/L) (p = 0.016, Mann-Whitney U-test). Patients with lower SHBG tended to have a better treatment outcome than those with higher values (odds ratio 0.983, 95% confidence interval 0.963-1.002, p = 0.079). CONCLUSIONS: Patients with a positive response to metformin treatment had significantly lower pre-treatment SHBG levels. For every unit increase in SHBG, the odds of a patient having a positive outcome to metformin treatment fell by a factor of 0.983.

Polycystic ovary syndrome and pregnancy outcome: red herring or red flag?

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, associated with a characteristic ovarian appearance at ultrasound scan, hyperandrogenism, and ovulatory disorders. The pathogenesis appears to be mainly related to reduced insulin sensitivity in peripheral tissues, leading to hyperinsulinaemia. There is a wide variation in the severity of PCOS symptoms. Women with PCOS are believed to be predisposed to a variety of complications in pregnancy. We present a summary of the evidence surrounding these claims and discuss the weaknesses of the available to date studies.

Cohort study of the neonatal outcome of twin pregnancies that were treated with prophylactic or rescue antenatal corticosteroids.

OBJECTIVE: The purpose of this study was to compare the neonatal outcome of 2 approaches to antenatal corticosteroid therapy for threatened preterm delivery in twins: a prophylactic approach in which corticosteroids were administered every 2 weeks from 24 to 32 weeks of gestation and a rescue approach in which corticosteroids were given to women at immediate risk of preterm delivery. STUDY DESIGN: A retrospective cohort study of 1038 twin babies delivered between 1990 and 1996 in a University Teaching Hospital. One hundred thirty-six babies were exposed to prophylactic therapy, and 902 babies were treated expectantly with rescue therapy. RESULTS: Prophylactic corticosteroids were not associated with a significant reduction in respiratory distress syndrome (adjusted odds ratio, 0.7; 95% CI, 0.2-2.0). Unnecessary therapy was more likely with a prophylactic policy (relative risk, 7.5; 95% CI, 5.3-10.7) and was associated with a reduction in mean birth weight in term babies of 129 g (95% CI, -218 to -33; P =.008). CONCLUSION: Prophylactic corticosteroids have no proven beneficial effect on the risk of respiratory distress syndrome in preterm twin babies. Such a policy exposes a large number of babies to unnecessary treatment that adversely affects growth.

Test of "Light" cigarette counter-advertising using a standard test of advertising effectiveness.

OBJECTIVE: To evaluate systematically the effectiveness of six advertising strategies (two message strategies presented in three different contexts) designed to promote smoking cessation by addressing smokers' misperceptions about Light cigarettes. DESIGN: Smokers viewed one of six, 30 second test television concept advertisements, which varied by message (one emphasising how the sensory effects of Lights can be deceptive, the other describing the effects of vent blocking) and by ad context (non-commercial public service announcement (PSA), promotion of unbranded nicotine replacement therapy (NRT), or promotion of branded NRT). The effectiveness of each advertisement was determined using a validated advertising testing system in which ads were viewed in the context of reviewing a pilot television programme. Response to ads is assessed through shifts in subject choices of products offered as prizes before and after viewing the test advertisements. Included among the possible prizes were cigarettes and various pharmacotherapies for smoking cessation. SUBJECTS: Daily smokers (n = 1890) of Regular (34%), Light (47%), and Ultra Light (19%) cigarettes recruited from eight US cities. MAIN OUTCOMES MEASURES: The primary outcome of interest was the shift away from cigarettes as the selected prize following exposure to the test advertisements. Secondary outcomes of interest included movement away from Light cigarettes and movement towards assisted quitting products. RESULTS: Smokers who saw the advertisement emphasising the sensory characteristics of Light cigarettes were more likely than subjects who saw the advertisement emphasising the effect of vent blocking to move away from cigarettes (OR = 1.97, 95% confidence interval CI 1.25 to 3.09; chi(2)(1) = 8.69, p = 0.003). Similarly, subjects who saw the advertisement framed as a PSA, rather than as a promotion for either a branded or unbranded NRT product, were also somewhat more likely to move away from cigarettes (OR = 1.51, 95% CI 0.94 to 2.40; chi(2)(1) = 2.97, p = 0.085). The effect was observed regardless of sex, age, or type of cigarette smoked. CONCLUSIONS: Addressing smokers' sensory perceptions of Light cigarettes and presenting this information in an impartial way is likely to be an effective communication strategy for counter-marketing Light cigarettes.

Expected contribution to serum oestradiol from individual ovarian follicles in unstimulated cycles.

Data relating serum oestradiol concentration to follicle size in unstimulated cycles are lacking. We provide precise data on serum concentrations expected for any follicle diameter (FD) in the mid- to late follicular phase. Infertile women (n = 35) with apparently normal ovulatory cycles were studied in detail in 128 unstimulated monofollicular cycles leading to IVF. Using mathematical modelling to account for repeated cycles in the same woman, the relationship between serum oestradiol and FD was explored and reference ranges for serum oestradiol at individual FD were calculated. Serum oestradiol concentrations [number of patients, geometric mean, 95% confidence interval (CI)] at the onset of the LH surge were higher in 'fertilized' cycles (73, 1279, 1180-1378 pmol/l) compared with 'unfertilized' cycles (31, 1055, 929-1197 pmol/l, P: = 0.008) and 'no oocyte' cycles (24, 1064, 922-1227 pmol/l, P: = 0.03) respectively. In 'fertilized' cycles, oestradiol concentrations rose exponentially with FD and for each size of follicle the oestradiol distribution was skewed. Functional oocyte competence varied in apparently normal ovulatory cycles and was correlated with pre-ovulatory serum oestradiol but not FD. Serum oestradiol varies within wide limits for maturing follicles of any given diameter prior to the onset of the LH surge.

Inhibin A, inhibin B and activin A in follicular fluid of infertile women with tubal damage, unexplained infertility and emdometriosis.

PROBLEM: To measure and compare concentrations of inhibin A, inhibin B, activin A and oestradiol in the follicular fluid of women with endometriosis, tubal damage and unexplained infertility with oocyte quality and fertilising capacity. Also, to assess whether impaired follicular function in women with endometriosis might be related to altered inhibin or activin concentrations and whether this correlated. METHOD OF STUDY: Follicular fluids were collected from individual follicles during oocyte retrieval for in vitro fertilisation (IVF) in natural cycles. Inhibin A, inhibin B and activin A were measured using two-site enzyme immunoassay, and oestradiol was assayed by fluoro-immunometric method. RESULTS: Follicular fluid inhibin A levels were found to be significantly higher in women with endometriosis. Inhibin A was directly correlated with follicle size. There was no correlation between the levels of inhibin A, inhibin B, activin A and oocyte quality or fertilising capacity in the three groups of women. CONCLUSIONS: Follicular fluid concentration of inhibin A is elevated in follicles of women with endometriosis and is positively correlated with follicle maturation. However, we were unable to demonstrate any association between the follicular fluid concentrations of inhibin A, inhibin B, activin A or oestradiol and the quality and fertilisation capacity of oocytes in women with tubal damage, unexplained infertility or endometriosis.

Onset of the preovulatory luteinizing hormone surge: diurnal timing and critical follicular prerequisites.

OBJECTIVE: To determine the diurnal variation in the onset of the preovulatory LH surge in women. DESIGN: Prospective open cohort study. SETTING: University hospital research program. PATIENT(S): Thirty-five women with infertility resulting from tubal damage that was associated with minor endometriosis or with infertility of prolonged unexplained etiology. INTERVENTION(S): Women underwent transvaginal ultrasonography and serum E2 estimation daily during monitored cycles before unstimulated natural cycle IVF: exogenous gonadotropins were not administered. MAIN OUTCOME MEASURE(S): Serum E2 concentration, follicle diameter, and endometrial thickness. RESULTS: Of 169 cycles. 155 progressed to an ovulatory LH surge, of which 146 occurred within 8 hours of assessment of the outcome measures. The relationship between follicle diameter and E2 was weak, but an abnormal value for one always was countered by a normal value for the other. CONCLUSIONS: Most women begin the preovulatory LH surge between midnight and 8:00 A.M., but with no particular variation by day of the week. The relationship between follicle size and serum E2 is not sufficiently strong to predict the LH surge confidently on the basis of only one variable, but the LH surge is unlikely to occur before either the follicle diameter has reached 15 mm and/or the serum E2 level has reached 600 pmol/L.

Serial transvaginal ultrasonography following McDonald cerclage and repeat suture insertion.

The aim of this study was to explore the hypothesis that serial transvaginal ultrasonography identifies early evidence of suture failure and that repeat cerclage delays delivery. We undertook a review of our policy of transvaginal ultrasonographic cervical surveillance after McDonald cerclage and of repeat suture insertion if persistent cervical effacement developed. Data from 26 pregnancies in 26 women are analyzed. The women had had a total of 57 mid-trimester miscarriages with a median of 2 (1-6) mid-trimester losses per woman. Twelve (46%) of the 26 women developed cervical changes at scan and underwent repeat cerclage. All 14 women who had a single suture inserted progressed to live births but 1 of the 13 women who had repeat cerclage had a mid-trimester miscarriage (p>0.05). The median gestation at delivery for the women who had repeat cerclage was 35 (22-39) weeks compared with 38 (36-40) weeks for those who had a single suture (p>0.05). The median interval from the detection of cervical changes at scan to delivery was 13 (4-19) weeks. Serial transvaginal ultrasonography after cervical cerclage identifies a group of women who are more likely to deliver preterm, and provides an opportunity for intervention (repeat cerclage) which appears to delay delivery by an average of 7 weeks.

Managed care of hormone replacement therapy in the menopause.

The principles of managed care are more difficult to apply to preventive medical treatments, such as hormone replacement therapy, than to the investigation and treatment of established disease. In addition to an ageing society with increased health demands, the use of hormone replacement therapy is increasing in most developed countries. Clinical guidelines for the counselling of post-menopausal women and the use of hormone replacement therapy have been prepared by the American College of Physicians. There is limited information about the benefits and risks of hormone replacement therapy from randomized prospective studies and these guidelines are based on the best available data from observational studies and meta-analysis. More secure data will become available within the next decade from long-term studies that are currently in progress. Managed care proposals for hormone replacement therapy must be flexible enough to adjust to new data as they become available while recognizing that, given current knowledge, hormone replacement is healthcare-cost-effective for the vast majority of menopausal women.

Ovarian response to purified FSH in infertile women with long-standing hypogonadotrophic hypogonadism.

It has previously been proposed that all anovulatory women requiring exogenous gonadotrophin therapy could be treated by purified FSH alone in the follicular phase. We have studied the ovarian response to purified FSH in 5 amenorrhoeic women with low endogenous LH production as a result of long-standing hypothalamic amenorrhoea. Follicles developed in all of the women but the rise in oestradiol was very slow. As a consequence of the HCG injection being delayed to allow the follicles to become functionally mature, too many follicles attained a preovulatory size. After the treatment was changed to more conventional preparations containing both FSH and LH, the women had improved ovarian responses and 3 of them conceived. It is clear that FSH alone will promote follicular growth but that LH is needed to stimulate follicular function. We conclude that LH does play an important role in follicular maturation and that it is a critical component of exogenous gonadotrophin therapy for women with prolonged hypogonadotrophic hypogonadism.

Ovarian dysfunction in endometriosis-associated and unexplained infertility.

PURPOSE: The impact of endometriosis and unexplained infertility on follicular function and fertilization of oocytes in cycles totally unperturbed by exogenous gonadotrophins, when compared with controls with tubal damage, were examined. METHODS: In natural cycles, without any exogenous gonadotropins, endocrine and ultrasonographic studies of follicular maturation in 18 women with minor endometriosis (41 cycles), 15 women with unexplained infertility (31 cycles), and 34 women with tubal damage (88 cycles) were performed. RESULTS: The endometriosis group had a significantly longer follicular phase (median: 15, 13, and 13 days). Both endometriosis and unexplained infertility had significantly reduced LH concentrations in follicular fluid compared with tubal damage (median: 12.1, 11.5, and 15.9 IU/L, respectively). Endometriosis was associated with a significantly reduced fertilization rate compared with unexplained infertility or tubal damage (46, 65, and 69%, respectively). CONCLUSIONS: These data show continuing evidence of ovulatory dysfunction leading to reduced fertilization rates in women with minor endometriosis.