bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytokine profile in women with preeclampsia
Authors: Jonsson Yvonne , Ekerfelt Christina , Berg Göran , Ernerudh Jan , Nieminen Katri , Matthiesen Leif
Published: March 2003

Preeclampsia is a severe complication engaging 5–10% of all pregnancies. Immune mechanisms have been suggested in the etiology of this disease.

AIM:  To study the systemic spontaneous and fetus‐specific cytokine production by peripheral blood mononuclear cells (PBMCs) in women with preeclampsia and normal pregnancies.

METHODS:  PBMCs from nine women with preeclampsia and five women with normal pregnancies were stimulated in mixed leukocyte cultures with paternal cells (representing the fetus) and autologous blood lymphocytes. The stimulated and spontaneous production of IL‐4, IL‐10 and IFN‐α were analysed by ELISPOT and IL‐12 and IL‐13 in cell‐culture supernatants by ELISA. Cell‐culture supernatants were collected for 2–7 days of incubation.

RESULT:  The results are preliminary since analysis of data is going on. We found a trend of decreased IL‐10 production in response to paternal cells in preeclamptic women. Data for the other cytokines did not show any differences between groups.

CONCLUSION:  The material studied so far is limited and further studies are needed to draw any safe conclusions.
Enhancement of immunogenicity of JEG‐3 Cells by ectopic expression of HLA‐A*0201 and CD80
Authors: Koc Serpil , Kather Angela , Markert Udo , Schneider Achim , Dürst Matthias , Kaufmann Andreas M.
Published: March 2003

The chorioncarcinoma cell line JEG‐3 escapes immunity by secretion of leukocyte inhibitory factor suppressing leukocyte proliferation. The cells lack expression of classical HLA alleles but express nonclassical HLA‐G, which binds to killer inhibitory receptor of natural killer cells, preventing cytolysis. We investigated whether JEG‐3 cells are capable of immune stimulation after introduction of classical HLA and T‐cell costimulatory signals. JEG‐3 cells were transduced with vectors for HLA‐A*0201 and/or CD80. Parental JEG‐3, or JEG‐3/A2, JEG‐3/CD80, or JEG‐3/A2/CD80 were used to stimulate allogeneic T cells. While parental JEG‐3 cells induced only marginal proliferation of resting T cells, HLA‐A2 or CD80 expressing JEG‐3 induced enhanced proliferation. Double transfectants were most efficient. This difference was more obvious when T cells were preactivated by PHA. T cell lines restimulated with JEG‐3 transfectants were characterized for expansion, phenotypes, and cytolytic activity. HLA‐A2 matched and nonmatched donors were compared. T cells stimulated with JEG‐3/A2 or JEG‐3/CD80 were cytolytic towards parental JEG‐3 cells. Again double positive JEG‐3/A2/CD80 induced highest cytolytic activity, most obvious in HLA‐nonmatched donors suggesting alloreactivity to HLA. Our data suggest that, in spite of immunosuppressive mechanisms, proliferative and cytolytic T cell responses are induced by JEG‐3 cells when classical HLA and/or costimulatory signals are present on the cells.
Systemic cytokine response during listeria monocytogenes infection in pregnant BALB/C Mice
Authors: Abram Maja , Vuckovic Darinka , Doric Miljenko , Wraber Branka
Published: March 2003

Pregnancy has an important impact on the maternal immune system, associated with a shift in the Th1/Th2 cytokine balance towards a type‐2 response. However, listeria induced Th1 type cytokines are essential in host protection against this facultative intracellular bacterium. We have analyzed and compared the kinetics of maternal serum concentrations of IFN‐γ, IL‐10, TNF‐α, IL‐6 and KC by ELISA. Serum IFN‐γ levels in infected pregnant mice were significantly reduced in comparison to infected virgin animals, while IL‐10 levels were increased, being significantly higher on days 3 and 6 p.i. as compared to infected virgin mice. Upon L. monocytogenes infection, circulating TNF‐α concentrations were below the detection limit. However, on day 6 p.i., in pregnant mice elevated levels of TNF‐α were noticed, correlating to the severity of disease. Increased concentrations of IL‐6 have been shown to follow the kinetics of bacterial numbers in the liver of infected animals. Murine chemokine KC production in maternal circulation followed a similar pattern as IL‐6.

In comparison to virgin animals, pregnant mice mount lower levels of protective Th1 cytokines and are unable to eliminate the pathogen. Increased serum concentrations of IL‐10, along with proinflammatory cytokines, may well contribute to the severity of pregnancy‐associated listeriosis.

Maternal serum IL‐6 level showed the highest correlation with the course of infection and pregnancy outcome.
Protective effect of Vitamin E in an animal model of LPS‐Induced inflammation
Authors: Iborra A. , Mayorga M. , Estany S. , Martínez P.
Published: March 2003

Most sterility outcomes may be associated with the presence of an inflammatory response due to infections. This environment would lead to an inability of the endometrium to implant, protect and maintain viable embryos. We have established an animal model of inflammation in which the systemic administration of bacterial endotoxin (LPS) results in a low embryo implantation rate.

OBJECTIVES:  To investigate the effect of the inflammatory agent LPS on the embryo viability. To verify the ability of vitamin E (VE) in preventing the effect of LPS.

For preimplantation studies we used pregnant mice B6CBAF1 which were intraperitoneally (i.p.) inoculated with LPS alone or with liposomes containing different concentrations of VE 24 hr after LPS injection. The embryos were obtained from the oviduct and the preimplantation rate was evaluated.

The treatment of pregnant female mice with LPS inoculated i.p. produces a decrease in the number of preimplantational embryos in a concentration dependent manner: as compared with non‐treated LPS mice (100%), we obtained a 50–35% of preimplantational embryos with LPS treated mice. This LPS effect can be partially reverted by the administration of VE in animals treated with 4 or 6 mg/kg of LPS, but not in 10 mg/kg LPS treated mice. Preliminary results show that inflammatory cytokines are secreted by i.p. macrophages in LPS treated mice. In the present work we demonstrate the ability of VE to avoid an inflammatory environment and to allow viability.
Expression of HLA‐G in the human placenta
Authors: Dohr G. , Blaschitz A. , Juch H. , Hutter H.
Published: March 2003

The unique structure of the human placenta provides a separation between maternal and fetal tissues and circulations. Although the maternal–fetal proximity is very close, the placenta and the fetus are not rejected by the maternal immune system. Among the various factors implicated in the mother's tolerance of the fetus, a key factor has been attributed to HLA‐G molecules, which are expressed by specialized trophoblast cells. By the alternative splicing of its primary mRNA, HLA‐G, belonging to Class I MHC molecules, results in four membrane bound (HLA‐G1, ‐G2, ‐G3, ‐G4) and three soluble proteins (HLA‐G5, ‐G6, ‐G7). Which of these HLA‐G isoforms are expressed on the cell surface and which are secreted was the aim of our study.

Whereas the generally agreed upon opinion is that the full length HLA‐G1 isoform is expressed by extravillous cytotrophoblast cells, the source of soluble HLA‐G5 isoform and the expression of all other isoforms in the human placenta is still under debate. However, soluble HLA‐G products, which might be present in body fluids, could also come from membrane bound HLA‐G1 by shedding; a process, that has been described for classical HLA molecules. HLA‐G expression in organs, other than placenta and certain tumors, has not yet been explained convincingly.

Since immunological detection methods crucially depend on the antibodies and preparation techniques used, we investigated HLA‐G specific antibodies for their specificity and binding properties. We compared the binding ability of some antibodies on HLA‐G1, G2, ‐G5 transfected cell lines with naturally expressed placental HLA‐G molecules. A broad range of methods, from immunolocalization to protein‐biochemical and Elisa techniques, were used to clarify which HLA‐G isoform is actually expressed in the normal placenta.
Inducible H‐2M and constitutive H‐2O/H‐2A expression on trophoblast cells
Authors: Athanassakis Irene , Ranella Aathi , Voglis Ioannis , Simon Vassiliadis
Published: March 2003

Trophoblast cells escape maternal immune attack due to their class II negative state. This generally accepted hypothesis, however, became complicated when these antigens were shown induced by IFN‐γ, 5‐AzaC, LPS, mycobacterium and other factors, an expression correlated, as expected, to fetal abortion. Using untreated trophoblast cells as controls in the study of class II antigen regulation we found that, although the cells were not expressing surface class II molecules, they contained class II positive intracellular pools, which after short treatment with IFN could be emptied to the culture supernatants. Using immunofluorescence, ELISA, confocal microscopy, immunoaffinity purification, subcellular fractionation as well as Western blots and RT‐PCR experiments we localized, identified the class II proteins in trophoblasts and studied their mechanisms of excretion. It was shown that classical class II molecules co‐localized with the invariant chain in rab7 and rab11 positive endosomes and could be secreted from the cells via the endosomal pathway, since their extracellular detection could be inhibited by pepstatin, brefeldin and leupeptin. RT‐PCR experiments using H‐2M, H‐2O and H‐2A specific primers showed that H‐2O and H‐2A are constitutively expressed in trophoblasts, whereas H‐2M is inducible by IFN. Cyclohexamide treatment blocked secretion of class II antigens from these cells indicating that H‐2M is involved in the secretion and/or appearance to the membrane.
The significance of women's natural killer cell receptors repertoire in the maintenance of pregnancy
Authors: Varla‐Leftherioti. Marighoula
Published: March 2003

It has been suggested that decidual NK cells play a regulatory role in pregnancy with their heterocladic (activating/inhibitory) receptor repertoire to control trophoblast infiltration. Most of the NK receptors (NKRs) have as ligands HLA molecules (HLA‐C,‐G,‐E), which are expressed on invading trophoblast and they may interact with their NKR counterparts and provide self‐signals to evade trophoblastic damage.

When we studied the NKR repertoire in couples with unexplained recurrent spontaneous abortions by genotyping partners for NKRs (KIR and CD94/NKG receptors, known to have as ligands HLA molecules present on trophoblast), we found that aborting women usually have a limited inhibitory KIR (inhKIR) repertoire.

Our hypothesis that a limited inhKIR repertoire predisposes to miscarriage, because it is ineffective to abort activating signals and protect trophoblast, is supported by studies in selected couples, known to posses HLA‐Cw antigens interacting with inhKIRs and by studies on the placental material of spontaneously lost or electively terminated pregnancies. Most of the aborters did not have inhKIRs specific for the HLA‐C antigens possibly expressed on trophoblast and this seems to be confirmed when KIRs and HLA‐Cs are genotyped using DNA extracted from decidual and trophoblastic cells, respectively.

Increasing knowledge about KIR haplotypes is expected to be helpful in the study of the suggestedinhKIR – HLA‐C allorecognition system in pregnancy.
Effects of Cytokines on VEGF Expression and Secretion by Human First Trimester Trophoblast Cell Line
Authors: CHOI SUN JU , PARK JOO YOUNG , LEE YOUNG KYU , CHOI HYUN IL , LEE YOUNG SIM , KOH CHOON‐MYUNG , CHUNG IN‐BAI
Published: March 2003

PROBLEM: The mechanism through which vascular endothelial growth factor (VEGF) regulation occurs at the feto‐maternal interface is poorly understood. The aim of this study was to investigate the effects of various cytokines on VEGF expression and secretion by trophoblast cells.

METHOD OF STUDY: We investigated the effects of cytokines on VEGF expression in human first trimester trophoblast cell line by analyzing VEGF messenger RNA (mRNA) by reverse transcription‐polymerase chain reaction and VEGF protein secretion by enzyme linked immunosorbent assay.

RESULTS: The trophoblast cells expressed VEGF mRNA constitutively and the main subtypes were identified as VEGF121 and VEGF165. When cultured in the presence of interferon (IFN)‐γ, interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, IL‐2, or IL‐10, VEGF mRNA expression was found to be significantly increased by IL‐1β, IFN‐γ and TNF‐α but to be unaffected by IL‐2 and IL‐10. Moreover, VEGF secretion was most significantly increased by IFN‐γ treatment.

CONCLUSION: These results suggest that IL‐1β, IFN‐γ, and TNF‐α may regulate the production of VEGF in early gestational trophoblasts.
Collagenase‐3 (MMP‐13) in Fetal Membranes and Amniotic Fluid During Pregnancy*
Authors: Fortunato Stephen J. , LaFleur Bonnie , Menon Ramkumar
Published: March 2003

OBJECTIVE:  To examine the expression, site of production and a role of collagenase‐3 in human fetal membranes and amniotic fluid (AF).

METHODS:  Amniochorion collected at the time of elective repeat cesareans prior to labor from normal term gestation, were placed in an organ explant system for 72 hr. The AF was collected from the following groups of women: women at term; women at third trimester pregnancy: women at mid‐trimester pregnancy. Women with premature rupture of the membranes (PROM) with or without pre‐term labor and infection delivered by cesareans before term; women with pre‐term labor and no rupture of membranes and delivered by cesareans before term; The mRNA expression of collagenase‐3 was studied by reverse transcriptase–polymerase chain reaction (RT–PCR) and protein concentrations in the AF were assayed by enzyme‐linked immunosorbent assay (ELISA). Site of collagenase‐3 production was documented by immunohistochemistry. Statistical comparisons were made using ANOVA. All statistical hypotheses were adjusted for multiple comparisons using the Scheffe method of adjustment.

RESULTS:  Amniochorion at term expressed collagenase‐3 mRNA. Immunohistochemistry localized collagenase‐3 in both amnion and chorion. Collagenase‐3 was seen in AF from all gestational age groups with lowest levels at mid‐trimester [167.8 pg/mL] and highest during term labor (323.92 pg/mL) with no statistically significant difference between term and third trimester (310.11 pg/mL). AF levels of collagenase‐3 were significantly higher in women with pre‐term labor (370.02 pg/mL; Padj = 0.046) or pre‐term labor and infection (628.73 pg/mL; Padj = 0.002) compared with PROM with pre‐term labor and infection (87.19 pg/mL).

CONCLUSION:  Collagenase‐3 mRNA is constitutively expressed and produced in amniochorion. It is a normal physiologic constituent of AF. PROM is not associated with an increase in the AF collagenase‐3.
Pre‐ovulatory Granulosa Cells of Infertile Women with Endometriosis are Less Sensitive to Luteinizing Hormone
Authors: Cahill David J. , Harlow Christopher R. , Wardle Peter G.
Published: March 2003

Cahill DJ, Harlow CR, Wardle PG. Pre‐ovulatory granulosa cells of infertile women with endometriosis are less sensitive to luteinizing hormone. AJRI 2003; 49:66–69 © Blackwell Munksgaard, 2003

PROBLEM:  Reduced fertilization rates in women with minor endometriosis may be the result of direct effects on the ovary or to primary dysfunction within the hypothalamic–pituitary–ovarian axis. This controlled study was designed to examine the steroidogenic potential of luteinized granulosa cells in women with minor endometriosis.

METHOD OF STUDY:  Granulosa cells were harvested at oocyte recovery and incubated for 3 hr in increasing concentrations of luteinizing hormone (LH). The dissociation constant for added concentrations of LH was computed (as Km LH) and the results were compared between women with endometriosis and controls.

RESULTS:  Women with minor endometriosis had a higher dissociation constant than women with tubal damage [Km 0.98 (0.58–9.24) versus 0.33 (0.28–0.72) ng/mL, P=0.019], indicating reduced sensitivity to LH.

CONCLUSIONS:  In women with endometriosis, granulosa cells were less sensitive to LH stimulation. This provides further evidence for primary ovarian dysfunction as a significant contributory cause of the associated subfertility.
Traumatic dental injuries and Alpine skiing
Authors: Gassner R. , Garcia J. Vàzquez , Leja W. , Stainer M.
Published: March 2003

Abstract – The purpose of this study was to determine the occurrence and type of traumatic dental injuries after maxillofacial injuries as a result of Alpine skiing. During an 8‐year period (from January 1991 to December 1998) 7600 patients with facial injuries were registered at the Department of Oral and Maxillofacial Surgery, University of Innsbruck, Austria. Of 784 patients with skiing‐related facial injuries (524 males, 260 females) 326 (41.6%) sustained injuries to 639 teeth. The age groups predominantly affected were between 7 and 32 years. Luxation injuries occurred in 338 (53%) teeth, fractures accounted for 270 tooth injuries (42%), and only 35 (5%) were lost at the place of the accident. Of skiers with traumatic dental injuries 58% had concomitant soft tissue injuries, while 23.3% had associated facial bone fractures. The most common causes of injury were falls in 42% (329 patients) and collisions with other persons in 24.1% (189 patients). Being hit by one's own sports equipment (11%) was the third most common cause. Collisions with obstacles accounted for 9% and lift accidents for 5.6% of injuries. The probability of suffering dentoalveolar trauma during skiing varied depending on the injury mechanism. There was a 2–fold risk for dentoalveolar trauma when colliding with objects, a 3.5‐fold risk when hit by one's own equipment and a 8.5‐fold risk during lift accidents. Dental injuries occurred in about 2% of all injured skiers. Dental health professionals should be aware of the high incidence and the distribution of dental trauma and facial injuries caused by skiing.
Radiographic analysis of the development of periapical lesions in normal rats, sialoadenectomized rats and sialoadenectomized‐immunosuppressed rats
Authors: Teixeira F. B. , Gomes B. P. F. A. , Ferraz C. C. R. , Souza‐Filho F. J. , Zaia A. A.
Published: March 2003

Abstract – The purpose of this study was to investigate and to compare radiographically the development of periapical lesions in the lower left first molar of normal rats, sialoadenectomised rats and sialoadenectomised‐immunosuppressed rats. Sixty male Wistar rats, weighing from 170 to 200 g were utilized. The animals were divided equally into three groups: group I – 20 normal rats; group II – 20 sialoadenectomised rats; and group III – 20 sialoadenectomised‐immunosuppressed rats. Groups II and III were sialoadenectomized using the modified Cheyne technique. After 2 weeks, group III was submitted to a immunosuppression regimen by daily subcutaneous cyclosporin A injection (10 mg/kg body weight). After 1 week of immunosuppression for this group, the pulps of all the animals (group I, II and III) were exposed to the oral cavity, to produce apical periodontitis. Five animals of each group were killed 7, 14, 21 and 28 days after pulpal exposure. Their mandibles were surgically removed and radiographically analysed. The lesions were measured using ‘Global Lab Image’ software. The results showed predictable growth of the lesions during the experimental period. No significant difference was observed between the groups. It was concluded that possible changes in the oral flora and in the host immune response due to xerostomia associated or not to the immunosuppression did not alter the development of the periapical lesions in rats.
Pulp capping with adhesive resin‐based composite vs. calcium hydroxide: a review
Authors: Schuurs A. H. B. , Gruythuysen R. J. M. , Wesselink P. R.
Published: March 2003

Abstract – The results of some short‐term experiments suggest that direct capping of a vital pulp with the modern resin‐based composite systems may be as effective as capping with calcium hydroxide. Total cavity etching with 10% phosphoric acid seems to be safe for the exposed pulp, but unless annulled by calcium hydroxide 35% phosphoric acid may be disastrous. For hemostasis and cleaning of the pulp wound both sodium hypochlorite and saline seem suitable, whereas the effectiveness of a 2% chlorhexidine solution is questionable. Although hard‐setting calcium hydroxide cements may induce the formation of dentin bridges, they appear not to provide an effective long‐term seal against bacterial factors. Within a few years, the majority of mechanically exposed and capped pulps show infection and necrosis due to microleakage of such capping materials and tunnel defects in the dentin bridges. It is unknown whether newer types of resin containing calcium‐hydroxide‐products will act as a permanent barrier. The cytotoxicity of the resin‐based composites and the temperature rise during polymerisation may not be of concern, but microleakage, sensitisation and allergic reactions may pose problems. Based on available data, pulp capping with resin‐based composites may be said to be promising, but more and long‐term research is mandatory before the method can be recommended.
Influence of surgical repositioning of mature permanent dog teeth following experimental intrusion: a histologic assessment
Authors: Cunha R. F. , Pavarini A. , Percinoto C. , Lima J. E. O.
Published: March 2003

Abstract –  The aim of this study was to evaluate, through histologic examination, the effect of surgical repositioning of intruded dog teeth upon the pulpal and surrounding tissues. Thirty teeth in 10 adult dogs, aged 2–3 years, were used. Fifteen teeth were intruded, surgically repositioned and fixed using orthodontics wire, composite resin, and enamel acid conditioning. All these teeth served as the experimental group. The remaining intruded teeth were not treated (control group). The animals were sacrificed to allow observations at 7, 15, and 30 post‐operative days. The maxillary and mandibular archs were removed and processed for histologic exam. Based on the methodology and observed results, we concluded that: pulpal necrosis, external root resorption and ankylosis were common sequelae to severe traumatic intrusion; a careful immediate surgical repositioning of severed intruded permanent tooth with complete root formation has many advantages with few disadvantages.
Knowledge and prevention of dental trauma in team handball in Switzerland and Germany
Authors: Lang Björn , Pohl Yango , Filippi Andreas
Published: March 2003

Abstract   –  The aim of this work was to conduct a comparative study between Switzerland and Germany about the frequency of dental injuries in handball, athletes' habits of wearing mouthguard, as well as the general level of information about first emergency measures after a dental trauma and the resulting consequences for athletes and their coaches alike. For this, using interviews, seven handball teams each in two countries (Switzerland/Germany) belonging to the amateur and semiprofessional leagues were surveyed. A total of 112 individuals, 28 females and 84 males, were interviewed. Thirty‐two of the 112 interviewees have once observed a dental injury; 12 have experienced a dental injury themselves. Only 10 individuals wore a mouthguard. The results show that the area of handball still requires more information and education.
An investigation of root‐fractured permanent incisor teeth in children
Authors: Feely Laura , Mackie Iain Campbell , Macfarlane Tatiana
Published: March 2003

Abstract  – The aim of this retrospective study was to determine the type of healing which occurred in root‐fractured permanent incisor teeth in children. The objectives were to determine whether gender, age, stage of root development or location of the fracture affected the healing type. The method involved careful scrutiny of clinical records and radiographs of children who attended a unit of paediatric dentistry in a dental hospital. Relevant information was entered onto a data collection sheet. The results were tabulated and analysed by the χ2‐tests using the SPSS statistical package. The results are based on 34 root‐fractured teeth in 33 children aged 8–15 years. Root development was incomplete in 27 of the root‐fractured teeth and complete in seven teeth. A good healing outcome was seen in 27 (79.4%) of the teeth and poor healing in 7 (20.6%). The only factor which was found to be statistically significantly related to healing was the stage of root development. It can be concluded that root‐fractured teeth with immature roots have a better chance of showing good healing than teeth with mature roots.
Radiological aspects of apical periodontitis
Authors: Huumonen Sisko , Ørstavik Dag
Published: March 2003

The diagnosis and management of periapical pathosis requires a thorough clinical and radiographic examination. As chronic apical periodontitis often develops without subjective symptoms, the radiological diagnosis is particularly important. However, radiography is not a perfect diagnostic tool, partly because radiographs are two‐dimensional representations of three‐dimensional structures, and partly because particular clinical and biological features may not be reflected in radiographic changes. The presence of a lesion may not be directly evident and its real extent and the spatial relationships to important anatomical landmarks are not always easily visualized. This paper reviews the usefulness and limitations of the radiological examination in periapical diagnosis.
Transgenic and knock‐out mouse pups: the growing need for behavioral analysis
Authors: Branchi I. , Ricceri L.
Published: March 2003

Few laboratories working with transgenic and knock‐out mice analyze the neurobehavioral consequences of genetic manipulation in early ontogeny. However, the study of behavioral endpoints during the early postnatal period in genetically modified mice is important not only to assess possible developmental abnormalities, but also to better understand and disentangle the effects of genetic manipulations in adulthood. We propose that the assessment of neurobehavioral development represents an appropriate strategy to identify possible compensatory and/or unexpected effects. Nowadays, a large number of experimental protocols that take into account the practical constraints imposed by the peculiar physiological and behavioral responses of an immature subject are available to assess the neurobehavioral profile of developing mice. While this knowledge should be applied to the field of transgenic and knock‐out mice in general, it should be recommended, in particular, for the study of mouse models of neurodevelopmental disorders.
Day surgery and body mass index:  results of a national survey
Authors: Atkins M. , White J. , Ahmed K.
Published: March 2003

Summary In March 1992, the Royal College of Surgeons issued Guidelines for Day Case Surgery. Patients with a body mass index (BMI) > 30 were deemed unsuitable for operations to be performed as a day case. Since these guidelines were issued, many changes have occurred. Two years ago we successfully increased the BMI limit for patients undergoing general anaesthesia in our day surgery unit from 30 to 34. The success of this led us to question the current validity of the Royal College of Surgeons guidelines. A postal questionnaire was conducted surveying current practice in day surgical units within the UK. We achieved a 96% response rate. The results demonstrated a range of acceptable BMI values, with 85% of units anaesthetising patients with a BMI > 30. We conclude that many day case units routinely anaesthetise patients with BMI values > 30. Therefore, the current guidelines, which were issued 9 years ago, are no longer being adhered to nationally.
Gabapentin: pharmacology and its use in pain management
Authors: Rose M. A. , Kam P. C. A.
Published: March 2003

Summary Although its exact mode of action is not known, gabapentin appears to have a unique effect on voltage‐dependent calcium ion channels at the postsynaptic dorsal horns and may, therefore, interrupt the series of events that possibly leads to the experience of a neuropathic pain sensation. Gabapentin is especially effective at relieving allodynia and hyperalgesia in animal models. It has been shown to be efficacious in numerous small clinical studies and case reports in a wide variety of pain syndromes. Gabapentin has been clearly demonstrated to be effective for the treatment of neuropathic pain in diabetic neuropathy and postherpetic neuralgia. This evidence, combined with its favourable side‐effect profile in various patient groups (including the elderly) and lack of drug interactions, makes it an attractive agent. Therefore, gabapentin should be considered an important drug in the management of neuropathic pain syndromes.
The effects of β2 adrenoceptor gene polymorphisms  on pressor response during laryngoscopy and tracheal intubation
Authors: Kim N.‐S. , Lee I.‐O. , Lee M.‐K. , Lim S.‐H. , Choi Y.‐S. , Kong M.‐H.
Published: March 2003

We investigated whether human β2 adrenoceptor (β2AR) gene polymorphisms are associated with the pressor response to laryngoscopy and tracheal intubation. Ninety‐two patients undergoing elective surgery under general anaesthesia were enrolled into this study. Arterial systolic pressure, heart rate and rate pressure product were measured before induction of anaesthesia and 1 min following laryngoscopy and tracheal intubation. Genomic DNA was then used to identify the β2AR‐16 and β2AR‐27 genes using an allele‐specific polymerase chain reaction method. Using multiple linear regression models, controlling for age, sex, weight, baseline blood pressure, heart rate and rate pressure product, we found that patients who possessed the glutamic acid homozygote of β2AR‐27 produced significantly greater changes in mean arterial pressure and rate pressure products than patients with the glutamine homozygote of β2AR‐27 (β coefficient for mean blood pressure = 11.81, β coefficient for pulse−pressure product = 8.76, both p‐values = 0.023). These findings suggest that genetic variability in the human β2AR gene polymorphisms may be associated with the pressor response to laryngoscopy and tracheal intubation.
Tracheal trauma from percutaneous tracheostomy  using the Griggs method
Authors: Watters M. , Thorne G. , Cox C. , Monk C.
Published: March 2003

In a safety evaluation study, relative force and distance measurements during percutaneous tracheostomy were recorded using specially monitored Griggs guidewire dilating tracheostomy forceps on 12 cadavers scheduled to undergo postmortem examination the same day. All measurements were recorded in millivolts and were converted to force and distance via appropriate calibration tables. Markedly more force was required for tracheal destruction than for therapeutic tracheal dilation (87.7 N ± 19 N vs. 31.6 N ± 17.1 N, p < 0.001). Also relatively less force was required for therapeutic tracheal dilation than for dilation of the pretracheal tissues␣(44.4 N ± 17.1␣N vs. 31.6 N ± 17.1 N, p < 0.05). These results suggest that the Griggs tracheostomy forceps have a reasonable margin of safety in that tracheal destruction is unlikely to occur inadvertently during therapeutic dilation. Second, the dilation of pretracheal tissues can act as useful guide in knowing how much force to apply in a therapeutic dilation.
Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for inhalation conscious sedation in children having dental treatment: a randomised controlled trial
Authors: Lahoud G. Y. , Averley P. A.
Published: March 2003

Summary We studied 411 children aged 3–10 years who were referred for dental treatment. They were randomly allocated to have inhalation conscious sedation with either sevoflurane/nitrous oxide mixture or nitrous oxide alone. Dental treatment was satisfactorily completed in 215/241 children who were given sevoflurane/nitrous oxide mixture (89%) compared with 89/170 who were given nitrous oxide alone (52%) (Chi square 70.3, p < 0.0001). All children remained conscious and responsive to verbal contact throughout the treatment and in the recovery room. No adverse side‐effects were recorded in either group and there were no significant differences in oxygen saturation, heart rate, recovery profile, or time to discharge home between the groups. The study concluded that, for every 100 children treated with sevoflurane/nitrous oxide mixture, 37 children would be saved a general anaesthetic if given combined sevoflurane and nitrous oxide mixture rather than nitrous oxide alone. The use of sevoflurane in low concentrations 0.1–0.3% to supplement nitrous oxide and oxygen for inhalation conscious sedation is safe, practical, and significantly more effective than nitrous oxide alone in children having dental treatment.
Evaluation of the clinical usefulness of isolation of fetal DNA from the maternal circulation
Authors: Siva Sashi C. , Johnson Sylvia I. , Mccracken Sharon A. , Morris Jonathan M.
Published: March 2003

Objective: To assess the reliability of isolating free fetal DNA from maternal plasma and to evaluate its clinical usefulness.

Design: Fetal DNA was isolated from plasma or serum that was either collected prospectively or from archived samples collected for the purposes of second trimester screening.

Methods: Prospective samples were collected from patients undergoing prenatal diagnostic procedures (n = 24). A second group of samples from Rhesus negative women (n = 28) were assayed in which blood had originally been collected for maternal triple serum screening. DNA was extracted from all samples and assayed for the presence of the β‐globin gene, sex‐determing region Y (SRY) gene and Rh gene. All DNA sample handling and extraction was carried out by a single operator, and polymerase chain reaction (PCR) was carried out using previously published PCR primers and appropriate controls. The accuracy of results was assessed relative to the karyotype in the case of the SRY gene or cord blood phenotype in the case of the Rh gene.

Results: The SRY PCR results were compared to fetal cell karyotypes obtained from invasive diagnostic testing, 21 out of the 24 samples were correctly ‘sexed’. The RhD PCR results were compared to fetal cord blood samples at the time of delivery, and showed both false positive and false negative results. Two RhD negative babies were genotyped as RhD positive, despite repeat analysis.

Conclusion: It is possible to isolate fetal DNA from maternal serum. It is a potentially clinically useful technique in our laboratory and can be used to detect male fetuses, and Rh negative fetuses. To be useful in clinical practice, it is necessary to safeguard against contamination at the time of sample handling, and to use the optimal range of primers available to cover the polymorphisms present within the RhD gene. Although not robust enough yet to be used with diagnostic certainty in our hands, immense improvements in technique, probes and real‐time PCR equipment make this type of diagnosis a reality in the near future.
Effect of laparoscopic hysterectomy on bladder neck and urinary symptoms
Authors: Long Cheng‐Yu , Hsu Shih‐Cheng , Wu Tung‐Pi , Fu Jung‐Chung , Hsu Yu‐Sin , Su Jiun‐Huang
Published: March 2003

Objective: To assess the effect of laparoscopic hysterectomy (LH) on the mobility and position of bladder neck (BN) and urinary symptoms.

Design: We assessed the BN and urinary symptoms of 151 patients by introital ultrasonography and questionnaires before and after LH.

Sample: One hundred and fifty‐one women who underwent LH from June 1999 to June 2001.

Results: A significant decrease was noted in the number of women exhibiting one or more urinary symptoms from 81 (53.6%) preoperatively to 58 (38.4%) postoperatively (P < 0.01). The incidence of urinary frequency, mild stress incontinence and nocturia decreased significantly after laparoscopic hysterectomy (P < 0.01). Changes in other urinary symptoms following hysterectomy showed no statistical significance (P > 0.05). During straining, the postoperative position of the BN localised more dorsally (P < 0.01) and the ventral mobility of the BN decreased significantly following surgery (P < 0.05). There was no significant difference in the location of the BN with respect to the pubis at rest and during straining, in the cephalocaudal direction, before and after hysterectomy (P > 0.05).

Conclusion: Some patients experienced a substantial improvement of preoperative urinary symptoms following LH, partly as a result of a decrease in the hypermobility of BN.
Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients
Authors: Preston F. E. , Laidlaw S. T. , Sampson B. , Kitchen S.
Published: March 2003

Summary.  Beriplex, a prothrombin complex concentrate (PCC), was administered to 42 patients requiring immediate reversal of their oral anticoagulant therapy. The dose administered was determined using the pretreatment International Normalized Ratio (INR). Blood samples were obtained before treatment and at 20, 60 and 120 min after treatment. The following investigations were performed on all samples – INR, clotting factors II, VII, IX and X, coagulation inhibitors protein C (PC) and antithrombin (AT), and other markers of disseminated intravascular coagulation, plasma fibrinogen, d‐dimer and platelet count. Immediate reversal of the INR, the vitamin K‐dependent clotting factors and PC was achieved in virtually all patients. Reduced AT levels were present in 18 patients before treatment. Further slight AT reductions occurred in four patients, but other associated abnormalities of haemostasis were observed in only one of the four patients. One patient with severe peripheral vascular disease, sepsis and renal and cardiac failure died of a thrombotic stroke following leg amputation, 48 h after receiving Beriplex. No other arterial and no venous thromboembolic events occurred within 7 d of treatment. Beriplex is effective in rapidly reversing the anticoagulant effects of warfarin, including PC deficiency, without inducing coagulation activation. Caution should continue to be exercised in the use of these products in patients with disseminated intravascular coagulation, sepsis or liver disease.
The incidence of recurrent venous thromboembolism in carriers of factor V Leiden is related to concomitant thrombophilic disorders
Authors: Meinardi Johan R. , Middeldorp Saskia , De Kam Pieter J. , Koopman Maria M. W. , Van Pampus Elisabeth C. M. , Hamulyák Karly , Prins Martin H. , Büller Harry R. , Van Der Meer Jan
Published: March 2003

Summary. The duration of anticoagulant treatment after a first episode of venous thromboembolism primarily depends on the risk of recurrence. Variability of recurrence rates in factor (F) V Leiden carriers may be due to concomitant thrombophilic disorders. A retrospective study was performed in 329 FV Leiden carriers with a history of venous thromboembolism (262 probands, 67 relatives). The annual rate of first recurrence was estimated in relatives. The contribution of concomitant thrombophilic disorders to the recurrence rate was evaluated in probands and relatives by a nested case–control analysis in 105 matched pairs of carriers either with or without recurrence. The overall annual recurrence rate was 2·3 per 100 patient–years. The adjusted risk of recurrence for concomitant thrombophilic disorders was: 9·1 (1·3–62·8) for the FII mutation; 1·0 (0·2–4·9) for homozygosity for FV Leiden; 1·5 (0·2–9·5) for inherited deficiencies of protein C or S; 1·8 (0·7–4·9) for FVIII coagulant activity (FVIII:C) levels > 122%; 5·4 (1·6–18·6) for fasting homocysteine levels > 15·2 µmol/l; and 4·4 (1·0–18·7) for loading homocysteine levels > 45·8 µmol/l. Of these disorders, only the FII mutation and hyperhomocysteinaemia significantly increased the risk of recurrence in FV Leiden carriers. The estimated recurrence rate ranged from 0·45 per 100 patient–years after a secondary first event in the absence of concomitant disorders to 4·8 per 100 patient–years when a spontaneous first event was combined with concomitant disorders. Our study provides supportive evidence that the incidence of recurrent venous thromboembolism in heterozygous FV Leiden carriers depends on the concomitance of other thrombophilic disorders, in addition to whether the first thrombotic event occurred spontaneously.
Increased incidence of mitochondrial cytochrome c‐oxidase gene mutations in patients with myelodysplastic syndromes
Authors: Reddy Poluru L. , Shetty Vilasini T. , Dutt Diya , York Aaron , Dar Saleem , Mundle Suneel D. , Allampallam Krishnan , Alvi Sairah , Galili Naomi , Saberwal Gurveen Sethi , Anthwal Shalini , Shaikh Malihi , Suleman Samia , Kamal Shaista Y. , Raza Azra
Published: March 2003

Summary.  Mitochondria (mt) play an important role in both apoptosis and haem synthesis. The present study was conducted to determine DNA mutations in mitochondrial encoded cytochrome c‐oxidase I and II genes. Bone marrow (BM) biopsy and aspirate, peripheral blood (PB) and buccal smear samples were collected from 20 myelodysplastic syndrome (MDS) patients and 10 age‐matched controls. Cytochrome c‐oxidase I (CO I) and II (CO II) genes were amplified using polymerase chain reaction and sequenced. CO I mutations were found in 13/20 MDS patients and the CO II gene in 2/10 normal and 12/20 MDS samples, irrespective of MDS subtype. Mutations were substitutional, deletional and insertional. CO I mutations were most common at nucleotide positions 7264 (25%) and 7289 (15%), and CO II mutations were most common at nucleotide positions 7595 (40%) and 7594 (30%), suggesting the presence of potential ‘hot‐spots’. Mutations were not found in buccal smears of MDS patients and were significantly higher in MDS samples compared with age‐matched controls in all cell fractions (P < 0·05), with bone marrow high‐density fraction (BMHDF) showing a higher mutation rate than other fractions (P < 0·05). MDS marrows showed higher levels of apoptosis than normal controls (P < 0·05), and apoptosis in BMHDF was directly related to cytochrome c‐oxidase I gene mutations (P < 0·05). Electron microscopy revealed apoptosis affecting all haematopoietic lineages with highly abnormal, iron‐laden mitochondria. These results suggest a role for mt‐DNA mutations in the excessive apoptosis and resulting cytopenias of MDS patients.
A highly specific and sensitive fluorescence in situ hybridization assay for the detection of t(4;11)(q21;q23) and concurrent submicroscopic deletions in acute leukaemias
Authors: König Margit , Reichel Martin , Marschalek Rolf , Haas Oskar A. , Strehl Sabine
Published: March 2003

Summary. The translocation t(4;11)(q21;q23) is one of the most frequent 11q23 abnormalities associated with infant leukaemia as well as topoisomerase inhibitor‐induced secondary leukaemias. On the molecular level, the MLL gene on 11q23 is fused to the AF4 gene in the 4q21 region, resulting in a chimaeric MLL/AF4 fusion transcript. These particular chromosome rearrangements are generally considered to be associated with poor prognosis, and therefore accurate detection at diagnosis is of clinical significance. In this study we developed a highly specific dual‐colour fluorescence in situ hybridization (FISH) assay for the detection of the t(4;11) and demonstrate its usefulness for interphase molecular cytogenetics. In our approach, differentially labelled genomic clones that span the breakpoint cluster regions of both genes involved in the specific translocation were used. Thus, t(4;11)‐positive nuclei will display two fusion signals and for t(4;11) cases with concurrent 3′MLL deletions only one fusion signal will be displayed. A very low false‐positive value of less than 0·1% was obtained for interphase cells with two fusion signals. In contrast, in cases with 3′MLL deletions that display only one fusion signal, the rate of false‐positive nuclei was 10·4%. This FISH assay enables the screening of larger series of patients with haematological diseases for t(4;11) translocations and allows the unambiguous detection of associated cryptic deletions.
Systematic review of antiplatelet therapy for the prevention of myocardial infarction, stroke or vascular death in patients with peripheral vascular disease
Authors: Robless P , Mikhailidis D P , Stansby G
Published: March 2003

Background

Antiplatelet agents may prevent vascular events and death in patients with peripheral vascular disease (PVD).

Methods

A systematic review of 39 randomized controlled trials of antiplatelet therapy in patients with PVD was performed.

Results

For patients with PVD the number suffering a non-fatal myocardial infarction, non-fatal stroke or vascular death in the antiplatelet group was 6·5 per cent compared with 8·1 per cent in the placebo group (odds ratio 0·78 (95 per cent confidence interval (c.i.) 0·63–0·96); P = 0·02), favouring antiplatelet treatment. For infrainguinal bypass surgery (ten trials) and balloon angioplasty (two) the differences were still in favour of antiplatelet therapy, but they did not reach statistical significance. In five trials of aspirin against another antiplatelet agent, 8·4 per cent in the aspirin group suffered a vascular event compared with 6·6 per cent in the second antiplatelet group (odds ratio 0·76 (95 per cent c.i. 0·64–0·91); P < 0·01), favouring ticlopidine/clopidogrel/aspirin + dipyridamole against aspirin alone.

Conclusion

Antiplatelet therapy reduces serious vascular events and vascular death in patients with PVD. For infrainguinal arterial surgery or balloon angioplasty the benefit remains unproven, but the number of trials to date is small. There is also evidence to support the use of antiplatelet drugs other than aspirin for the prevention of vascular events in those with PVD.
Systematic review and meta-analysis of emergency ultrasonography for blunt abdominal trauma
Authors: Stengel D , Bauwens K , Sehouli J , Porzsolt F , Rademacher G , Mutze S , Ekkernkamp A
Published: March 2003

Background

How precise and reliable is ultrasonography as a primary tool for injury assessment in blunt abdominal trauma?

Methods

A systematic review and meta-analysis were conducted of prospective clinical trials of ultrasonography for blunt abdominal trauma. Publications were retrieved by structured searching among databases, review articles and major text books. Authors and experts in the field were contacted for original and unpublished data. For statistical analysis, summary receiver operating characteristic curves (SROCs) were computed using weighted and robust regression models, with Q* denoting the shoulder of the curve. Post-test probabilities were calculated as a function of pooled likelihood ratios (LRs).

Results

Thirty of 123 trials enrolling 9047 patients were eligible for final analysis. With respect to targeting organ lesions, ultrasonography showed a summary Q* value of 0·91 (inverse variance weights, 95 per cent confidence interval (c.i.) 0·76–1·07); negative predictive values ranged from 0·72 to 0·99. A similar SROC slope was calculated for screening for free fluid (Q* = 0·89 (95 per cent c.i. 0·73–1·05)). Ultrasonography detects the presence of organ lesions, but fails to exclude abdominal injuries (random effects negative LR 0·23 (95 per cent c.i. 0·18–0·28)). Given a pretest probability of 50 per cent for blunt abdominal injury, a post-test probability of nearly 25 per cent remains in the case of a negative sonogram.

Conclusion

Despite its high specificity, ultrasonography has an unexpectedly low sensitivity for the detection of both free fluid and organ lesions. In clinically suspected abdominal trauma, another assessment (e.g. helical computed tomography) must be performed regardless of the initial ultrasonographic findings.