Breast milk retinol concentrations are not associated with systemic inflammation among breast-feeding women in Malawi

The acute phase response and inflammation are associated with lower plasma retinol concentrations, but their effect on breast milk retinol concentrations is unclear. We measured plasma retinol concentrations, acute phase proteins, and breast milk retinol concentrations in 237 breast-feeding women at 2 wk postpartum in Blantyre, Malawi; 16.5% of the women had plasma retinol < 0.70 micromol/L and 14.8% had breast milk retinol < 1.05 micromol/L. Among women with and without inflammation [alpha(1)-acid glycoprotein (AGP) > 1 g/L and/or C-reactive protein (CRP) > 5 mg/L], geometric mean (95% CI) plasma retinol was 0.89 (0.84, 0.94) and 1.05 (1.01, 1.17) mumol/L, respectively (P < 0.0001). Among women with and without inflammation, geometric mean (95% CI) breast milk retinol was 2.12 (1.89, 2.36) and 2.05 (1.75, 2.39) micromol/L, respectively (P = 0.74). In multiple linear regression models adjusting for age, parity, education, BMI, and days postpartum, plasma retinol concentrations were associated with plasma AGP and CRP concentrations (P < 0.0001 and P = 0.01, respectively), whereas breast milk retinol concentrations were unaffected by plasma AGP and CRP concentrations (P = 0.22 and P = 0.86, respectively). These findings suggest that breast milk retinol concentrations are not affected by systemic inflammation.     

Impact of colloid response on survival after preoperative radiotherapy in locally advanced rectal carcinoma

Neoadjuvant therapy for rectal carcinoma modifies morphology and natural history of the tumor. Colloid response defined by predominant colloid changes with or without residual tumor cells is a form of tumor response whose impact on survival is unknown. This study evaluated influence of tumor histologic response, especially of colloid response, on survival in patients treated by long-course preoperative radiotherapy for rectal cancer. In 200 patients with uT3-T4 or N1 rectal carcinomas, influence of type of surgery, dose of radiotherapy, residual tumor size, surface tumor aspect, tumor response (downstaging vs. colloid or no response), tumor grade, vascular and neural invasion, circumferential margin, and postoperative chemotherapy on 5-year overall and disease-free survival were studied by univariate and multivariate analyses. A colloid response was observed in 20% of the cases. Tumor response, circumferential margin, and vascular invasion were independently associated with the disease-free survival. Patients with downstaging had a better disease-free survival than patients without response (80% vs. 54%), whereas those with colloid response had an intermediate survival (64%). After colloid response, the rate of recurrence was similar to patients with downstaging for local recurrence (0%-3%) and to those with no response for distant recurrence (28%). After preoperative radiotherapy for rectal cancer, survival and type of recurrence are influenced by the tumor response. The intermediate natural history of patients with colloid response suggests taking colloid response into account in postoperative tumor staging to optimize adjuvant therapy.     

Current strategies in the treatment of childhood Hodgkins disease

Dramatic changes in the treatment of childhood Hodgkins disease have taken place during the past three decades. Contemporary combined modality treatment regimens produce durable disease-free survival in 90 to 100%of patients with early disease and in 70 to 85%of patients with advanced disease. Studies using chemotherapy alone also report high survival rates, and current studies are few to highlight the superiority of chemo-radiotherapy vs. chemotherapy alone. After the prodigious improvement achieved in response and survival rates, current strategies aim at reducing late effects of therapy, reserving more aggressive treatment modalities for patients with high risk features.     

Expression of collapsin response mediator proteins 1, 2 and 5 is differentially regulated in newly generated and mature neurons of the adult olfactory system

Collapsin-response mediator proteins (CRMPs) are highly expressed in the developing brain where they take part in several aspects of neuronal differentiation. CRMPs are still present postnatally, but their function remains speculative in the adult brain. We studied the expression and localization of CRMP1, CRMP2 and CRMP5 in two areas of the nervous system with persistent neurogenesis in adult mice, the olfactory mucosa and the olfactory bulb. In the olfactory mucosa, we have established that CRMP expression is restricted to postmitotic cells of the olfactory neurons lineage. CRMP5 is coexpressed with growth associated protein of 43 kDa (GAP43) in immature olfactory neurons and is down-regulated in olfactory marker protein-positive mature neurons. In contrast, CRMP1 and CRMP2 persist at all stages of differentiation from immature GAP43-positive to fully mature olfactory neurons. In the olfactory bulb, CRMP1, CRMP2 and CRMP5 are abundant in neuronal progenitors of the subependymal layer and in differentiating interneurons. In both areas, the subcellular distribution of CRMP1 or CRMP2 is different in mature vs. immature neurons, suggesting that these proteins are sequentially involved in various cellular events during neuronal lifetime. The variations of CRMP expression following axotomy are consistent with their differential localization and functional involvement in immature vs. mature neurons of the olfactory system. Our data bring new insight to the putative functions of CRMPs within areas of the adult nervous system with permanent neurogenesis, some related to differentiation of newly generated neurons but others occurring in mature neurons with a limited lifespan.     

Maternity wards or emergency obstetric rooms? Incidence of near-miss events in African hospitals

BACKGROUND: This study examines near-miss obstetric events in African hospitals as to the frequency, nature, and ratio of near miss to death and considers whether these could become useful indicators for monitoring the performance of obstetric services in Africa. METHODS: Prospective or retrospective reviews of medical records were conducted in nine referral hospitals in three countries (Benin, C?te d'Ivoire, and Morocco). We calculated the incidence of near-miss obstetric events, near-miss cases, and maternal deaths related to hemorrhage, hypertensive diseases of pregnancy, dystocia, infections, and anemia and analyzed these according to hospital and timing relative to admission. RESULTS: The incidence of near-miss cases was varied, and in some hospitals extremely large: from 1% to almost a quarter of all deliveries were near misses. Near-miss cases were 15 times more common than deaths (ranging from a ratio of 9:1-108:1). Most of the women with near-miss events (NMEs) (83%) were already in a critical condition on arrival at the hospital (range 54-90%), and two in three were referred from another facility. The most frequent types of NMEs were hemorrhage and hypertensive diseases of pregnancy, but anemia was the leading cause in three first referral level hospitals in Benin and C?te d'Ivoire. Near-miss events due to infections were rare. CONCLUSIONS: Near-miss events are extremely common in some African hospitals, with a high proportion arriving in critical conditions. Near-miss events must be estimated separately for those already in a critical condition on arrival and those developing after admission; the first as a good indicator of the effectiveness of emergency referrals and the second as a potential tool for monitoring the performance of obstetric services.     

Heterogeneity of anti-beta2-glycoprotein I antibodies. A factor of variability in test results

The aim of this study was to evaluate the heterogeneity of IgGanti-beta2-glycoprotein I antibodies (IgG-abeta2GPI) as regarding their reactivity pattern against different sources of human beta2 GPI, their avidity and their association with clinical events of antiphospholipid syndrome (APS). Three thousand six hundred and eighty-four consecutive patient sera were routinely tested for IgGabeta2 GPI over 1 year using an in-house ELISA with 2 different commercial preparations of human purified beta2GPI. Of the 340 sera found positive, all those clinically documented were included in this study; 61 were positive with only one preparation (S1) and 59 with both (S2). The results of ELISA were confirmed by Western blot. Heterogeneity was stressed by testing sera with a human recombinant protein and 3 beta2GPI-related peptides. No contribution of glycosylation in the binding to beta2GPI was found. The avidity indices for each protein were significantly higher in S1 than in S2 (p=0.0021). S2 were more associated with antiphospholipid antibodies than S1 (75% versus 21% ; p<0.0001). A similar frequency of the main clinical features of APS was found in S1 and S2 sera (69% and 71%, respectively). In conclusion, our data show a heterogeneity in the antigenic reactivity pattern of IgG- abeta2 GPI and a relationship between a binding profile and antibody avidity. This heterogeneity could represent a crucial factor of variability in test results and underlines the difficulty of getting standardisation.     

Clorazepate affects cell surface regulation of delta and kappa opioid receptors, thereby altering buprenorphine-induced adaptation in the rat brain

Concomitant abuse of buprenorphine (BPN) and benzodiazepines (BZD) may relate to a pharmacodynamic interaction between the two. The objective of the present work was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with BPN on selective kappa opiate tritiated ligand [3H]-U69 593 and delta opiate radioligand [3H]-deltorphine II binding in the rat brain. Bmax (maximal receptor density) and Kd (the dissociation constant) were directly determined at different brain regions of interest (ROI) selected for high densities of kappa and/or delta receptors in rats treated with BPN and/or CRZ. The agents were administered either once or for 21 consecutive days. Differences in Bmax and Kd (for both specific ligands) were related to drug treatment and receptor location. Globally, single BPN administration induced no changes in kappa or delta opiate receptor binding, whereas repeated BPN administration up-regulated kappa receptor density and decreased delta affinity. At the kappa receptor level, repeated administration of CRZ acted only on Kd, whereas the delta receptor was up-regulated. Repeated addition of CRZ to BPN had no effect on kappa receptor Bmax versus chronic controls. By significantly decreasing Bmax, CRZ nullified the effect of chronic BPN on the kappa receptor. The modifications were strongest in the nucleus accumbens, where both types of receptor occur. Treatments had region-selective effects in some brain areas, such as the amygdala, periaqueductal gray matter, hypothalamus and caudate putamen. Increased mu and delta receptor densities would be expected to provide reinforcement by enhancing reward, and impairment of kappa receptor availability would be expected to decrease aversion. The effects described are likely to influence addictive behavior among people abusing BZD and BPN.     

Changes in internal mechanical cost during overground running to exhaustion

PURPOSE: The purpose of this study was to determine, during an overground supra-threshold run, whether a change in the internal mechanical cost could occur during an exhaustive run and whether this change was related to the increase in the energy cost of running (C(r)). METHODS: The Cr of 14 endurance runners was measured from pulmonary gas exchange using a breath-by-breath portable gas analyzer (Cosmed K4b, Rome, Italy), at the third and the last minute of an exhaustive exercise performed at their velocity corresponding to 95% of the maximal oxygen uptake (4.88 +/- 0.38 m.s(-1)). At the same time, potential, kinetic, and internal mechanical costs (C(pe), C(ke), and C(int)) were measured with a 3D motion analysis system (ANIMAN3D). RESULTS: C(int) and C(r) increased significantly within the third minute and the end of the supra-threshold exercise (respectively, 0.55 +/- 0.07 vs 0.60 +/- 0.07 J.kg(-1).m(-1) and 4.10 +/- 0.39 vs 4.32 +/- 0.42 J.kg(-1).m(-1); P < or = 0.03). However, the percentage of variation of C(int) and C(r) were not correlated (r = 0.06; P = 0.84). Contrary to C(int), C(ke) and C(pe) remained constant during the exercise (respectively, 1.33 +/- 0.33 vs 1.38 +/- 0.29 J.kg(-1).m(-1) P = 0.79 and 0.47 +/- 0.11 vs 0.48 +/- 0.10 J.kg(-1).m(-1); P = 0.67), but both parameters were significantly correlated with C(r) (r = 0.43; P = 0.03 and r = 0.40; P = 0.03). CONCLUSION: During overground running to exhaustion, a significant increase in C(int) occurred, but this did not account for the increase in C(r). Moreover, the increase in C(int) has yet to be explained.