Patrick J. Kelly

Bio: Patrick J. Kelly is an academic researcher from Orlando Health. The author has contributed to research in topics: Physics & Stereotactic biopsy. The author has an hindex of 91, co-authored 449 publications receiving 26459 citations. Previous affiliations of Patrick J. Kelly include Beth Israel Deaconess Medical Center & Brigham and Women's Hospital.

Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease.

Abstract: Objective Glial cell line–derived neurotrophic factor (GDNF) exerts potent trophic influence on midbrain dopaminergic neurons. This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin). Methods Thirty-four PD patients were randomized 1 to 1 to receive bilateral continuous Ipu infusion of liatermin 15μg/putamen/day or placebo. The primary end point was the change in Unified Parkinson Disease Rating Scale (UPDRS) motor score in the practically defined off condition at 6 months. Secondary end points included other UPDRS scores, motor tests, dyskinesia ratings, patient diaries, and 18F-dopa uptake. Results At 6 months, mean percentage changes in “off” UPDRS motor score were −10.0% and −4.5% in the liatermin and placebo groups, respectively. This treatment difference was not significant (95% confidence interval, −23.0 to 12.0, p = 0.53). Secondary end point results were similar between the groups. A 32.5% treatment difference favoring liatermin in mean 18F-dopa influx constant (p = 0.019) was observed. Serious, device-related adverse events required surgical repositioning of catheters in two patients and removal of devices in another. Neutralizing antiliatermin antibodies were detected in three patients (one on-study and two in the open-label extension). Interpretation Liatermin did not confer the predetermined level of clinical benefit to patients with PD despite increased 18F-dopa uptake. It is uncertain whether technical differences between this trial and positive open-label studies contributed in any way this negative outcome. Ann Neurol 2006

Grading of astrocytomas: A simple and reproducible method

Abstract: This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on "ordinary astrocytoma" cell types, i.e., fibrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiotherapeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 "ordinary astrocytomas" were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar-type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2, 18% of grade 3, and 65.3% of grade 4. A 15-year period of follow-up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P less than 0.0001). Median survival was 4 years in grade 2, 1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 tumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double-blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low-grade (grades 1 and 2) and 96% in high-grade (grades 3 and 4) astrocytomas of ordinary type.(ABSTRACT TRUNCATED AT 400 WORDS)

Imaging-based stereotaxic serial biopsies in untreated intracranial glial neoplasms

Abstract: ✓ Forty patients with previously untreated intracranial glial neoplasms underwent stereotaxic serial biopsies assisted by computerized tomography (CT) and magnetic resonance imaging (MRI). Tumor volumes defined by computer reconstruction of contrast enhancement and low-attenuation boundaries on CT and T1 and T2 prolongation on MRI revealed that tumor volumes defined by T2-weighted MRI scans were larger than those defined by low-attenuation or contrast enhancement on CT scans. Histological analysis of 195 biopsy specimens obtained from various locations within the volumes defined by CT and MRI revealed that: 1) contrast enhancement most often corresponded to tumor tissue without intervening parenchyma; 2) hypodensity corresponded to parenchyma infiltrated by isolated tumor cells or in some instances to tumor tissue in low-grade gliomas or to simple edema; and 3) isolated tumor cell infiltration extended at least as far as T2 prolongation on magnetic resonance images. This information may be useful in plann...

Glial neoplasms: dynamic contrast-enhanced T2*-weighted MR imaging.

Abstract: PURPOSE: To evaluate the role of T2*-weighted echo-planar perfusion imaging by using a first-pass gadopentetate dimeglumine technique to determine the association of magnetic resonance (MR) imaging–derived cerebral blood volume (CBV) maps with histopathologic grading of astrocytomas and to improve the accuracy of targeting of stereotactic biopsy. MATERIALS AND METHODS: MR imaging was performed in 29 patients by using a first-pass gadopentetate dimeglumine T2*-weighted echo-planar perfusion sequence followed by conventional imaging. The perfusion data were processed to obtain a color map of relative regional CBV. This information formed the basis for targeting the stereotactic biopsy. Relative CBV values were computed with a nondiffusible tracer model. The relative CBV of lesions was expressed as a percentage of the relative CBV of normal white matter. The maximum relative CBV of each lesion was correlated with the histopathologic grading of astrocytomas obtained from samples from stereotactic biopsy or vo...

The 2007 WHO Classification of Tumours of the Central Nervous System

Abstract: The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide.

Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association

Abstract: The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.

A Randomized Trial of Surgery in the Treatment of Single Metastases to the Brain

Abstract: To assess the efficacy of surgical resection of brain metastases from extracranial primary cancer, we randomly assigned patients with a single brain metastasis to either surgical removal of the brain tumor followed by radiotherapy (surgical group) or needle biopsy and radiotherapy (radiation group). Forty-eight patients (25 in the surgical group and 23 in the radiation group) formed the study group; 6 other patients (11 percent) were excluded from the study because on biopsy their lesions proved to be either second primary tumors or inflammatory or infectious processes. Recurrence at the site of the original metastasis was less frequent in the surgical group than in the radiation group (5 of 25 [20 percent] vs. 12 of 23 [52 percent]; P less than 0.02). The overall length of survival was significantly longer in the surgical group (median, 40 weeks vs. 15 weeks in the radiation group; P less than 0.01), and the patients treated with surgery remained functionally independent longer (median, 38 weeks vs. 8 weeks in the radiation group; P less than 0.005). We conclude that patients with cancer and a single metastasis to the brain who receive treatment with surgical resection plus radiotherapy live longer, have fewer recurrences of cancer in the brain, and have a better quality of life than similar patients treated with radiotherapy alone.