Search PubMed⌕ Search

Biomedical subjects

R A Abrams

Publications and source records attributed to R A Abrams.

At least 127 records · Page 7Linked to original sources

Postcryopreservation growth of human CFU-GM: sequential examination of methodologic factors.

Postcryopreservation growth of human CFU-GM might provide insight into the reconstitutive potential of human marrow preparations cryopreserved for subsequent autologous hematopoietic reconstitution. Ultimately, the utility of such measurements will depend on: whether comparison of pre- and postcryopreservation CFU-GM values is a guide to loss of reconstitutive potency during or following cryopreservation, and whether such measurements are consistent and reproducible. In our hands, direct, unmanipulated plating of CFU-GM after freezing and thawing resulted in extremely poor CFU-GM growth. Consequently, we undertook a set of sequential experiments designed to optimize technical conditions for growing human CFU-GM after cryopreservation. Utilizing stepwise examinations of washing, multiple plating factors, dilution rate, and diluent, we were able to increase consistently fractional recovery of postcryopreservation CFU-GM growth per 2 X 10(5) cells plated from 8% to 56%. Our results underscore the importance that technical factors (other than freezing conditions) play in the postcryopreservation growth of human CFU-GM.

Bone Marrow Cells↗

Cyclophosphamide treatment expands the circulating hematopoietic stem cell pool in dogs.

Increased numbers of circulating granulocyte-monocyte precursor cells (CFUc) have been observed in the peripheral blood of man after antineoplastic chemotherapy. We have developed a canine model to study the biologic significance of this phenomenon for hematopoietic reconstitution following hematopoietically lethal exposure to total body irradiation (TBI). After cyclophosphamide administration, a 16-fold expansion of circulating CFUc numbers was observed during the period of rapid leukocyte recovery that occurred after the chemotherapy-induced leukocyte nadir. We had previously noted this association between leukocyte recovery and CFUc expansion in our human studies. After 900 rad TBI hematopoietic reconstitution was attempted with autologous, cryopreserved collections of peripheral blood mononuclear cells obtained either at times of post-cyclophosphamide CFUc expansion (group A, 14 dogs) or without CFUc expansion (group B, 12 dogs). Asd compared to group B collections, group A collections contained 11-fold more CFUc and were 12.5-fold more potent in fostering hematopoietic recovery after TBI. These results suggest that the expansion of CFUc numbers we observed was accompanied by a similar expansion of more primitive hematopoietic stem cell numbers. We conclude that chemotherapy-induced expansion of circulating CFUc numbers appears to be of substantial import in effecting hematopoietic reconstitution--an observation that may be of significance for further studies of autologous hematopoietic reconstitution in man.

Animals↗

Amplification of circulating granulocyte-monocyte stem cell numbers following chemotherapy in patients with extensive small cell carcinoma of the lung.

Circulating numbers of committed granulocyte-monocyte hematopoietic stem cells (CFUc) were measured in the peripheral blood of 20 patients with extensive-stage small cell lung carcinoma during induction chemotherapy. All patients received cyclophosphamide, doxorubicin, VP16-213, and vincristine. CFUc measurements were made either weekly or twice weekly. As leukocytes declined following chemotherapy, circulating CFUc numbers also declined. However, as leukocytes recovered from their nadir levels, circulating CFUc numbers per mononuclear cell and per ml of whole blood became substantially expanded in 19 and 17, respectively, of the 20 patients studied. Per mononuclear cell, the median CFUc expansion was 7.9-fold, and the highest expansion seen was 157-fold. Per mol of blood, the median CFUc expansion was 6.7-fold, and the highest expansion seen was 46-fold. The magnitude of the amplification, its occurrence in 85 to 95% of patients studied, and its association with leukocyte recovery strongly suggest that appropriately timed collections of peripheral blood mononuclear cells obtained during leukocyte recovery from nonablative chemotherapy could be used to provide hematopoietic stem cells in numbers sufficient to effect hematopoietic reconstitution after subsequent marrow-ablative therapy.

Adult↗

Haemopoietic recovery in Ewing's sarcoma after intensive combination therapy and autologous marrow infusion.

After the completion of combination therapy designed to achieve local control of Ewing's sarcoma, 13 patients with either truncal primary lesions or proven metastases were given 150 rad of total body irradiation over 5 weeks followed by cyclophosphamide, doxorubicin, imidazole carboxamide, and vincristine. 11 patients received autologous cryopreserved marrow infusions. In 2 patients marrow collections were not attempted. Two patterns of haemopoietic recovery were observed: 8 patients, who had received marrow infusions, showed leucocyte, granulocyte, and platelet recovery by 27, 28, and 30 days. 5 patients, 3 of whom had also received marrow, showed more delayed recovery with leucocyt, granulocyte, and platelet recovery at 45, 53, and 77+ days. Delayed recovery in patients receiving marrow seemed to correlate with aberrations in marrow freezing-rate during phase change, and these aberrations could be shown to diminish post-freeze recovery of marrow granulocyte-monocyte precursor cells.

Adolescent↗

Attitudes toward National Health Insurance: dentists, dental students, and dental hygiene students.

The attitudes toward National Health Insurance held by 126 second year dental students and 108 second year dental hygiene students enrolled in the state of Wisconsin, U.S.A., were measured and compared with the attitudes held by practicing dentists in the U.S.A. Although some similarities were noted, marked differences were revealed, with students, generally, preferring broader coverage and more government involvement than practicing dentists. There is virtually no published data in this area, and more research is needed, as the success or failure of any National Health Insurance plan depends critically on the attitudes of both health care providers and those studying to become health care providers.

Adult↗

Result of attempted hematopoietic reconstitution using isologous, peripheral blood mononuclear cells: a case report.

In order to test the effect of peripheral blood mononuclear cell infusions on hematopoietic recovery in man we intensively leukapheresed a normal identical twin and obtained 9.8 x 10(10) peripheral blood mononuclear cells containing 4 x 10(5) CFU-C. These isologous cells were infused into his identical twin brother who had received 150 rad of total body irradiation and intensive combination chemotherapy as adjuvant therapy for Ewing's sarcoma. When compared to other patients receiving similar treatment, leukocyte recovery was accelerated by 3-4 wk, and occurred at a rate comparable to that induced by infusion of autologous cryopreserved marrow. Recovery of granulocytes, monocytes and platelets was not accelerated. The low number of CFU-C present in the preparation used ((one-eighth the number of CFU-C we usually obtain from bone marrow autograft collections) may have led to the pattern of hematopoietic recovery we observed in this patient.

Adolescent↗

Prospects for accelerating hematopoietic recovery following myelosuppressive therapy by using autologous, cryopreserved hematopoietic stem cells collected solely from the peripheral blood.

Cryopreserved, autologous stem cells collected from human marrow have been used to accelerate hematopoietic recovery following intensive radiation or chemotherapy. The harvesting of adequate numbers of bone marrow cells for purposes of hematopoietic reconstitution is a potentially morbid procedure and requires the use of general anesthesia and blood transfusion during anesthesia. The ability to accelerate hematopoietic recovery using cells collected solely from the peripheral blood would obviate the requirement for a general anesthetic and avoid the discomfort experienced by patients following the procedure. Collection of hematopoietic stem cells from the peripheral blood should involve limited morbidity and risk and be well suited to repeated application in individual cases. An increasing body of in vitro and in vivo data in animals and man suggests that this goal may soon be within reach.

Blood Preservation↗

Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators.

This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72% of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P < 0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P < 0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.

Adenocarcinoma↗