Tibolone,transdermal estradiol or oral estrogen–progestin therapies: Effects on circulating allopregnanolone,cortisol and dehydroepiandrosterone levels

The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5?mg), transdermal estradiol (50?μg) (TE) and different oral estrogen–progestin regimens, conjugated equine estrogens (0.625?mg) plus medroxyprogesterone acetate (5?mg) (CEE?+?MPA) and estradiol (2?mg) plus norethisterone acetate (1?mg) (E2?+?NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p?<?0.001) in the TE, CEE?+?MPA and E2?+?NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2?+?NETA and tibolone treatments induced an increase in progesterone levels (p?<?0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p?<?0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p?<?0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE?+?MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2?+?NETA treatments modified circulating cortisol levels. DHEA levels significantly (p?<?0.05) decreased after 6 months of TE or estrogen–progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the androgen deficiency syndrome in postmenopausal women.     

Effect of heterologous antibody on human platelets

The effect of heterologous anti-human platelet antibody on human platelet function was examined in the presence and absence of whole plasma as an in vitro model for antibody-induced immune damage to cells. Heterologous IgG anti-human platelet antibody mediated platelet aggregation and released serotonin from both platelets in plasma and from platelets isolated by gel filtration and increased the availability of platelet acid phosphatase in a dose-response fashion. Anti-platelet antibody failed to release beta-glucuronidase (lysosomal enzyme marker) or cause lactic dehydrogenase loss (cytolysis). The effect of the antiplatelet antibody on platelets proceeded in the absence of complement. The active molecule in the anti-platelet antiserum was isolated in the IgG fraction and all three indicators of platelet injury were mediated by purified monomeric IgG. Thrombin was not required for the antibody-mediated effects, as three thrombin inhibitors failed to block the reaction. EDTA was an effective inhibitor, suggesting a cation requirement; however, as little as 38 muM calcium was sufficient for effective platelet aggregation and release. The inability of acetylsalicylic acid to inhibit the effect of the antiplatelet antibody suggests that heterologous antibody (IgG) induced platelet alteration proceeds by a different mechanism than that mediated by ADP and epinephrine and does not involve endogenous platelet prostaglandin synthesis.     

A systematic review and meta-analysis of complications following the posterior and lateral surgical approaches to total hip arthroplasty

IntroductionTotal hip arthroplasty is one of the most commonly performed orthopaedic procedures. Despite this, medical evidence to inform the choice of surgical approach is lacking. Currently in the UK, the two most frequently performed approaches to the hip are the posterior and the direct lateral.MethodsThis systematic review was performed according to Cochrane guidelines following an extensive search for prospective controlled trials published in any language before January 2014. Of the 728 records identified from searches, 6 prospective studies (including 3 randomised controlled trials) involving 517 participants provided data towards this review.FindingsCompared with the lateral approach, the posterior approach conferred a significant reduction in the risk of Trendelenburg gait (odds ratio [OR]: 0.31, p=0.0002) and stem malposition (OR: 0.24, p=0.02), and a non-significant reduction in dislocation (OR: 0.37, p=0.16) and heterotopic ossification (OR: 0.41, p=0.13). Neither approach conferred a functional advantage. We draw attention to the paucity of evidence and the need for a further randomised trial.     

Recombinant alpha-2-interferon for hairy cell leukemia

Twenty-two patients with hairy cell leukemia were treated with biosynthetic (recombinant) alpha-2-interferon in an open-label, single- arm efficacy study. Patients received 2 X 10(6) U/m2 recombinant alpha- 2-interferon three times weekly. Therapy was well tolerated subjectively with minimal short-term hematologic toxicity. Two patients had bacterial infections during the period of study, and one patient experienced a short-lived readily reversible rejection of a corneal transplant. Statistical comparison of the mean hematologic indices at study entry and after three to six months of therapy with recombinant alpha-2-interferon indicates a significant improvement in hemoglobin, granulocyte, and platelet counts. Bone marrow biopsies in six of 14 patients after six months of therapy showed a greater than 50% decrease in the infiltration of leukemia cells. We conclude that recombinant alpha-2-interferon is highly effective therapy for hairy cell leukemia.     

The process of HIV status disclosure to HIV-positive youth in Kinshasa, Democratic Republic of the Congo

As access to HIV/AIDS treatment increases in sub-Saharan Africa, greater attention is being paid to HIV-infected youth. Little is known about how HIV-positive youth are informed of their HIV infection. As part of a larger formative study informing a treatment program in Kinshasa, Democratic Republic of the Congo, semi-structured interviews were conducted with 19 youth (10-21 years) who had previously been told their HIV status and 21 caregivers who had disclosed the youth's HIV status to the youth. Questions explored youth's and caregivers' experiences of and immediate reactions to disclosure. Youth's median age at disclosure was 15 years old, with a range of 10-18 years based on caregiver reports (n=21) and from 10-19 years based on youth reports (n=18). The most common reasons spontaneously given for disclosing were the child's adherence to their treatment regimen (5/16), the need of the child to protect her/himself or stay healthy (5/16), the child's increasing age (4/16) and so that the child would know why they are suffering (3/16). Most youth (16/19) were surprised to learn of their diagnosis; 50% (8/16) wondered about the infection's origins. A large majority felt that it is better for them to know their HIV status (88%; 15/17). HIV care and treatment programs must be prepared to address the psychosocial needs of youth and their caregivers during the disclosure process.     

Effect of papain on the interaction between human monocytes, erythrocytes, and IgG

The mechanism by which papain detaches IgG-sensitized erythrocytes from the monocyte surface has been explored in an in vitro assay for the monocyte IgG receptor using red cells quantitatively sensitized with IgG anti-Rh D immunoglobulin. Papain treatment of IgG-sensitized erythrocytes diminished the ability of these cells to bind to the monocyte surface; however, treatment of erythrocytes with papain prior to sensitization with IgG did not inhibit binding, and at papain concentrations is greater than or equal to 38 mug/ml binding was enhanced. IgG receptor activity was not diminished by prior treatment of monolayer cells with papain and was enhanced with high concentrations of papain. These studies suggest that papain detaches erythrocytes from the monocyte surface by virtue of its proteolytic effect on IgG and not by an effect of papain on the D antigen of red cells or the IgG receptor on monocytes.