bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic efficacy of lithium administered every second day: a WHO multicentre study
Authors: Plenge P , Amin M , Agarwal Ak , Greil W , Kim M‐J , Panteleyeva G , Park J‐M , Prilipko L , Rayushkin V , Sharma M , Mellerup E
Published: March 2003

Objectives:

To study the prophylactic efficacy of lithium administered every second day to patients with bipolar disorder or recurrent unipolar depressive disorder.   Methods: The study was carried out as a WHO multicentre study in five different psychiatric clinics: Russia (Moscow), Canada (Montreal), India (Lucknow), Germany (Munich) and South Korea (Pusan), with the lithium tablets being supplied from Denmark (Copenhagen). Participation in the study was conditional on the patient having been in prophylactic lithium treatment for the preceding 2‐year period and having been free of depressive or manic phases during the preceding 6 months. After a 2‐month baseline period during which lithium was administered every day, the treatment was changed to lithium intake every second day, this regimen in most cases being continued for 22 months.   Results: Forty‐seven patients, 42 with a diagnosis of bipolar disorder and five with a diagnosis of recurrent unipolar depressive disorder, participated in the study. The number of patients from each centre ranged from six to 11. The mean lithium dose every second day was 36 mmol lithium, leading to a mean 12‐h standard serum lithium concentration during the last month of treatment at 0.78±0.16 mmol/L. Lithium intake every second day was effective in 38 out of 47 patients. The remaining nine patients had recurrences, a number not differing from the 16 patients in the same group of 47 patients who, during the 2‐year period preceding the study, had recurrences. The mean 12‐h standard serum lithium concentration was lower in the patients who had recurrences than in those who stayed euthymic. The results suggest that to be effective when administered every second day, lithium must be given in a dose leading to a 12‐h standard serum lithium concentration at 0.8 mmol/L or above.   Conclusions: In the dose administered, lithium intake every second day was as effective as lithium intake every day. The amount and severity of lithium‐related side effects were apparently not influenced by the change to lithium intake every second day.
Searching high and low: a review of the genetics of bipolar disorder
Authors: Potash James B , DePaulo Jr J Raymond
Published: March 2003

Objectives: To review the methodologies and findings in the genetics of bipolar disorder (BPD), and to suggest future directions for research.   Methods: Reports of family, twin, adoption, linkage, association, cytogenetic, and animal model studies, and segregation analyses in English, were identified from multiple MEDLINE searches. Hand searches were carried out in bibliographies from review articles.   Results: Family, twin, and adoption studies have provided strong evidence for a genetic etiology in BPD. Early reports of linkage of BPD to DNA markers at several chromosomal sites have not proven robust, perhaps because of the complex nature of BPD inheritance. However, linkage findings in the 1990s, on chromosomes 18, 21q, 12q, and 4p, have provided leads that are being pursued through both genetic and physical mapping. No gene has yet been definitively implicated in BPD.   Conclusions: Strategies for increasing the power to detect BPD genes include: (1) dividing the phenotype into genetically meaningful subtypes to decrease heterogeneity; and (2) ascertaining a very large family sample – a multicenter study now in progress will collect 700 bipolar I sibling pairs. BPD may result from several genes acting in concert so that new multilocus statistical methods could enhance the capacity to detect loci involved. Family‐based association studies using a very large number of newly identified single nucleotide polymorphisms (SNPs) may allow for more efficient screening of the genome. As the Human Genome Project approaches its goal of isolating all genes by 2003, the data generated is likely to speed identification of candidate BPD genes.
An open study of methylphenidate in bipolar depression
Authors: El‐Mallakh Rif S
Published: March 2003

Background:

The treatment of bipolar depression is problematic. Mood stabilizing agents are often inadequate, while antidepressants may induce mania or mood destabilization. Methylphenidate has been advocated as an effective antidepressant agent in unipolar depression, and depression secondary to medical illness. Amphetamine administration has been shown to reduce manic behavior. These independent observations suggest that methylphenidate may be a safe and effective agent in bipolar depression.   Methods: Fourteen depressed subjects with DSM‐IV bipolar illness and a Hamilton‐depression (HAM‐D) scale score of at least 15 had methylphenidate added to a stable mood stabilizer regiment. Patients were followed weekly for 4 weeks and then biweekly for an additional 8 weeks.   Results: HAM‐D scores dropped from 16.9±1.79 SD at baseline to 9.4±9.73 on week 12 (p=0.12, t=1.84, df=6) and 9.8±7.56 on last observation carried forward (LOCF) (p=0.019, t=2.8, df=10). Psychiatric symptom assessment scale (PSAS) scores dropped from 17.9±5.63 at baseline to 4.8±7.47 at week 12 (p=0.016, t=4.02, df=4) and 6.3±6.75 on LOCF (p=0.007, t=3.74, df=7). Three individuals stopped secondary to anxiety, agitation, and hypomania, respectively.   Conclusion: In this brief, open study, methylphenidate was effective and relatively safe in depressed bipolar subjects.
Family environment of children and adolescents with bipolar parents
Authors: Chang Kiki D , Blasey Christine , Ketter Terence A , Steiner Hans
Published: March 2003

Objectives:
The effect of family environment on the development of bipolar disorder (BD) in children is not known. We sought to characterize families with children at high risk for developing BD in order to better understand the contributions of family environment to the development of childhood BD.   Methods: We collected demographic data and parental ratings on the Family Environment Scale (FES) for 56 children (aged 6–18 years) from 36 families with at least one biological parent with BD. The cohort had previously been psychiatrically diagnosed according to semi‐structured interviews.   Results: Statistical comparisons with normative data indicated that parents’ ratings were significantly lower on the FES Cohesion and Organization scales and were significantly higher on the FES Conflict scale. Multivariate analyses of variance indicated that families with both parents having a mood disorder had no significantly different FES scores than families with only one parent with a mood disorder (BD). Diagnostic data indicated that while 54% of the children in the sample had an Axis I disorder and 14% had BD, FES scores did not differ significantly for subjects with or without an Axis I disorder, or with or without BD.   Conclusions: Families with a bipolar parent differ from the average family in having less cohesion and organization, and more conflict. Despite this difference, it does not appear that the environment alone of families with a bipolar parent determines the outcome of psychopathology in the children, or that the psychopathology of the children determines the family environment.
Quetiapine in bipolar disorder and cocaine dependence
Authors: Brown E Sherwood , Nejtek Vicki A , Perantie Dana C , Bobadilla Leonardo
Published: March 2003

Objective:  Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric illness. Therefore, treatments that stabilize mood and decrease drug use or cravings are of great interest. Atypical antipsychotics are in widespread use in patients with bipolar disorder. However, minimal data are available on their use in bipolar patients with comorbid substance abuse.

Methods:  Open‐label, add‐on, quetiapine therapy was examined for 12 weeks in 17 outpatients with bipolar disorder and cocaine dependence. Subjects were evaluated with a structured clinical interview; Hamilton Depression Rating (HDRS), Young Mania Rating (YMRS), Brief Psychiatric Rating (BPRS) scales; and Cocaine Craving Questionnaire (CCQ). Urine samples and self‐reported drug use were also obtained. Data were analyzed using a last observation carried forward method on all subjects given medication at baseline.

Results:  Significant improvement from baseline to exit was observed in HDRS, YMRS, BPRS and CCQ scores (p ≤ 0.05). Dollars spent on cocaine and days/week of cocaine use decreased non‐significantly, and urine drug screens did not change significantly from baseline to exit. Quetiapine was well tolerated, with no subjects to our knowledge discontinuing because of side‐effects.

Conclusions:  The use of quetiapine was associated with substantial improvement in psychiatric symptoms and cocaine cravings. The findings are promising and suggest larger controlled trials of quetiapine are needed in this population.
Functional correlates of effect: the relevance of regional cerebral brain dysfunction
Authors: Schneider F
Published: March 2003

Schneider F. Functional correlates of effect: the relevance of regional cerebral brain dysfunction. Bipolar Disord 2002: 4(Suppl. 1): 51. © Blackwell Munksgaard, 2002
Neuroplasticity and cellular resilience in bipolar disorder
Authors: Manji HK , Zhou R , Chen G
Published: March 2003

Manji HK, Zhou R, Chen G. Neuroplasticity and cellular resilience in bipolar disorder.  Bipolar Disord 2002: 4(Suppl. 1): 56–57. © Blackwell Munksgaard, 2002
Neurogenesis, neuroplasticity and severe affective disorder
Authors: Reid IC
Published: March 2003

Reid IC. Neurogenesis, neuroplasticity and severe affective disorder.  Bipolar Disord 2002: 4(Suppl. 1): 58. © Blackwell Munksgaard, 2002
Bipolar disorders and suicidal behaviour
Authors: Rihmer Zoltán , Kiss Kitty
Published: March 2003

Rihmer Z, Kiss K. Bipolar disorders and suicidal behaviour.  Bipolar Disord 2002: 4(Suppl. 1): 21–25. © Blackwell Munksgaard, 2002

Major depressive disorder is the leading cause of suicide, particularly in the absence of adequate treatment. The aim of this paper is to analyse the relationship between different forms of major mood disorders and suicidal behaviour. Population‐based epidemiological surveys as well as clinical studies on the clinically explorable suicide risk factors in bipolar and unipolar depressive disorders are reviewed. The present literature shows that patients with bipolar disorders are at higher risk of attempted and completed suicide than that of patients with unipolar major depression. Contrasting only bipolar I and bipolar II patients, current findings indicate that the rate of prior suicide attempt is higher in bipolar II patients, and bipolar II disorder is overrepresented in depressed suicide victims. Among patients with different clinical manifestations of major mood disorders (unipolar major depression, bipolar I and bipolar II disorder), bipolar patients in general, and bipolar II subjects in particular carry the highest risk of suicide.
TMS in depression. A treatment whose time has come?
Authors: Garcia‐Toro M , Romera M , Andrés J , Echevarría M
Published: March 2003

Garcia‐Toro M, Romera M, Andrés J, Echevarría M. TMS in depression. A treatment whose time has come?  Bipolar Disord 2002: 4(Suppl. 1): 100. © Blackwell Munksgaard, 2002
Relevance of the catatonic syndrome to the mixed manic episode
Authors: Bräunig Peter , Krüger Stephanie , Cooke Robert G
Published: March 2003

Bräunig P, Krüger S, Cooke RG. Relevance of the catatonic syndrome to the mixed manic episode.  Bipolar Disord 2002: 4(Suppl. 1): 45. © Blackwell Munksgaard, 2002
The volumetric findings in MRI brain study of bipolar twins and their healthy co‐twins
Authors: Kieseppä T , Van Erp TGM , Haukka J , Partonen T , Cannon TD , Poutanen V‐P , Kaprio J , Lönnqvist J
Published: March 2003

Kieseppä T, van Erp TGM, Haukka J, Partonen T, Cannon TD, Poutanen V‐P, Kaprio J, Lönnqvist J. The volumetric findings in MRI brain study of bipolar twins and their healthy co‐twins Bipolar Disord 2002: 4(Suppl. 1): 29–30. © Blackwell Munksgaard, 2002
Comorbidity in the Dutch twin study on bipolar disorder: challenge or methodological problem?
Authors: Vonk Ronald , Van Der Schot Astrid C , Kahn René S , Nolen Willem A
Published: March 2003

Vonk R, van der Schot AC, Kahn RS, Nolen WA. Comorbidity in the Dutch twin study on bipolar disorder: challenge or methodological problem?  Bipolar Disord 2002: 4(Suppl. 1): 33–34. ©Blackwell Munksgaard, 2002
Transvaginal ultrasonographic findings in the uterus and the endometrium: Low prevalence of leiomyoma in a random sample of women age 25–40 years
Authors: BORGFELDT CHRISTER , ANDOLF ELLIKA
Published: March 2003

Background. In articles and textbooks the prevalence of uterine leiomyomas is said to be 20–25% in women over the age of 30. The aim of this study was to investigate the rate of uterine leiomyoma, the thickness and the texture of the endometrium, and the size of the uterus in a random sample of asymptomatic women 25–40 years old.

Methods. A random sample of women 25–40 years old was offered a transvaginal ultrasonographic examination and 335 (72%) accepted the invitation.

Results. In 18 women uterine leiomyomas were detected, i.e. 5.4% (95% CI 3.0–7.8%). The prevalence of leiomyomas increased with age, being 3.3% (95% CI 0.7–6.0%) in the 25–32 years age group and 7.8% (95% CI 3.6–12.0%) in the 33–40 age group. The size of the uterus correlated to parity, age and height. In women on combined oral contraceptives the size of the uterus was smaller than in women with natural cycles. The size of the uterus did not correlate to body mass index, cycle day or smoking habits. The endometrium increased in thickness and had in most cases a triple line appearance during the proliferative phase until day 15, whereafter it was unchanged in thickness throughout the secretory phase and hyperechogenic in appearance.

Conclusions. This study confirms earlier studies on the endometrium based on selected populations. The size of the uterus increased with parity, age and height, and was smaller in combined oral contraceptive users. The prevalence figures for uterine leiomyomas in textbooks are not confirmed.
Systemic estrogens have no conclusive beneficial effect on human skin connective tissue
Authors: OIKARINEN AARNE
Published: March 2003

Subject. Aging of the skin is affected by intrinsic and extrinsic factors. Especially important extrinsic factor is ultraviolet radiation, which causes premature aging of the skin. Intrinsic aging is influenced by genetic factors, and changes in hormones. In menopause, changes in hormonal balance have been suggested to enhance aging of the skin.

Discussion. Accordingly, several studies have been accomplished, in which hormone replacement therapy (HRT) has been used in order to prevent skin aging at or after the menopause. In this overview the results of previous studies, and a study done recently, are critically reviewed.

Conclusion. One year systemic replacement therapy has no beneficial effect on the skin thickness, collagen synthesis, or elastin. Topical estrogens might have some beneficial effects. However, since the number of patients treated with topical estrogens is relatively small, further studies are needed.
Fetal erythropoietin and endothelin‐1: relation to hypoxia and intrauterine growth retardation
Authors: ÖSTLUND EVA , LINDHOLM HENRY , HEMSEN ANNETTE , FRIED GABRIEL
Published: March 2003

Background. We have examined whether endothelin‐1 (ET‐1) and erythropoietin (EPO) in amniotic fluid, and EPO in fetal serum obtained by cordocentesis from fetuses with signs of intrauterine growth retardation (IUGR), were correlated to fetal growth and/or chronic fetal hypoxia.

Methods. Amniotic fluid and fetal serum were obtained by cordocentesis from 28 fetuses suspected to have IUGR and subsequently analyzed for EPO and ET‐1 by ELISA. These data were correlated to blood gas results and fetal/maternal parameters at delivery.

Results. A novel finding was that ET‐1 correlated to pO2 in amniotic fluid. The average level of ET‐1 in amniotic fluid was 48.3±4.7 pmol/L. The results also showed a correlation between EPO levels in amniotic fluid and EPO in fetal serum. Furthermore, EPO correlated weakly to birth weight at delivery. Children with the lowest birth weights had the highest EPO levels. High EPO values, similarly to ET‐1, correlated to low pO2 values. The level of EPO in amniotic fluid was 8.0±1.6 mIU/ml and in cord blood 29.5±9.6 mIU/ml.

Conclusions. The results indicate that ET‐1 levels may be a marker for short‐term hypoxia, but not for fetal growth, since ET‐1 in amniotic fluid was correlated to pO2 at the time of cordocentesis, but not to birth weight. The results also indicate that EPO levels in amniotic fluid and in fetal cord serum are highly correlated, and thus both can be used as markers for fetal growth and chronic hypoxia before the onset of labor.
Factors associated with climacteric symptoms and the use of hormone replacement therapy
Authors: STADBERG ELISABETH , MATTSSON LARS‐ÅKE , MILSOM IAN
Published: March 2003

Background. To investigate factors associated with climacteric symptoms and the use of hormone replacement therapy (HRT).

Methods. A random sample of women aged 46, 50, 54, 58 and 62 years resident in Göteborg, Sweden (n=5,990) were invited by letter to complete a postal questionnaire concerning the menopause and HRT use.

Results. The response rate was 76% (n=4,504). Women with a higher education, who exercised regularly and who had regular spare‐time activities felt better and had fewer climacteric complaints (p<0.001) compared to lower educated women, women who exercised infrequently and women who had no spare‐time activities. Climacteric symptoms were associated with dryness symptoms (dry eyes, skin, hair and mouth), bilateral salpingo‐oophorectomy (SOE), use of psychotropical drugs and use of alternative remedies, previous hysterectomy and full‐time occupation. Stepwise multiple regression analysis showed significant correlations between vasomotor symptoms and various dryness symptoms, no menstrual periods and use of alternative remedies. Current HRT‐users (13%) had used estrogens for 4.0 years and past users (14%) for 4.3 years. A correlation (p<0.005) was found between HRT use and previous use of contraceptive pills, use of alternative remedies and hysterectomy. Education, occupation and the frequency of exercise did not influence the prevalence of HRT use.

Conclusions. This study has shown that the experience of climacteric symptoms and well‐being is associated with many different factors. Women with a higher education and those who exercised regularly were more often symptom‐free. HRT use was associated with previous use of contraceptive pills, use of alternative remedies and hysterectomy.
A follow‐up study of birth outcome in users of pivampicillin during pregnancy
Authors: LARSEN HELLE , NIELSEN GUNNAR LAUGE , SØRENSEN HENRIK TOFT , MØLLER MARGRETHE , OLSEN JØRN , SCHØNHEYDER HENRIK C.
Published: March 2003

Background. Pivampicillin is a prodrug which is widely used in Scandinavian countries for oral antibiotic therapy. The pivaloyl moiety has a carnitine depleting effect, which has caused doubts about the safety of administering pivampicillin during pregnancy. The aim of the study was to evaluate the risk of congenital malformations in general, preterm delivery and low birth weight in users of pivampicillin.

Methods. Seven hundred and ninety‐one women who had redeemed a prescription of pivampicillin during their first pregnancy from 1 January 1991 to 31 December 1996 were identified in the North Jutland Pharmaco‐Epidemiological Prescription Database. By linkage to the Danish Medical Birth Registry and Regional Hospital Discharge Registry we compared their birth outcomes (malformations, preterm delivery and low birth weight) with the outcomes in 7472 reference pregnancies on which the mother had not redeemed any prescription at all during pregnancy.

Results. The prevalence of malformations was 5.5% (11 cases) in offspring of 199 women who had used pivampicillin during the first trimester, and 5.6% (420 cases) in offspring of controls (OR: 0.95, 95% CI: 0.51–1.76). Furthermore, we did not find any significant risk of preterm delivery (OR: 0.75, 95% CI: 0.54–1.05) or low birth weight (OR: 0.93, 95% CI: 0.55–1.57).

Conclusion. This study showed no increased risk of congenital malformations, preterm delivery or low birth weight in offspring of women who had redeemed a prescription for pivampicillin during pregnancy.
Association between external pelvimetry and vertex delivery complications in African women
Authors: LISELELE HUBERT BOLEMBA , TSHIBANGU CLÉOPHAS KALALA , MEURIS SYLVAIN
Published: March 2003

Objective. To assess association between external pelvimetry and delivery complications in vertex presentation.

Methods. Prospective cohort study of 2413 pregnant women antenatally measured for height and external pelvimetry in four hospitals of the former Republic of Zaire. Outcome measures: Complications during delivery of single fetus weighing 2000 g or more in vertex presentation. Cut‐off values at risk for delivery complications were height and pelvic distances closest to the study population 10th percentile.

Results. In univariate analysis, maternal height showed significant relative risk for predicting primary cesarean section for failure to progress: 2.0 (95%
CI=1.0–4.1; p=0.050) and vacuum or forceps delivery: 15.7 (95%
CI=6.6–37.5; p<0.001). Selected external pelvic distances showed significant relative risks for predicting the following complications: primary cesarean section for failure to progress, elective repeat cesarean section, vacuum or forceps delivery and spontaneous intrapartum stillbirth. Among pelvic predictors, transverse diagonal (TD) of Michaelis sacral rhomboid area was associated with all of these complications. Intertrochanteric (IT) diameter was associated with three of them. The relative risks ranged from 2.3 (95%
CI=1.1–6.3; p=0.030) to 9.6 (95%
CI=4.1–22.5; p<0.001) for these strongest predictors.

Conclusions. External pelvic distances help to predict vertex delivery complications in African women. The predicted complications are compatible with the cephalopelvic disproportion concept (CPD). After validation of current results in a separate cohort, measurements of IT and/or TD are recommended to improve antenatal screening of women at risk for CPD in limited resources settings.
Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy
Authors: BERKANE NADIA , COCHETON JEAN‐JACQUES , BREHIER DELPHINE , MERVIEL PHILIPPE , WOLF CLAUDE , LEFÈVRE GUILLAUME , UZAN SERGE
Published: March 2003

Objective. We studied the clinical and biological effects and safety of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy (ICP).

Methods. All cases of ICP treated with ursodeoxycholic acid in our department from January 1st, 1991 to May 31st, 1997 were reviewed.

Results. Forty‐three patients had ICP, of whom 19 received ursodeoxycholic acid. The first symptoms appeared after a mean of 29.7 weeks of pregnancy (WP). Treatment was started after a mean of 32 WP, and lasted a mean of 28.5 days. Fourteen patients showed a clinical improvement on UDCA, and 11 showed a biological improvement. Two had a biological deterioration with increased liver enzyme concentrations.

Conclusions. Ursodeoxycholic acid appears to be an effective treatment for ICP, but further studies are needed to confirm its safety in pregnancy.
Do practice guidelines guide practice? A prospective audit of induction of labor – three years experience
Authors: MOUSA HATEM A. , MAHMOOD TAHIR A.
Published: March 2003

Background. To examine the effect of implementation of guidelines for induction of labor on the process of care and outcome measures.

Method. Guidelines for induction of labor were implemented in January 1996 following an audit report identifying inconsistency in clinical practice. A prospective audit was carried out following the implementation of a new strategy directed towards pre‐induction cervical ripening in nulliparae with unfavorable cervices and the use of low dosages of vaginal prostaglandin E2 for induction of labor. Level of compliance and outcome measures were compared before and after implementation of guidelines.

Results. In the period of January 1995 to November 1997, 1,230 women were induced with a singleton viable pregnancy in a cephalic presentation with a gestational age ≥37 weeks with no history of rupture of membranes or cesarean section. Completed forms were available for 1,147 women (370, 421 and 356 in 1995, 1996 and 1997, respectively). Among nulliparous women, there was a reduction in the number of women who were admitted with cervical score of ≤4 (24%, 40%, and 54% in 1997, 1996, and 1995, respectively; p=0.0001), an increase in the number of women who had amniotomy on admission (32%, 25% and 12% in 1997, 1996, and 1995, respectively; p=0.0001) and a shorter induction‐delivery interval. No change in outcome measures was noted among multiparous women despite reduced dose of prostaglandin E2 used for induction of labor. A marginal reduction of both Cesarean section and failed induction rates were noted in both nulliparae and multiparae. Level of compliance improved with successive rounds of audit.

Conclusion. Explicit guidelines do improve clinical practice, when introduced and monitored in the context of rigorous evaluations. However, the size of improvement could vary.
Induction of endometriosis in the mouse inhibits spleen leukocyte function
Authors: Somigliana Edgardo , Viganò Paola , Zingrillo Beatrice , Ranieri Stefania , Filardo Paola , Candiani Massimo , Vignali Mario
Published: March 2003

Background. It is still unclear whether the immunologic perturbation observed in women with endometriosis represents an intrinsic defect of the immune system or it is consequent to the presence of endometrium in ectopic sites. The present study was aimed to evaluate the immunoregulatory properties of ectopic endometrial implants in a model of experimental endometriosis in mice.

Methods. Endometriosis was induced in n=10 mice by inoculating endometrial fragments obtained from syngenic donor mice into the peritoneal space. Twelve mice were similarly treated but were not inoculated with endometrium and were used as control mice. At an explorative laparotomy performed in all the animals after three weeks, the extent of peritoneal lesions, when present, was evaluated by weight assessment and surface area measurement. In both mice that were inoculated with endometrium and control animals, spleens were removed. The effect of endometriosis induction on concanavalin A‐induced spleenocyte proliferation was investigated.

Results. A significant inhibition of spleenocyte growth was demonstrated in mice in which endometriosis was induced (36156±3061 cpm) compared to control animals (47172±3210 cpm; p<0.05). Moreover, a significant inverse correlation was found between spleenocyte proliferation and weight and surface area of the peritoneal endometriotic lesions (r=0.76; p<0.02 and r=0.75; p<0.02, respectively).

Conclusion. These findings suggest that the presence of ectopic endometrial implants within the peritoneal cavity leads to substantial changes of the immune response in vivo. These changes may have significant implications for the understanding of the etiopathogenesis of endometriosis.
Risk for anogenital cancer and other cancer among women hospitalized with gonorrhea
Authors: Johansen Christoffer , Mellemkjær Lene , Frisch Morten , Kjær Susanne K. , Gridley Gloria , Olsen Jørgen H.
Published: March 2003

Background. We investigated the relationship between infections with Neisseria gonorrhoeae and anogenital and other cancers.

Methods. Nationwide and population based register linkage study utilizing prospectively notified information. The observed numbers of cancers among the women were compared with those expected on the basis of national incidence rates.

Results. In a cohort of 4440 women hospitalized for gonorrhea we observed a total of 227 cases of cervical intraepithelial neoplasia grade III (CIN III), with 103 expected (standardized incidence ratio (SIR), 2.2; 95% confidence interval (CI), 1.9–2.5). No significantly increased risk for other anogenital cancers or cancer at other sites was seen.

Conclusions. These results support the view that the observed association between gonorrheal infection and subsequent cervical preneoplasia is due mainly to surveillance bias. However, our results also indicate that women hospitalized with a N. gonorrhoeae infection will benefit from the compliance with the regular Pap smear screening programs.
Can the endometrial thickness as measured by trans‐vaginal sonography be used to exclude polyps or hyperplasia in pre‐menopausal patients with abnormal uterine bleeding?
Authors: Dueholm Margit , Jensen Marianne Lidang , Laursen Hanne , Kracht Per
Published: March 2003

Background. To combine findings of normal mid‐line echoes from TVS (trans‐vaginal sonography) with cut‐off levels for endometrial thickness, in order to examine the associated risk of abnormalities in the uterine cavity.

Design and Setting. Two center prospective study at a university clinic and a central hospital in Denmark.

Participants. Three hundred and fifty‐five pre‐menopausal patients with abnormal uterine bleeding, and indications for endometrial sampling or surgery.

Interventions. The thickness of the endometrium was measured, and the mid‐line echoes were evaluated using TVS. The findings from the endometrial sampling, combined with the evaluation of the uterine cavity using operative hysteroscopy (115), hysterectomy (74) or HSE (hysterosonographic examination) (166), were used as the true values.

Results. The mean (±s.d.) endometrial thickness was significantly different in patients with hyperplasia 11.5 mm (±5.0), polyps 11.8 mm (±5.1), sub‐mucous myomas 7.1 mm (±3.4) and in patients without these abnormalities 8.37 (±3.9) (p<0.001). Hyperplasia and/or polyps were present in 20% of all patients, and in 8% of 143 patients with an endometrial thickness of ≤7 mm. This proportion did not decrease with lower cut‐off levels for endometrial thickness. Receiver operating characteristic (ROC) curves were not optimal for excluding hyperplasia or polyps by endometrial thickness. In 173 cases with a distinct, regular midline echo without echo‐dense foci in TVS the proportion of patients with abnormalities was 16% (11–23). This proportion did not decrease with cut‐off levels for endometrial thickness.

Conclusions. Using TVS, low levels of endometrial thickness reduced the possibility of abnormalities such as polyps and hyperplasia, but did not exclude them. Low cut‐off levels for endometrial thickness did not increase the diagnostic performance in cases with normal sonograms.
Y‐chromosomal microdeletions among infertile Finnish men
Authors: Aho Milla , Härkönen Kati , Suikkari Anne‐Maria , Juvonen Vesa , Anttila Leena , Lähdetie Jaana
Published: March 2003

Background. Microdeletions in the Y‐chromosome are known to cause a significant proportion of azoo‐ and oligozoospermia in men. The reported frequency of deletions varies greatly between the studies. Probable reasons for this variation are different selection criteria and number of patients included, and possibly also methodological aspects, whereas the contribution of environmental and genetic factors is not known. The aim of this study was to determine the incidence of Y‐chromosome microdeletions among infertile Finnish men.

Methods. Two hundred and one men showing azoospermia (n=68) or severe oligozoospermia (n=133) were included. Multiplex polymerase chain reaction method was used to amplify specific sequence tagged sites (STS) along the Y chromosome.

Results. Microdeletions were observed in 18 men (9%), of whom four were azoospermic and 14 oligozoospermic.

Conclusions. The incidence of Y‐deletions in the study population of infertile Finnish men falls within the range published in other countries.
Immunolocalization of transforming growth factor‐β3 in pregnant human myometrium
Authors: Kuşcu Naci Kemal , Laçin Selman , Vatansever Seda , Yildirim Yasemin , Var Ahmet , Uyanik Bekir Sami , Koyuncu Faik
Published: March 2003

Background. Transforming growth factor‐β3 is a cytokine which is involved in cell growth regulation and differentiation, stimulation of extracellular matrix and modulation of immune responses. The goal of this study was to detect the presence of this cytokine in the myometrium of preterm and term, nonlaboring and laboring patients, and to measure serum levels of interleukin‐1β (IL‐1β), IL‐6 and IL‐8 before cesarean section.

Methods. In this prospective study, we obtained samples of myometrium from the lower uterine segment during elective and emergency cesarean sections (term non‐laboring, n=8; term laboring, n=7; preterm non‐laboring, n=3; and preterm laboring, n=19) and stained for transforming growth factor‐β3. Blood was also sampled from the same patients to determine IL‐1β, IL‐6 and IL‐8 levels.

Results. Different intensities of staining were detected in preterm laboring, term nonlaboring and term laboring groups, but there was no staining in preterm nonlaboring group. We also found a statistically significant difference in IL‐6 levels between laboring and nonlaboring groups (p=0.028).

Conclusion. Different intensities of TGF‐β3 which appeared in different stages of myometrium made us consider that TGF‐β3 might prepare myometrium to labor, and IL‐6 was more important than the other interleukins in initiation of labor.
Dilatation and curettage fails to detect most focal lesions in the uterine cavity in women with postmenopausal bleeding
Authors: Epstein Elisabeth , Ramirez Anette , Skoog Lennart , Valentin Lil
Published: March 2003

Objective. To determine the prevalence of focally growing lesions in the uterine cavity in women with postmenopausal bleeding and endometrium ≥5 mm and the extent to which such lesions can be correctly diagnosed by D&C.

Methods. In a prospective study, 105 women with postmenopausal bleeding and endometrium ≥5 mm at transvaginal ultrasound examination underwent diagnostic hysteroscopy, D&C and hysteroscopic resection of any focally growing lesion still left in the uterine cavity after D&C. Twenty‐four women also underwent hysterectomy. If the histological diagnosis differed between specimens from the same patient, the most relevant diagnosis was considered the final one.

Results. Eighty percent (84/105) of the women had pathology in the uterine cavity, and 98% (82/84) of the pathological lesions manifested a focal growth pattern at hysteroscopy. In 87% of the women with focal lesions in the uterine cavity, the whole or parts of the lesion remained in situ after D&C. D&C missed 58% (25/43) of polyps, 50% (5/10) of hyperplasias, 60% (3/5) of complex atypical hyperplasias, and 11% (2/19) of endometrial cancers. The agreement between the D&C diagnosis and the final diagnosis was excellent (94%) in women without focally growing lesions at hysteroscopy.

Conclusion. If there are focal lesions in the uterine cavity, hysteroscopy with endometrial resection is superior to D&C for obtaining a representative endometrial sample in women with postmenopausal bleeding and endometrium ≥5 mm.
Patient accept questionnaires integrated in clinical routine: a study by the Swedish National Register for Gynecological Surgery
Authors: Ladfors Mona B. , O. Löfgren Mats. E. , Gabriel Barbara , Olsson Jan‐Henrik A.
Published: March 2003

Background. In 1996, the Swedish National Register for Gynecological Surgery started to collect pre‐ and postoperative information on patients using questionnaires given out as part of routine medical care. The information is used in providing clinical care to the patient and for quality assessment.

Aims. To evaluate patients' acceptance of questionnaires as a means of collecting information, and to investigate whether the questionnaire is a suitable tool for follow‐up of patients.

Methods. In 1998, evaluations of the ordinary questionnaires were done by an evaluation questionnaire mailed to 80 patients who had been recently hysterectomized. The results were triangulated with results from the register's database and data from interviews with physicians and secretaries.

Results. The majority of the patients appreciated the questionnaires. Patients did not report any major problems in filling in the questionnaires. Most problems were due to administrative errors of the departments. Up to 36% of the patients missed the scheduled follow‐up visit 2 months after the operation. Two out of four departments regarded the follow‐up visit necessary and requested by the patients. Out of 1226 patients followed up postoperatively by questionnaire, 75% stated that they did not need any medical care. Among physicians, some distrust of questionnaires was noted.

Conclusions. The patients in this study preoperatively, and for short‐ and long‐term follow‐up, accepted the questionnaire as an instrument of data collection. Questionnaires provide a more complete collection of post‐treatment information than follow‐up visits do. A large number of unnecessary follow‐up visits can be avoided through use of a questionnaire.
Intra‐hepatic cholestasis of pregnancy in hepatitis C virus infection*
Authors: Paternoster Delia M. , Fabris Franco , Palù Giorgio , Santarossa Cinzia , Bracciante Roberto , Snijders Deborah , Floreani Annarosa
Published: March 2003

Background. Aims of this study were to investigate whether hepatitis C virus infection influences the incidence and natural history of intrahepatic cholestasis of pregnancy (ICP) and whether ICP has different characteristics in hepatitis C virus (HCV) positive women from ICP in HCV negative women.

Methods. A prospective study for the prevalence of the HCV infection and for the incidence of ICP was carried out in the 5840 patients admitted to the Prenatal Department of Padua University, Italy, between January 1996 and January 1999. Testing was done for HCV by the enzyme linked immunosorbent assay (ELISA 3), recombinant immuno blot assay (RIBA 3) and polymerase chain reaction (PCR). The diagnosis of ICP was made on clinical grounds based on the occurence of pruritus with onset during pregnancy, persisting up to the time of delivery and disappearing after delivery, supported by demonstrating an elevation of both serum ALT and total serum bile acids. The Student's t‐test, one way anova and chi‐square tests were used for statistical analysis.

Results. During the study period, 56 of 5840 patients developed ICP (0.96%). Of these, 12 were also HCV‐RNA positive. The rate of ICP was observed more commonly in HCV‐RNA positive women than in HCV‐RNA negative women (20.33% or 12/59 versus 0.78% or 44/5767, P = 0.001

Conclusions. Occurrence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Although the diagnosis of ICP is not confirmed by specific tests, we confirmed a higher risk of HCV infection in this condition. Therefore, occurence of ICP during the third trimester should be an indication to investigate the HCV status of the patient. Broader studies are necessary to assess the impact of infection on the perinatal outcome of ICP.
Risk factors for cesarean section of primiparous women aged over 35 years
Authors: Kozinszky Zoltán , Orvos Hajnalka , Zoboki Tünde , Katona Márta , Wayda Kornélia , Pál Attila , Kovács László
Published: March 2003

Background.  To determine the perinatal outcome of pregnancy in primiparous women over 35 years of age and to evaluate determinants predicting cesarean delivery in these women.

Methods.  Two hundred and seven mothers aged at least 35 years (1.8% of the total deliveries) delivered in the Department of Obstetrics and Gynecology between 1995 and 2000. These women were matched with women aged 20–29 years according to gravidity. Multiple logistic regression analysis was used to evaluate the risk of cesarean delivery, with controls for possible confounding factors.

Results.  Cesarean section was 2.09‐fold more prevalent among the older than among the younger women; the difference being significant (odds ratio, OR=3.36, 95%CI 2.22–5.09; p<0.001). The advanced maternal age was associated with a significantly higher rate of assisted reproductive techniques involvement (OR 6.54; 95%CI 3.54–12.38; p<0.001). The difference between the rates of preeclampsia in the two groups did not reach the level of significance (OR 1.85; 95%CI 1.02–3.34; p=0.056). There were no significant differences in perinatal outcome between the two groups. The logistic regression model demonstrated an increased risk of cesarean section among the primiparous women aged over 35 years.

Conclusions.  The risk of cesarean section at this advanced age is 6.54‐fold. The determinants are included in the pregnancy, delivery and neonatal outcome.
Hemorrhage risk during operative hysteroscopy
Authors: Agostini Aubert , Cravello Ludovic , Desbrière Raoul , Maisonneuve Anne Sophie , Roger Valérie , Blanc Bernard
Published: March 2003

Background.  To evaluate the risk of hemorrhage during hysteroscopic surgery.

Methods.  Cases of hemorrhage during hysteroscopic surgery were assessed in a single center, observational, prospective study conducted from 1990 to 2000, including 2116 surgical hysteroscopies. Risk of hemorrhage was evaluated according to the hysteroscopic procedure. The management of this complication was also noted.

Results.  Thirteen cases (0.61%) were reported. In six cases, hemorrhage stopped spontaneously. For six patients, a Foley (no. 10) probe was introduced into the uterine cavity and inflated for 24 h to stop hemorrhage. For one patient, immediately from the start of the procedure, the uterine arteries were ligatured through the vaginal route in order to stop bleeding. Haemorrhage risk was higher during hysteroscopic adhesiolysis compared with endometrial ablation {Relative risk [RR] 5.22 (1.26–21.64); p = 0.02}, polyp [RR 5.3 (1.04–27.09); p = 0.04], and fibroid resections [RR 6.55 (1.58–27.17); p = 0.01]. Haemorrhage risk was however, comparable for endometrial ablation, uterus septa section, polyp, and fibroid resections (p = 0.92).

Conclusions.  Hemorrhage risk is higher during synechiolysis compared with other procedures. An inflated Foley probe may be an efficient means of stopping hemorrhage.
Randomized clinical trial of total vs. subtotal hysterectomy: validity of the trial questionnaire
Authors: Gimbel Helga , Zobbe Vibeke , Ottesen Bent S. , Tabor Ann
Published: March 2003

Background.  To ensure the internal validity of a trial it is recommended to undertake a validation study of the method measuring the outcome.

Aims.  To validate a self‐administered, postal questionnaire (http://www.gyncph.suite.dk/praes/gimbel/gihtm) used for measuring the outcomes of a randomized clinical trial of total vs. subtotal abdominal hysterectomy.

Methods.  A study of the content validity (10 patients) and a combined qualitative and quantitative validation study (20 patients) were performed.

Results.  The median kappa of the 74 questions was 0.71 (range 0.22–1.00) and the median overall agreement was 0.76 (range 0.25–1.00). Five questions (7%) had kappa values below 0.40, 11 questions (15%) between 0.40 and 0.60, and 58 questions (78%) above 0.61. Three questions with a kappa value below 0.40 had an overall agreement of 0.75 or more. Significant logical inconsistencies were found in five questions, where the operation method was expected to be known. The qualitative validation resulted in a total of 80 comments. The number of comments for any given subject ranged from 0 to 12. The comments could be grouped and processed into four categories.

Conclusions.  The agreement was high. Inconsistencies regarding questions on the operation methods were found. Potential problems were identified in five questions (7%). The validation studies resulted in some changes to the questionnaire and we became aware of areas in which caution should be taken in the interpretation of the results of the randomized trial.
Plasma oxytocin levels in women during labor with or without epidural analgesia: a prospective study
Authors: Rahm Vivi‐Anne , Hallgren Anita , Högberg Hans , Hurtig Ingalill , Odlind Viveca
Published: March 2003

Background.  Epidural analgesia (EDA) has been reported to prolong labor. Whether this is by interference with endogenous oxytocin release or other mechanisms is unclear. With increasing numbers of women receiving an EDA, it is important to study its effects on labor. The aim was to study the concentration of plasma oxytocin and the progress of labor in women with and without EDA.

Methods.  Thirty‐four full‐term women in spontaneous labor were included, 17 with epidural and 17 controls, matched for cervical dilatation and parity. Oxytocin was measured by radioimmunoassay before analgesia, 60 min later and after placental discharge. No oxytocin augmentation was given during the first hour.

Results.  EDA during labor was associated with a fall in plasma oxytocin. There was no difference in plasma oxytocin levels between the groups at inclusion. One hour later, oxytocin concentrations had decreased in the epidural and increased in the control group (Student's t‐test, p= 0049). The change in oxytocin levels between the first and second sample differed significantly between the groups (ancova, p= 0.028). No difference in cervix dilatation between the groups 1 h after inclusion was noted, but women with EDA had a longer labor compared with those without, especially those with epidural and oxytocin augmentation during the later phase of the first stage of labor.

Conclusion.  EDA during labor may interfere with the release of plasma oxytocin, which may be one mechanism behind prolongation of labor. Larger studies are needed to clarify the effects of epidural analgesia and the role of oxytocin during labor.
Glaucoma following congenital cataract surgery: An 18‐year longitudinal follow‐up
Authors: Magnusson G. , Abrahamsson M. , Sjöstrand J.
Published: March 2003

Purpose: To report the occurrence of postoperative glaucoma and to evaluate risk factors.

Methods: Children born in four of the western counties of Sweden who were diagnosed with congenital cataracts formed a cohort (n=137). The following parameters were evaluated: age at cataract surgery; type of surgery; visual outcome; postoperative IOP; optic disc abnormalities; date of onset of the complication; number of reoperations, including treatment for secondary cataract; presence of systemic anomalies; microphthalmus; and eye‐related anomalies.

Results: A diagnosis of glaucoma was recorded for 12% of the eyes. The mean follow‐up time was 9.6 years. There is a relationship between surgery before the age of 10 days and development of glaucoma. Microphthalmus is an important risk factor as well.

Conclusions: Despite modern surgical techniques the incidence of aphakic glaucoma is 10% or higher. No time‐dependent increase in the incidence of late‐onset glaucoma between the 1980s and the 1990s could be proven.