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Biomedical subjects

J P Steele

Publications and source records attributed to J P Steele.

18 recordsLinked to original sources
PubMed2003

IPM chemotherapy in cytokine refractory renal cell cancer.

Renal cell carcinoma (RCC) is notoriously chemoresistant. Current management of metastatic disease usually includes immunological agents of which the most clearly evaluated is alpha interferon. Following the failure of such agents no clear second-line therapy exists. The use of a novel combination of cisplatin, irinotecan and mitomycin may offer some palliative benefit in this situation. Thirty-three patients with cytokine refractory RCC and documented progression and documented active progressive disease with performance status 0-3 were enrolled. Therapy consisted of cisplatin 40 mg m(-2) on day 1 and day 15, irinotecan 100 mg m(-2) on day 1 and day 15, and mitomycin 6 mg m(-2) on day 1 of a 28-day cycle. The results showed that one patient (3%) had a partial response, eight (24%) had minor responses and nine (27%) had stable disease, overall 61% had symptomatic responses. Quality-of-life (QOL) assessment did not change significantly during therapy. Seventy-one percent of those who had primary refractory disease to cytokine therapy subsequently responded to IPM. The median progression-free interval was 4.8 months in this cohort on chemotherapy, compared to 3.9 months with their previous cytokine treatment. In conclusion, IPM produced symptomatic relief for a majority of patients with cytokine refractory RCC without any deterioration in QOL. Disease stabilisation on radiological assessment and symptomatic improvement were associated with prolonged survival. A degree of non-crossresistance to cytokine therapy was seen. IPM may be considered in patients with renal cancer following failure of cytokines.

Adult↗
PubMed2001

Phase II trial of liposomal daunorubicin in malignant pleural mesothelioma.

BACKGROUND: To assess the response rate, toxicity and survival in patients with malignant pleural mesothelioma treated with liposomal daunorubicin. The study design allowed for dose escalation pending toxicity. PATIENTS AND METHODS: Liposomal daunorubicin (DaunoXome, Nexstar, USA) 120 mg/m2 was administered every 21 days to a maximum of 6 cycles. Patients had to have histologically-proven malignant pleural mesothelioma. Patients were all chemotherapy-naïve with ECOG performance status 0-2. RESULTS: Fourteen patients were enrolled. There were no objective or symptomatic responses though nine patients (64%) had stable disease on therapy. Myelosuppression was the major toxicity with 9 of 11 patients evaluable for toxicity experiencing grade 3 or 4 neutropenia. Other toxicities seen in at least 30% of patients included grade 3 infection and grade 2 nausea and vomiting. The median overall survival by intention-to-treat analysis was 6.1 months from the time of first treatment. The median duration of stable disease from time of first treatment for patients not progressing on therapy was 5.1 months. CONCLUSIONS: Liposomal daunorubicin 120 mg/m2 has no useful clinical activity in patients with malignant pleural mesothelioma. Toxicity was substantial with most patients experiencing at least one episode of grade 3 or 4 neutropenia. Liposomal daunorubicin cannot be recommended for patients with malignant pleural mesothelioma.

Adult↗
PubMed2001

Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation.

Small cell lung cancer is a chemosensitive disease; however, patients with extensive-stage disease or adverse prognostic factors are rarely cured. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with good tolerability, interacts synergistically with platinum agents. Carboplatin is as effective as cisplatin, but is less toxic. The London Lung Cancer Group is conducting a multicenter, open-label, randomized, phase III trial in patients with histologically or cytologically proven small cell lung cancer and extensive-stage, limited-stage but locally-advanced, or limited-stage disease with poor prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200 mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2) IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22 completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients experienced significant alopecia, nephrotoxicity, nausea and vomiting, and neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may define an active, safe, and acceptable treatment for patients with extensive-stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18.

Adult↗
PubMed2000

Phase II study of vinorelbine in patients with malignant pleural mesothelioma.

PURPOSE: To evaluate the response rate and impact on quality of life of vinorelbine given as cycles of 30 mg/m(2) weekly for 6 weeks to patients with malignant pleural mesothelioma. PATIENTS AND METHODS: Twenty-nine patients with histologically proven malignant pleural mesothelioma were enrolled (26 male patients and three female patients; median age, 58 years [range, 29 to 77 years]). Seventeen patients had epithelioid tumors, two had sarcomatoid tumors, and 10 had biphasic tumors. The International Mesothelioma Interest Group staging system was used: one patient had stage Ib disease, 10 had stage II disease, eight had stage III disease, and 10 had stage IV disease. Patients were treated with weekly injections of vinorelbine 30 mg/m(2). A cycle consisted of six weekly injections. The new guidelines to evaluate the response to treatment in solid tumors were used. Responses were measured by spiral computed tomography scan. RESULTS: All twenty-nine patients had measurable disease and were assessed for response. There were seven partial responses (24% [95% confidence interval, 10% to 44%]), 16 patients had stable disease (55%), and six patients had disease progression on therapy (21%). The median number of vinorelbine injections was 12 (range, 2 to 30). Quality-of-life analyses showed a benefit for vinorelbine therapy. CONCLUSION: Vinorelbine shows promise in the palliation of patients with malignant pleural mesothelioma. The relatively low toxicity of the drug suggests that trials of vinorelbine in combination with other agents should be feasible.

Adult↗
PubMed2000

Membranous nephropathy resolving with treatment of bronchial carcinoid tumor.

The nephrotic syndrome and membranous nephropathy is well recognized in association with solid tumors, although less is understood of the process that links them. We report a 27-year-old man presenting with the nephrotic syndrome and stage I membranous glomerulonephritis on biopsy. A bilar mass with regional lymphadenopathy was found simultaneously, the histology of which was shown to be an infiltrative atypical bronchial carcinoid tumor. The neoplasm was successfully treated with combined chemotherapy and radiotherapy, and over this period his nephrotic-range proteinuria resolved. As has been described with other malignancies, membranous nephropathy associated with a bronchial carcinoid tumor may resolve with treatment of the underlying condition.

Adult↗
PubMed1998

Liposomal vincristine for the treatment of human acute lymphoblastic leukaemia in severe combined immunodeficient (SCID) mice.

Non-obese diabetic NOD/SCID mice have been used to grow human leukaemia as a systemic disease. The animals were inoculated with leukaemic cells obtained from a 36-year-old male with early B-cell precursor acute lymphoblastic leukaemia and on day 15 were given the first of three weekly injections of 1 mg/kg vincristine or equimolar liposomal vincristine. The development of leukaemia in the mice was monitored by taking weekly blood samples and measuring the cell content by flow cytometry. The median time to 50% human cells in the peripheral blood of mice treated with free vincristine was 41 d from the start of treatment compared with 49 d for mice treated with liposomal vincristine (P < 0.01). The median day of death for mice treated with free vincristine was 47 d from the start of treatment and 57 d for mice receiving liposomal vincristine (P<0.01), thus providing a 21% increase in lifespan for animals treated with the liposomal preparation. There was slightly greater weight loss in mice treated with free vincristine than those given liposomal vincristine. Measurement of in vitro colony forming bone marrow progenitor cells in similarly treated, tumour-free mice, showed no difference in progenitor cell survival between mice that received either type of vincristine. We conclude that encapsulating vincristine in liposomes improves the therapeutic index of this drug measured in mice bearing human leukaemia. This may lead to use of the drug in conventional combination chemotherapy with greater safety or, in this setting, at higher dosage.

Adult↗
PubMed1997

Growth of human T-cell lineage acute leukemia in severe combined immunodeficiency (SCID) mice and non-obese diabetic SCID mice.

Primary leukemic cells from patients with acute lymphoblastic leukemia (ALL) can be injected intravenously into mice with severe combined immunodeficiency (SCID) to create a model of human leukemia. Leukemic cells disseminate to murine tissues in a clinicopathologic pattern similar to that seen in humans. Thus far, reports of engraftment of lymphoid leukemia in SCID mice have mainly been from patients with B-cell lineage ALL, for which engraftment occurs more frequently with cells from high-risk patients. There are few data on the engraftment of T-cell lineage ALL in SCID mice. Leukemic cells from 19 patients (16 adult and three pediatric) with T-cell lineage ALL were injected into SCID mice, with overt engraftment of 12 cases (63%). Engraftment of leukemia in SCID mice was associated with earlier death due to leukemia of the patient donors (P < .01, log-rank test). The recently developed non-obese diabetic (NOD)/SCID mouse may expand the uses of the SCID model. Cells from the seven patients with T-cell lineage ALL that failed to cause leukemia in SCID mice were injected into NOD/SCID mice. Overt leukemia engraftment was observed in all seven cases. Thus, growth of human T-cell lineage ALL cells in SCID mice was associated with a high-risk patient group. However, this association was not observed when NOD/SCID mice were used, suggesting that this model would no longer predict patients likely to die early of leukemia, but may provide a more realistic system for studying the biology and treatment of the disease.

Acute Disease↗
PubMed1990

Effect of on-site facilities on use of diagnostic radiology by non-radiologists.

This study uses self-reports from a nationwide sample of 5447 physicians in ten medical and surgical specialties to assess the impact of on-site facilities on the use of radiologic examinations by non-radiologists. Data from 169,559 patient visits show that when on-site radiologic facilities are available to non-radiologists, radiographs increase by a factor of 1.2 (internal medicine) to 1.7 (pediatrics). Use of radiologic examinations is up to four times greater for hospitalized compared with nonhospitalized patients and is slightly higher for hospital-based physicians and for younger physicians.

Analysis of Variance↗
PubMed1982

Mastoid development in ancient and modern populations. A longitudinal radiological study.

The effect of otitis media on the human mastoid process in a common milieu over a millennium was evaluated by comparing two present and four ancient populations. Temporal bone pneumatization patterns indicate that otitis media and mastoiditis existed in antiquity, and there were more altered pneumatization patterns in skulls from the era following European contact than from eras before European contact. Pneumatization patterns were similar in ancient skulls and in a preponderantly white male population mostly born before antibacterial availability. Both ancient and modern pre-antibacterial era temporal bones show more effect of otitis media during childhood than is found in present day schoolchildren. Reasons for differences are explored. It is inferred that upper respiratory tract infections were prevalent in the Upper Missouri River Basin during the past millennium. Furthermore, microbiological agents with virulence similar to today's flora were prevalent in this region more than 1,000 years ago.

Adolescent↗
PubMed1982

Unusual osteolytic defects in ancient South Dakota skulls.

Unusual osteolytic defects in eight skulls culled from over 4000 ancient South Dakota burials are presented, discussed briefly, and assigned to what we think is their most likely cause. Because these are collection skeletons, histological and microbiological and microbiological confirmation of interpretations concerning specific lesions are not possible. Corroboration of our opinions has been sought through radiographs and by expert consultation elsewhere. Although our opinions are interpretative and subject to rebuttal, they can serve as a base for future research if and when similar specimens are discovered elsewhere. In addition, these specimens are indicators of other than usual ancient skull pathology from a limited geographic area, representing people who lived there during a known time frame.

Adult↗
PubMedDate not supplied

Otolaryngic osteopathology in 14th century mid-america. The crow creek massacre.

Over 486 people were massacred and buried communally at the Crow Creek Village Site, South Dakota, about 1350 AD. Osseous pathology in the craniofacial area of the victims' skeletons is reviewed and compared to data from other indigenous skeletal populations past and present. The Crow Creek mastoid x-rays are analyzed and compared to four other studies which span over 1000 years of Dakota Territory history. Findings regarding external auditory canal exostoses in the different groups are compared. Unusual findings in the craniofacial area are assessed. Insight into longitudinal epidemiology in one portion of the U.S. is possible through this study.

Adolescent↗