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Biomedical subjects

M Mullen

Publications and source records attributed to M Mullen.

10 recordsLinked to original sources
PubMed1992

Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple courses of dose-intensive therapy.

PURPOSE: The trial was undertaken to study the effect of administering granulocyte-macrophage colony-stimulating factor (GM-CSF) with and without peripheral-blood progenitor cells (PBPC) on the hematologic and nonhematologic toxicity observed with multiple cycles of high-dose carboplatin chemotherapy. PATIENTS AND METHODS: Eighteen patients with a variety of solid tumors received a total of 40 cycles of carboplatin, 1,200 mg/m2 per cycle, administered by continuous infusion over 96 hours. All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF. The first 20 courses were administered without PBPC support (treatment A). Because of severe neutropenia and thrombocytopenia, the next 20 courses of therapy were administered with GM-CSF, PBPC, and oral antibiotic prophylaxis (treatment B). RESULTS: The addition of PBPC support led to a significant reduction in the duration of neutropenia (10.5 v 7.5 days; P = .027) and thrombocytopenia (12.4 v 5.2 days; P = .001), number of RBC transfusions (six v three; P = .01) and platelet transfusions (10.3 v 3.7; P = .013), number of hospital days (12.6 v 2.9; P = .01), and days of IV antibiotics (11.8 v 2.4; P = .007) per cycle. Significant increases in the weekly dose intensity (206 v 285 mg/m2/wk; P = .014) and total dose (2,287 v 3,600 mg/m2; P = .018) of carboplatin delivered were also observed with treatment B. The overall response rate in this study was 70%, with 11 of 16 assessable patients achieving either a complete (three patients) or partial (eight patients) remission. CONCLUSION: This combination of GM-CSF and PBPC infusion represents an effective method for delivering multiple cycles of high-dose carboplatin chemotherapy and may serve as a model for the administration of high-dose chemotherapy in future trials.

Adult↗
PubMed1992

A dose-escalation study of carboplatin/cyclophosphamide/etoposide along with autologous bone marrow or peripheral blood stem cell rescue.

Twenty patients have received 21 courses of high-dose cyclophosphamide (6 g/m2 over 4 days), etoposide (1,800 mg/m2 over 3 days), and carboplatin (800 to 1,600 mg/m2 by continuous infusion over 96 hours) and autologous bone marrow or peripheral blood stem cell rescue. The maximum tolerated dose of this regimen included these doses of cyclophosphamide and etoposide with a total of 1,600 mg/m2 carboplatin. Acute renal failure was the dose-limiting toxicity and, at the maximum tolerated dose, was observed in two patients of 14 evaluable courses. Nonhematologic toxicity was otherwise modest, and the overall response rate was 70% in patients with a wide variety of solid hematologic neoplasms.

Acute Kidney Injury↗
PubMed1991

Alcohol counseling in a general medicine clinic. A randomized controlled trial of strategies to improve referral and show rates.

We conducted a controlled trial of two interventions to increase the number of patients receiving alcohol counseling in an academic, general medicine clinic. Ongoing randomization yielded similar groups of patients and providers. By applying a two-item alcoholism-screening instrument incorporated into the routine intake process, nursing staff were successful in screening 90.4% of the 1,328 eligible patients seen during a 4-month study period. Of the patients screened, 428 (35.6%) were found to be positive. In those groups where nurses were allowed to refer directly on the basis of a positive screening result, over four times as many patients (10.8% versus. 2.3%) accepted appointments for counseling, as did patients seen by physicians providing standard care. Patients who were briefly introduced to the alcohol counselor at the time referral were no more likely to keep their first, formal appointments than were patients scheduled in the usual manner. Patients who did receive counseling had their diagnoses confirmed by the 25-item Michigan Alcoholism Screening Test. We conclude that the adoption of an alcohol screening program in our clinic increased the number of patients appropriately referred for counseling.

Alcoholism↗
PubMed1988

High-pressure pulsation of central and microvessel pulmonary artery endothelial cells.

We developed an in vitro method of pulsating central and microvessel pulmonary artery endothelial cells that would allow us to study the effects of increased distending pressures over a prolonged period of time. Preservation of the contact-inhibited monolayer was assessed on phase contrast microscopy and, in addition, scanning and transmission electron microscopy (SEM, TEM) were used to determine whether there were alterations in the surface characteristics or intracytoplasmic organelles that suggested cellular damage. The cells used were obtained from Rambouillet lambs, age 3-5 days, anesthetized with halothane and ventilated. The endothelium was harvested from the central pulmonary artery (CPA) by scraping the luminal surface and from the microvessels (MPA) by infusing microcarrier beads 40-140 microns external diameter. After the second passage in culture, the cells were seeded onto the translucent, flexible polyvinylchloride membrane of a transducer dome and grown to confluence. The cell dome was then connected to a blank dome with an attached quartz transducer, to a reservoir, and to stainless steel bellows tubing, all filled with culture medium and affixed to a pulsation generator. By varying the height of the reservoir, the amplitude of excursion of the bellows tubing, and the rate, the cells could be pulsated at a given distending pressure and frequency. Confluent CPA endothelial cells from three lambs and MPA cells from two others were studied after pulsation at both 100/60 and 20/10 mmHg, 60 times/min for 48 h and after nonpulsation. On phase contrast light microscopy and on SEM, the cells remained confluent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Angiotensin II prevents hypoxic pulmonary hypertension and vascular changes in rat.

Angiotensin II, a vasoconstrictor, has been previously demonstrated to produce a secondary vasodilatation due to release of prostaglandins. Because of this effect, we investigated whether infusion of exogenous angiotensin II via miniosmopumps in rats during a 1-wk exposure to chronic hypobaric hypoxia might prevent pulmonary hypertension, right ventricular hypertrophy, and vascular changes. We instrumented the rats with indwelling cardiovascular catheters and compared the hemo-dynamic and structural response in animals given angiotensin II, indomethacin in addition to angiotensin II (to block prostaglandin production), or saline with or without indomethacin. We then determined whether angiotensin II infusion also prevents acute hypoxic pulmonary vasoconstriction. We observed that exogenous angiotensin II infusion abolished the rise in pulmonary artery pressure, the right ventricular hypertrophy, and the vascular changes induced during chronic hypoxia in control saline-infused rats with or without indomethacin. The protective effect of angiotensin II was lost when indomethacin was given to block prostaglandin synthesis. During acute hypoxia, both angiotensin II and prostacyclin infusions similarly prevented the rise in pulmonary artery pressure observed in saline-infused rats and in rats given indomethacin or saralasin in addition to angiotensin II. Thus exogenous angiotensin II infusion prevents chronic hypoxic pulmonary hypertension, associated right ventricular hypertrophy, and vascular changes and blocks acute hypoxic pulmonary hypertension, and this is likely related to its ability to release vasodilator prostaglandins.

Acute Disease↗
PubMed1986

Effect of intravenous papain on tracheal pressure-volume curves in rabbits.

To investigate the effects of airway cartilage softening on tracheal mechanics, pressure-volume (PV) curves of excised tracheas were studied in 12 rabbits treated with 100 mg/kg iv papain, whereas 14 control animals received no pretreatment. The animals were killed 24 h after the injection and the excised specimens studied 24 h later. Treated tracheas exhibited decreased ability to withstand negative transmural pressures, reflected in increased collapse compliance: 6.2 +/- 2.1 vs. 2.0 +/- 0.5% peak volume (Vmax)/cmH2O means +/- SD, P less than 0.001, (Vmax = extrapolated maximal tracheal volume), increased kc (exponential constant that reflects the shape of collapse limb of the PV curve): 0.244 +/- 0.077 vs. 0.065 +/- 0.015 (P less than 0.001). The distension limb of the PV curve greater than 2.5 cmH2O transmural pressure (Ptm) was no different. Compliance between 0 and 2.5 cmH2O Ptm was increased in papain-treated rabbits: 4.97 +/- 1.73 vs. 2.30 +/- 0.31% Vmax/cmH2O (P less than 0.001). Tracheal volume, and therefore mean diameter, was decreased at 0 Ptm: 2.7 +/- 0.26 vs. 3.2 +/- 0.27 mm (P less than 0.001). We conclude that airway cartilage softening increases the compliance of the trachea at pressures less than 2.5 cmH2O Ptm.

Animals↗
PubMed1985

Pulmonary toxicity of monocrotaline differs at critical periods of lung development.

We injected 3-day-old (neonatal), 8-day-old (infant), and 8-wk-old (adult) Sprague-Dawley rats with monocrotaline to examine the effect of a toxic agent at various stages of lung development. Two and four weeks after injection the rats were killed and the heart and lungs removed: the right and left ventricles were separated and weighed, the pulmonary artery was injected with barium-gelatin, and the lung was fixed in the inflated state. Morphometric techniques were applied to assess lung volume, alveolar size and number, and arterial size, muscularity, and concentration relative to alveolar. Rats injected with monocrotaline in the neonatal period did not survive to 3 wk. After 2 wk, there was no significant right ventricular hypertrophy and pulmonary vascular changes were no worse than in the other rat groups injected with monocrotaline, but alveolar development was severely impaired; less than one-third the normal number was present. Rats injected with monocrotaline in infancy had normal alveolar development. After 2-wk, the arterial changes, i.e. extension of muscle into peripheral arteries, medial hypertrophy of muscular arteries, and decreased arterial concentration relative to alveolar were similar to those observed in adult rats. After 4 wk, there was a decrease in medial hypertrophy associated with growth in artery size and only a lack of regression of right ventricular weight. In adult rats, after 4 wk medial hypertrophy became progressively more severe, the arterial concentration relative to alveolar decreased further, and right ventricular hypertrophy developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Hyperoxia-induced pulmonary vascular and lung abnormalities in young rats and potential for recovery.

We carried out morphometric studies to assess the effects of increasing durations of hyperoxic exposure on the developing rat lung and to evaluate the potential for new growth and for regression of structural abnormalities on return to room air. From day 10 of life Sprague-Dawley rats were either exposed to hyperoxia (0.8FIO2) for 2-8 wk or were removed after 2 wk and allowed to "recover" in room air for 2-6 wk. Litter mates maintained in room air served as age matched controls. Every 2 wk experimental and control rats from each group were weighed and killed. The heart and lungs were removed, the pulmonary artery was injected with barium-gelatin, and the lung was fixed in formalin in the inflated state. Morphometric assessments were made of right and left ventricular weights, lung volume, axial artery lumen diameter, alveolar number and concentration, and arterial number, concentration and muscularity. Rats continuously exposed to hyperoxia and rats exposed for only 2 wk showed the same degree of impaired parenchymal lung growth, as judged by a decrease in the concentration and number of alveoli. A significant decrease in arterial concentration, increase in muscularization of peripheral arteries, and medial hypertrophy of muscular arteries occurred after 2 wk of hyperoxia. Despite an initial trend toward regression, these features became progressively severe with continued hyperoxic exposure and by 8 wk were associated with a decreased arterial lumen diameter, with right ventricular hypertrophy and with failure to thrive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗