Chorioamnionitis and colonization of the newborn infant with genital mycoplasmas.

To study the role of Mycoplasma hominis and T-mycoplasmas (Ureaplasma urealyticum) in chorioamnionitis, we obtained culture from 249 puerperal women and their babies. The placentas were examined histologically. Infants whose placentas showed inflammation (chorioamnionitis) had cultures positive for T-mycoplasmas more frequently (37.5 per cent) than those with normal placentas (19.0 per cent) (P = 0.021). Colonization with M. hominis was found in 16.0 per cent of the babies and was not significantly associated with chorioamnionitis. Material colonization with mycoplasmas was more frequent (73.4 per cent) and was not correlated with placental inflammation. We conclude that a substantial proportion of cases of chorioamnionitis may be caused by prenatal infection with T-mycoplasmas. The fact that these organisms are not highly virulent could explain the frequent finding of inflammed placentas from otherwise normal pregnacies. No adverse clinical effects of the placental lesions or of mycoplasmal colonization could be detected in this small study.     

The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells

In this study, we explored whether thrombopoietin (Tpo) has a direct in vitro effect on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC). We previously reported a cell separation method that uses the fluorescence-activated cell sorter selection of low Hoescht 33342/low Rhodamine 123 (low Ho/low Rh) fluorescence cell fractions that are highly enriched for LTR-HSC and can reconstitute lethally irradiated recipients with fewer than 20 cells. Low Ho/low Rh cells clone with high proliferative potential in vitro in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6 (90% to 100% HPP-CFC). Tpo alone did not induce proliferation of these low Ho/low Rh cells. However, in combination with SCF or IL-3, Tpo had several synergistic effects on cell proliferation. When Tpo was added to single growth factors (either SCF or IL-3 or the combination of both), the time required for the first cell division of low Ho/low Rh cells was significantly shortened and their cloning efficiency increased substantially. Moreover, the subsequent clonal expansion at the early time points of culture was significantly augmented by Tpo. Low Ho/low Rh cells, when assayed in agar directly after sorting, did not form megakaryocyte colonies in any growth condition tested. Several days of culture in the presence of multiple cytokines were required to obtain colony-forming units-megakaryocyte (CFU-Mk). In contrast, more differentiated, low Ho/high Rh cells, previously shown to contain short- term repopulating hematopoietic stem cells (STR-HSC), were able to form megakaryocyte colonies in agar when cultured in Tpo alone directly after sorting. These data establish that Tpo acts directly on primitive hematopoietic stem cells selected using the Ho/Rh method, but this effect is dependent on the presence of pluripotent cytokines. These cells subsequently differentiate into CFU-Mk, which are capable of responding to Tpo alone. Together with the results of previous reports of its effects on erythroid progenitors, these results suggest that the effects of Tpo on hematopoiesis are greater than initially anticipated.     

Hypertension in dialysis and kidney transplant patients

For the first time, the Canadian Hypertension Education Program has studied the evidence supporting blood pressure control in people requiring renal replacement therapy for end-stage kidney disease, including those on dialysis and with renal transplants. According to the Canadian Organ Replacement Registry’s 2008 annual report, there were an estimated 33,832 people with end-stage renal disease in Canada at the end of 2006, an increase of 69.7% since 1997. Of these, 20,465 were on dialysis and 13,367 were living with a functioning kidney transplant. Thus, it is becoming more likely that primary care practitioners will be helping to care for these complex patients. With the lack of large controlled clinical trials, the consensus recommendation based on interpretation of the existing literature is that blood pressure should be lowered to below 140/90 mmHg in hypertensive patients on renal replacement therapy and to below 130/80 mmHg for renal transplant patients with diabetes or chronic kidney disease.     

Adolescents with type 1 diabetes and risky behaviour

Aim: The aim of the student is to assess whether adolescents with type 1 diabetes mellitus (T1DM) in Italy differ from their healthy peers in regard to risky behaviour. Methods: Data were collected from 215 patients, aged 14 ± 2 years with a mean disease duration of 7 ± 5 years. The control group was comprised of 464 healthy adolescents recruited among high school students. Each patient completed an anonymous confidential questionnaire to determine the prevalence of sexual behaviour, alcohol and tobacco consumption, illicit drug use, and, among patients with diabetes and frequency of mismanagement related to diabetes care. Results: Compared with controls, subjects with diabetes showed a similar rate of sexual intercourse among males and lower rates among females (34.8% vs 35.5%, p NS and 29.4% vs 41.4%, p < 0.05, respectively). Males in the diabetes group reported a higher rate of tobacco use, whereas females showed similar or higher rates of use for every illicit drug studied. Among patients with diabetes, those who are engaged in risky behaviour showed a higher rate of treatment mismanagement (76% vs 34%, p < 0.01). Conclusion: Adolescents with T1DM are as likely as their healthy peers to engage in risky behaviour, indicating the potential benefit of anticipatory guidance concerning glycaemic control and increased risk of acute and chronic complications.     

Oligosaccharides in human milk during different phases of lactation

Twenty-one oligosaccharides of human milk were quantified by high-performance anion-exchange chromatography. Milk samples were collected from 18 mothers during the first 3 mo of lactation. The data show that the highest amount of all oligosaccharides is present at day 4 postpartum (20 g l⁻¹) and then decreases by about 20% at day 30 of lactation. The protective role played by these substances against different infectious agents, in different organs and systems of the breastfed baby, is emphasized.     

Buffy coat transfusions in neutropenic neonates with presumed sepsis: a prospective, randomized trial

Neonatal sepsis, accompanied by neutropenia, is associated with a high mortality. To determine whether granulocyte transfusions improve the survival of critically ill neutropenic infants, we prospectively randomized 25 infants to transfusion and nontransfusion groups, matching for birth weight (less than or equal to 1,500 g or greater than 1,500 g). Infants with necrotizing enterocolitis were randomized separately. Neutropenia was established by two successive absolute neutrophil counts less than or equal to 1,500 cells prior to randomization. The transfusion (n = 12) and nontransfusion (n = 13) groups did not differ with respect to clinical or hematologic characteristics. In 23 of 25, bone marrow aspirations were performed to determine the percentage of neutrophil storage pool. Granulocyte transfusions of buffy coats from single units of whole blood (0.1 to 0.9 X 10(9) polymorphonuclear leukocytes per kilogram) were given daily until the absolute neutrophil count increased to more than 1,500/microL. Only five infants, mostly those with necrotizing enterocolitis, required more than one transfusion. A circulating immature to total neutrophil ratio (I:T) greater than or equal to 0.80 was not predictive of an infant with a neutrophil storage pool less than or equal to 7%, and neither an I:T less than 0.80 nor a neutrophil storage pool greater than 7% were predictive of survival. Granulocyte transfusions did not improve survival when either comparing the whole group, those 17 infants with cultures positive for bacteria or viruses, the 19 infants with a circulating I:T greater than or equal to 0.80, or the nine infants with a neutrophil storage pool less than or equal to 7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local administration of IL-12-transfected dendritic cells induces antitumor immune responses to colon adenocarcinoma in the liver in mice

Colorectal cancer is one of the most common fatal malignancies in the United States, with an incidence second only to lung cancer. The liver is the most common site of colorectal metastases and frequently the only affected organ once the primary tumor has been surgically removed. The only potentially curative treatment for metastatic colorectal cancer in the liver is surgery, although most patients are not eligible for resection. We have therefore, evaluated the therapeutic efficacy of dendritic cells (DCs) engineered to express IL-12 in a liver metastasis model. Direct administration of DCs into the portal vein significantly inhibited the growth of established MC38 colon carcinoma in the liver in C57BL/6 mice. This effect was accompanied by an intratumoral accumulation of CD4+, CD8+, and NLDC-145+ immune effector cells, and also resulted in a systemic immune response as determined by enhanced production of IFN-gamma by T lymphocytes isolated from both spleen and draining lymph nodes. Evaluation of homing of Cy3-labeled DCs following the portal vein injection confirmed their distribution in the liver and lymphoid tissue. Thus, a local delivery of DCs transduced with the IL-12 gene can not only inhibit colorectal tumor growth in vivo but also mount systemic antitumor immune responses. This approach is likely to improve the outcome of immunotherapy for metastatic colorectal cancer since high numbers of tumor-associated DCs positively correlate with a more favorable prognosis. Simultaneous local gene therapy with IL-12 will further improve clinical efficacy without placing the patient at risk for systemic toxicity.