Is Helicobacter pylori infection associated with alopecia areata?

Background  Alopecia areata (AA) is an immune-mediated form of hair loss that occurs in all ethnic groups, ages, and both sexes. Helicobacter pylori has been associated with certain extra-digestive dermatological conditions, including chronic urticaria, rosacea, Schönlein-Henoch purpura, Sweet syndrome, systemic sclerosis, and atopic dermatitis.
Objective  The causal relation between alopecia areata and H. pylori is discussed. We have screened for the presence of H. pylori in patients with AA in order to determine any potential role in its pathophysiology.
Patients and methods  We have prospectively studied 31 patients with AA and 24 healthy volunteers of similar gender for the presence of H. pylori surface antigen (HpSag) in stool.
Results  Optical density values for H. pylori infection were positive in 18 of all 31 patients evaluated (58.1%), while in 13 patients, values did not support H. pylori infection (41.9%). While in the control group, 10 of 24 (41.7%) had positive results. Within the group of AA, there was no significant difference between HpSag-positive and HpSag-negative patients.
Conclusions  Based on these results, the relation between H. pylori and AA is not supported. We advise that H. pylori detection should not be included in the laboratory workup of AA.     

FK506 in combination with methotrexate for the prevention of graft- versus-host disease after marrow transplantation from matched unrelated donors

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus- host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno- occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan- Meier estimates of disease-free survival at 2 years for good-risk, poor- risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.     

Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.     

Left atrial thrombi in non-rheumatic atrial fibrillation: assessment of prevalence by transesophageal echocardiography

To determine the prevalence of left atrial thrombus in hospitalized patients with non-rheumatic atrial fibrillation, 48 patients were consecutively studied with single-plane transesophageal echocardiography. There were 23 males (48%) and 25 females (52%). The mean age was 66±11 years (range 43–87). Thrombus was detected in 13 patients (27%) 11 were confined to the left atrial appendage, 1 to the atrial body and appendage, and 1 to the left upper pulmonary vein. Prevalence of atrial thrombus was not different among those patients with or without previous stroke [4/16 (25%) vs 9/32 (28%), p=NS] or between patients > 65 years and patients ≤ 65 years old (p=NS). Atrial thrombus was detected more frequently in patients with reduced left ventricular global systolic function than in those with normal function [7/14 (50%) vs 6/34 (17%), p<0.05]. In patients with spontaneous contrast echoes in the left atrium, thrombi were visualized more often than in those without spontaneous echoes [10/24 (41%) vs 3/24 (12%), p<0.05]. The finding of the atrial spontaneous contrast echoes was more frequent among patients with reduced left ventricular global systolic function [11/14 (78%) vs 13/34 (37%), p<0.02]. We conclude that in hospitalized patients with non-rheumatic atrial fibrillation the prevalence of left atrial thrombus is high. Reduced left ventricular global systolic function identifies a subset of patients at high risk for formation of thrombus in the left atrium.     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

Women’s Perceptions and Experiences of Breastfeeding Support: A Metasynthesis

Abstract: Background: Both peer and professional support have been identified as important to the success of breastfeeding. The aim of this metasynthesis was to examine women’s perceptions and experiences of breastfeeding support, either professional or peer, to illuminate the components of support that they deemed “supportive.” Methods: The metasynthesis included studies of both formal or “created” peer and professional support for breastfeeding women but excluded studies of family or informal support. Qualitative studies were included as well as large‐scale surveys if they reported the analysis of qualitative data gathered through open‐ended responses. Primiparas and multiparas who initiated breastfeeding were included. Studies published in English, in peer‐reviewed journals, and undertaken between January 1990 and December 2007 were included. After assessment for relevance and quality, 31 studies were included. Meta‐ethnographic methods were used to identify categories and themes. Results: The metasynthesis resulted in four categories comprising 20 themes. The synthesis indicated that support for breastfeeding occurred along a continuum from authentic presence at one end, perceived as effective support, to disconnected encounters at the other, perceived as ineffective or even discouraging and counterproductive. A facilitative approach versus a reductionist approach was identified as contrasting styles of support that women experienced as helpful or unhelpful. Conclusions: The findings emphasize the importance of person‐centered communication skills and of relationships in supporting a woman to breastfeed. Organizational systems and services that facilitate continuity of caregiver, for example continuity of midwifery care or peer support models, are more likely to facilitate an authentic presence, involving supportive care and a trusting relationship with professionals. (BIRTH 38:1 March 2011)