The superiority of Dexpanthenol or Vaseline as excipient in nasal formulations.

OBJECTIVE: Dexpanthenol is an ingredient in multiple topical pharmaceutical preparations thanks to its high penetration and localized concentration. It is included in many ointments or lotions for dermatological use, assisting in healing and reducing pruritus. Vaseline is a synthetic product obtained by distilling crude oil. It is commercially available in several grades. The study presented here examined how topically applied agents (dexpanthenol or vaseline) affect nasal epithelial cells in culture. In particular, the study aimed to identify any alterations to epithelial cells which might indicate toxicity. MATERIALS AND METHODS: The nasal epithelial cells used were sourced from mucosal tissue fragments left over the following septorhinoplasty on five patients not suffering from rhinosinusitis. The first step was to dissect the mucosal fragments into smaller pieces on a sterilized Petri dish. These fragments were then placed into the DMEM-F12 cell culture medium, which had been freshly prepared. The dexpanthenol and vaseline were diluted in dimethylsulfoxide (DMSO) to a concentration of 5 mg/mL. The cells in the wells were exposed to varying concentrations of dexpanthenol or vaseline. The actual concentration of the test reagent to which the epithelial cells were exposed ranged from 0.15 mg/mL to 5 mg/mL. The exposure period was 24 hours. The cells were finally examined using a Leica SP5II confocal microscope. The features sought were DNA fragmentation, condensation of the nuclei, changes in the outer membrane, or cytoskeletal abnormality. These features, if present, indicate cytotoxicity. RESULTS: The viability of the cultured nasal epithelial cells was unaltered by a 24-hour exposure to dexpanthenol, nor was the cellular proliferation rate affected at the level of statistical significance. There was evidence of a cytotoxic effect from exposing nasal epithelial cells to vaseline in liquid form for 24 hours. There was a reduction in cellular viability in the plates where the highest dose of vaseline (5 mg/mL) was used. Cellular viability was not affected significantly at any of the doses below 5 mg/mL. CONCLUSIONS: The absence of cytotoxic effects from the application of dexpanthenol to the nasal mucosa indicates that this agent may be safely used within the nose. The cytotoxic effects of liquid vaseline observed in this trial (condensed nuclear chromatin, loss of cellular volume) indicate that this agent may be harmful when used intranasally. For patients who require nasal packing due to nose bleeds or following endoscopic sinus surgical procedures, dexpanthenol should be preferred to vaseline from the point of view of maximizing healing of a nasal injury.

Acoustic, perceptual and aerodynamic voice evaluation in an obese population.

OBJECTIVE: To investigate perceptual, acoustic and aerodynamic voice parameters in obese individuals. METHODS: Twenty obese and 20 normal-weight volunteers underwent voice evaluation by laryngoscopy, acoustic analysis, aerodynamic measurement and perceptual analysis (using the grade-roughness-breathiness-asthenia-strain ('GRBAS') scale and the Voice Handicap Index 10 scale). Data from both subject groups were compared. RESULTS: No difference was found in acoustic analysis parameters between the two groups (p > 0.05). Maximum phonation time in the obese group (mean ± standard deviation, 19.6 ± 4.9 seconds) was significantly shorter than in controls (26.4 ± 4.1 seconds) (p < 0.001), although the s/z ratio was very similar between the two groups. In the obese and control groups, the mean ± standard deviation grade-roughness-breathiness-asthenia-strain scores were 1 ± 1.3 and 0.2 ± 0.6 (p = 0.002) and the mean ± standard deviation Voice Handicap Index 10 scores were 0.5 ± 1.2 and 1.2 ± 1.7 (p = 0.27), respectively. CONCLUSION: Obese individuals had poorer vocal quality as judged by the grade-roughness-breathiness-asthenia-strain scale, and reduced maximum phonation time. However, there was no change in voice quality as assessed by acoustic analysis and Vocal Handicap Index 10 score, compared with controls.

Polymorphisms in angiotensin-converting enzyme and glutathione s-transferase genes in Turkish population and risk for preeclampsia.

AIMS: This study was conducted to investigate whether insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene and polymorphisms in glutathione S-transferase (GST) M1 and T1 genes are associated with increased risk for preeclampsia. MATERIALS AND METHODS: Sixty-three patients with hypertensive disorder of pregnancy and 85 controls were evaluated in a prospective case-control study. All subjects were genotyped by polymerase chain reaction (PCR) followed by agarose gel electrophoresis. RESULTS: Allele frequencies of ACE gene I/D polymorphism were found significantly different between preeclampsia and the control groups (p = 0.001). Differences in genotype frequencies of ACE gene I/D polymorphism between the two groups were statistically significant (p = 0.004). Individuals homozygous for D allele were more likely to develop preeclampsia (OR = 2.29; 95% CI, 1.39-3.79), whereas heterozygous individuals were not at increased risk (OR = 0.92; 95% CI, 0.56-1.49), compared to individuals homozygous for I allele. The differences in frequencies of functional and null alleles of GSTM1 and GSTT1 genes between the two groups were not significant (p = 0.46 and p = 0.44, respectively). CONCLUSION: ACE gene DD genotype was found to be associated with increased risk of preeclampsia development, whereas the authors did not find any significant relationship with polymorphisms of the GSTM1 and GSTT1 genes and preeclampsia.

Perinatal asphyxia is associated with the umbilical cord nucleated red blood cell count in pre-eclamptic pregnancies.

Nucleated red blood cells are commonly present in the blood of newborns. Our objective was to investigate the value of umbilical cord nucleated red blood cell (NRBC) count in predicting fetal asphyxia in pre-eclamptic women. NRBCs were counted in umbilical cord blood samples of neonates born to 43 pre-eclamptic and 25 healthy pregnant women. Pre-eclamptic women were further subgrouped based on the presence or absence of intrauterine growth restriction. The NRBC count differed significantly between pre-eclamptic women with and without intrauterine growth restriction, and controls (26.3 +/- 7.5; 17.1 +/- 6.8; and 9.9 +/- 2.7; p < 0.001). A NRBC count of 18.5 or above could predict fetal asphyxia with a sensitivity of 94.4% and a specificity of 80.0%. The umbilical cord NRBC count is effective in predicting fetal asphyxia in pre-eclamptic women.

A comparison of low-dose and high-dose protocols of vaginal misoprostol for second trimester termination of pregnancy.

Sixty patients were randomized to low-dose and high-dose groups, receiving a maximum total dose 1400 g of misoprostol by the vaginal route to compare the efficacy of the protocols for second trimester termination of pregnancy. Outcome measures to be compared between the groups were success rates, time to termination, blood loss, complications and side-effects. Yet time to termination was significantly shorter in the high-dose than in the low-dose group (923 +/- 571 vs 1307 +/- 828 min; p < 0.05). The distance between the internal cervical os and the placenta was positively correlated with the duration of the termination process (r = 0.508, p < 0.001). Induction to the fetal expulsion period is shorter with the higher dose without any significant increase in morbidity. A shorter distance between the internal cervical os and the placenta may forecast a shorter termination process.

Idiopathic thrombocytopenic purpura in pregnancy: a single institutional experience with maternal and neonatal outcomes.

We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by preeclampsia, one by ablatio placentae, and one by intrauterine death. Seven mothers received corticosteroid treatment, four high-dose immunoglobulin therapies, and one underwent splenectomy in the second trimester of gestation. At the time of delivery six mothers had normal platelet counts and seven had low platelet counts. Nine deliveries were by vaginal route and four were by cesarean section. Eleven infants were born with normal platelet counts and one was thrombocytopenic at the time of delivery. No infant showed any clinical signs of hemorrhage and there were no neonatal complications. Two fetuses died; one of them because of ablatio placentae and the other was intrauterine dead. In conclusion, ITP in pregnancy requires the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, anesthesiologist, and neonatologist is essential.

Placental and decidual lipid peroxidation and antioxidant defenses in preeclampsia. Lipid peroxidation in preeclampsia.

We evaluated lipid peroxidation in serum, placenta and decidua basalis and antioxidant defenses in preeclampsia and normal pregnancy. The study group consisted of 70 women with preeclampsia and 72 healthy pregnant women. Lipid peroxides in serum, placenta and decidua basalis, and serum vitamin E and total carotene were measured by spectrophotometric methods. Unpaired Student's t-test, chi(2)-test and Pearson correlation test were used for the statistical analyses. Levels of lipid peroxides in serum, placenta and decidua basalis were markedly higher; and serum vitamin E, total carotene, bilirubin, albumin levels were markedly lower in preeclamptic pregnants compared with healthy pregnant women. Our findings demonstrated that both placenta and decidua basalis tissues may be a source of lipid peroxides in preeclamptic pregnancies. Prophylactic antioxidant therapy may abate the disease process. Further studies are needed to clarify the pathophysiology of preeclampsia and effectiveness of prophylactic antioxidant therapy in preeclampsia.

The role of plasma renin activity in distinguishing patients with polycystic ovary syndrome (PCOS) from oligomenorrheic patients without PCOS.

All the components of the renin-angiotensin system have been identified in the human ovary. Renin plays a major role in folliculogenesis, and possibly in follicular atresia. Polycystic ovary syndrome (PCOS) is characterized by early follicular atresia. We studied whether assessment of plasma renin activity would be useful for diagnosing PCOS and distinguishing PCOS and non-PCOS in oligomenorrheic patients. Patients were divided into three groups: PCOS group (group 1, n = 40), non-PCOS oligomenorrheic group (group 2, n = 30) and ovulatory control group (group 3, n = 30). Plasma renin activity was determined in the early follicular phase of the menstrual cycle. Baseline serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, aldosterone and androgens (total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and 17alpha hydroxyprogesterone) were determined in all groups. The mean LH level was lower (4.94 +/- 4.65 mIU/ml) in control patients than in PCOS patients (12.9 +/- 1.75 mIU/ml) and non-PCOS oligomenorrheic patients (10.8 +/- 1.65 mIU/ml). There was no statistically significant difference between the groups regarding FSH levels. The mean plasma renin activity was 3.47 +/- 0.29 ng/ml in the PCOS group. The mean plasma renin activity was 1.59 +/- 0.21 ng/ml the non-PCOS oligomenorrheic group (statistically significiant differrence). There was no statistically significant difference between the non-PCOS oligomenorrheic (1.59 +/- 0.21 ng/ml) and control groups (1.2 +/- 0.16 ng/ml). Use of plasma renin activity alone as a diagnostic marker in PCOS is not useful, because the clinical findings of PCOS are heterogeneous and the pathogenesis is unclear. However, it can be used together with other variables to diagnose women with PCOS and to distinguish non-PCOS oligomenorrheic women from those with PCOS.

Peritoneal tuberculosis with pelvic abdominal mass, ascites and elevated CA 125 mimicking advanced ovarian carcinoma: a series of 10 cases.

Ten patients with peritoneal tuberculosis who were operated on for suspected advanced ovarian cancer during a 5-year period were analyzed. These 10 cases constituted 1.4% of the 728 new gynecologic cancer cases diagnosed and treated at our department during the same time period. Data were obtained from patients' files and pathology reports. The mean age of cases was 40.6 +/- 6.1 (median 37; range 18-72). Ascites was present together with ill-defined nodularities or thickening in the Douglas pouch and/or in the adnexal areas on pelvic examination in all patients but three, who presented with well-demarcated adnexal masses of about 5 cm in diameter. All patients had elevated serum CA 125 levels with a median of 331 U/ml, (40-560 U/ml). Ultrasound and abdominopelvic CT examinations revealed omental and mesenteric thickening in addition to ascites in all patients, cystic ovarian masses or ovarian enlargement in five, and peritoneal implants in two. Abdominal paracentesis performed in the six cases in whom the findings were felt to be most inconclusive for the diagnosis of ovarian cancer revealed clear exudative fluid with benign cells. Mycobacteria could not be demonstrated on direct preparations. Tuberculosis was diagnosed at laparotomy in all. Patients received antituberculous therapy and serum CA 125 levels returned to normal within 2 months after the beginning of treatment. This case series demonstrates a high rate of misdiagnosis between advanced ovarian cancer and peritoneal tuberculosis. Whereas abdominal paracentesis is useless in ruling out peritoneal tuberculosis, and serum CA 125 levels are not helpful in the differential diagnosis, the latter marker may be useful in the follow-up of patients.

Detection of endometrial pinopodes by light microscopy.

OBJECTIVE: To study the value of light microscopy (LM) in the assessment of endometrial pinopodes. DESIGN: Comparative histologic study. SETTING: Outpatient infertility clinic in an academic teaching institution. PATIENT(S): Eighteen oocyte donors undergoing controlled ovarian hyperstimulation. INTERVENTION(S): Endometrial biopsies on days 14-24 of the cycle. MAIN OUTCOME MEASURE(S): Assessment of pinopodes by scanning electron microscopy (SEM) and of endometrial surface projections by LM. RESULT(S): The luminal surface was identified by LM in 36 of 38 endometrial specimens obtained. Although apical projections could be recognized in all, they were few, moderate, and abundant in 20, 12, and 4 cases, respectively. Pinopodes were detected by SEM in all 4 samples with abundant projections, but in only 14 of 32 samples with lesser quantities of these surface features. No predictive value could be ascribed to apical projections viewed by LM for the developmental stage of pinopodes as defined by SEM. CONCLUSION(S): The LM of routine endometrial specimens can serve as a preliminary tool in the evaluation of surface morphology. Although abundant apical projections by LM are compatible with the presence of pinopodes by SEM, the latter modality remains as the definitive method in cases with few or moderate projections and for the evaluation of the stage of pinopode development.

Endometrial estrogen and progesterone receptor and pinopode expression in stimulated cycles of oocyte donors.

OBJECTIVE: To study the effect of controlled ovarian hyperstimulation and the ovarian response on several features of endometrial morphology simultaneously. DESIGN: Prospective controlled study. SETTING: Academic infertility center. PATIENT(S): Twenty-five oocyte donors undergoing COH and 10 ovulatory controls. INTERVENTION(S): Endometrial biopsies during the luteal phase and measurement of serum E2 and progesterone levels on days 12, 13, and 18-20. MAIN OUTCOME MEASURE(S): Endometrial morphology as judged by histologic dating, pinopode expression, and estrogen and progesterone receptor content. RESULT(S): Controlled ovarian hyperstimulation caused the early expression of endometrial features as judged by histologic dating criteria, estrogen and progesterone receptor expression, and the timing of pinopode expression in many of the subjects. A significant correlation within subjects with regard to their particular result on any one measure (e.g., histologic examination) and the others (e.g., estrogen and progesterone receptors, pinopodes) was observed. Those with higher levels of progesterone the day after hCG administration exhibited the most prematurity of morphologic features. CONCLUSION(S): Many controlled ovarian hyperstimulation cycles are associated with synchronous early expression of the expected pattern of histologic features, estrogen and progesterone receptors, and pinopodes. The most predictive feature of this premature expression was the level of progesterone the day after hCG administration.

The value of basal serum follicle stimulating hormone, luteinizing hormone and oestradiol concentrations following pituitary down-regulation in predicting ovarian response to stimulation with highly purified follicle stimulating hormone.

The value of gonadotrophin and oestradiol concentrations following pituitary down-regulation with leuprolide acetate in predicting ovarian response to stimulation was evaluated in three groups of women undergoing ovarian stimulation for in-vitro fertilization with highly purified follicle stimulating hormone (FSH). Leuprolide acetate was started in the midluteal phase, and either stopped at menses (IVF-SL group, n = 3), or continued throughout stimulation (IVF-LL group, n = 38; oocyte donors, n = 58). Ovarian stimulation was started on cycle day 3, after blood was drawn for down-regulated FSH, luteinizing hormone (LH) and oestradiol. Higher down-regulated LH was predictive of higher oestradiol on day 5 of stimulation in both IVF groups, and of need for fewer ampoules in the IVF-LL group, but not of oestradiol on day of human chorionic gonadotrophin (HCG) administration or number of oocytes retrieved. Higher FSH after down-regulation predicted yield of fewer oocytes in the donor and IVF-LL groups, and higher oestradiol on day 5 of stimulation, need for fewer ampoules and a shorter duration of therapy in both IVF groups. Higher oestradiol after down-regulation was associated with higher oestradiol on day 5 of stimulation and on day of HCG administration, a shorter duration of therapy and need for fewer ampoules in all groups. Whereas these results do not ascribe any predictive significance to LH, they suggest that oestradiol and FSH concentrations after down-regulation are predictive of the pattern of ovarian response to stimulation and of oocyte yield.

Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles.

The formation of endometrial pinopodes detected by scanning electron microscopy may be a specific marker for uterine receptivity. Aiming to assess the effects of ovarian stimulation on pinopode formation, we examined sequential endometrial biopsies from 17 oocyte donors. Seven normally menstruating women served as controls. Up to four samples were taken from each woman at 24-72 h intervals between days 14 and 24, giving a total of 69 samples. The day of oocyte retrieval was designated day 14 in ovarian stimulation cycles and the day of luteinizing hormone surge was designated day 13 in natural cycles. Endometrial morphology and pinopode numbers were similar in both groups. Fully developed pinopodes appeared in only one sample per cycle, indicating their short life span. However, the cycle day these structures appeared varied up to 5 days between women and the distribution was as follows: day 18 (n = 2), day 19 (n = 7), day 20 (n = 4), day 21 (n = 3), day 22 (n = 1) in ovarian stimulation cycles, and day 20 (n = 2), day 21 (n = 2), day 22 (n = 3) in natural cycles. Furthermore, accelerated pinopode formation in ovarian stimulation cycles was positively correlated with day 13 progesterone. Our findings show that ovarian stimulation does not affect endometrial pinopode formation in terms of quantity and life span. The cycle days when pinopodes form are specific to the individual, being on average 1-2 days earlier in ovarian stimulation than in natural cycles. These changes in pinopode expression may reflect shifts in the window of receptivity, resulting in ovo-endometrial asynchrony and limiting implantation success in in-vitro fertilization.

Adjunctive use of the uterine artery resistance index in the preoperative prediction of myometrial invasion in endometrial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the value of transvaginal ultrasonography (TVUS) and uterine artery flow velocimetry indices in the preoperative detection of deep myometrial invasion in endometrial carcinoma (EC). METHODS: Thirty-nine patients with EC underwent TVUS and Doppler flow velocimetry studies, during which endometrial, myometrial, and uterine measurements, presence and depth of myometrial invasion, and pulsatility and resistance indices (PI and RI, respectively) of uterine arteries were noted. TVUS and Doppler findings were correlated with pathological findings obtained by surgical staging. The respective diagnostic accuracies of these variables, and of age and grade, in detecting deep myometrial invasion were assessed with the use of histological findings as the standard. RESULTS: All patients with Grade 3 tumors had deep myometrial invasion, compared to 19% of patients with Grade 1 tumors. The mean age of patients with deep invasion was significantly higher, and their mean PI and RI were significantly lower, than patients with lesser degrees of invasion. While the sensitivity and specificity of TVUS in detecting deep invasion were 37 and 90%, respectively, the corresponding figures for age, grade, and uterine artery RI, found to be independent discriminators of deep invasion, were in the range of 58-84% and 60-70%. The combined use of the latter three parameters resulted in a sensitivity of 100% and specificity of 95%. CONCLUSIONS: Our findings indicate that TVUS is unreliable in diagnosing deep myometrial invasion. Detection rates of this pathological feature can be greatly improved, however, with the concomitant use of age, tumor grade, and uterine artery RI.

Risk factors for groin node metastasis in squamous carcinoma of the vulva: a multivariate analysis of 39 cases.

This study includes 39 patients with squamous carcinoma of the vulva subjected to radical surgery. Stage, tumor description, cell type, lesion localization, lesion size, depth of invasion, grade, lymphovascular space invasion, number of mitoses, degree of stromal inflammatory reaction, and tumors in surgical margins were analyzed for groin metastasis. Of the factors analyzed, stage (P = 0.018), grade (P = 0.007) and depth of invasion (P = 0.001) were found to be the most important predictors of node metastasis. While a combination of factors permitted to define a low-risk group with 0% node metastasis, it seems hard to identify preoperatively those patients with no risk of nodal metastasis.

Activated protein C levels in patients with gynecologic tumors.

Activated protein C (APC) levels were measured in the plasma of patients with benign and malignant gynecologic tumors preoperatively, and on postoperative days 1 and 7. Preoperative levels of APC were found to be significantly low in both groups of patients compared to a group of healthy subjects. On postoperative day 1, levels of APC decreased significantly in both groups of patients compared to preoperative levels. By the 7th postoperative day, levels of APC in patients with benign tumors had increased significantly compared to postoperative day 1; levels in patients with malignant tumors, however, remained low. Our findings imply that there is a substantive correlation between gynecologic tumors, gynecologic surgery and the coagulation inhibitor, APC, which, in turn, can presumably be used to identify gynecologic patients who are at high risk for venous thrombosis.

Pelvic-peritoneal tuberculosis with elevated serum and peritoneal fluid Ca-125 levels. A report of two cases.

We report 2 patients with pelvic-peritoneal tuberculosis and elevated serum and peritoneal fluid levels of Ca-125. The first was a young and infertile women who had cul-de-sac nodularity and dysmenorrhea. The other was postmenopausal and presented with weight loss and ascites. While a preoperative diagnosis of endometriosis was made in the former, intraperitoneal malignancy was considered in the latter. The diagnosis of pelvic-peritoneal tuberculosis was reached by laparoscopic-directed biopsy in both patients. Serum levels of Ca-125 returned to normal limits following antituberculous drug treatment.

Complications of radical vulvectomy and inguinal lymphadenectomy for the treatment of carcinoma of the vulva.

Forty-two patients with invasive carcinoma of the vulva, subjected to radical vulvectomy and inguinal lymphadenectomy, were evaluated retrospectively. The mean age of patients was 61.6 years. Fifteen patients (35.7%) had complicating medical diseases, the histopathological diagnoses were squamous carcinoma (n = 39), undifferentiated carcinoma (n = 1), and malignant melanoma (n = 2). The postoperative morbidity and mortality rates were found to be 73.8% and 11.6%, respectively.

Laparoscopic CO2 laser uterine nerve ablation for treatment of drug resistant primary dysmenorrhea.

Twenty women with drug-resistant primary dysmenorrhea were subjected to laparoscopic CO2 laser uterine nerve ablation. Menstrual pain assessed by a linear analog pain score showed a reduction of 33%, decreasing from 7.5 +/- 0.5 preoperatively to 5.0 +/- 1.7 postoperatively. The procedure was free of major complications and should be considered as a second-line therapeutic option in women who have failed medical treatment using nonsteroidal antiinflammatory agents or OCs.