Optimizing dose and scheduling of filgrastim (granulocyte colony- stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers [see comments]

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients.     

Role of urethral reconstruction and artificial sphincter in complicated salvage radical prostatectomy

Patients undergoing radical prostatectomy following failed definitive radiation therapy for adenocarcinoma of the prostate run a substantial risk of refractory bladder neck contractures and urinary incontinence developing. A combined reconstructive technique utilizing a urethral pull-through procedure and implantation of an artificial urinary sphincter to treat these complications is described. When a patient can truly be cured by radical prostatectomy, this relatively straightforward reconstruction can salvage what otherwise would be considered a surgical failure.     

Innervation of the large intestine of the toad (bufo marinus)

The morphology, physiology and pharmacology of the innervation of the toad (Bufo marinus) large intestine have been studied. The large intestine can be divided into the regions colon, rectum and cloaca, on morphological grounds, but acts as a unit in response to nerve stimulation. Of the right and left nerves, each appears to supply the entire large intestine. Autonomic innervation of the large intestine of Bufo marinus is as follows: (1) The 9th and 10th spinal nerves (pelvic) contain predominantly excitatory preganglionic cholinergic fibres, but some inhibitory adrenergic fibres are also present in most preparations. (2) The splanchnic nerves contain inhibitory postganglionic adrenergic fibres from the 3rd to 5th sympathetic ganglia, and a small number of excitatory cholinergic fibres. The pathway of adrenergic inhibitory fibres to the large intestine alongside the posterior mesenteric artery as seen in mammals is rarely present in the toad. Several nonspecific actions of autonomic drugs on the large intestine are discussed. The functional organization of the autonomic innervation of the toad large intestine is similar to that in mammals, that is the large intestine is controlled by antagonistic cholinergic and adrenergic nerves. However, the separation of these two types of nerve fibres into anatomically distinct nerves does not appear to be as complete as in mammals. It is suggested that inhibitory autonomic control of the alimentary canal in vertebrates first appears in the hind-gut region.     

Red cell membrane stiffness in iron deficiency

The purpose of this study was to characterize red blood cell (RBC) deformability by iron deficiency. We measured RBC deformability to ektacytometry, a laser diffraction method for determining the elongation of suspended red cells subjected to shear stress. Isotonic deformability of RBC from iron-deficient human subjects was consistently and significantly lower than that of normal controls. In groups of rats with severe and moderate dietary iron deficiency, RBC deformability was also reduced in proportion to the severity of iron deficiency. At any given shear stress value, deformability of resealed RBC ghosts from both iron-deficient humans and rats was lower than that of control ghosts. However, increase of applied shear stress resulted in progressive increase in ghost deformation, indicating that ghost deformability was primarily limited by membrane stiffness rather than by reduced surface area-to-volume ratio. This was consistent with the finding that iron-deficient cells had a normal membrane surface area. In addition, the reduced mean corpuscular hemoglobin concentration (MCHC) and buoyant density of the iron-deficient rat cells indicated that a high hemoglobin concentration was not responsible for impaired whole cell deformability. Biochemical studies of rat RBC showed increased membrane lipid and protein crosslinking and reduced intracellular cation content, findings that are consistent with in vivo peroxidative damage. RBC from iron-deficient rats incubated in vitro with hydrogen peroxide showed increased generation of malonyldialdehyde, an end-product of lipid peroxidation, compared to control RBC. Taken together, these findings suggest that peroxidation could contribute in part to increased membrane stiffness in iron- deficient RBC. This reduced membrane deformability may in turn contribute to impaired red cell survival in iron deficiency.     

Basal cell carcinoma in young women: an evaluation of the association of tanning bed use and smoking

Basal cell carcinomas (BCCs) typically occur in middle-aged to elderly patients but less commonly in younger ones. In our experience, most BCCs seen in patients younger than 40 years are found in women. We evaluated 30 women with biopsy-proven BCC and 30 control patients matched for sex, age, and skin type to determine potential risk factors for this population. Tanning bed visits, pack-years of cigarette smoking, recreational sun exposure, number of blistering sunburns, and use of sunscreens were determined for both groups. Among patients with a BCC, the histologic type of tumor, site of involvement, method of treatment, follow-up period, incidence of recurrence, and presence of actinic keratoses were also evaluated. Patients with a BCC had a statistically greater number of pack years of smoking (P =.045), and a greater percentage of these women had experienced blistering sunburns (P =.028). Although women with a BCC had, on average, almost twice as many tanning salon visits (152.2 vs 83.1), this was not statistically significant. Sunscreen use and amount of recreational ultraviolet light exposure were essentially equal between the two groups. Young women with a BCC are more likely to have a past or current history of cigarette smoking and blistering sunburns. Repeated exposure to tanning beds may also be a contributory factor.     

The Effect of Residential Aged Care Size,Ownership Model,and Multichain Affiliation on Resident Comfort and Symptom Management at the End of Life

Context

In most resource-rich countries, a large and growing proportion of older adults with complex needs will die while in a residential aged care (RAC) facility.

Transport of amino acids by the human placenta: Predicted effects thereon of maternal hyperphenylalaninaemia

Summary Brush border and basal plasma membrane vesicles prepared from normal term human placental syncytiotrophoblast have been used to study amino acid transport. Such studies are reviewed and novel results presented which confirm that saturation of placental transport by phenylalanine is unlikely to limit delivery of this amino acid to the fetus even with grossly raised maternal concentrations. Such raised maternal levels of phenylalanine are, however, likely to severely embarrass the delivery to the fetus across the placental brush border membrane ofl-tyrosine and, to a lesser extent, ofl-tryptophan. Reasons for thinking that this may be relevant to the fetal damage found in maternal PKU are discussed.