Penicillin Allergy label - the unmet needs - causes and potential solutions.

Summary: Background. Penicillin allergy is the most prevalent drug allergy. Its overdiagnosis has been associated with inappropriate antibiotic prescribing, increased antimicrobial resistance, worse clinical outcomes, and increased healthcare costs. Methods. 403 inpatients were audited against National Institute of Clinical Excellence (NICE) Clinical Guidance 183 (CG183) on diagnosis, investigations, documentation, and management of penicillin allergy. 50 junior doctors were surveyed to explore barriers to best practice, investigating their knowledge of, and confidence using the NICE CG183 guidelines. Their views on potential solutions were also explored. Results. The audit identified: 13% (54/403) of patients labelled penicillin allergic; 24% (13/54) fulfilled criteria for referral but none were referred to specialists. With regards to documentation: 33% (18/54) documented exact drug name; 72% (39/54) documented signs and symptoms; 20% (11/54) documented reaction severity; 2% (1/54) documented indication for the drug taken; 4% (2/54) documented number of doses taken or days before onset of the reaction and 0% documented route of administration. The survey revealed barriers including: 1- lack of awareness and confidence in applying the NICE CG183 on diagnosis and management; 2- tendency to err on the side of caution when de-labelling patients. All agreed that decision support tools would address barriers to best practice and appropriate penicillin allergy de-labelling Conclusions.The current practice of diagnosing, documenting, and managing penicillin allergies does not meet NICE CG183. A lack of awareness and confidence using NICE CG183 are the main contributing barriers to best practice. Decision support tools, including a drug allergy app, would help overcome these barriers.

The addition of flexible endoscopic suturing to stenting for the management of transmural esophageal wall defects: a single tertiary center experience.

BACKGROUND AND AIMS: Endoscopic stenting is the standard of care for full thickness esophageal wall defects. The aim of this study is to evaluate outcomes of endoscopic closure of esophageal defects using stenting, with or without endoscopic suturing. METHODS: This is a single-center retrospective study of patients with esophageal wall defects who underwent endoscopic interventions. Outcomes of stenting with or without endoscopic suturing of the defect were assessed. Univariate and multivariate logistic regression models were used to examine factors associated with successful defect closure. RESULTS: One hundred and fourteen patients with esophageal wall defects underwent 254 endoscopies with an overall complete closure rate of 75.8%. Twenty-three (20.2%) patients underwent primary closure using endoscopic suturing and subsequent esophageal stenting, while 91 (79.8%) underwent esophageal stenting only. The dual modality group (versus the stent-only group) had similar defect closure rates (84.2 vs. 73.8%, p = 0.55) and time to stent migration (37 vs. 12.5 days, p = 0.07), but was associated with longer procedure times (60 vs. 36 min, p < 0.01) and fewer additional endoscopic procedures (13.6 vs. 43.2%, p = 0.01). Stent suturing significantly decreased migration (35.5 vs. 58.5%, p = 0.04), was associated with fewer additional endoscopies (15.4 vs. 50%, p < 0.01) and reduced need for additional stents (7.7 vs. 34.3%, p < 0.01). On multivariate analysis, chronic defects (> four weeks old) were 81% less likely to close compared to acute (≤ 4 weeks) defects (OR 0.19, CI 0.04-0.77, p = 0.02), and large diameter stents (23 mm) were associated with higher odds of defect closure (OR 3.36, CI 1.02-11.4, p = 0.04). CONCLUSION: Endoscopic treatment of esophageal wall defects is safe, effective, and more likely to be successful in acute defects using larger caliber stents. Stent suturing reduces migration, need for additional endoscopic procedures, and stent exchanges. Further comparative studies with larger cohorts are needed to validate our results.

A case-control study of epidemiological factors associated with leptospirosis in South Gujarat region.

BACKGROUND: The current study was planned to identify the epidemiological factors associated with leptospirosis in South Gujarat region using neighborhood controls. METHODS: A total of 100 cases of leptospirosis occurred in South Gujarat region during the year 2012 were selected using simple random sampling. Three neighbors of the selected cases formed the controls (n = 300). A pretested structured questionnaire was used for data collection and data were analyzed using Epi Info 2007. RESULTS: There was significant association of illiteracy (odds ratio [OR] =1.82, 95% confidence interval [CI] =1.14-2.89), working in waterlogged fields during the reference season (OR = 4.6, 95% CI = 1.6-17.9), swimming/bathing in canals, open air defecation practices, storage of cow dung in or surrounding house, residence in the house made up of cow dung walls, households with access of food to rodents, injuries over hands/foot during the endemic season (OR = 3, 95% CI = 1.8-4.8), and history of skin disease during the endemic season (OR = 4.2, 95% CI = 2-8.5), with leptospirosis. Only 10% of individuals had gumboots for protection. A total of 83 (83%) cases and 240 (80%) controls had taken oral doxycycline chemoprophylaxis (P > 0.05). Cases had taken chemoprophylaxis for a median 4 weeks (range: 1-8) while controls had taken the same for median 8 weeks (range = 1-8) (P < 0.002). CONCLUSIONS: Although the commonly established factors appear to be associated with leptospirosis, the role of host factors seems to play a more important role in determining susceptibility to leptospirosis in exposed individuals.

Elevated land runoff after European settlement perturbs persistent foraminiferal assemblages on the Great Barrier Reef.

Coral reefs are under pressure from a variety of human-induced disturbances, but demonstration of ecosystem changes and identification of stressors are often difficult. We tested whether global change or increased agricultural runoff after European settlement of Northeast Australia (ca. 1860) has affected inshore reefs of the Great Barrier Reef. Eleven sediment cores were retrieved from inner reefs, intermediate reefs, and outer-island reefs, and benthic foraminiferal assemblages were analyzed in dated (14C, 210Pb, 137Cs) core sections (N = 82 samples). Data were grouped into six age bands (< 55, 55-150, 150-500, 500-1000, 1000-1500, and > 1500 yr). Principal component analysis and two-factor (Zone and Age) permutational analysis of variance (PERMANOVA) suggested that assemblages from the three zones were significantly different from each other over several millennia, with symbiont-bearing (mixotrophic) species dominating the outer reefs. A significant interaction term indicated that within-zone patterns varied. Assemblages in outer reefs unaffected from increased land runoff were persistent until present times. In both other zones, assemblages were also persistent until 150 yr ago, suggesting that benthic foraminiferal assemblages are naturally highly persistent over long (> 2000 yr) timescales. Assemblages in core sections < 55 yr old from inner reefs were significantly (post hoc t test) different from those older than 150 yr. Similarly, assemblages < 55 yr old from intermediate reefs were significantly different compared to older assemblages. A multivariate regression tree (environmental variables: Zone and Age) explained 56.8% of the variance in foraminiferal assemblages and confirmed patterns identified by PERMANOVA. With some exceptions, changes on the inner and intermediate reefs were consistent with a model predicting that increased nutrients and higher turbidity enhance relative abundance of heterotrophic species. Given that assemblages did not change in outer-island reefs (not impacted by runoff) we argue that changes in assemblages due to global change can be rejected as an explanation. Thus, the findings are more consistent with the hypothesis that agricultural runoff since European settlement altered foraminiferal assemblages than with the hypothesis that global forcing caused changes.

Advanced germ cell malignancies of the ovary: should neo-adjuvant chemotherapy be the first line of treatment?

Malignant germ cell tumours of the ovary, though classically known for 'young age' and 'early stage' at presentation, are not uncommonly identified at advanced stages. Little is available in literature on the role of neo-adjuvant chemotherapy (NACT) in this group of tumours. Two patients with advanced stage ovarian germ cell tumours, including one with 45XO/46XY chromosomal mosaicism, were treated at our Institute with neo-adjuvant chemotherapy with Bleomycin, Etoposide and Cisplatin followed by surgery. Besides marked clinical improvement, intraoperatively both the patients presented no difficulty otherwise expected with widespread tumours, and histopathology report revealed no evidence of viable tumour. The article discusses the experience and suggested course of management of these tumours with NACT, which could be offered to patients with advanced malignancy in whom high surgical morbidity is anticipated or in whom only an operative biopsy was performed at laparatomy. Behaviour and management guidelines of dysgenetic gonads with XY mosaicism have also been discussed.

Simulated future conditions of ocean warming and acidification disrupt the microbiome of the calcifying foraminifera Marginopora vertebralis across life stages.

Foraminifera host diverse microbial communities that can shift in response to changing environmental conditions. To characterize climate change impacts on the foraminifera microbiome across life stages, we exposed adult Marginopora vertebralis (Large Benthic Foraminifera) to pCO2 and temperature scenarios representing present-day, 2050 and 2100 levels and raised juveniles under present-day and 2050 conditions. While treatment condition had no significant effect on the seawater microbial communities, exposure to future scenarios significantly altered both adult and juvenile microbiomes. In adults, divergence between present-day and 2050 or 2100 conditions was primarily driven by a reduced relative abundance of Oxyphotobacteria under elevated temperature and pCO2 . In juveniles, the microbial shift predominantly resulted from changes in the proportion of Proteobacteria. Indicator species analysis identified numerous treatment-specific indicator taxa, most of which were indicative of present-day conditions. Oxyphotobacteria, previously reported as putative symbionts of foraminifera, were indicative of present-day and 2050 conditions in adults, but of present-day conditions only in juveniles. Overall, we show that the sensitivity of the M. vertebralis microbiome to climate change scenarios extends to both life stages and primarily correlates with declines in Oxyphotobacteria and shifts in Proteobacteria under elevated temperature and pCO2 .

Effects of larvae density and food concentration on Crown-of-Thorns seastar (Acanthaster cf. solaris) development in an automated flow-through system.

Coral-eating Crown-of-Thorns Sea stars (Acanthaster spp.) are major contributors to coral reef loss in the Indo-Pacific region. A release from food limitation of their planktotrophic larvae through enhanced pelagic productivity is one of the main hypothesis explaining population outbreaks ('nutrient limitation hypothesis'). To improve the understanding of these outbreaks we developed an automated flow- through larvae rearing system that maintained food (microalgae) at set levels over the course of four 15d experiments. This resulted in stable food concentrations in experimental tanks. Increased algae concentrations had a significant positive effect on larval development and size at 10 and 15 days post fertilization (dpf). Larvae densities had no effect at 10 dpf. At 15 dpf greater larvae densities were associated with declines in larvae size. Larval development was slowed under higher larvae densities. Thus, the effects of algae concentration and larvae density were additive at 15 dpf, with larvae under low densities at a given algae concentration being further developed than those under higher densities. The development of a flow-through system gives greater insight into the effect of algae and larvae concentrations on Acanthaster development, and the system can be applied to further test the nutrient-limitation hypothesis for present and future outbreaks.

Author Correction: Effects of larvae density and food concentration on Crown-of-Thorns seastar (Acanthaster cf. solaris) development in an automated flow-through system.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

The sodium/proton exchanger Nhx1p is required for endosomal protein trafficking in the yeast Saccharomyces cerevisiae.

We show that the vacuolar protein sorting gene VPS44 is identical to NHX1, a gene that encodes a sodium/proton exchanger. The Saccharomyces cerevisiae protein Nhx1p shows high homology to mammalian sodium/proton exchangers of the NHE family. Nhx1p is thought to transport sodium ions into the prevacuole compartment in exchange for protons. Pulse-chase experiments show that approximately 35% of the newly synthesized soluble vacuolar protein carboxypeptidase Y is missorted in nhx1 delta cells, and is secreted from the cell. nhx1 delta cells accumulate late Golgi, prevacuole, and lysosome markers in an aberrant structure next to the vacuole, and late Golgi proteins are proteolytically cleaved more rapidly than in wild-type cells. Our results show that efficient transport out of the prevacuolar compartment requires Nhx1p, and that nhx1 delta cells exhibit phenotypes characteristic of the "class E" group of vps mutants. In addition, we show that Nhx1p is required for protein trafficking even in the absence of the vacuolar ATPase. Our analysis of Nhx1p provides the first evidence that a sodium/proton exchange protein is important for correct protein sorting, and that intraorganellar ion balance may be important for endosomal function in yeast.

Evaluation of late toxicities of patients with carcinoma of the cervix treated with radical radiotherapy: an audit from India.

AIMS: To evaluate the incidence of, and factors affecting, late toxicities of women with carcinoma of the cervix treated with radical radiotherapy. MATERIALS AND METHODS: Between 1996 and 2001, 1069 women with carcinoma of the cervix (stage I-IVA) were treated at our centre with external-beam radiotherapy (EBRT) and intra-cavitary radiotherapy (ICRT) (n = 871) or EBRT alone (n = 198). Median follow-up was 34 months. Median dose to point A was 81 Gy. RESULTS: Five-year actuarial incidence of overall (all grades) and severe (grade 3/4) late toxicities in the rectum, bladder, small intestine and subcutaneous tissue were 12.3% and 1.1%, 11.2% and 1.2%, 9.2% and 0.2%, and 23.1% and 1.2%, respectively. Vaginal adhesions were seen in 29.6% of cases and stenosis in 33.9% of cases. On multivariate analysis, factors adversely affecting overall incidence of proctitis were anterior-posterior (AP) separation of patient more than 18 cm and presence of comorbid diseases. Presence of comorbid diseases was the only factor affecting the incidence of severe proctitis (grade 3/4). AP separation more than 18 cm adversely affected the incidence of cystitis, both overall and severe. Late toxicities (all grades) in small bowel were increased in subsets, like women younger than 50 years and women with comorbid diseases, but no factor emerged as significant for incidence of severe toxicities. Subcutaneous fibrosis was significantly higher in patients with AP separation over 18 cm, those treated by cobalt machines and those who received EBRT only. Severe subcutaneous fibrosis was influenced by the use of EBRT alone. Overall incidence of vaginal toxicity was higher in women whose overall treatment time (OTT) was shorter and in women who received ICRT. Vaginal stenosis was higher in elderly women and in women who received ICRT by low dose rate. CONCLUSIONS: Even with telecobalt machines, impressive results with acceptable late toxicity can be achieved in the treatment of cancer of the cervix using an ideal combination of EBRT with ICRT.

Results of external-beam radiotherapy alone in invasive cancer of the uterine cervix: a retrospective analysis.

AIMS: In this retrospective audit, we describe the results of external-beam radiotherapy (EBRT) alone in patients with invasive cancer of the cervix treated at our centre. MATERIAL AND METHODS: We included 146 patients with invasive cancer of the cervix who were treated with EBRT to a total dose of 60-66 Gy between January 1996 and December 2001. None of these patients were suitable for intracavitary radiotherapy (ICRT) after a median dose of 46 Gy. A boost dose of 14-20 Gy was given after a gap of 2-4 weeks. Most patients belonged to stage IIIB (n = 124). RESULTS: Follow-up of patients at risk ranged from 19 to 89 months (median 48 months). One hundred and thirty-six patients (93.2%) received EBRT to a dose of 66 Gy, and 10 patients (6.8%) received 60 Gy. Overall treatment time (OTT) ranged from 56 to 160 days (median 78 days). At completion of 46 Gy of EBRT, 63 patients achieved partial response and 83 patients had stable disease. Five-year overall survival, disease-free survival (DFS) and pelvic control were 15.1% (median 9 months), 11.6% (median 5 months) and 21.9% (median 6 months), respectively. Factors found to affect 5-year pelvic control in univariate analysis by Kaplan-Meier method were response to EBRT at 46 Gy (partial response 36.5% and stable disease 10.8%), age (> or = 50 years 28.8% and < 50 years 13.6%) and OTT (< 90 days 26.5% and > or = 90 days 12.5%). For DFS and overall survival, response to EBRT was the only factor that was significant in univariate analysis. In multivariate analysis by Cox's proportional hazard model, response to EBRT was the only factor to influence pelvic control (P = 0.007), DFS (P = 0.01) and overall survival (P < 0.001). CONCLUSIONS: Overall outcome of patients in whom ICRT was not given remains less than satisfactory. Response to EBRT emerged as the most important factor to predict all clinical outcomes. To improve upon the dismal results of EBRT alone, we will have to decrease the OTT and consider concurrent chemo-radiation with cisplatin.

Clinical significance of geographic miss when using conventional four field radiotherapy technique in treatment of locally advanced carcinoma cervix.

BACKGROUND: Although conventional four- field radiotherapy based on bony landmarks has been traditionally used, areas of geographical miss due to individual variation in pelvic anatomy have been identified with advanced imaging techniques. AIMS: The primary aim of this study is to evaluate the geographical miss in patientswhen using the conventional four-field planningplanning and to find out the impact of 3-D conformal CT based in patients with locally advanced carcinoma cervix. MATERIALS AND METHODS: In 50 patients, target volume delineation was done on planning computed tomography (CT) scans, according to guidelines by Taylor et al. Patients were treated with modified four field plan, except for the superior, where field border was kept at L4-L5 interspace A dosimetric comparison was done between the conventional four-field based on bony landmarks and the target volume delineated on computed tomography. The disease free survival, pelvic and para aortic nodal free survival, distant failures free survival were calculated using Kaplan Meir Product Limit Method. RESULTS: Patients were followed-up for a median period of 11 months. The median V95 for conventional and modified extended four field plans were 89.4% and 91.3% respectively. Patients with V95 for modified extended pelvic fields less than 91.3% had a trend toward inferior disease free survival (mean DFS 9.8 vs. 13.9 months) though the difference was not statistically significant log rank test. CONCLUSIONS: Our preliminary data shows trend toward lower DFS in patients with inadequate target volume coverage. We recommend routine use of CT based planning for four field technique.

Suicide - a statistical analysis by age, sex and method.

A total of 115 suicide cases dealt with by St. Pancras Coroner's Court, London, UK were studied in order to determine what patterns exist regarding the age and gender of the victims and chosen method of suicide. The results were compared with those of a 1998 study of suicides in England and Wales commissioned by the UK Home Office. It was found that suicides in the male population are approximately twice as common as female victims of suicide. In terms of gross number of cases, the peak age group for both males and females resorting to suicide was found to be the 15-44 age group. When the results were standardised according to 2001 census data, however, the most vulnerable age group per head of population for both sexes was 75 and over. Good agreement was found between the results of this study and those of the Home Office Study.

Patterns of non-firearm homicide.

Sixty-two recent non-firearm homicides dealt with by an inner London public mortuary were studied. The majority of homicides involved stabbing--usually multiple wounds to the trunk. These were followed by blunt instrument homicides--nearly all involved multiple blows to the head, and asphyxiation--usually consisting of strangulation with a ligature being employed in the majority of cases. Homicides tended to occur during the evening and night in spring and early summer. Most victims were found to be in the 20-39 age group, with male victims outnumbering females in a 2:1 ratio. A marked difference in homicide pattern existed between the male and female victims. Males tended to fall victim to strangers encountered while socialising in and around bars and clubs. Females were most often killed by close acquaintances in domestic disputes at home.

Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

AIMS: Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. MATERIALS AND METHODS: In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. RESULTS: The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. CONCLUSION: Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy.

Dosimetric evaluation and clinical outcome in post-operative patients of carcinoma vulva treated with intensity-modulated radiotherapy.

BACKGROUND: To compare dosimetric parameters of intensity-modulated radiation therapy (IMRT) with 3D conformal radiotherapy (3DCRT) in post-operative patients of vulvar cancer and to assess clinical outcome and toxicity with IMRT. MATERIALS AND METHODS: A total of 8 post-operative patients of vulvar cancer were treated with IMRT. All patients were also planned by 3DCRT for comparison with IMRT. The two plans were compared in terms of conformity index, homogeneity index, tumor control probability (TCP) and normal tissue complication probability (NTCP) for the planning target volume and organs at risk (OAR). RESULTS: IMRT resulted in significantly lesser doses to rectum, bladder, bowel and femoral head as compared with 3DCRT plans. Mean conformity and homogeneity indices were better and within range with IMRT. The TCP was comparable between the two treatment plans and NTCP for rectum, bladder, bowel and femoral head was significantly less with IMRT as compared with 3DCRT. Treatment was well-tolerated and none of the patients developed Grade 3 or higher toxicity. CONCLUSION: IMRT yielded superior plans with respect to target coverage, homogeneity and conformality while lowering dose to adjacent OAR as compared with 3DCRT. Thus, IMRT offers a reduction in NTCP while maintaining TCP.

Bladder-Rectum Spacer Balloon versus Vaginal Gauze Packing in High Dose Rate Brachytherapy in Cervical Cancer: A Randomised Study. Part II.

AIMS: To compare the inter-fraction dose variation for bladder and rectum using a bladder-rectum spacer balloon (BRSB) versus vaginal gauze packing (VGP) in patients treated with high dose rate intracavitary brachytherapy for carcinoma cervix. MATERIALS AND METHODS: After the completion of external radiotherapy, 80 patients were randomised to receive intracavitary brachytherapy using either the BRSB or VGP. The procedure was carried out under general anaesthesia using tandem ovoid applicators. Computed tomography-based planning was carried out and the dose was prescribed to point A. Doses to 0.1, 1 and 2 cm(3) volumes were reported for bladder and rectum for each fraction. The absolute inter-fraction dose variation for each subvolume was compared using the independent sample t-test. RESULT: The mean bladder and rectal volumes, as well as the inter-fraction volume variation, were comparable for the BRSB and VGP. The BRSB resulted in a significant reduction in absolute dose as well as the inter-fraction variation for dose to 2 cm(3) rectum volumes (BRSB 0.80 Gy, standard deviation 0.71 Gy versus VGP 1.16 Gy, standard deviation 0.83 Gy; P = 0.04). Cumulative bladder D2cm(3) doses of more than 90 Gy3 were observed in six patients in the BRSB arm versus four patients in the VGP arm (P = 0.73). In both the arms, the rectal D2cm(3) doses did not exceed 75 Gy3. CONCLUSIONS: Use of a BRSB resulted in a significant reduction in inter-fraction variation in D2cm(3) rectal dose. However, no significant difference in the inter-fraction dose variation for the other subvolumes of bladder and rectum could be shown between the BRSB and VGP. The use of a BRSB may enable rectal dose reduction and inter-fraction variation where anaesthesia is not routinely used or where there is limited physician expertise. The modification suggested in the BRSB may facilitate its additional usage.

Local modulation by 11beta-hydroxysteroid dehydrogenase of glucocorticoid effects on the activity of 15-hydroxyprostaglandin dehydrogenase in human chorion and placental trophoblast cells.

NAD+-dependent 15-hydroxy-PG dehydrogenase (PGDH) is the major enzyme involved in the initial inactivation of PGs, and its activity is reduced by glucocorticoids, cortisol (F), and dexamethasone (DEX). In turn, glucocorticoid regulation of PGDH activity in placenta and chorion could be regulated indirectly by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity. In the placenta, 11beta-HSD2 is the dominant isoform, acting as a dehydrogenase [F to cortisone (E)]; and in chorion, 11beta-HSD1 predominates as a reductase (E to F). The present study was designed to determine whether glucocorticoid regulation of PGDH activity in placenta and chorion could be regulated indirectly by 11beta-HSD activity. We obtained Percoll-purified human placental and chorion trophoblast cells from uncomplicated term pregnancies, cultured them for 72 h, then treated the cells with cortisol (100 nmol/L), cortisone (1 micromol/L), or DEX (100 nmol/L), in the presence or absence of carbenoxolone (CBX, 800 nmol/L), an 11beta-HSD inhibitor, for 24 h. Activity of PGDH was assessed by incubation (4 h) with PGF2alpha (282 nmol/L) and measurement of conversion to 13,14-dihydro-15-keto PGF2alpha. CBX alone had no effect on PGDH activity in either placenta or chorion trophoblast cells. In chorion, E significantly inhibited PGDH activity, and this effect was reversed by addition of CBX. F and DEX significantly inhibited PGDH, and this effect was unaltered by coadministration of CBX. In contrast, in placenta, there was no effect of E, or of E with CBX, on PGDH activity. However, F and DEX inhibited PGDH, and the effect of F (but not DEX) was greater in the presence of CBX. In conclusion, we suggest that effects of E and F on PGDH are modified by the tissue-specific expression of 11beta-HSD isoforms.