Cushing's syndrome caused by use of synthetic ocular steroid.

WHAT IS KNOWN AND OBJECTIVE: Cases of Cushing's syndrome (CS) following ocular steroid use have been reported in recent years, albeit rarely. CASE DESCRIPTION: We report a case of iatrogenic CS in a child induced by fluorometholone-containing eyedrops. Our patient was referred to our endocrinology clinic due to rapid weight gain. His history revealed that 1.5 months previously he had been started on fluorometholone eyedrops. WHAT IS NEW AND CONCLUSION: To the best of our knowledge, no cases of CS have been reported following ocular fluorometholone use. Although eyedrops containing potent glucocorticoids may lead to CS, fluorometholone, a relatively less potent steroid, may also cause the syndrome, as in our case.

EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases.

To develop recommendations for the management of medium to high-dose (ie, >7.5 mg but ≤100 mg prednisone equivalent daily) systemic glucocorticoid (GC) therapy in rheumatic diseases. A multidisciplinary EULAR task force was formed, including rheumatic patients. After discussing the results of a general initial search on risks of GC therapy, each participant contributed 10 propositions on key clinical topics concerning the safe use of medium to high-dose GCs. The final recommendations were selected via a Delphi consensus approach. A systematic literature search of PubMed, EMBASE and Cochrane Library was used to identify evidence concerning each of the propositions. The strength of recommendation was given according to research evidence, clinical expertise and patient preference. The 10 propositions regarded patient education and informing general practitioners, preventive measures for osteoporosis, optimal GC starting dosages, risk-benefit ratio of GC treatment, GC sparing therapy, screening for comorbidity, and monitoring for adverse effects. In general, evidence supporting the recommendations proved to be surprisingly weak. One of the recommendations was rejected, because of conflicting literature data. Nine final recommendations for the management of medium to high-dose systemic GC therapy in rheumatic diseases were selected and evaluated with their strengths of recommendations. Robust evidence was often lacking; a research agenda was created.

Changes in the ovarian stromal blood flow in patients treated with laparoscopic salpingostomy for ectopic pregnancy.

This study is aimed to evaluate the impact of laparoscopic salpingostomy on ovarian stromal blood flow indices in patients with ectopic pregnancy, and to compare the ovarian stromal blood flow indices with matched paired healthy women. We included 37 patients who underwent laparoscopic salpingostomy and 37 age- and parity-matched women as controls. The main outcome was the differences in ovarian volume, antral follicle count (AFC), and ovarian stromal blood flow indices between the study group participants after the surgery and the healthy controls. Comparison of the ovarian parameters between the study group after the surgery and the control group revealed no significant differences in terms of ovarian volume (p = 0.783), AFC (p = 0.253), ovarian stromal S/D ratios (p = 0.054), pulsatility index (PI; p = 0.938) and resistance index (RI; p = 0.041). In addition, comparison of the ovarian parameters before and after the surgical treatment revealed no significant differences in the ovarian volume (p = 0.141), AFC (p = 0.084), ovarian stromal S/D ratios (p = 0.187), PI (p = 0.102) and RI (p = 0.108). In conclusion, laparoscopic salpingostomy does not affect ovarian function in terms of ovarian stromal blood flow indices, ovarian volume, and AFC.

Adverse events of intravenous glucocorticoid pulse therapy in inflammatory diseases: a meta-analysis.

OBJECTIVES: To systematically analyse the literature on reported adverse events (AEs) of intravenous pulse glucocorticoids (GCs) (≥ 250 mg prednisone equivalent) for inflammatory diseases. METHODS: A literature search was done using PubMed, Embase, and Cochrane databases. Studies were selected by two reviewers (NAMS and ND). Available data on the prevalence of GC-related AEs in patients with inflammatory diseases were retrieved. RESULTS: In only 8 studies (344 patients), 4 placebo-controlled and 4 not placebo-controlled studies, intravenous pulse GC-related AEs had been documented (in total 323 AEs), with an AE rate of 35/100 patient-years. In the 4 placebo-controlled studies among RA and systemic sclerosis patients, most of the odds ratios of individual AEs were not statistically significant, except for flushing, heart rhythm disorder, disturbance of taste, lower respiratory infection, and headache. In the 4 not placebo-controlled studies increased diastolic blood pressure was most frequent, followed by flushing and diabetes mellitus. Adverse events seen in more than 15% of patients of all included studies were increased blood pressure, flushing, headache, disturbance of taste, tachycardia and hyperglycemia. CONCLUSIONS: GC pulse therapy results in a high AE rate, i.e. 35/100 patient-years. Cardiovascular AEs are most frequently reported in the literature. Furthermore, flushing had the highest odds ratio in the placebo-controlled studies and also a high event rate in the not placebo-controlled studies.

Quality of Life and Psychological Screening in Children with Type 1 Diabetes and their Mothers.

This study aimed to assess the levels of depression in children with type 1 diabetes mellitus (T1DM) and evaluate the quality of life as well as levels of depression and anxiety of their mothers.30 children with T1DM (mean age: 12.9±2.9 years) and their mothers (mean age: 40.0±7.5 years) were included in the study. Control group consisted of 30 healthy children (mean age: 12.7±2.7 years) and their mothers (mean age: 39.8±7.2 years). The presence and severity of depressive symptoms in the children were evaluated using the Children's Depression Inventory (CDI). The short form 36-health survey (SF-36), the Beck Depression Inventory (BDI), and Spielberg's State-Trait Anxiety Inventory (STAI) were administered to all mothers.The children with T1DM had higher scores of depression compared to healthy children in the control group. The mothers of children with T1DM had significantly lower scores on all subscales of SF-36 except the bodily pain subscale. We observed a significant difference between groups in their BDI scores; the mean BDI score was higher in mothers of children with T1DM (p=0.004). There was a significant difference in STAI scores between groups. CDI scores positively correlated with the ages of and HgA1C levels in the children with T1DM. There was a positive correlation between CDI scores of children with T1DM and BDI scores of their mothers. In addition, CDI sores negatively correlated with the scores of vitality and social functioning subscales of SF-36.Our findings suggest screening for mental health issues and quality of life in diabetic children and their mothers.

Which tonometry in eyes with keratoconus?

AIMS: To compare intraocular pressure (IOP) measurements obtained with Goldmann applanation tonometery (GAT), dynamic contour tonometry (DCT), tonopen (TP), and ocular response analyzer (ORA), and to determine the influence of Amsler grade and central corneal thickness (CCT) on the IOP readings in eyes with keratoconus that are classified into four groups according to the Amsler-Krumeich classification. METHODS: All eyes with keratoconus were separated into four groups using Amsler-Krumeich classification for keratoconus. IOP was measured in 202 eyes of 202 patients with keratoconus using GAT, DCT, TP, and ORA. RESULTS: The IOP differences revealed no significant difference among the Amsler degree in the DCT and corneal-compensated IOP (IOPcc) measurements (P>0.05 for all). There was no statistically significant difference in terms of IOP differences between GAT and IOPcc (P>0.05), TP and Goldmann-correlated measure of IOP (IOPg; P>0.05) in the Amsler I, while the IOP measurements revealed significant difference among the measurements of the four different tonometers in the Amsler II, Amsler III, and Amsler IV (P<0.05 for all). CONCLUSIONS: There was no significant association between DCT IOP or IOPcc and CCT in eyes with keratoconus; no statistically significant difference was found between keratoconus stages and the control group in terms of the IOP analyzed with these two techniques. These two techniques may be the most stable in the measurement of IOP in different keratoconus stages. However, no IOP technique can be used interchangeably with other techniques in the follow-up of keratoconus patients.

Assessment of sperm cryodamage and strategies to improve outcome.

Sperm cryopreservation still represents a valuable clinical aid in the management of infertility. Its current principal indications include (1) donor sperm insemination; (2) freezing before cancer therapy to maintain reproductive capacity; (3) patient's convenience; and (4) because of the outstanding success with ICSI, even patients with different degrees of oligo-asthenoteratozoospermia can now be offered the use of frozen/thawed sperm for oocyte micromanipulation. Although sperm cryopreservation/thawing and results of insemination and IVF have been consistently good using donor semen, results of infertile men (with or without various degrees of oligoasthenoteratozoospermia) have yielded remarkably lower rates of survival and pregnancy. Freezing/thawing techniques have not been subjected to major changes in the last years, Furthermore, the exact nature of sperm cryodamage still remains to be elucidated. Various aspects of sperm freezing are revisited here (1) development of new technical approaches for cryopreservation; (2) analysis of the stimulatory effect of putative cryoprotectant additives; (3) the use of intrauterine insemination-ready processed samples; and (4) selection and optimization of end-points for analysis of cryodamage. It is expected that advances in such areas will improve significantly the cryopreservation/thawing outcome particularly as related to semen samples of subfertile men.

Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa.

OBJECTIVE: To evaluate the effects of oxidative stress on DNA and plasma membrane integrity of human spermatozoa. DESIGN: Prospective cohort study. SETTING: University-based, tertiary-care infertility center. PATIENT(S): Men (n = 10) undergoing infertility investigation. INTERVENTION(S): Purified populations of sperm with high motility were separated using Percoll density gradients. Then, spermatozoa were incubated with 0, 10, 100, and 200 microM hydrogen peroxide (H(2)O(2)) under capacitating conditions. MAIN OUTCOME MEASURE(S): Motion parameters were assessed by computer analysis. Genomic integrity was examined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay. Plasma membrane integrity was evaluated by the annexin V-binding assay, a measure of phosphatidylserine translocation. RESULT(S): Under basal conditions, there was a significant and negative relationship between sperm motility and the percentages of sperm with DNA fragmentation and membrane translocation of phosphatidylserine. After a 2-h incubation, there was a significant, dose-dependent effect of H(2)O(2) on motion parameters (decrease) and DNA fragmentation (increase). The percentage of annexin V(-) live (normal) cells declined significantly as the level of oxidative stress increased. Although the percentages of annexin V(+) live cells (sperm depicting translocation of phosphatidylserine) and necrotic cells increased at the highest H(2)O(2) levels, these changes were not significant. CONCLUSION(S): In vitro sperm incubation with H(2)O(2) induces DNA fragmentation in a dose-dependent fashion. The sublethal effects of oxidative stress on motion parameters were not significantly associated with membrane translocation of phosphatidylserine.

Cryopreservation-thawing of fractionated human spermatozoa and plasma membrane translocation of phosphatidylserine.

OBJECTIVE(S): [1] To evaluate sperm membrane damage during cryopreservation-thawing by the assessment of phosphatidylserine (PS) translocation and [2] to examine the relationship between reactive oxygen species (ROS) and cryopreservation-related alterations. DESIGN: Prospective cohort study. SETTING: University-based center. PATIENT(S): Men consulting for infertility and fertile donors (controls). INTERVENTION(S): Semen processing was performed by density gradient separation followed by cryopreservation and thawing. MAIN OUTCOME MEASURE(S): Membrane PS translocation was evaluated with annexin V binding, generation of ROS was detected by chemiluminescence, and motion parameters were assessed by computer analysis. RESULT(S): Annexin V binding was detected in the prefreeze fractions with high and low sperm motility. In the patient group, there were significantly higher postthaw levels of annexin V binding in both fractions when compared with prefreezing values. However, such induction of PS translocation was significantly higher in the fractions with high sperm motility. Significantly higher ROS levels were detected in prefreeze samples of the fractions with low sperm motility. CONCLUSION(S): In the population of men studied, [1] cryopreservation-thawing was associated with induction of membrane PS translocation; [2] postthaw ROS levels were lower than before freezing; and [3] neither annexin V binding results nor the generation of ROS were able to accurately predict sperm cryosurvival rates.

Semen treatment with progesterone and/or acetyl-L-carnitine does not improve sperm motility or membrane damage after cryopreservation-thawing.

OBJECTIVE: To assess the effects of progesterone and acetyl-L-carnitine used before semen cryopreservation-thawing on sperm motility parameters and plasma membrane integrity. DESIGN: Prospective cohort study. SETTING: Academic tertiary center. PATIENT(S): Subfertile men undergoing semen evaluation. INTERVENTION(S): Before cryopreservation, spermatozoa were incubated with water-soluble progesterone (1 and 10 microM), acetyl-L-carnitine (2.5, 5, 10, and 20 mM), or both (progesterone, 1 microM; and acetyl-L-carnitine, 5 mM). MAIN OUTCOME MEASURE(S): Postthaw change of motility parameters (computer-assisted measurements) and vitality-membrane integrity (examined with eosin-Y staining and annexin V-Cy3 binding assay). RESULT(S): There were no statistically significant differences between control samples and samples treated with progesterone and/or acetyl-L-carnitine for cryosurvival rate, motility parameters, or membrane integrity. The percentages of postthaw cells identified as live showed significantly different results with use of the eosin-Y staining and annexin V binding assay. CONCLUSION(S): Neither progesterone nor acetyl-L-carnitine seemed to prevent cryodamage assessed by motility changes or membrane integrity in human spermatozoa of subfertile men. Annexin V binding, a reflection of membrane translocation of phosphatidylserine, provided more distinct information about postfreezing membrane integrity changes than eosin-Y staining.

Cryopreservation-Thawing of fractionated human spermatozoa is associated with membrane phosphatidylserine externalization and not DNA fragmentation.

The objective of these studies was to evaluate the effect of cryopreservation-thawing of human spermatozoa on DNA fragmentation and membrane integrity. This was a prospective, controlled cohort study, performed at a university-based infertility center. Ejaculates were examined from 5 donors and 16 men undergoing infertility evaluation. Purified sperm populations were prepared by gradient centrifugation, cryopreserved using a manual method and TEST-yolk buffer and glycerol (TYB-G), followed by quick-thaw. Annexin V binding was used for assessing membrane translocation of phosphatidylserine, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was utilized for the evaluation of DNA fragmentation. The results were as follows: the percentage of live cells with intact membranes (annexin V-, live) was significantly reduced after cryopreservation-thawing. On the other hand, the percentages of live cells with phosphatidylserine translocation (annexin V-, live) and of necrotic (dead) cells increased significantly after thawing. TUNEL revealed percentages of cells with DNA fragmentation in the prefreeze and postthaw samples that were not significantly different. In a further attempt to examine differences in response to various cryoprotection protocols, experiments were carried out using no cryoprotection, glycerol alone, or TYB-G. Samples frozen with TYB-G demonstrated significantly higher percentages of live cells without phosphatidylserine translocation than the other conditions. We concluded that cryopreservation-thawing of human sperm from patients and donors was associated with membrane change, as revealed by membrane translocation of phosphatidylserine, while having no major impact on DNA fragmentation.

Is adjuvant therapy necessary for peritoneal cytology-positive surgical-pathologic Stage I endometrial cancer? Preliminary results.

OBJECTIVE: To compare the clinical and laboratory findings between adjuvant therapy performed and not performed on peritoneal cytology-positive patients with cytology-negative cases of surgical-pathologic Stage I endometrial cancer. METHODS: Twelve peritoneal cytology-positive and 12 negative surgical-pathologic Stage I endometrial cancer cases were used in the study. Adjuvant radiotherapy was performed for six cytology-positive patients (group I); no adjuvant therapy was performed for six cytology-positive (group II) and 12 cytology-negative patients (control group). Pelvic examination, vaginal cytology, serum CA125 levels and routine blood tests were checked at two-month intervals for two years and at six-month intervals for the third year. Abdominopelvic computerized tomography was planned annually. RESULTS: There was no statistically significant difference among the three groups and no recurrence in any group. CONCLUSION: We do not recommend adjuvant therapy for cytology-positive patients if the tumor is confined to the uterus.

CA19-9 may have clinical significance in mature cystic teratomas of the ovary.

The objective of this study was to evaluate size, bilaterality, histopathologic origin, and the serum levels of some tumor markers in patients with mature cystic teratomas (MCTs) of the ovary. Retrospective study of 80 patients operated at Department of Obstetrics and Gynecology, Gulhane Military Medical Academy, Turkey, between the years 1998 and 2003 was performed. The mean age was 33.1 +/- 11.3 years (median 34; range 15-69). The mean tumor diameter was 7.2 +/- 4.5 cm (median 5; range 3-20). The mean serum CA19-9 level was 101.2 +/- 179.7 IU/mL (range 1-841, normal value < 37), the mean serum CA125 level was 32.0 +/- 37.8 U/mL (range 2.2-205, normal value < 35), the mean carcino-embryogenic antigen (CEA) level was 1.46 +/- 1.20 ng/mL (range 0.2-4.8, normal value 3.4), and the mean serum alpha-fetoprotein (AFP) level was 2.7 +/- 3.0 ng/mL (range 0.1-10.5, normal value <8.1). The elevated rate of CA19-9, CA125, CEA, and AFP was 38.8% (31/80), 25% (18/72), 9.1% (4/44), and 8.7% (4/46), respectively. The bilaterality rate was 27.5% (22/80). Patients with an elevated serum CA19-9 level showed significantly higher bilaterality rate (51.6% versus 12.2%, P < 0.05) than the patients with low levels. Likelihood ratio for bilaterality was 2.8 for CA19-9 and 4.6 for CA125. Bilateral teratomas showed a significantly higher rate of ectodermal component than the unilateral ones (100% versus 74.3%, P < 0.05). Ovarian MCTs were diagnosed especially during the reproductive period. CA19-9 may be the only important marker in the diagnosis of MCTs. Elevated levels of CA19-9 and CA125 may be an indicator of bilaterality. Since levels of CA19-9 and CA125 may be elevated in both benign and malignant conditions, interpretation of these findings must be made in light of the clinical condition of the patient.

Predictive value of amniotic fluid volume measurements on perinatal outcome.

Amniotic fluid volumes were measured in 1,659 pregnant women to determine the predictive value of these measurements on perinatal outcome. All cases were evaluated by other tests of fetal well-being. 128 cases were oligohydramniotic, and 1,531 cases were normal. In all cases, several parameters were assayed, e.g. fetal distress, way of delivery, meconium in amniotic fluid, Apgar score, transfer to pediatric clinics and early-late neonatal complications. The results of the perinatal evaluation of oligohydramnios were as follows: assessing fetal distress: specificity 94.2%, sensitivity 18.4%, positive predictive value 35.9%, negative predictive value 86.7% and accuracy 82.8%, and assessing low Apgar score the values were 93.0, 21.3, 95.9 and 89.5%, respectively. As a result, measurement of the amniotic fluid volume is an important parameter predicting perinatal outcome, and its predictive value increases if it is combined with other fetal well-being tests with different end points.

Three sisters with septate uteri: another reference to bidirectional theory.

A case report of three sisters with different degrees of septate uteri, a rare familial aggregation, is presented. The youngest sister was diagnosed with a complete uterine septum with cervical duplication and complete longitudinal vaginal septum. She also had a bilateral partial ureteral duplication. Investigation of the family showed that the eldest sister had a complete uterine septum and her pregnancy had terminated with a vaginal delivery following premature rupture of the membranes. The asymptomatic middle sister showed an incomplete uterine septum. Finally, the mother was normal with respect to urogenital anatomy. These types of Müllerian anomalies cannot be explained by the classical theory of unidirectional Müllerian duct development; the alternative bidirectional theory is proposed instead. Additionally, the results are suggestive that the prevalence of major uterine malformations may be higher than generally thought, due to asymptomatic cases.

Percutaneous treatment of hepatic hydatid cyst in pregnancy.

A 20 cm hepatic hydatid cyst with daughter cysts, was diagnosed in a primigravida in the fifteenth week of pregnancy and was managed percutaneously. No complications occurred and the patient subsequently gave birth to a healthy baby.

Yolk sac size and shape as predictors of poor pregnancy outcome.

Two hundred and fifty women, underwent endovaginal sonography in the first trimester to establish the normal size and shape of the secondary yolk sac and to assess the value of yolk sac evaluation in predicting poor pregnancy outcome. We calculated the correlation coefficients between yolk sac and menstrual age, yolk sac and crown-rump length and between yolk sac and mean gestational yolk sac diameter as r: 0.9581 (p < 0.001), r: 0.9427 (p < 0.0001) and r: 0.8855 (p < 0.0001), respectively. Of 250 cases, 219 had a normal pregnancy course through the end of the first trimester (Group I) while 31 had a poor prognosis such as abortion or embryonic demise (Group II). Eight of 219 in Group I and 20 of 31 in Group II had an abnormal yolk sac size. A yolk sac diameter out of two standard deviations of the mean for the menstrual age allowed prediction of an abnormal pregnancy outcome with a sensitivity of 65%, a specificity of 97%, a positive predictive value of 71%, and a negative predictive value of 95%. Ten of 219 and 9 of 31 had abnormal yolk sac shape. An abnormal yolk sac shape allowed prediction of an abnormal pregnancy outcome with a sensitivity of 29%, a specificity of 95%, a positive predictive value of 47% and a negative predictive value of 90.5%. We concluded that secondary yolk sac evaluation is a valuable tool to predict pregnancy outcome.

Development of an integrated laboratory information management system for the maize mapping project.

MOTIVATION: The development of an integrated genetic and physical map for the maize genome involves the generation of an enormous amount of data. Managing this data requires a system to aid in genotype scoring for different types of markers coming from both local and remote users. In addition, researchers need an efficient way to interact with genetic mapping software and with data files from automated DNA sequencing. They also need ways to manage primer data for mapping and sequencing and provide views of the integrated physical and genetic map and views of genetic map comparisons. RESULTS: The MMP-LIMS system has been used successfully in a high-throughput mapping environment. The genotypes from 957 SSR, 1023 RFLP, 189 SNP, and 177 InDel markers have been entered and verified via MMP-LIMS. The system is flexible, and can be easily modified to manage data for other species. The software is freely available. AVAILABILITY: To receive a copy of the iMap or cMap software, please fill out the form on our website. The other MMP-LIMS software is freely available at http://www.maizemap.org/bioinformatics.htm.