bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of a calcium antagonist (nifedipine) to suppress preterm labour
Authors: READ M. D. , WELLBY D. E.
Published: August 2005

Summary. The efficacy of an orally administered calcium antagonist, nifedipine, in suppressing premature uterine activity, was compared with intravenous ritodrine and no treatment. Nifedipine was found to be significantly more effective than ritodrine or withholding therapy, and was almost devoid of side‐effects.
Langerhans' cell density in the normal exocervical epithelium and in the cervical intraepithelial neoplasia
Authors: CAORSI I. , FIGUEROA C. D.
Published: August 2005

Summary. A morphometric analysis was performed of the Langerhans' cell density in epithelial sheets obtained from normal exocervices and from exocervices with squamous carcinoma. Laminae of exocervices with squamous carcinoma that showed cervical intraepithelial neoplasia (CIN) were classified according to its predominant degree of severity as CIN I, CIN II and CIN III or as normal when no neoplastic changes were found. Laminae with CIN showed a higher Langerhans' cell density than the laminae from normal exocervices and than the normal laminae of exocervices with carcinoma. The magnitude of the increase of Langerhans' cell density and the degree of severity of the neoplastic changes appear as closely related phenomena. An increase of the more ramified types of Langerhans' cell in the laminae containing CIN was found, with the most ramified being more frequent in the most severe lesions.
Nutritional management of pregnancy in patients on home parenteral nutrition
Authors: MUGHAL M. M. , SHAFFER J. L. , TURNER M. , IRVING M. H.
Published: August 2005

Summary. Three pregnancies are reported in two patients on home parenteral nutrition for intestinal failure. The nutritional regimen, 2300 kcal (9.63 MJ) (18% as lipid emulsion), 14 g amino acid nitrogen and electrolytes supplied daily in a‘big bag’, was based on the measured resting energy expenditure and urinary nitrogen excretion during the third trimester in a 30‐year‐old woman on home parenteral nutrition. Commercial preparations of trace elements were added to the infusion as dictated by serum levels. Iron, iodine and fluoride were given orally, and vitamin B12 by monthly intramuscular injection. There were no serious deficiencies in trace elements and maternal weight‐gain and fetal growth were satisfactory in all three pregnancies. The two pregnancies in one patient went to term and both infants had birthweights at the 50th centile for gestational age. The second patient who had had two spontaneous abortions went into premature labour at 30 weeks and gave birth to a baby with a minor facial deformity who subsequently developed the idiopathic respiratory distress syndrome. All three placentas were histologically normal. The growth and development of all three babies has been satisfactory. This nutritional regimen should be adequate for most pregnant patients who have attained a normal nutritional status on parenteral nutrition.
Renal biopsy: indications and complications in pregnancy
Authors: PACKHAM DAVID , FAIRLEY KENNETH F.
Published: August 2005

Summary. A series of 111 renal biopsies performed in 104 pregnant women during the past 20 years at The Royal Melbourne Hospital and Royal Women's Hospital, Melbourne were reviewed. The indications for biopsy and the histological findings are detailed. The complication rate was very low (4.5%). It is concluded that the procedure is safe and that renal biopsy during pregnancy yields a definitive histological diagnosis in almost all cases. The indications for renal biopsy in pregnancy are discussed.
Menstrual regulation by intramuscular injections of 16‐phenoxy‐tetranor PGE2 methyl sulfonylamide or vacuum aspiration. A randomized multicentre study
Authors:   WORLD HEALTH ORGANIZATION, Dhall G. I. , Can Nguyen , Andolsek‐Jeras L. , Narone J. N. , Jia‐Zheng Chen , Hingorani V. , Yu‐Fen Zhou , Zhi‐heng Chen , Prasad R. N. V. , Bygdeman M. , Herczeg J. , Huai‐yin Ye , Farley T.M.M. , Rowe P. I. , Van Look P. F. A.
Published: August 2005

Summary. A multicentre trial was conducted to compare the efficacy and side‐effects of an intramuscularly administered PGE2 analogue and vacuum aspiration in women with a delay of up to 21 days in the expected onset of menses. A total of 473 such women were randomly allocated to treatment with either 16‐phenoxy‐W‐17, 18, 19, 20‐tetranor PGE2 methyl sulfonylamide (three intramuscular injections of 0.5 mg at 3‐h intervals) or vacuum aspiration, and the outcome of therapy assessed 1, 2 and 6–8 weeks later. Retrospective analysis of hCG levels indicated that 419 (88.6%) women had been pregnant at the time of treatment. With few exceptions, administration of the PGE2 analogue induced vaginal bleeding in both pregnant and non‐pregnant women but the duration and subjectively perceived amount of bleeding were greater than after vacuum aspiration. Both treatments were equally effective. In pregnant women the overall frequency of complete abortion was 91% for prostaglandin treatment and 94% for vacuum aspiration. If non‐pregnant women were included, the respective success rates (i.e. percentages of women not pregnant 2 weeks after treatment) were 92% and 95%. Gastrointestinal side‐effects and lower abdominal pain requiring intramuscular analgesia were more common after prostaglandin therapy than following vacuum aspiration in both pregnant and non‐pregnant women.
The continuous measurement of transcutaneous carbon dioxide tension (TcPCO2), an atraumatic tool to verify fetal acidosis?
Authors: SALING ERICH Z. , SCHMIDT STEPHAN CH.
Published: August 2005

Summary. TcP CO2 monitoring of the fetus during labour was evaluated as an atraumatic tool to identify or exclude fetal acidosis in 224 high‐risk deliveries. A heated electrochemical sensor with a measuring temperature of 39°C (n= 105) or 44°C(n=119) was applied to the fetal scalp. There was a statistically significant correlation between the TcP CO2 and the fetal blood pH at both temperatures. The sensitivity of the method was 0.90 and 0.61 at the two measuring temperatures of 44° or 39° respectively and the specificity was 0.93 and 0.79 respectively. The negative predictive value was high (0.99 and 0.95 respectively), but the respective positive predictive values were only 0.53 and 0.24. We conclude that the continuous measurement of the TcP CO2 is a valid additional tool to exclude fetal acidosis in most cases where fetal distress is indicated by the heart rate pattern but a TcP CO2 value above the cut‐off point should be verified by an additional method to avoid unnecessary‐operative deliveries.
Steroid conversion and prostaglandin production by chorionic and decidual cells in relation to term and preterm labour
Authors: BERNAL A. LÓPEZ , HANSELL D. J. , ALEXANDER S. , TURNBULL A. C.
Published: August 2005

Summary. The production of progesterone from prcgnenolone, of cor‐tisol from cortisone and of prostaglandin E (PGE) under basal and arachidonic acid‐stimulated conditions was measured in cells dispersed from chorion and decidua. The cells were obtained after delivery from four groups of women: following spontaneous labour at term (38–42 weeks gestation), at elective caesarean section at term before the onset of labour, after induced labour at term, and after uncomplicated preterm (27–36 weeks) labour. Chorionic cells had a high progesterone output with relatively low cortisol and PGE production, whereas decidual cells had a high cortisol and PGE production rate. Free arachidonic acid stimulated PGE production in both decidual and chorionic cells. There were no significant differences in either steroid or PGE production among the four groups studied. These data suggest that steroid dehydrogenase activity in choriodecidual cells is not related to the mode of onset of labour and that the increased prostaglandin production in intrauterine tissues associated with parturition is due to enhanced availability of arachidonic acid.
Effect of nomegestrol acetate, a new 19‐nor‐progesterone derivative, on pituitary‐ovarian function in women
Authors: BAZIN BRIGTTTE , THEVENOT ROGER , BURSAUX CLAUDE , PARIS JACQUES
Published: August 2005

Summary. After two control cycles, 13 normally menstruating women were treated from day 5 to 25 of the third consecutive cycle with nomegestrol acetate (NOM Ac) 1.25, 2.5 or 5 mg once a day. Plasma oestradiol, FSH and LH concentrations were assayed daily from day 5 to day 25 and plasma progesterone concentrations from day 12 to day 25. Ovulation was inhibited in every woman; LH and progesterone levels were uniformly depressed. With 5 and 2.5 mg/day, plasma oestradiol remained low with high FSH values. With 1.25 mg/day, oestradiol concentrations reached levels similar to those achieved during the control follicular phase, with a concomitant decrease in FSH secretion. These results show an hypothalamic‐pituitary effect and suggest an ovarian action, both responsible for a potentially useful contraceptive property.
Bonney's test—fact or fiction?
Authors: MIGLIORINI GEOFFREY D. , GLENNING PETER P.
Published: August 2005

Summary. A prospective urodynamic study in 61 incontinent women assessed the validity of the Bonney test in the diagnosis of true sphincter weakness stress incontinence. The urodynamic findings in all the patients indicated that the Bonney test produced significant increases in the urethral closure pressure and transmission of impulse from the abdomen to the urethra which indicated occlusion of the urethra rather than elevation of the bladder neck. The Bonney test does not differentiate between patients with sphincter weakness and those with bladder instability and therefore should be discarded.
Tumour‐associated monoclonal antibodies for the diagnosis and assessment of ovarian cancer
Authors: SHEPHERD JOHN H. , GRANOWSKA M. , BRITTON K. E. , MATHER S. , SLEVTN MAURICE , EPENETOS A. A. , WARD E.G.
Published: August 2005

Summary. A tumour‐associated radiolabelled monoclonal antibody (HMFG 2) was used to investigate 51 patients who were referred with a pelvic mass and suspected ovarian cancer or recurrent disease. The day before operation the 123I‐labelled antibody was injected and the patients then underwent radioimmunoscintigraphy immediately and again 4 and 22 h after the injection. An exploratory laparotomy with appropriate surgery was then performed and the tumours were staged. Tumours were positively imaged 3 min‐22 h after injection in all the patients with ovarian cancer, with a mean 0.6% of the injected antibody taken up by the tumour. The presence of HMFG antigen on the tumour was confirmed by immunoperoxidase staining of the surgically‐removed tissues. Of the 51 patients, 39 proved to have ovarian cancer. The accuracy of diagnosis and detection of primary and metastatic malignant disease was 95% when correlating pre‐operative radioimmune scan findings and laparotomy findings. The procedure is minimally invasive, apparently without side‐effects and offers information for tumour detection as an adjunct or alternative to existing methods.
A random plasma glucose method for screening for abnormal glucose tolerance in pregnancy
Authors: HATEM M. , DENNIS K. J.
Published: August 2005

Summary. A method is described for screening all pregnant women for abnormal glucose tolerance. It is based on determining random plasma glucose at 28–30 weeks gestation, having simply noted whether the woman had eaten within the preceding 2 h. If the random plasma glucose level was 97.5th centile, a 75 g oral glucose tolerance test was performed. This method of screening is cheaper and slightly more efficient than screening based on conventional risk indications.
A comparison of the effects of maternally administered meptazinol and pethidine on neonatal acid‐base status
Authors: De BOER FRANCES C. , CLIFFORD WAYNE A. , SHORTLAND DAVID , SIMPSON RONALD L. , CATLEY DAVID M.
Published: August 2005

Summary. A randomized double‐blind study compared the effects of equi‐analgesic doses of maternally administered meptazinol (1.5 mg/kg) and pethidine (1.5 mg/kg) on neonatal acid‐base status. Heel‐prick samples were taken for assessment of acid‐base status at 10 and 60 min after delivery. Maternal antenatal history, details of labour and neonatal status at delivery were also recorded. Meptazinol produced less neonatal respiratory depression than pethidine: the mean 10 min acid‐base data from 16 infants whose mothers received pethidine were indicative of a respiratory acidosis (pH 7.13, SD 0.08, P co2,9.11, SD 2.2 kPa; standard bicarbonate 22.3, SD 3.1 mmol/1). This was not evident in the mean acid‐base data from 16 infants whose mothers received meptazinol (pH 7.23, SD 0.07; P co2 6.83, SD 1.6 kPa; standard bicarbonate 20.9, SD 4.2 mmol/1). The mean pH and P co2 in the two treatment groups were significantly different (P<0.002) at 10 min but not at 60 min after delivery.
Serial urinary cyclic guanosine monophosphate measurements in the assessment of response to treatment in epithelial ovarian cancer
Authors: LUESLEY D. M. , CHAN K. K. , NEWTON J. R. , BLACKLEDGE G. R.
Published: August 2005

Serial measurements of urinary cyclic guanosine monophosphate (cGMP) were performed in 47 patients with epithelial ovarian cancer. In 30 patients, the pre‐chemotherapy cGMP level was above the range for normal controls (marker positive); the remainder were within the normal range. Marker positive patients demonstrated a 96% correlation of disease regression with a fall in marker level and a 75% correlation of disease progression with a rise in marker level. The corresponding correlations in the marker negative group were 41% and 39%. Marker positive patients also demonstrated a rise in marker before clinical recognition of disease progression in six of 11 instances whereas only one of nine instances in marker negative patients showed such a rise. Patients with evidence of static disease had normal and stable marker levels.
Oestradiol‐17β and progesterone level changes in peritoneal fluid around the time of ovulation
Authors: KRUITWAGEN R. F. P. M. , JANSSEN‐CASPERS H. A. B. , WLADIMIROFF J. W. , SCHATS R. , JONG F. H. DE , DROGENDIJK A. C.
Published: August 2005

In 15 women, peritoneal fluid was obtained by either culdocentesis (n= 20) or laparoscopy (n= 3), before (n= 9) and after (n= 14) ovulation. Ultrasound was used for ovulation detection. Before ovulation the mean oestradiol‐17β level in plasma and peritoneal fluid was not essentially different; the mean progesterone level was significantly higher in peritoneal fluid. After ovulation both the mean oestradiol‐17β and progesterone levels were significantly higher in peritoneal fluid than in plasma. In peritoneal fluid, there was a wide distribution of individual oestradiol‐17β values before and after ovulation; no significant difference existed between the mean pre‐ and postovulatory oestradiol‐17[3 level. More consistent changes were seen in peritoneal fluid progesterone levels; the mean level was significantly higher after ovulation. In three subjects, a low postovulatory progesterone level in peritoneal fluid was associated with a cystic luteal structure observed by ultrasound, suggesting a reduced leakage of fluid from the ovulation stigma.

Erasmus University, Rotterdam Department of Obstetrics and Gynaecology R. F. P. M. KRUITWAGEN
The effect of fetal heart rate on umbilical artery flow velocity waveforms
Authors: MIRES G. , DEMPSTER J. , PATEL N. B. , CRAWFORD J. W.
Published: August 2005

Umbilical artery flow velocity waveforms were obtained using continuous wave Doppler ultrasound in 85 normal pregnancies (25 antepartum, 60 intrapartum) to examine the relation between fetal heart rate, end systolic/end diastolic ratio (A/B ratio) and resistance index (RI). Our results demonstrated a significant negative correlation between fetal heart rate, A/B ratio and RI (in the antepartum group r= ‐0·49, and in the labouring group r= ‐0·65). It is therefore important when performing mathematical analysis of umbilical artery flow velocity profiles to make a statistical allowance for fetal heart rate.
An immunohistochemical study of steroid binding by endornetrial glandular epithelial cells throughout the menstrual cycle
Authors: SIVRIDIS E. , BUCKLEY C. H. , FOX H.
Published: August 2005

An immunohistochemical technique was used to demonstrate oestrogen and progesterone binding by endornetrial glandular epithelial cells at various stages of the menstrual cycle. A cross‐section of steroid binding sites, including low affinity, concentration dependent Type 11 and III binding sites, were demonstrated but only in cells which contain the classical high affinity receptor. The technique demonstrated both free binding sites and receptor‐hormone complexes within the cytoplasm but was poorly effective in demonstrating nuclear complexes. Oestrogen binding sites were shown to reach a peak during the late proliferative and early secretory phases of the cycle: oestrogen binding capacity remained high during the mid and late secretory phases. Progesterone binding capacity rose progressively throughout the proliferative and early secretory phase.
Ultrasound exposure time in routine obstetric scanning
Authors: ANDREWS MARGARET , WEBSTER MARY , FLEMING JOHN E. E. , MCNAY MARGARET B.
Published: August 2005

Summary. The duration of exposure to ultrasound was measured in 1274 patients having a routine examination during their first visit to an antenatal clinic. The measured median exposure time was 105 s. Since pulsed ultrasound was used (duty cycle of 1 in 800) the actual median maternal exposure time was 131 ms. Exposure of the fetus would usually be less since it rarely occupies the full width of the image. The relevance of exposure time to the safety of diagnostic ultrasound and the implications for users and manufacturers are discussed.
Prostaglandin E production by amniotic cells in relation to term and preterm labour
Authors: LÓPEZ BERNAL A. , HANSELL DEBBIE J. , ALEXANDER OPHIE , TURNBULL A. C.
Published: August 2005

Summary. The rate of prostaglandin E (PGE) production was measured in collagenase‐dispersed amniotic cells obtained from 14 women after spontaneous labour at term—seven after spontaneous preterm labour, nine after delivery by elective caesarean section at term and six after induction of labour at term. Cells were incubated with and without arachidonic acid and PGE was estimated by specific radioimmunoassay. Basal PGE output (pmol/106 cells per 3 h) was highest in the spontaneous labour group, 27·5 (SEM 5·5) and lowest in the preterm labour group, 4 (SEM 1·2) (P<0·001). Values in the elective section and induction groups were 13·6 (SEM 2·7) and 10 (SEM 3·1), respectively; these values were significantly higher than in the preterm labour group and the values after induction were significantly lower than after spontaneous labour. Addition of arachidonic acid resulted in a significant increase in PGE output in all groups, but the values after preterm labour remained significantly lower than those of any group at term. These data indicate that towards term there is a maturation in the PG synthetase activity of the amnion and that PGE output in this tissue is increased in spontaneous labour.
Weak D type 1.1 exemplifies another complexity in weak D genotyping
Authors: Doescher Andrea , Flegel Willy A. , Petershofen Eduard K. , Bauerfeind Ursula , Wagner Franz F.
Published: August 2005

BACKGROUND: Weak D expression is caused by a large number of RHD alleles. Increasingly recommendations for D+ or D– transfusions are based on polymerase chain reaction (PCR) identification of certain RHD alleles. Possible sources of error are rare D variants that are inadvertently carrying known polymorphisms of frequent weak D types.

STUDY DESIGN AND METHODS: Weak D donors were checked by direct column agglutination. In donors with unusually weak expression of D, the molecular weak D type was determined by weak D PCR and nucleotide sequencing. The serologic profile of a weak D type 1 variant was determined by agglutination serology and flow cytometry.

RESULTS: Several donors in whom direct agglutination barely revealed any D expression were shown to carry the new RHD(L18V,V270G) allele dubbed weak D type 1.1. Initially, such donors had been mistyped as weak D type 1 by PCR. In a systematic study, weak D type 1.1 was shown to be present in 7 of 23 donors with very weak D expression who all lived in a restricted area of Northern Germany. Although weak D type 1.1 was typed D– or barely D+ by direct agglutination, it was easily detected by antiglobulin technique and was shown to carry about 600 antigens D per red blood cell.

CONCLUSION: The observation of weak D type 1.1 with its distinct phenotype pinpointed to two general problems of current RHD genotyping strategies: Mistyping of alleles with additional mutations and striking geographic variation of the allele distributions.
White blood cell–reactive antibodies are undetectable in solvent/detergent plasma
Authors: Sachs Ulrich J.H. , Kauschat Dörte , Bein Gregor
Published: August 2005

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is a life‐threatening complication of transfusion. Although all types of blood products have been associated with TRALI, fresh‐frozen plasma (FFP) is the most commonly implicated component. It has been postulated that TRALI is an immune‐mediated event, because white blood cell (WBC)‐reactive antibodies in the donor's plasma are frequently associated with the syndrome. In contrast to single donor–derived FFP, solvent/detergent (S/D) plasma is produced from multiple donations, leading to an at least 500‐fold dilution of a single plasma unit. It was hypothesized that WBC‐reactive antibodies are undetectable in S/D FFP.

STUDY DESIGN AND METHODS: Twenty batches of S/D FFP (5 of each ABH group) were analyzed with well‐established routine techniques to detect WBC antibodies.

RESULTS: All samples tested negative for granulocyte‐specific as well as HLA Class I and Class II antibodies.

CONCLUSIONS: Different strategies to reduce the risk of TRALI are currently discussed. These include screening of all potentially immunized donors for WBC‐reactive antibodies and exclusion of multiparous or all women from donating FFP. Here, it is demonstrated that neither granulocyte‐ nor lymphocyte‐reactive antibodies are detectable in S/D FFP. Thus, S/D FFP may represent a potential alternative to reduce the risk of TRALI associated with the transfusion of FFP.
Host response modulation in the management of periodontal diseases
Authors: Salvi Giovanni E. , Lang Niklaus P.
Published: August 2005

Objective: To review the biological mechanisms and clinical utility of therapeutic modulation of the host response in the management of periodontal diseases.

Material and methods: A search of MEDLINE–PubMed was performed up to and including December 2004. The search was limited to in vitro, experimental animal and clinical studies published in English. The selection criteria included all levels of available evidence: systematic reviews, randomised‐controlled clinical trials, controlled clinical trials, prospective and retrospective cohort studies and case reports of human and experimental animal studies.

Results: Six targets for non‐microbial chemotherapeutic intervention were identified. Clinical trials have demonstrated the ability of non‐steroidal anti‐inflammatory drugs to slow periodontal disease progression. However, recently reported serious adverse effects preclude the use of cyclooxygenase‐2 inhibitors as an adjunct to periodontal therapy. Adjunctive use of subantimicrobial dose doxycycline to non‐surgical periodontal therapy is beneficial in the management of chronic periodontitis over 12 months. Controversial data exist on the effects of bisphosphonate administration as an adjunct to periodontal therapy. Evidence on modulation of other host mediators including lipoxins, cytokines and nitric oxide synthase is limited to animal research.

Conclusion: After validation in long‐term clinical trials, adjunctive host modulation therapy may prove advantageous in the management of periodontal diseases.
Mechanisms of action of environmental factors – tobacco smoking
Authors: Palmer Richard M. , Wilson Ron F. , Hasan Adam S. , Scott David A.
Published: August 2005

Aim:To review the potential biological mechanisms underlying the effects of tobacco smoking on periodontitis.

Main findings:Smoking has major effects on the host response, but there are also a number of studies that show some microbiological differences between smokers and non‐smokers.

Smoking has a long‐term chronic effect on many important aspects of the inflammatory and immune responses. Histological studies have shown alterations in the vasculature of the periodontal tissues in smokers. Smoking induces a significant systemic neutrophilia, but neutrophil transmigration across the periodontal microvasculature is impeded. The suppression of neutrophil cell spreading, chemokinesis, chemotaxis and phagocytosis have been described. Protease release from neutrophils may be an important mechanism in tissue destruction. Tobacco smoke has been found to affect both cell‐mediated immunity and humoral immunity. Research on gingival crevicular fluid has demonstrated that there are lower levels of cytokines, enzymes and possibly polymorphonuclear cells in smokers. In vitro studies have shown detrimental effects of nicotine and some other tobacco compounds on fibroblast function, including fibroblast proliferation, adhesion to root surfaces and cytotoxicity.

Conclusion:Tobacco smoking has widespread systemic effects, many of which may provide mechanisms for the increased susceptibility to periodontitis and the poorer response to treatment.
Dental plaque: biological significance of a biofilm and community life‐style
Authors: Marsh P. D.
Published: August 2005

Background: Most microorganisms in nature attach to surfaces and form matrix‐embedded biofilms. Biofilms are highly structured and spatially organized, and are often composed of consortia of interacting microorganisms, termed microbial communities, the properties of which are more than the sum of the component species. Microbial gene expression alters markedly in biofilms; organisms communicate by gene transfer and by secretion of diffusible signalling molecules. Cells in biofilms are less susceptible to antimicrobial agents.

Aim and Materials & Methods: To comprehensively review the literature to determine whether dental plaque displays properties consistent with those of a typical biofilm and microbial community.

Results: Novel microscopic and molecular techniques have demonstrated that plaque has a structured architecture with an extracellular matrix, and a diverse composition (around 50% of cells are unculturable). The constituent species communicate by gene transfer, by secreted peptides (Gram‐positive bacteria) and autoinducer‐2 (Gram‐positive and Gram‐negative bacteria). These organisms are functionally organized for increased metabolic efficiency, greater resistance to stress and for enhanced virulence. Plaque formation has direct and indirect effects on gene expression.

Conclusion: Dental plaque displays properties that are typical of biofilms and microbial communities in general, a clinical consequence of which is a reduced susceptibility to antimicrobial agents as well as pathogenic synergism.
Analytical epidemiology of periodontitis
Authors: Borrell Luisa N. , Papapanou Panos N.
Published: August 2005

Aims: To review the literature related to the analytical epidemiology of periodontitis generated over the past decade. This review does not deal with descriptive epidemiologic studies of the prevalence, extent and severity of periodontitis with respect to global geography, but focuses exclusively on analytical epidemiology issues, including the challenges posed by the use of different case definitions across studies, current theories and models of disease progression, and risk factors associated with the onset and progression of periodontitis.

Methods: Relevant publications in the English language were identified after Medline and PubMed database searches.

Findings and conclusions: There is a conspicuous lack of uniformity in the definition of periodontitis used in epidemiologic studies, and findings from different research groups are not readily interpretable. There is a lack of studies that specifically address the distinction between factors responsible for the onset of periodontitis versus those affecting its progression. Colonization by specific bacteria at high levels, smoking, and poorly controlled diabetes have been established as risk factors for periodontitis, while a number of putative factors, including specific gene polymorphisms, have been identified in association studies. There is a clear need for longitudinal prospective studies that address hypotheses emerging from the cross‐sectional data and include established risk factors as covariates along with new exposures of interest. Intervention studies, fulfilling the “targeting” step of the risk assessment process, are particularly warranted. Obvious candidates in this context are studies of the efficacy of elimination of specific bacterial species and of smoking cessation interventions as an alternative to the traditional broad anti‐plaque approach in the prevention and control of periodontitis. Ideally, such studies should have a randomized‐controlled trial design.
Immune responses and vaccination against periodontal infections
Authors: Persson G. Rutger
Published: August 2005

Background: The infectious aetiology of periodontitis is complex and no curative treatment modality exists. Palliative therapy is available.

Aims: To review the evidence that active or passive immunization against periodontitis provides immune protection.

Material and Methods: PubMed (Medline), the National Institutes of Health, the Food and Drug Administration, and the Center for Disease Control electronic databases were searched to extrapolate information on immune responses to immunization against periodontitis.

Results: Studies in non‐human primate models using ligature‐induced experimental periodontitis suggest that antibody responses by active immunization against Porphyromonas gingivalis can safely be induced, enhanced, and obtained over time. Immune responses to whole bacterial cell and purified protein preparations considered as vaccine candidates have been evaluated in different animal models demonstrating that there are several valid vaccine candidates. Data suggest that immunization reduces the rate and severity of bone loss. It is also, temporarily, possible to alter the composition of the subgingival microflora. Natural active immunization by therapeutic interventions results in antibody titre enhancement and potentially improves treatment outcomes. Passive immunization of humans using P. gingivalis monoclonal antibodies temporarily prevents colonization of P. gingivalis. Probiotic therapy may be an alternative approach. Regulatory and safety issues for human periodontal vaccine trials must be considered. Shared infectious aetiology between periodontitis and systemic diseases may enhance vaccine effort developments.

Conclusions: Proof of principle that active and passive immunization can induce protective antibody responses is given. The impact of natural immunization and passive immunization in humans should be explored and may, presently, be more feasible than active immunization studies.
Transmission of periodontal bacteria and models of infection
Authors: Van Winkelhoff A. J. , Boutaga K.
Published: August 2005

Background: Bacteria play an essential role in the aetiology of periodontitis. Most bacterial species isolated from subgingival plaque are indigenous to the oral cavity. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis are detected infrequently in periodontal health, which makes these species prime candidates to study person‐to‐person transmission. The aim of the present study was to review the literature on transmission of these periodontal bacterial species.

Method: We review the literature on bacterial typing techniques and summarize the information on clonal distribution of A. actinomycetemcomitans and P. gingivalis in family units based on different typing techniques in order to establish the likelihood for person‐to‐person transmission of these periodontal pathogens.

Results: Vertical transmission of A. actinomycetemcomitans is estimated to be between 30% and 60%, whereas vertical transmission of P. gingivalis has rarely been observed. Horizontal transmission between spouses ranges between 14% and 60% for A. actinomycetemcomitans and between 30% and 75% for P. gingivalis. There is some evidence to show that cohabitation with a periodontitis patient influences the periodontal status of the spouse; however, substantially more information is needed to prove this hypothesis.

Conclusions: Transmission of putative periodontal pathogens between family members has been shown. The clinical consequences of these events have been poorly documented. Based on the current knowledge, screening for and prevention of transmission of specific virulent clones of A. actinomycetemcomitans may be feasible and effective in preventing some forms of periodontal disease. P. gingivalis is usually recovered from diseased adult subjects, and transmission of this pathogens seems largely restricted to adult individuals. Horizontal transmission of P. gingivalis may therefore be controlled by periodontal treatment involving elimination or significant suppression of the pathogen in diseased individuals and by a high standard of oral hygiene.
Identification of genetic risk factors for periodontitis and possible mechanisms of action
Authors: Loos Bruno G. , John Raymond P. , Laine Marja L.
Published: August 2005

Aim: To review the literature for genetic risk factors associated with periodontitis.

Methods: Computerized search of the literature in English using key words: Periodontitis; Genes; Mutation; Polymorphism; Risk.

Results and Conclusions: Mutations in the cathepsin C gene (CTSC) have been identified as causal for the Papillon–Lefèvre syndrome (PLS), which includes prepubertal periodontitis (PP). Some CTSC mutations are causal for PP without PLS. No relationship has been demonstrated between CTSC mutations and other forms of periodontitis. Genetic polymorphisms in a candidate gene approach have been explored as risk factors for periodontitis. There is limited evidence that some polymorphisms in the genes encoding interleukins (IL)‐1, Fcgamma receptors (FcγR), IL‐10 and the vitamin D receptor, may be associated with periodontitis in certain ethnic groups. However relatively large variations in carriage rates of the Rare (R)‐alleles among studies on any polymorphism were observed. The available studies appear under‐powered and do not adequately take into account other pertinent risk factors for periodontitis. Future studies should include larger cohorts, should clearly define phenotypes and should adequately control for other risk factors. In addition to the candidate gene approach, alternative strategies need to be considered to elucidate the gene variations, which confer risk for periodontitis.
Effect of genetic variability on the inflammatory response to periodontal infection
Authors: Shapira Lior , Wilensky Asaf , Kinane Denis F.
Published: August 2005

Aim: To review the association between genetic variability and the inflammatory response induced by periodontal infection.

Material and Methods: A search of MEDLINE‐PubMed was performed from January 2000 up to and including March 2005. The search included all types of publications, published in English without other limitations. The following search terms were used: “cytokine polymorphism”, “gene polymorphism”, “periodontitis”, “gingivitis”, “inflammation” and “host‐response”. The papers resulting from the above search were used as an additional source for relevant articles.

Results: Genetic variability was examined for the correlation to clinical indicators of inflammation such as bleeding on probing (BOP), gingival inflammation, cytokine in gingival crevicular fluid (GCF) and cytokine production by inflammatory cells. According to the current literature, most of the studies found no association between genetic variability and BOP, gingival inflammation or cytokine concentrations in the GCF. These studies were hampered by inappropriate study designs and the use of inflammatory parameters as secondary rather than primary outcome variables. The data suggest that the production of inflammatory mediators by inflammatory cells may be affected by different genetic traits but further studies are needed in order to establish this association.

Conclusions: To date, there is no clear correlation between any of the gene polymorphisms and clinical indicators of inflammation. The powering of studies to reveal associations between single or multiple nucleotide polymorphisms and inflammatory parameters will need to involve a much larger number of subjects than were used in the past. The available data (including the interleukin‐1 composite genotype) do not currently support the utility of such tests in the diagnosis and prognostic assessments of periodontal diseases.
Critical pathways in microbial virulence
Authors: Curtis M. A. , Slaney J. M. , Aduse‐Opoku J.
Published: August 2005

The virulence of a microbe represents a combination of complex factors including the agent's transmissibility and the severity of the disease associated with infection and is also significantly influenced by the susceptibility of the colonized host. Virulence factors may be defined as those products of the organism which are required to complete the various stages of the life cycle leading to pathology in the host. In this review, we examine some of the approaches which have been adopted in other fields of infectious disease in order to categorically identify virulence factors using a classical genetics approach with relevant models or human subjects. The absence of an accurate experimental model for periodontal disease means that our understanding of the microbial virulence determinants and pathways in this disease remains hypothetical and based largely on observations in vitro. However, factors which enable the organism to persist in spite of the elevated immune and inflammatory pressure at sites of disease are liable to be critical. Periodontal bacterial genomics is liable to make a significant impact on the field through an increased appreciation of the role of gene acquisition and gene loss in the evolution of periodontal bacteria and of the consequences of strain variation in gene content on virulence potential.
Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva
Authors: Madianos P. N. , Bobetsis Y. A. , Kinane D. F.
Published: August 2005

Objectives: The primary aetiologic factor of periodontal disease is the bacterial biofilm. Gram‐positive and Gram‐negative bacteria possess a plethora of structural or secreted components that may cause direct destruction to periodontal tissues or stimulate host cells to activate a wide range of inflammatory responses. These responses are intended to eliminate the microbial challenge, but may often cause further tissue damage.

Methods: This review has been divided into three parts: (a) bacterial virulence factors, which includes basic information on bacterial virulence factors, and the principle inflammatory responses that host cells elicit against these factors, (b) main receptors and signalling pathways, which includes basic information about the main receptors that interact with the bacterial virulence factors, the nature of these interactions, and the activated signalling pathways that lead to inflammatory responses, and (c) initiation of inflammation, which includes a model by which the virulence factors may interact with host cells and lead to inflammatory responses in the gingiva.

Findings and Conclusions: Bacterial components/virulence factors may be involved in modulating inflammatory responses and include: lipopolysaccharides (LPS), peptidoglycans, lipotechoic acids, fimbriae, proteases, heat‐shock proteins, formyl‐methionyl peptides, and toxins. Potential host cell receptors involved in recognizing bacterial components and initiating signalling pathways that lead to inflammatory responses include: Toll‐like receptors (TLRs), CD14, nucleotide‐binding oligomerization domain proteins (Nod) and G‐protein‐coupled receptors, including formyl‐methionyl peptide receptors and protease‐activated receptors. Of the above bacterial and host molecules, evidence from experimental animal studies implicate LPS, fimbriae, proteases, TLRs, and CD14 in periodontal tissue or alveolar bone destruction. However, evidence verifying the involvement of any of the above molecules in periodontal tissue destruction in humans does not exist.
The Myotubularin Family of Lipid Phosphatases
Authors: Clague Michael J. , Lorenzo Óscar
Published: August 2005

The myotubularins (MTMs) constitute a large family of phosphoinositide lipid 3‐phosphatases with specificity for PtdIns3P and PtdIns (3,5)P2. Mutations in MTM proteins are associated with inherited conditions such as myotubular myopathy and Charcot–Marie–Tooth syndrome. The substrate lipids are known to be regulators of the endosomal pathway through recruitment of specific effector proteins. Hydrolysis of PtdIns (3,5)P2 provides a biosynthetic pathway to the production of PtdIns5P, which itself can allosterically activate MTMs. We review the properties of this intriguing family of proteins and discuss potential physiological functions that include regulation of the endocytic pathway.
Small molecule regulation of Sir2 protein deacetylases
Authors: Grubisha Olivera , Smith Brian C. , Denu John M.
Published: August 2005

The Sir2 family of histone/protein deacetylases (sirtuins) is comprised of homologues found across all kingdoms of life. These enzymes catalyse a unique reaction in which NAD+ and acetylated substrate are converted into deacetylated product, nicotinamide, and a novel metabolite O‐acetyl ADP‐ribose. Although the catalytic mechanism is well conserved across Sir2 family members, sirtuins display differential specificity toward acetylated substrates, which translates into an expanding range of physiological functions. These roles include control of gene expression, cell cycle regulation, apoptosis, metabolism and ageing. The dependence of sirtuin activity on NAD+ has spearheaded investigations into how these enzymes respond to metabolic signals, such as caloric restriction. In addition, NAD+ metabolites and NAD+ salvage pathway enzymes regulate sirtuin activity, supporting a link between deacetylation of target proteins and metabolic pathways. Apart from physiological regulators, forward chemical genetics and high‐throughput activity screening has been used to identify sirtuin inhibitors and activators. This review focuses on small molecule regulators that control the activity and functions of this unusual family of protein deacetylases.
Physiological relevance of the endogenous mono(ADP‐ribosyl)ation of cellular proteins
Authors: Di Girolamo Maria , Dani Nadia , Stilla Annalisa , Corda Daniela
Published: August 2005

The mono(ADP‐ribosyl)ation reaction is a post‐translational modification that is catalysed by both bacterial toxins and eukaryotic enzymes, and that results in the transfer of ADP‐ribose from βNAD+ to various acceptor proteins. In mammals, both intracellular and extracellular reactions have been described; the latter are due to glycosylphosphatidylinositol‐anchored or secreted enzymes that are able to modify their targets, which include the purinergic receptor P2X7, the defensins and the integrins. Intracellular mono(ADP‐ribosyl)ation modifies proteins that have roles in cell signalling and metabolism, such as the chaperone GRP78/BiP, the β‐subunit of heterotrimeric G‐proteins and glutamate dehydrogenase. The molecular identification of the intracellular enzymes, however, is still missing. A better molecular understanding of this reaction will help in the full definition of its role in cell physiology and pathology.
Toxicological and Pharmacological Effects of D‐Arginine
Authors: Navarro Eduardo , Alonso Simeona J. , Martín Felipe A. , Castellano Miguel A.
Published: August 2005

Abstract: D‐Arginine is extensively used in studies on L‐arginine/nitric oxide pathway as an inactive form of L‐arginine, even in man. In addition, it has previously been reported that this D‐amino acid appears to have pharmacological activity. The present work aimed at evaluating the toxicity and pharmacology of D‐arginine administered by the intraperitoneally route in albino male mice. Toxicity of D‐arginine, alone as well as in the presence of propranolol and betamethasone was evaluated. D‐Arginine in mice showed a light toxicity order (DL50: 2800 mg/kg). Previous injection of the β‐adrenoceptor blocker, propranolol (2 mg/kg, intraperitoneally), or betamethasone (0.5 mg/kg, intraperitoneally) produced a decrease in the toxicity of D‐arginine (LD50: 3600 mg/kg, 3300 mg/kg, respectively). Also, a neuropharmacological screening of D‐arginine using behavioural, neurological, autonomic, barbiturate‐induced sleep time and pentylenetetrazole‐induced convulsions tests were performed. D‐Arginine 700 mg/kg displayed central stimulant properties, whereas a depressant profile was observed at a dose of 1400 mg/kg. In addition, D‐arginine 1400 mg/kg produced a potentiation of pentobarbital sleeping time and a marked anticonvulsivant action against pentylenetetrazole.
Cyclosporine A‐Induced Changes to Erythrocyte Redox Balance is Time Course‐Dependent
Authors: Lexis Louise A. , Richards Ross S. , Fassett Robert G. , Coombes Jeff S.
Published: August 2005

Abstract: Cyclosporine A‐treated transplant recipients develop pronounced cardiovascular disease and have increased oxidative stress and altered antioxidant capacity in erythrocytes and plasma. These experiments investigated the time‐course of cyclosporine A‐induced changes to redox balance in plasma and erythrocytes. Rats were randomly assigned to either a control or cyclosporine A‐treated group. Treatment animals received 25 mg/kg of cyclosporine A via intraperitoneal injection for either 7 days or a single dose. Control rats were injected with the same volume of the vehicle. Three hours after the final injections, plasma was analysed for total antioxidant status, α‐tocopherol, malondialdehyde, and creatinine. Erythrocytes were analysed for reduced glutathione (GSH), α‐tocopherol, methaemoglobin, malondialdehyde, and the activities of superoxide dismutase, catalase, GSH peroxidase, and glucose‐6‐phosphate dehydrogenase (G6PD). Cyclosporine A administration for 7 days resulted in a significant increase (P<0.05) in plasma malondialdehyde, methaemoglobin, and superoxide dismutase and catalase activities. There was a significant decrease (P<0.05) in erythrocyte GSH concentration and G6PD activity in cyclosporine A animals. There were no significant differences (P>0.05) between groups following a single dose of cyclosporine A in any of the measures. In summary, cyclosporine A alters erythrocyte redox balance after 7 days administration, but not after a single dose.