Search PubMed⌕ Search

Biomedical subjects

M Phelps

Publications and source records attributed to M Phelps.

At least 19 recordsLinked to original sources
PubMed2002

Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide.

Cyclophosphamide (Cy) is a potent immunosuppressive agent that is selectively toxic to lymphocytes proliferating in response to recent antigen stimulation. In animal models, both graft rejection and GVHD after histoincompatible BMT can be inhibited by the posttransplantation administration of high-dose Cy. Therefore, a phase I clinical trial was undertaken to determine the minimal conditioning, including posttransplantation Cy, that permits the stable engraftment of partially HLA-mismatched marrow (up to 3 HLA antigens) from first-degree relatives. Thirteen patients (median age, 53 years) with high-risk hematologic malignancies received conditioning with fludarabine, 30 mg/m2 per day from days -6 to -2, and TBI, 2 Gy on day -1. All patients received Cy, 50 mg/kg on day 3, mycophenolate mofetil from day 4 to day 35, and tacrolimus from day 4 to day > or = 50. Three patients in cohort 1 received no additional conditioning, and 2 experienced graft rejection. Ten patients in cohort 2 received identical conditioning with the addition of Cy 14.5 mg/kg on days -6 and -5. Sustained donor cell engraftment occurred in 8 of these patients, with a median time to absolute neutrophil count > 500/microL of 15 days (range, 13-16 days) and to unsupported platelet count > 20,000/microL of 14 days (range, 0-26 days). All patients with engraftment achieved > or = 95% donor chimerism within 60 days of transplantation. Two patients with myelodysplastic syndrome rejected their grafts but experienced autologous neutrophil recovery at 24 and 44 days. Histologic acute GVHD developed in 6 patients (grade II in 3 patients, grade III in 3 patients) at a median of 99 days (range, 38-143 days) after transplantation and was fatal in 1 patient. At a median follow-up of 191 days (range, 124-423 days), 6 of 10 patients in cohort 2 were alive, and 5 were in complete remission of their disease, including both patients with graft rejection. These data demonstrate that partially HLA-mismatched bone marrow can engraft rapidly and stably after nonmyeloablative conditioning that includes posttransplantation Cy. Clinically significant antitumor responses occur, even among patients who reject their donor grafts.

Adolescent↗
PubMed2001

An emergency department-based randomized trial of nonbronchoscopic bronchoalveolar lavage for early pathogen identification in severe community-acquired pneumonia.

STUDY OBJECTIVES: Many patients with community-acquired pneumonia are treated empirically without an aggressive search for causative pathogens, an approach adopted largely because of the costs and difficulties encountered during efforts to identify the causative organisms. Blood and sputum cultures are not sensitive, and the more invasive techniques of bronchoscopy and lung biopsy are generally time consuming and not cost-effective. The technique of nonbronchoscopic bronchoalveolar lavage (BAL) has been shown to accurately diagnose the causes of nosocomial pneumonia. The purpose of this study was to determine whether an emergency department-based BAL protocol would lead to more frequent isolation of pneumonia pathogens and result in more changes to tailored antibiotic therapy in comparison with standard care. METHODS: We studied all adult patients admitted with a diagnosis of pneumonia who were tracheally intubated and who had obtainable familial consent in the ED of an urban county hospital from March 1998 to October 1999. Exclusions included antibiotic use within the past 5 days, pneumothorax, hemoptysis, or persistent hypoxia using 100% oxygen. Patients were randomized to standard care versus standard care plus BAL. Blood culture specimens were drawn from all patients before the initiation of antibiotics. All other diagnostic tests were ordered at the discretion of treating physicians. BAL fluid, sputum, and blood culture specimens were tracked, and patient antibiotic course was followed to assess any change in regimen. RESULTS: Twenty-six of 64 patients evaluated for study participation met all eligibility criteria; 14 patients received standard care, and 12 patients received standard care plus BAL. Pneumonia pathogens were identified in 10 (83.3%) of 12 patients in the BAL group and in 4 (28.6%) of 14 patients in the standard care group (P =.007). Comparing BAL versus non-BAL groups, there was no significant difference in the likelihood of overall antibiotic regimen changes (P =.149), but there was a difference with regard to antibiotic changes made in patients with positive culture test results (P =.026). No major complications occurred with BAL catheterizations. CONCLUSION: ED-based BAL catheterization allows for early identification of pathogens in severe community-acquired pneumonia, which leads to changes in antibiotic therapy.

Adult↗
PubMed2000

Selective genetic analysis of p53 immunostain positive cells.

The isolation of p53 immunostain positive cells from histological sections for molecular genetic studies is a difficult task, especially if there are few positive cells. To eliminate contaminating DNA from p53 negative cells, which can obscure the results of molecular assays, a variation on the technique of immunohistoselective sequencing was developed. This is a highly selective approach, whereby immunostained sections of formalin fixed, paraffin wax embedded tissue are exposed to ultraviolet irradiation to damage the DNA in p53 negative cells. The DNA in positive cells remains unaffected because the dark immunostain protects their nuclei from ultraviolet light. Polymerase chain reaction single strand conformation polymorphism of samples enriched with p53 immunostain positive cells has shown that this method can produce pure samples of mutated DNA. The isolation of DNA from minority immunostain positive cells allows a wide range of molecular analyses to be carried out on these samples, which would otherwise be hampered by the problem of contaminating background cells.

DNA Damage↗
PubMed1997

Intracarotid infusion of RMP-7, a bradykinin analog, and transport of gallium-68 ethylenediamine tetraacetic acid into human gliomas.

The bradykinin analog, RMP-7, was investigated for its ability to increase selectively the transport of 68Ga ethylenediamine tetraacetic acid (EDTA) into recurrent malignant gliomas in nine patients. For each patient, two position emission tomography (PET) studies (one with and one without RMP-7) were performed. For studies with RMP-7, 10 to 300 ng/kg of the compound was infused into the supraophthalmic carotid artery over 15 minutes. In each PET study, a sequence of PET scans was initiated simultaneously with an intravenous bolus of 68Ga EDTA (5-10 mCi). Arterial samples were taken to provide the input function. All PET scans were coregistered to the magnetic resonance (MR) images of the patient. Regions of interest were defined for tumor and normal tissue regions on MR images and were copied to the coregistered PET dynamic images to provide brain tissue-time activity curves. The constant (Ki) for the transport of gallium-68 from plasma to brain tissue was determined using a simple compartmental model. Intracarotid infusion of RMP-7 significantly increased transport into tumor regions with an average increase of 46 +/- 42% (mean +/- standard deviation, p < 0.05). Permeability in normal tissue regions was not significantly increased. Tumors in three of six patients treated with 300 ng/kg RMP-7 and carboplatin had at least a 50% reduction in tumor volume as measured by MR imaging. Intracarotid infusion of RMP-7 is a novel technique for selective delivery of antitumor compounds into brain tumors.

Adult↗
PubMed1996

Production of [18F]F2 using the 16O(3He,p)18F reaction.

For the first time, the 16O(3He,p)18F reaction has been used for the production of 18F electrophilic reagents. The predominant reactive chemical specie recovered in the single-step postirradiation gases was [18F]F2. Decay curve and Ge(Li) analyses established the main radionuclidic impurities in this nuclear reaction as 11C and 15O. Recovery of the 18F activity was exceptionally high, approaching 90% using an electroformed nickel target body. Consistent 18F recoveries for this nuclear reaction (approximately 70%) were realized with a novel aluminum target body. The utility of the [18F]F2 recovered from this oxygen gas target system in radiopharmaceutical preparations is demonstrated by the successful synthesis of 6-[18F]fluoro-L-dopa (11.0 mCi at EOB) via a fluorodemercuration method.

Fluorine Radioisotopes↗
PubMed1996

Proton irradiation of [18O]O2: production of [18F]F2 and [18F]F2 + [18F] OF2.

The production of 18F electrophilic reagents via the 18O(p,n)18F reaction has been investigated in small-volume target bodies made of aluminum, copper, gold-plated copper and nickel, having straight or conical bore shapes. Three irradiation protocols-single-step, two-step and modified two-step-were used for the recovery of the 18F activity. The single-step irradiation protocol was tested in all the target bodies. Based on the single-step performance, aluminum targets were utilized extensively in the investigation of the two-step and modified two-step irradiation protocols. With an 11-MeV cyclotron and using the two-step irradiation protocol, > 1Ci [18F]F2 was recovered reproducibly from an aluminum target body. Probable radical mechanisms for the formation of OF2 and FONO2 (fluorine nitrate) in the single-step and modified two-step targets are proposed based on the amount of ozone generated and the nitrogen impurity present in the target gases, respectively.

Aluminum↗
PubMed1996

Metals suitable for fluorine gas target bodies: first use of aluminum for the production of [18F]F2.

A comprehensive evaluation of different metals (aluminum, silver, copper, nickel, and gold-plated copper) was undertaken for the fabrication of target bodies with straight and conical bore shapes for the production of [18F]F2 via the 20Ne(d,alpha)18F nuclear reaction. Of these metals, aluminum, silver and copper have never been used for the production of [18F]F2. All these target bodies were easily passivated using a mild beam-induced plasma technique in the presence of 1% F2 in neon or argon. The recovery of 18F activity was higher with electroformed nickel and silver bodies, probably due to favorable thermal conductivities. Aluminum proved to be a useful material for fluorine gas targets. The consistent recovery of 18F activities, ease and low cost of manufacturing and low nuclear activation properties all make aluminum an ideal choice for fluorine gas targetry. To our knowledge, this investigation is the first to highlight the use of aluminum as a target body material for the routine production of [18F]F2. A reasonable mechanism based on the Langmuir-Rideal surface atom recombination is also proposed for the behavior of [18F]F2 recovery from a nickel target body.

Aluminum↗
PubMed1996

Identification and quantitation of gaseous compounds of fluorine generated in [18F]F2 target systems.

The first direct evidence for the chemical identity of the electrophilic fluorinating agents generated in 20Ne(d, alpha)18F (single-step), 18O(p,n)18F (single-step and two-step) and 16O(3He2+, p)18F (single-step) gas target systems, utilizing aluminum, silver, copper, nickel and gold plated copper target bodies, has been established with multinuclear NMR and mass spectral techniques. The major components of the reactive fraction from these targets were also quantitated using 19F NMR. Fluorine-19 NMR data of the reactive fraction of all proton and 3He2+ irradiated oxygen gas target systems showed the presence of oxygen difluoride in various proportions. Samples from the single-step method contained up to 20% OF2 while those from the two-step process had 0-5%. Fluorine nitrate (FONO2) was observed only as a minor component (0-3%) in the reactive fraction. The presence of OF2 and FONO2 was further confirmed by 17O and 15N NMR, respectively, using [17O]O2 and [15N]N2 spiked oxygen gas targets. The NMR results were supported by mass spectral data collected with a residual gas analyzer (RGA). Both 19F NMR and mass spectroscopy showed CF4 as the only major inert component in the single-step oxygen target products. As expected, the 19F NMR and mass spectral data showed that the reactive fraction of the neon gas target constituted only F2 and the inert fraction comprised of CF4 and NF3.

Fluorine Compounds↗
PubMed1996

The use of positron emission tomography imaging in the management of patients with ischemic cardiomyopathy.

Rational management of patients with CAD and poor left ventricular function relies on proper identification of the subgroup at high risk and those who have the highest potential of benefiting from a particular type of treatment. It is now well recognized that patients with CAD and left ventricular dysfunction have a high but variable mortality rate while receiving medical therapy. Many of these patients who have intractable heart failure are considered candidates for cardiac transplantation. Despite favorable survival after cardiac transplantation, this procedure cannot be performed in 90% of the heart failure patients who are potentially eligible because of the shortage of donor hearts. Cardiac transplantation is also an expensive procedure. Perfusion-FDG metabolism PET imaging has become the gold-standard noninvasive imaging method to identify the presence and extent of hibernating myocardium. Positron emission tomography accurately predicts recovery of regional and global left ventricular dysfunction after revascularization. In patients with poor left ventricular function, the PET pattern of perfusion metabolism mismatch is also predictive of improvement in heart failure symptoms and survival benefit after myocardial revascularization. These data suggest that a rational approach may be developed for cost-effective management of patients with CAD and poor left ventricular function.

Cell Survival↗
PubMed1995

Effect of acute and long-term smoking on myocardial blood flow and flow reserve.

BACKGROUND: Cigarette smoking is a major preventable risk factor for coronary artery disease and sudden cardiac death. However, the effect of acute and long-term cigarette smoking on coronary vasodilatory capacity and myocardial flow reserve has not been quantified in humans. METHODS AND RESULTS: To examine the effect of short-term and long-term smoking, myocardial blood flow was quantified at rest and during dipyridamole-induced hyperemia (0.56 mg/kg) in 12 smokers (10 males and 2 females; mean age, 27 +/- 4 years) under baseline conditions (reflecting the effect of long-term smoking) and during short-term cigarette smoking with 13N ammonia, positron emission tomography, and a two-compartment model. Twelve sex- and age-matched nonsmokers served as control subjects. Smoking significantly increased the rate-pressure product at rest from 7525 +/- 1290 to 9160 +/- 1125 (P < .001 versus baseline), which was paralleled by a proportional increase in myocardial blood flow at rest (0.70 +/- 0.17 versus 0.88 +/- 0.17 mL.g-1.min-1; P < .05 versus baseline). In contrast, hyperemic blood flow declined from 2.23 +/- 0.35 at baseline (P = NS versus control) to 1.98 +/- 0.32 mL.g-1.min-1 during smoking (P < .01 versus baseline). Accordingly, the myocardial flow reserve declined from 3.36 +/- 0.83 in smokers at baseline to only 2.28 +/- 0.28 during smoking (P < .0001 versus baseline). Thus, myocardial blood flow and flow reserve were similar in young, long-term smokers and young, healthy nonsmokers. CONCLUSIONS: Short-term smoking increases the coronary vasomotor tone during dipyridamole-induced hyperemia and markedly reduces the myocardial flow reserve. In contrast, long-term smoking does not attenuate the coronary vasodilatory capacity in young individuals with a relatively short smoking history. It might be speculated that the short-term reduction in the coronary vasodilatory capacity during smoking could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for sudden cardiac death.

Adult↗
PubMed1995

Effects of modified pharmacologic stress approaches on hyperemic myocardial blood flow.

UNLABELLED: Pharmacologic stress testing with 0.56 mg/kg of intravenous dipyridamole is frequently used to noninvasively detect coronary artery disease (CAD). However, high-dose dipyridamole (0.80 mg/kg) or the combination of standard-dose dipyridamole (0.56 mg/kg) with the isometric handgrip maneuver might evoke a greater coronary hyperemic response. METHODS: To evaluate the effect of modified pharmacologic stress tests, myocardial blood flow as quantified in 11 male subjects (mean age: 27 +/- 7 yr) during standard-dose dipyridamole (0.56 mg/kg), high-dose dipyridamole (0.80 mg/kg) and standard-dose dipyridamole combined with the isometric handgrip exercise using dynamic PET and a two-compartment model for 13N-ammonia. RESULTS: Systolic blood pressure, heart rate and rate pressure product remained unchanged from standard to high-dose dipyridamole but increased with the addition of the isometric handgrip. Myocardial blood flow was unchanged from standard to high-dose dipyridamole but was lower with the addition of the isometric handgrip. CONCLUSION: The hyperemic response induced by standard-dose dipyridamole cannot be further enhanced by high-dose dipyridamole. The addition of the isometric handgrip exercise results in a modest, but significant decline in hyperemic blood flow possibly due to increased extravascular resistive forces or an increase in a mediated coronary vasoconstriction associated with exercise.

Adult↗
PubMed1994

Myocardial viability in asynergic regions subtended by occluded coronary arteries: relation to the status of collateral flow in patients with chronic coronary artery disease.

OBJECTIVES: This study aimed to determine whether angiographically visualized collateral vessels in patients with chronic coronary artery disease imply the presence of viable myocardium in asynergic regions subtended by completely occluded coronary arteries. BACKGROUND: Patients with chronic coronary artery disease who are being considered for revascularization frequently exhibit angiographically visualized collateral vessels to completely occluded coronary arteries supplying severely asynergic myocardial regions. However, little is known about the relation between angiographic collateral flow and myocardial viability in these patients. METHODS: We studied 42 patients with 78 completely occluded coronary arteries supplying asynergic territories. Angiographic collateral vessels were interpreted as absent (grade 1) in 14 patients, minimal (grade 2) in 27 and well developed (grade 3) in 37. Myocardial viability was determined with positron emission tomography using nitrogen-13 (N-13) ammonia and fluorine-18 (F-18) deoxyglucose for assessment of regional perfusion and glucose uptake, respectively. Positron emission tomographic patterns were interpreted as mismatch (perfusion defect with enhanced F-18 deoxyglucose uptake); transmural match (severe concordant reduction or absence of both perfusion and F-18 deoxyglucose uptake) or nontransmural match (mild to moderate concordant reduction of both perfusion and F-18 deoxyglucose uptake). RESULTS: There was no significant correlation (p = 0.14) between the severity of perfusion deficit assessed by positron emission tomography and the collateral grade. The extent of mismatch was unrelated to either the presence or the magnitude of collateral vessels. Conversely, with increasing collateral vessels from grade 1 to 3, the total extent of positron emission tomographic match remained similar, whereas the ratio of transmural to nontransmural match decreased. Myocardial viability was usually present in severely hypokinetic regions (82%). It was lower in akinetic-dyskinetic regions (49%). Of the 64 regions with angiographic collateral vessels, 37 (58%) (95% confidence interval [CI] 46% to 70%) showed positron emission tomographic mismatch. In contrast, 7 (50%) of 14 (95% CI 24% to 76%) regions without collateral vessels on angiography exhibited positron emission tomographic mismatch. The presence of angiographically visualized collateral vessels was a sensitive (84%) but not specific (21%) marker of viability. CONCLUSIONS: In patients with chronic coronary artery disease, angiographically visualized collateral vessels to asynergic myocardial regions subtended by occluded coronary arteries do not always imply the presence of viable myocardium, suggesting that revascularization may not always provide a functional benefit.

Adult↗
PubMed1994

Positron emission tomography diagnosis of pulmonary metastases in osteogenic sarcoma.

Positron emission tomography (PET) is an imaging technique that can produce high-quality tomographic images reflective of the metabolic characteristics of imaged tissue. Among the many positron-emitting tracers utilized in conjunction with PET is [18F]fluoride ion; it is actively taken up in bone in proportion to bone metabolic activity, analogous to standard nuclear medicine bone scanning agents such as technetium methylenediphosphonate ([99mTc]MDP). Whole-body imaging with PET and [18F]fluoride ion generates tomographic images that are useful in mapping patterns of bone metabolism, as well as identifying extraosseous site of bone formation or calcification. We report the case of a patient with polyostotic fibrous dysplasia, metastatic osteogenic sarcoma, and a breast mass, who presented with pulmonary nodules, in whom [18F] fluoride ion/PET imaging was useful in confirming the nature of the pulmonary nodules.

Adult↗
PubMed1994

Quinapril and hydrochlorothiazide combination for control of hypertension: assessment by factorial design. Quinapril Investigator Group.

A factorial design method was applied in this multicentre trial of the angiotensin-converting enzyme inhibitor quinapril hydrochloride (Accupril) in combination with the diuretic hydrochlorothiazide (HCTZ) to assess the additive effects of the combination versus monotherapy, to characterise the dose-response relationship of each drug in the presence of the other and to determine if quinapril would attenuate the hypokalemic effect of HCTZ. Following a two to four week placebo-baseline period, 460 qualifying patients with a DBP > or = 100 mmHg and < or = 115 mmHg were randomised to an eight week double-blind phase with one of 16 parallel treatments: placebo, one of three doses of quinapril monotherapy, one of three doses of HCTZ monotherapy or one of nine possible corresponding combinations of quinapril and HCTZ. Mean reductions in sitting SBP/DBP at trough with combination therapy ranged from 7.8 mmHg/7.2 mmHg to 19.6 mmHg/15.1 mmHg (n = 458). Results of the response surface analyses indicate that the effects of the two drugs were additive and that the maximum antihypertensive effect of quinapril in combination with HCTZ within the doses studied is achieved approximately at a dose of 26 mg quinapril and 25 mg HCTZ. The degree of attenuation of the hypokalemic effect of HCTZ was directly related to the dose of quinapril. At 40 mg quinapril, the HCTZ dose-related decreases of serum potassium were not apparent and overall hypokalemic effects were attenuated by quinapril. Thus, the combination of quinapril and HCTZ given once daily provided additive antihypertensive effects of predictable degrees and the addition of quinapril attenuated the hypokalemic effect of HCTZ.

Adult↗
PubMed1992

Detection of coronary artery disease with positron emission tomography and rubidium 82.

Myocardial blood flow was evaluated in 31 subjects with not only visual but also, for the first time, circumferential profile analysis of rubidium 82 (82Rb) images acquired with positron emission tomography. Fifteen were control subjects and 16 subjects had significant coronary artery disease, defined as 50% or greater diameter stenosis in a major coronary artery or a first-order branch. Simultaneous 82Rb images at three myocardial levels were obtained before and after intravenous dipyridamole plus handgrip stress. In patients with significant coronary artery disease, visual analysis correctly identified significant disease in 26 (76%) of 34 arteries and its absence in 12 (86%) of 14 normal arteries. According to circumferential profile analysis, these numbers were 91% and 86%, respectively. Thus circumferential analysis of 82Rb images, obtained before and after intravenous dipyridamole plus handgrip stress, yielded improved sensitivity and comparable specificity compared with visual analysis.

Coronary Disease↗