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Biomedical subjects

F M Stewart

Publications and source records attributed to F M Stewart.

At least 73 records · Page 4Linked to original sources
PubMed1993

Sinonasal undifferentiated carcinoma: a ray of hope.

In 1987, we published a case series of a newly-described, highly malignant neoplasm, termed sinonasal undifferentiated carcinoma, in which treatment results were poor. In this updated study, we report the followup for the original three surviving patients and for six additional cases whose tumors were diagnosed between January 1987 and October 1991. These data suggest that the prognosis for patients with localized disease may be better than originally described.

Carcinoma↗
PubMed1993

Indications and relative indications for stem cell transplantation in non-Hodgkin's lymphoma.

High dose chemotherapy with or without total body irradiation and autologous stem cell rescue has proven to be effective treatment to cure patients with relapsed intermediate grade and high grade non-Hodgkin's lymphoma. Important factors for selection of candidates most likely to do well with these approaches include patients whose disease is responsive to conventional therapy and those who have minimal disease volume at the time of transplant. The treatment-related mortality of autologous stem cell transplantation has diminished from 20% to less than 5% with improved supportive care and selection of patients with less advanced disease. Although the treatment-related mortality of allogeneic stem cell transplantation may be as high as 20-40%, a graft versus lymphoma effect may decrease relapse with the result that overall survival is not substantially different between autologous and allogeneic transplantation. The definitive indications for stem cell transplantation include patients who have relapsed with intermediate or high grade NHL. Relative indications include intermediate/high grade non-Hodgkin's lymphoma patients, "high risk" first complete remission (CR), resistant relapse; low grade non-Hodgkin's lymphoma in sensitive or resistant relapse, advanced disease (sensitive or resistant relapse, transformation), first CR (younger patients). Relative contraindications include specific patient profiles such as bulky high grade lymphoma which progresses on appropriate conventional therapy, poor performance status, active serious infection, serious cardiac, renal, pulmonary or liver dysfunction, active, central nervous system (CNS) disease unresponsive to cranial irradiation/intrathecal therapy. For patients with previous marrow involvement or active marrow involvement at the time of harvest or transplant, "purged" autografts, peripheral blood stem cell transplantation and allografts have been used successfully.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The addition of oatbran to a low fat diet has no effect on lipid values in hypercholesterolaemic subjects.

AIMS: to assess the hypocholesterolaemic effect of adding 50 g of oatbran to the diet of hypercholesterolaemic subjects already prescribed a diet with less than 30% of energy from fat. METHODS: twenty-nine volunteers aged 21-67 years with total serum cholesterol levels 5.59-8.5 mmol/L prescribed a diet containing less than 30% of energy intake as fat, and with a body mass index between 19.8 and 29.3, were enrolled in a crossover study to assess the effect of the addition to the diet of 50 g daily of oatbran. After six weeks of an oat-free control diet, subjects were randomised to eat 50 g daily of oatbran or to continue on the oat-free diet. Six weeks later the subjects crossed to the alternative diet for a further six week period. Lipid levels were assessed in weeks five and six of each study period. RESULTS: twenty-four subjects completed the study consuming 51.7 (SD 15.5) g of oatbran daily during the treatment phase. No significant difference was seen between the oatbran and control diet periods in body mass index, energy or fat intake, or in total cholesterol, LDL and HDL fractions, apolipoprotein A1 and B levels, or triglyceride levels. Considerable variation was observed between the paired lipid results. CONCLUSIONS: ingestion of 50 g of oatbran daily by hypercholesterolaemic subjects on a low fat diet showed no influence on serum lipid levels. The importance of using at least duplicate samples in assessing changes in lipid values is emphasised.

Adult↗
PubMed1992

Hypoplastic/aplastic anemia. Role of bone marrow transplantation.

For young patients with SAA, allogeneic bone marrow transplantation is the best curative approach. Major obstacles to the success of allogeneic bone marrow transplantation include GVHD, infections, and graft rejection. A careful management approach to patients prior to transplant may decrease some of these complications. Immunosuppressive therapy should be utilized in older patients with SAA. Underlying clonal disorders, eg, acute leukemia and recurrent aplasia, are late complications.

Anemia, Aplastic↗
PubMed1991

Fluctuation analysis: the effect of plating efficiency.

This paper supplements an earlier paper which explained how to calculate the probability distribution of the number of mutants that would be observed in a fluctuation test experiment. The formulas in that work give the distributions to be expected under a wide variety of experimental conditions, but the method it uses when only a fraction of the mutants will produce visible colonies are clumsy and inefficient. Here I describe efficient procedures for dealing with that case, provided that the mutation rate per cell division remains constant during the experiment.

Colony Count, Microbial↗
PubMed1991

The role of the chest roentgenogram in febrile neutropenic patients.

In a retrospective review of patients with neutropenia and fever, we sought to determine how often roentgenograms detected pulmonary disease, especially pneumonia, not suggested by signs and symptoms. Further, we sought to determine how often therapy was changed as a result of roentgenographic findings. Overall, 41 (22%) of 187 chest roentgenograms obtained during initial febrile episodes, recurrent fevers, or persistent fevers were abnormal. While most patients had signs and symptoms suggesting the presence of pulmonary disease, 17% had roentgenographic abnormalities detected in the absence of such findings. During initial febrile episodes, therapy was not changed in response to findings on the chest roentgenogram. However, during episodes of persistent or recurrent fever, findings on chest roentgenograms led to changes in therapy in eight (61%) of 13 episodes of which six (40%) resulted in clinical improvement. Chest roentgenograms were therefore found to be an important diagnostic tool in evaluating recurrent or persistent fever in the neutropenic patient but of little use during initial febrile episodes.

Bone Marrow Transplantation↗
PubMed1990

Treatment of small-cell carcinoma of the cervix with weekly combination chemotherapy.

Three patients with small-cell carcinoma of the cervix entered a pilot study of combination chemotherapy with agents that are not cross-resistant. Two patients had local disease and the third had extensive metastatic disease of the liver. The regimen consisted of weekly chemotherapy for 16 weeks with cisplatin, vincristine, methotrexate, doxorubicin, cyclophosphamide and etoposide followed by radiotherapy and/or surgery. The two patients with local disease achieved a pathological complete response, with no evidence of disease at 24 months and 15 months from diagnosis. The third patient achieved a partial response and is alive at 13 months with progressive disease. Side-effects were tolerable.

Adult↗
PubMed1990

Fluctuation analysis: the probability distribution of the number of mutants under different conditions.

In the 47 years since fluctuation analysis was introduced by Luria and Delbrück, it has been widely used to calculate mutation rates. Up to now, in spite of the importance of such calculations, the probability distribution of the number of mutants that will appear in a fluctuation experiment has been known only under the restrictive, and possibly unrealistic, assumptions: (1) that the mutation rate is exactly proportional to the growth rate and (2) that all mutants grow at a rate that is a constant multiple of the growth rate of the original cells. In this paper, we approach the distribution of the number of mutants from a new point of view that will enable researchers to calculate the distribution to be expected using assumptions that they believe to be closer to biological reality. The new idea is to classify mutations according to the number of observable mutants that derive from the mutation when the culture is selectively plated. This approach also simplifies the calculations in situations where two, or many, kinds of mutation may occur in a single culture.

Bacteria↗
PubMed1990

Acute promyelocytic leukemia: impact of hemorrhagic complications on response to induction chemotherapy and survival.

From 1976 to 1989, 21 adult patients with previously untreated acute promyelocytic leukemia were seen at the University of Virginia Hospital. We reviewed their cases retrospectively to determine the impact of hemorrhagic complications and other factors on treatment outcome. We observed a complete remission rate of 35%; the median survival in complete responders was 15 months. Evidence of disseminated intravascular coagulation was found in 13 (62%) of the 21 cases at diagnosis. Fatal intracranial hemorrhage was the leading cause of death, occurring in eight (40%) of the 20 patients evaluated. Initial leukocyte count greater than 4.0 x 10(9)/L and platelet count less than 20 x 10(9)/L were significantly associated with an increased risk of intracranial hemorrhage. In patients with disseminated intravascular coagulation, the rate of intracranial hemorrhage was reduced by treatment with heparin. The high mortality of 40% (8/20) due to intracranial hemorrhage during induction was a major contributor to the low complete remission rate of 35% (7/20) in this series of consecutive unselected patients with newly diagnosed acute promyelocytic leukemia.

Adolescent↗
PubMed1990

Estimating the rate of plasmid transfer: an end-point method.

We describe a method for determining the rate parameter of conjugative plasmid transfer that is based on single estimates of donor, recipient and transconjugant densities and the growth rate in exponential phase of the mating culture. The formula for estimating the plasmid transfer rate, gamma, was derived from a mathematical model describing cell growth and plasmid transfer in batch culture. Computer simulations were used to explore the sensitivity of this method to the realities of bacterial life, such as growth rate differences, plasmid segregation and transitory derepression of pilus synthesis. As predicted by the theory, mating experiments with the plasmid R1 in Escherichia coli K12 demonstrated that the estimate gamma is unaffected by cell density, donor:recipient ratio and mating time. Unlike previous techniques, our method allows us to investigate the effect of environmental factors on plasmid transfer rates when these factors also influence population growth rates. To illustrate this, we examined the effect of temperature on the rate of plasmid transfer.

Computer Simulation↗
PubMed1990

Cunninghamella bertholletiae: an unusual agent of zygomycosis.

Cunninghamella bertholletiae shares many of the features typical of the other agents causing zygomycoses. Those who are immunocompromised constitute the major patient population at risk; the agents as a group are aggressive, the disease is often disseminated, and the pathologic picture of vascular invasion and tissue infarction is common. Unlike other agents of zygomycoses, Cunninghamella bertholletiae infection remains difficult to treat successfully even after early diagnosis and appropriate therapy.

Humans↗
PubMed1989

Cisplatin, 5-fluorouracil, mitomycin C, and concurrent radiation therapy with and without esophogectomy for esophageal carcinoma.

Twenty-nine patients with carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) (1000 mg/m2/d as a continuous intravenous [IV]infusion on days 1 through 4), cisplatin (100 mg/m2 IV on day 1), mitomycin C (10 mg/m2 IV on day 1), and concurrent radiation therapy (4500 cGy/4.5 wk). If no disease progression was observed, operable patients underwent surgery 4 to 6 weeks after completion of radiation therapy. A thoracotomy with a gastric pull-through operation was performed in the first six patients. Subsequently, a transhiatal ("blunt") esophagectomy was used. Twenty-five patients had squamous cell histology and four had adenocarcinoma. Of 25 patients with squamous cell carcinoma, 13 underwent esophagectomy. The clinical complete response rate was 61% (eight of 13 patients), with a pathologic complete remission documented in five of 13 patients (38%). The overall local tumor sterilization rate was 53% (seven of 13 patients). In the 12 patients who did not undergo surgery after chemoradiotherapy, four had a complete clinical response (33%) and five had a partial response (41%). Symptoms or signs of local disease recurrence or stricture were noticed in ten of 12 patients who did not undergo surgery (83%), compared with 28% of patients who underwent surgery. The median survival time of the group receiving surgery was 10 months, compared with 5 months for those who did not undergo operation (P = 0.027). Patients undergoing transhiatal esophagectomy had shorter postoperative hospital stays and fewer serious complications, compared with patients undergoing transthoracic esophagectomy. The use of chemoradiotherapy and transhiatal esophagectomy for esophageal carcinoma should be evaluated using alternative sequences of treatment (e.g., postoperative therapy) to reduce toxicity while maintaining local control of disease.

Adenocarcinoma↗
PubMed1989

Detection of a human CFC with a high proliferative potential.

Colony forming cells (CFC) with high proliferative potential have been detected in nutrient agar cultures of human bone marrow cells containing recombinant human interleukin-3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF). These CFC were detected by the formation of large colonies with diameters greater than 0.5 mm and containing approximately 50,000 cells after 28 days incubation. The incidence of these CFC was only two in 100,000 normal bone marrow cells; however, bone marrow from patients treated with 5-fluorouracil contained up to sevenfold higher numbers of these CFC. The characteristics of these CFC, multifactor-responsive progenitors with high proliferative potential, requiring a prolonged growth period in culture and showing a relative preservation in marrow from individuals pretreated with 5-fluorouracil, are consistent with a human cell type equivalent to the primitive murine progenitor termed HPP-CFC.

Adolescent↗
PubMed1989

High-dose chemotherapy and autologous marrow transplantation for esthesioneuroblastoma and sinonasal undifferentiated carcinoma.

Eight patients with recurrent esthesioneuroblastoma or sinonasal undifferentiated carcinoma of the nasal or sinus cavities were treated with high-dose chemotherapy and autologous bone marrow transplantation. All patients had stage C disease initially and had received extensive prior conventional treatment with surgery, radiotherapy, and chemotherapy. Two patients achieved prolonged relapse-free survival for 18+ and 60 months. The latter patient relapsed at 60 months, but died of progressive disease after a second transplant. Two additional patients remain alive without disease progression at 17+ and 31+ months posttransplant. No deaths occurred secondary to toxicity. Progression of tumor accounted for failure in five patients. High-dose chemotherapy and autologous bone marrow transplantation should be considered as a salvage regimen for selected patients who fail conventional therapy for these diseases.

Adult↗
PubMed1989

Unusual sinonasal small-cell neoplasms following radiotherapy for bilateral retinoblastomas.

Two patients developed sinonasal small-cell neoplasms that arose 22 years and 37 years, respectively, following radiotherapy for bilateral retinoblastomas. The tumors were composed of small cells with scant cytoplasm and had a few scattered Homer-Wright rosettes. Immunohistochemically, one tumor was positive for keratin (CAM 5.2 and AE1/AE3), epithelial membrane antigen, and neuron-specific enolase. The other neoplasm was immunoreactive for keratin (CAM 5.2 only) and neuron-specific enolase; it also had focal immunopositivity for S-100 protein, desmin, and muscle-specific actin. Both were negative for CEA, vimentin, melanocyte-specific antigen (HMB45), chromogranin A, synaptophysin, Leu-7, 200 kd neurofilament, and retinal S-antigen. Despite aggressive multimodal therapy, the patients died of metastatic tumor 7 months and 10 months following their initial diagnosis, respectively. Although osteosarcoma is the most frequent second cancer following bilateral retinoblastomas, some patients develop clinically aggressive sinonasal small-cell tumors that are difficult to place into conventional classifications. Both of our cases showed evidence of multidirectional differentiation; one tumor labeled with epithelial and neural markers, and the other expressed epithelial, neural, and myogenous antigens.

Adult↗
PubMed1989

Progenitor cell numbers (CFU-GM, CFU-D, and CFU-Mix) and hemopoietic recovery following autologous marrow transplantation.

Forty-one consecutive patients were treated with high-dose chemotherapy with or without total body irradiation followed by autologous marrow transplantation. Four treatment regimens of varying intensity were used. Every patient's harvested marrow was evaluable for nucleated cell and progenitor cell loss during the cell separation and cryopreservation process. Of the 41 patients, 38 were evaluable for peripheral blood count recovery. Multivariate analysis of colony-forming cell assays and recovery of neutrophils and platelets showed a significant association with absolute numbers of post-thaw mixed colony-forming units (CFU-Mix) infused (p less than 0.002). Prefreeze CFU-Mix also correlated with recovery to a lesser degree, as did absolute numbers of nucleated cells. The number of diffusion chamber colony-forming units (CFU-D) prefreeze, but not post-thaw infused into the patient, was associated with recovery of neutrophils (p = 0.0001), but not platelets. When the precursor cell numbers were adjusted for body weight, post-thaw CFU-Mix showed the best correlation with recovery of both platelets and neutrophils. Prefreeze CFU-D per kg was also associated with recovery of neutrophils (p = 0.02). To some extent nucleated cells per kg predicted for recovery with neutrophils and platelets (p less than 0.05). When analyzed according to treatment regimen, cyclophosphamide-BCNU-VP16 (CBV) or cyclophosphamide-total body irradiation (CY/TBI) was associated with prolonged recovery compared to cyclophosphamide-adriamycin-vinblastine (CAV) or etoposide-cyclophosphamide (EC). In this setting only CFU-D number predicted neutrophil recovery (p less than 0.002). We conclude that determination of the number of total nucleated cells, CFU-D, and CFU-Mix, before cryopreservation of the sample is important in predicting hemopoietic reconstitution in autologous bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗