Waldenstrom's macroglobulinemia with an IgM paraprotein that is both a cold agglutinin and a cryoglobulin and has a suppressive effect on progenitor cell growth

BACKGROUND: A patient with Waldenstrom's macroglobulinemia was admitted to the hospital with fever, leg pain, and dyspnea. The patient had gas gangrene of the left leg that required above-the-knee amputation. Plasmapheresis was instituted to treat hyperviscosity. STUDY DESIGN AND METHODS: The patient's serum contained an IgM-kappa paraprotein, a cryoglobulin, and a cold agglutinin. The serum was studied. RESULTS: The patient's red cells typed as A1, Rh-positive. The direct antiglobulin test was negative. The serum contained a cold agglutinin with anti-Pr cold agglutinin specificity (titer 4096). Maximal thermal range was 30 degrees C. Following dithiothreitol treatment, the cold agglutinin activity disappeared. The serum IgM concentration in the tested sample was 62.3 g per L. The cold agglutinin titer in the supernatant after removal of the cryoglobulin was 256, and the IgM level was 0.31 g per L. Redissolving the cryoglobulin in a equivalent volume of saline resulted in a cold agglutinin titer of 4096 and an IgM level of 68.4 g per L. These results indicate that the cryoglobulin and the cold agglutinin are the same paraprotein. Serum protein electrophoresis using agarose gel and immunofixation of the serum revealed an IgM-kappa monoclonal band. Progenitor cell assays were performed by adding the patient's serum at final concentrations of 0, 1, 5 and 10 percent (vol/vol) to patient's and normal donor's peripheral blood mononuclear cells. Inhibition of burst-forming units- erythroid and colony-forming units-granulocyte/macrophage by the patient's serum was demonstrated. Appropriate controls and the use of the serum of another patient with Waldenstrom's macroglobulinemia did not suppress progenitor cell growth. The patient's serum inhibited colony formation in a dose-response fashion. CONCLUSION: Reports of cryoprecipitable cold agglutinins are rare. This case is unusual because the IgM-kappa paraprotein was also a cold agglutinin with anti- Pr specificity and erythroid and granulocyte-macrophage progenitor cell- suppressive properties.     

HIV testing preferences among pregnant women attending antenatal care and their male partners: a discrete choice experiment in Uganda

HIV testing rates remain stubbornly low among men – a crucial target population for reaching the ambitious global and regional goals of the HIV programme. In an era of declining donor funding, identifying cost-effective strategies to increase testing rates amongst men remains paramount. Antenatal care is an effective entry-point for the delivery of HIV testing services for women, and partner testing presents an important opportunity to reach their male partners. We present the results of a discrete choice experiment in Uganda, examining preferences among 824 pregnant women and 896 male partners regarding service delivery characteristics of HIV testing. Both men and women preferred nurse administered testing to self-testing (OR = 0.835; p < 0.001), oral testing over a finger-prick test (OR = 1.176; p < 0.001) and testing with a partner over testing alone (OR = 1.230; p < 0.001). Men had a preference for testing at home compared to testing at a clinic (OR = 1.099; p = 0.024), but women were indifferent regarding the testing location. The cost of testing had the biggest effect on preferences. Free testing was preferred over a cost of US$2.90 (OR = 0.781; p < 0.001) or US$2.00 (OR = 0.670; p < 0.001). Offering an incentive of US$3.40 increased men’s preferences compared to a free test (OR = 1.168; p < 0.001), although this did not affect women’s preferences. Partner testing linked to antenatal care is a potential strategy to increase testing coverage among men, particularly given the preference for partner testing – provided costs to clients remain low. Future cost-effectiveness evaluations should investigate the economic impact of reaching men using these strategies.     

A bioartificial transgenic porcine whole liver expressing human proteins alleviates acute liver failure in pigs

Background: Preventing heterologous protein influx in patients is important when using xenogeneic bioartificial livers(BALs) to treat liver failure. The development of transgenic porcine livers synthesizing human proteins is a promising approach in this regard. Here, we evaluated the safety and efficacy of a transgenic porcine liver synthesizing human albumin(h ALB) and coagulation factor VII(h FVII) within a bioartificial system. Methods: Tibetan miniature pigs were randomly subjected to differ...     

Screening for neonatal hyperbilirubinaemia and ABO alloimmunization at the time of testing for phenylketonuria and congenital hypothyreosis

In a population-based study including 2463 infants, serum bilirubin measurements were added to the neonatal screening programme for phenylketonuria and congenital hypothyreosis. This screening programme detected 11/17 (65%) of infants with serum bilirubin levels > 350/μmol l⁻¹, of whom 7 (3 per 1000) were readmitted from home (6 treated with phototherapy). A total of 139 infants (5.6%) received phototherapy. Maternal blood type O occurred significantly more often in term infants treated (30/54; 55.6%) compared with preterm infants treated (32/85; 37.6%) and with blood type O occurrence in the total population of mothers (906/2426; 37.3%) ( p < 0:05). The blood type constellations mother O/infant A or B showed a sensitivity of 64%, specificity 65%, positive predictive value 12% and a negative predictive value of 96% for the requirement of phototherapy for the whole material. Exchange transfusion was not required in any of the infants. No infant developed bilirubin encephalopathy (kernicterus). Adding bilirubin to a neonatal screening programme detects some cases with unexpectedly high bilirubin levels in need of intervention. Routine ABO blood typing of pregnant women, ABO cord blood typing and Coombs' test in infants of mothers with blood type O cannot be recommended because of low positive predictive value for the requirement of intervention (phototherapy) by these tests.