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Biomedical subjects

S Selinger

Publications and source records attributed to S Selinger.

8 recordsLinked to original sources
PubMed2004

Mobilized blood cells vs bone marrow harvest: experience compared in 171 donors with particular reference to pain and fatigue.

This prospective study compared the donor experience of blood cell (BC) mobilization and leukapheresis (n=116) with that of bone marrow (BM) harvest (n=55). Internal jugular catheters were inserted electively in 89% of BC donors. Most (80%) BM donors had a harvest with general anesthesia; 20% had epidural or spinal anesthesia. Pain and fatigue were frequent with both procedures and were compared in responses to questionnaires. A total of 85% of BM donors reported moderate or severe pain compared with 68% of BC donors (P=0.02). The median duration of pain was 14 days for BM donors compared with 3 days after BC mobilization (P<0.0001). More BM donors had pain for more than 7 days (75% vs 0%, P<0.0001). Severe fatigue was experienced by more BM donors (49 vs 16%, P<0.0001). Fatigue lasted significantly longer in BM donors (median 11 vs 4 days, P<0.0001) and more BM donors were fatigued for more than 1 week (69 vs 0%, P<0.0001). A total of 11 donors had both BM and BC collection; seven preferred the latter. Simply considered with respect to pain and fatigue, BC donation appears better tolerated by donors. However, there are other sequelae of both influencing the acceptability for individual donors.

Adolescent↗
PubMed2003

CpG-A oligonucleotides induce a monocyte-derived dendritic cell-like phenotype that preferentially activates CD8 T cells.

Human B cells and plasmacytoid dendritic cells recognize CpG motifs within microbial DNA via Toll-like receptor 9. Two functionally distinct types of CpG motif containing oligonucleotides (CpG ODN) have been described, CpG-A and CpG-B. In contrast to CpG-B, CpG-A induces high amounts of type I IFN (IFN-alpha and IFN-beta) in plasmacytoid dendritic cells. In the present study, we examined the effects of CpG-A on human primary monocytes. In PBMC stimulated with CpG-A and GM-CSF, monocytes showed excellent survival, increased in size and granularity, and within 3 days developed a dendritic cell-like phenotype that was characterized by down-regulation of CD14, partial up-regulation of CCR7, and an increased surface expression of costimulatory and Ag-presenting molecules. This effect could be inhibited by a combination of blocking Abs to type I IFN, and no such CpG-A-induced changes were observed in purified monocytes. Although IL-12 production by this dendritic cell-like phenotype required additional stimulation with CD40 ligand, this cell type spontaneously up-regulated IL-15 expression. Consistent with the known effect of IL-15 on effector and memory CD8 T cells, the frequency of CCR7(-)/CD45RA(-) CD8 T cells was selectively increased in allogeneic T cell assays. Furthermore, this dendritic cell type was more potent to support both the generation and the IFN-gamma production of autologous influenza matrix peptide-specific memory CD8 T cells as compared with dendritic cells generated in the presence of GM-CSF and IL-4. In conclusion, monocytes exposed to the cytokine milieu provided by CpG-A rapidly develop a dendritic cell-like phenotype that is well equipped to support CD8 T cell responses.

Adjuvants, Immunologic↗
PubMed2000

Image-guided central venous catheter placement for apheresis in allogeneic stem cell donors.

Peripheral blood stem cell harvest by apheresis is an increasingly important procedure utilized in the treatment of many malignancies. Whether autologous or allogeneic, it is frequently performed via peripheral access because of concern over major complications associated with central venous catheter placement. This study was to determine the safety and success, complications and premature failure rates for radiolocally placed ultrasound-guided non-tunneled central venous catheters placed for apheresis in a donor (allogeneic) population. One hundred central venous catheters were placed in ninety-one individuals for allogeneic stem cell harvest. Procedural success and complications relating to placement were noted in all. In 97 cases the number of needle passes required for venous cannulation and whether this was achieved with a single wall puncture was noted. Duration of catheterization and reason for removal were recorded in all cases. All catheters were placed by a right transjugular route. Venous cannulation and functioning line placement was achieved in every case; 92/97 (95%) required only a single needle pass and 84/97 (87%) only a single wall puncture. There were no placement related complications; 94 catheters were removed the same day with the remainder removed within 48 hr. All completed apheresis. Our study demonstrates the safe use of central venous catheters for apheresis in normal donors if ultrasound guidance is used for the puncture and the duration of catheterization is short.

Adolescent↗
PubMed1997

Factors influencing yields of progenitor cells for allogeneic transplantation: optimization of G-CSF dose, day of collection, and duration of leukapheresis.

Mobilization of hematopoietic progenitor cells by G-CSF was attempted on 89 occasions in 85 healthy donors. Three dose ranges of G-CSF were chosen for analysis: low (4-7.4 micrograms/kg), intermediate (7.5-10 micrograms/kg) and high (> 10 micrograms/kg). A target blood level for apheresis of 20 x 10(6)/L CD34+ cells was reached by day 3 in 75 patients (84%) and by day 4 in all but 1 (99%). Target yields above 2.5 x 10(6)/kg for 75 unmanipulated transplants were exceeded in a single collection in 73 donors (97%). Correlation of CD34+ cell yields to blood CD34+ cell level before leukapheresis was moderate only (r2 = 0.32). There was close linear correlation between processed volume and cumulative CD34+ cell yield, with a median r2 value of 0.98 (range 0.74-1.00). Yields of CD34+ cells achieved on day 3 were significantly lower after the high dose than after the intermediate G-CSF dose (21 +/- 3 versus 29 +/- 6 x 10(6)/L blood processed, p = 0.03). After the low dose of G-CSF, yields on day 4 were higher than on day 3 (48 +/- 10 versus 22 +/- 4 x 10(6)/L blood processed, p = 0.01). There was no difference between day 3 and day 4 yields with the intermediate G-CSF dose. In 73 of 93 (78%) leukaphereses, the CD34+ cell yield was more than 100% of the estimated intravascular CD34+ cells at the beginning of collection and ranged up to 342%. These data indicate that a daily dose of 7.5-10 micrograms/kg G-CSF, given as a multiple of 300 and 480 micrograms ampoules, is a convenient regimen giving adequate yields from a single collection on day 3 or 4 in most donors. Measuring blood CD34+ cell levels is of limited value in predicting yields, but monitoring CD34+ cell yields during leukapheresis may help to minimize unnecessary or inefficient collection.

Antigens, CD34↗
PubMed1995

Collection of progenitor cells for allogeneic transplantation from peripheral blood of normal donors.

Fourteen donors were given recombinant G-CSF to mobilize progenitor cells. Circulating CD34+ cells were monitored daily and leukapheresis was performed at 3-5 days when the level exceeded 20 x 10(6)/L. Monitoring of CD34+ cells collected at intervals during apheresis gave results within 20 min. Yields of 2.6-7.4 x 10(6) per kg recipient body weight were achieved in single aphereses of 2-4 h in all but two cases where the donor was substantially smaller than the recipient. These products were sufficient to establish engraftment, at least of granulocytes, in 11 five or six antigen matched recipients with high risk malignancy. Despite some complications donors tolerated the procedure well and the five individuals who had previously given marrow preferred these manoeuvres to bone marrow harvest. The ability to monitor CD34+ cells rapidly in the circulation and leukapheresis product facilitates an efficient collection technique for allogeneic BCT donors. Adequate yields could probably be achieved by a single harvest on days 2-4 in most donors.

Acute Disease↗
PubMed1987

Autoimmune thrombocytopenia and primary biliary cirrhosis with hypoglycemia and insulin receptor autoantibodies. A case report.

A 43-year-old woman with spontaneous episodes of neuroglycopenic hypoglycemia was found to have immune-mediated thrombocytopenic purpura and primary biliary cirrhosis. Hypoglycemia along with hyperinsulinemia suggested insulinoma. Serum c-peptide levels were disproportionately low, raising the possibility of factitious hypoglycemia. The patient's plasma contained circulating insulin receptor autoantibodies, thought to cause hypoglycemia by their insulin-like actions. With prednisone therapy, her other autoimmune features improved, and the hypoglycemia eventually resolved. Hypoglycemia mediated by insulin receptor autoantibodies should be considered in patients with fasting hypoglycemia and features suggesting an underlying autoimmune disorder before pursuing more invasive procedures. High-dose steroids may be life-saving in this disorder.

Adult↗
PubMed1985

Use of calcium channel blockers in hypoxic lung disease.

COPD patients who are hypoxic develop pulmonary hypertension primarily because alveolar hypoxia induces muscular hypertrophy of pulmonary arteries. This muscular hypertrophy will regress in animals if they receive continuous oxygen therapy. Since many COPD patients refuse to use oxygen continuously, calcium channel blockers, which inhibit hypoxic pulmonary vasoconstriction, may be effective adjuvant therapy. Nifedipine lowers pulmonary vascular resistance during rest and exercise in hypoxic COPD patients.

Calcium Channel Blockers↗