The natural course of primary cytomegalovirus infection in blood donors.

BACKGROUND AND OBJECTIVES: As cytomegalovirus (CMV) DNA is frequently detectable in the plasma of recently infected sero-positive blood donors, information concerning primary CMV infection is important for the identification of possibly infectious donors. MATERIALS AND METHODS: Monitoring of 17 982 donors for CMV antibodies and DNA in plasma identified 14 subjects with ongoing primary CMV infection. Thirteen donors were interrogated for possible sources of infection and CMV-related symptoms, and monitored for CMV antigens, CMV DNA in plasma, leucocytes and urine, course of IgG and IgM antibodies as well as markers of systemic infection and parameters of organ function. RESULTS: CMV antigens and DNA were detectable in peripheral blood for up to 54 and 269 days respectively. Clearance of CMV DNA from blood correlated with clearance of IgM antibodies, development of IgG antibodies against the membrane glycoprotein gB and development of high avidity IgG antibodies. Eighty-five percent of subjects with primary CMV infection, but even 69% of matched controls reported possibly CMV-related symptoms. Sixty-two and 23%, respectively, had contact with possible sources of infection. One donor developed a febrile illness accompanied by increased levels of CMV DNA in peripheral blood 2 to 3 weeks after seroconversion. In other donors, neither markers of systemic infection nor parameters of organ function correlated with the course of CMV DNA and antigens. CONCLUSION: Potentially infectious donors can be identified by measuring CMV DNA, IgM antibodies or avidity of IgG antibodies. Alternatively, blood products donated during the first year after seroconversion should not be used for immunocompromised patients.

A prospective multicentre study on the safety of long-term intensive plasmapheresis in donors (SIPLA).

BACKGROUND AND OBJECTIVES: The safety of chronic intensive donor plasmapheresis has not been determined in large prospective studies examining dropout rates, dropout reasons and predictors of withdrawals. MATERIALS AND METHODS: Twenty-one plasma centres recruited 3783 donors who were switched from a moderate to an intensive plasmapheresis programme and observed over a 3-year period. Individuals weighing < 70 kg and > or = 70 kg donated 750 ml and 850 ml of plasma per session, respectively. The maximum of annual donations was limited to 60. Total serum protein (TSP) and haemoglobin (Hb) or haematocrit (Hct) were determined at each donation, and immunoglobulin G (IgG) at every fifth donation. Dropout rates, dropout reasons and potential predictors of withdrawal were analysed. RESULTS: Dropouts were predominantly due to socioeconomic (49.2% of all donors) or medical reasons not related to plasma donations (10.4% of all donors). Sixteen per cent of donors dropped out when IgG, TSP or Hb levels fell below threshold values. Severe clinical adverse events related to plasmapheresis were observed in five subjects. The incidence in severe cardiovascular diseases was lower in donors than in the general population. The risk factors that led to dropping out as a result of low IgG, TSP or Hb levels included younger age, female gender, low initial IgG levels and a high donation frequency. Neither body weight nor the amounts of plasma donated per kilogram of body weight per session were associated with ceasing due to medical reasons, whether related or unrelated to plasma donations. Females and males within the respective lowest body weight category were not at higher risk of dropping out. CONCLUSION: Long-term intensive donor plasmapheresis under conditions investigated in this study is safe. All donors weighing > or = 70 kg are safely able to donate 850 ml of plasma in each session up to 60 times per year, provided that they are carefully monitored.

Stage-adapted treatment of Wegener's granulomatosis. First results of a prospective study.

Considering cyclophosphamide's severe side effects there is a need for a new, less toxic treatment protocol for Wegener's granulomatosis. Here we report the first results of a prospective study using cyclophosphamide pulse therapy (monthly application) (a) as an alternative treatment in seven cases of active generalized Wegener's granulomatosis, which either showed complications under continuous cyclophosphamide treatment or in which the partial remission was not steady, and (b) as the initial treatment in five newly diagnosed patients with active generalized disease. After complete remission had been achieved in all cases in group (a), but only two cases in group (b), we started treatment with trimethoprim/sulfamethoxazole (cotrimoxazole) to maintain remission. Three of 8 patients suffered from severe relapses 9, 11 and 12 months after discontinuation of cyclophosphamide. The 3 patients in group (b) who could not be brought into remission had to be put on continuous cyclophosphamide. In addition, we treated 3 patients with newly diagnosed locoregional disease with cotrimoxazole alone. Two of these patients responded promptly and have only minor symptoms after 13 and 27 months, respectively. In one patient the disease continued to progress in the upper respiratory tract, and treatment was switched to cyclophosphamide and prednisolone after a period of 3 months. From these results we believe that cyclophosphamide pulse therapy is a successful alternative treatment protocol after partial remission has been achieved with a daily administration of cyclophosphamide or if complications, e.g-. leukopenia, arise with the continuous use of this drug. As an initial treatment, however, bolus treatment still appears to be an experimental protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

T-cell influence on the B-cell differentiation process induced by Klebsiella.

Klebsiella pneumoniae K43 cell membrane preparations (Klebs M) have been characterized previously as a human polyclonal B cell activator (PBA) that stimulates purified B cells to differentiate into immunoglobulin (Ig) secreting cells with negligible prior or parallel proliferation and in the absence of T cells. The aim of the present study was to define the cellular interactions in the regulation of Klebs M induced B-cell differentiation. For this purpose OKT4+ and OKT8+ cell populations were negatively selected with reasonable purity by means of a panning technique or by complement-mediated cytolysis using monoclonal OKT4 and OKT8 antibodies. The resulting cell populations were added to purified autologous B cells exposed to Klebs M or, as a control, pokeweed mitogen (PWM). In the Klebs M system both the OKT4+ and the OKT8+ cell subsets markedly enhanced IgM production; however, the helper effect of the OKT4+ cell subset was much more intense than that of the OKT8+ subset. In the PWM system only the OKT4+ cells provided help for B-cell differentiation. The OKT8+ subset demonstrated suppressor activity in the presence of an adequate helper cell (OKT4+ subset) function. These results indicate that Klebs M behaves like a "relatively T cell-independent PBA".