Direct binding of C1q to apoptotic cells and cell blebs induces complement activation

Deficiency of early components of the classical pathway of complement, particularly C1q, predisposes to the development of systemic lupus erythematosus. Several studies have suggested an association between the classical complement pathway and the clearance of apoptotic cells. Mice with a targeted deletion of the C1q gene develop a lupus-like renal disease, which is associated with the presence of multiple apoptotic bodies in the kidney. In the present study we demonstrate that highly purified C1q binds to apoptotic cells and isolated blebs derived from these apoptotic cells. Binding of C1q to apoptotic cells occurs via the globular heads of C1q and induces activation of the classical complement pathway, as shown by the deposition of C4 and C3 on the surface of these cells and on cell-derived blebs. In addition, for the first time, we demonstrate that surface-bound C1q is present on a subpopulation of microparticles isolated from human plasma. Taken together, these observations demonstrate that C1q binds directly to apoptotic cells and blebs derived therefrom and support a role for C1q, possibly in concert with C4 and C3, in the clearance of apoptotic cells and blebs by the phagocytic system.     

A new clinical classification for undescended testis

A new classification for undescended testis (UDT), suitable for a clinical setting, is proposed. UDT is categorized into congenital and acquired forms. Congenital forms include intra-abdominal, intra-canalicular, supra-scrotal and ectopic testes. Acquired forms can be divided into primary and secondary types. Primary forms are described as either ascending testes, i.e. those which cannot be manipulated into the scrotum, or high scrotal testes, i.e. those which can still be brought through the scrotal entrance into a high scrotal (unstable) position. Secondary forms are the result of ipsilateral groin surgery and are termed "trapped testes". Congenital forms of UDT should be treated surgically at an early age, preferably at 1 year. Therapy for primary acquired forms remains controversial. Therapeutic modalities include orchidopexy, hormonal treatment (preferably with human chorionic gonadotrophin) or waiting for spontaneous descent during the peripubertal period ("laissez faire policy"). Secondary acquired forms are probably best treated surgically.     

Randomised controlled trial of prophylactic etamsylate: follow up at 2 years of age

AIM: To assess the role of etamsylate in reducing the risk of haemorrhagic brain damage and its consequences. DESIGN: Follow up of babies recruited into a randomised controlled trial. METHODS: A total of 334 infants born before 33 weeks gestation in France and Greece were randomly allocated within the first four hours of birth either to receive etamsylate or to act as controls. The principal outcomes in the trial were death or impairment and/or disability at the age of 2 years. RESULTS: Fifty nine children were lost to follow up. A total of 115 (34%) either died or had some impairment or disability, and 88 (26%) either died or had severe impairment or disability at 2 years of age. These outcomes did not differ significantly between the two randomised groups: relative risks and 95% confidence intervals 1.14 (0.78 to 1.4) and 1.17 (0.82 to 1.68) respectively. The findings were similar for all the prespecified subgroup analyses stratified by key prognostic factors at trial entry: country of birth, gestational age < or >or= 29 weeks, inborn or outborn, age < or >or= 1 hour, and with or without cerebral scan abnormality. CONCLUSION: These findings do not support the use of etamsylate. Other strategies need to be evaluated for the prevention of mortality and morbidity in these vulnerable infants.     

Perinatal correlates and neonatal outcomes of small for gestational age infants born at term gestation

OBJECTIVE: We sought to examine the current perinatal correlates and neonatal morbidity associated with intrauterine growth failure among neonates born at term gestation. STUDY DESIGN: We compared 372 small for gestational age (SGA, birth weight <10th percentile) infants born at term gestation to 372 appropriate for gestational age controls (AGA, birth weight 10th to 90th percentile) matched by sex, race, and gestational age within 2 weeks. RESULTS: Compared with AGA controls, significant (P < .05) maternal risk factors for SGA status included single marital status (59% versus 53%), lower prepregnancy weight (144 +/- 41 lbs versus 153 +/- 40 lbs), lower weight gain during pregnancy (29 +/- 15 lbs versus 33 +/- 15 lbs), smoking (25% versus 17%), hypertension (14% versus 7%), and multiple gestation (9% versus 2%). Mothers of SGA infants were more likely to undergo multiple (>or=3) antenatal ultrasound evaluations (19% versus 7%), biophysical profile monitoring (11% versus 4%), and oxytocin delivery induction (28% versus 16%) (P < .05). Pediatrician attendance was more common among SGA deliveries (50% versus 37%, P < .05). SGA infants had significantly higher rates of hypothermia (18% versus 6%) and symptomatic hypoglycemia (5% versus 1%). These neonatal problems remained significant even when medical or pathologic causes of intrauterine growth failure, including pregnancy hypertension, multiple gestation, and congenital malformations, were excluded. CONCLUSION: Despite higher rates of pregnancy complications among mothers of SGA infants, the rates of neonatal adverse outcomes are low. However, SGA infants remain at risk for hypothermia and hypoglycemia and require careful neonatal surveillance.     

Successful treatment of acquired undescended testes with human chorionic gonadotropin

Human chorionic gonadotrophin therapy may have its place in the management of acquired undescended testes and surgery should be reserved for those who fail to respond to therapy. Further studies are necessary to evaluate these preliminary results.     

Previous testicular position in boys referred for an undescended testis: further explanation of the late orchidopexy enigma?

OBJECTIVE: To investigate the significance of the acquired undescended testis (UDT), which is differentiated into congenital and acquired forms, by assessing the previous testicular position in affected boys. PATIENTS AND METHODS: The study comprised 261 boys who had been referred for a non-scrotal testis to the outpatient clinic during an 8-year period (1993-2000). There was a bimodal distribution of age, with peaks at 2.0 and 10.0 years. In each boy with UDT the previous testicular position was ascertained. RESULTS: On referral, 340 testes were not in the scrotum (182 uni- and 79 bilateral). Of the 340 testes, 82 (24%) in 61 boys were diagnosed as retractile, whereas the remaining 258 in 221 boys were undescended. The previous testicular position was known in 208 of 221 boys (94%), with 244 UDTs. In 65 of these 244 (26.6%) the testis had never been scrotal (congenital UDT); in 179 (73.4%) a previous intrascrotal position was recorded in early childhood (acquired UDT) at least once, in 149 (61%) at least twice and in 117 (48%) at least three times. The mean age at referral for congenital UDT was 2.1 years and for acquired UDT was 8.4 years. CONCLUSIONS: These results show that acquired UDT is frequent, and occurs at about three times the rate of congenital UDT. Because these boys are referred for treatment later in childhood, the acquired UDT probably accounts for the high rate of (late) orchidopexy.     

Searching for moderators and mediators of pharmacological treatment effects in children and adolescents with anxiety disorders

OBJECTIVE: To examine whether age, gender, ethnicity, type of anxiety disorder, severity of illness, comorbidity, intellectual level, family income, or parental education may function as moderators and whether treatment adherence, medication dose, adverse events, or blinded rater's guess of treatment assignment may function as mediators of pharmacological treatment effect in children and adolescents with anxiety disorders. METHOD: The database of a recently reported double-blind placebo-controlled trial of fluvoxamine in 128 youths was analyzed. With a mixed-model random-effects regression analysis of the Pediatric Anxiety Rating Scale total score, moderators and mediators were searched by testing for a three-way interaction (strata by treatment by time). A two-way interaction (strata by time) identified predictors of treatment outcome. RESULTS: No significant moderators of efficacy were identified, except for lower baseline depression scores, based on parent's (but not child's) report, being associated with greater improvement (p < .001). Patients with social phobia (p < .05) and greater severity of illness (p < .001) were less likely to improve, independently of treatment assignment. Blinded rater's guess of treatment assignment acted as a possible mediator (p < .001), but improvement was attributed to fluvoxamine, regardless of actual treatment assignment. Treatment adherence tended to be associated (p = .05) with improvement. CONCLUSIONS: In this exploratory study, patient demographics, illness characteristics, family income, and parental education did not function as moderators of treatment effect. Social phobia and severity of illness predicted less favorable outcome. Attribution analyses indicated that study blindness remained intact. The presence of concomitant depressive symptoms deserves attention in future treatment studies of anxious children.