Immunohistochemical expression of MTA1 and MTA3 in placental tissue of normal and preeclamptic pregnancies.

PURPOSE: The aim of this preliminary study was to evaluate and compare MTAI andMTA3 antigens expression in normal and preeclamptic placentas in order to demonstrate their possible functional relationship during pathogenesis of preeclampsia. MATERIALS AND METHODS: A series including 20 paraffin-embedded placentas, ten of which originated from normal patients and ten from preeclamptic patients, that were examined by immunohistochemistry using the polyclonal antibodies MTAI and MTA3. RESULTS: The results of this study showed a positive nuclear staining reaction against MTAI and MTA3 in both normal and preeclamptic placentas. However, in preeclamptic chorionic villi, cytotrophoblast and syncytiotrophoblast cells demonstrated increased expression of MTAI and MTA3 than in normal ones. CONCLUSION: The present observations indicate a potential role for MTAI and MTA3 for normal human placental function, playing an essential role in the pathogenesis of preeclampsia. Nevertheless, the precise relationship between these antigens' expression and pathological pregnancies remains to be elucidated.

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis).

The oestrogenised vagina is colonised by Candida species in at least 20% of women; in late pregnancy and in immunosuppressed patients, this increases to at least 30%. In most cases, Candida albicans is involved. Host factors, particularly local defence mechanisms, gene polymorphisms, allergies, serum glucose levels, antibiotics, psycho-social stress and oestrogens influence the risk of candidal vulvovaginitis. Non-albicans species, particularly Candida glabrata, and in rare cases also Saccharomyces cerevisiae, cause less than 10% of all cases of vulvovaginitis with some regional variation; these are generally associated with milder signs and symptoms than normally seen with a C. albicans-associated vaginitis. Typical symptoms include premenstrual itching, burning, redness and odourless discharge. Although itching and redness of the introitus and vagina are typical symptoms, only 35-40% of women reporting genital itching in fact suffer from vulvovaginal candidosis. Medical history, clinical examination and microscopic examination of vaginal content using 400× optical magnification, or preferably phase contrast microscopy, are essential for diagnosis. In clinically and microscopically unclear cases and in chronically recurring cases, a fungal culture for pathogen determination should be performed. In the event of non-C. albicans species, the minimum inhibitory concentration (MIC) should also be determined. Chronic mucocutaneous candidosis, a rarer disorder which can occur in both sexes, has other causes and requires different diagnostic and treatment measures. Treatment with all antimycotic agents on the market (polyenes such as nystatin; imidazoles such as clotrimazole; and many others including ciclopirox olamine) is easy to administer in acute cases and is successful in more than 80% of cases. All vaginal preparations of polyenes, imidazoles and ciclopirox olamine and oral triazoles (fluconazole, itraconazole) are equally effective (Table ); however, oral triazoles should not be administered during pregnancy according to the manufacturers. C. glabrata is not sufficiently sensitive to the usual dosages of antimycotic agents approved for gynaecological use. In other countries, vaginal suppositories of boric acid (600 mg, 1-2 times daily for 14 days) or flucytosine are recommended. Boric acid treatment is not allowed in Germany and flucytosine is not available. Eight hundred-milligram oral fluconazole per day for 2-3 weeks is therefore recommended in Germany. Due to the clinical persistence of C. glabrata despite treatment with high-dose fluconazole, oral posaconazole and, more recently, echinocandins such as micafungin are under discussion; echinocandins are very expensive, are not approved for this indication and are not supported by clinical evidence of their efficacy. In cases of vulvovaginal candidosis, resistance to C. albicans does not play a significant role in the use of polyenes or azoles. Candida krusei is resistant to the triazoles, fluconazole and itraconazole. For this reason, local imidazole, ciclopirox olamine or nystatin should be used. There are no studies to support this recommendation, however. Side effects, toxicity, embryotoxicity and allergies are not clinically significant. Vaginal treatment with clotrimazole in the first trimester of a pregnancy reduces the rate of premature births. Although it is not necessary to treat a vaginal colonisation of Candida in healthy women, vaginal administration of antimycotics is often recommended in the third trimester of pregnancy in Germany to reduce the rate of oral thrush and napkin dermatitis in healthy full-term newborns. Chronic recurrent vulvovaginal candidosis continues to be treated in intervals using suppressive therapy as long as immunological treatments are not available. The relapse rate associated with weekly or monthly oral fluconazole treatment over 6 months is approximately 50% after the conclusion of suppressive therapy according to current studies. Good results have been achieved with a fluconazole regimen using an initial 200 mg fluconazole per day on 3 days in the first week and a dosage-reduced maintenance therapy with 200 mg once a month for 1 year when the patient is free of symptoms and fungal infection (Table ). Future studies should include Candida autovaccination, antibodies to Candida virulence factors and other immunological experiments. Probiotics with appropriate lactobacillus strains should also be examined in future studies on the basis of encouraging initial results. Because of the high rate of false indications, OTC treatment (self-treatment by the patient) should be discouraged.

Point-of-care (POC) diagnosis of bacterial vaginosis (BV) using VGTest™ ion mobility spectrometry (IMS) in a routine ambulatory care gynecology clinic.

PURPOSE: A new CE-marked portable desktop ion mobility spectrometer (VGTest) was used for detection of malodorous biogenic amines indicative of bacterial vaginosis (BV). This study aimed to assess the performance of this testing method for the first time in a routine ambulatory care clinic and to determine the relative levels of biogenic amines in vaginal fluid of BV. METHODS: Vaginal and cervical swabs (n = 57) were surveyed for infections. Cases of BV (n = 18) confirmed positive according to "Amsel" criteria and normal controls (n = 39) showing no infection under clinical examination and testing negative in wet mount microscopy were included in the IMS analysis. RESULTS: The trimethylamine (TMA) content in vaginal fluid of the BV-positive cases, AUCTMA/AUCTotal [mean 0.215 (range 0.15-0.35)] was significantly higher than normal controls [mean 0.06 (range 0.048-0.07)] p < 0.0001. The putrescine (1,4-diaminobutane, PUT) and cadaverine (1,5-diaminopentane, CAD) of BV-positive cases were above controls at borderline significance. The AUCTMA/AUCTotal ratios correlated neither with AUCPUT/AUCTotal nor AUCCAD/AUCTotal among BV-positive patients. In contrast, among normal controls all the biogenic amines were at a low level and the linear regression analysis revealed striking positive correlations of AUCTMA/AUCTotal with AUCPUT/AUCTotal (p < 0.05) and AUCCAD/AUCTotal (p < 0.001). The test shows 83 % sensitivity and 92 % specificity at a cut-off of AUCTMA/AUCTotal = 0.112 and AUC of receiver operator characteristic = 0.915 (0.81-0.97, 95 % CI). CONCLUSIONS: VGTest-IMS is accurate and feasible for point-of-care testing of BV in the ambulatory care setting. Further evaluations are in progress to assess the utility of VGTest-IMS for differential diagnosis of candidosis, non-BV infection and common inflammatory conditions.

Managing hyperemesis gravidarum: a multimodal challenge.

Up to 90% of pregnant women experience nausea and vomiting. When prolonged or severe, this is known as hyperemesis gravidarum (HG), which can, in individual cases, be life threatening. In this article the aetiology, diagnosis and treatment strategies will be presented based on a selective literature review. Treatment strategies range from outpatient dietary advice and antiemetic drugs to hospitalization and intravenous (IV) fluid replacement in persistent or severe cases. Alternative methods, such as acupuncture, are not yet evidence based but sometimes have a therapeutic effect.In most cases, the condition is self limiting and subsides by around 20 weeks gestation. More severe forms require medical intervention once other organic causes of nausea and vomiting have been excluded. In addition, a psychosomatic approach is often helpful.In view of its potential complexity, general practitioners and obstetricians should be well informed about HG and therapy should be multimodal.

Interleukin-6, interleukin-10 and interleukin-12 in vaginal fluid from women with bacterial vaginosis.

BACKGROUND: There has been a recent recognition on the influence of local vaginal immunity on the acquisition of vulvovaginal disorders and their adverse consequences. Variations in local immune responses seem to play an important role in susceptibility to different vaginal infections as well as to the likelihood of recurrences. Bacterial vaginosis (BV), the most frequent vaginal disorder in most populations, is enigmatic in that the etiology is unknown, recurrences are common and vaginal inflammation is absent. We investigated the influence of BV on the vaginal concentration of the pro-inflammatory cytokine interleukin (IL)-12, the pleiotropic cytokine IL-6 and the anti-inflammatory cytokine IL-10 in non-pregnant women. METHODS: Vaginal lavage samples were obtained from 45 patients with BV and from 46 asymptomatic controls. The supernatant fractions were examined for IL-6, IL-10 and IL-12 by commercial ELISAs. Analysis of the cytokine levels in the two groups was by the Mann-Whitney test. RESULTS: IL-6 concentrations varied considerably among women in the BV and control groups but the median levels were almost identical. The median concentrations of IL-10 and IL-12 were uniformly low in both groups but median levels were not statistically different. CONCLUSION: The marked alteration in the vaginal bacterial flora that is characteristic of BV does not result in enhancement or inhibition of the vaginal levels of IL-6, IL-10 and IL-12. Mechanisms to explain this striking lack of immune system variation remain to be determined.

Genital tuberculosis as the cause of tuboovarian abscess in an immunosuppressed patient.

BACKGROUND: Although tuberculosis (TB) is a major health problem worldwide, primary extrapulmonary tuberculosis (EPTB), and in particular female genital tract infection, remains a rare event. CASE REPORT: A 35-year-old human immunodeficiency virus (HIV) seropositive woman of African descent with lower abdominal pain and fever of two days duration underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The surgical situs showed a four quadrant peritonitis, consistent with the clinical symptoms of the patient, provoked by a tuboovarian abscess (TOA) on the left side. All routine diagnostic procedures failed to determine the causative organism/pathogen of the infection. Histopathological evaluation identified a necrotic granulomatous salpingitis and specific PCR analysis corroborated Mycobacterium tuberculosis (M. Tb). Consequently, antituberculotic therapy was provided. CONCLUSION: In the differential diagnosis of pelvic inflammatory disease, internal genital tuberculosis should be considered. Moreover, physicians should consider tuberculous infections early in the work-up of patients when immunosuppressive conditions are present.

Extended hyperemesis gravidarum in a patient after total thyroidectomy.

INTRODUCTION: Human chorionic gonadotropin is regarded as, at least, one of the main factors responsible for hyperemesis gravidarum by direct stimulation of the thyroid gland on the basis of a close homology to the structure of TSH. However, questions to this theory of hCG-induced gestational hyperthyroidism still remain. CASE REPORT: We present for the first time a rare case of hyperemesis gravidarum in a patient with a previous removed thyroid gland and an adequate thyroxin replacement. In this case report we present an extended hyperemesis gravidarum in a patient after total thyroidectomy and thus artificially well-set thyroid parameters. CONCLUSION: Although transient hyperthyroidism is widely thought to be causative of a hyperemesis during pregnancy, this case report with a mildly hypothyroidism emphasizes that there might be other, yet unknown, factors that can cause such a severe complication.

Relationship between clinical diagnosis of recurrent vulvovaginal candidiasis and detection of Candida species by culture and polymerase chain reaction.

BACKGROUND: Recurring vulvovaginal candidiasis (RVVC) is a common vaginal discharge affecting 75% of all women at least once in their life. In 5% of these women, infection is recurring. Aim of the study was to determine the sensitivity of detecting Candida species by culture and polymerase chain reaction (PCR) in women with a clinical diagnosis of RVVC. METHODS: A total number of 104 patients referred with a clinical diagnosis of RVVC and therefore at least four episodes in the previous year were evaluated. In order to detect Candida, vaginal swabs were cultured on Sabouraud and chromagar. Furthermore, the supernatant from the vaginal lavage was examined for the presence of Candida by PCR. RESULTS: When the culture was analyzed, only 31 (29.8%) of the 104 patients diagnosed with RVVC were positive for Candida species in their vagina. Candida albicans was identified in 25 women and six were positive for Candida glabrata. When analyzed by PCR, 44 (42.3%) patients were positive for Candida species. In 13 women (12.5%) only the PCR was positive, while in 31 patients both culture and PCR were positive. CONCLUSION: The diagnostic method of PCR is more sensitive than culture in detecting Candida species in the vagina. The results also suggest further investigation to verify the complaints of the negative tested patients.

Expression of galectin-1, -3 (gal-1, gal-3) and the Thomsen-Friedenreich (TF) antigen in normal, IUGR, preeclamptic and HELLP placentas.

BACKGROUND: Galectin-1 (gal-1) and galectin-3 (gal-3), which are members of the mammalian beta-galactoside-binding proteins, recognise preferentially (Galbeta1-4GlcNAc) sequences of several cell surface oligosaccharides. In addition, gal-1 also binds to the Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc-). MATERIALS AND METHODS: Slides of frozen and paraffin-embedded placental tissue of patients with fetal intrauterine growth retardation (IUGR), preeclampsia, haemolysis, elevated liver enzymes, low platelets (HELLP) and normal term placentas were incubated with monoclonal and polyclonal antibodies against gal-1, gal-3 and TF. Staining reaction was performed with the avidin-biotinylated peroxidase complex (ABC) reagent. The intensity of the immunohistochemical reaction on the slides was analysed using a semi-quantitative score. The identity of galectin-expressing cells was analysed by using a double immunofluorescence method. RESULTS: We demonstrated immunohistochemically that the expression of gal-1 and gal-3 on the extravillous trophoblast (EVT) is significantly up-regulated in preeclamptic and HELLP placentas and unchanged compared with normal controls in IUGR placentas. The expression of the TF antigen is significantly up-regulated in IUGR and preeclamptic extravillous trophoblast cells and unchanged in HELLP placentas compared with normal controls. In addition, the expression of gal-1 is significantly up-regulated in the decidual tissue of preeclamptic placentas and in the villous trophoblast tissue of HELLP placentas. CONCLUSION: Our data showed that gal-1, gal-3 and TF were up-regulated on the membrane of EVT in preeclamptic placentas. In addition, the expression of gal-1 is significantly up-regulated in decidual tissue of preeclamptic placentas and villous trophoblast tissue of HELLP placentas. Taking into consideration the results of this study, we speculate that expression of both galectins and TF on the membrane of preeclamptic EVT and up-regulation of gal-1 in preeclamptic decidual cells may at least in part compensate for the apoptotic effects of maternal immune cells.

Quality of life among breast cancer patients undergoing autologous breast reconstruction versus breast conserving therapy.

PURPOSE: Besides the quality of the aesthetic results, the quality of life after surgery is one of the most important criteria when reviewing different operation methods, especially in oncologic diseases. This study was performed to evaluate the difference in the health-related quality of life following breast conserving surgery and autologous breast reconstruction after mastectomy. PATIENTS AND METHODS: Hundred and forty-four breast cancer patients were included in this study. Sixty seven patients underwent breast conserving surgery followed by radiotherapy. In 77 patients a mastectomy was performed with immediate or late reconstruction. To evaluate the health-related quality of life we used the SF-36 self-administered questionnaire. RESULTS: A significant difference was found in quality of life in the subscale "physical functioning" showing better results in the breast reconstruction group (P = 0.01). No significant difference was found in the other subscales, but there was a tendency to a better "emotional role" among the breast reconstruction patients. CONCLUSION: Our study demonstrated that autologous tissue breast reconstruction in breast cancer patients did not affect adversely the health-related quality of life compared to breast conserving therapy when the quality of life is assessed by the standardized questionnaire SF-36. In particular, the physical function is not reported to be significantly influenced negatively by the more extensive surgical therapy.

Maternal serum corticotropin-releasing hormone and ACTH levels as predictive markers of premature labor.

OBJECTIVE: To investigate whether corticotropin-releasing hormone (CRH) and corticotropin (ACTH) plasma concentrations in women diagnosed with preterm labor are of potential clinical value in the assessment of the risk of preterm birth. METHOD: Plasma samples of 79 women diagnosed with preterm labor were used in this study. Samples were divided into three groups based on the week of gestation (24th-28th, 29th-32nd, 33rd-37th). CRH and ACTH values were determined by ELISA. RESULT: Mean maternal peripheral plasma values of CRH and ACTH were significantly higher (p<0.001) in women who were initially diagnosed with preterm labor and finally delivered a preterm birth, compared to women with the same diagnosis but with term birth. CONCLUSION: CRH and ACTH serum levels in women diagnosed with preterm labor could be used as predictors for the timing of parturition.

Expression of inhibin/activin subunits alpha (-alpha), betaA (-betaA), and betaB (-betaB) in placental tissue of normal, preeclamptic, and HELLP pregnancies.

During human pregnancy the placenta produces a variety of proteins for the establishment of the fetoplacental unit, including inhibins and activins. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB). Aims of the present study were (a) the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and (b) the assessment of a combined expression of inhibin-alpha- and both beta-subunits (betaA-and betaB-subunits) using double immunofluorescence technique. A significant lower expression of the inhibin-alpha subunit in preeclamptic and HELLP placental tissue compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytotrophoblast. Additionally, we demonstrated a significant down-regulation of inhibin-betaB subunit in extravillous trophoblast cells between normal and preeclamptic compared to HELLP placental tissue, while inhibin-betaA-subunit was significantly higher in preeclamptic syncytotrophoblast cells. A colocalization of inhibin-alpha and the beta-subunits could be demonstrated, suggesting a production and secretion of intact inhibin A and inhibin B. Therefore, inhibin A and activin A might be useful markers in preeclampsia. Valuable parameters in HELLP syndrome could be inhibin A, rather than inhibin B, and activin B. Furthermore, the lower betaB-subunit production in extravillous trophoblast cells demonstrates that this subunit might have an important role in the pathogenesis of HELLP syndrome. Additionally, the higher production of the betaA-subunit in syncytotrophoblast cells suggest a higher production of activin A rather than inhibin A in preeclampsia that might be utilized as a marker of placental function.

[Systemic infections in obstetrics]. / Systemische Infektionen in der Geburtshilfe.

The importance of systemic infections in pregnancy is often underestimated. This is primarily due to the fact that pregnant women, in the majority of cases, do not notice any complaints or only have unspecific flu-like symptoms (e.g. toxoplasmosis). Serological screening within the framework of German maternity care is often insufficient to diagnose existing or emerging infections in time. However, the long-term consequences for the affected children and their parents can be immense. A serological TORCH analysis should be performed if a pregnant woman complains about any typical or unspecific symptoms on suspicion of an infection.

Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015)

Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

Expression of glycodelin A in decidual tissue of preeclamptic, HELLP and intrauterine growth-restricted pregnancies.

During pregnancy, the placenta produces a variety of proteins that are responsible for the establishment of the foeto-maternal tolerance and circulation. The aim of this study was to investigate the expression of glycodelin A (formerly named PP14) in decidual tissue of placentas with intrauterine growth restriction (IUGR), preeclamptic patients, hemolysis, elevated liver, low-platelet (HELLP) patients and normal decidual tissue. Slides of paraffin-embedded decidual tissue of patients with IUGR, preeclamptic patients, HELLP patients and normal-term placentas were incubated with either polyclonal or monoclonal antibodies against glycodelin A. Staining reaction was performed with the ABC reagent. Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score. In addition, expression of glycodelin mRNA was analysed by in situ hybridisation. Expression of glycodelin A was significantly reduced in decidual cells of placentas with IUGR and HELLP, as investigated with both monoclonal and polyclonal antibodies and in situ hybridisation. However, preeclamptic decidual tissue showed no significantly different expression of intensity of glycodelin mRNA compared with normal placental tissue controls. A reduced expression of glycodelin A by decidual cells seems to be related to IUGR and HELLP. Therefore, glycodelin A might play an important role in the pathogeneses of these diseases.

Normal and malignant human endometrium express immunohistochemically estrogen receptor alpha (ER-alpha), estrogen receptor beta (ER-beta) and progesterone receptor (PR).

Human endometrium expresses estrogen (ER) and progesterone (PR) receptors, which are related to autocrine and paracrine processes that respond to estrogen and progesterone. The ER and PR expression and distribution pattern may play an important role in endometrial function and pathogenesis. The aim of this study was to evaluate the distribution pattern of ER-alpha, ER-beta and PR in normal (n=15) and malignant (n=11) human endometrial tissue. Commercially available monoclonal antibodies against ER-alpha, ER-beta and PR were used. The distribution of the steroid receptors was evaluated using the IRS-score and the Mann-Whitney rank-sum test was used to compare the means. Correlation was assessed with the Spearman factor and linear regression analysis. ER-alpha, ER-beta and PR declined significantly (p <0.05) in normal glandular epithelium from proliferative to late secretory phase, although the staining intensity of ER-beta was lower than that of ER-alpha. ER-alpha, ER-beta and PR were also expressed in malignant endometrial tissue. A significant correlation by regression analysis of ER-alpha and ER-beta was demonstrated, showing a dependence in the expression of these steroid receptors. The ER-alpha/ER-beta ratio decreased significantly from normal to malignant endometrial tissue (p<0.05), while the ER-beta/ER-alpha ratio showed statistical differences within normal endometrial tissue. These results showed the presence of steroid receptors in normal and malignant human endometrium, indicating a significant role in endometrial physiology and malignant transformation.

Expression of inhibin/activin subunits, sialyl-lewis A (CA 19-9, sLea) and sialyl-Lewis X (sLex) carbohydrate antigens in a hydatidiform mole with persistent polymorphic trophoblastic hyperplasia.

UNLABELLED: The persistence of polymorphic trophoblastic hyperplasia in a hydatidiform mole is an extremely rare condition. Its early diagnosis is essential since such cases can transform into invasive tumours. MATERIALS AND METHODS: The paraffin-embedded biopsies were routinely stained with HE. Immunohistochemical staining reactions were performed with monoclonal antibodies against inhibin-alpha, inhibin-betaA and inhibin-betaB subunits. Additional immunohistochemical reaction was performed with, Sialyl-Lewis A and Sialyl-Lewis X and glycodelin. RESULTS: Large villi and hydatidiform villi with ranging syncyctio- and cytotrophoblasts were seen. Intervillous proliferating trophoblasts showed cell- and nuclear polymorphy with invasion of the myometrium wall. The immunohistochemistry exhibited strong positivity for inhibin-alpha, inhibin-betaA and inhibin-betaB subunits in trophoblastic tissue, while the decidua was negative. Sialyl-Lewis A and Sialyl-Lewis X showed no or minimal focal immunohistochemical reaction. CONCLUSION: A complete hydatidiform mole with hyperplasia and proliferation presents a high risk of developing a persistent (eventually metastatic) trophoblastic disorder and, in up to 15% of the cases, an invasive mole. In 2.5% of the cases it can transform into a choriocarcinoma. Since the inhibin/activin subunits reacted positively with trophoblastic tissue, they might be a useful diagnostic marker for hydatidiform mole with persistence of polymorphic trophoblastic hyperplasia.

A pilot, open label, clinical trial using hydroxyzine in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disorder of myelin destruction. Blood-brain-barrier (BBB) disruption precedes pathological or clinical findings and could involve mediators from perivascular brain mast cells, such as histamine and vascular endothelial growth factor (VEGF). Mast cells could be activated by many triggers, including acute stress that has been correlated with MS exacerbations. We considered that the histamine-1 (H1) receptor antagonist hydroxyzine, which also partially inhibits brain mast cells and has anxiolytic properties, may reduce MS symptoms. This open label, pilot, clinical trial investigated the effect on MS of an oral solution of hydroxyzine (100 mg per day), together with caffeine (200 mg per day) to reduce sedation. Twenty patients (8 males; 12 females) with relapsing-remitting or relapsing-progressive MS completed the study (12 +/- 1 months) and were evaluated using disability scales. Most patients on hydroxyzine (75%) remained stable or improved neurologically and all but one showed improved mood. Hydroxyzine could be used as an adjuvant in MS, but the small number of patients enrolled and the short duration of the study precludes any definitive conclusions. A double-blind, placebo-controlled study is warranted.