bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Appropriateness of Pacemaker Mode Selection in Bradycardia Pacing:
Authors: IRWIN MARLEEN E. , BAINEY KEVIN R. , SENARATNE MANOHARA P. J.
Published: December 2003

Although guidelines for selection of the appropriate pacing mode have been published, little data is available on how closely these are followed in the clinical setting. All 738 patients (men 412, women 326; age 73.4 ± 0.46 years; range 19–101 years) who underwent pacemaker implantation from 1996 to 2000 were reviewed to determine if the appropriate mode was selected based on the ACC/AHA guidelines with the data collected prospectively. Demographic, investigational, and implantation data including the presence of sinus disease and/or atrioventricular block, diagnosis, indication for pacing, ACC/AHA class indication for device therapy, recommended ACC/AHA mode, implanted mode, and reason for not using the recommended mode were entered into an SPSS data base. Of 738 patients, 708 were cross‐tabulated for a match to the guidelines of which 358 (50.6%) had a mode selected that did not conform. The reasons were advanced physical disability (16%), physician choice without identifiable reason (21%), rate modulation selected without identifiable indication (16%), DDD implanted instead of VDD (25%), advanced age (9%), rare need for pacing (6%), a need for specific device features (5%), and unstable stimulation thresholds or difficult venous access (2%). In the treatment of bradyarrhythmias, deviation from the ACC/AHA indicated mode occurred in a substantial proportion of pacing system implantations. However, in many, the deviation appeared appropriate considering the patient's clinical status. Nevertheless, in a smaller proportion of patients the deviation appeared inappropriate requiring rectification. The two outstanding categories were: (1) elderly denied a dual chamber system with no clinical explanation and (2) selection of rate‐modulated devices without any indication of chronotropic incompetence. (PACE 2000; 26:2301–2307)
The Nature and Frequency of Postimplant Surgical Interventions:
Authors: PARSONNET VICTOR , CHEEMA ASAD
Published: December 2003

The purpose of this retrospective study was to investigate the nature and frequency of surgical reinterventions after primary pacemaker implantation in patients who survived at least 20–30 years. Eighty‐five such patients were identified, 32 of whom had radioisotopic (nuclear) implants, and 53 lithium battery powered lithium units. Excluding reoperations within the first 3 months, patients with nuclear implants experienced about two reoperations in 25 years, while those with lithium experienced one every 8 years. The most frequent reasons for surgery were pulse generator replacements, lead revisions, and mode changes, particularly in the nuclear group. There were no premature device failures. This study allows us to make reasonable predictions to patients about the experience a pacemaker implantation, and reassures us about the reliability of the devices that were implanted in the past. (PACE 2003; 26:2308–2312)
Permanent Pacing Lead Insertion Through the Cephalic Vein Using an Hydrophilic Guidewire
Authors: NERI ROBERTO , CESARIO ANTONIO SILVIO , BARAGLI DANIELA , MONTI FRANCESCO , DANISI NICOLA , GLACIALE GIOIA , GAMBELLI GIANCARLO
Published: December 2003

The cephalic vein (CV) should be preferred to the subclavian vein for the insertion of permanent pacing leads because of better results. Unfortunately, the direct lead introduction using the standard CV cutdown is often unsuccessful. This study evaluated the efficacy and safety of a steerable hydrophilic guidewire (HGW) for lead insertion through the CV. An HGW was successfully introduced through the cephalic vein and into the subclavian vein. Over a 6‐month period, 115 consecutive patients underwent pacemaker implantation. In nine (7.8%) patients, the cephalic vein did not allow lead or guidewire introduction. The direct introduction of the leads through the CV was successful in 55 (51.9%) of 106 patients. In 14 (12.2%) additional patients, a lead was inserted through the CV using a standard guidewire. The use of an HGW and of a split introducer allowed successful insertion of at least one lead in 35 (30.4%) additional patients. Overall, the HGW was successful in 35 (94.6%) of 37 of patients in which the technique was attempted. The CV approach was successful in 104 (90.4%) of 115 patients. In conclusion, the use of an HGW allows the insertion of a pacing lead through the CV in the great majority of patients in whom direct introduction and the use of a standard guidewire had failed. The technique significantly improves the success rate of the CV approach and may help to improve the acute and long‐term results of permanent cardiac pacing. (PACE 2003; 26:2313–2314)
Quinolones:
Authors: KATRITSIS DEMOSTHENES , CAMM A. JOHN
Published: December 2003

Quinolones block the rapid component of the delayed rectifier potassium current (Ik) in a dose dependent manner. This electrophysiological action translates into prolongation of the QT interval and may predispose to development of torsades de pointes. QT prolongation appears to be a class effect but there is a wide range of potency among class members. According to the available evidence, the fluoroquinolones that are currently on the market present a low risk of drug induced torsades de pointes, with a frequency of this adverse event occurring at a rate of approximately 0.2–2.7 per million prescriptions. The safest member of the class appears to be ciprofloxacin. ECG monitoring during initiation of quinolone treatment is indicated only in patients with conditions known to predispose to torsades or to those receiving concomitant medications that prolong the QT interval. (PACE 2003; 26:2317–2320)
Reproducible Induction of Atrioventricular Nodal Reentrant Tachycardia with Adenosine Triphosphate
Authors: OKUMURA YASUO , WATANABE ICHIRO , OSHIKAWA NAOHIRO , MASAKI RIKO , OHKUBO KIMIE , YAMADA TAKESHI , KOFUNE TATSUYA , WAKITA RIE , TAKAGI YASUHIRO , HASHIMOTO KENICHI , SAITO SATOSHI , OZAWA YUKIO , KANMATSUSE KATSUO
Published: December 2003

A 29‐year‐old woman was referred for electrophysiological testing and radiofrequency ablation because of repeated episodes of palpitation of a 8‐year duration. The 12‐lead ECG during palpitations showed narrow QRS tachycardia at a rate of 160 beats/min. Dual AVN physiology according to electrophysiological criteria was not shown by single atrial extrastimulation and the tachycardia could not be induced. Slow/fast atrioventricular nodal reentrant tachycardia (AVNRT) was induced once by double atrial extrastimuli, but it was not reproducible. However, intravenous bolus injection of adenosine triphosphate (12.5 mg) during sinus rhythm led to reproducible initiation of slow/fast AVNRT. (PACE 2003; 26:2321–2323)
Upgrade of a Chronic Unipolar Pacemaker to a Biventricular Pacemaker System
Authors: DELACEY WILLIAM A. , DOW MARLENE T.
Published: December 2003

With the development of cardiac resynchronization for patients with symptomatic heart failure and electrical dyssynchrony, there are patients with chronic pacemakers that meet the indications for biventricular pacing. Typically, this involves placement of the left ventricular lead with generator change to a dual chamber biventricular pacemaker, maintaining use of the right‐sided leads. There are patients with older pacemaker systems that have unipolar leads with 5/6‐mm pin connectors. These patients present challenges to upgrade that are separate from typical IS‐1 system upgrades. Currently there are no pacemakers manufactured that accept the chronic 5/6‐mm unipolar leads directly with the additional IS‐1 left heart lead. This report presents one such case in which a combination of adaptor and lead replacement resulted in upgrade to a biventricular system. (PACE 2003; 26:2324–2325)
Arrhythmogenic Right Ventricular Cardiomyopathy (Naxos Disease):
Authors: NARIN NAZMI , AKCAKUS MUSTAFA , GUNES TAMER , ALPAY CELIKER  , BAYKAN ALI , UZUM KAZIM , FERAHBAS AYTEN
Published: December 2003

Naxos disease is a recessively inherited arrhythmogenic right ventricular cardiomyopathy in which the cardiac phenotype is associated with palmoplantar keratoderma and woolly hair. This disease is a heart muscle disorder causing life‐threatening ventricular arrhythmias, heart failure, and sudden cardiac death. The pathological hallmark of the disease is the progressive replacement of myocardial cells by fat and fibrous tissue. It appears in families descending from the Hellenic island of Naxos. We presented a 13‐year‐old Turkish boy with Naxos disease associated with ventricular tachycardia because of its rarity, and reviewed the literature. (PACE 2003; 26:2326–2329)
Acute Pulmonary Edema Secondary to Myocardial Damage After Electrical Cardioversion
Authors: ROLLÁN MARÍA JESÚS , SAN ROMÁN JOSÉ ALBERTO , BRATOS JOSÉ LUIS , MUÑOZ ANA CRISTINA , CASERO ANTONIO , CARRASCO FRANCISCO JAVIER
Published: December 2003

Direct cardioversion used in the treatment of various cardiac arrhythmias is a highly effective and simple procedure with infrequent complications. An uncommon complication is the occurrence of pulmonary edema. This report describes a 68‐year‐old woman with normal coronary arteries who experienced pulmonary edema following cardioversion secondary to myocardial injury demonstrated by ECG changes and elevation of troponin T. (PACE 2003; 26:2330–2332)
Treatment of Pacemaker Induced Severe Mitral Regurgitation with Biventricular Pacing in Two Patients with a Normal Left Ventricular Ejection Fraction
Authors: IRWIN JAMES M. , GLOVER MATTHEW U. , BAROLD S. SERGE
Published: December 2003

This report describes two patients who developed severe mitral regurgitation and drug refractory congestive heart failure after implantation of a conventional pacemaker. Both patients had a normal left ventricular ejection fraction. Dramatic long‐term improvement occurred following the institution of biventricular pacing that resulted in mild mitral regurgitation. The findings illustrate the benefit of cardiac resynchronization therapy in pacemaker induced left ventricular dyssynchrony causing severe mitral regurgitation and severe congestive heart failure in selected patients with a normal left ventricular ejection fraction. (PACE 2003; 26:2333–2335)
A Safe and Simple Method for Management of Frozen Pacemaker Leads
Authors: GÜLDAL MUHARREM , ALTIN ALI TIMUÇIN , ÖZDEMIR AYDAN ONGUN , AKYÜREK ÖMER , KARAOǦUZ REMZI , ORAL DERVIŞ
Published: December 2003

The traction of frozen leads from the generator header is difficult in some patients. This report describes the authors' experience with frozen leads in which the lead pins were removed by pushing with the tip of screwdriver from the hole created with a scalpel blade at the closed end of the generator header. (PACE 2003; 26:2336–2337)
Pseudotermination of Atrioventricular Nodal Reentrant Tachycardia Related to Isorhythmic Atrioventricular Dissociation
Authors: MARUYAMA MITSUNORI , KAWAGUCHI NAOMI , MIYAMOTO SHINJIRO , TADERA TAKESHI , INO TAKESHI , ATARASHI HIROTSUGU
Published: December 2003

Unusual manifestations of the mode of termination were observed in a patient with atrioventricular nodal reentrant tachycardia (AVNRT). After administration of verapamil during AVNRT, isorhythmic atrioventricular dissociation occurred without termination of the tachycardia. The sinus rate was slightly faster than that of the AVNRT, leading to the P wave preceding the QRS complex with a normal PR interval (e.g., pseudotermination). This phenomenon emphasizes the importance of continuous monitoring during an attempt to terminate AVNRT. (PACE 2003; 26:2338–2339)
The clinical relevance of cytokeratin phenotyping in needle biopsy of liver metastasis
Authors: TOT TIBOR , SAMII SIRI
Published: December 2003

Although cytokeratin (CK) phenotyping of metastatic tumors is now routine in many laboratories, the clinical relevance of the procedure has seldom been addressed. We carried out a prospective clinical study of 134 consecutive cases of metastatic adenocarcinoma of the liver diagnosed by needle biopsies stained routinely for CK20 and CK7. The most probable localization of the primary tumor, deduced from this staining pattern, was stated in the original pathology report. The present study compared this assignment with the information available at the time of interpretation of the liver biopsy, to the results of the subsequent clinical investigation, and to the officially reported cause of death as outcome. As expected, the primary tumors were localized in the colon or in the rectum in 85% (34/40) of the CK20+/CK7− metastases. The definite diagnosis remained metastatic colorectal carcinoma in 83% (15/18) of the cases with diagnosed colorectal cancer before the liver biopsy. In the cases without a known primary tumor when the liver biopsy was interpreted, primary colorectal localization was accurately predicted in 86% (19/22) of the patients. Compared to the outcome, 77% (36/47) of the CK20+/CK7+ metastases had the expected pancreaticobiliary primary localization in 83% (30/36) without any primary tumor being known at the time of interpretation of the liver biopsy. In contrast, the majority of CK20− metastatic carcinomas had an unexpected primary localization, 50% (16/32) in the CK20−/CK7+ and 60% (9/15) in the CK20−/CK7− subgroup. In addition, the origin of the liver metastasis remained unknown in 37% (12/32) of CK20−/CK7+ cases. Thus, the CK20+/CK7− phenotype indicates a colorectal origin of the liver metastasis with considerable accuracy and independently of the available clinical information. The same is true for CK20+/CK7+ metastases, which indicate primary tumor localization in the pancreas or in the biliary tree. The results in the CK20− subgroups of the liver metastases are disappointing and cannot substantially help the clinical investigation.
Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis
Authors: NAM SEON YOUNG , LEE HYE SEUNG , JUNG GYUNG‐AH , CHOI JIMI , CHO SUNG JIN , KIM MIN KYU , KIM WOO HO , LEE BYUNG LAN
Published: December 2003

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt‐positive and lymph node‐negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.
Altered immunoglobulin isotype profile and anti‐immature worm surface immunoglobulins in mice harboring a praziquantel‐resistant Schistosoma mansoni isolate
Authors: HANALLAH SOAD , EL‐LAKKANY NAGLAA , MAHMOUD SOHEIR , MOUSA MONA , BOTROS SANAA
Published: December 2003

After placement in mice of PZQ‐sensitive and ‐insensitive S. mansoni isolates obtained from villagers responding and not responding to PZQ, parasitological criteria reflecting their biological development and also the host anti‐immature worm immunoglobulin isotypes were examined 8 and 10 weeks post infection. Hepatic granuloma diameter, hepatic histopathological changes and immunolocalization of IgG and IgM on the surface of PZQ‐sensitive and ‐resistant worms were also examined 10 weeks post infection. Data showed that parasitological criteria were not significantly different between mice infected with the PZQ‐sensitive and ‐insensitive S. mansoni isolates. As regards serum immunoglobulins, in mice infected with the PZQ‐insensitive S. mansoni isolate, IgG and IgG1 were significantly (p<0.05) lower 8 and 10 weeks post infection, respectively (1.41±0.07 & 1.08±0.10 and 1.35±0.06 & 1.09±0.07) than in mice infected with the PZQ‐sensitive S. mansoni isolate (1.73±0.15 & 1.38±0.10 and 1.73±0.17 & 1.54+0.21) after the same observation periods. IgM level was nearly the same while IgE was lower than that recorded in mice infected with the PZQ‐sensitive S. mansoni isolate. IgG immunofluorescence was also lower (60%±6.78) on the surface of resistant worms than that of sensitive worms (66.6%±5.27); meanwhile, hepatic granuloma diameter was significantly larger (296.5±3.0 vs 283.6±4.0) in mice infected with the PZQ‐insensitive S. mansoni isolate with higher percentage of intact eggs. Differences in the immunogenic make up of PZQ‐sensitive and ‐insensitive S. mansoni isolates qualitatively and/or quantitatively favoring a certain Th cell subpopulation response could be the underlying reason for such differences recorded in the host immunoglobulin isotype response and also the egg‐induced hepatic histopathological changes.
New Prehistoric sites along the Omani coast from Ra's al‐Hadd to Ra's al‐Jins
Authors: USAI DONATELLA
Published: December 2003

The information gathered from the study of surface collections is still an extremely important source of knowledge of prehistoric Oman. The data presented here come from some sites found during a survey by the Italian‐French team working in the Ra's al‐Hadd Project. Technological, typological and typometric analyses of the lithic material are used to suggest a tentative chronology.
Dilmun stamp seals and the royal cap
Authors: HØJLUND FLEMMING
Published: December 2003

It will be argued in this article that the specific shape of the stamp seals used around 2000 BC in eastern Arabia (ancient Dilmun) was charged with a meaning that can be retrieved when viewed within a culturally and historically specific situation (1).
Reflections on the linguistic map of pre‐Islamic Arabia
Authors: MACDONALD M. C. A.
Published: December 2003

At a workshop on ‘Civilisations de l’Arabie préislamique' in Aix‐en‐Provence in February 1996, I was asked by the organizers to give a survey of the state of our knowledge of the languages and scripts of pre‐Islamic Arabia and to propose a coherent set of definitions and terms for them, in an attempt to clarify the numerous misapprehensions and the somewhat chaotic nomenclature in the field. I purposely concentrated on the languages and scripts of the Arabian Peninsula north of Yemen, and only mentioned in passing those of Ancient South Arabia, since these were to be the subject of another paper. Unfortunately, four years after it took place, the proceedings of this workshop remain unpublished. In the meantime, the contents of my paper have circulated widely and I, and others, are finding it increasingly frustrating having to refer to it as ‘forthcoming’. I am therefore most grateful to the editor of AAE for allowing a considerably revised version of my paper to be published here. It should be seen as an essential preliminary ground‐clearing for my detailed discussion of the Ancient North Arabian languages and scripts which will appear early in 2001 in The Cambridge Encyclopedia of the World's Ancient Languages (ed. R.D. Woodard, Cambridge University Press) and my book Old Arabic and its legacy in the later language. Texts, linguistic features, scripts and letter‐orders, which is in preparation.
Early settlement in Hadramawt: preliminary report on prehistoric occupation at Shi'b Munayder
Authors: McCORRISTON JOY
Published: December 2003

While excavation and survey in Wadi Hadramawt itself has documented extensive first‐millennium population centres and complex irrigation systems, earlier settlement and production remain poorly documented. Results of recent survey and test excavations in the mountainous hinterlands of southern Arabia have revealed scattered settlement near fossil springs that may have provided an important focus from as early as 6000 years ago. Lithic studies of surface material suggest that the widespread house sites at Shi'b Munayder in Wadi Idim were re‐occupied or re‐used as late as the Iron Age early‐mid‐first millennium BC. But stratigraphic evidence and a radiocarbon date point to an earlier establishment of settlement during at least the post‐Neolithic second millennium BC. The site of Shi'b Munayder, the earliest reported settlement in Hadramawt, seems to suggest that Hadrami peoples living at the time of the early establishment of complex centres retained ties with cultural groups to the east rather than with highland northern Yemen.
Notes on the shell and bone rings from Sharm
Authors: BARKER DIANE
Published: December 2003

A group of thirteen fragmentary and complete shell and bone rings was excavated at Sharm, including one example likely to be a bracelet. The function of the objects as rings is undisputed. A number of the rings appear to be manufactured from Conus sp., whereas the remainder are apparently made from bone.
Notes on a decorated spiny oyster from Sharm
Authors: BARKER DIANE , HARTNELL TOBY
Published: December 2003

S‐305 is the worked remnant of one half of a spiny oyster which exhibits drill marks consistent with single and double dot‐in‐circle motifs. The object is briefly described with a view to determining its function. The manufacturing marks are analysed elsewhere in this volume by Katia Davis.
Iron Age Gold Mining: A Preliminary Report on Camps in the Al Maraziq Region, Yemen
Authors: MALLORY‐GREENOUGH LEANNE , GREENOUGH JOHN D. , FIPKE CHARLES
Published: December 2003

Ancient geologists in Yemen and Egypt recognized that quartz veins surrounding caldera‐collapse complexes (exhumed explosive volcanoes) were gold bearing and actively sought out these geologic environments. Rock hammerstones, anvils and grinders are found in camps on both sides of the Red Sea, indicating that mining and metallurgical extraction technology and knowledge were also widespread during the Iron Age. The technology and overall layout of the Yemen sites is equivalent with New Kingdom to Late Period Egyptian sites, and there is no evidence of smelting, which is a Greco‐Roman Period development. It is not known who controlled the Yemen mines, but the large number of adits in the Al Maraziq area suggests that these gold mines may have been important to local, regional and possibly international economies.
Altsüdarabisches aus dem Nachlaß Mahmud al‐Ghul
Authors: HAYAJNEH HANI
Published: December 2003

A part of the papers of the late Professor Mahmud al‐Ghul is presently housed at the Institute of Archaeology & Anthropology at the Yarmouk University in Jordan. This article shall give a brief overview of this Nachlaß that contains casts and photos of inscriptions. Then we will deal with the casts of several Old South Arabian inscriptions which the author has found in the Nachlaß. The other material of the Nachlaß will be published systematically.
Asimah: Neue 14C‐Datierungen zum späten 3. vorchristlichen Jahrtausend auf der Halbinsel Oman
Authors: GÖRSDORF JOCHEN , VOGT BURKHARD
Published: December 2003

The third millennium BC domestic sites of Asimah (Emirate of Ras al‐Khaimah, U. A. E.), excavated in 1988 and published in 1994, produced a common Umm an‐Nar inventory, but with a high percentage of imported Indus Valley pottery. A comparison of finds with the well‐stratified Hili‐8 sequence is contrasted with five new radiocarbon dates which, together with the artefacts recovered, place Asimah in the late third millennium BC chronological and cultural context of Tell Abraq.
Notes on two alabaster fragments from Sharm
Authors: BARKER DIANE
Published: December 2003

Two alabaster objects were recovered from the excavations at Sharm, both having unusual shapes. The function of each piece is unknown, although it is suggested that they may have been blanks or cores for the manufacture of other alabaster items.
The Influence of Different Types of Antibodies on In Vitro Fertilization Results
Authors: MARDESIC T. , HUTTELOVA R. , MULLER P. , VOBORIL J. , MIKOVA M. , HULVERT J. , ULCOVA‐GALLOVA Z.
Published: December 2003

PROBLEM: The influence of anti‐sperm (ASA), anti‐phospholipid (APA), and anti‐zonal (AZA) antibodies on in vitro fertilization (IVF) results and the need for intracytoplasmic sperm injection (ICSI) were assessed. METHOD OF STUDY: Forty‐four couples with infertility of immunologic origin were investigated. ASA in serum and ovulatory mucus were studied by a tray agglutination test (TAT) and indirect mixed anti‐globulin reaction test (MAR) test, AZA were studied by passive hemagglutination and commercial enzyme‐linked immunosorbent assay (ELISA; BioGen, Germany), and APA were tested by ELISAs in immunoglobulin isotypes IgG and IgM. RESULTS: Because of failed or very low fertilization after standard IVF in the previous cycle, ICSI had to be used in five out of 15 cases with ASA (33.3%), in 16 out of 18 couples with AZA (89.4%), and in only one case if APA were present (9%). Clinical pregnancy rate was 60% in cases with ASA, 38.5% with AZA, and 27.3% per embryo transfer (ET) if APA were detected. CONCLUSIONS: Immunologic infertility can be treated by IVF with very good results. The most important group are women with AZA, in whom IVF–ICSI without any delay is recommended.
Interleukin‐1 Levels in the Supernatant of Conditioned Media of Embryos Grown in Autologous Endometrial Coculture: Correlation with Outcome After In Vitro Fertilization
Authors: SPANDORFER S.D. , NEUER A. , LIU H.‐C. , BIVIS L. , CLARKE R. , VEECK L. , WITKIN S.S. , ROSENWAKS Z.
Published: December 2003

PROBLEM: To determine if interleukin (IL)‐1 produced by autologous endometrial coculture (AECC) was associated with outcome in patients with a history of multiple in vitro fertilization (IVF) failures.
METHOD OF STUDY: The conditioned media (CM) from AECC cells exposed or
non‐exposed to human embryos was analyzed for IL‐1.
RESULTS: Embryos grown on AECC demonstrated a significant improvement in
number of blastomeres and fragmentation (frag) when compared to embryos
grown in conventional media without ECC (6.4±1.3 vs.
5.5±1.2 blastomeres and 14.6±9.3% vs. 18.4±9.8%
frag; P<0.008 and 0.003, respectively). When IL‐1α and
IL‐1β were undetectable in the CM, the embryos grown in ECC were of
improved quality as compared to the embryos grown only in conventional
media. Conversely, IL‐1ra levels in the CM were positively associated
with embryo quality. Exposure or non‐exposure to an embryo did not result
in differing levels of IL‐1α, IL‐1β, or IL‐1ra in the CM.
IL‐1β levels were negatively associated with clinical pregnancy
outcome (3.3 pg/mL (pregnant, n=12) vs. 27.1pg/mL (not pregnant, n=17);
P=0.008, Mann–Whitney U‐test). IL‐1α and IL‐1ra levels were not associated with outcome. CONCLUSIONS: We have demonstrated a significant improvement in blastomere number and frag with ECC. The presence of IL‐1β in the CM was negatively associated with embryonic development and clinical pregnancy. The presence of IL‐1α in the CM was negatively associated with embryonic development and the presence of IL‐1ra in the CM was positively associated with embryonic development. Whether IL‐1β itself interferes with successful outcome after embryo transfer or if it is a marker for undetected endometritis in the biopsy specimens remains to be determined.
Relationship Between Ovarian Stimulation Regimen and Cytokine Concentration in Follicular Fluid and Their Effect on Fertilization and Pregnancy Outcome of Patients Undergoing ICSI Program
Authors: HAMMADEH M.E. , BRAEMERT B. , BALTES S. , ROSENBAUM P. , SCHMIDT W. , GEORG T.
Published: December 2003

PROBLEM: The aims of this study were to evaluate the presence of insulin‐like growth factor (IGF)‐I, platelet‐derived growth factor (PDGF), and epidermal growth factor (EGF) in pre‐ovulatory follicular fluid (FF) in patients undergoing ovarian hyperstimulation for intra‐cytoplasmic sperm injection (ICSI) treatment, to determine the differences between the concentrations of these cytokines in relation to ovarian stimulation regimens, and to find the relationship between these parameters and estradiol 17‐β, progesterone, and luteinizing hormone (LH) concentration in serum, as well as ICSI outcome. METHOD: IGF‐I and PDGF were measured in the FF of 85 patients. The IGF‐I levels were measured by radioimmunoassay, whereas the concentrations of PDGF and EGF were measured by enzyme‐linked immunosorbent assay technique, using commercially available kits. RESULTS: IGF‐I (0.42±0.09 ng/mL), PDGF (307.3±274.5 pg/mL), and EDF (8.88±6.4 pg/mL) were present in pre‐ovulatory FF in patients undergoing ovarian hyperstimulation for ICSI treatment. The mean concentration of IGF‐I in the follicle‐stimulating hormone (FSH) group was significantly higher (P=0.036) than that found in the human
menopausal gonadotrophin (hMG)/FSH group, whereas no significant
difference in the mean concentrations of PDGF (P=0.58) and EGF was shown between all investigated groups. CONCLUSION: Controlled ovarian stimulation regimens affect only IGF‐I levels in FF and the cytokine concentrations of all investigated groups, in turn, showed no correlation either with steroid hormones in serum or ICSI outcome.
CA‐125 Levels are Related to the Likelihood of Pregnancy After In Vitro Fertilization and Embryo Transfer
Authors: BAALBERGEN A. , VAN DER WEIDEN R.M.F. , JANSSEN J.W.
Published: December 2003

PROBLEM: To assess the relationship between serum cancer antigen (CA)‐125 concentrations and the likelihood of pregnancy after in
vitro fertilization/embryo transfer (IVF/ET).
METHOD OF STUDY: A prospective longitudinal follow‐up study was conducted
in 44 IVF patients receiving luteinizing hormone‐releasing hormone (LHRH)
suppression, followed by human menopausal gonadotrophin (hMG). There were
no indications of endometriosis. Progesterone or human chorionic
gonadotrophin (hCG) were given as luteal support. Serum samples were
taken just before oocyte pick‐up (OPU), 14 days after ET and, after the
establishment of a clinical pregnancy, on day ET+21. Samples were stored
at −80°C until analysis. CA‐125 was measured using a
commercially available enzyme immunoassay (IMx CA‐125; Abbott, North
Chicago, IL, USA). The signed rank (paired samples) and Wilcoxon tests
were used for statistical analysis.
RESULTS: There were no differences in CA‐125 concentrations at the time
of OPU between pregnant (n=18) and non‐pregnant (n=26) IVF
patients. After OPU, the CA‐125 concentrations rose both in pregnant
(P<0.0001) and in non‐pregnant (P<0.001) patients.
This rise was greater after successful implantation, and 14 days after
ET, higher CA‐125 concentrations were found in the pregnant patients
(P<0.01). CONCLUSIONS: Differences in serum CA‐125 concentrations between pregnant and non‐pregnant IVF patients appear to be related to the likelihood of successful implantation.
No Cyclicity in Serum Vascular Endothelial Growth Factor During Normal Menstrual Cycle but Significant Luteal Phase Elevation During an In Vitro Fertilization Program
Authors: UNKILA‐KALLIO L. , VUORELA‐VEPSÄLÄINEN P. , TIITINEN A. , HALMESMÄKI E. , YLIKORKALA O.
Published: December 2003

PROBLEM: To compare changes in serum vascular endothelial growth factor (VEGF) levels during normal and in vitro fertilization
(IVF) cycles.
METHOD OF STUDY: Ten healthy women with ovulatory cycles and 37 infertile
women participating in an IVF program were followed by frequent serum
samples and with VEGF measurements throughout their cycles.
RESULTS: Serum VEGF remained unchanged during the normal menstrual cycle,
whereas the IVF program participants showed elevations in serum VEGF in
the luteal phase of the cycle. When data from controls and patients were
pooled, redundant midluteal VEGF level correlated with progesterone and
with peak follicular phase estrogen level. The midluteal VEGF level in
the IVF cycles was associated with body mass index (P<0.01) and
progesterone level (P<0.05) by multiple regression. The 14 women conceiving tended to have higher VEGF levels than those failing to become pregnant. CONCLUSIONS: The IVF program was associated with increased synthesis of VEGF either in the ovaries, endometrium, or at other sites and this may be of significance for the outcome of IVF.
Activated Protein C Resistance and Factor V Leiden Mutation can be Associated with First‐ as well as Second‐Trimester Recurrent Pregnancy Loss1
Authors: YOUNIS JOHNNY S. , BEN‐AMI MOSHE , BRENNER BENJAMIN , OHEL GONEN , TAL JOSEPH
Published: December 2003

PROBLEM: To examine whether the occurrence of activated protein C resistance (APCR) and factor V Leiden mutation differs in women with first‐ compared to women with second‐trimester unexplained recurrent pregnancy loss. METHOD OF STUDY: Seventy eight consecutive women with two or more unexplained post‐embryonic recurrent pregnancy losses and 139 fertile women with at least one successful pregnancy and no abortions were prospectively investigated for APCR and the factor V Leiden mutation. No women were pregnant at the time of investigation. APCR was defined as APC–sensitivity ratio (APC–SR) of ≤2.0. All patients with an APC–SR ≤2.4 were investigated for the factor V Leiden mutation. Women in this study were divided into three groups. Group A included only women with a history of recurrent first‐trimester embryonic loss (37 women) and Group B included women with second‐trimester abortions with or without additional first‐trimester abortions (41 women). Group C included the controls (139 women). RESULTS: APCR and factor V Leiden mutations were significantly more prevalent in all recurrent pregnancy loss patients in this study as compared to controls, 38% (30/78) and 19% (15/78) in contrast to 8% (11/139) and 6% (8/139), respectively. All three groups in the study were comparable regarding age, parity, and number of living children, whereas Groups A and B were also comparable regarding gravidity. Mean APC–SRs were significantly higher in Group C as compared to Groups A and B. The incidence of APCR was significantly higher in Groups A and B, as compared to controls, 27 and 49% in contrast to 8%, respectively. Moreover, the incidence of the factor V Leiden mutation was significantly higher in Groups A and B as compared to Group C, 16 and 22% as distinct from 6%, respectively. The incidence of APCR was higher in Group B as compared to Group A, 49% in contrast to 27%, with borderline significance; however, the factor V Leiden mutation did not significantly differ between the two groups. CONCLUSIONS: APCR and factor V Leiden are associated with unexplained recurrent pregnancy loss. The occurrence of APCR and factor V Leiden seems to be linked to post‐embryonic first‐trimester as well as second‐trimester recurrent pregnancy loss. The significance of acquired, non‐heritable APCR in recurrent fetal loss patients, especially in the second‐trimester aborters, is still to be determined.
Prednisone and Aspirin Improve Pregnancy Rate in Patients with Reproductive Failure and Autoimmune Antibodies: A Prospective Study
Authors: GEVA ELI , AMIT AMI , LERNER‐GEVA LIAT , YARON YUVAL , DANIEL YAIR , SCHWARTZ TAMAR , AZEM FOAD , YOVEL ISRAEL , LESSING JOSEPH B.
Published: December 2003

PROBLEM: The study was conducted to investigate the efficacy of prednisone and aspirin in autoantibody seropositive patients with repeated in vitro fertilization–embryo transfer (IVF–ET) failure. METHODS OF STUDY: The study group comprised 52 consecutive patients seropositive for non‐organ‐specific autoantibodies, i.e., anti‐cardiolipin antibodies (ACA), anti‐nuclear antibodies (ANA), anti‐double‐stranded (ds) DNA, rheumatoid factor (RF), and lupus anti‐coagulant (LAC). These patients were treated with prednisone, 10 mg per day, and aspirin, 100 mg per day, starting 4 weeks before induction of ovulation in 52 IVF cycles. RESULTS: The clinical pregnancy rate per cycle was 32.7% (17/52). No increased incidence of pregnancy complications, including premature labor, gestational diabetes mellitus, and pregnancy‐induced hypertension, were found. CONCLUSIONS: Combined treatment of prednisone for immunosupression and aspirin as an anti‐thrombotic agent, starting before ovulation induction, may improve pregnancy rate in autoantibody seropositive patients who have had repeated IVF–ET failures.
Involvement of Serum and Lipopolysaccharide in the Production of Interleukin‐1‐ and Interleukin‐6‐like Molecules by Human Sperm Cells
Authors: HULEIHEL MAHMOUD , HOROWITZ SHULAMITH , LEVY AYELET , HULEIHEL MAHMOUD , LUNENFELD EITAN , POTASHNIK GAD , MAZOR MOSHE , HOROWITZ SHULAMITH , HULEIHEL MAHMOUD , LUNENFELD EITAN , HOROWITZ SHULAMITH , LEVY AYELET , POTASHNIK GAD , MAZOR MOSHE , GLEZERMAN MAREK
Published: December 2003

PROBLEM: To examine the capacity of sperm cells from fertile and infertile men to secrete interleukin (IL)‐6, and the involvement of serum factors and lipopolysaccharide (LPS) in the regulation of IL‐6 and IL‐1 production by sperm cells. METHODS: Swim‐up sperm cells from fertile (donors) and oligoteratoasthenospermic (OTA)‐infertile men were incubated with or without 5% fetal calf serum (FCS) and LPS (10 μg/mL) for 2–24 hr. After incubation, IL‐6 and IL‐1 bioactivities were measured in supernatants and lysates by specific bioassays (B9 cell proliferation assay and 1A‐5 system, respectively). RESULTS: IL‐6‐ and IL‐1‐like activities were observed to be produced by swim‐up sperm cells from both study groups. Stimulation of swim‐up sperm cells with either LPS or FCS or both together did not affect their capacity to produce IL‐1. However, LPS, but not serum increased the secretion levels of IL‐6 by swim‐up sperm cells. CONCLUSIONS: Swim‐up sperm cells from both study groups constitutively produce IL‐6 and IL‐1, and serum components did not affect this capacity. However, LPS was shown to increase the capacity of swim‐up sperm cells of both study groups to secrete IL‐6, but not IL‐1. Cytokines may be involved in the physiology and pathophysiology of sperm functions and, thus, may affect male fertility.
Effects of Interferon‐Γ on Secretion of Vascular Endothelial Growth Factor by Endometrial Stromal Cells
Authors: KAWANO YASUSHI , MATSUI NAOHIKO , KAMIHIGASHI SHOUKO , NARAHARA HISASHI , MIYAKAWA ISAO
Published: December 2003

PROBLEM: The aim of this study was to clarify the physiological effects of interferon (IFN)‐Γ on secretion of vascular endothelial growth factor (VEGF) by endometrial stromal (ES) cells. METHOD OF STUDY: ES cells were obtained from human uterine endometrium by enzymic digestion and filtration. The effects of IFN‐Γ on production of VEGF by ES cells were examined by analyzing VEGF mRNA expression with Northern blotting analysis and by assaying VEGF protein. RESULTS: IFN‐Γ inhibited VEGF mRNA and protein expression by ES cells in a dose‐dependent manner. In ES cells treated with IFN‐Γ, VEGF production was not significant until 6 hr of incubation and was significantly affected after 6 hr of incubation, but decreased significantly after 12 to 48 hr. IFN‐Γ also suppressed VEGF mRNA expression by ES cells. CONCLUSIONS: ES cells produce VEGF, which may contribute to endometrial neovascularization and proliferation. IFN‐Γ may play an important role in regulating VEGF production by ES cells.
Decreased Expression of Mac25 mRNA in Uterine Leiomyomata Compared with Adjacent Myometrium
Authors: KIM JUNG GU , KIM MYUNG HEE , MOON SHIN YONG , KANG SOON BEOM , LEE HYO PYO , LEE JIN YONG , KIM IK SANG
Published: December 2003

PROBLEM: The pathogenesis of uterine leiomyomata is still unclear. Recently it has been suggested that mac25 plays a tumor‐suppressive role in various tumors. The aims of this study were to evaluate a possible involvement of mac25 in the growth of leiomyoma and in the mechanism of a gonadotropin‐releasing hormone agonist (GnRHa) inducing shrinkage of leiomyoma. METHODS OF STUDY: Mac25 mRNA transcript was measured by Northern blot in total RNA extracted from the paired specimens of leiomyoma and adjacent myometrium from untreated patients (n=25) and from leiomyoma
specimens from GnRHa‐pretreated patients (n=10).
RESULTS: Mac25 mRNA expression was significantly lower in large leiomyoma
(more than 150 cm3 in volume) than in adjacent myometrium and
small leiomyoma (less than 120 cm3 in volume) from untreated patients. There was no difference in this expression between the proliferative and secretory phases of the menstrual cycle. Leiomyoma from GnRHa‐pretreated patients had mac25 gene expression levels similar to myometrium and small leiomyoma from untreated patients. CONCLUSIONS: Mac25 may be involved in the growth of uterine leiomyoma and the action of GnRHa may, in part, be mediated by mac25.
Inhibin A, Inhibin B and Activin A in Follicular Fluid of Infertile Women with Tubal Damage, Unexplained Infertility and Endometriosis1
Authors: AKANDE A.V. , KEAY S.D. , CAHILL D.J. , WARDLE P.G. , ASSELIN* J. , MUTTUKRISHNA S. , GROOME N.P.
Published: December 2003

PROBLEM: To measure and compare concentrations of inhibin A, inhibin B, activin A and oestradiol in the follicular fluid of women with endometriosis, tubal damage and unexplained infertility with oocyte quality and fertilising capacity. Also, to assess whether impaired follicular function in women with endometriosis might be related to altered inhibin or activin concentrations and whether this correlated. METHOD OF STUDY: Follicular fluids were collected from individual follicles during oocyte retrieval for in vitro fertilisation (IVF) in natural cycles. Inhibin A, inhibin B and activin A were measured using two‐site enzyme immunoassay, and oestradiol was assayed by fluoro‐immunometric method. RESULTS: Follicular fluid inhibin A levels were found to be significantly higher in women with endometriosis. Inhibin A was directly correlated with follicle size. There was no correlation between the levels of inhibin A, inhibin B, activin A and oocyte quality or fertilising capacity in the three groups of women. CONCLUSIONS: Follicular fluid concentration of inhibin A is elevated in follicles of women with endometriosis and is positively correlated with follicle maturation. However, we were unable to demonstrate any association between the follicular fluid concentrations of inhibin A, inhibin B, activin A or oestradiol and the quality and fertilisation capacity of oocytes in women with tubal damage, unexplained infertility or endometriosis.
Localization of Nitric Oxide Synthase in Human Trophoblast Cells: Role of Nitric Oxide in Trophoblast Proliferation and Differentiation
Authors: DAS CHANDANA , SANYAL MRINMOY , CHANDRA NAG TAPAS
Published: December 2003

PROBLEM: There are conflicting reports about the isoform of nitric oxide synthase (NOS) present in trophoblast cells. In this study, we have examined the presence of different NOS isoforms in trophoblast cells. In addition, the role of nitric oxide (NO) in trophoblast function has also been studied by investigating the possible role of nitric oxide in trophoblast proliferation and differentiation. METHOD OF STUDY: NOS isoforms in primary‐term trophoblast and JEG‐3 cells were identified by immunocytochemistry. The intracellular localization of this enzyme was determined by confocal laser scanning microscopy. Trophoblast proliferation was studied by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrasolium bromide (MTT) conversion assay and cellular differentiation was monitored by human chorionic gonodotropin (hCG) and progesterone secretion, measured by radioimmunoassay. RESULTS: The immunoreactive NOS was present in human trophoblast cells of normal term placenta and JEG‐3 cells (a choriocarcinoma cell line) maintained in culture. Nicotinamide adenine dinucleotide phosphate (NADPH)‐dependent diaphorase activity overlapped with the immunostaining of NOS. Specific antibodies against the different isoforms of NOS detected the presence of neuronal‐type NOS (nNOS) only. The other two isoforms, i.e., eNOS (endothelial) and iNOS (macrophage specific) were completely absent. The nNOS was localized in cell cytoplasm. In culture, JEG‐3 cells normally undergo proliferation and cytotrophoblast cells in primary culture differentiate to form hormone‐secreting syncytial cells. Sodium nitroprusside (SNP), a nitric oxide donor, when added to the culture, significantly increased proliferation of JEG‐3 cells and inhibited the differentiation of cytotrophoblast cells. The arrest by SNP in the formation of syncytial cells was further evidenced by the low secretion profile of hCG and progesterone. CONCLUSIONS: Our findings suggest for the first time the presence of nNOS in the human trophoblast cells and a previously unrecognized role of NO in trophoblast proliferation and differentiation.
Interleukin‐8 Levels and Granulocyte Counts in Cervical Mucus During Pregnancy
Authors: LUO LIHUA , IBARAGI TAMOTSU , MAEDA MAKIKO , NOZAWA MASAYUKI , KASAHARA TADASHI , SAKAI MASATOSHI , SASAKI YASUSHI , TANEBE KYOKO , SAITO SHIGERU
Published: December 2003

PROBLEM: We measured interleukin‐8 (IL‐8) and granulocyte counts in cervical mucus to assess local immunity and parturition. METHOD OF STUDY: We detected IL‐8 by enzyme linked immunosorbent assay (ELISA) and Western blotting. Granulocytes were counted on a slide glass containing mucus from the external cervical os. RESULTS: ELISA and Western blotting revealed IL‐8 in cervical mucus from both nonpregnant and pregnant women. There were no significant differences in cervical mucus IL‐8 levels or granulocyte counts between follicular, ovulatory, and luteal phases. However, IL‐8 and granulocyte counts were significantly decreased after menopause. IL‐8 and granulocyte counts were increased significantly during pregnancy, and were further increased after 38 weeks of gestation and at labor. IL‐8 levels were significantly correlated with granulocyte counts, based on the study of 678 samples (P<0.0001). CONCLUSION: IL‐8 is involved in the increase of cervical granulocytes and in the process of parturition.
Interleukin‐1β Down‐Regulates the Oxytocin Receptor in Cultured Uterine Smooth Muscle Cells
Authors: RAUK PHILLIP N. , FRIEBE‐HOFFMANN ULRIKE
Published: December 2003

PROBLEM: Intrauterine infection accounts for 20% of preterm labor and results in the production of decidual inflammatory cytokines, including interleukin‐1 (IL‐1). The oxytocin receptor plays a key role in the onset of preterm labor. Cytokines likely regulate oxytocin receptor expression through several cytokine‐induced DNA‐binding proteins. METHOD OF STUDY: The objective of this study was to evaluate the effect of the IL‐1 alone on oxytocin receptor number as measured by radioligand binding and immunocytochemistry, and oxytocin receptor mRNA as measured by reverse transriptase‐polymerase chain reaction (RT‐PCR) in cultured uterine myocytes. RESULTS: Unexpectedly, IL‐1 treatment decreased oxytocin receptor number from 111,067 to 23,941 receptors/cell. Loss of oxytocin receptor binding began after 8 hr of IL‐1 treatment and was reversible after IL‐1 removal. Immunocytochemistry confirmed a loss of cellular oxytocin receptors. Oxytocin receptor mRNA decreased beginning after 2 hr of IL‐1 treatment. CONCLUSIONS: IL‐1 down‐regulates the uterine oxytocin receptor in a time‐ and dose‐dependent fashion.