bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel exopolysaccharide from a clinical isolate of Prevotella nigrescens: purification, chemical characterization and possible role in modifying human leukocyte phagocytosis
Authors: Yamane K. , Yamanaka T. , Yamamoto N. , Furukawa T. , Fukushima H. , Walker C. B. , Leung K.‐P.
Published: December 2004

Prevotella nigrescens, a gram‐negative black‐pigmented anaerobic rod, has frequently been isolated from periodontitis and periapical periodontitis lesions. We have isolated an exopolysaccharide‐producing P. nigrescens, strain 22, from a chronic periodontitis lesion. The purpose of this study was to determine the chemical composition and function of the exopolysaccharide associated with this clinical isolate. The chemical composition and structure of the purified exopolysaccharide from strain 22 were determined by high performance liquid chromatography and methylation analysis. To define the biological function of this exopolysaccharide, a chemically induced exopolysaccharide nonproducing mutant, strain 328, which was derived from strain 22, was established. The biological effects of exopolysaccharide were determined by comparing the ability of strain 22, strain 328 or heat‐killed strain 22 to form abscesses in mice and to interfere with the phagocytic activity of peripheral blood polymorphonuclear leukocytes. Chemical analysis showed that isolated exopolysaccharide consisted of mannose (521.6 μg/mg), glucose (25.6 μg/mg), fructose (65.8 μg/mg), galactose (12.5 μg/mg), arabinose (6.2 μg/mg), xylose (3.2 μg/mg), rhamnose (6.1 μg/mg), and ribose (0.6 μg/mg). Methylation analysis of exopolysaccharide indicated that the linkages of mannose were primarily (1→2, 1→6) (1→2) (1→6), and (1→3). Strain 22 and, to a lesser extent, its heat‐killed counterpart induced greater abscess formation in mice than strain 328, even though the enzymatic profile of strain 22 was similar to that of strain 328. The ability of strain 328 to induce abscess formation was restored by adding the purified exopolysaccharide isolated from strain 22 to the cell suspension of strain 328. Exopolysaccharide alone failed to induce abscess formation in mice. Further, strain 328 but not the untreated or heat‐killed strain 22, was phagocytosed by polymorphonuclear leukocytes both in the presence and in the absence of opsonic factors. The results suggest that these polysaccharides isolated from strain 22, which primarily consisted of mannose, may play a key role in the development of the chronic inflammatory lesion from which this strain was isolated.
Virulence, phenotype and genotype characteristics of endodontic Enterococcus spp.
Authors: Sedgley C. M. , Molander A. , Flannagan S. E. , Nagel A. C. , Appelbe O. K. , Clewell D. B. , Dahlén G.
Published: December 2004

Background/aims:  Enterococci have been implicated in persistent root canal infections but their role in the infection process remains unclear. This study investigated the virulence, phenotype and genotype of 33 endodontic enterococcal isolates.

Methods:  Phenotypic tests were conducted for antibiotic resistance, clumping response to pheromone, and production of gelatinase, hemolysin and bacteriocin. Genotype analysis involved polymerase chain reaction amplification of virulence determinants encoding aggregation substances asa and asa373, cytolysin activator cylA, gelatinase gelE, gelatinase‐negative phenotype ef1841/fsrC, adherence factors esp and ace, and endocarditis antigen efaA. Physical DNA characterization involved pulsed‐field gel electrophoresis of genomic DNA, and plasmid analysis.

Results:  Potential virulence traits expressed included production of gelatinase by Enterococcus faecalis (n = 23), and response to pheromones in E. faecalis culture filtrate (n = 16). Fourteen strains produced bacteriocin. Five strains were resistant to tetracycline and one to gentamicin, whereas all were susceptible to ampicillin, benzylpenicillin, chloramphenicol, erythromycin, fusidic acid, kanamycin, rifampin, streptomycin and vancomycin. Polymerase chain reaction products encoding efaA, ace, and asa were detected in all isolates; esp was detected in 20 isolates, cylA in six isolates, but asa373 was never detected. The gelatinase gene (gelE) was detected in all isolates of E. faecalis (n = 31) but not in Enterococcus faecium (n = 2); a 23.9 kb deletion sequence corresponding to the gelatinase‐negative phenotype was detected in six of the eight E. faecalis isolates that did not produce gelatinase. Pulsed‐field gel electrophoresis and plasmid analyses revealed genetic polymorphism with clonal types evident. Plasmid DNA was detected in 25 strains, with up to four plasmids per strain and a similar (5.1 kb) plasmid occurring in 16 isolates.

Conclusions:  Phenotypic and genotypic evidence of potential virulence factors were identified in endodontic Enterococcus spp., specifically production of gelatinase and response to pheromones.
Down‐regulation of interleukin‐1α‐induced matrix metalloproteinase‐13 expression via EP1 receptors by prostaglandin E2 in human periodontal ligament cells
Authors: Noguchi K. , Ruwanpura S. M. P. M. , Yan M. , Yoshida N. , Ishikawa I.
Published: December 2004

In the present study, we investigated the effect of prostaglandin (PG) E2 on matrix metalloproteinase (MMP)‐13 production in human periodontal ligament cells stimulated with interleukin (IL)‐1α. IL‐1α enhanced both MMP‐13 and PGE2 production. Indomethacin, a nonselective cyclooxygenase inhibitor, and NS‐398, a specific cyclooxygenase‐2 (COX‐2) inhibitor, significantly enhanced IL‐1α‐induced MMP‐13 production in periodontal ligament cells, although both the agents completely inhibited IL‐1α‐induced PGE2 production. Exogenous PGE2 reduced IL‐1α‐induced MMP‐13 mRNA and protein production in a dose‐dependent manner. 17‐phenyl‐ω‐trinor PGE2, a selective EP1 receptor agonist, mimicked the inhibitory effect of PGE2 on IL‐1α‐induced MMP‐13 mRNA and protein production. On the basis of these data, we suggest that COX‐2‐dependent PGE2 down‐regulates IL‐1α‐elicited MMP‐13 production via EP1 receptors in human periodontal ligament cells. PGE2 may be involved in the regulation of destruction of extracellular matrix components in periodontal lesions.
Comparative analysis of the antibacterial effects of combined mouthrinses on Streptococcus mutans
Authors: Menendez A. , Li F. , Michalek S. M. , Kirk K. , Makhija S. K. , Childers N. K.
Published: December 2004

Background/aims:  Chlorhexidine has been proposed as a potent chemotherapeutic agent against oral bacteria. However, there are some inconsistent results regarding the usefulness of chlorhexidine mouthrinse as an antimicrobial for Streptococcus mutans. The purpose of this study was to investigate the effectiveness of combining oral rinses to reduce S. mutans levels in human saliva.

Methods:  Sixteen healthy adult subjects were randomly assigned to one of four rinse groups using a 4‐cell crossover design. The groups rinsed twice a day for 7 days with one of the following: 0.12% chlorhexidine (PerioGard®), 1.5% hydrogen peroxide (Peroxyl®), a combined chlorhexidine + hydrogen peroxide, or water (control). Every 5 weeks, each group initiated a different rinse. Saline wash samples were collected on days 7 and 21 for assessment of S. mutans and total streptococci.

Results:  No significant differences were seen in S. mutans levels among the groups; however, the levels of total streptococci on day 7 samples were significantly lower in the chlorhexidine and chlorhexidine + hydrogen peroxide groups than in the hydrogen peroxide and control groups. There was no additional decrease seen in S. mutans or total streptococci levels in the group receiving chlorhexidine + hydrogen peroxide compared to chlorhexidine alone.

Conclusions:  Sample variation was high throughout the study, with a significant trend toward lower counts as the study progressed. Adding hydrogen peroxide to the chlorhexidine mouthrinse did not result in a further decrease in S. mutans levels.
Efficacy and safety of single‐ and multiple‐dose ketotifen fumarate 0.025% ophthalmic solution in a pediatric population
Authors: Abelson Mark B. , Ferzola Nancy J. , McWhirter Cecilia L. , Crampton Henry J.
Published: December 2004

Allergic conjunctivitis can seriously disrupt children's daily activities. This study assessed the efficacy (onset and duration of action) and safety of ketotifen fumarate 0.025% ophthalmic solution compared with vehicle placebo in pediatric subjects after single and multiple dosing. This was a double‐masked, multicenter, fellow‐eye, placebo‐controlled, conjunctival allergen challenge trial. Eligible subjects (8–16‐yr‐olds) who produced a qualifying reaction to allergen were randomized to a single dose (one drop) of ketotifen fumarate in one eye and vehicle placebo in the fellow eye, followed by an allergen challenge at 15 min and 8 h post‐dose. Subjects who had a qualifying reaction to allergen in the placebo‐treated eye and a qualifying response to ketotifen in the active‐treated eye following the single dose were re‐randomized to a multiple‐dose treatment period. They were instructed to instill one drop of ketotifen fumarate in one eye and placebo in the other eye twice daily for 4 wk. An allergen challenge was conducted 8 h after the last dose. The primary efficacy assessment was ocular itching, judged by the subject at 3, 7, and 10 min post‐allergen challenge after single‐ and multiple‐dose treatments. Other ocular signs and symptoms were assessed at 7, 10, and 15 min post‐dose. A total of 133 subjects were randomized to single‐dose treatment; 105 were evaluable for efficacy. Of these, 60 were re‐randomized to multiple‐dose treatment, and 55 were evaluable for efficacy. After single and multiple doses, ketotifen fumarate significantly inhibited ocular itching compared with placebo at all post‐challenge timepoints (p < 0.001) and also significantly reduced hyperemia, chemosis, and lid swelling (p = 0.031). No drug‐related systemic adverse events were reported, and ocular adverse events were comparable to placebo. No subject discontinued prematurely due to an adverse event. These results indicate that ketotifen fumarate 0.025% ophthalmic solution is an effective and safe treatment option for children with allergic conjunctivitis.
Gender‐limited association of cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) polymorphism with cord blood IgE levels
Authors: Chang Jen‐Chieh , Liu Chieh‐An , Chuang Hau , Ou Chia‐Yu , Hsu Te‐Yao , Huang Eng‐Yen , Yang Kuender D.
Published: December 2004

Allergic mechanism has long been attributed to IgE‐mediated reaction. The relationship between gene polymorphism and cord blood IgE (CB IgE) is unclear. We investigated whether elevation of CB IgE levels was associated with polymorphisms of cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) at (−318) CT and (+49) AG positions in a gender‐limited fashion. CB IgE levels were determined by Pharmacia CAP system and the CTLA‐4 polymorphisms at (−318) and (+49) were determined by restriction fragment length polymorphism (RFLP). A total of 644 consecutive umbilical cord bloods were collected for this study. 32.9% of newborn infants had detectable IgE levels (≥0.35 kU/l). 25.6% of the male newborns had elevated CB IgE levels (≥0.5 kU/l) similar to those of the female newborns (22.7%). The CTLA‐4 polymorphism at (+49) but not (−318) was significantly associated with elevated CB IgE levels (p = 0.004). The association of CTLA‐4 (+49) A allele with elevated CB IgE levels was found only in females. Both male and female infants with different CTLA‐4 (−318) genotypes had no difference in the rates of elevated CB IgE levels. A linkage disequilibrium between CTLA‐4 (+49) G and (−318) C allele was found in this Chinese population. Subjects with the (+49, GG and −318, CC) genotype had a significantly lower rate of elevated CB IgE levels. Association of the CTLA‐4 (+49) polymorphism with elevated CB IgE levels was found only in female infants. Newborn infants with the (+49, GG and −318, CC) genotype tended to have a low rate of elevated CB IgE.
Are oral contraceptive use and pregnancy complications risk factors for atopic disorders among offspring?
Authors: Brooks Kevin , Samms‐Vaughan Maureen , Karmaus Wilfried
Published: December 2004

In utero programming of atopic manifestations has been suggested. We investigated the association between oral contraceptive (OC) use before, and complications during pregnancy (CDP) and asthma, along with other atopic manifestations. The study is based on neonates from Kingston and St Andrew, a geographic subcohort from the Jamaican Perinatal Morbidity, Mortality Survey conducted in 1986–1987. Information on OC use and CDP was extracted from maternal interviews and medical records. In a follow up in 1997–1998, via interviews with mothers, trained nurses collected information on asthma/wheezing, coughing, eczema, and hay fever. Data, specific to this paper, from birth and 11–12 yr of age was available for a total of 1040 of the 1720 members of the geographic subcohort. Using logistic regression, controlling for confounders, we estimated adjusted odds ratio (aOR) and corresponding 95% confidence intervals (CI). For asthma or wheezing, and coughing, aOR for OC use were 1.81 (95% CI: 1.25–2.61), and 2.72 (95% CI: 1.41–5.24), respectively. CDP was only shown to be a significant risk factor for hay fever. Additionally, a higher number of older siblings were protective for hay fever. The results suggest that asthma in childhood may be programmed in utero.
Effect of omega‐3 fatty acid concentrations in plasma on symptoms of asthma at 18 months of age
Authors: Mihrshahi Seema , Peat Jennifer K. , Webb Karen , Oddy Wendy , Marks Guy B. , Mellis Craig M. ,   the CAPS Team
Published: December 2004

The objective of this study was to assess the relation between observed levels of omega‐3 fatty acids in plasma and symptoms of asthma and atopy in children at 18 months of age. A total of 616 women at risk of having a child who would develop asthma because of a family history were recruited from the antenatal clinics of six hospitals in Sydney, Australia. Families were randomized to either active omega‐3 supplemented or control group. The active group received a daily tuna fish oil supplement and omega‐3‐rich margarines and cooking oils and the control group received a placebo supplement with polyunsaturated margarines and cooking oils. When the children were 18 months of age an assessment of symptoms was carried out by a research nurse blinded to treatment group allocation. Atopy was measured by skin prick tests, blood was collected to determine serum immunoglobulin E (IgE), and plasma fatty acid concentrations. A total of 376 children (61.0% of total recruited) completed an assessment at 18 months and had blood taken to determine plasma fatty acid concentrations. Omega‐3 fatty acid levels were expressed in quintiles of exposure ‘as treated’ without reference to treatment group allocation. Wheeze ever, doctor visits for wheeze, bronchodilator use and nocturnal coughing were significantly reduced in children in the higher exposure quintiles. Serum IgE was reduced in the highest quintile but not significantly so. There was no difference in diagnosed asthma or atopy between the exposure quintiles. Although wheeze at this age may not be a good indicator of asthma in later childhood, it is encouraging that some symptoms have been reduced in children with high omega‐3 fatty acid concentrations in plasma.
Bimodal skin reactivity to histamine in atopic children in Singapore: influence of specific sensitizations
Authors: Kidon Mona Iancovici , See Yvonne , Bun Cheung Yin , Goh Anne , Chay Oh Moh , Balakrishnan Abhilash
Published: December 2004

Histamine skin prick test (SPT) is used as the ‘golden standard’ for positive control in in vivo immediate type hypersensitivity testing. The skin reactivity to histamine can, however, be modulated by a bevy of extraneous factors. We aimed to define whether histamine skin reactivity in atopic children in Singapore is influenced by age, ethnic origin, gender, environmental exposure or specific sensitization patterns. A retrospective analysis of children, with specific aeroallergen sensitization (as measured by at least one allergen‐specific SPT with a wheal size >3 mm compared with the negative control) from the outpatient speciality clinic of the KK Children's Hospital, during 06/2002–06/2003. A total of 315 patients were included, 235 (75%) were males, 252 (80%) were Chinese, age mean was 7.7 yr (range: 2–15). Patients were referred to the SPT with a diagnosis of one or more of: allergic rhinitis 287 (91%), asthma 112 (36%) or atopic dermatitis 60 (19%). The mean histamine response showed a bimodal distribution, independent of age, ethnic origin, gender or phenotypical expression of allergic disease. Histamine skin reactivity was higher in atopic patients with polysensitization (mean 5.0 mm vs. 2.9 mm in monosensitized patients, p < 0.001), and in patients with mould sensitization (mean 5.1 mm vs. 3.3 mm in patient not sensitized to moulds, p < 0.001). The presence of passive smoking increased the likelihood of a diminished histamine skin response. Histamine skin response data strongly suggested the presence of two heterogeneous subpopulations. Children with polysensitization and mould sensitization were more likely to show a large significant histamine response, whereas children with passive smoke exposure, showed a diminished skin reactivity to histamine.
Maternal pollen allergy may be more important than birch pollen exposure during pregnancy for atopic airway disease in the child
Authors: Kihlström Anne , Lilja Gunnar , Pershagen Göran , Hedlin Gunilla
Published: December 2004

In 1993 extremely high levels of birch pollen were recorded in Stockholm, Sweden. We investigated the effects of this exposure on sensitization and development of atopic airway disease in children. The aim of this study was to assess the influence of maternal birch sensitization and symptoms of pollen allergy, as well as exposure to birch pollen during pregnancy, on sensitization and development of atopic airway disease in children. A total of 387 children with atopic heredity (70% had atopic mothers) and born in Stockholm 1993 or 1994 were investigated at age 4.5–5 yr. The children were examined and skin prick tested with inhalant and food allergens. IgE‐antibodies against birch pollen and recombinant birch pollen allergen were analyzed in serum. The same tests were performed on the mothers. Children of mothers with symptoms of pollen allergy more often showed symptoms of rhinoconjunctivitis at age 4.5–5, after both high dose [Odds ratio (OR) 5.3; 95% confidence interval (CI): 2.0–13.7] and low dose (OR 4.0; 95% CI: 1.5–10.9) exposure to birch pollen during pregnancy. Similar tendencies were noted for children of mothers sensitized to birch, where stronger effects were suggested in boys (OR 3.8; 95% CI: 1.3–11.5) than in girls (OR 1.2; 95% CI: 0.2–5.5) in the high‐dose exposed group. For asthma symptoms and sensitization to birch in the children the results were less consistent. It may be concluded that, maternal pollen allergy seems to have a stronger influence on the development of rhinoconjunctivitis in children with a family history of atopy than the degree of allergen exposure during pregnancy.
Leptin and asthma in overweight children at 12 years of age
Authors: Mai Xiao‐Mei , Böttcher Malin F. , Leijon Ingemar
Published: December 2004

Obesity is suggested as a risk factor for asthma, but the mechanisms are unclear. The relationship between obesity and asthma has not been considered in children born with very low‐birth weight (VLBW). We hypothesized that overweight was a contributing factor for asthma in VLBW children, and that leptin and leptin‐associated cytokines might play roles in overweight‐related asthma. Seventy‐four VLBW and 64 normal birth weight (NBW) children participated in a 12‐yr follow up study assessing asthma and allergy. Twenty‐seven (12 VLBW) of the 138 children were overweight according to the proposed international definition. The diagnosis of current asthma was made by a pediatrician. Serum levels of leptin and interferon (IFN)‐γ were analyzed by enzyme‐linked immunosorbent assay (ELISA). Leptin levels were considerably higher in the overweight than in the non‐overweight children (median value: 18.1 vs. 2.8 ng/ml, p < 0.001). In the overweight children, current asthmatics had twice as high levels of leptin as children without current asthma (median value: 30.8 vs. 14.3 ng/ml, p = 0.14), but this was not the case in the non‐overweight children. IFN‐γ was more often detected in the overweight than in the non‐overweight children (61% vs. 12%, p < 0.001), and there was a positive correlation between the levels of leptin and the levels of IFN‐γ (Rho = 0.40, p < 0.001). In the VLBW group, the overweight children had a significantly increased risk for current asthma compared with the non‐overweight children after adjustment for the neonatal risk factors [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 1.2–27]. Thus, overweight was associated with asthma in the VLBW children. Our hypothesis remained that leptin might be involved in the pathogenesis of asthma in the overweight children, and IFN‐γ might be a pathway in the process of leptin‐induced inflammation.
Lamotrigine treatment of bipolar disorder: data from the first 500 patients in STEP‐BD
Authors: Marangell Lauren B , Martinez James M , Ketter Terence A , Bowden Charles L , Goldberg Joseph F , Calabrese Joseph R , Miyahara Sachiko , Miklowitz David J , Sachs Gary S , Thase Michael E ,   STEP‐BD investigators
Published: December 2004

Objective:  To describe the frequency and correlates of lamotrigine therapy among the first 500 patients enrolled into the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD) study.

Method:  Systematic recording of psychiatric history and medication data at intake into the STEP‐BD project.

Results:  Of the participants with bipolar disorder type I or II (n = 483), 77 (15.4%) were currently taking lamotrigine (mean dose: 258.12 mg/day) and 52 (10.4%) reported prior lamotrigine use. The groups were comparable with regard to duration of illness and mood state at study entry. Compared with participants who had never taken lamotrigine, those currently treated with lamotrigine were significantly more likely to have a prior history of rapid cycling (62.5% vs. 43.1%; p < 0.01) and an antidepressant‐induced switch to (hypo)mania (49.3% vs. 33.3%; p < 0.01). In contrast, only 16.9% of lamotrigine‐treated participants were taking an antidepressant at study intake, as compared with 29.1% of participants with no history of lamotrigine therapy (p < 0.03).

Conclusions:  While noting the limitations of a cross‐sectional assessment, these data suggest that lamotrigine therapy was commonly used in these academic centers for patients with bipolar disorder several years before it was recommended in the American Psychiatric Association practice guidelines, particularly in patients with a history of rapid cycling or antidepressant‐induced mania.
Folie a deux in bipolar affective disorder: a case report
Authors: Patel Anish S , Arnone Danilo , Ryan William
Published: December 2004

Background:  The syndrome of folie a deux is uncommon and often described in the context of schizophrenia. We report a case of induced delusional disorder associated with bipolar affective disorder (BAD).

Case report:  We present a case of monozygotic twins in their late 60s with an unusually close relation with one another and relative isolation from other people. Both twins have been diagnosed as suffering from BAD and relapsed into mania with psychotic symptoms. During their hospital stay they exhibited features consistent with folie a deux. Separation caused disappearance of the phenomenon whilst the affective disorder persisted.

Conclusion:  This case highlights the unusual and rare phenomenon of folie a deux occurring in the context of BAD. It also suggests current difficulty in defining folie a deux as an entity according to current diagnostic criteria.
Two peptidase activities decrease in treated bipolar disorder not schizophrenic patients
Authors: Breen Gerome , Harwood Adrian J , Gregory Kathryn , Sinclair Maggie , Collier David , Clair David St , Williams Robin SB
Published: December 2004

Background:  Inhibition of prolyl oligopeptidase (PO) in primary neuronal cultures has been shown to reverse the effect of the common mood‐stabilizers lithium, valproic acid and carbamazepine. In clinical studies, abnormal plasma PO activity has been associated with bipolar disorder (BD) and schizophrenia. However, this association is complicated by the discovery in bovine plasma of a Z‐Pro‐prolinal‐insensitive peptidase (ZIP), a novel enzyme that cleaves the same substrate as PO.

Methods:  We developed an assay to distinguish between ZIP and PO and measured both activities in plasma from 48 BD and 50 schizophrenic patients undergoing treatment and compared them with 50 control subjects.

Results:  ZIP activity is restricted to blood plasma, whereas PO activity is present in the cytosol of lymphocytes, but can also be detected in blood plasma. Significant decreases in their plasma activities were found between treated BD (p = 0.007 and 0.03 respectively) but not schizophrenic (p > 0.05) patients and controls.

Conclusions:  We have found that the enzyme activity previously reported as plasma PO actually comprises two enzymes, PO and ZIP. This study shows a statistically significant decrease of both enzymes in BD patients undergoing lithium treatment. No statistically significant change in PO or ZIP activity is observed in schizophrenic patients.
Bipolar disorder. III: Harm avoidance a risk factor for suicide attempts
Authors: Engström Christer , Brändström Sven , Sigvardsson Sören , Cloninger C Robert , Nylander Per‐Olof
Published: December 2004

Objectives: The aim of the study was to examine whether personality, i.e. temperament and character influence suicide attempts in bipolar patients.

Methods: Bipolar patients were recruited from lithium dispensaries. Temperament and character inventory (TCI) was administered to 100 euthymic bipolar patients and 100 controls.

Results: Age of onset was significantly lower in patients with suicide attempts in the total bipolar group (I and II) and bipolar I patients compared with patients without suicide attempts. Bipolar (I and II) and bipolar I patients with suicide attempts were significantly higher in harm avoidance (HA) and reward dependence compared with patients without suicide attempts. Patients (I and II) with suicide attempts had significantly more anticipatory worry, fatigability and asthenia than patients without suicide attempts. Bipolar I patients with suicide attempts had significantly more fatigability and asthenia and were more dependent than patients without suicide attempts. HA was lowest in patients with no suicide attempts and no family history of suicide, higher in patients with family history of suicide or patients with suicide attempts, and significantly highest in patients with suicide attempts and family history of suicide. Patients with suicide attempts and family history of suicide had more anticipatory worry, fatigability and asthenia. Bipolar disorder was significantly correlated to HA and suicide attempts to HA and PS. Family history of suicide and gender were significantly correlated to suicide attempts.

Conclusions: Age of onset, HA, PS, gender and family history of suicide had a moderate to very strong effect on suicide attempts in bipolar patients.
Major stressful life events and other risk factors for first admission with mania
Authors: Kessing Lars Vedel , Agerbo Esben , Mortensen Preben Bo
Published: December 2004

Objectives:  To investigate whether first admission with mania is associated with the occurrence of death in the family or with major stressful life events and to explore whether the associations change with age.

Methods:  Case register study with linkage of the Danish Psychiatric Central Research Register, including data on all admissions at psychiatric wards in Denmark from 1981 to 1998, and the Civil Registration System, including data on death and on socio‐demographic variables. All patients who got a diagnosis of mania/mixed episode at the first ever admission at a psychiatric ward and a random gender‐ and age‐matched control group of subjects who had never been admitted to psychiatric ward were identified.

Results:  A total of 1565 patients and 31 300 control subjects were identified. Suicide of a mother or of a sibling was associated with a highly increased risk of being admitted for the first time ever at a psychiatric ward with a diagnosis of mania/mixed episode. Death of a relative by other causes than suicide was not associated with increased risk of getting hospitalized with mania. Recent unemployment, recent divorce, but also a recent marriage showed moderate effects. No interaction was found on the association between life events and the first admission with mania, totally, or for men or women, separately regarding ageing.

Conclusions:  The occurrence of death in the family and the experience of major life events are associated with increased risk of first admission with bipolar disorder. The susceptibility to major life stressors of inducing mania does not seem to change throughout life.
A survival analysis for recurrent events in psychiatric research
Authors: Baethge Christopher , Schlattmann Peter
Published: December 2004

Objectives: Time to first recurrence, as analyzed by the Kaplan–Meier (KM) survival analysis, is a commonly applied statistical method in psychiatric research. However, many psychiatric disorders are characterized not by a single event, but rather by recurrent events, such as multiple affective episodes. This study aims to demonstrate a method of survival analysis that takes multiple recurrences into account.

Methods: We examined data on sex differences in a sample of 181 patients undergoing prophylactic treatment with lithium or carbamazepine (serum level assayed) for bipolar disorder (ICD‐10). The classical KM method was compared with an approach developed by Peña, Strawderman and Hollander (PSH) that uses recurrent event data to estimate survival function.

Results: The results obtained with the multiple events method differed considerably from those acquired using the standard KM analysis. When taking recurrent event data into account, the probability of remaining well was lower and survival times were longer. In addition, whereas the standard KM analysis indicated that male patients had a higher likelihood of remaining well, the alternative method revealed that both sexes were similarly likely to remain well.

Conclusions: Survival analysis techniques that take recurrent events into account are potentially important instruments for the study of psychiatric conditions characterized by multiple recurrences. In many cases, the standard KM analysis appears to provide only a rough approximation of the course of illness.
Psychosocial variables in children and teens of extended families identified through bipolar affective disorder probands
Authors: Petti Theodore , Reich Wendy , Todd Richard D , Joshi Paramjit , Galvin Matthew , Reich Theodore , Raymond DePaulo J , Nurnberger John
Published: December 2004

Objectives:  This multi‐site study investigated the frequency of risk‐related variables for developing an affective disorder using a within‐pedigree control group. We wished to determine the effect of life events, social relationships, self‐perceived competence, and aspects of home environment for youngsters from extended families with loading for bipolar disorder. Using a within‐family contrast group, we address the following two issues: (1) Do offspring or their parents from families who do and do not have an affected parent report differences (i) in home environment? (ii) in frequency and type of offspring life events? and (iii) in social relations and self‐perception? and (2) Do children or their parents who do or do not have an affective disorder report differently on these areas?

Methods:  Juvenile offspring (n = 50) and their parents from 14 bipolar pedigrees were assessed. Structured interviews and self‐ or parent‐reported instruments were used to compare offspring with an affected first‐degree relative to those without and to compare offspring with or without an affective disorder.

Results:  Only one significant psychosocial difference was found between offspring with or without a parent with an affective disorder but several were found between offspring who themselves did or did not have an affective disorder. These differences are in the areas of the need for discipline, social support, and dependent negative life events.

Conclusions:  The findings identify potential early psychosocial markers for affective disorder in high risk offspring.
All‐trans retinoic acid enhances differentiation and influences permeability of intestinal Caco‐2 cells under serum‐free conditions
Authors: Baltes Steffen , Nau Heinz , Lampen Alfonso
Published: December 2004

Vitamin A and retinoids are essential nutrients for the differentiation of epithelia. Vitamin A deficiency is accompanied by an impairment in intestinal integrity. We investigated whether retinoids influence the differentiation and permeability of Caco‐2 cells under serum‐free culture conditions as a model for the intestinal epithelium. Treatment of the Caco‐2 cells with retinoic acids (RA) resulted in an increased specific activity, enhanced mRNA expression, and induction of the 5′‐flanking promoter activity of the marker enzyme for the differentiation intestinal alkaline phosphatase. Surprisingly, permeability of the Caco‐2 monolayer, as measured by transepithelial electric resistance and [3H]‐mannitol flux, was found to be enhanced by RA. Treatment with RA had only a slight effect on the mRNA expression of the tight junction‐associated proteins occludin, ZO‐1, claudin‐1, ‐3, and ‐4, but enhanced the expression of claudin‐2, which was recently suggested to form a paracellular ion channel. The role of retinoids as potent inducers of epithelial differentiation was confirmed for the Caco‐2 cells under serum‐free culture conditions and it was concluded that IAP is a target gene of RA. The inverse regulation of the permeability by RA under these serum‐free conditions showed that other mechanisms, which are essential to regulate intestinal epithelial integrity with respect to decreased permeability, have to be identified.
Repulsive guidance molecule/neogenin: a novel ligand‐receptor system playing multiple roles in neural development
Authors: Matsunaga Eiji , Chédotal Alain
Published: December 2004

The repulsive guidance molecule (RGM) is a membrane‐bound protein originally isolated as an axon guidance molecule in the visual system. Recently, the transmembrane protein, neogenin, has been identified as the RGM receptor. In vitro analysis with retinal explants showed that RGM repels temporal retinal axons and collapses their growth cones through neogenin‐mediated signaling. However, RGM and neogenin are also broadly expressed at the early embryonic stage, suggesting that they do not only control the guidance of visual axons. Gene expression perturbation experiments in chick embryos showed that neogenin induces cell death, and its ligand, RGM, blocks the pro‐apoptotic activity of neogenin. Thus, RGM/neogenin is a novel dependence ligand/receptor couple as well as an axon guidance molecular complex.
How does Fgf signaling from the isthmic organizer induce midbrain and cerebellum development?
Authors: Sato Tatsuya , Joyner Alexandra L. , Nakamura Harukazu
Published: December 2004

The mesencephalic/rhombomere 1 border (isthmus) is an organizing center for early development of midbrain and cerebellum. In this review, we summarize recent progress in studies of Fgf signaling in the isthmus and discuss how the isthmus instructs the differentiation of the midbrain versus cerebellum. Fgf8 is shown to play a pivotal role in isthmic organizer activity. Only a strong Fgf signal mediated by Fgf8b activates the Ras‐extracellular signal‐regulated kinase (ERK) pathway, and this is sufficient to induce cerebellar development. A lower level of signaling transduced by Fgf8a, Fgf17 and Fgf18 induce midbrain development. Numerous feedback loops then maintain appropriate mesencephalon/rhombomere1 and organizer gene expression.
Role of TSC‐22 during early embryogenesis in Xenopus laevis
Authors: Hashiguchi Akiko , Okabayashi Koji , Asashima Makoto
Published: December 2004

Transforming growth factor‐β1‐stimulated clone 22 (TSC‐22) encodes a leucine zipper‐containing protein that is highly conserved. During mouse embryogenesis, TSC‐22 is expressed at the site of epithelial–mesenchymal interaction. Here, we isolated Xenopus laevis TSC‐22 (XTSC‐22) and analyzed its function in early development. XTSC‐22 mRNA was first detected in the ectoderm of late blastulae. Translational knockdown using XTSC‐22 antisense morpholino oligonucleotides (XTSC‐22‐MO) caused a severe delay in blastopore closure in gastrulating embryos. This was not due to mesoderm induction or convergent‐extension, as confirmed by whole‐mount in situ hybridization and animal cap assay. Cell lineage tracing revealed that migration of ectoderm cells toward blastopore was disrupted in XTSC‐22‐depleted embryos, and these embryos had a marked increase in the number of dividing cells. In contrast, cell division was suppressed in XTSC‐22 mRNA‐injected embryos. Co‐injection of XTSC‐22‐MO and mRNA encoding p27Xic1, which inhibits cell cycle promotion by binding cyclin/Cdk complexes, reversed aberrant cell division. This was accompanied by rescue of the delay in blastopore closure and cell migration. These results indicate that XTSC‐22 is required for cell movement during gastrulation though cell cycle regulation.
Identification of differentially expressed genes in yeast Saccharomyces cerevisiae cells with inactivated Mmf1p and Hmf1p, members of proteins family YERO57c/YJGF
Authors: Pozdniakovaite Natalija , Popendikyte Violeta
Published: December 2004

We used differential display analysis of mRNA to investigate the differences between gene expression in wild‐type (wt) yeast Saccharomyces cerevisiae cells and mutated ones with disrupted activity of genes MMF1 and HMF1, members of the YERO57c/YJGF family. Reverse transcription‐polymerase chain reaction (RT‐PCR) analysis was performed to determine the differences in the degree of expression of 14 specific transcripts in normal and mutated yeast cells. Obtained data demonstrate that disruption of genes encoding proteins Mmf1p, Hmf1p (or both of them) result in the correlative variation of expression level of the target 12 genes both in the cells with changed phenotype (mmf1 and mmf1 hmf1) and in the cells retaining w.t. shape and growth rate (wt cells, hmf1). Metabolic processes and cellular pathways have been indicated for Mmf1p and Hmf1p based on the different profiles of the expression of 14 genes in mmf1, hmf1 yeast S. cerevisiae cells.
Labour pain experience and intensity: A Jordanian perspective
Authors: Abushaikha Lubna , Oweis Arwa
Published: December 2004

In this descriptive study, 100 low‐risk participants who delivered vaginally were recruited from the postpartum unit of a major hospital in the city of Amman. Three instruments, the Numeric Pain Intensity Scale (NPIS), a pain assessment questionnaire and a demographic questionnaire were used to assess labour experiences and labour pain intensity levels. The majority of Jordanian parturients did not receive pain relief. Eighty‐one women reported pain intensity levels of ≥ 8 on the NPIS (ranging from 0–10). The mean pain intensity level during the second stage of labour was 8.83. A significant difference in age was found between primiparas and multiparas. Jordanian parturients reported painful labour experiences; therefore, re‐evaluation of current maternity nursing and midwifery practices and roles regarding labour pain management are warranted. The roles of supporter and educator among maternity nurses and midwives in Jordan also need to improve considerably.
The effects of health beliefs on health care‐seeking decisions of Jordanian patients with myocardial infarction symptoms
Authors: Al‐Hassan Musa A , Omran Suha M
Published: December 2004

The main purpose of this study was to examine the significance of health beliefs, perceived seriousness of harmful consequences and perceived barriers in explaining health care‐seeking decisions of patients experiencing myocardial infarction symptoms. A structured interview guide developed by the researchers that included health beliefs, patient delay, sociodemographics and clinical characteristics of the patients was introduced to 79 myocardial infarction patients on the third day of hospitalization. Thirty‐eight per cent of the patients delayed the health care‐seeking decision > 1 h. Gender, age and perceived seriousness of the consequences significantly distinguished between delayers and non‐delayers, correctly classifying 77% of the cases. Delayers were more likely to be female and young adults, and those who perceived increased negative consequences to myocardial infarction. Educational and counselling programmes for individuals at increased risk for myocardial infarction should consider the negative influence of perceived seriousness of consequences on the decision‐making process of the patients. Also, interventions to change women's perception of their vulnerability to this illness are needed.
Efficacy of extended‐release doxazosin and doxazosin standard in patients with concomitant benign prostatic hyperplasia and sexual dysfunction
Authors: Kirby Roger S. , O'Leary Michael P. , Carson Culley
Published: December 2004

Associate Editor  Michael G. Wyllie  Editorial Board  Ian Eardley, UK  Jean Fourcroy, USA  Sidney Glina, Brazil  Julia Heiman, USA  Chris McMahon, Australia  Bob Millar, UK  Alvaro Morales, Canada  Michael Perelman, USA  Marcel Waldinger, Netherlands

OBJECTIVE

To report a comprehensive retrospective analysis of the favourable effects of doxazosin extended‐release (XL) and doxazosin standard on the sexual health of patients with comorbid benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), augmenting a previous study of 680 patients with symptomatic BPH.

PATIENTS AND METHODS

Men with BPH and aged 50–80 years participated in a randomized, double‐ blind, double‐dummy, parallel‐group, multicentre trial, completing a 2‐week, single‐blind, placebo run‐in period before receiving doxazosin XL 4 or 8 mg once daily or doxazosin standard 1–8 mg once daily for 13 weeks. Baseline sexual function and changes from baseline after treatment with doxazosin were evaluated from responses of the International Index of Erectile Function (IIEF) questionnaire (with dysfunction defined as a score of ≤ 3 for any question) and the five domains for erectile function (intercourse satisfaction, orgasmic function, sexual desire and overall sexual satisfaction).

RESULTS

Of 680 patients randomized into the trial, 237 (35%) had ED at baseline; in these patients there were statistically and clinically significant improvements in each of the five IIEF domains with XL and standard doxazosin (P ≤ 0.0019), with the range of improvement being from 13% to 41%. There were no significant differences between treatment groups. Doxazosin XL consistently improved sexual function, as assessed by the individual questions of the IIEF questionnaire. There was no statistically significant difference between groups for any sexual function question analysed.

CONCLUSION

Doxazosin XL and standard improved sexual function in men with concomitant BPH and ED at baseline. This may represent an action independent of relieving lower urinary tract symptoms, because the beneficial effect of doxazosin was reported in patients with no symptomatic BPH.
Acute urinary retention: what is the impact on patients’ quality of life?
Authors: Thomas Kay , Oades Grenville , Taylor‐Hay Cathy , Kirby Roger S.
Published: December 2004

OBJECTIVE

To evaluate the impact of admission for acute urinary retention (AUR) on patients’ health‐related quality of life (HRQoL) compared with that on admission for elective surgery for benign prostatic hyperplasia (BPH) and emergency admission for renal colic (RC).

PATIENTS AND METHODS

Over a 2‐year period, three groups of men were recruited from one institution: group 1, men aged >50 years presenting to the accident and emergency (A&E) department with AUR; group 2, for comparison, men aged >50 years admitted for elective surgery for BPH; and group 3, men aged >40 years presenting to A&E with RC. A self‐completed HRQoL questionnaire was administered at five visits (72 h from admission, and 1, 2, 3 and 6 months afterward) over a 6‐month follow‐up.

RESULTS

Group 1 reported mean pain scores on admission of 7.7, compared with 5.6 for group 2 and 8.3 for group 3. Patients in group 1 had the most investigations and recurrent attendance to A&E throughout the study, compared with almost none for the other two groups. There was a substantial economic burden for group 1; 15% had extra help at home at a mean cost of £403 for the duration of the study. For the other domains assessed (e.g. emotions, mental state, general health) groups 1 and 2 were similar.

CONCLUSIONS

An episode of AUR has a measurable impact on patients’ HRQoL, which often occurs in the community and therefore may not be appreciated by the urology team providing their care. Further work is therefore required to improve the ‘patient journey’ for those with AUR, and to prevent patients developing AUR in the future.
Improved quality of life in patients with overactive bladder symptoms treated with solifenacin
Authors: Kelleher Con J. , Cardozo Linda , Chapple Christopher R. , Haab Francois , Ridder Arwin M.
Published: December 2004

OBJECTIVE

To assess the effect of solifenacin succinate treatment on quality of life (QoL) measured in clinical trials in patients with overactive bladder (OAB).

PATIENTS AND METHODS

QoL data using the King's Health Questionnaire (KHQ) were analysed from two phase‐3, 12‐week studies (1984 patients) and a long‐term extension of these studies (1637 patients) where patients received solifenacin for up to an additional 40 weeks (i.e. a 52‐week exposure to solifenacin). The 12‐week studies were multinational, multicentre, randomized, double‐blind, and placebo‐controlled. The 10 domains from the KHQ evaluated were general health perception, incontinence impact, role limitations, physical limitations, social limitations, personal relationships, emotions, sleep/energy, severity measures, and symptom severity. Changes from baseline to endpoint in QoL variables were assessed by analysis of variance, and from pooled outcomes of the 12‐week studies by analysis of covariance. Descriptive statistics were used to evaluate data in the extension study.

RESULTS

In the two 12‐week studies (1033 and 857 patients), those receiving once‐daily solifenacin had statistically significantly better QoL than those on placebo. Changes in the KHQ were statistically significantly (P < 0.05) different from placebo for both solifenacin 5 and 10 mg once daily on five of the 10 KHQ domains in each of the studies. Pooled data from the two 12‐week studies showed statistically significant (P < 0.05) differences from placebo for both solifenacin doses in nine of the 10 domains. Improvements in QoL scores for solifenacin were 35–48% in nine of the 10 domains for the 1347 patients providing QoL data in the extension study. About two‐thirds of this overall improvement occurred during the original 12‐week study, with an additional third reported during the extension, with an improvement in QoL over time in patients treated with solifenacin.

CONCLUSIONS

Results from the KHQ in study participants in the two double‐blind studies showed that solifenacin significantly improved the QoL in patients with OAB symptoms after 12 weeks of treatment, with further improvements during long‐term administration up to 1 year. Clinical trial outcomes show a favourable balance of efficacy and tolerability with solifenacin; the present report further supports this efficacy and tolerability by providing evidence for both short‐ and long‐term improvements in QoL.