bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced cyclosporine–itraconazole interaction with cola in lung transplant recipients
Authors: Wimberley Sl , Haug Iii Mt , Shermock Km , Qu A , Maurer Jr , Mehta Ac , Schilz Rj , Gordon Sm
Published: March 2003

Background: Invasive aspergillosis is a major cause of morbidity and mortality in lung transplant recipients (LTR), occurring in up to 15% of patients post‐transplant. The 14% aspergillus incidence at the Cleveland Clinic Foundation prompted institution of universal prophylaxis with oral itraconazole (ICZ) in 1997. We report our experience with two protocols of ICZ administration in non‐cystic fibrosis LTR and the interaction with cyclosporine (CSA).  Methods: Group 1 patients (n=12) were administered ICZ capsules in a fasting or fed state, with or without a histamine‐2 (H‐2) receptor antagonist or proton pump inhibitor. Group 2 patients (n=12) received the same protocol as group I, but in a fed state with a carbonated beverage (cola) to increase acidity in the stomach to enhance absorption of ICZ. The ICZ dose was 200 mg/d, given as one daily dose. A historical control group (n=10) did not receive chemoprophylaxis with ICZ. CSA daily doses, dose intervals, concentration, cost, and random ICZ levels were documented over a 4‐month period of time and compared using generalized estimating equations.  Results: The daily CSA mg/kg/d dose decreased over time in all three groups, but no differences were found between the three groups. The CSA dosing interval over time was significantly prolonged in group 2 compared to group 1 or the control group (p≤0.003). Over time, there was no difference in CSA concentration between all groups. There was no difference in cost over time between the three groups; however, the mean cost of CSA therapy was significantly lower in group 2 compared to the control group (p=0.025). Group 2 administered ICZ with cola had greater random blood concentrations of ICZ (p=0.019).  Conclusions: ICZ capsules administered in a fed state with a cola resulted in greater random levels of ICZ, a decrease in cost/d of CSA, and a prolongation of CSA dosing interval. Although daily CSA dosage trended lower in group 2, it did not reach statistical significance. We believe these changes in CSA dosing over time reflect increased absorption of ICZ and recommend verifying ICZ absorption with an itraconazole level, especially when CSA intervals are not prolonged.
Pharmacokinetics of intravenous mycophenolate mofetil after allogeneic blood stem cell transplantation
Authors: Jenke Andreas , Renner Ulf , Richte Maria , Freiberg‐Richter Jens , Platzbecker Uwe , Helwig Anett , Thiede Hans‐M , Schäfer‐Eckart Karin , Ehninger Gerhard , Bornhäuser Martin
Published: March 2003

Background. Mycophenolate mofetil (MMF) has shown synergistic effects in combination with cyclosporin A (CsA) in prevention of acute graft versus host disease (GvHD) after allogeneic blood stem cell transplantation (BSCT) in preclinical animal models. After having measured low plasma levels of the active metabolite mycophenolic acid (MPA) in recipients of allogeneic blood stem cell transplants after oral administration of MMF, we initiated a phase I/II study evaluating different dose levels of the intravenous (i.v.) formulation together with standard dose CsA.   Methods. A total of 15 patients received i.v. MMF in two split doses for 21 d after allogeneic BSCT from related (n=9) and unrelated (n=6) donors. Total daily doses of 25, 28, 31 and 34 mg/kg were investigated in 3–5 patients at each dose level. Plasma concentrations of MPA and its metabolite mycophenolic acid glucuronide (MPAG) were measured by high‐performance liquid chromatography (HPLC).   Results. Mean trough blood levels of MPA ranged between 68.8 and 340 ng/mL with a median of 146.7 ng/mL. The mean MPA AUC0–12 h after first dose ranged between 19349±5087 ng * h/mL and 25705±3042 ng * h/mL and correlated with the dose level of MMF. The incidence of acute GvHD>grade I was 40%. No dose limiting toxicities were observed.   Conclusions. The application of i.v. MMF is safe at a weight‐adjusted dose between 25 and 34 mg/kg after allogeneic BSCT. The measured trough blood levels of MPA in patients after BSCT were ten times lower than in healthy volunteers. The toxicity induced by the conditioning therapy seems to negatively influence the pharmacokinetic behavior of MMF, MPA and MPAG.
The hepatic artery in liver transplantation and surgery: vascular anomalies in 701 cases
Authors: Gruttadauria Salvatore , Scotti Foglieni Carlo , Doria Cataldo , Luca Angelo , Lauro Augusto , Marino Ignazio R
Published: March 2003

The purpose of this study is to report the variations in hepatic arterial supply of a mixed population of organ donors in which the anatomy was individually examined during the bench surgery, and patients who underwent a selective angiogram of the celiac axis and superior mesenteric artery.  We reviewed the donor forms and/or angiograms of 701 patients. The donor forms were completed personally by one of the authors, while all the radiology images were obtained through studies performed by one single radiologist. The arterial anatomy was anomalous in 296 out of 701 cases with an overall incidence of hepatic artery anomalies of 42.22%.  In this paper we describe previously unreported arterial anomalies of the hepatic artery, collecting the second largest series of hepatic artery anatomical variations of the English literature. This anatomical update can be useful for transplant and general surgeons, as well as vascular radiologists.
Liver preservation with HTK: salutary effect of hypothermic aerobiosis by either gaseous oxygen or machine perfusion
Authors: Minor Thomas , Olschewski Peter , Tolba Rene H , Akbar Susanne , Kočálková Mariana , Dombrowski Frank
Published: March 2003

The aim of the present study was to improve the viability of marginal livers from non‐heart beating donors upon cold preservation using two different techniques for the provision of tissue aerobiosis. Livers from male Wistar rats (250–300 g bw) were harvested after 60 min of cardiac arrest, flushed via the portal vein with 20 mL of heparinized Ringer's solution and 60 mL of histidine–tryptophan–ketoglutarate (HTK) preservation solution. Control livers were then stored submerged in HTK for 24 h at 4°C while other organs were subjected to aerobic conditions by either insufflation of gaseous oxygen via the venous vascular system of the cold stored organ (VSOP) or pulsatile machine perfusion (MP) with oxygenated HTK at 5 mL/min at 4°C. Superoxide dismutase (SOD) (7500 IU) was added to the last 10 mL of HTK in order to prevent adverse effects of high oxygen tensions at hypothermia. Viability of the livers was assessed upon isolated perfusion in vitro with oxygenated Krebs–Henseleit buffer at constant flow. VSOP or MP, both significantly improved vascular conductivity upon reperfusion as evaluated by portal venous pressure, reduced hepatic enzyme release and led to a rise in hepatic bile production upon reperfusion. Induction of apoptosis was also looked for in tissue homogenates by Western analysis for cleavage of poly(ADP‐ribose)polymerase (PARP). Expression of cleaved PARP fragment could be found in reperfused control livers but also, though to a lesser extend, after VSOP or MP. In conclusion, provision of oxygen during cold preservation significantly contributes to improve organ viability upon reperfusion and must be regarded as a useful adjunct for marginal or pre‐damaged livers. HTK has been shown for the first time to be also suitable for long‐term MP preservation of the liver, but, as inferred from these data, simple insufflation of gaseous O2 may be considered a feasible alternative.
Internal hernia of the small bowel around infrarenal arterial conduits after liver transplantation
Authors: Nishida Seigo , Pinna Antonio G , Nery Jose R , Levi David , Kato Tomoaki , Madariaga Juan , Tzakis Andreas G
Published: March 2003

Nishida S, Pinna AG, Nery JR, Levi D, Kato T, Madariaga J, Tzakis AG. Internal hernia of the small bowel around infrarenal arterial conduits after liver transplantation. Clin Transplant 2002: 16: 334–338. © Blackwell Munksgaard, 2002

Internal hernia of the small bowel is an uncommon but fatal complication of liver transplantation. The placement of infrarenal arterial conduits for arterial revascularization is an important technique for arterial reconstruction after liver transplantation. We report three cases of internal hernia with volvulus of the small bowel caused by the use of infrarenal arterial conduits. We reviewed the records of 1066 consecutive patients who underwent orthotopic liver transplantation between June 1994 and April 2000 at the University of Miami. In 271 of these patients, grafts were revascularized by anastomosing the donor iliac artery to the infrarenal aorta (an infrarenal arterial conduit).

Two patients died after the surgery. One patient died of multiple organ failure because of sepsis 1 month after the surgery that involved reduction of the internal hernia and biliary reconstruction. Another patient died of multiple organ failure because of sepsis 8 days after the surgery that involved reduction of the internal hernia and adhesiolysis. One patient survived after the surgery that involved thrombectomy of the arterial graft and reduction of the internal hernia. Although there was ischemic damage to the liver after the surgery, the patient recovered. However, he died of liver failure because of recurrent infection with the hepatitis C virus 18 months after the surgery.

Transplant surgeons should be aware that this complication causes not only bowel obstruction but also hepatic arterial thrombosis and ischemic liver damage. In order to prevent this complication, the arterial conduit should be retroperitonealized at the time of transplantation.
Latency and episodes before treatment: response to lithium maintenance in bipolar I and II disorders 1
Authors: Baldessarini Ross J , Tondo Leonardo , Hennen John , Floris Gianfranco
Published: March 2003

Objectives:

To test whether longer treatment‐delays or more pretreatment illness episodes are followed by diminished response to lithium maintenance.   Methods: In 360 DSM‐IV bipolar I (n=220) or II (n=140) patients, effects of latency from illness onset to starting lithium and number of pretreatment episodes were evaluated by survival analysis based on the number of months stable before a first recurrence on lithium. Factors associated with treatment latency were identified by regression modeling. Relationships of time, episode number, and morbidity before treatment to the overall proportion of time ill on lithium were also tested by nonparametric correlation.   Results: Latency to first lifetime lithium maintenance averaged 8.3 years, with 9.3 episodes/subject. Time stable before a first recurrence on lithium averaged 29.6 months and was unrelated to treatment latency (in terciles) or to a high (≥ten), intermediate (four–nine), or low (<four) number of prior episodes. Overall morbidity during 4.6 years of lithium maintenance was also unrelated to these pretreatment factors. More episodes/year and percentage of time ill before treatment anticipated shorter treatment latency, with greater relative improvement, but were unrelated to morbidity during treatment.   Conclusions: Treatment latency and prelithium episode number were unrelated to morbidity during treatment. Although multiple untreated episodes can lead to severe disability, lithium evidently can greatly limit morbidity, even after years of delay and multiple episodes of bipolar illness.
The use of nimodipine in the treatment of mood disorders
Authors: Goodnick Paul J
Published: March 2003

Nimodipine, a dihydropyridine calcium entry blocker, has been shown to protect from neuronal damage due to ischemia by providing for increased postischemic perfusion. Further, it has also been demonstrated to have antiepileptic properties. These two properties – calcium channel blockade and anticonvulsant benefits – have been applied with success to mood disorder treatment. Although found helpful nearly a decade ago for uncomplicated mania, nimodipine may have particular benefits for those diagnostic subclasses of bipolar disorder most resistant to therapy, e.g., ultra‐rapid‐cycling bipolars and brief recurrent depressions.
Onset of action of antipsychotics in the treatment of mania
Authors: Tohen Mauricio , Jacobs Thomas G , Feldman Peter D
Published: March 2003

Introduction:

An important consideration in treating acute mania is the promptness with which a chosen therapy can bring symptom amelioration. This article reviews the available published data from controlled, blinded studies regarding the latency of responses to antipsychotics in patients with acute mania.

  Methods: Articles for this review were obtained from a search of the Medline database (1966–1999), using the following keywords and phrases: antipsychotic, atypical, bipolar disorder, mania, neuroleptic, typical. The bibliographic sections of articles gleaned from this search were used to direct further inquiries.

  Results: Although information regarding the onset of action of antipsychotics is limited, we discovered data for four typical and three atypical antipsychotics. Drugs with the fastest onsets include haloperidol, risperidone, and olanzapine, with onsets appearing in 2–6 days. Chlorpromazine and thiothixene were at the slowest end of the continuum, with onsets of 2 weeks or longer. Data regarding pimozide are mixed, with some studies showing an onset equivalent to that of the ‘fast’ compounds and others showing one similar to that of the ‘slow’ compounds.

  Conclusions: Choice of therapy should consider not only efficacy and safety, but also onset speed. Atypical antipsychotics appear to offer safer, faster, and more effective therapies.
Ethical issues in bipolar disorders pedigree research: privacy concerns, informed consent, and grounds for waiver1
Authors: Parker Lisa S
Published: March 2003

Focusing on bipolar disorders research, this article considers ethical issues of informed consent and privacy arising in genetic pedigree research at two stages: the construction of tentative pedigrees to determine family eligibility for study and, subsequently, the enrollment of subjects in and conduct of the family study. Increasing concern to protect the privacy of family members of primary subjects or probands, following ethical controversy over a survey study at Virginia Commonwealth University, has led some researchers and Institutional Review Boards (IRBs) to apply informed consent requirements to those represented on a tentative pedigree at the initial stage of research. This article analyzes the possible benefits, risks, and burdens to prospective subjects of seeking prospective consent for pedigree construction at this initial stage. It argues that the likely risk–benefit ratio favors granting a waiver of consent requirements for this stage of pedigree research and presents grounds for IRBs to grant such a waiver. The article closes by considering particular ethical concerns that should be addressed in the informed consent discussion when enrolling subjects in pedigree studies of bipolar disorder, including concerns about subjects' competence to consent, management of interim and incidental findings, and issues particular to psychiatric research.
Impact of axis II comorbidity on the course of bipolar illness in men: a retrospective chart review
Authors: Kay Joanne H , Altshuler Lori L , Ventura Joseph , Mintz Jim
Published: March 2003

Objectives:
 The purpose of this study was to investigate whether the presence of comorbid personality disorder influences the course of bipolar illness.

Methods:
 Fifty‐two euthymic male bipolar I out‐patients were assessed using the Structured Clinical Interview for DSM‐III‐R Personality Disorders (SCID II). Bipolar patients with an axis II diagnosis were compared with those without an axis II diagnosis on retrospectively obtained demographic, clinical and course of illness variables.

Results:
 Thirty‐eight percent of the bipolar patients met criteria for an axis II diagnosis. Two (4%) met criteria for (only) a Cluster A disorder, four (8%) for (only) a Cluster B, and six (12%) for (only) a Cluster C disorder. One (2%) bipolar patient met criteria a disorder in both Clusters A and B, and one (2%) for a disorder in Clusters B and C. Five (10%) met criteria for at least one disorder in Clusters A and C, and one met criteria for disorders in Clusters A, B, and C. The presence of a personality disorder was significantly associated with a lower rate of current employment, a higher number of currently prescribed psychiatric medications, and a higher incidence of a history of both alcohol and substance use disorders compared with the bipolar patients without axis II pathology.

Conclusions:
 Our results extend previous findings of an association between comorbid personality disorder in bipolar I patients and factors that suggest a more difficult course of bipolar illness.
Pramipexole in treatment‐resistant depression: a 16‐week naturalistic study
Authors: Lattanzi Lorenzo , Dell'Osso Liliana , Cassano Paolo , Pini Stefano , Rucci Paola , Houck Patricia R , Gemignani Alfredo , Battistini Giulia , Bassi Annalisa , Abelli Marianna , Cassano Giovanni B
Published: March 2003

Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB. Pramipexole in treatment‐resistant depression: a 16‐week naturalistic study. Bipolar Disord 2002: 4: 307–314. © Blackwell Munksgaard 2002

Objective: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2–D3 dopamine agonist, in patients with drug‐resistant depression.

Methods:
 The study sample consisted of in‐patients with major depressive episode, according to the DSM‐IV, and drug resistance. Pramipexole was added to antidepressant treatment with TCA or SSRI, at increasing doses from 0.375 to 1.0 mg/day. Two independent response criteria were adopted: a >50% reduction of the Montgomery–Asberg Depressive Rating Scale (MADRS) total score and a score of 1 or 2 on the Clinical Global Impression scale (CGI‐I) at endpoint. Side‐effects were assessed by the Dosage Record Treatment Emergent Symptom Scale (DOTES).

Results:
 Thirty‐seven patients were enrolled. Of these, 16 had unipolar depression and 21 had bipolar depression. Six patients dropped out in the first week. Of the 31 patients included in the analyses, 19 completed the 16‐week follow‐up. Mean maximal dose of pramipexole was 0.95 mg/day. Mean scores on MADRS decreased from 33.3 ± 8.4 at baseline to 13.9 ± 11.5 at endpoint (p < 0.001) and the CGI‐S decreased from 4.6 ± 0.8 at baseline to 2.8 ± 1.3 at endpoint (p < 0.001). At endpoint, 67.7% (21/31) of patients were responders on MADRS and 74.2% on CGI‐I. Of the 37 patients enrolled, 10 discontinued pramipexole because of adverse events.

Conclusions:
 These preliminary data suggest that pramipexole adjunction to antidepressant treatment may be effective and well tolerated in patients with resistant major depression.
A pilot study of loading versus titration of valproate in the treatment of acute mania
Authors: Oluboka OJ , Bird DC , Kutcher S , Kusumakar V
Published: March 2003

Objective:  This double‐blind pilot study compares the effectiveness and incidence of adverse effects of oral loading versus titration schedules of valproate in acute mania.

Method:  Consecutive new admissions for an acute manic episode were prescribed either an oral loading dose (20 mg/kg/day; n=5; mean age=33.4) or slower titration dose (10 mg/kg/day; n=6, mean age=30.6) of valproate for 7 days without other psychotropic agents, with the exception of benzodiazepines. Daily outcome measures included: serum valproic acid levels, the Young Mania Rating Scale (YMRS), the Brief Psychiatry Rating Scale (BPRS), the Clinical Global Impression Scale (CGI) and the Adverse Effect Rating Scale.

Results:  The mean serum valproic acid levels were significantly higher in the loading group when compared with the titration group after 1 and 2 days following the initiation of treatment (p < 0.05). After 3 days of treatment there was a trend for the group that received the loading regimen to have slightly more improvement in YMRS scores compared with the titration group. Side‐effects were minor for both treatments, however, a higher incidence of side‐effects was reported in the titration group, with 50% of patients reporting sedation most likely because of increased use of benzodiazepines.

Conclusion:  This suggests that a loading dose of valproate is likely safe and may provide an earlier onset of antimanic effects in patients with bipolar disorder. Future studies with larger sample sizes are indicated.
The impact of response to previous mood stabilizer therapy on response to olanzapine versus placebo for acute mania
Authors: Baker Robert W , Goldberg Joseph F , Tohen Maurico , Milton Denái R , Stauffer Virginia L , Schuh Leslie M
Published: March 2003

Objectives:
A clinically important question for any new treatment for bipolar disorder is whether its efficacy extends to patients who have both responded and failed to respond to other mood stabilizers. In this secondary analysis of a placebo‐controlled trial demonstrating olanzapine's efficacy for acute mania, we explore whether its usefulness extends to those patients with a history of poor response to other mood stabilizers.

  Methods: This 4‐week, double‐blind, placebo‐controlled trial studied olanzapine monotherapy 5–20 mg/day for hospitalized patients in acute manic or mixed bipolar episodes. The primary outcome variable was beginning to endpoint change in the Young‐Mania Rating Scale (Y‐MRS) total score. We investigated whether prospectively identified history of recent failure to respond to other mood stabilizers predicted response to olanzapine.

  Results: As previously reported, olanzapine‐treated patients experienced significantly greater improvement in Y‐MRS total score and higher remission rates relative to placebo‐treated patients. The current analysis compared these outcome parameters in patients with known poor prior response to lithium and/or valproate with all other patients and found no significant group by treatment interactions, i.e., treatment effects were not significantly diminished in non‐responders to older mood stabilizing agents.

  Conclusions: Olanzapine has been shown to be superior to placebo for the treatment of mania. This secondary analysis suggests that olanzapine monotherapy is similarly effective for patients whether or not they previously have failed to respond to another mood stabilizer for mania. A study limitation is that response to lithium or valproate was determined retrospectively.
Different dependence of lithium and valproate on PI3K/PKB pathway
Authors: Mora Alfonso , Sabio Guadalupe , Alonso Juan C , Soler Germán , Centeno Francisco
Published: March 2003

Objectives:Acute treatment with valproate (VPA) or lithium (Li+) protects cerebellar granule cells (CGC) against apoptosis induced by low potassium (K+) (5 mM). As the protection induced by VPA is absolutely dependent on insulin, in contrast to the observed effects of Li+, we decided to study the different role of the PI3K/PKB pathway in the neuroprotective effects of both drugs.   Methods:We have studied the neuroprotection elicited by Li+or VPA in cultures of rat CGC. We induced the apoptosis by switching to a medium with a low concentration of K+or by adding C2‐ceramide to the cultures. We studied the effect of Li+and VPA on viability and on the regulation of the PI3K/PKB pathway.   Results and conclusions:Insulin also protects against low K+‐induced apoptosis in CGC, probably through its interaction with an insulin‐like growth factor receptor. Moreover, whereas Li+protects against the apoptosis induced by C2‐ceramide, VPA cannot, probably due to the inhibition of protein kinase B (PKB) caused in this apoptotic stimulus. These results suggest that VPA protects against low K+‐induced apoptosis by acting on the PI3K/PKB pathway; however, VPA does not affect the increase of PKB activity caused by insulin in these cells. The protection by Li+is independent of this transduction pathway. Moreover, Li+blocks the caspase 3 activation induced by low K+, whereas neither VPA nor insulin affects this activation.
Cytoarchitectonic changes in bipolar disorder using stereology
Authors: Cotter David
Published: March 2003

Cotter D. Cytoarchitectonic changes in bipolar disorder using stereology.  Bipolar Disord 2002: 4(Suppl. 1): 48. © Blackwell Munksgaard, 2002
A depression neurocircuit. Evidence from structural and functional studies
Authors: Baumann B , Bielau H , Bernstein H‐G
Published: March 2003

Baumann B, Bielau H, Bernstein H‐G. A depression neurocircuit. Evidence from structural and functional studies.  Bipolar Disord 2002: 4(Suppl. 1): 85. © Blackwell Munksgaard, 2002
Regional cerebral blood flow in bipolar disorder measured with PET: trait effects at rest and after mood induction
Authors: Krüger S , Goldapple K , Kennedy S , Houle S , Mayberg H
Published: March 2003

Krüger S, Goldapple K, Kennedy S, Houle S, Mayberg H. Regional cerebral blood flow in bipolar disorder measured with PET: trait effects at rest and after mood induction.  Bipolar Disord 2002: 4(Suppl. 1): 88. © Blackwell Munksgaard, 2002
Transcranial magnetic stimulation and neuroimaging
Authors: Ebmeier KP
Published: March 2003

Ebmeier KP. Transcranial magnetic stimulation and neuroimaging.  Bipolar Disord 2002: 4(Suppl. 1): 96–97. © Blackwell Munksgaard, 2002
A randomized controlled study of cognitive therapy of relapse prevention for bipolar affective disorder: outcome of the first year
Authors: Lam Dominic
Published: March 2003

Lam D. A randomized controlled study of cognitive therapy of relapse prevention for bipolar affective disorder: outcome of the first year.  Bipolar Disord 2002: 4:(Suppl. 1): 104. © Blackwell Munksgaard, 2002
Levetiracetam and ethosuximide in the treatment of acute mania in an open study with an on‐off‐on design
Authors: Walden Joerg , Langosch Jens , Born Christoph , Schaub Gabriele , Grunze Heinz
Published: March 2003

Walden J, Langosch J, Born C, Schaub G, Grunze H. Levetiracetam and ethosuximide in the treatment of acute mania in an open study with an on‐off‐on design.  Bipolar Disord 2002: 4(Suppl. 1): 114. © Blackwell Munksgaard, 2002
Hydramnios and small for gestational age: prevalence and clinical significance
Authors: FURMAN BORIS , EREZ OFFER , SENIOR LEON , SHOHAM‐VARDI ILANA , BAR‐DAVID JURY , MAYMON ELI , MAZOR MOSHE
Published: March 2003

Objective. To investigate the clinical significance of combined obstetrical pathology of small for gestational age and hydramnios as a predictor of peripartum complications, intrapartum morbidity and poor neonatal outcome.

Methods. The study population consisted of 152 small for gestational age neonates with hydramnios out of 67,806 singleton deliveries during the study period (0.22%). We compared the 152 small for gestational age neonates with hydramnios (hydramnios/small for gestational age) to a sample of 1% of the appropriate for gestational age neonates with normal amniotic fluid (normal amniotic fluid/appropriate for gestational age) (582 cases). Analyses were conducted for the entire cohort as well as for the cohort in which all cases with congenital malformations were excluded.

Results. There was a significantly higher rate of congenital anomalies in the hydramnios/small for gestational age group compared with the normal amniotic fluid/appropriate for gestational age group (25% vs. 2.4%, p<0.001). There were significantly more previous perinatal deaths, infertility treatments and diabetes type B‐R among the hydramnios/small for gestational age group. These findings remained significant after exclusion of the neonates with congenital malformations. The rates of labor dystocia, placental abruptio, abnormal presentations, prolapse of cord and cesarean sections were significantly higher in the hydramnios/small for gestational age group compared with normal amniotic fluid/appropriate for gestational age group (5.9/2.4%, p<0.05; 5.9/0.7%, p<0.001; 14.5/3.2%, p<0.001; 2/0.2%, p<0.01; 24.3/8.2%, p<0.001; respectively). Rates of ante partum death and post partum death as well as low 1 and 5 minute Apgar scores were significantly higher in the hydramnios/small for gestational age group (9.9/0.3%; 14.5/0.3%; 12.8/2.1%; 11.7/0.6%, p<0.001, respectively).

Conclusions. The combination of small for gestational age and hydramnios is a risk factor for peripartum complications and perinatal mortality even in the absence of congenital malformations.
Addition of gonadotrophin‐releasing hormone agonist and/or two inseminations with husband's sperm do not improve the pregnancy rate in superovulated cycles
Authors: KARLSTRÖM PER‐OLOF , BERGH TORBJÖRN , LUNDKVIST ÖRJAN
Published: March 2003

Background. A prospective randomized study was performed to evaluate the addition of a gonadotropin releasing hormone agonist (GnRH‐a) during treatment with human menopausal gonadotropins (hMG) in cycles with artificial inseminations with husband's washed sperm (AIH). We also compared the pregnancy rate per cycle after one versus two AIHs.

Methods. We designed a 22 factorial trial. A total of 172 couples with unexplained infertility (n=88), endometriosis (n=39), or cervical (n=24) or male (n=21) factors were included, of whom 161 fulfilled the inclusion criteria and treatment. Eighty‐one women were treated with GnRH‐a/hMG and another 80 with hMG only, respectively.

Results. The pregnancy rates did not differ between the two stimulation protocols (12% for GnRH‐a/hMG and 9% for hMG). With GnRH‐a/hMG more follicles >15 mm (3.4 and 2.4, respectively; p<0.01) and a higher multiple pregnancy rate after 20 weeks of gestation were observed (55% vs. 0%; p<0.05). Eighty‐seven women were treated with one AIH, whereas 65 women received two AIHs on two consecutive days. The pregnancy rates were similar in these two groups (11% and 9% respectively; n.s.)

Conclusion. It is concluded that neither addition of GnRH‐a before and during controlled ovarian hyperstimulation nor two AIHs compared with one single AIH per cycle has a beneficial effect on the pregnancy rate. However, GnRH‐a increases the risk for multiple pregnancies.
Attitudes among health care professionals on the ethics of assisted reproductive technologies and legal abortion
Authors: DE LA FUENTE FONNEST ISABEL , SØNDERGAARD FINN , FONNEST GERT , VEDSTED‐JACOBSEN AGNETE
Published: March 2003

Background. The purpose of the present study was to study the attitudes among Danish health care professionals likely to encounter ethical controversies of ART and related subjects.

Methods. Anonymous questionnaire study design. A total number of 993 were asked to participate from May‐July 1994.

Results. There was a tendency towards a more liberal attitude among gynecologists than among nurses. There was a majority for legal abortion (before 12 weeks of gestation), for selective reduction in multiple pregnancies, and for donor anonymity. There was a majority against sex selection, artificial reproduction as to single women and lesbians, and against adoption by homosexuals. The multivariate analysis showed a strong correlation between attitude and background variables, especially as to religion and profession.

Conclusion. Religion and profession are determinants for the attitude towards several of the ethical controversies of ART and related subjects asked for in this study. We found a discrepancy between recommendations by the Ethical Council of Denmark and the attitudes among health care professionals.
Perioperative morbidity of gynecological laparoscopy
Authors: LEONARD FRANCK , LECURU FABRICE , RIZK ELIE , CHASSET SOPHIE , ROBIN FRANÇOIS , TAURELLE ROLAND
Published: March 2003

Background. To study the morbidity rate of gynecological laparoscopy and to the most influential variables.

Methods. We conducted a prospective observational study from January 1st 1992 to December 31st 1998 in a single tertiary care center. It concerned patients who underwent gynecological laparoscopic surgery performed by seniors and residents. We have prospectively recorded patients characteristics, indications for laparoscopy, leading diagnosis, main operative procedures, post‐operative course, surgical and anesthetic incidents and accidents. Complications were defined as any event that would modify the usual course of laparoscopy or of the post‐operative period.

Results. One thousand and thirty‐three laparoscopies were included. 80.1% of the procedures were major or advanced laparoscopies. The overall complication rate was 3%, with a laparotomy rate of 1.2%. About half of those complications (54.8%) occurred during the installation of laparoscopy. Veress needle and first trocar insertion accounted for 23.5% of those accidents (0.3% of the procedures) and suprapubic trocar insertion for 76.5%. Hemorrhages constituted almost all of the complications occurring during the operative stage (80%). The risk increased with the level of surgery and decreased with surgeon's experience. Prior abdominal surgery had no significant effect on the overall morbidity rate. Post‐operative and anesthetic complications were rare. The overall complication rate as well as the laparotomy rate were stable all along the course of the study.

Conclusions. Complication rate of gynecological laparoscopy is not negligible. Efforts should be made to lower the complications induced by the installation of laparoscopy, especially for secondary trocars.
Treatment with 2% clindamycin vaginal cream prior to first trimester surgical abortion to reduce signs of postoperative infection: A prospective, double‐blinded, placebo‐controlled, multicenter study
Authors: LARSSON PER‐GÖRAN , PLATZ‐CHRISTENSEN JENS‐JÖRGEN , DALAKER KNUT , ERIKSSON KATARINA , FÅHRAEUS LARS , IRMINGER KRISTINE , JERVE FRITJOF , STRAY‐PEDERSEN BABILL , WÖLNER‐HANSSEN PÅL
Published: March 2003

Background. Bacterial vaginosis (BV) and intermediate flora is known risk‐factor for postoperative infection after surgical termination of pregnancy. Vaginal application of 2% clindamycin cream is an efficacious treatment for BV, but it is not known whether preoperative administration of clindamycin cream might reduce the signs of post‐abortion infection after surgical termination of pregnancy.

Aim. To evaluate whether preoperative treatment with clindamycin cream might reduce the signs of post‐abortion infection after legal abortion.

Design. Prospective, double‐blinded, placebo‐controlled, multicenter study.

Material and methods. Consecutive women attending for surgical termination prior to 11+4 gestational weeks were approached. We randomized participants to preoperative vaginal treatment with 2% clindamycin cream or placebo cream in a double‐blinded fashion. At all visits vaginal smears were air dried on microscopy slides to be stored. The rate of postoperative pelvic infection according to our definition was the main outcome variable, the cure rates of BV and of intermediate flora were secondary outcome variables.

Results. Of 1655 enrolled women, 1102 were evaluable for analyses. Fifty‐eight women developed signs of post‐abortion infection. Preoperative treatment with clindamycin cream significantly (RR: 4.2, 95% C.I. 1.2–15.9) reduced the risk of post‐abortion infection among women with abnormal vaginal flora (BV and intermediate flora). Treatment with clindamycin cream in women with normal lactobacilli flora did not demonstrate any difference compared to the non‐treatment group.

Conclusion. Preoperative treatment for at least three days with clindamycin cream significantly reduced the risk for developing signs of post‐abortion infection only among women with preoperative abnormal vaginal flora (BV and intermediate flora).
Microlaparoscopy: a new approach to the reassessment of ovarian cancer patients
Authors: FRANCHI MASSIMO , GHEZZI FABIO , BERETTA PAOLO , DONADELLO NICOLETTA , MIGLIERINA MASSIMILIANO , ZANABONI FLAVIA
Published: March 2003

Background. The purpose of the work was to determine the feasibility and accuracy of microlaparoscopy as diagnostic method for the reassessment of ovarian cancer patients.

Methods. Eight patients scheduled for second‐look laparoscopy who had undergone primary surgery for ovarian cancer followed by 6 cycles of chemotherapy were included in the study. Microlaparoscopy was performed using a 2.8 mm laparoscope followed by conventional 10‐mm laparoscopy. Three additional 5‐mm ancillary trocars were inserted to perform intra‐abdominal biopsies. Pelvic washings were performed in all cases.

Results. Microlaparoscopy was feasible in all cases and as accurate as conventional laparoscopy in seven cases. In one case the procedure was terminated before conventional laparoscopy because of positive biopsies at frozen section examination. There were no intra‐operative complications related to microlaparoscopy. The median time from skin incision to the removal of the microlaparoscope was 47 minutes (range 30–70).

Conclusion. Microlaparoscopy seems to be a safe, accurate, minimally invasive method and therefore we suggest its use as primary approach to the reassessment of ovarian cancer patients.
Birthweight percentiles by gestational age in multiple births
Authors: GLINIANAIA SVETLANA V. , SKJÆRVEN ROLV , MAGNUS PER
Published: March 2003

Objective. To assess secular trends for birthweight by gestational age in twins in Norway and to develop current national birthweight standards by gestational age for twin and triplet births using population‐based data.

Material and methods. The analysis of secular trends for birthweight and gestational age in twins was based on 32,379 twin livebirths (1967–95). Taking into account the observed secular trends in birthweight for 35–40 weeks of gestation, data on twins born during 1987–95 only were included in the calculation of birthweight percentiles for 35–40 weeks, while for lower and upper weeks, data on twins born during 1967–95 were used. The construction of birthweight‐for‐gestation curves for triplets was based on the data on 690 triplets.

Results. Whereas the overall mean birthweight and gestational age decreased in 1987–95 compared with the previous years, the mean birthweights by gestational age for the 35–40 weeks of gestation was significantly higher in 1987–95. Male twins weighed more than female twins throughout the gestation with consistent and significant differences from 27 to 42 weeks of gestation. Smoothed curves for birthweight‐by‐gestational‐age percentiles of male and female twins are plotted. The birthweight‐by‐gestational‐age curves of triplets were almost identical with twin curves before 30 weeks of gestation, starting to diverge from them progressively thereafter. The intrauterine growth of twin births also starts to differ markedly from singletons at approximately 30 weeks of gestation.

Conclusion. This study shows that plurality‐specific birthweight‐by‐gestation standards should be used for assessment of fetal growth in multiple births rather than singleton standards.
Significance of endovaginal ultrasonography in assessing tamoxifen‐associated changes of the endometrium
Authors: STRAUSS HANS‐GEORG , WOLTERS MATTHIAS , METHFESSEL GISELA , BUCHMANN JUERGEN , KOELBL HEINZ
Published: March 2003

Background. A prospective study was conducted investigating the value of endovaginal ultrasound in the assessment of tamoxifen‐associated changes of the endometrium in patients with breast cancer.

Methods. Seventy postmenopausal patients with breast cancer treated with anti‐estrogens for at least 6 months were entered. Those with bleeding disorders and/or an endometrial thickness of ≥10 mm found on ultrasonography underwent hysteroscopy and dilatation and curettage (D&C) for further histological evaluation. In 22 patients, positive ultrasound findings could be compared with histopathology.

Results. 82% of the 22 patients with positive sonographic findings had a glandular‐cystic hyperplasia or a glandular‐cystic polyp. No adenomatous hyperplasia or endometrial cancer was observed in our series.

Conclusion. Vaginal ultrasound represents a useful diagnostic tool to detect tamoxifen‐associated changes of the endometrium. A threshold of 10 mm endometrial thickness appears suitable to identify endometrial abnormalities while reducing the rate of false‐positive findings to an acceptable level. However, the role of vaginal ultrasound in screening for endometrial cancer or premalignant lesions remains uncertain.
Upregulation of interleukin‐8 and polarized epithelial expression of interleukin‐8 receptor A in ovarian carcinomas
Authors: IVARSSON KARIN , EKERYDH ANNE , FYHR ING‐MARIE , JANSON PER OLOF , BRÄNNSTRÖM MATS
Published: March 2003

Background. The chemokine interleukin‐8 is present in a variety of tumor types with suggested effects on proliferation, migration, and angiogenesis. Elevated levels of interleukin‐8 are present in cyst fluids from malignant ovarian tumors. The origin and potential targets for this chemokine in ovarian tumors were investigated in this study.

Methods. Interleukin‐8 and its receptors were analyzed in 26 ovarian samples, including both normal and neoplastic tissue, with immunohistochemistry, Western blotting, and in situ hybridization.

Results. The mRNA for IL‐8 was detected in higher amounts in the epithelial compartments compared to stromal areas, while the IL‐8 protein was present in both epithelial and stromal areas, and in cystic formations of the tumors. The tissue levels of IL‐8 protein increased with lower differentiation of the tumors. Both types of IL‐8 receptors were detected in most specimens. A typical expression pattern for IL‐8 receptor A was detected, with expression only on the luminal side of the epithelial tumor cells, while IL‐8 receptor B was more evenly distributed in the tissue.

Conclusions. An increased synthesis of IL‐8 during dedifferentiation of the tumor, and a typical expression pattern of the IL‐8 receptor A were detected, indicating a function for IL‐8 in biology of epithelial ovarian cancer.
Prevalence of nocturnal hypoglycemia in first trimester of pregnancy in patients with insulin treated diabetes mellitus
Authors: HELLMUTH ELLINOR , DAMM PETER , MØLSTED‐PEDERSEN LARS , BENDTSON INGER
Published: March 2003

Background. Excellent metabolic control before conception and during diabetic pregnancies is the aim in order to avoid malformations and perinatal morbidity. Since an inverse correlation between median blood glucose concentration (BG) and hypoglycemia as well as a high prevalence of nocturnal hypoglycemia have been described, we investigated the frequency of nocturnal hypoglycemia and the predictive value of bedtime blood glucose concentration for development of this condition in insulin treated diabetic patients.

Methods. During hospitalization, with no other changes in the patients' normal schedules, hourly blood samples were drawn from an iv‐cannula from 22.00 h to 07.00 h for one night. BG (venous whole blood) and hemoglobin A1c were determined the following day.

Results. Fifty‐three patients participated; subsequently ten were excluded due to discontinuation of blood sampling during the night, caused by either discomfort or cannula problems. Of the remaining 43 patients, 16 (37%) had at least one blood glucose <3.0 mmol/l. The duration of hypoglycemia was 2.4 (1–7) h with the highest prevalence at 05 h. Only one patient felt hypoglycemic during the night. Hemoglobin A1c was similar in patients with (7.1±1.2%, mean±s.d.) and without (6.8±0.8%) nocturnal hypoglycemia. Women with nocturnal hypoglycemia had significantly lower BG before bedtime compared to patients without hypoglycemia, 6.4±3.6 mmol/l vs. 7.9±2.4 mmol/l, p<0.05. The best predictive value for nocturnal hypoglycemia was a BG below 6.0 mmol/l at 23.00, which resulted in a risk of nocturnal hypoglycemia of 71%. Conversely, if the BG was ≥6.0 mmol/l, the chance of avoiding nocturnal hypoglycemia was 83%.

Conclusion. Nocturnal hypoglycemia was seen with a prevalence of 37% during a night in the first trimester of pregnancy in insulin treated patients. Only one patient registered the hypoglycemia. Nocturnal hypoglycemia could be predicted in the majority of patients by measurements of BG before bedtime.
Antenatal, neonatal and post neonatal deaths evaluated by medical audit
Authors: DAHL LAURITZ BREDRUP , BERGE LILLIAN NORDBØ , DRAMSDAHL HARALD , VERMEER ADRI , HUURNINK AART , KAARESEN PER IVAR , ØIAN PÅL
Published: March 2003

Background. Perinatal committees evaluate deaths by medical audit to improve antenatal and neonatal care. We report data from Troms County from 1976 to 1997.

Subjects and methods. Antenatal, neonatal and post neonatal deaths (n=472) at ≥20 weeks of gestation have been evaluated. Data were collected from the Medical Birth Registry of Norway and from medical records. Pregnancy risk factors, mortality rates, causes of deaths, non‐optimal care and avoidable deaths were recorded.

Results. The death rate (all deaths per thousand total births) declined from 13.8 (1976–80) to 7.7 (1992–97), (p<0.001), due to a reduced death rate in preterms ≥24 weeks (p<0.001) and in those between 500 and 1995 g (p<0.001). Antenatal deaths decreased (p<0.001) due to reduced intrapartum deaths (p<0.001). Prelabor deaths, unexpected intrauterine pre‐hospitalization deaths included, did not change. Postnatal deaths declined (p=0.01) due to reduced early neonatal mortality (p=0.002). Deaths from malformations (p<0.001), fetal and neonatal infections (p=0.03) and placental disorders (p<0.001) declined. Non‐optimal care (22.5% of deaths, 2.3‰ of total births), avoidable deaths (13.1% of deaths, 1.3‰ of total births), and maternal neglect (7.5% of cases with non‐optimal care, 0.6‰ of total births) did not change. Death during transport was rare (n=5), and no deaths occurred at maternity homes. Non‐cohabitance, smoking and undiagnosed SGA new borns declined, and the level of education increased in the study population.

Conclusion. The improvement is due to a reduction in intrapartum deaths and early neonatal mortality in preterms. A constant high rate of unexpected intrauterine deaths in non‐hospitalized patients is a challenge for antenatal health care providers.
Schwannoma of the clitoris
Authors:   Plácido Llaneza, Fresno Florentino , Ferrer Javier
Published: March 2003

Schwannoma is a tumor of the peripheral nerve sheath, which rarely affects the female genitalia. These tumors are often associated with von Recklinghuasen neurofibromatosis; however, they have also been reported in patients without that disease, and its most common location is the posterior mediastinum, the retroperitoneum, the head and neck, and the extremities. Simple surgical excision and follow up is the most convenient treatment (1).
Value of urinary prophylaxis with methenamine in gynecologic surgery
Authors: Schiøtz Hjalmar A. , Guttu Kristian
Published: March 2003

Background.  There is a high risk of postoperative bacteriuria and urinary tract infection after gynecologic surgery. Postoperative asymptomatic bacteriuria often disappears without treatment, but 15–20% of patients still require treatment for postoperative urinary tract infection. This study was carried out to assess the value of prophylactic treatment with methenamine hippurate after routine gynecologic surgery.

Methods.  This was a prospective, randomized, double‐blind, placebo‐controlled clinical trial comprising 145 patients undergoing routine gynecologic laparotomy or vaginal plastic surgery using a Foley catheter for 24 h. Antibiotics were not used. Subjects received 1 g Hiprex or placebo twice daily for 5 days. Urine was cultured preoperatively, at catheter removal, and 2 days later. Patients with positive cultures were not given antibiotics unless they were symptomatic. The follow‐up period was 1 month.

Statistics.  The chi‐square test, Fisher exact test, and t‐test were used with level of significance at 0.05, and odds ratios with 95% confidence intervals were calculated.

Results.  Asymptomatic bacteriuria was diagnosed in 36 cases (50.0%) in the placebo group and 22 cases (30.1%) in the methenamine group (p = 0.02). Urinary tract infection was diagnosed in 10 cases (13.9%) in the placebo group and two cases (2.7%) in the methenamine group (p = 0.03). There were few adverse events.

Conclusions.  Prophylactic treatment with methenamine hippurate significantly reduces the incidence of postoperative bacteriuria and urinary tract infection.