Search PubMed⌕ Search

Biomedical subjects

S Rowley

Publications and source records attributed to S Rowley.

At least 37 records · Page 2Linked to original sources
PubMed1995

Engraftment of patients with lymphoid malignancies transplanted with autologous bone marrow, peripheral blood stem cells or both.

Forty six patients with lymphoid malignancies receiving autologous transplants using three different sources of hematopoietic stem cells were compared for engraftment parameters. Thirteen patients (five with multiple myeloma, seven with non-Hodgkin's lymphoma and one with Hodgkin's lymphoma) received autologous marrow with post-transplant growth factors (group 1). During the same time interval, 14 patients (five with multiple myeloma, six with non-Hodgkin's lymphoma and three with Hodgkin's lymphoma) were transplanted with autologous marrow plus recombinant granulocyte colony-stimulating factor (rhG-CSF)-mobilized peripheral blood stem cells (PBSC) and post-transplant growth factors (group 2). Nineteen patients (seven with multiple myeloma and 12 with non-Hodgkin's lymphoma) received rhG-CSF mobilized PBSC and post-transplant growth factors (group 3). All PBSC were collected after G-CSF mobilization (16 micrograms/kg/day s.c. for 6 days) without prior chemotherapy. After high-dose myeloablative chemotherapy or chemoradiotherapy, the median days to recovery of neutrophils to levels of 0.5 and 1.0 x 10(9)/l were 12 vs. 9 vs. 9 days (P = 0.0003 (group 1 vs. group 2) and P = 0.53 (group 2 vs. group 3)) and 13 vs. 10 vs. 10 days (P = 0.0003 (group 1 vs. group 2) and 0.92 (group 2 vs. group 3)) for groups 1, 2 and 3, respectively. The median day to platelet transfusion independence was 22 vs. 11 vs. 11 days (P = 0.001 (group 1 vs. group 2) and P = 0.50 (group 2 vs. group 3)) for groups 1, 2 and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Symptoms, health and illness behaviour in cystic fibrosis.

A health diary was administered for 28 consecutive days over 3 non-consecutive months to 53 children and adolescents with Cystic Fibrosis (age 11-17 years). Response rates were 96% for the first, 84% for the second and 58% for the third month. Ill health actions such as missing school or staying in bed, ranged from 0 to 21% of diary days and showed an apparent seasonal variation being highest in the month of May. Analysis of variance demonstrated significant association between health actions, use of additional medicines and disease severity although no such associations were found for worries and concerns and overall assessment of the day. Most were not very bothered by symptoms or complaints, the highest visual analogue score on a scale of 0-10 in a single patient was 2.4 for coughing. A striking finding was the disparity between perceived vulnerability and subsequent experience with predictions of common symptoms such as cough and shortness of breath scoring 4-5 times higher than actually experienced. These children and adolescents were coping very successfully with their disease although the disparity between perceived vulnerability and subsequent experience indicates some uncertainty about the effects of the disease and/or lack of understanding about medical therapy.

Activities of Daily Living↗
PubMed1994

Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation.

Factors affecting mobilization and engraftment were analysed in 54 patients undergoing transplant using autologous PBSCs mobilized with high-dose recombinant granulocyte stimulating factor (rhG-CSF). Patients received 5-7 d of rhG-CSF, 16 micrograms/kg/d, administered subcutaneously. PBSCs were harvested by leukapheresis using automated continuous-flow blood cell separators beginning on day 4 of rhG-CSF, processing 10 litres of whole blood, for 2-6 consecutive days. Transplants were performed for the following diseases: breast cancer (n = 22), non-Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7). Engraftment was rapid with patients reaching a neutrophil count of 1 x 10(9)/l a median of 12 d (range 9-22) after transplant. Platelets > 20 x 10(9)/l independent of transfusion support were achieved a median of day 10 (range 7-60) after infusion. Multiple factors potentially influencing engraftment were examined using a Cox regression model. The number of CD34+ cells per kg was highly correlated with the time to achievement of granulocyte and platelet recovery (P < 0.012, 0.0001). The use of a post-infusion growth factor and a radiation preparative regimen was important for neutrophil recovery, and a diagnosis of breast cancer was important for platelet recovery. In an analysis by linear regression of the logarithm of CD34+ cells collected, lower age, marrow without disease, no prior radiation, and lower number of prior chemotherapy regimens, were important factors influencing larger numbers of CD34+ cells in collections.

Adolescent↗
PubMed1994

Isolation of human hematopoietic stem cells.

Human hematopoietic stem cells are contained within a population of marrow cells that expresses the CD34 antigen but not other antigens associated with commitment to specific lineages. Evidence that stem cells capable of maintaining long-term hematopoiesis are within this CD34+ lineage-negative (Lin-) population is reviewed, including in vivo studies in humans and nonhuman primates. In vitro studies of the CD34+ Lin- population have indicated that the blast-sized cells, which are presumably in cycle, proliferate and give rise to colony-forming cells in the presence of combinations of growth factors, including c-kit ligand and interleukin-3 (IL-3). Recent studies have examined the factors required for the growth of the quiescent subset of the CD34+ Lin- cells, identified as small to medium lymphocyte-sized cells that resist treatment with 4-hydroperoxycyclophosphamide, a known characteristic of the marrow-repopulating cell. These studies have shown that an interaction with marrow stromal cells is required, in addition to c-kit ligand and IL-3, to induce these cells to proliferate and form multiple colony-forming cells. These studies have further indicated that this effect of stroma is mediated by a soluble factor(s). This activity may represent a novel factor(s) and/or a novel combination of growth factors.

Antigens, CD↗
PubMed1994

Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies.

The purpose of this study was to determine the maximal tolerated dose of thiotepa administered with busulfan 12 mg/kg and melphalan 100 mg/m2 followed by autologous stem cell transplantation in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose busulfan 12 mg/kg, melphalan 100 mg/m2 and escalating doses of thiotepa 450-550 mg/m2 followed by infusion of cryopreserved autologous peripheral blood stem cells (n = 26) or marrow (n = 2). The maximum tolerated dose was determined to be busulfan 12 mg/kg, melphalan 100 mg/m2 and thiotepa 500 mg/m2. Two of three patients receiving thiotepa 550 mg/m2 experienced grade 3 colitis. Twenty patients were enrolled at the maximum tolerated dose and the incidence of grade 3-4 regimen-related toxicity and mortality was 10% and 5%, respectively. Ninety-five per cent of patients experienced grade 1-2 mucositis, 50% grade 1-2 gastrointestinal toxicity, 35% grade I hepatic toxicity and 20% experienced grade 1-2 skin toxicity. The median time to achieve a granulocyte count of 0.5 x 10(9)/I was 10 days (range 8-20 days) and platelet transfusion independence was 10 days (range 1-26 days). Five of ten patients with stage 4 refractory breast cancer achieved a complete and two a partial remission with a complete response rate of 50% and a overall response rate of 70%. In conclusion, busulfan, melphalan and thiotepa can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy sensitive malignancies are warranted.

Adolescent↗
PubMed1994

[Otorhinolaryngologic symptoms caused by the intranasal abuse of cocaine. Report of a case].

Cocaine abuse is associated with medical complications that depends on the route of administration. Intranasal "snorting" is associated with complications secondary to chronic irritation on the nasal mucosa. A case of long-standing intranasal cocaine abuse is presented with unusual complications: septal and palatal necrosis, osteolytic sinusitis and bilateral optic neuropathy. The CT scan demonstrated a soft-tissue mass in etmoid and sphenoidal sinus and orbits. The histopathologic examination revealed a nonspecific pattern of chronic inflammation with no evidence suggestive of infection, neoplasm or lethal midline granuloma. The case had a fatal outcome. Because of the constellation of singular manifestations we discuss the differential diagnosis. Interdisciplinary approach is stressed. Emphasis is made in early diagnosis.

Administration, Intranasal↗
PubMed1993

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor.

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.

Adult↗
PubMed1993

Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor.

Peripheral blood mononuclear cells (PBMC) were collected after the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and used as the sole source of hematopoietic stem cells after myeloablative therapy with busulfan (Bu) and cyclophosphamide (Cy). These studies were performed in 12 patients with malignancies (4 non-Hodgkin's lymphoma, 5 breast cancer, 1 testicular carcinoma, 1 Wilm's tumor, and 1 undifferentiated carcinoma) who had bone or bone marrow disease or had low marrow cellularity. rhG-CSF (16 micrograms/kg/d) was administered for 5 to 7 days by subcutaneous injection and PBMC were collected for 2 to 5 days beginning on day 4 after initiation of rhG-CSF, using continuous-flow blood-cell separators that processed 10 to 12 L of whole blood. From a median of three collections, a mean of 24.0 x 10(8) (+/- 10.5 SD) total nucleated cells/kg containing 12.6 x 10(8) (+/- 4.5 SD) mononuclear cells/kg, 7.3 x 10(6) (+/- 4.3 SD) CD34+ cells/kg and 20.5 x 10(4) (+/- 28.1 SD) granulocyte-macrophage colony-forming units (CFU-GM)/kg were harvested and cryopreserved. After the administration of Bu 14 to 17 mg/kg and Cy 120 to 150 mg/kg, PBMC were thawed and infused. One patient received rhG-CSF after the infusion of PBMC and the remaining 11 patients did not receive postinfusion growth factors. Mean days to recovery of neutrophil levels of 0.1, 0.5, and 1.0 x 10(9)/L were 11.4 (range, 9 to 13), 12.7 (range, 10 to 15), and 13.6 (range, 11 to 16) and the mean day to platelet transfusion independence was 13.3 (range, 7 to 49). Time to recovery of neutrophils to 0.5 and 1.0 x 10(9)/L and platelets to 20 x 10(9)/L was more rapid than in historical patients treated with Bu and Cy who received marrow alone or marrow followed by the posttransplant administration of rh-G or GM-CSF. No graft failures have been observed with a follow-up of 4 to 12 months. These results indicate that PBMC collected after rhG-CSF lead to rapid hematopoietic recovery after myeloablative chemotherapy.

Antigens, CD↗
PubMed1993

Chromosome abnormalities in patients treated with 4-hydroperoxycyclophosphamide-purged autologous bone marrow transplantation.

Autologous bone marrow transplantation (ABMT) offers potentially curative therapy for patients with acute leukemia and lymphoma, yet little information exists about the chromosome abnormalities observed in ABMT recipients. Clonal abnormalities of chromosome 1 were reported by van den Akker. We report the cytogenetic results of 55 patients who underwent ABMT between November 1987 and July 1990: acute nonlymphocytic leukemia (ANLL, 22), acute lymphocytic leukemia (ALL, eight), Hodgkin's disease (seven), lymphoma (16), other (two). ANLL patients received busulfan and cytoxan, and the others received cytoxan and total body irradiation as their preparative regimen before transplant. BM was purged ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 30-100 micrograms/ml before reinfusion to kill tumor cells. Cytogenetic analysis was performed before and after transplant. Between one and four posttransplant specimens of BM were analyzed per patient (range 36-921 days). Chromosome abnormalities were observed in 14 of 55 patients after transplant. Seven had clonal abnormalities; all were in leukemic relapse, and one karyotype had complex rearrangements. Clonal abnormalities of chromosome 1 were not observed. Seven patients had nonclonal changes, and three of these have had overt clinical relapse. Our data suggest that clonal abnormalities observed posttransplant are best explained by clinical relapse of tumor and that ex vivo marrow purging with 4-HC is not likely to induce clonal chromosome abnormalities in normal cells. Long-term observation of these patients will be required to answer that question definitively, however.

Adolescent↗
PubMed1993

Consequences of cryopreserving first remission autologous marrow for use after relapse in patients with acute myeloid leukemia.

Ninety-eight patients with AML had marrow harvested and cryopreserved at a median of 6 months (range 1-36 months) after achieving first CR with the intent of performing an ABMT at the first sign of relapse. Thirty-three of the 98 patients have not relapsed and 32 survive at a median of 64 months (range 10-105 months) after marrow storage. Sixty-five of the 98 patients relapsed at a median of 7 months (range 1-53 months) after marrow storage. The survival at 2 and 4 years for the 65 patients who relapsed was 22% and 8% respectively. Sixteen of 24 patients treated initially with chemotherapy were ultimately transplanted and two are surviving 21 and 41 months following ABMT and allogeneic marrow transplant respectively. There were no survivors among the eight patients treated with chemotherapy who were not transplanted. Thirty-eight of the 65 patients who relapsed proceeded directly to ABMT without attempts at remission induction, and eight survive disease-free 15-114 months following ABMT. One of the first 17 patients treated with cyclophosphamide and total body irradiation survives without relapse. The probabilities of relapse-free survival, non-relapse mortality, and relapse for the 17 most recent patients prepared with busulfan-containing regimens were 41%, 39% and 32% respectively. Surviving patients had longer first remissions (p = 0.08) and lower peripheral blood blast counts at the time of transplant (p = 0.02) when compared with patients who died. These data suggest that ABMT in untreated first relapse is a reasonable approach for the treatment of patients with AML who relapse.

Adolescent↗
PubMed1991

Arachidonic acid and docosahexaenoic acid are increased in human colorectal cancer.

Increased arachidonic acid concentrations in experimental rodent colonic cancer have been described recently. In humans, a reduced erythrocyte stearic acid to oleic acid ratio has been reported in patients with colorectal cancer and it has been proposed that similar changes exist in the cancer tissue. The long chain fatty acids in the cancers of 15 patients with colorectal cancer were measured and compared with values in the unaffected mucosa. The values were expressed as mean (SD) mg fatty acid/g tissue and compared by analysis of variance. In the cancer tissue arachidonic acid was increased (0.703 (0.109) mg/g v 0.603 (0.127) mg/g, p less than 0.05) as was docosahexaenoic acid (0.211 (0.066) mg/g v 0.148 (0.039) mg/g, p less than 0.001). In contrast, the stearic acid to oleic acid ratio in the cancer tissue was increased rather than decreased, as previously suggested (0.36 (0.05) v 0.29 (0.7), p less than 0.01). Increased arachidonic acid and docosahexaenoic acid concentrations may be related to reduced lipid peroxidation, which is a feature of rapidly growing cells. Alternatively, the increased arachidonic acid values could be due to enhanced desaturase activity upon linoleic and linolenic acid, leading perhaps to increased formation of prostaglandins and other lipoxygenase products.

Aged↗
PubMed1991

Use of the OM-11-906 monoclonal antibody for determining p62 c-myc expression by flow cytometry in relation to prognosis in colorectal cancer.

The expression of the c-myc protein product (p62 c-myc) and deoxyribonucleic acid (DNA) ploidy status was determined by a flow cytometric technique in 83 patients with colorectal cancer followed up for a median of 30 months (range 6-60 months). The OM-11-906 antibody, used to detect p62 c-myc, revealed a 62 kDa and 45 kDa band on Western blots in tumours. Correlation of quantitative dot blotting of tumour mRNA to flow cytometric p62 c-myc expression was good (r = 0.87, P less than 0.01). Levels of p62 c-myc varied in colorectal cancer and low levels (less than 20 fluorescein units) correlated with improved survival (log rank chi 2 = 4.69, df = 1, P = 0.03), and this was a better prognostic index than DNA ploidy (log rank analysis chi 2 = 2.38, df = 1, P less than 0.1). Although expression of the c-myc gene was found, using the OM-11-906 antibody, to be a prognostic feature in colorectal cancer, these and other results need to be interpreted with caution given the presence of two protein bands by Western blotting.

Adult↗
PubMed1990

Reduced tumour growth of the human colonic cancer cell lines COLO-320 and HT-29 in vivo by dietary n-3 lipids.

Seventy-five nude mice received subcutaneous inoculation with 1 X 10(7) cells of the human colonic cancer cell lines COLO-320 or HT-29. Tumour growth was assessed over 4 weeks in animals given one of three iso-caloric diets; standard diet, high saturated fat (20% coconut) diet and high n-3 fat (20% Maxepa fish oil) diet. The n-3 diet produced significant tumour growth reduction compared to the other diets for COLO-320 at 3 to 4 weeks (P less than 0.05 at least) and similarly for HT-29 at 4 weeks (P less than 0.05). Significant incorporation of n-3 fatty acids occurred in red cell membranes, adipose tissue and both neutral lipid and phospholipid fractions of tumour lipids in animals fed Maxepa (P less than 0.01 at least). This was accompanied by reduction of linoleic acid and arachidonic acid in these tissues (P less than 0.01 at least) but was most marked in the metabolically labile phospholipid fraction. There was high mitotic activity in the tumours from all the groups but there was no difference according to diet.

Animals↗
PubMed1990

Density-gradient separation for 4-hydroperoxycyclophosphamide purging of autologous bone marrow grafts.

We studied density-gradient separation of autologous bone marrow grafts in preparation for ex vivo 4-hydroperoxy-cyclophosphamide (4-HC) purging. A two-step procedure of buffy coat isolation followed by Ficoll-diatrizoate separation was used. Buffy-coat cells were isolated primarily either using the COBE 2991 Blood Cell Processor or Haemonetics 30 Cell Separator. All density-gradient separations were performed using the COBE 2991. The nucleated cell recoveries after buffy-coat isolation were 44.3 +/- 10.4% and 85.1 +/- 10.5% (+/- standard deviation, P less than 0.001) for the Haemonetics 30 and COBE 2991 isolated grafts, respectively. The final nucleated cell recoveries after density-gradient separation for these two buffy-coat techniques were 24.2 +/- 10.1% and 29.5 +/- 14.7% (p = 0.30). Compared to manual density-gradient separation, the techniques using the COBE 2991 recovered slightly higher numbers of nucleated cells and CFU-GM. The red blood cell concentration of the 4-HC incubation mixture was 1.0 +/- 0.6% and the CFU-GM survival after treatment was 2.4 +/- 2.6%. The variability in CFU-GM survival after 4-HC incubation of the density-gradient separated grafts appears less than previous experience treating buffy-coat cells. Density-gradient separation of autologous bone marrow appears to provide a more uniform treatment with 4-HC and may improve the clinical transplant course of the autograft recipient.

Bone Marrow↗
PubMed1989

Advantages of nonsurgical treatment of bile duct stones.

A variety of effective nonsurgical forms of treating bile duct stones have emerged to challenge the traditional role of surgery. Four distinct philosophies have evolved upon which to base treatment: the partisan, supermarket, combination, and deductive philosophies. Adopting the latter, it is argued that surgery remains the gold standard for the great majority of patients. Surgery should, however, give way to non-operative forms of treatment in those who are at high surgical risk because of concomitant medical problems, acute cholangitis and severe gallstone pancreatitis. These newer treatments should increase the proportion of symptomatic patients amenable to treatment.

Bile Duct Diseases↗