Prenatal exposure to persistent organic pollutants in Northern Tanzania and their distribution between breast milk, maternal blood, placenta and cord blood.

Human exposure to persistent organic pollutants (POPs) begins during pregnancy and may cause adverse health effects in the fetus or later in life. The present study aimed to assess prenatal POPs exposure to Tanzanian infants and evaluate the distribution of POPs between breast milk, maternal blood, placenta and cord blood. For assessment of prenatal exposure, 48 maternal blood samples from Mount Meru Regional Referral Hospital (MMRRH), Arusha Tanzania, were analyzed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), dioxin-like (DL) activity and perfluorinated alkyl substances (PFASs). For evaluation of POPs distribution between maternal/infant compartments, breast milk, placenta and cord blood corresponding to the maternal blood were analyzed for OCPs, PCBs and BFRs. In maternal blood, p,p´- DDE was detected in 100% of the samples ranging between 29 and 1890 ng/g lipid weight (lw). PCB-153 was the only PCB detected in maternal blood, with detection rate of 29% and concentrations up to 116 ng/g lw. BDE-47 was detected in 65% of the maternal blood samples, ranging between

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human breast milk and associated health risks to nursing infants in Northern Tanzania.

This is the first study to report organochlorines (OCs), including chlorinated pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human milk from Tanzania. The main aims of this study were to assess the level of contamination and the possible health risks related to OC exposure in nursing infants from the Northern parts of Tanzania. Ninety-five healthy mother-infant couples attending Mount Meru Regional Referral Hospital (MMRRH), Arusha, Tanzania, were assessed for associations between maternal/infant characteristics, i.e. mother's age, BMI, gestational weight gain, occupation, residence and fetal growth parameters and breast milk levels of OCPs, such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, dieldrin and PCBs. p,p'-DDE and p,p'-DDT were detected in 100% and 75% of the breast milk samples, respectively, and ranged between 24 and 2400ng/g lipid weight (lw) and

How to escape from crop-to-weed gene flow: phenological variation and isolation-by-time within weedy sunflower populations.

The evolution of crop-related weeds may be constrained by recurrent gene flow from the crop. However, flowering time variation within weedy populations may open the way for weed adaptation by allowing some weeds to escape from this constraint. We investigated this link between phenology, gene flow and adaptation in weedy sunflower populations that have recently emerged in Europe from crop-wild hybridization. We studied jointly flowering phenology and genetic diversity for 15 microsatellite loci in six cultivated sunflower (Helianthus annuus) fields infested by weedy sunflower populations. The flowering overlap of cultivated and weedy sunflowers varied between and within populations: some weedy individuals were found to be completely isolated from the crop, the frequency of these plants being higher in populations from highly infested fields. Within weedy populations, we detected a pattern of isolation-by-time: the genetic divergence between individuals was positively correlated with their divergence in flowering period. In addition, earlier weeds, which flowered synchronously with the crop, were genetically more similar than late-flowering weeds to the cultivated varieties. Overall, our results suggest that crop-to-weed gene flow occurred, but was limited by divergent phenologies. We discuss the roles of weed adaptation and population history in the generation of this partial reproductive isolation.

Estimation of mating system parameters in an evolving gynodioecous population of cultivated sunflower (Helianthus annuus L.).

Cultivated plants have been molded by human-induced selection, including manipulations of the mating system in the twentieth century. How these manipulations have affected realized parameters of the mating system in freely evolving cultivated populations is of interest for optimizing the management of breeding populations, predicting the fate of escaped populations and providing material for experimental evolution studies. To produce modern varieties of sunflower (Helianthus annuus L.), self-incompatibility has been broken, recurrent generations of selfing have been performed and male sterility has been introduced. Populations deriving from hybrid-F1 varieties are gynodioecious because of the segregation of a nuclear restorer of male fertility. Using both phenotypic and genotypic data at 11 microsatellite loci, we analyzed the consanguinity status of plants of the first three generations of such a population and estimated parameters related to the mating system. We showed that the resource reallocation to seed in male-sterile individuals was not significant, that inbreeding depression on seed production averaged 15-20% and that cultivated sunflower had acquired a mixed-mating system, with ∼50% of selfing among the hermaphrodites. According to theoretical models, the female advantage and the inbreeding depression at the seed production stage were too low to allow the persistence of male sterility. We discuss our methods of parameter estimation and the potential of such study system in evolutionary biology.

[Learning from aviation - how to increase patient safety in surgery]. / Kann die Chirurgie wirklich von der Luftfahrt lernen?

During the last years attempts have been made to draw lessons from aviation to increase patient safety in medicine. In particular similar conditions are present in surgery as pilots and surgeons may have to support high physical and mental pressure. The use of a few safety instruments from aviation is feasible in an attempt to increase safety in surgery. First a "root caused" accident research may be established. This is achievable by morbidity and mortality conferences and critical incident reporting systems (CIRS). Second, standard operating procedures may assure a uniform mental model of team members. Furthermore, crew resource management illustrates a strategy and attitude concept, which is applicable in all situations. Safety instruments from aviation, therefore, seem to have a high potential to increase safety in surgery when properly employed.

Using linked markers to estimate the genetic age of a volunteer population: a theoretical and empirical approach.

Volunteers deriving from unharvested seeds of a crop can lead to persistent feral populations and participate in genetic exchanges across the agro-ecosystem, both between crop varieties and between crops and their wild relatives. A first step to understand the importance of volunteers is to characterize their capacity to reproduce autonomously for several generations. For that purpose, we constructed and evaluated a maximum-likelihood method to estimate the genetic age of a population deriving from one of the most common field crop type: an F1-hybrid variety. The method estimates the number of reproduction cycles that occurred since the cultivation of that variety. It makes use of genotypic data at a number of linked microsatellite loci pairs, thus exploiting the recombination of parental haplotypes, which is expected to occur as the population is reproducing. Estimates with moderate bias and variance were found for a broad range of parameter values in simulations, and the method revealed robust to some deviations from the assumptions of the underlying model. We propose a specific procedure to test the hypothesis of persistence, that is has a given volunteer population experienced more than one cycle of reproduction since the F1-hybrid state? The method was applied to both an experimental and a natural sunflower volunteer population and revealed promising, considering these ideal case studies. Possible further developments toward more complex natural systems are discussed.

Genome-wide effects of postglacial colonization in Arabidopsis lyrata.

The perennial outcrossing Arabidopsis lyrata is becoming a plant model species for molecular ecology and evolution. However, its evolutionary history, and especially the impact of the climatic oscillations of the Pleistocene on its genetic diversity and population structure, is not well known. We analyzed the broad-scale population structure of the species based on microsatellite variation at 22 loci. A wide sample in Europe revealed that glaciations and postglacial colonization have caused high divergence and high variation in variability between populations. Colonization from Central Europe to Iceland and Scandinavia was associated with a strong decrease of genetic diversity from South to North. On the other hand, the Russian population included in our data set may originate from a different refugium probably located more to the East. These genome-wide patterns must be taken into account in studies aiming at elucidating the genetic basis of local adaptation. As shown by sequence data, most of the loci used in this study do not evolve like typical microsatellite loci and show variable levels of homoplasy: this mode of evolution makes these markers less suitable to investigate the between-continent divergence and more generally the worldwide evolution of the species. Finally, a strong negative correlation was detected between levels of within-population diversity and indices of differentiation such as F(ST). We discuss the causes of this correlation as well as the potential bias it induces on the quantification and interpretation of population structure.

Brominated flame retardants (BFRs) in breast milk and associated health risks to nursing infants in Northern Tanzania.

The main aim of this study was to assess brominated flame retardants (BFRs) in breast milk in the Northern parts of Tanzania. Ninety-five colostrum samples from healthy, primiparous mothers at Mount Meru Regional Referral Hospital (MMRRH), Arusha Tanzania, were analyzed for polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), hexabromobenzene (HBB), (2,3-dibromopropyl) (2,4,6-tribromophenyl) ether (DPTE), pentabromoethylbenzene (PBEB) and 2,3,4,5,6-pentabromotoluene (PBT). The Æ©7PBDE (BDE 28, 47, 99, 100, 153, 154, 183) ranged from below level of detection (

Sensitization of mesenteric afferents to chemical and mechanical stimuli following systemic bacterial lipopolysaccharide.

BACKGROUNDS AND AIMS: The mechanisms underlying endotoxin-induced hyperalgesia remain unknown. We aimed to study the mechanisms underlying the sensitizing action of lipopolysaccharide (LPS) on intestinal afferent responses to mechanical and chemical stimuli. METHODS: Extracellular recordings of jejunal afferent nerve discharge were obtained from pentobarbitone-anaesthetized rats. RESULTS: Lipopolysaccharide (6 mg kg(-1), i.v.) stimulated a short-term, transient (<30 min) increase in chemosensitivity to systemic 5-HT (6 microg kg(-1)) and responses to mechanical distension and a delayed but maintained (>30 min) increase in spontaneous afferent discharge. Naproxen (10 mg kg(-1)) and the prostaglandin receptor antagonist AH6809 (1 mg kg(-1)) significantly attenuated both the short-term sensitization to mechanical distension and 5-HT and the long-term increase in baseline afferent firing following LPS. In contrast, the iNOS inhibitor aminoguanidine (15 mg kg(-1)) and the L-type calcium channel antagonist nifedipine (1 mg kg(-1)) both prolonged the period of afferent sensitization to distension and 5-HT without influencing the augmented baseline-firing rate. omega-Conotoxin GVIA attenuated the increase in afferent discharge to LPS, without any change in mechano- and chemosensitivity. CONCLUSIONS: The long-term (>30 min) increase in afferent firing following systemic LPS involves neurogenic release of prostanoids. The short-term (<30 min) sensitization also appears to depend on prostanoid release, while nitric oxide production may serve to down-regulate LPS-induced afferent hypersensitivity.

Modulation of intestinal afferent nerve sensitivity to inflammatory mediators following systemic endotoxin in mice.

BACKGROUND: Endotoxin exposure may be followed by visceral hypersensitvity but potential mechanisms are not fully explored. We aimed to test the hypothesis that mast cells and the cyclooxygenase pathway (COX) mediate modulation of afferent nerve sensitivity following systemic endotoxin. METHODS: C57Bl6 mice received endotoxin injection i.p. to induce systemic inflammation. Control animals received normal saline. Extracellular multi-unit afferent nerve discharge was recorded from jejunal mesenteric nerves in vitro. Afferent nerve response to 5-hydroxytryptamine (5-HT, 250 µmol/L), bradykinin (BK, 0.5 µmol/L), and to mechanical ramp distension of the intestinal lumen from 0 to 60 cmH2O were recorded 2 h following endotoxin administration. KEY RESULTS: Following endotoxin administration peak afferent discharge to 5-HT and BK was increased compared to controls (p < 0.05). Pre-perfusion with the mast cell stabilizer Doxantrazole (10(-4) M), or the cyclooxygenase inhibitor Naproxen inhibited the increased response to 5-HT and BK (p < 0.05 vs endotoxin pretreatment). Mechanosensitivity during luminal ramp distension from 10 to 60 cmH2O was increased following endotoxin pretreatment compared to controls (p < 0.05). This increase in sensitivity following endotoxin was no longer observed after Doxantrazole or Naproxen administration for pressures from 10 to 30 cmH2O (p < 0.05). Selective COX-2 inhibition by NS398 (10 µM) but not COX-1 inhibition by SC560 (300 µM) reduced increased afferent discharge in endotoxin pretreated animals to 5-HT, BK and mechanical ramp distension from 10 to 40 cmH2O (all p < 0.05). CONCLUSIONS & INFERENCES: Systemic endotoxin sensitizes mesenteric afferent nerve fibers to 5-HT, BK and mechanical stimuli. The underlying mechanism responsible for this sensitization seems to involve mast cells and the COX-2 pathway.

Orally active fibrinogen receptor antagonists. 2. Amidoximes as prodrugs of amidines.

The potent and selective GP IIb-IIIa antagonist lamifiban (1, Ro 44-9883) is currently in clinical development as an injectable antithrombotic agent for treating and preventing acute coronary syndromes. However, for secondary prevention of thrombotic occlusions, orally active inhibitors are needed. By means of a prodrug strategy, the modest oral absorption of 1 in mice was improved by a factor of 9. In addition, these studies demonstrated that an amidoxime group can serve as a prodrug functionality for an amidino group. Application of this principle to the structurally related amidino carboxylate 13 led to the amidoxime ester 18 which was absorbed approximately 20 times better, after oral administration to mice, than 13. Due to the modification of the amidino group as well as of the carboxylate group, 18 completely lost its ability to interact with purified platelet GP IIb-IIIa. After oral administration of 18 to rats, dogs, and rhesus monkeys, the bioavailability of the active derivative 13 was 26 +/- 5, 25 +/- 6, and 33 +/- 6%, respectively, and the elimination half-life was 4.1 +/- 1.7, 11.4 +/- 1.1, and 5.1 +/- 1.4 h, respectively. On the basis of these properties, the orally active 18 (Ro 48-3657), a double prodrug of the potent and selective non-peptide GP IIb-IIIa antagonist 13 (Ro 44-3888), was selected as clinical candidate for evaluation as a prophylactic agent in patients at high risk for arterial thrombosis.

The herbal preparation STW 5 (Iberogast) desensitizes intestinal afferents in the rat small intestine.

INTRODUCTION: Visceral hypersensitivity in the upper gastrointestinal tract is a potential pathomechanism of functional dyspepsia. The herbal preparation STW 5 (Iberogast) provides symptomatic relief for this condition. We aimed to investigate whether STW 5 modulates intestinal afferent sensitivity. METHODS: The herbal preparation STW 5 or vehicle (30.8% ethanol) were administered orally in male Wister rats. After 2 h animals were anaesthetized and extracellular multi-unit intestinal afferent nerve recordings were secured from the neurovascular bundle of the mesentery in the proximal jejunum. Afferent discharge to ramp distension of the intestinal loop (0-60 cm H2O) and dose-response curves for i.v. bradykinin (10, 20 and 40 microg kg(-1)) and 5-HT (5, 10, 20 and 40 microg kg(-1)) were recorded. RESULTS: Baseline discharge was not different between the vehicle and treatment group. Ramp distension was followed by a pressure dependent increase in afferent nerve discharge that was decreased following STW 5 pretreatment for all distending pressures reaching 147 +/- 8 impulses s(-1) (imp s(-1)) following STW 5 vs 171 +/- 5 imp s(-1) following vehicle at 60 cm H2O (mean +/- SEM; P < 0.05). A dose-dependent increase in afferent discharge was observed for 5-HT and bradykinin. Following STW 5 pretreatment, afferent discharge was reduced at all doses of 5-HT to 110 +/- 5 at the maximum dose after STW 5 and 128 +/- 3 imp s(-1) in controls (all P < 0.05). Afferent discharge to bradykinin was similarly reduced at 20 and 40 microg kg(-1) but not at 10 microg kg(-1) of bradykinin with a discharge rate of 176 +/- 7 imp s(-1) following STW 5 and 200 +/- 6 imp s(-1) in controls at 40 microg kg(-1) (P < 0.05). CONCLUSIONS: The preparation STW 5 reduces intestinal afferent nerve discharge following chemical and mechanical stimuli, while baseline discharge is not affected. This effect of STW 5 on afferent sensitivity may contribute to its therapeutic relief of dyspeptic symptoms.

Childhood tuberculosis in a low-income Paris suburb: lessons from a resurgence brought under control.

SETTING: Few series of paediatric tuberculosis (TB) have been reported in the last 20 years. OBJECTIVE: To describe diagnostic and treatment practices in children with TB living in Seine-Saint-Denis, a low-income Paris suburb. METHODS: Local TB incidence in 1998 was 34.2/100,000 overall and 10.2/100,000 in children. Between September 1996 and December 1997, the hospitals and prevention units serving the area's paediatric population were sent questionnaires to identify TB cases in children aged under 15 living in Seine-Saint-Denis and treated with at least one anti-tuberculosis drug. RESULTS: Of 92 cases identified, 60 (65%) had been diagnosed during contact tracing; for 52 patients (60%), the index case had been found. The reason for anti-tuberculosis treatment was active TB in 26 (28.3%), latent TB in 46 (50%), and prophylaxis in 20 (21.8%). Forty per cent (37/92) of the patients were aged under 5. Only 15 of the 35 notified cases met the criteria for mandatory notification (at least three anti-tuberculosis drugs). CONCLUSION: TB remains a public health problem in Seine-Saint-Denis. The high proportion of cases identified by contact tracing attests to the efficacy of the local contact-tracing programme. The criteria for mandatory notification in France were too restrictive to ensure effective surveillance of childhood TB. Since 2002, notification has included cases of tuberculous infection in children.

Idiopathic pulmonary fibrosis in infants.

Idiopathic pulmonary fibrosis is a poorly characterized disease in infants. In the present report, we reviewed our experience with 10 infants during a 10-year period. In 9 patients, onset of symptoms occurred before the age of 2 months and included tachypnea, cough, and inadequate weight gain. However, despite the presence of these symptoms, diagnosis was delayed for 3 months at which time the infants were referred to the pediatric pulmonary department, when the diagnosis was confirmed by open lung biopsy. At the time of admission, bronchoscopy with alveolar lavage was performed in 9 children and showed severe alveolitis with an increase in the neutrophil count. Nine infants were treated with prednisone alone or in combination with chloroquine, colchicine, or cyclophosphamide; all these patients died despite treatment. One infant was treated with pulses of methylprednisolone because of a failure in response to oral prednisone. This girl who displayed similar clinical, radiological, and histological abnormalities as the other children at the time of diagnosis is the only child still alive after 3 years of follow-up. She is now free of respiratory symptoms and has a normal growth curve. The present report raised two important points: (1) a thorough evaluation of characteristic symptoms should lead to an early diagnosis of pulmonary fibrosis in infants; and (2) administration of pulse therapy using corticosteroids has been helpful and needs to be evaluated further.

[Hyperglycemia revealing neonatal infection]. / Hyperglycémie révélatrice d'une infection néonatale.

BACKGROUND: Hyperglycemia as the first manifestation of neonatal sepsis is rare. CASE REPORT: A breast-fed neonate was admitted at the age of 6 days because of vomiting. Group B streptococci had been isolated in secretions of the ear at birth but the neonate had not been treated. At admission, physical examination was normal but glucosuria, without ketonuria, and hyperglycemia (9.7 mmol/l) were noted. Because hyperglycemia was not explained by usual causes, the baby was systemically given antibiotics. The next day, blood, spinal fluid and urine cultures taken on admission were positive for group B streptococci while blood fibrinogen and C-reactive protein were increased. Hyperglycemia and glycosuria were normal after 24 hours of antibiotic therapy and follow-up was uneventful. Subsequently, the same bacteria was isolated from the mother's milk. CONCLUSION: Isolated hyperglycemia may reveal an infection; therefore its discovery might contribute to early diagnosis and treatment.

[Child and adolescent victims of sexual abuse. Diagnosis and management]. / Les enfants et adolescents victimes d'abus sexuels. Diagnostic et prise en charge.

Sexual abuse against children is common. Both medical and social workers must understand the conditions which suggest the possibility of sexual abuse. To protect children from further abuse and prevent future psychological sequellae, it is necessary to make a multidisciplinary assessment, which is usually followed by referral to justice or to the children's protective services. Legislation concerning medical confidentiality must be well-known and understood by physicians. If the child is left in his family, supportive measures may help him and his family to modify interrelations. If he is sent away from his family, to a foster home or to a foster family, it is very important to maintain the bonds between the child and his family.

[Homozygote CB deficiency revealed by recurrent Neisseria meningitidis infections in an adolescent]. / Déficit homozygote en C8 révélé par des infections récidivantes à Neisseria meningitidis chez un adolescent.

BACKGROUND: Meningococcal infections associated with late complement component deficiency are rarely severe and usually occur during adolescence and adulthood. We report severe manifestations in a boy in whom the first episode appeared early. CASE REPORT: A 14 year-old gypsy boy was admitted because of a febrile meningococcal meningitis that was complicated by a rapidly extensive and necrotic purpura, obnubilation and clotting abnormalities without hemodynamic anomalies. The patient was given symptomatic therapy and a 12-day course of antibiotics that resulted in rapid and complete recovery. Medical history of this patient showed that he had been admitted at the age of 3 years for a severe febrile purpura with septic shock and clotting abnormalities followed by rapid and complete recovery after symptomatic and antibiotic therapy. No germ had been then isolated. The complement system was studied 3 weeks after the second hospitalization: total hemolytic complement activity could not be detected and C2, C3 and C4 were normal. Examination of the terminal pathway-revealed total C8 deficiency. The patient received meningococcal vaccine and was discharged on oral penicillin prophylaxis. He remained healthy during the ensuing 4 years. CONCLUSIONS: Meningococcal infections associated with late complement component deficiency are generally uncomplicated but they remain potentially severe. Early screening for this late complement component deficiency should be considered after severe clinical manifestations.

[The sickle cell anemia lung from childhood to adulthood]. / Le poumon drépanocytaire de l'enfant à l'adulte.

The pulmonary complications remain the prime cause of morbidity and mortality in sickle cell disease. The pathogenetic mechanisms consists both of an alteration of the rheological properties of the blood, the existence of a hypercoagulability state and above all specific interactions between the abnormal sickle cells and the vascular endothelium and a dysregulation of the vascular reactivity in which nitrous oxide intervenes. The acute chest syndrome (ACS) is characterised by chest pain with dyspnoea and recent radiological abnormalities and it is an acute lung complication whose problem is one of aetiology. The infectious pneumonias are rarely documented. On the other hand, alveolar hypoventilation linked to infarcts of the thoracic ribs, thoracoabdominal trauma, subdiaphragmatic pain, the administration of analgesics causing respiratory depression, obesity or sleep disturbance are frequent causes of ACS. Bronchoalveolar lavage has revealed a frequency of fat emboli following infarcts in the long bones. Pulmonary emboli is rarely a cause. Pulmonary thrombosis is a serious complication, the diagnosis is difficult and is seen in a predisposed clinical setting. The treatment of ACS rests on controlled hydration and antibiotic therapy, oxygen therapy and controlled analgesic therapy. The indications for blood transfusion and for exchange transfusion merits a better evaluation. In the long term patients with sickle cell disease present with a failure of normal thoracopulmonary growth with a restrictive ventilatory defect and progressive diminution in the transfer factor of carbon monoxide with age. A history of ACS favours chronic lung disease. Pulmonary arterial hypertension is less frequent.

Changes in peptidergic neurotransmission during postoperative ileus in rat circular jejunal muscle.

BACKGROUND: Our aim was to explore unknown changes in neurotransmission with vasoactive intestinal peptide (VIP) and Substance P (Sub P) during postoperative ileus (POI). METHODS: Contractile activity of rat circular jejunal muscle strips was studied in five groups (n = 6/group): Naïve controls, sham controls 12 h and 3 days after laparotomy, and rats 12 h, 3 days after induction of POI. Dose-responses to VIP (10(-10) -10(-7) M), Sub P (3 × 10(-10) -3 × 10(-7) M), and electrical field stimulation (EFS, to study endogenous release of neurotransmitters) were studied with different antagonists. Intestinal transit, inflammatory cells and immunoreactivity for VIP and Sub P were investigated in the bowel wall and cellular Finkel osteo sarcoma expression was determined in vagal afferent and efferent nuclei of the brainstem. KEY RESULTS: Postoperative ileus characterized by delayed intestinal transit and intramural inflammation was associated with an increased inhibitory effect of VIP on contractile activity. A biphasic impact was observed for Sub P with a decrease in its excitatory potential on contractility at 12 h, followed by a later increase 3 days postoperatively. Inhibitory response to EFS was increased, whereas the excitatory response decreased in ileus animals. VIP expression was increased in all postoperative animals while only animals 3 days after ileus induction showed increased Sub P expression in the myenteric plexus. These changes were associated with an activation of afferent but not efferent vagal nuclei in the brain stem. CONCLUSIONS & INFERENCES: Specific, time-dependent changes in peptidergic neurotransmission with VIP and Sub P occur during POI that are associated with vagal afferent activation, but are independent of the activation of efferent vagal pathways.