John McCann

Baystate Medical Center

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Margaret Priestley

Children's Hospital of Philadelphia

Andreas W. Loepke

Children's Hospital of Philadelphia

C. Dean Kurth

Children's Hospital of Philadelphia

C. Dean Kurth

Humboldt-Universität zu Berlin

Jeffrey A. Golden

Saint Ambrose University

John J. McAuliffe

Cincinnati Children's Hospital Medical Center

Elizabeth Hughes

Sandwell & West Birmingham Hospitals NHS Trust

Irene B. OʼHara

Children's Hospital of Philadelphia

Steve C. Danzer

Cincinnati Children's Hospital Medical Center

George K. Istaphanous

Children's Hospital of Los Angeles

Cooperative Institutions

Cincinnati Children's Hospital Medical Center

University of Pennsylvania

Queen's University Belfast

Children's Hospital of Philadelphia

Harvard University

Dana-Farber Cancer Institute

University of Cincinnati

Philadelphia University

University of Cincinnati Medical Center

Almac (United Kingdom)

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Room F, 10/16/2000 9: 00 AM - 11: 00 AM (PS) Brain Caspase Activity Is Significantly Elevated 72 Hours after Deep Hypothermic Circulatory Arrest in Newborn Pigs

Anesthesiology (2000)

Margaret Priestley Chandra Ramamoorthy John McCann C. Dean Kurth

10.1097/00000542-200009001-00705

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Citations (0)

Lowering Immune Suppression Drugs Post-Transplant May Cut Cancer Risk

JNCI Journal of the National Cancer Institute (2003)

John McCann

10.1093/jnci/95.12.848

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Citations (6)

A phase I dose-escalation study of the novel peptide ALM201 in patients (pts) with advanced solid tumours

Annals of Oncology (2017)

Aya El Helali Ruth Plummer Gordon C. Jayson Vicky M. Coyle Yvette Drew

Tolerability

10.1093/annonc/mdx367.017

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Citations (8)

A Combination of Mild Hypothermia and Sevoflurane Affords Long-Term Protection in a Modified Neonatal Mouse Model of Cerebral Hypoxia-Ischemia

Anesthesia & Analgesia (2014)

Erica P. Lin Lili Miles Elizabeth Hughes John McCann Charles V. Vorhees

Infant brain injury from hypoxia-ischemia (HI) can lead to life-long impairment, but protective strategies are lacking. Short-term but not long-term protection has been demonstrated in the Rice-Vannucci neonatal brain ischemia model (RVM) by volatile anesthetic administration before HI, while exposure during HI has not been tested. In the current study, we evaluated a combination of sevoflurane and mild hypothermia as a protective approach during HI, both short- and long-term, by introducing intubation and mechanical ventilation to the RVM.The right common carotid artery was ligated in 10-day-old mice during brief sevoflurane anesthesia, followed by a 2-hour recovery with the dam. Littermates were then randomized to either: HI spontaneously breathing 10% oxygen for 60 minutes (the classical RVM); HI-Protect mild hypothermia and orotracheal intubation and mechanical ventilation with 3.5% sevoflurane in 10% oxygen for 60 minutes; or Room Air spontaneously breathing room air for 60 minutes. In a nonsurviving cohort, cerebral oxygenation was monitored in the area at risk and the contralateral hemisphere during HI or HI-Protect using visible-light spectroscopy (Spectros Corp). Mean arterial blood pressure and heart rate were measured. Arterial blood gases were obtained. Right/left brain hemispheric weight ratios and brain damage scores were determined 1 week after HI. In another group, learning and behavior were assessed in young adulthood (9 weeks) using spontaneous locomotion, Morris water maze, and apomorphine injection.During HI, ipsilateral and contralateral brain oxygenation, arterial blood pressures, blood gases, and glucose levels were similar in both ischemic groups, while heart rate was slower in the HI-Protect group. One week after ischemia, brain hemispheric weight ratios and injury scores in several brain regions were significantly worse after HI, compared with HI-Protect. Nine weeks after HI, Morris water maze hidden platform and reversal platform escape latencies, measures of spatial memory function, were superior after HI-Protect, compared with HI (P < 0.0001). HI-Protect animals demonstrated significantly less circling behavior after an apomorphine challenge (P < 0.0001), a measure of striatal integrity.To test the neuroprotective effects of volatile anesthetics during neonatal brain ischemia, we developed a modification of the RVM. By using mechanical ventilation and endotracheal intubation, sevoflurane administration during HI was survivable. The combination of sevoflurane administration and mild hypothermia during HI conferred not only short-term structural, but also long-term functional protection, compared with littermates treated according to the RVM. These findings warrant further studies to improve neurological outcome in critically ill infants.

Hypoxia

Room air distribution

10.1213/ane.0000000000000262

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Citations (27)

Regional patterns of neuronal death after deep hypothermic circulatory arrest in newborn pigs

Journal of Thoracic and Cardiovascular Surgery (1999)

C. Dean Kurth Margaret Priestley Jeffrey A. Golden John McCann Ramesh Raghupathi

Neocortex

10.1016/s0022-5223(99)70103-0

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Citations (89)

Colon Cancer: New Drug Options Improve on 5-FU

JNCI Journal of the National Cancer Institute (1998)

John McCann

Cancer drugs

10.1093/jnci/90.13.963

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Citations (1)

Near-Infrared Spectroscopy Cerebral Oxygen Saturation Thresholds for Hypoxia–Ischemia in Piglets

Journal of Cerebral Blood Flow & Metabolism (2002)

C. Dean Kurth Warren J. Levy John McCann

Detection of cerebral hypoxia–ischemia remains problematic in neonates. Near-infrared spectroscopy, a noninvasive bedside technology has potential, although thresholds for cerebral hypoxia–ischemia have not been defined. This study determined hypoxic–ischemic thresholds for cerebral oxygen saturation (Sco 2 ) in terms of EEG, brain ATP, and lactate concentrations, and compared these values with CBF and sagittal sinus oxygen saturation (Svo 2 ). Sixty anesthetized piglets were equipped with near-infrared spectroscopy, EEG, laser-Doppler flowmetry, and a sagittal sinus catheter. After baseline, Sco 2 levels of less than 20%, 20% to 29%, 30% to 39%, 40% to 49%, 50% to 59%, 60% to 79%, or 80% or greater were recorded for 30 minutes of normoxic normocapnia, hypercapnic hyperoxia, or bilateral carotid occlusion with or without arterial hypoxia. Brain ATP and lactate concentrations were measured biochemically. Logistic and linear regression determined the Sco 2 , CBF, and Svo 2 thresholds for abnormal EEG, ATP, and lactate findings. Baseline Sco 2 was 68 + 5%. The Sco 2 thresholds for increased lactate, minor and major EEG change, and decreased ATP were 44 ± 1%, 42 ± 5%, 37 ± 1%, and 33 ± 1%. The Sco 2 correlated linearly with Svo 2 (r = 0.98) and CBF (r = 0.89), with corresponding Svo 2 thresholds of 23%, 20%, 13%, and 8%, and CBF thresholds (% baseline) of 56%, 52%, 42%, and 36%. Thus, cerebral hypoxia-ischemia near-infrared spectroscopy thresholds for functional impairment are Sco 2 33% to 44%, a range that is well below baseline Sco 2 of 68%, suggesting a buffer between normal and dysfunction that also exists for CBF and Svo 2 .

Hyperoxia

Normocapnia

Hypoxia

10.1097/00004647-200203000-00011

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Citations (228)

Phase II trial of huN901-DM1 in patients with relapsed small cell lung cancer (SCLC) and CD56-positive small cell carcinoma

Journal of Clinical Oncology (2007)

John McCann Frank V. Fossella Miguel A. Villalona‐Calero A. W. Tolcher Panos Fidias

18084 Background: HuN901-DM1, a humanized antibody-maytansinoid immunoconjugagte, binds to CD56 which is expressed in almost all cases of SCLC as well as in other small cell carcinomas (SCC), neuroendocrine carcinomas, and multiple myeloma. The immunoconjugate binds to its target antigen, is internalized, then releases DM1. Methods: Patients with relapsed SCLC and CD56- positive SCC of other sites are treated with huN901-DM1 given as an intravenous infusion at 60 mg/m 2 /week for four consecutive weeks every six weeks. The study consists of two stages. Fourteen patients were initially enrolled. The occurrence of an objective response among the initial 14 patients prompted expansion to a total of 35 evaluable patients. Clinical response is evaluated by RECIST criteria. Results: To date, thirty patients have been treated in the study. Four patients experienced drug related serious adverse events (SAEs). Three patients had severe headache after the initial infusion of study drug. Symptoms markedly improved after 24 hours and then completely resolved. Severe headaches did not occur in subsequent patients who were pre-medicated with steroids prior to all infusions. A patient with a history of diabetic neuropathy and prior cisplatin treatment had grade 4 hyperesthesia. There was no evidence of clinically significant myelosuppression. HuN901-DM1 generally was well tolerated and no serious infusion reactions occurred. Preliminary pharmacokinetic (PK) data reveal no prolongation of terminal half-life of the immunoconjugate when PK parameters are compared from the first and fourth dose of cycle 1. Further, there was no evidence of antibody formation to the antibody component (HAHA) or drug component (HADA) of huN901-DM1. One patient (pt) with relapsed, SCLC had an objective partial response lasting 18 weeks and a pt with cervical SCC had an unconfirmed partial response. Stable disease was observed in five patients and lasted about 6 (3 pts), 12 (1 pt), and 18 weeks (1 pt). Conclusions: The study provides evidence of clinical activity and safety of huN901-DM1. Pre-medication with steroids appears effective in preventing severe headaches. Enrollment of additional patients to the study is planned. No significant financial relationships to disclose.

Immunoconjugate

10.1200/jco.2007.25.18_suppl.18084

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Citations (21)

Pemetrexed, Bevacizumab, or the Combination As Maintenance Therapy for Advanced Nonsquamous Non–Small-Cell Lung Cancer: ECOG-ACRIN 5508

Journal of Clinical Oncology (2019)

Suresh S. Ramalingam Suzanne E. Dahlberg Chandra P. Belani Joel Saltzman Nathan A. Pennell

Pemetrexed or bevacizumab is used for maintenance therapy of advanced nonsquamous non-small-cell lung cancer (NSCLC). The combination of bevacizumab and pemetrexed has also demonstrated efficacy. We conducted a randomized study to determine the optimal maintenance therapy.Patients with advanced nonsquamous NSCLC and no prior systemic therapy received carboplatin (area under the curve, 6), paclitaxel (200 mg/m2), and bevacizumab (15 mg/kg) for up to four cycles. Patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab (15 mg/kg), pemetrexed (500 mg/m2), or a combination of the two agents. The primary end point was overall survival, with bevacizumab serving as the control group.Of the 1,516 patients enrolled, 874 (57%) were randomly assigned after induction therapy to one of the three maintenance therapy groups. With a median follow-up of 50.6 months, median survival with pemetrexed was 15.9 months, compared with 14.4 months with bevacizumab (hazard ratio [HR], 0.86; P = .12); median survival with pemetrexed and bevacizumab was 16.4 months (HR, 0.9; P = .28); median progression-free survival was 4.2, 5.1 (HR, 0.85; P = .06), and 7.5 months (HR, 0.67; P < .001) for the three groups, respectively. Incidence of worst grade 3 to 4 toxicity was 29%, 37%, and 51%, respectively, for bevacizumab, pemetrexed, and the combination regimen.Single-agent bevacizumab or pemetrexed is efficacious as maintenance therapy for advanced nonsquamous NSCLC. Because of a lack of survival benefit and higher toxicity, the combination of bevacizumab and pemetrexed cannot be recommended.

Pemetrexed

Maintenance therapy

Carboplatin

Regimen

Combination therapy

10.1200/jco.19.01006

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Citations (63)

COMPARISON OF NEUROLOGIC OUTCOME FOLLOWING DEEP HYPOTHERMIC CIRCULATORY ARREST USING ALPHA-STAT AND PH-STAT CARDIOPULMONARY BYPASS

Anesthesiology (1998)

Margaret Priestley C. Dean Kurth Irene B. OʼHara Jeffrey A. Golden John McCann

Clinical death

10.1097/00000542-199809120-00088

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Citations (0)