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Biomedical subjects

P L Mitchell

Publications and source records attributed to P L Mitchell.

12 recordsLinked to original sources
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↗
PubMed1997

Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.

PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.

Anti-Bacterial Agents↗
PubMed1996

Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia.

Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B-cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.

Animals↗
PubMed1994

Phase II trial of procarbazine, vincristine and lomustine (POC) chemotherapy in metastatic cutaneous malignant melanoma.

40 patients with symptomatic metastatic melanoma were treated with procarbazine, vincristine and lomustine (POC). 4 patients had received chemotherapy previously. Responses were seen in 8 patients (20%), 4 of whom had a complete remission. All responding patients had some tumour shrinkage after one cycle. The median duration of response was 27 weeks, with 2 patients remaining in complete remission at 6 and 6.5 years. The median survival for the whole group was 22 weeks, whilst that of the responding patients was 35 weeks. Using conventional anti-emetics, the principal toxicities were nausea and vomiting, severe in 15% of cycles. Other nonhaematological toxicity was uncommon. Neutropenia (WHO grade 3 or 4) occurred in 11% of cycles and thrombocytopenia in 8%. The response rate of metastatic melanoma to POC chemotherapy was similar to other cytotoxic regimens though toxicity, other than nausea and vomiting, was minimal. The rapid response allows patients with unresponsive disease to be identified early, avoiding continuing toxicity.

Adult↗
PubMed1994

Peripheral blood stem cells used to augment autologous bone marrow transplantation.

Peripheral blood stem cells (PBSC) were used to augment autologous bone marrow transplantation (ABMT), aiming to hasten engraftment after high dose treatment in a group of heavily pretreated patients. PBSC were obtained by leukapheresis during the rebound after standard chemotherapy. In 11 patients aged 7-17 years, high dose chemotherapy consisted of busulphan 16 mg/kg orally with melphalan 160 mg/m2 intravenously for seven patients, and melphalan 200 mg/m2 intravenously alone for four. The median number of granulocyte-macrophage colony forming units in the reinfused PBSC was 3.42 x 10(4)/kg (3.03-18.01) and bone marrow 12.4 x 10(4)/kg (4.16-28.6). Neutrophil recovery to > or = 0.5 x 10(9)/l and platelet transfusion independence occurred at a median of 14 days (11-18) and 22 days (9-84) respectively. In five patients the early engraftment was transient with neutrophils again dropping below 0.5 x 10(9)/l then slowly recovering. There was one toxic death due to sepsis. PBSC harvesting in these children was undertaken without interrupting routine chemotherapy and without the use of bone marrow growth factors. In some patients PBSC failed to influence engraftment and the use of combined chemotherapy and growth factor priming for PBSC collection may give improved results.

Acute Disease↗
PubMed1993

Palliation of biliary obstruction in patients with advanced breast cancer using endoscopic stents.

Endoscopic insertion of a biliary endoprosthesis was successful in eight patients with extrahepatic biliary obstruction caused by breast cancer metastases. The serum bilirubin level was significantly reduced in seven patients and in four this was accompanied by marked symptomatic improvement. Endoprostheses required replacement after a median of 8 (range 3-127) weeks. Two patients responding to systemic anticancer therapy survived 27 and 43 months. Endoscopically placed stents offer effective palliation of extrahepatic biliary obstruction caused by metastatic breast cancer and long-term survival may be possible.

Adult↗
PubMed1992

Ondansetron reduces chemotherapy induced nausea and vomiting refractory to standard antiemetics.

Ondansetron, a selective 5HT3 (serotonin) antagonist, was used in patients refractory to standard antiemetics. Seventy-five patients receiving chemotherapy without cisplatin were given ondansetron 4 mg IV and 4 mg orally immediately prior to chemotherapy, then 8 mg orally after six and 12 hours, followed by 8 mg orally eight hourly during days 2-5. Complete control of vomiting occurred in 52 patients (69%) on the first day and 45 patients (60%) on days 2-5. Sixty patients (80%) preferred ondansetron to their previous antiemetics. The efficacy of ondansetron was maintained over multiple chemotherapy cycles. Ondansetron was also given to 16 patients receiving cisplatin chemotherapy. They received 8 mg IV immediately prior to chemotherapy followed by an infusion of 1 mg/hr for 8 hr, with 8 mg orally at the end of the infusion and then 8 mg orally eight hourly during days 2-6. Some control of vomiting (less than = 5 vomits) was achieved in eight patients (50%) on the first day and in 14 patients (87%) on subsequent days. Eight patients (50%) preferred ondansetron to their previous antiemetics. Adverse events with ondansetron were frequent but mild, with constipation and headache being most common. Ondansetron is highly effective in patients refractory to standard antiemetics, especially after noncisplatin chemotherapy.

Adult↗
PubMed1991

Reduction of carboplatin induced emesis by ondansetron.

Ondansetron is a selective 5-HT3 antagonist with significant antiemetic properties in patients receiving cytotoxic chemotherapy. Patients who had suffered severe vomiting on carboplatin alone (23 patients with ovarian carcinoma) or in combination (two patients with testicular cancer) despite intensive antiemetic regimens were treated with ondansetron, given as 8 mg immediately prior to carboplatin followed by 8 mg orally, 8 hourly for 5 days. Twenty-five patients received 58 courses of ondansetron. In the first 24 h after the first course of chemotherapy with ondansetron, 17 patients (68%) experienced no vomiting, five patients (20%) had almost complete control and the other three patients had partial control. During the subsequent 4 days slightly lesser control was achieved. Nausea was similarly controlled in most patients. Twenty-two patients stated a preference for ondansetron with future chemotherapy. Fourteen patients received additional chemotherapy with ondansetron and in only three patients did the efficacy of therapy lessen. Toxicity was mild and transient with headache and constipation predominant. No extrapyramidal reaction was seen. Sedation was absent. Ondansetron is highly effective in refractory vomiting associated with carboplatin chemotherapy. It may be particularly beneficial when an extrapyramidal reaction has occurred on previous antiemetics and when sedation is unacceptable.

Antiemetics↗
PubMed1986

Neonatal screening for biotinidase deficiency: results of a 1-year pilot study.

We screened 81,243 infants born in Virginia during the 1-year period beginning Jan. 24, 1984, for deficiency of the enzyme biotinidase. A simple colorimetric screening procedure was used to detect the presence or absence of biotinidase activity on the same blood-soaked filter paper cards that are currently used in most neonatal metabolic screening programs. Two newborn infants with biotinidase deficiency were identified during the 12-month pilot study. In addition, two affected siblings of one of the newborn infants were detected through secondary family screening. On the basis of these results, the disorder appears to be at least as frequent as several others for which newborn screening is currently conducted. There were no known false-negative test results, and only 0.09% false-positive results that necessitated requests for second blood samples. False-positive test results can be readily identified by the use of a quantitative assay, which can also be used to confirm the diagnosis and to detect heterozygous family members in the case of true positives. On the basis of currently recognized criteria, biotinidase deficiency should be considered for inclusion among the metabolic disorders for which screening is performed in the neonatal period.

Age Factors↗
PubMed1984

Computer-aided tinnitus characterization.

A purpose-built tinnitus synthesizer interfaced to a computer has been designed which can be used to characterize most types of subjective tinnitus. A patient is able to match his own tinnitus by making responses to simple questions using push buttons on a hand-held box. The system can be used to determine the characteristics of tinnitus consisting of tones, random noise or combinations of these sounds; any sound can also be pulsed synchronously with a patient's pulse beat in order to match pulsatile tinnitus. It is then possible to use the frequency and loudness characteristics of tinnitus in order to determine the suitability of masking therapy for a patient.

Audiometry↗