Duplex sonography accurately assesses portacaval shunt patency

Among 42 patients who had undergone portacaval shunt (PCS) to treat bleeding esophageal varices, shunt patency was assessed with duplex sonography 1 month to 5 years postoperatively. Patency was confirmed in all patients (100%). Correlative angiograms confirming the sonographic findings were obtained in 24 patients. Duplex scanning showed hepatofugal or stagnant flow in the distal portal vein in all 42 patients. Very low rates of liver-failure-related mortality (6%) and morbidity (6% incidence of encephaloparthy) in this series despite loss of portal perfusion of the liver in patients incriminate factors other than magnitude and direction of portal vein flow as the cause of complications occurring after PCS. Duplex sonography offers accurate and relevant clinical and physiologic data about shunt hemodynamics in patients who have undergone PCS.     

Continuous oestrogen-progestogen treatment and bone metabolism in post-menopausal women

The suggestion that norethisterone acetate (NETA) stimulates bone formation prompted us to investigate calcium and bone metabolism in post-menopausal women treated with a continuous combination of oestrogen and NETA. The study included 49 healthy post-menopausal women. After an initial examination the women were randomly allocated to 2 yr of treatment with either hormones or placebo; 43 women completed the study. Within the first year of treatment the hormone group showed a slight, but significant, increase in bone mineral content in the forearms (single photon absorptiometry) and in the total skeleton (dual photon absorptiometry). After this initial increase the bone mass remained constant throughout the trial. Bone mineral density of the spine (dual photon absorptiometry) showed a significant increase of more than 5% in the hormone group. There were significant decreases of 4-7% in bone mass in the placebo group over 2 yr. Biochemical estimates of bone turnover (plasma bone Gla protein, serum alkaline phosphatase, fasting urinary calcium and fasting urinary hydroxyproline) fell significantly in the hormone group, but remained unchanged in the placebo group. We conclude that continuous administration of NETA in combination with oestrogen provides effective prophylaxis against post-menopausal bone loss, although it does not produce a persistent positive calcium balance in early post-menopausal women.     

Immunological,chemical and clinical aspects of exposure to mixtures of contact allergens

Allergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.     

Kinetics of antibody and memory B cell responses after MMR immunization in children and young adults

The persistence of antigen-specific memory B-cells (MBCs) in children and young adults long time after vaccination against measles, mumps and rubella (MMR) is not known. Here we have looked at the Swedish immunization program and examined children 1–10 years after the first MMR dose in early childhood, as well as young adults 7–18 years after the second dose of MMR. We show that Ab titers and MBCs against measles and rubella have different kinetics, indicating that the MBC pool and the corresponding Ab titers are regulated independently. These data fit well with other findings that continuous IgG secretion comes from long-lived plasma cells and not MBCs. We also demonstrate that individuals with low post-vaccination Ab titers might have an adequate MBC response. It remains to be shown if memory B-cells provide the same protection as specific antibodies, but our data is a valuable complement to the incomplete knowledge about correlates of protection after vaccination.     

Reasons for treating secondary AML as de novo AML

In a Danish bi‐regional registry‐based study, we conducted an analysis of the incidence and clinical importance of secondary acute myeloid leukaemia (AML). In a total of 630 cases of AML, we found 157 (25%) cases of secondary AML. The secondary leukaemia arose from MDS (myelodysplastic syndrome) in 77 cases (49%), CMPD (chronic myeloproliferative disorder) in 43 cases (27%) and was therapy‐related AML (t‐AML) in 37 cases (24%). Median age at diagnosis of AML was 69 yr in secondary cases when compared to 66 yr in de novo cases (P = 0.006). In univariate analyses, secondary AML was associated with an inferior complete remission (CR) rate (P = 0.008) and poorer overall survival (OS, P = 0.003) whereas in complete remitters, disease‐free survival (DFS) of secondary cases was equal to that of de novo cases. Interestingly, in all further analyses of CR‐rates, OS and DFS, when correcting for the influence of age, cytogenetic abnormalities, performance status and leucocyte count (WBC), presence of secondary AML completely lost prognostic significance. We conclude that the presence of secondary AML does not per se convey an unfavourable prognosis and that patients with secondary AML should be offered the chance of benefiting from treatment according to current frontline AML protocols.     

TRIM21 is important in the early phase of inflammation in the imiquimod‐induced psoriasis‐like skin inflammation mouse model

Tripartite motif‐containing protein 21 (TRIM21) regulates pro‐inflammatory cytokines and type I interferons and acts as an autoantigen in certain autoimmune diseases, but TRIM21 has not been investigated in psoriasis. It has been suggested that TRIM21 may have a dual function; in the early phase of inflammation, it may function as a stimulator; but upon immune stimulation, its ubiquitinating mode of action may shift from stabilization to degradation of IRF3 causing inhibition of the immune responses. The imiquimod (IMQ)‐induced psoriasis‐like mouse model displays features similar to those of human psoriasis. However, chronicity is lacking in this model. We investigated whether the role of TRIM21 in psoriasis was pro‐inflammatory or anti‐inflammatory. We hypothesized that a shift of the TRIM21‐ubiquitinating mode of action may explain the lack of chronicity in the IMQ‐induced psoriasis‐like mouse model. We showed that TRIM21 expression is increased in lesional psoriatic skin and in the early phase of IMQ‐induced inflammation both in vitro and in vivo. Surprisingly, inflammation was significantly less pronounced in TRIM21 knockout mice than in wild‐type mice as shown by ear thickness measured at days 8, 9 and 10 after treatment start, by spleen weight as a marker of systemic effect of IMQ at 10 days after treatment start and by expression of IL‐12p40 at days 3 and 10 after treatment start and IL‐17A at day 3 after treatment start. Therefore, induction of TRIM21 expression cannot explain the lack of chronicity in the IMQ‐induced psoriasis‐like skin inflammation mouse model.