Anti-CD3 mAbs may prolong β cell function up to 2 years in patients with new onset Type 1 diabetes (T1DM). A randomized open label trial of anti-CD3 mAb, Teplizumab, in T1DM was stopped after 10 subjects because of increased adverse events than in a previous trial related with higher dosing of drug. Teplizumab caused transient reduction in circulating T cells, but the recovered cells were not new thymic emigrants because T cell receptor excision circles were not increased. There was a trend for reduced loss of C-peptide over 2 yrs with drug treatment (p=0.1), and insulin use was lower (p<0.001). In 4 drug treated subjects followed up to 60 months, C-peptide responses were maintained. We conclude that increased doses of Teplizumab are associated with greater adverse events without improved efficacy. The drug may marginate rather than deplete T cells. C-peptide levels may remain detectable up to 5 yrs after treatment. KeywordsType 1 diabetes mellitus; immunotherapy; anti-CD3 monoclonal antibody; T lymphocyte Corresponding author: Kevan C. Herold, MD, Yale University, 10 Amistad St, 131D, New Haven, CT 06520, Fax: 203-785-7903. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe goal of newer therapies for treatment of Type 1 diabetes (T1DM) is to arrest the autoimmune destruction of β cells for an extended period of time without the need for continuous immune suppression. FcR non-binding anti-CD3 mAbs are thought to attenuate destruction of β cells in T1DM over the first 18 months to 2 years of the disease when they are administered at diagnosis, but the duration of this effect of a treatment dose and the mechanism of action of anti-CD3 mAb are not known [1;2][3]. In two previously published randomized trials that enrolled approximately 120 subjects, a single course of treatment with two different FcR non-binding anti-CD3 mAbs was shown to improve insulin production for 18 and 24 months after diagnosis[1;2][3]. In our previous study, glycated hemoglobin levels were also improved, suggesting a benefit of drug treatment in glucose control whereas in the study of Keymeulen et al, clinical management was aimed at maintaining similar glucose control in the control and drug treated subjects to avoid any differential effect of glycemic control on β cell function [3]. Despite these differences, both studies demonstrated significantly reduced insulin usage with drug treatment.The mechanism(s) of action of FcR non-binding anti-CD3 mAbs are not clear. It is possible that the mAbs deplet...

In parts of the developing world where fertility rates are high, teenage pregnancy and early marriage are common. Worldwide, adolescents have more than 14 million births each year, and more than 90% of these occur in developing countries. 1 The proportion of teenage women who are mothers or are currently pregnant is greatest in Sub-Saharan Africa (20-40%). 2 The proportions are lower in other regions: 6-21% in Asia-with Bangladesh an outlier at 35%-and 13-25% in Latin America.As a result of high levels of early childbearing in developing countries, pregnancy and childbirth are the leading causes of death among women aged 15-19. 3 Compared with older women, teenagers are at increased risk for poor maternal and infant outcomes, 4 particularly maternal death and having an infant who is low-birth-weight or dies. 5 The risk of maternal death during childbirth is 2-4 times as high among adolescents younger than 18 as among women aged 20 or older. 6 Compared with babies born to women aged 20-29, babies born to women younger than 20 have a 34% higher risk of death in the neonatal period, largely because of their increased risk of being low-birth-weight, 7 and a 26% higher risk of death by age five. 8 Determinants of poor maternal and infant outcomes include poverty; cultural factors that restrict women' s autonomy, promote early marriage or support harmful traditional practices; nutritional deficiencies; reproductive factors such as young age at first birth; distance to health services; and inadequate health care behavior or use of services. 9 Pregnant adolescents are disproportionately affected by these factors. 10 Programs to delay first births to adolescents would mitigate risks to maternal and infant health associated with maternal factors such as short height, low weight and inadequate nutrition, but it is not clear how delaying first births would affect the social advantages or disadvantages of early childbearing. For example, adolescents who become pregnant may cut their education short because they are forced to leave school. Yet early childbearing may improve a woman' s social status because in some cultures it is an important step toward marriage.For all women, use of health care services is a key proximate determinant of maternal and infant outcomes, 11 including maternal and infant mortality. 12 Moreover, the benefits of health care-seeking and positive health behaviors are relatively strong in settings and subgroups where socioeconomic and public health resources are constrained. 13 Timely and appropriate care can provide an opportunity to prevent or manage the direct causes of maternal mortality-hemorrhage, obstructed labor, unsafe abortion, infection and hypertensive disorders-and to reduce fetal and neonatal deaths related to obstetric complications. 14 CONTEXT: Because of high levels of early childbearing in developing countries, pregnancy and childbirth are the leading causes of death among women aged 15-19. Use of skilled antenatal and delivery care improves maternal outcomes through the preventio...

The use of a nonoxynol 9 vaginal film did not reduce the rate of new HIV, gonorrhea, or chlamydia infection in this group of sex workers who used condoms and received treatment for sexually transmitted diseases.

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