Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

The Pregnant Smoker Stigma Scale - Self Stigma (P3S-SS): development and validation in pregnant smoking women in France.

Pregnancy smoking self-stigma may be associated with mental health and smoking cessation. This study aims to validate the Pregnant Smoker Stigma Scale - Self-Stigma (P3S-SS) assessing perceived and internalized stigma. Between May 2021 and May 2022, French pregnant smokers recruited online (n = 143) took the P3S-SS and other scales assessing depressive symptoms (EPDS), social inclusion (SIS), dissimulation, dependence (CDS-5), cessation self-efficacy (SEQ), and intention. The two versions of the scale include four dimensions: derogatory cognitions ("People think/I feel I am selfish"), negative emotions and behaviors ("People make me feel/smoking makes me feel guilty"), personal distress ("People/I feel sorry for me/myself"), and information provision ("People tell me/I think about the risks of smoking"). Confirmatory factor analyses and multiple regressions have been computed. Model fit was good for perceived stigma and internalized stigma (X2/df = 3.06, RMSEA = .124, AGFI = .982, SRMR = .068, CFI = .986, NNFI = .985; X2/df = 3.31, RMSEA = .14, AGFI = .977, SRMR = .087, CFI = .981, NNFI = .979). Controlling for dependence, cessation intention was positively predicted by perceived and internalized personal distress and negatively predicted by perceived negative emotions and behaviors (Adj R2 = .143, F(8,115) = 3.567, p = .001). Controlling for dependence, dissimulation was positively predicted by internalized negative cognitions and perceived personal distress and negatively predicted by internalized personal distress (Adj R2 = .19, F(9,98) = 3.785, p = .000). The P3S-SS opens up exciting avenues for further research. Stigma does not motivate women to stop smoking but increases distress and dissimulation.

Screening Beyond Postpartum Depression: Occluded Anxiety Component in the EPDS (EPDS-3A) in French Mothers.

INTRODUCTION: According to many studies, anxiety in the perinatal period is widespread and has many detrimental effects. Thus, screening measures should not be limited to assessing depression symptoms. The widely used Edinburgh Postnatal Depression Scale (EPDS) might assess depression but also anxiety symptoms. This study explores whether an anxiety dimension (EPDS-3A) was found and valid in French women during pregnancy and the postpartum period. METHODS: French women were followed-up at late pregnancy and 2 and 4 months postpartum (N = 144, 138 and 129). They completed the EPDS and the Hospital Anxiety and Depression Scale (HADS-A). Exploratory factor analyses were performed. Then to test its validity, the EPDS-3A was correlated with anxiety (HADS-A) and depression (EPDS-D) scores. Finally, prevalence estimates were computed according to recommended cut off. RESULTS: The anxiety dimension assessed through the EPDS-3A was observed during the postpartum period but not during pregnancy. A two-factor structure (depression and anxiety) increases the variance explained at 2 and 4 months postpartum (respectively 6 and 12%). The EPDS-3A shows good internal consistency (≥ .70) and was more strongly associated with anxiety scores (HADS-A) (.48-.57) than with depression scores (EPDS-D) (.30-.39). Nearly 28% of mothers had scores that exceeded the EPDS-3A cut off (≥ 4) but not the full EPDS cut off (≥ 13 or more). DISCUSSION: The EPDS contains an anxiety component (EPDS-3A) that can be found in French women during the postnatal period but not during pregnancy. It shows signs of internal consistency and validity. The EPDS-3A could be considered when screening for postpartum anxiety.

Women with symptoms of a urinary tract infection but a negative urine culture: PCR-based quantification of Escherichia coli suggests infection in most cases.

OBJECTIVES: Our objective was to examine whether or not women with symptoms of a urinary tract infection but with a negative culture (20%-30%) do have an infection. METHODS: We performed quantitative PCR (qPCR) for Escherichia coli and Staphylococcus saprophyticus, on top of a standard culture, in urine samples from 220 women with dysuria and/or frequency and/or urgency and from 86 women without symptoms. For symptomatic women, qPCR was also carried out for four sexually transmitted agents. RESULTS: In the symptomatic group, 80.9% (178/220) of the urine cultures were positive for any uropathogen and 95.9% (211/220) were E. coli qPCR-positive. For the control group, cultures for E. coli and E. coli qPCR were positive in, respectively, 10.5% (9/86) and 11.6% (10/86). In the symptomatic group, qPCR yielded 19 positive samples for S. saprophyticus qPCR, one positive sample for Mycoplasma genitalium and one for Trichomonas vaginalis. CONCLUSIONS: These findings suggest that almost all women with typical urinary complaints and a negative culture still have an infection with E. coli.

The copulatory plug delays ejaculation by rival males and affects sperm competition outcome in house mice.

Females of many species mate with multiple males (polyandry), resulting in male-male competition extending to post-copulation (sperm competition). Males adapt to such post-copulatory sexual selection by altering features of their ejaculate that increase its competitiveness and/or by decreasing the risk of sperm competition through female manipulation or interference with rival male behaviour. At ejaculation, males of many species deposit copulatory plugs, which are commonly interpreted as a male adaptation to post-copulatory competition and are thought to reduce or delay female remating. Here, we used a vertebrate model species, the house mouse, to study the consequences of copulatory plugs for post-copulatory competition. We experimentally manipulated plugs after a female's first mating and investigated the consequences for rival male behaviour and paternity outcome. We found that even intact copulatory plugs were ineffective at preventing female remating, but that plugs influenced the rival male copulatory behaviour. Rivals facing intact copulatory plugs performed more but shorter copulations and ejaculated later than when the plug had been fully or partially removed. This suggests that the copulatory plug represents a considerable physical barrier to rival males. The paternity share of first males increased with a longer delay between the first and second males' ejaculations, indicative of fitness consequences of copulatory plugs. However, when males provided little copulatory stimulation, the incidence of pregnancy failure increased, representing a potential benefit of intense and repeated copulation besides plug removal. We discuss the potential mechanisms of how plugs influence sperm competition outcome and consequences for male copulatory behaviour.

Assessment of mechanisms driving non-linear dose-response relationships in genotoxicity testing.

In genetic toxicology, risk assessment has traditionally adopted linear dose-responses for any compound that causes genotoxic effects. Increasing evidence of non-linear dose-responses, however, suggests potential cellular tolerance to low levels of many genotoxicants with diverse modes of action. Such putative non-linear dose-responses need to be substantiated by strong mechanistic data that identifies the mechanisms responsible for the tolerance to low doses. This can be achieved by experimental demonstration of cytoprotective mechanisms and by providing experimental support for the existence of tolerance mechanisms against low dose effects. By highlighting key experiments into low dose mechanisms, this review aims to clarify which mechanistic data are required to support the use of non-linear dose-response models in risk assessment. Such key experiments are presented and discussed for alkylating agents, oxidants, particulate matter, nucleoside analogues, topoisomerase inhibitors and aneugens and exemplify the use of gene knockout models or transgenic models as well as chemical modulators of key effectors of relevant pathways and their impact on dose-response relationships. In vitro studies are particularly valuable to elucidate mechanisms of low-dose protection or lack thereof, while in vivo experiments are most appropriate for deriving a safe dose. In order to evaluate the existence of non-linear dose-response relationships for genotoxicants, we suggest that careful attention should be given to the mode of genotoxic action, relevant biomarkers of exposure, as well as to the existence and impact of potential cytoprotective mechanisms like detoxifying metabolism and DNA repair.

Clinical outcomes and costs associated with in-hospital biliary complications after liver transplantation: a cross-sectional analysis.

INTRODUCTION: In-hospital biliary complications (BCs) after liver transplantation (LT) are reported in up to 20 % of patients and contribute to poor outcomes and increased costs. Existing single-center outcome and cost analyses studies are limited in scope. METHODS: This is a cross-sectional analysis of national data involving 7,967 patients transplanted between 2011 and 2012 with the primary aim of determining the association between BCs and clinical outcomes and costs. Age, race, diagnosis, and severity of illness are associated with the development of BCs. RESULTS: BCs develop in 14.6 % of LT recipients and have substantial implications for perioperative outcomes, including length of hospital and ICU stay (27.9 vs 19.6 mean days, p < 0.001 and 12.0 vs 8.3 mean days, p < 0.001, respectively), in-hospital morbidity (39 vs 27 %, p < 0.001), 30-day readmissions (14.8 vs 11.2 %, p < 0.001), and in-hospital mortality (5.8 vs 4.0 %, p < 0.001). BCs contributed to a mean increase in in-hospital costs of $36,212 (p < 0.001), due to increases in accommodations ($9,539, p < 0.001), surgical services ($3,988, p < 0.001), and pharmacy services ($8,445, p < 0.001). DISCUSSION: BCs are a predominant etiology for in-hospital morbidity and mortality, while contributing significantly to the high cost of LT. Efforts should be focused on understanding salient and modifiable risk factors, while developing innovative strategies to reduce BCs.

Two case reports of a malignant germ cell tumor of ovary and a granulosa cell tumor: interest of tumoral immunochemistry in the identification and management.

OBJECTIVE: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23-year old woman and the second case was a bilateral undifferentiated granulosa cell tumor in a 71-year old woman. The aim of these reports is to illustrate the interest of the immunohistochemical analysis to define the correct diagnosis, to better classify these ovarian tumors and improve their management. METHODS: In this study, we report two cases. The first case concerns a 23-year old woman (A) with a mixed germ cell tumor of the right ovary [dysgerminoma (75%), yolk sac tumor (20%), and a mature teratoma (5%)], and the second case concerns a 71-year old woman (B) with a bilateral non-differentiated and necrotic granulosa cell tumor of both ovaries. The staging system was used according to both the classifications: International Federation of Gynaecology and Obstetrics 1987 for ovarian cancer and TNM code 2009. RESULTS: The immunostaining establishes the malignancy and the immunochemistry contributes to confirm effectively the right diagnosis (Tables 2 and 3). CONCLUSION: An immunohistochemical analysis is mandatory for the choice of chemotherapy to obtain a better response of the disease and improve the survival prognosis. The efficiency of the chemotherapy authorizes a conservative surgery including a unilateral salpingo-oophorectomy preserving fertility (A). Concerning the non-dysgerminoma tumor (B), and after a surgical staging and debulking, chemotherapy was recommended. The type of tumor and its histological feature conditioned the choice of treatment. The benefit of the immunohistological analysis in this case allowed the right adjuvant treatment.

Sex-specific clines support incipient speciation in a common European mammal.

Hybrid zones provide excellent opportunities to study processes and mechanisms underlying reproductive isolation and speciation. Here we investigated sex-specific clines of molecular markers in hybrid zones of morphologically cryptic yet genetically highly-diverged evolutionary lineages of the European common vole (Microtus arvalis). We analyzed the position and width of four secondary contact zones along three independent transects in the region of the Alps using maternally (mitochondrial DNA) and paternally (Y-chromosome) inherited genetic markers. Given male-biased dispersal in the common vole, a selectively neutral secondary contact would show broader paternal marker clines than maternal ones. In a selective case, for example, involving a form of Haldane's rule, Y-chromosomal clines would not be expected to be broader than maternal markers because they are transmitted by the heterogametic sex and thus gene flow would be restricted. Consistent with the selective case, paternal clines were significantly narrower or at most equal in width to maternal clines in all contact zones. In addition, analyses using maximum likelihood cline-fitting detected a shift of paternal relative to maternal clines in three of four contact zones. These patterns suggest that processes at the contact zones in the common vole are not selectively neutral, and that partial reproductive isolation is already established between these evolutionary lineages. We conclude that hybrid zone movement, sexual selection and/or genetic incompatibilities are likely associated with an unusual unidirectional manifestation of Haldane's rule in this common European mammal.

Inpatient mother-and-child postpartum psychiatric care: factors associated with improvement in maternal mental health.

PURPOSE: This study assessed the underexplored factors associated with significant improvement in mothers' mental health during postpartum inpatient psychiatric care. METHODS: This study analyzed clinical improvement in a prospective cohort of 869 women jointly admitted with their infant to 13 psychiatric Mother-Baby Units (MBUs) in France between 2001 and 2007. Predictive variables tested were: maternal mental illness (ICD-10), sociodemographic characteristics, mental illness and childhood abuse history, acute or chronic disorder, pregnancy and birth data, characteristics and mental health of the mother's partner, and MBU characteristics. RESULTS: Two thirds of the women improved significantly by discharge. Admission for 25% was for a first acute episode very early after childbirth. Independent factors associated with marked improvement at discharge were bipolar or depressive disorder, a first acute episode or relapse of such an episode. Schizophrenia, a personality disorder, and poor social integration (as measured by occupational status) were all related to poor clinical outcomes. DISCUSSION: Most women improved significantly while under care in MBUs. Our results emphasize the importance of the type of disease but also its chronicity and the social integration when providing postpartum psychiatric care.

Achievements of the Belgian Antibiotic Policy Coordination Committee (BAPCOC).

A Belgian Antibiotic Policy Coordination Committee (BAPCOC) was officially established in 1999 by Royal Decree. The overall objective of BAPCOC is to promote judicious use of antibiotics in humans and animals and to promote infection control and hospital hygiene, with the overall aim to reduce antibiotic resistance. BAPCOC fostered strong and interdisciplinary public health, scientific and political leadership, which led to many evidence-based interventions such as multimedia campaigns to promote the prudent use of antibiotics in the community, national campaigns to promote hand hygiene in hospitals, publication of clinical practice guidelines, staffing and technical support for establishment of antibiotic management teams in all Belgian hospitals, surveillance programmes on antibiotic use and resistance in humans and animals and the promotion of research. These activities and interventions resulted in a measurable decrease in antibiotic use and resistance in the community and hospitals.

Effects of social crowding on emotionality and expression of hippocampal nociceptin/orphanin FQ system transcripts in mice.

The novel nociceptin/orphanin FQ (N/OFQ) system was proposed to be an important component of neural circuits involved in stress-coping behaviour and fear. This study investigated whether variations between the mouse strains in vulnerability to social crowding stress might be linked to different regulation of N/OFQ system transcripts in mice. Three weeks old C57BL/6J (B6), BALB/cByJ (CBy) and 129S2/SvPas (129S2) male mice were housed individually or in crowded (7/cage) conditions and then tested as adults in a battery of anxiety tests (open field, elevated plus-maze and acoustic startle reflex tests). Both 129S2 and B6 mice displayed increased signs of anxiety under crowded housing, while CBy mice tended to show the opposite profile. Analysis of gene expression revealed a 10-fold increase of nociceptin precursor and 4-fold increase of the NOP receptor mRNAs contents in the hippocampus of CBy mice kept in crowded conditions compared to those housed individually. In B6 mice, mRNA level of the peptide precursor remained unchanged, while that of the receptor was increased by 2-fold under crowding compared to individual housing. No significant changes were detected in 129S2 mice. These findings show that social housing may be important environmental stress factor in mice depending on the strain. The possible involvement of central nociceptin mechanisms in behavioural resilience to social crowding stress is discussed.

Decreased brain tryptophan availability as a partial determinant of post-partum blues.

BACKGROUND: The post-partum blues is a transient mood alteration affecting most women a few days after delivery. Its stereotypic pattern of symptoms and time course, peaking on post-partum day 3-5, is suggestive of biological determinants superimposed on psycho-social factors. This study was designed to evaluate the possible role of the serotonin system during this period through assessment of brain tryptophan availability. METHODS: Blood samples from 50 women were collected just before (D0) and 3 days after (D3) delivery. Based on plasma concentration of tryptophan, amino acids competing with tryptophan for transport across the blood-brain barrier and on their respective affinities for this transporter, a brain tryptophan availability index (BTAI) was calculated and its variation correlated with the intensity of post-partum blues evaluated through the Kennerley and Gath score at D3. RESULTS: The BTAI showed a -15% decrease between D0 and D3 (p < 0.01, paired t-test). This decrease was not supported by a drop in plasma tryptophan since its level rather increased (+19%). There was no evidence for change in placental indoleamine-2,3-dioxygenase activity since the variation in plasma l-kynurenine (+12%) paralleled the change in tryptophan level. The decreased BTAI appeared the consequence of a dramatic increase in plasma levels of most amino acids, particularly the competitor aminoacids leucine, isoleucine, valine and tyrosine, during the early post-partum. This decrease in brain tryptophan availability was concomitant to the post-partum blues, whose intensity significantly correlated with the amplitude of BTAI variation (Pearson's coefficient -0.283, p < 0.05). CONCLUSION: This study suggests that generalized, large amplitude metabolic and/or nutritional changes occurring in the early post-partum result in a transient decrease in brain tryptophan availability, partly accounting for the mood alteration referred to as the post-partum blues, a model for the triggering of puerperal mood disorder in vulnerable women.

[Baby blues: characterization and influence of psycho-social factors]. / Le baby blues: caractérisation clinique et influence de variables psycho-sociales.

BACKGROUND: Within days following birth, most women are showing signs of mood changes, commonly named baby blues. Due to the frequency of this condition, baby blues is considered as a physiological state probably associated to biological modifications. Some studies have shown an existing link between the intensity of the baby blues and post-partum mood disorder. Therefore, it seems important to report and explore in more details the clinical background related the condition. The aim of this study was to demonstrate the possibility of a link between the intensity of the baby blues and some specific factors like maternal self-esteem, maternal childcare stress and social background, and also to define the symptoms of the baby blues from core dimensions in mood disorders. METHOD: Mothers were recruited few hours before giving birth in a teaching hospital. At the third day following birth, an appointment was made to obtain the necessary information (past medical history and social history) and history of previous mood disorders. The mood was evaluated from the scale of the intensity of baby blues from Kennerly and Gath (1989). Moreover, evaluations at day 3 and week 6 post birth of self-esteem in relation to motherhood (Maternal self-report Inventory from Shea and Tronick, 1988), stress in relation with the care of the baby (Childcare Stress Inventory from Cutrona, 1983) and the social support (Social Support scale from Bruchon-Schweitzer, 1998) were undertaken. RESULTS: 95 women were included in the final sample. The intensity of the baby blues was explained by the type of pregnancy (p=0.002), a low maternal self-esteem (p=0.025), high levels of stress in relation to the care of the baby (p=0.074). The basic clinical characteristic of the baby blues seems to be due to an increase in the emotional reaction with a sharp feelings, leading to a lability rather than an affect sad tonality. CONCLUSION: The baby blues seems to be a physiological process whereby the intensity is influenced by psychological factors. Consequently the diminution of self-esteem with motherhood and the increase of stress in relation to the care of the baby appeared to be significant factors in the intensity of the baby blues. Moreover, the clinical characteristics found in this study implies that the baby blues is more related to hypomania rather than to depression syndrome. This non-pathological state could be the first stage leading to a puerperal psychosis in predisposed women, which is mainly characterized by manic symptoms.

[Attachment and suffering mothers]. / Attachement et mères en souffrance.

Attachment between an infant and his/her parents is instinctive and vital for the psychoaffective development of the child. This process is fragile, and parents have to present with adaptive capacities. They need a good mental health to be able to welcome their child and to develop the interactions that will enable the baby to acquire an internal security. When mental disorders, especially maternal disorders, appear during this crucial perinatal period, the relationship between the parents and their baby may become unstable, and the attachment process can be disturbed.

Recent results in understanding molecular pathways in the medical treatment of esophageal and gastric cancer.

Cancers of the esophagus and stomach constitute a major cause of cancer deaths worldwide. Despite improvements in both surgical techniques and (radio) chemotherapy regimens, these tumors remain a great therapeutic challenge. Thus, there is a need for innovative medical treatment strategies effective even in advanced disease. An emerging understanding of the molecular events that characterize carcinogenesis, tumor growth and spread may provide novel targets in cancer therapy. In this review we discuss novel strategies to inhibit growth, angiogenesis, invasion, and spread of tumors and to induce apoptosis. Therapeutic strategies discussed include agents targeting the epidermal growth factor receptor (EGFR) family, the mitogen-activated protein kinase (MAPK) pathway, regulators of apoptosis (NF-kappaB, bcl-2, and the peripheral benzodiazepine receptor), cyclooxygenase-2, the vascular-endothelial growth factor receptor and matrix metalloproteinases.

A novel approach in the treatment of neuroendocrine gastrointestinal tumours. Targeting the epidermal growth factor receptor by gefitinib (ZD1839).

Therapeutic options to inhibit the growth and spread of neuroendocrine (NE) gastrointestinal tumours are still limited. Since gefitinib (4-(3-chloro-4-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline), an inhibitor of epidermal growth factor receptor-sensitive tyrosine kinase (EGFR-TK), had been shown to suppress potently the growth of various non-NE tumour entities, we studied the antineoplastic potency of gefitinib in NE gastrointestinal tumour cells. In human insulinoma (CM) cells, in human pancreatic carcinoid (BON) cells and in NE tumour cells of the gut (STC-1), gefitinib induced a time- and dose-dependent growth inhibition by almost 100%. The antiproliferative potency of gefitinib correlated with the proliferation rate of the tumour cells. So the IC(50) value of gefitinib was 4.7+/-0.6 microM in the fast-growing CM cells, still 16.8+/-0.4 microM in the moderate-growing BON cells, and up to 31.5+/-2.5 microM in the slow-growing STC-1 cells. Similarly, the induction of apoptosis and cell-cycle arrest by gefitinib differed according to growth characteristics: fast-growing CM cells displayed a strong G0/G1 arrest in response to gefitinib, while no significant cell-cycle alterations were seen in the slow-growing STC-1. Vice versa, the proapoptotic effects of gefitinib, as determined by caspase-3 activation and DNA fragmentation, were most pronounced in the slow-growing STC-1 cells. Using cDNA microarrays, we found extensive changes in the expression of genes involved in the regulation of apoptosis and cell cycle after incubation with gefitinib. Among them, an upregulation of the growth arrest and DNA damage-inducible gene GADD153 was observed. Phosphorylation of ERK1/2, which inhibits GADD153 expression, was reduced in a time-dependent manner. However, no gefitinib-induced activation of the GADD153-inducing p38 mitogen-activated protein kinase was detected. Our data demonstrate that the inhibition of EGFR-TK by gefitinib induces growth inhibition, apoptosis and cell-cycle arrest in NE gastrointestinal tumour cells. Thus, EGFR-TK inhibition appears to be a promising novel approach for the treatment of NE tumour disease.

Antihistamines for the common cold.

BACKGROUND: Although antihistamines are prescribed in large quantities for the common cold, there is little evidence to whether these drugs are effective. OBJECTIVES: To assess in patients with a common cold the effects of antihistamines in alleviating nasal symptoms, or in shortening of illness duration. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infections Group Specialized Register and EMBASE up to December 2002; Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE up to February 2003. We also followed up references in identified papers. We appealed for further articles at a major international conference on Acute Respiratory Infections (1997). We corresponded with experts and got in touch with pharmaceutical companies. SELECTION CRITERIA: Randomised, placebo-controlled trials on treatment of common cold with antihistamines, used either singly or in combination, in adults or children. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers and authors were contacted for further data. Trials were subdivided into monotherapy and combination therapy. Data on general recovery, nasal obstruction, rhinorrhea, sneezing, and side-effects were extracted and summarized in a systematic review. MAIN RESULTS: We included thirty two papers describing 35 comparisons; 22 trials studied monotherapy, 13 trials a combination of antihistamines with other medication. A total of 8930 people suffering from the common cold were included. There were large differences in study designs, participants, interventions, and outcomes. There was no evidence of any clinically significant effect - in children or in adults - on general recovery of antihistamines in monotherapy. First generation - but not non-sedating - antihistamines have a small effect on rhinorrhea and sneezing. In trials with first generation antihistamines the incidence of side effects (especially sedation) is significantly higher with active treatment. Two trials, studying a combination of antihistamines with decongestives in small children, both failed to show any effect. Of the eleven trials on older children and adults, the majority show an effect on general recovery and on nasal symptom severity. REVIEWER'S CONCLUSIONS: Antihistamines in monotherapy - in children as well as in adults - do not alleviate to a clinical extend nasal congestion, rhinorrhoea and sneezing, or subjective improvement of the common cold. First generation antihistamines also cause more side-effects than placebo, in particular they increase sedation in cold sufferers. Combinations of antihistamines with decongestives are not effective in small children. In older children and adults most trials show a beneficial effect on general recovery as well as on nasal symptoms. It is however not clear whether these effects are clinically significant.

A novel tetracycline-controlled transactivator-transrepressor system enables external control of oncolytic adenovirus replication.

The use of restricted replication-competent adenoviruses (RRCAs) inducing tumor cell-specific lysis is a promising approach in cancer gene therapy. However, the use of RRCAs in humans carries considerable risk, since after injection into the patient, further regulation or inhibition of virus replication from the outside is impossible. Therefore, we have developed a novel system allowing external pharmacological control of RRCA replication. We show here that a tumor-selective E1B-deleted RRCA can be tightly regulated by use of doxycycline (dox)-controlled adenoviral E1A gene expression, which in turn determines vector replication. RRCA replication is switched on by addition and switched off by withdrawal of dox. The system results in efficient tumor cell killing after induction by dox, whereas cells are unaffected by the uninduced system. It was also employed for efficient external control of transgene expression from cotransfected replication-deficient adenovectors. Furthermore, the use of a liver cell-specific human alpha1-antitrypsin (hAAT)-promoter driving a tetracycline-controlled transcriptional silencer allowed specific protection of cells with hAAT-promoter activity in the absence of dox in vitro and in vivo, delineating a new principle of 'tissue protective' gene therapy. The concept of external control of RRCAs may help to improve the safety of cancer gene therapy.