Pneumonitis after inhalation of mercury vapours

A 43-year-old man presented to hospital with pneumonia but only after discharge from hospital did he admit to deliberate prior inhalation of mercury. His pulmonary involvement appeared to resolve almost completely with antibiotics and supportive care. Nevertheless, persisting elevated urinary excretion of mercury required two courses of chelation therapy. No serious systemic sequelae were observed.     

The specific antigen-binding cell populations of individual fetal mouse spleens: repertoire composition, size, and genetic control

In order to analyze the genetic and physiological basis of controls affecting the generation of the repertoire of antigen-binding cells in fetal mice, we have measured the numbers of spleen cells specific for each of four antigens as a function of the total numbers of nucleated and Ig-bearing cells in inbred, hybrid, and random bred fetuses. For each of the two inbred strains BALB/c and CBA/J, the proportion of nucleated cells specific for a given antigen was the same for all individuals of the strain at the 18th day of gestation. The proportion did vary from antigen to antigen, however, and for each antigen the proportion of specific cells observed in CBA/J fetuses was approximately four times that observed in BALB/c fetuses. This difference appeared to be due to a difference between the two strains in the relative size of the repertoire of antigen-binding spleen cells at this stage of development, inasmuch as the frequency of Ig-bearing spleen cells in CBA/J fetuses was likewise approximately four times that observed in BALB/c fetuses. In random bred Swiss-L fetal mice at the 18th day of gestation, the proportion of cells specific for a given antigen varied significantly from one individual to the next. The ratio of proportions of the two antigens observed was constant from individual to individual, however, and this constant ratio differed significantly from the ratio observed for the same two antigens in fetal BALB/c and CBA/J inbred mice. These data suggest that the ontogeny of the repertoire of antigen-binding cells in fetal mice is subject to at least two independent sets of controls, one affecting the relative size of the repertoire in the spleen, and the other affecting the distribution of antigen-binding specificities within that repertoire. Analysis of repertoire size and composition in the spleens of hybrid fetuses confirmed the observation that the two parameters are controlled independently, and suggested further that the control of repertoire size in these fetuses is due to the action of one or a few closely-linked autosomal Mendelian genes. These data are consistent with models for the origin of antibody diversity in which the genes coding for the full repertoire of antibodies are generated somatically from a small number of germ-line genes early in development and in the absence of any strong positive or negative selection with respect to antigenic specificity.     

Potential for transfusion-associated graft-versus-host disease due to apheresis platelets matched for HLA class I antigens

Transfusion-associated graft-versus-host disease (TA-GVHD) has been reported in immunocompetent recipients of nonirradiated cellular blood components from donors who are homozygous for an HLA haplotype shared with the patient. In these cases, donor lymphocytes have no antigens foreign to the recipient, and this similarity in HLA antigens appears important for the development of TA-GVHD. Experience with 65 patients receiving apheresis platelets matched for class I HLA antigens was reviewed to determine the incidence of such a transfusion among HLA- matched, unrelated donor-recipient pairs. In 5 percent of transfusions (31/673), the patient received lymphocytes from a donor exhibiting no antigens foreign to the recipient, but the patient had additional HLA-A or -B antigens not present on donor lymphocytes. Twenty-three percent (n = 15) of patients received at least one such transfusion. In addition, most patients were immunosuppressed as a result of their underlying disease or therapy, which may decrease the degree of antigen matching required to initiate TA-GVHD. Until the pathogenesis of this disease is better understood, it is recommended that the transfusion of an HLA-matched cellular blood component be considered a risk factor for the development of TA-GVHD regardless of the patient's immune status, and that all such blood components be irradiated.     

CLIMACTERIC SYMPTOMS IN HEALTHY MIDDLE-AGED WOMEN

SUMMARY The incidence of climacteric symptoms was determined in 247 healthy premenopausal women in a community setting. These volunteers had been recruited to a longitudinal study of bone density. Of these subjects, 46 ceased to menstruate during the study, and in this subgroup symptoms were compared before and after cessation of menstruation. Only hot flushes increased after cessation of menstruation in the longitudinal study and showed age correlation in the cross-sectional study. Hot flushes thus emerged as a true menopausal symptom. Although evidence for this is weaker, cold sweats and suffocation seem likely to be genuinely menopausal. Breast discomfort and the four mood symptoms of irritability, excitability, depression and poor concentration improved after cessation of menstruation, and this study gives no support for their being part of the menopausal syndrome; it suggests that these symptoms are more likely to be related to menstruation than to the menopause.     

The effect of an intraoperative treatment algorithm on physicians' transfusion practice in cardiac surgery

Background : Inappropriate transfusion in cardiac surgery may, in part, be due to empiric transfusion therapy instituted in the absence of timely laboratory data. Therefore, the effect of a transfusion decision algorithm based on intraoperative coagulation monitoring of physicians' transfusion practice and the transfusion outcome was evaluated. Study Design and Methods : In a randomized, controlled trial, cardiac surgical patients determined to have microvascular bleeding at the cessation of cardiopulmonary bypass were assigned to algorithm (A) or standard (S) therapy. Group A was treated with plasma and platelet therapy according to a transfusion algorithm based on on-site coagulation data available within 4 minutes. For Group S, the use of laboratory-based data and the decision to transfuse blood components were at physician discretion. Results : Sixty-six patients were entered into the study (Group A, n = 30; Group S, n = 36). Other than the fact that there were significantly more female patients in Group S than in Group A, no differences between cohorts in regard to perioperative risk factors for blood transfusion needs were identified. Therefore, gender was factored in as a covariate in the statistical analysis. Group A patients received fewer hemostatic blood component units (p = 0.008) and had fewer total donor exposures (p = 0.007) during the entire hospitalization period. Linear regression analysis of the differences in slopes in Groups A and S for the relationships between the red cell volume lost and the red cell volume transfused (p < 0.03), non-red cell units transfused (p < 0.0001), and total number of blood components transfused (p < 0.0001) demonstrated that physicians' transfusion practice was significantly altered by the use of a transfusion algorithm with on-site coagulation data, independent of surgical blood losses. Conclusion : The use of algorithms by transfusion decision makers can serve as an effective physician education intervention.     

Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light

BACKGROUND: A photochemical treatment process has been developed for the inactivation of viruses and bacteria in platelet concentrates. This process is based on the photochemical reaction of a novel psoralen, S- 59, with nucleic acids upon illumination with long-wavelength ultraviolet light (UVA, 320–400 nm). STUDY DESIGN AND METHODS: High levels of pathogens were added to single-donor platelet concentrates containing 3 to 5 × 10(11) platelets in 300 mL of 35-percent autologous plasma and 65-percent platelet additive solution. After treatment with S-59 (150 microM) and UVA (0-3 J/cm2), the infectivity of each pathogen was measured with established biologic assays. In vitro platelet function after photochemical treatment was evaluated during 7 days of storage by using a panel of 14 assays. The in vivo recovery and life span of photochemically treated platelets were evaluated after 24 hours of storage in a primate transfusion model. RESULTS: The following levels of pathogen inactivation were achieved:>10(6.7) plaque-forming units (PFU) per mL of cell-free human immunodeficiency virus (HIV),>10(6.6) PFU per mL of cell-associated HIV,>10(6.8) infectious dose (ID50) per mL of duck hepatitis B virus (a model for hepatitis B virus),>10(6.5) PFU per mL of bovine viral diarrhea virus (a model for hepatitis C virus),>10(6.6) colony-forming units of Staphylococcus epidermidis, and>10(5.6) colony-forming units of Klebsiella pneumoniae. Expression of integrated HIV was inhibited by 0.1 microM S- 59 and 1 J per cm2 of UVA. In vitro and in vivo platelet function were adequately maintained after antiviral and antibacterial treatment. CONCLUSION: Photochemical treatment of platelet concentrates offers the potential for reducing transfusion-related viral and bacterial diseases.     

A comparative trial of granulocyte-colony-stimulating factor and dexamethasone, separately and in combination, for the mobilization of neutrophils in the peripheral blood of normal volunteers

BACKGROUND: The clinical utility of polymorphonuclear neutrophil (PMN) transfusion therapy has been compromised, in part, by the inability to obtain sufficient quantities of functional neutrophils from donors. To define the optimal conditions for mobilization of PMNs in granulocyte donors, the effects of granulocyte-colony-stimulating factor (G-CSF) and dexamethasone, separately and in combination, on PMN counts in normal volunteers were compared. STUDY DESIGN AND METHODS: Five normal subjects were randomly assigned to each of the following single-dose regimens in 5 consecutive weeks: 1) G-CSF, 300 micrograms given subcutaneously; 2) G-CSF, 600 micrograms subcutaneously: 3) dexamethasone, 8 mg given orally; 4) G-CSF, 300 micrograms subcutaneously, plus dexamethasone, 8 mg orally; and 5) G-CSF, 600 micrograms subcutaneously, plus dexamethasone 8 mg orally. Venous blood was collected at 0, 6, 12, and 24 hours after drug administration for the determination of absolute neutrophil counts (ANCs). RESULTS: Maximal ANC was achieved at 12 hours after each regimen, except dexamethasone alone (maximum, 24 hours). Dexamethasone significantly increased the maximal ANC induced by either dose of G-CSF alone (p < 0.05). The greatest mobilization of PMNs occurred after the administration of G-CSF (600 micrograms) and dexamethasone (8 mg); the ANC increased from a mean baseline value of 3,594 per microL to 43,017 per microL at 12 hours. All of the drug regimens were well tolerated. CONCLUSION: Dexamethasone significantly increases the level of neutrophilia induced in normal subjects by G-CSF. The combination of dexamethasone and G-CSF (at the dosages used in this study) is a convenient, well-tolerated regimen for the mobilization of PMNs in the peripheral blood of granulocyte donors. Moreover, the optimal quantitative yield of PMNs is likely to be achieved by leukapheresis 12 hours after drug administration.