Treatment with blood components and coagulation factor concentrates--modern concepts of hemotherapy

Transfusion of whole blood is the most common and successful organ transplantation world wide. It is in use longer than any other transplantation procedure. With the exception of uses in situations of crisis, treatment with whole blood is nowadays obsolete. This is due to enormous progress in preparation technologies. As a result blood from volunteer donors is separated before therapeutic use into its cellular and plasmatic components. The latter may be further processed into subfractions or secondary products. The advantages of this strategy are evident: a) the crude pharmaceutic material blood is used optimally, b) the isolated components may be stored over periods appropriate for their stability be it in a cryopreserved state or after biochemical, immunologic or biological modification, c) the patient receives only the blood components he needs, d) the transfusion of unnecessary fractions of blood is avoided, e) the rate of transfusion-associated adverse events is reduced, f) the physician has a basis for customized hematotherapy. Important implications concern logistics, economy, differentiated therapy and drug safety consideration. This contribution gives an overview on progress made in therapy of hematologic and oncologic patients with blood products and concentrates of coagulation factors. It demonstrates selected aspects of actual interest for optimal hemotherapy.     

Brief assessments of dietary behavior in field settings

Our research team is involved in ongoing research in both worksites and medical office settings. These settings offer great potential for reaching individuals who would not otherwise participate in health promotion, but they also place considerable constraints on assessment time and efforts, especially if one's goal is to attract a high and representative proportion of employees or patients. This paper reports on our experience with measures of dietary behavior in these two settings. We found it problematic to collect detailed assessments such as 4-day food records or comprehensive food frequency/history checklists in worksites or medical office settings using population-based samples. Instead, we recommend and provide data on the utility of a dietary-fat screening instrument, and on the Food Habits Questionnaire (FHQ-Kristal, Shattuck, & Henry, 1990), a brief measure of dietary behaviors associated with high-fat eating patterns. The FHQ, in particular, was found to correlate well with other more costly and time-consuming methods of assessment, to be reliable and responsive to intervention effects, and to provide behavioral targets for intervention. The strengths and limitations of these measures for tailoring intervention and assessing outcomes are discussed.     

Expandable metal stents for the treatment of colonic obstruction: techniques and outcomes

Modulation of CD8(+) T-cell responses specific for an exogenous antigen by epitope variants would be advantageous to develop a novel means of antigen-specific immune regulation. We have analyzed CD8(+) T-cell responses to single amino acid-substituted variants of a peptide corresponding to residues 142-149 (p142-149; LAYFYPEL) of alphas1-casein, a major milk allergen, which is a dominant determinant restricted by H-2Kb. An analog peptide L142I with a substitution of Ile for Leu at the nonanchor N-terminal residue induced more IFN-gamma secretion than p142-149 from specific CD8(+) T cells. Furthermore, L142I could prime CD8(+) T cells more efficiently in vivo, and these L142I-primed cells secreted more IFN-gamma than p142-149-primed CD8(+) T cells upon stimulation with p142-149 in vitro. These findings are mainly explained by the greater ability of L142I to form stable Kb-peptide complexes. These findings indicate that appropriate analog peptides may be useful as efficient inducers of CD8(+) T cells which recognize the parent peptide and secrete IFN-gamma, a potent inhibitor of Th2-dependent events, including IgE production.     

Identification of residues in the cysteine-rich domain of Raf-1 that control Ras binding and Raf-1 activity

We have identified mutations in Raf-1 that increase binding to Ras. The mutations were identified making use of three mutant forms of Ras that have reduced Raf-1 binding (Winkler, D. G., Johnson, J. C., Cooper, J. A., and Vojtek, A. B. (1997) J. Biol. Chem. 272, 24402-24409). One mutation in Raf-1, N64L, suppresses the Ras mutant R41Q but not other Ras mutants, suggesting that this mutation structurally complements the Ras R41Q mutation. Missense substitutions of residues 143 and 144 in the Raf-1 cysteine-rich domain were isolated multiple times. These Raf-1 mutants, R143Q, R143W, and K144E, were general suppressors of three different Ras mutants and had increased interaction with non-mutant Ras. Each was slightly activated relative to wild-type Raf-1 in a transformation assay. In addition, two mutants, R143W and K144E, were active when tested for induction of germinal vesicle breakdown in Xenopus oocytes. Interestingly, all three cysteine-rich domain mutations reduced the ability of the Raf-1 N-terminal regulatory region to inhibit Xenopus oocyte germinal vesicle breakdown induced by the C-terminal catalytic region of Raf-1. We propose that a direct or indirect regulatory interaction between the N- and C-terminal regions of Raf-1 is reduced by the R143W, R143Q, and K144E mutations, thereby increasing access to the Ras-binding regions of Raf-1 and increasing Raf-1 activity.     

Long-term sweat collection using salt-impregnated pads

To facilitate a study of the pharmacokinetics of drugs dissolved in sweat, a technique was devised for collecting sweat at a steady rate over an 8-day period. Three normal subjects each wore 4 absorbent pads applied to their skin under waterproof dressings for 8 days. The absorbent pads were either plain cotton or cotton impregnated with sodium chloride crystals. Each pad (3 cm x 3 cm) was applied to an area of skin (2 cm x 2 cm) defined by an adhesive template, and was removed daily, weighed, and replaced, to determine progressive uptake of sweat. Sweat uptake by plain cotton pads reached a plateau value within 2 to 3 days and did not significantly increase thereafter; in contrast, uptake by the salt-impregnated pads continued at a steady rate for the full 8 days of the study (mean rate 0.79 mg/cm2/hr, SD = 0.16, N = 6). This effect may be related to an osmotic gradient across the skin, but the physiologic mechanisms are not completely clear. This appears to be a convenient tool for the collection of sweat over long periods at a steady rate.