Unrelated donor bone marrow transplantation for chronic myelogenous leukemia: a decision analysis

BACKGROUND: Chronic myelogenous leukemia (CML) is an indolent but ultimately fatal disease. Because the natural history of CML varies and quality of life with CML may be excellent until shortly before death, deciding whether and when to pursue unrelated donor bone marrow transplantation is often difficult. OBJECTIVE: To compare early transplantation, delayed transplantation, and no transplantation for patients with chronic-phase CML on the basis of discounted, quality-adjusted life expectancy. DESIGN: A markov model comparing different strategies was constructed. This model considers patient age, quality of life, risk aversion, and the competing risks for CML progression and transplant toxicity. SETTING: Therapeutic decision at the time of diagnosis of CML. PATIENTS: The base case is a 35-year-old patient with intermediate-prognosis CML. Younger and older patients with better and worse prognoses are also evaluated. INTERVENTION: Early transplantation, delayed transplantation, and no transplantation. MEASUREMENTS: Quality-adjusted, discounted life expectancy. RESULTS: For patients with newly diagnosed CML, transplantation within the first year provides the greatest quality-adjusted expected survival, although this benefit decreases with increasing patient age. For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 53 more discounted, quality-adjusted years of life expectancy than does no transplantation. This finding is robust even with varying baseline assumptions. CONCLUSIONS: These results support the use of early unrelated donor bone marrow transplantation for most patients with CML.     

Acquired inhibitors to factors V and X after exposure to topical thrombin: interference with monitoring of low molecular weight heparin and warfarin

Repeated surgical exposure to topical bovine thrombin is known to be associated with the development of antibodies to bovine and human thrombin and factor V. This is demonstrated by abnormalities of in vitro coagulation assays and, rarely, postoperative bleeding. We describe a 4-year-old child in whom an antibody to bovine factor X developed after cardiac surgery; this antibody interfered with the heparin anti-Xa assay, thereby complicating the monitoring of heparin therapy.     

Variation of nitric oxide concentration during inspiration

OBJECTIVE: To evaluate the pattern of inspiratory nitric oxide concentration in a simple, constant flow delivery system during the use of two phasic-flow ventilatory modes. DESIGN: Laboratory study in a lung model. SETTING: University experimental laboratory. SUBJECT: Nitric oxide (800 ppm in nitrogen) was administered continuously into the inspiratory circuit to deliver a nitric oxide concentration of 10 and 40 ppm to a test lung during volume-controlled (constant flow) and pressure-controlled (decelerating flow) ventilation, with an FIO2 of 1.0. INTERVENTIONS: In each mode, minute ventilation of 7, 14, and 21 L/min and installation of mixing chambers (none, 1-L, 2-L, and 3.2-L turbulence boxes) were studied, respectively. Nitric oxide and nitric dioxide were monitored by chemiluminescence. Since the nitric oxide/nitrogen gas is the only nitrogen source in the system during ventilation with an FIO2 of 1.0, we evaluated the fluctuation in the inspiratory nitric oxide (NOx) concentration by measuring nitrogen with a fast-response analyzer. To test the effect of the measurement site, we measured nitric oxide concentrations using chemiluminescence at different positions in the inspiratory and expiratory limbs, with and without the mixing chambers, with a minute ventilation of 14 L/min and a nitric oxide concentration of 40 ppm. MEASUREMENTS AND MAIN RESULTS: Nitrogen dioxide production was not influenced by the flow pattern. During a nitric oxide concentration of 10 ppm, nitrogen dioxide was always < 0.6 ppm. During a nitric oxide concentration of 40 ppm, the highest nitrogen dioxide (4.47 ppm) concentration was found at the lowest minute ventilation and the largest inspiratory circuit volume. Nitric oxide values displayed by chemiluminescence indicated stable concentrations at all settings. However, without mixing chambers, NOx concentration calculated from nitrogen measurements demonstrated marked inspiratory fluctuations and was highest with a minute ventilation of 21 L/min and higher during pressure-controlled ventilation compared with volume-controlled ventilation (nitric oxide concentration of 40 ppm, pressure-controlled ventilation: 14.5 to 130.5 ppm; volume-controlled ventilation: 21.6 to 104.7 ppm; nitric oxide concentration of 10 ppm, pressure-controlled ventilation: 3.2 to 30.9 ppm; volume-controlled ventilation: 4.5 to 27.1 ppm). NOx concentration fluctuation decreased with an increasing mixing chamber, and was negligible at all settings with the 3.2-L turbulence box. Nitric oxide concentration fluctuation influenced chemiluminescence measurements. The displayed nitric oxide values varied, depending on the sampling site, and did not accurately reflect mean inspiratory nitric oxide concentration. Incorporation of a mixing chamber eradicated this sampling site influence. CONCLUSIONS: Continuous flow delivery of nitric oxide into the circuit of a phasic-flow ventilator results in marked inspiratory nitric oxide concentration fluctuation that is not detected by a slow-response chemiluminescence analyzer. Moreover, nitric oxide concentration fluctuation can influence the accuracy of the chemiluminescence measurements. These effects can be diminished by using additional mixing chambers to facilitate a stable gas concentration. As these mixing volumes increase the contact time of nitric oxide with oxygen, an increase of nitrogen dioxide has to be taken into account.     

Changing patterns of localization of the tobacco mosaic virus movement protein and replicase to the endoplasmic reticulum and microtubules during infection

Tobacco mosaic virus (TMV) derivatives that encode movement protein (MP) as a fusion to the green fluorescent protein (MP:GFP) were used in combination with antibody staining to identify host cell components to which MP and replicase accumulate in cells of infected Nicotiana benthamiana leaves and in infected BY-2 protoplasts. MP:GFP and replicase colocalized to the endoplasmic reticulum (ER; especially the cortical ER) and were present in large, irregularly shaped, ER-derived structures that may represent "viral factories." The ER-derived structures required an intact cytoskeleton, and microtubules appeared to redistribute MP:GFP from these sites during late stages of infection. In leaves, MP:GFP accumulated in plasmodesmata, whereas in protoplasts, the MP:GFP was targeted to distinct, punctate sites near the plasma membrane. Treating protoplasts with cytochalasin D and brefeldin A at the time of inoculation prevented the accumulation of MP:GFP at these sites. It is proposed that the punctate sites anchor the cortical ER to plasma membrane and are related to sites at which plasmodesmata form in walled cells. Hairlike structures containing MP:GFP appeared on the surface of some of the infected protoplasts and are reminiscent of similar structures induced by other plant viruses. We present a model that postulates the role of the ER and cytoskeleton in targeting the MP and viral ribonucleoprotein from sites of virus synthesis to the plasmodesmata through which infection is spread.     

Bacterial hemagglutination by Neisseria gonorrhoeae

Direct bacterial hemagglutination was investigated with 20 clinical isolates of Neisseria gonorrhoeae. The hemagglutination tests were performed by both a macrotechnique with glass slides and a microtechnique with autotrays. Only organisms from form type 1 or 2 colonies caused hemagglutination. There was no statistical difference at a 10% or higher level in hemagglutination powers of type 1 and type 2 organisms, of male urethral and female cervical isolates, and of the eight major human blood types (ABO-Rh). Of seven erythrocyte species tested, only human cells were agglutinated. D-Mannose did not prevent the agglutination. Rabbit antigonococcal serum and high-titer antigonococcal human sera inhibited the hemagglutination. The results suggest the pili are the mediators of hemagglutination and that their specific agglutination of human erythrocytes may be a correlate of their adherence to human mucosal cells in natural infection. Also, although the procedure is presently insensitive, it is possible to detect human antigonococcal antibody by inhibition of direct bacterial hemagglutination.     

The role of state policies and programs in buffering the effects of poverty on children's immunization receipt

OBJECTIVES: This study assessed the influence of public policies on the immunization status of 2-year old children in the United States. METHODS: Up-to-dateness for the primary immunization series was assessed in a national sample of 8100 children from the 1988 National Maternal and Infant Health Survey and its 1991 Longitudinal Follow-Up. RESULTS: Documented immunization rates of this sample were 33% for poor children and 44% for others. More widespread Medicated coverage was associated with greater likelihood of up-to-dateness among poor children. Up-to-dateness was more likely for poor children with public rather than private sources of routine pediatric care, but all children living in states where most immunizations were delivered in the public sector were less likely to be up to date. Poor children in state with partial vaccine replacement programs were less likely to be up to date than those in free-market purchase states. CONCLUSIONS: While state policies can enhance immunization delivery for poor children, heavy reliance on public sector immunization does not ensure timely receipt of vaccines. Public- and private-sector collaboration is necessary to protect children from vaccine-preventable diseases.