Key Performance Indicators in Paediatric Anaesthesia

Aims Currently no national guidelines on performance measurement exist for paediatric anaesthesia in Ireland1. The purpose of this study was to ascertain if we are achieving Key Performance Indicators (KPIs) in areas of post-operative nausea and vomiting (PONV) and post-operative pain when compared to international standards. Methods The study was carried out from January 2018 to February 2018 at Temple Street Children's University Hospital. In total 743 patients were included. Results 743 patients were included in the study. 86 (12%) were recorded as having a post-operative pain score of >4/10. 15 (1.2%) of patients were recorded as experiencing PONV. Orthopaedic surgery had the highest frequency of post-operative pain accounting for 33% of all cases. General surgery was associated with highest risk of PONV. Discussion The results from the study indicate we are achieving results similar to data from international centres. There is a paucity of published data from Irish centres and as national guidelines are developed for a model of care for paediatric anaesthesia we hope this data can be used when comparing other paediatric centres within Ireland.

Pulsed radiofrequency of the brachial plexus in the treatment of chemotherapy-induced peripheral neuropathy of the upper limb.

We describe the treatment of chemotherapy-induced peripheral neuropathy in the upper limb of a patient via ultrasound-guided pulsed radiofrequency of the brachial plexus. A 54-year-old female, who underwent chemotherapy and mastectomy for left-sided breast cancer, presented to the pain clinic describing continuous and severe shock-like pain in the posterolateral aspect of the left upper limb, above the elbow. A diagnosis of chemotherapy-induced peripheral neuropathy was made. Pain management with multi-modal analgesia was not fully effective and pulsed radiofrequency was offered as an alternative. Ultrasonography of the supraclavicular region was used to identify the brachial plexus, followed by pulsed radiofrequency using an insulated-tip needle that produced paraesthesia in the affected area. Onset of pain relief occurred one week post-procedure and lasted approximately 10 weeks. An estimated 80% decrease in pain intensity was reported by the patient. We propose that pulsed radiofrequency can be offered as a pain management alternative in certain presentations of chemotherapy-induced peripheral neuropathy.

Neither Basic Life Support knowledge nor self-efficacy are predictive of skills among dental students.

AIM: Basic life support (BLS) is considered a core competence for the graduating dentist. This study aimed to measure BLS knowledge, self-efficacy and skills of undergraduate dental students in Dublin. METHODS: This study consisted of a cross-sectional survey measuring BLS knowledge and self-efficacy, accompanied by a directly observed BLS skills assessment in a subsample of respondents. Data were collected in January 2014. Bivariate correlations between descriptive and outcome variables (knowledge, self-efficacy and skills) were tested using Pearson's chi-square. We included knowledge and self-efficacy as predictor variables, along with other variables showing association, into a binary logistic regression model with BLS skills as the outcome measure. RESULTS: One hundred and thirty-five students participated. Almost all (n = 133, 98.5%) participants had BLS training within the last 2 years. One hundred and four (77%) felt that they were capable of providing effective BLS (self-efficacy), whilst only 46 (34.1%) scored >80% of knowledge items correct. Amongst the skills (n = 85) subsample, 38.8% (n = 33) were found to pass the BLS skills assessment. Controlling for gender, age and skills assessor, the regression model did not identify a predictive relationship between knowledge or self-efficacy and BLS skills. CONCLUSIONS: Neither knowledge nor self-efficacy was predictive of BLS skills. Dental students had low levels of knowledge and skills in BLS. Despite this, their confidence in their ability to perform BLS was high and did not predict actual competence. There is a need for additional hands-on training, focusing on self-efficacy and BLS skills, particularly the use of AED.

Therapeutic Hypothermia in ICUs.

Recent research on Therapeutic Hypothermia (TH) post cardiac arrest has raised questions about its implementation and benefits. TH to 32-34 degrees C is still included in international guidelines for post-cardiac arrest care. We investigated how Irish ICUs are utilising TH as part of their management of patients post cardiac arrest using a telephone survey of all Irish ICUs. All 25 ICUs in Ireland participated. As of quarter 2 2014, TH was part of post-cardiac arrest management in 20 ICUs (80%), which is similar to international figures. 2011 was the median year for units to start using TH in Ireland. Over half 13 (52%) of Irish ICUs have experience with cooling more than 10 patients. Despite lack of evidence for its benefit, 12 ICUs (48%) use TH for OHCA non VF-VT arrests. Lack of resources was cited by 2 ICUs (8%) as well as no local consensus by 1 ICU (4%) prevented a small minority adopting the protocol. Similar methods of inducing and maintaining TH were found in Ireland as with overseas. Interest was expressed in recent research on TH and in 2 ICUs local practice had changed because of it. An updated international resuscitation guideline is awaited.

Burnout in emergency department healthcare professionals is associated with coping style: a cross-sectional survey.

INTRODUCTION: Ineffective coping may lead to impaired job performance and burnout, with adverse consequences to staff well-being and patient outcomes. We examined the relationship between coping styles and burnout in emergency physicians, nurses and support staff at seven small, medium and large emergency departments (ED) in a Canadian health region (population 500,000). METHODS: Linear regression with the Coping Inventory for Stressful Situations (CISS) and Maslach Burnout Inventory (MBI) was used to evaluate the effect of coping style on levels of burnout in a cross-sectional survey of 616 ED staff members. CISS measures coping style in three categories: task-oriented, emotion-oriented and avoidance-oriented coping; MBI, in use for 30 years, assesses the level of burnout in healthcare workers. RESULTS: Task-oriented coping was associated with decreased risk of burnout, while emotion-oriented coping was associated with increased risk of burnout. DISCUSSION: Specific coping styles are associated with varied risk of burnout in ED staff across several different types of hospitals in a regional network. Coping style intervention may reduce burnout, while leading to improvement in staff well-being and patient outcomes. Further studies should focus on building and sustaining task-oriented coping, along with alternatives to emotion-oriented coping.

Adverse event recording post hip fracture surgery.

Accurate recording of adverse events post hip fracture surgery is vital for planning and allocating resources. The purpose of this study was to compare adverse events recorded prospectively at point of care with adverse recorded by the Hospital In-Patient Enquiry (HIPE) System. The study examined a two month period from August to September 2011 at University Hospital Limerick. Out of a sample size of 39, there were 7 males (17.9%) and 32 females (82.1%) with an age range of between 53 and 98 years. The mean age was 80.5 years. 55 adverse events were recorded, in contrast to the HIPE record of 13 (23.6%) adverse events. The most common complications included constipation 10 (18.2%), anaemia 8 (14.5%), urinary retention 8 (14.50%), pneumonia 5 (9.1%) and delirium 5 (9.1%). Of the female cohort, 24 (68.8%) suffered an adverse event, while only 4 (57%) males suffered an adverse event.

Successful Day 5 embryo transfer and pregnancies resulting after transport of embryos by air for biopsy and genetic analysis.

PURPOSE: Case studies of four in vitro fertilization (IVF) cycles where embryo transport by commercial airline followed by biopsy and genetic analysis with subsequent culture to Day 5 and resulting ongoing pregnancy. METHOD: Retrospective clinical case study of 4 patients requiring preimplantation genetic diagnosis (PGD) testing. Normally fertilized embryos were transported in a battery-powered portable incubator by commercial airline following evaluation for fertilization under controlled conditions from the Center for Assisted Reproduction, Bedford, Texas to the Reproductive Genetic Institute, Chicago, Illinois. Following Day 3 embryo biopsy and genetic analysis, embryos were transported back to the Center for Assisted Reproduction for Day 5 embryo transfer. RESULTS: Ongoing clinical pregnancy resulted for all patients receiving embryo transfer. CONCLUSION: These results demonstrate the feasibility of embryo transport by air for centers that do not have the in-house capabilities to perform genetic analysis. With successful pregnancies obtained through extended culture to Day 5, embryos requiring genetic analysis can be successfully transported by air, tested, and returned to the initial facility for embryo transfer without time restriction.

Extended embryo culture in human assisted reproduction treatments.

In order to evaluate the niche of extended embryo culture in an IVF programme, retrospective analysis of non-selected IVF patients, who underwent ovarian stimulation from April 1998 to June 1999 in a single private practice assisted reproductive technology centre, was performed. Embryos were cultured for 48 h in S1/G1.2 medium followed by 48 to 72 h of culture in S2/G2.2 to day 5 or day 6. Only fertilized oocytes exhibiting two pronuclei from donor and non-donor IVF and intracytoplasmic sperm injection (ICSI) cases were examined to determine the relationship between embryo cell number on day 3 and subsequent rate of blastocyst formation. Results indicated that a proportional relationship existed between the number of blastomeres present in day 3 embryos and the rate of blastocyst formation. Fifty-four per cent of embryos that had six cells on day 3 formed blastocysts, while 76% of those embryos with eight cells formed blastocysts. Blastocyst development did not increase further when embryos had more than eight cells on day 3, indicating that embryos with greater cell numbers on day 3 are not always predictive of a greater likelihood of blastocyst formation. Fertilized oocytes exhibiting two pronuclei from donors produced significantly more blastocysts (67%) than those from IVF patients (52%; P < 0.01), and had a significantly higher implantation rate (54%) compared with IVF patients (30%; P < 0.01). Furthermore, blastocyst cryopreservation resulted in significantly higher implantation rates than cryopreserved cleavage stage embryos (P < 0.001).

Introduction of blastocyst culture and transfer for all patients in an in vitro fertilization program.

OBJECTIVE: To evaluate the nonselective application of extended embryo culture on the outcome of IVF. DESIGN: Retrospective analysis. SETTING: Private practice assisted reproductive technology center. PATIENT(S): Seven hundred ninety nonselected patients undergoing IVF with controlled ovarian stimulation. INTERVENTION(S): For day 3 ET, multicell embryos were cultured in human tubal fluid medium and 12% synthetic serum substitute. For day 5 ET, embryos were cultured for 48 hours in S1 medium and then for 48 hours in S2 medium. MAIN OUTCOME MEASURE(S): Implantation rate (determined by total no. of visualized gestational sacs), ongoing pregnancy rate, and number of embryos available for ET. RESULT(S): Respective day 3 and day 5 implantation rates for patients aged <35 years (29.5% and 38.9%), patients aged 35-39 years (20.7% and 28.2%), and all patients combined (23.3% and 32.4%) were statistically significantly different. Significantly more embryos were transferred on day 3 than on day 5 for patients aged <35 years (2.9 vs. 2.4), patients aged 35-39 years (3.1 vs. 2.6), and all patients combined (3.0 vs. 2.5). The difference in ongoing pregnancy rates per retrieval was statistically significant for day 3 compared with day 5 transfers for all patients combined (35.9% vs. 43.8%). Cancellation rates for transfer after retrieval increased significantly for day 3 compared with day 5 transfer (2.9% vs 6.7%). CONCLUSION(S): These results demonstrate the feasibility of using extended embryo culture in a nonselective manner for couples undergoing IVF. Overall, extended embryo culture was associated with a significant increase in pregnancy rates and implantation rates and a significant decrease in the number of embryos transferred. The rate of multiple implantation among patients aged <35 years warrants consideration of single blastocyst transfers for this group.

Regulation of expression of the 3 beta-hydroxysteroid dehydrogenases of human placenta and fetal adrenal.

The appropriate expression of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase (3 beta-HSD) is vital for mammalian reproduction, fetal growth and life maintenance. Several isoforms of 3 beta-HSD, the products of separate genes, have been identified in various species including man. Current investigations are targeted toward defining the processes that regulate the levels of specific isoforms in various steroidogenic tissues of man. High levels of expression of 3 beta-HSD were observed in placental tissues. It has been generally considered that the multinucleated syncytiotrophoblastic cells are the principal sites of 3 beta-HSD expression and, moreover, that 3 beta-HSD expression is intimately associated with cyclic AMP-promoted formation of syncytia. Herein we report the presence of 3 beta-HSD immunoreactive and mRNA species in uninucleate cytotrophoblasts in the chorion laeve, similar to that in syncytia but not cytotrophoblast placenta. In vitro, 3 beta-HSD levels in chorion laeve cytotrophoblasts were not increased with time nor after treatment with adenylate cyclase activators, whereas villous cytotrophoblasts spontaneously demonstrated progressive, increased 3 beta-HSD expression. Moreover, 3 beta-HSD synthesis appeared to precede morphologic syncytial formation. Thus high steroidogenic enzyme expression in placenta is not necessarily closely linked to formation of syncytia. Both Western immunoblot and enzymic activity analyses also indicated that the 3 beta-HSD expressed in these cytotrophoblastic populations was the 3 beta-HSD type I gene product (M(r), 45K) and not 3 beta-HSD type II (M(r), 44K) expressed in fetal testis. In cultures of fetal zone and definitive zone cell of human fetal adrenal, 3 beta-HSD expression was not detected until ACTH was added. ACTH, likely acting in a cyclic AMP-dependent process, induced 3 beta-HSD type II activity and mRNA expression. The higher level of 3 beta-HSD mRNA in definitive zone compared with fetal zone cells was associated with parallel increases in cortisol secretion relative to dehydroepiandrosterone sulfate formation.

Laparoscopic removal of 46XY gonads located within the inguinal canals.

Male pseudohermaphrodites require gonadectomy for the prevention of gonadal malignancy. Laparoscopic gonadectomy has been performed in patients with intra-abdominal gonads and can also be performed in patients whose gonads are located within the inguinal canals.

Inverse relationship between ovarian aromatase cytochrome P450 and 5 alpha-reductase enzyme activities and mRNA levels during the estrous cycle in the rat.

In the present study, we examined the changes in enzyme activity and mRNA levels of aromatase cytochrome P450 (P450AROM) and 5 alpha-reductase in ovarian tissue from adult cyclic rats. For each stage of the estrous cycle, the enzymatic activities were quantified by means of the 3H2O-release assay in the case of P450AROM and thin-layer chromatography in the case of 5 alpha-reductase. Levels of mRNA encoding P450AROM and 5 alpha-reductase in the ovary were determined by Northern blot analysis utilizing 32P-labeled rat cDNAs as probes. Serum LH levels were determined by RIA. Three P450AROM mRNA species were detected (at 1.7, 2.2 and 2.7 kb) in ovarian tissue from cyclic rats. All three P450AROM transcripts were expressed in a co-ordinated fashion throughout the cycle. The P450AROM levels were highest during diestrus and proestrus, decreased during estrus while at metestrus the levels were nearly nondetectable. Conversely, one 5 alpha-reductase mRNA species at 2.5 kb was detected in ovarian tissue from cyclic animals. Ovarian 5 alpha-reductase mRNA levels were lowest during diestrus and proestrus, increased at estrus and were most abundant during metestrus; a pattern opposite to that of P450AROM. The pattern of change in P450AROM and 5 alpha-reductase activities paralleled that of the respective mRNA profiles but lagged behind the mRNA profiles by about 24 h, or one stage of the estrous cycle. Aromatase activity was 1.5 pmol/h/mg protein during diestrus, increased over 3-fold at proestrus (approximately 5.5 pmol/h/mg protein), decreased at estrus and declined to the lowest values at metestrus (approximately 1.0 pmol/h/mg protein). In contrast, the 5 alpha-reductase activity pattern was essentially the mirror image of the P450AROM activity pattern during the estrous cycle. 5 alpha-Reductase levels were lowest during proestrus (approximately 5 pmol/h/mg protein) and estrus (approximately 8 pmol/h/mg protein), increased over 3-fold during metestrus, while the highest activity levels occurred during diestrus (approximately 36 pmol/h/mg protein). The normalization of the P450AROM and 5 alpha-reductase mRNA levels and their respective enzyme activities revealed a correspondence between mRNA abundance and subsequent increases (24 h later) in enzyme activity levels during the estrous cycle. These findings suggest that: (a) a temporal relationship exists between the profiles of the enzymatic activities that follows the changes in the levels of their respective mRNAs and (b) an inverse pattern exists between P450AROM and 5 alpha-reductase in terms of both enzymatic activity and mRNA expression during the estrous cycle in rat.

3 beta-Hydroxysteroid dehydrogenase activity in glandular and extraglandular human fetal tissues.

The expression of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) in steroidogenic tissues is an absolute requirement for mammalian reproduction, fetal growth, and life maintenance. We sought to identify extraglandular tissue sites in the human fetus where 3 beta HSD is expressed. To this effect, we conducted in vitro studies by use of homogenates prepared from second trimester fetal tissues. To facilitate the determination of 3 beta HSD activity, an abbreviated technique was developed that consisted in the use of [3 alpha-3H]dehydroepiandrosterone [( 3 alpha-3H]DHEA) as the substrate and NAD+ as the cofactor. With these reagents, the enzymatic reaction leads to the production of both nonradiolabeled androstenedione and NAD3H in equimolar amounts, and the radioactivity associated with NAD3H is used for quantification of 3 beta HSD activity. The kinetic isotope effect introduced by substitution of tritium for hydrogen at the C-3 alpha position of DHEA, determined with six different tissues, was 2.5 +/- 0.7 (mean +/- SD). The specific activities of the enzyme in peripheral tissues and ovary were relatively low, in the range of 0.03 nmol/mg protein.h for stomach (n = 2) to 0.18 +/- 0.14 nmol/mg protein.h for liver (mean +/- SD; n = 13), while in fetal testis and placenta the specific activities were relatively high, viz. 3.4 +/- 0.7 nmol/mg protein.h (mean +/- SD; n = 4) and 2.8 +/- 1.8 nmol/mg protein.h (mean +/- SD; n = 13), respectively. The findings of this study serve to demonstrate that 3 beta HSD is distributed widely among tissues of the human fetus. Although the enzymatic activity was easily demonstrated in peripheral tissues by the use of radiolabeled DHEA as the substrate, 3 beta HSD protein was not readily detected by Western analysis.

Expression of mRNA species encoding steroidogenic enzymes in the rat ovary.

We have examined the levels of expression of mRNA species encoding cholesterol side-chain cleavage cytochrome P-450 (P-450scc), 17 alpha-hydroxylase cytochrome P-450 (P-450(17 alpha), aromatase cytochrome P-450 (P-450AROM) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in rat ovaries throughout the oestrous cycle, during pregnancy and in immature animals treated with pregnant mare serum gonadotrophin (PMSG). Total or poly(A)(+)-enriched RNA was prepared from adult rat ovaries throughout the oestrous cycle, from immature rat ovaries 24 and 48 h after treatment and from adult rat ovaries on days 10, 14, 17 and 21 of gestation. Expression of the mRNA species was examined by Northern analysis using specific [32P]cDNA probes. During the oestrous cycle P-450scc mRNA of approximately 1.9 kb was detected at low levels, while 3 beta-HSD mRNA of 1.7 kb was in relatively high abundance throughout the oestrous cycle. While P-450(17) alpha mRNA of 1.9 kb and P-450AROM of 2.7, 2.2 and 1.7 kb were highly abundant during dioestrus, pro-oestrus and oestrus, the levels of these mRNA species decreased markedly to be nearly undetectable during metoestrus. During pregnancy there was considerably more variation in the expression of the mRNA species examined. Expression of P-450scc mRNA was at low, but detectable, levels until day 14, thereafter expression increased to high levels (day 14-21 of gestation). Levels of P-450(17) alpha mRNA on day 10 of gestation were lower than at pro-oestrus during the oestrous cycle and decreased further on days 14 and 17. Expression of 3 beta-HSD was decreased on day 10, but on days 14, 17 and 21 of gestation high mRNA levels were detectable. Ovarian expression of the three P-450AROM species was dramatically increased between days 14 and 17 of pregnancy, but declined by day 21. In immature rats, P-450scc mRNA was detected at low levels in unstimulated animals and increased markedly after treatment with PMSG, while subsequent treatment with human chorionic gonadotrophin (hCG) had a minimal effect on expression. Expression of P-450(17) alpha mRNA was high in unstimulated immature and PMSG-treated rats, but diminished after treatment with hCG. All three P-450AROM mRNA species were undetectable in ovaries from unstimulated immature animals; however, induction of all three was observed in PMSG-treated rats, but this expression decreased to undetectable levels upon subsequent administration of hCG.(ABSTRACT TRUNCATED AT 400 WORDS)

Amenorrhea.

Amenorrhea, the lack of menstruation, is a gynecologic disorder that may arise from a variety of causes. If a logical and orderly schema is followed, the correct diagnosis and appropriate management plan can be formulated.

3 beta-hydroxysteroid dehydrogenase/isomerase in the fetal zone and neocortex of the human fetal adrenal gland.

The fetal zone of the human fetal adrenal (HFA) gland is established to have decreased 3 beta-hydroxysteroid dehydrogenase/delta 4-5 isomerase (3 beta HSD) activity compared to the neocortex or definitive zone. 3 beta HSD activity, however, can be induced in primary cell culture through treatment with ACTH. Therefore, the HFA with two distinct steroidogenic zones with differences in 3 beta HSD activity as well as the capacity to increase 3 beta HSD activity in response to ACTH provides an excellent model to study the regulation of this enzyme. The presence of 3 beta HSD in the fetal and neocortex zones of the HFA was examined using a polyclonal antibody raised against purified human placental microsomal 3 beta HSD. After homogenates of the fetal and neocortical zones of the HFA were electrophoresed on a sodium dodecyl sulfate-polyacrylamide gel and immunoblotted, the presence of the 3 beta HSD protein with a molecular size of 45 kDa could be demonstrated only in the neocortical zone. ACTH treatment (greater than 2 days) of fetal and neocortical zone explant cultures produced increases in cortisol secretion associated with the respective levels of immunodetectable 3 beta HSD protein. Cortisol and dehydroepiandrosterone sulfate were the respective principal steroid products of neocortical and fetal zone explants. After ACTH treatment, immunodetectable 3 beta HSD was induced to a greater magnitude in the neocortex. These findings provide evidence that the lack of 3 beta HSD activity in the fetal zone, previously considered to be the result of the presence of an endogenous inhibitor, is due to an absence of the protein in this portion of the gland. The lack or minimal expression of 3 beta HSD in the fetal zone of HFA may be due to the action (or lack thereof) of a tissue-specific factor regulating the synthesis of 3 beta HSD.

Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle.

The levels of expression of mRNA species encoding cholesterol side-chain cleavage cytochrome P-450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P450(17 alpha], aromatase cytochrome P-450 (P-450AROM), and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) were examined in human follicles and corpora lutea (CL) throughout the menstrual cycle. Tissues were obtained from women undergoing hysterectomy and oophorectomy. The largest follicle or the CL was dissected from the ovary depending on whether the surgery was performed in the follicular or luteal phase. The day of the cycle was determined by onset of last menstrual period and was confirmed by endometrial histology. Total RNA was examined by Northern blot analysis, using as probes specific 32P-labeled cDNA inserts encoding each human enzyme. Early follicles demonstrated detectable mRNA for both P450scc and P450(17 alpha), but not for P450AROM or 3 beta HSD. P450AROM was detectable late in the follicular phase and appeared markedly induced in the CL. 3 beta HSD was detectable only in the CL. Levels of P450(17 alpha) mRNA remained relatively unchanged throughout the cycle, whereas P450scc mRNA levels were greatly increased in the CL. The presence of P450(17 alpha) mRNA in the human CL is of interest, since it is absent from the bovine CL, and this is consistent with the ability of the human, but not the bovine, CL to synthesize 17 alpha-hydroxyprogesterone and estrogens. The fact that P450AROM expression is highest in CL is surprising, since plasma estrogen levels are highest during the late follicular phase of the cycle, and may suggest that CL estrogen biosynthesis is limited by 17 alpha-hydroxylase or 17,20-lyase activities.

The use of rat Leydig tumor (R2C) and human hepatoma (HEPG2) cells to evaluate potential inhibitors of rat and human steroid aromatase.

The efficacies of 10-propargylestr-4-ene-3,17-dione (PED), 4-hydroxyandrostenedione (4-OHA) and the imidazole broad spectrum antimycotic drugs, econazole, imazalil, miconazole and ketoconazole, to inhibit the steroid aromatase activities of rat Leydig tumor (R2C) cells and human hepatoma (HEPG2) cells have been determined. The analysis of inhibition of steroid aromatase activity of intact cells provided further insight into the potential use of such drugs to block cellular estrogen synthesis. The IC50 values for the inhibition of aromatase activity of R2C cells by econazole, imazalil, miconazole, ketoconazole, 4-OHA and PED were 4, 9, 40, 1100, 11 and 10 nM, respectively. These drugs also inhibited the steroid aromatase activity of HEPG2 cells with corresponding IC50 values of 13, 27, 20, 15000, 2 and 2 nM, respectively; these findings were suggestive that the steroid aromatase of rat has many similarities to the human enzyme in its interaction with putative inhibitory compounds. Importantly, however, ketoconazole inhibited the rat aromatase more effectively than it did the human enzyme, while PED and 4-OHA were less effective inhibitors of the rat enzyme compared to that of human. These findings indicate differences in the potencies of various drugs to inhibit estrogen biosynthesis in human and rat cells. These may relate to differences in the two aromatase systems and/or differences in the stability of the drugs in the human hepatoma and rat Leydig tumor cells.