Cyclosporine and lactation: when the mother is willing to breastfeed.

We describe a woman treated with cyclosporine after renal transplantation who commenced breastfeeding of her newborn infant. The child had no apparent clinical adverse effects to cyclosporine. To confirm the safety of breastfeeding and guide the patient and her clinician, cyclosporine concentrations in maternal blood, breast milk, and infant blood were measured. Maternal cyclosporine concentration (1-hour postdose) was 49 µg/L, and the breast milk cyclosporine concentration (2-hour postdose) was 46 µg/L. Infant cyclosporine blood concentration shortly after breastfeeding was undetectable (<10 µg/L). Analysis revealed that the estimated infant exposure to cyclosporine via breast milk was minimal and provided reassurance to continue breastfeeding in this case.

Nicotine replacement therapy during pregnancy: recommended or not recommended?

Smoking during pregnancy increases the risks of maternal and fetal complications and adverse neonatal outcomes, and it remains a significant health problem. Although pregnancy is often a strong motivator for smoking cessation, many pregnant women continue to smoke. Effective smoking cessation strategies for use during pregnancy are therefore clearly needed. Behavioural support provided by prenatal smoking cessation programs is safe and effective during pregnancy, but it generates a relatively modest reduction in smoking cessation rates. Nicotine replacement therapy (NRT), in conjunction with behavioural support, may offer an effective alternative to help pregnant women quit smoking. This suggestion is based on the convincing research evidence for the effectiveness of NRT in the general population. There is no consensus, however, on whether or not care providers should recommend NRT during pregnancy because of persistent concerns about its safety and effectiveness. We reviewed the data on the safety and effectiveness of NRT and on the possible physiological reasons for NRT's low effectiveness in pregnant women, and conclude that it is prudent to advise pregnant women who smoke 5 cigarettes or fewer per day to use behavioural support, and not NRT, to help them quit. Pregnant women with a moderate or high level of addiction may use NRT under the supervision of their physician. A combination of cognitive-behavioural therapy and counselling with NRT is the most effective strategy to achieve smoking cessation during pregnancy.

Age-related leukocyte and cytokine patterns in community-acquired bronchopneumonia.

BACKGROUND: Community-acquired bronchopneumonia in children is frequently accompanied by extreme leukocytosis, whereas in adults with the same diagnosis a high leukocyte count is uncommon. Data regarding differences in the serum levels of inflammatory cytokines between children and adults are limited. OBJECTIVES: To compare leukocyte counts and blood levels of various inflammatory cytokines in children and adults diagnosed with community-acquired bronchopneumonia. METHODS: We prospectively evaluated all pediatric and adult patients admitted for bronchopneumonia based on clinical and chest X-ray findings. Blood was drawn for complete blood count and serum concentration of the following cytokines: granulocyte colony-stimulating factor, interleukins-6, 8 and 10, interferon-gamma, tumor necrosis factor, as well as matrix metalloproteinase-9 and intercellular adhesion molecule-1. RESULTS: There were 31 children and 32 adults. The patients in both groups had similar parameters of infection severity. None of them required admission to the Intensive Care Unit. Mean (+/- SD) leukocyte counts in the pediatric and adult groups were 21,018/mm3 (+/- 10,420) and 12,628/mm3 (+/- 6735) respectively (P = 0.02). Age was inversely correlated with leukocytes in the pediatric group (P = 0.0001). A significant inverse correlation was also found between age and platelet counts. Although cytokine levels in both groups were not significantly different, age was directly correlated with MMP-9 (P= 0.03), IL-8 (P= 0.03) and G-CSF (P= 0.014). CONCLUSIONS: The immune response in community-acquired bronchopneumonia is, at least partly, age-dependent.

Effect of domperidone on insufficient lactation in puerperal women: a systematic review and meta-analysis of randomized controlled trials.

Background. There is a controversy within the medical community regarding the role of domperidone as a galactagogue and the drug has been removed from the US market owing to safety concerns. Objective. To perform a systematic review and meta-analysis of the available data assessing the effect of domperidone on breast milk production in women experiencing insufficient lactation. Study Selection. Randomized controlled trials (RCTs) examining the effect of domperidone on breast milk production of puerperal women were eligible for inclusion. Data Analysis. Absolute and relative changes from baseline were calculated for individual studies and pooled using a random effects model. Results. Three RCTs including 78 participants met the inclusion criteria. All showed a statistically significant increase in breast milk production following treatment with domperidone. The analysis of pooled data demonstrated a statistically significant relative increase of 74.72% (95% CI = 54.57; 94.86, P < 0.00001) in daily milk production with domperidone treatment compared to placebo. No maternal or neonatal adverse events were observed in any of the trials. Conclusions. Evidence from a few small RCTs of moderate to high quality suggests that domperidone produces a greater increase in breast milk supply than placebo.

Ocular toxicity in children exposed in utero to antimalarial drugs: review of the literature.

OBJECTIVE: The antimalarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have been used for decades to treat rheumatic diseases. CQ is still beneficial for the management of malaria during pregnancy. A growing body of research suggests that antimalarials are safe during pregnancy. There have been concerns about adverse longterm effects, mainly retinal toxicity, in offspring of women exposed to antimalarials during pregnancy. Our objective was to review the published evidence on safety of antimalarials during pregnancy, focusing on ocular toxicity in the offspring. METHODS: Ovid Medline, Embase, and Cochrane Library databases were searched for the period from their inception to May 2010 inclusive with no restrictions on language or year of publication. Randomized controlled trials (RCT) and observational studies examining the safety of CQ or HCQ during pregnancy and reporting on visual function or ocular toxicity in the offspring of exposed women at any point of the followup were eligible for inclusion. The quality of evidence was assessed according to established criteria (the GRADE approach). RESULTS: Twelve studies with a total of 588 offspring born to mothers treated with CQ or HCQ during pregnancy met the inclusion criteria. Five studies with a total of 251 exposed children reported no clinical visual abnormalities in any case. In an RCT on malaria prophylaxis, visual acuity in 251 infants exposed to CQ in utero did not differ from the placebo group. Detailed ophthalmological examination was performed in 4 studies and normal results were reported in all children (n = 59). Electro-physiological testing using electroretinogram was performed in 3 small cohorts and results were normal in all but 6 infants aged 3-7 months. All 6 children had normal fundoscopy before 4 years of age. Heterogeneity in comparison groups and in outcome measures precluded formal metaanalysis. CONCLUSION: Current evidence suggests no fetal ocular toxicity of antimalarial medications during pregnancy. The clinical significance of early electroretinogram anomalies reported in a small subset of infants remains to be established. Larger followup studies are warranted to confirm low risk of ocular toxicity in children following antenatal exposure to antimalarial medications.

Toward improved pregnancy labelling.

Information about the use of a medication in pregnancy is part of overall drug labelling as prepared by the pharmaceutical company and approved by the regulators. It is aimed at assisting clinicians in prescribing, however, very few drugs are labelled for specific indications in pregnancy, since there is rarely information about the use of a drug in this condition. Recently the FDA has drafted new guidelines for the labeling of drugs in pregnancy and breastfeeding, to replace the A,B,C,D,X system that was used for more than 30 years. Here we document the use of the new system through 3 different medications; each representing a different clinical situation in pregnancy--acute infection, chronic pain, and drug use during labor. Advantages and challenges in the new system are being highlighted.

Microenvironment factors do not afford myeloma cell lines protection from simvastatin.

BACKGROUND: The intensive interactions of myeloma cells (multiple myeloma, MM) with microenvironmental components of the bone marrow contribute significantly to their proliferation and survival. It has been shown that these signals confer drug resistance, delineating their circumvention as a primary objective in disease treatment. This study was designed to assess the effect of some major extracellular factors on the previously established anti-neoplastic response of myeloma cells to simvastatin (Sim). STUDY DESIGN: RPMI8226, U266, and ARH77 seeded in culture plates precoated with fibronectin (FN)/agarose/none were treated with Sim, insulin-like growth factor-I (IGF-I), interleukin-6 (IL-6) or combinations for 5 d. Then we assessed cell morphology, viability (WST1), cell cycle (propidium iodide, PI, staining and flow cytometric analysis), total cell count, and cell death (trypan blue exclusion), and DNA fragmentation. RESULTS AND CONCLUSIONS: Reduced viability was demonstrated with Sim in all treated cell lines with and without co-administration of IGF-I or IL-6 (P < 0.05). The extent of inhibition did not vary between Sim only and combinations (NS). FN did not influence cell response to Sim alone or combined with IL-6/IGF-I (NS). We conclude that IL-6, IGF-I, and FN do not afford myeloma cell lines protection from Sim modulation.