Creating the socially marginalised youth smoker: the role of tobacco control

We discuss how the tobacco control discourse on youth smoking in Canada appears to be producing and constituting socially marginalised smokers. We analyse material from a study on social inequalities in Canadian youth smoking. Individual interviews were conducted in 2007 and 2008 with tobacco control practitioners specialising in youth smoking prevention in British Columbia and Quebec. We found that the discourse on youth smoking is creating a set of divisive practices, separating youths who have a capacity for self‐control from those who do not, youths who are able to make responsible decisions from those who are not – with these distinctions often framed as a function of social class. Youths who smoke were not described simply as persons who smoke cigarettes but as individuals who, through their economic and social marginalisation, are biologically fated and behaviourally inclined to be smokers. This ‘smokers’ risk’ discourse obscures the social structural conditions under which people smoke and reproduces the biological and behavioural reductionism of biomedicine. The collision of risk and class in the discourse on poor youth who smoke may not only be doubly burdening but may intensify social inequalities in youth smoking by forming subcultures of resistance and risk‐taking.     

Epstein-Barr virus lymphoproliferation after bone marrow transplantation

We review 15 cases of secondary B-cell lymphoproliferative disorders that occurred among 2,475 patients who received allogeneic bone marrow transplants (BMTs) at the Fred Hutchinson Cancer Research Center (Seattle) between 1969 and 1987. The histopathologic findings in 14 of the 15 patients spanned a wide spectrum of lymphoproliferative lesions. One patient had features characteristic of angioimmunoblastic lymphadenopathy. Epstein-Barr virus (EBV) genomic sequences were identified by Southern blot analysis in each of the 13 patients evaluated. Ten of the 12 lesions evaluated originated in donor cells. In two patients, who had mixed chimerism after transplantation, the lesions originated in host cells. The combined evidence from immunoglobulin light chain staining and the analysis of immunoglobulin heavy chain gene rearrangement indicated that the lesions in most patients represented polyclonal proliferations that gave rise to clonal subpopulations. The results indicate an overall actuarial incidence of 0.6% for this complication in BMT recipients. Anti-CD3 monoclonal antibody (MoAb) treatment of acute graft-v-host disease (GVHD) and T cell depletion of the donor marrow were statistically significant risk factors, and GVHD appeared to play a contributing role, particularly in the setting of human leukocyte antigen (HLA) disparity. Two patients had no identifiable risk factors. Prophylaxis or treatment with acyclovir had no detectable effect in the patients; all but two died with uncontrolled lymphoproliferation.     

Atrial natriuretic peptide decreases circulatory capacitance in areflexic rats

The short-term hemodynamic response to atrial natriuretic peptide appears to be partly mediated by decreased venous return, which could result from increased circulatory capacitance or decreased blood volume. To determine if rat atrial natriuretic peptide 99-126 (0.5 microgram/kg/min IV for 30-70 minutes) dilated capacitance vessels or decreased blood volume, mean circulatory filling pressure (measured during brief circulatory arrest by inflating an intraatrial balloon) and blood volume (51Cr-erythrocytes) were measured in anesthetized rats. Mean circulatory filling pressure, central venous pressure, and blood volume decreased by 0.4 mm Hg, 0.5 mm Hg, and 3.4 ml/kg, respectively. To determine the total circulatory pressure-volume relationship without influence from autonomic reflexes, mean circulatory filling pressure and blood volume were measured in spinal-cord-transected rats before and immediately after infusing or withdrawing 5 ml blood. Atrial natriuretic peptide decreased mean circulatory filling pressure, central venous pressure, and blood volume by 0.9 mm Hg, 1.7 mm Hg, and 8.0 ml/kg, respectively, and displaced the pressure-volume relationship toward the pressure axis by decreasing extrapolated unstressed volume. Similar results were obtained in spinal-cord-transected rats that had initial vascular tone restored to a greater level by norepinephrine infusion. In anephric rats, atrial natriuretic peptide decreased central venous pressure by 0.3 mm Hg and blood volume by 1.6 ml/kg. The results indicate that short-term infusion of atrial natriuretic peptide reduced circulatory capacitance in rats and suggest that this reduction resulted from diminished blood volume due to urinary fluid loss followed by passive vascular recoil and active venoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monoclonal antibody BA-1 does not bind to hematopoietic precursor cells

Monoclonal antibody BA-1 binds to B lymphocytes, to cells from most cases of non-T acute lymphoblastic leukemia (ALL), and weakly to neutrophils. To determine whether BA-1 also reacts with hematopoietic progenitor cells (HPC), we studied the effect of removal of BA-1+ cells from human bone marrow on the proliferation in vitro of the trilineage precursor cell CFU-GEMM, and on the committed progenitor cells of granulopoiesis (CFU-C) and erythropoiesis (BFU-E/CFU-E). Complement- mediated cytotoxicity using BA-1 at concentrations far beyond those required to lyse BA-1+ bone marrow cells and ALL cells did not result in inhibition of colony formation in any of the assays. A rosette separation method, using ox red blood cells coated with BA-1, resulted in enrichment of HPC in the BA-1-depleted interface, whereas very few HPC were found in the BA-1-enriched pellet. Both methods indicate that BA-1 does not bind to HPC, although binding of the antibody to the lymphohematopoietic stem cell cannot be excluded yet. The high cytotoxic capacity of the IgM antibody BA-1, and the lack of reactivity with HPC, make the antibody particularly suitable for use in autologous bone marrow transplantation for patients with ALL.     

Fanconi's anemia treated by allogeneic marrow transplantation

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647- 3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

Marrow transplantation from HLA-identical siblings for treatment of aplastic anemia: is exposure to marrow donor blood products 24 hours before high-dose cyclophosphamide needed for successful engraftment?

The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the rejection rate, in particular in transfused patients who may already have been exposed to donor antigens by blood products, or (3) was of no relevance to the outcome of transplantation of marrow from HLA-identical siblings. One- hundred fifty-five patients were studied, of whom 78 received blood products from the marrow donor 24 hr before cyclophosphamide and 77 did not. A binary logistic regression analysis was applied to the data, simultaneously considering five previously known risk factors for rejection. Results showed that preceding transfusion of donor blood products had neither a significant beneficial nor detrimental effect on the incidence of sustained engraftment.     

Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide

A prospective randomized study was conducted comparing two conditioning regimens for the treatment of patients with chronic myeloid leukemia in chronic phase by marrow transplantation from HLA identical siblings. Sixty-nine patients received 60 mg/kg of cyclophosphamide on each of 2 successive days followed by 6 fractions of total body irradiation each of 2.0 Gy (CY-TBI), and 73 patients received 16 mg/kg of busulfan delivered over 4 days followed by 60 mg/kg CY on each of 2 successive days (BU-CY). There was no significant difference between the CY-TBI and the BU-CY groups in the 3-year probabilities of survival (0.80 for both), relapse (0.13 for both), or event-free survival (CY-TBI, 0.68; BU-CY, 0.71) or in speed of engraftment or incidence of venocclusive disease of the liver. The 4-year probabilities of survival and event- free survival for patients transplanted within 1 year of diagnosis were 0.86 and 0.72, respectively, for each group. Significantly more patients in the CY-TBI group experienced major creatinine elevations. There was significantly more acute graft-versus-host disease in the CY- TBI group. Fever days, positive blood cultures, hospitalizations, and inpatient hospital days were significantly more common in the CY-TBI group than in the BU-CY group. In conclusion, the BU-CY regimen was better tolerated than, and associated with survival and relapse probabilities that compare favorably with, the CY-TBI regimen.     

Continued gains in hypertension

Although a variety of vasodilator drugs produce acute hemodynamic Improvement in patients with severe chronic heart failure, long-term treatment with these agents may be associated with the development of drug tolerance and loss of initial beneficial effects. Five serial right heart catheterlzations in a 78 year old man with severe chronic heart failure due to idiopathic cardlomyopathy documented the development of hemodynamic and clinical tolerance to oral hydralazine and oral captopril after Initial responses were observed to both agents. However, sustained hemodynamic and clinical improvement by invasive testing was noted with minoxidil (20 mg orally twice daily) after 4 and 9 weeks of continuous therapy. These observations indicate that pharmacologic tolerance may occur with a variety of vasodilator drugs and may account for the failure of some patients to improve clinically with long-term therapy despite initial favorable hemodynamic effects. However, such tolerance seems to be drug-specific and, hence, its recognition in an individual patient does not preclude responsiveness to other vasodilator agents.