PubMed Health⌕ Search

Biomedical subjects

Patrick J Kelly

Publications and source records attributed to Patrick J Kelly.

At least 19 recordsLinked to original sources
PubMed2006

Perfusion magnetic resonance imaging predicts patient outcome as an adjunct to histopathology: a second reference standard in the surgical and nonsurgical treatment of low-grade gliomas.

OBJECTIVE: To determine whether relative cerebral blood volume (rCBV) can predict patient outcome, specifically tumor progression, in low-grade gliomas (LGGs) and thus provide a second reference standard in the surgical and postsurgical management of LGGs. METHODS: Thirty-five patients with histologically diagnosed LGGs (21 low-grade astrocytomas and 14 low-grade oligodendrogliomas and low-grade mixed oligoastrocytomas) were studied with dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging. Wilcoxon tests were used to compare patients in different response categories (complete response, stable, progressive, death) with respect to baseline rCBV. Log-rank tests were used to evaluate the association of rCBV with survival and time to progression. Kaplan-Meier time-to-progression curves were generated. Tumor volumes and CBV measurements were obtained at the initial examination and again at follow-up to determine the association of rCBV with tumor volume progression. RESULTS: Wilcoxon tests showed patients manifesting an adverse event (either death or progression) had significantly higher rCBV (P = 0.003) than did patients without adverse events (complete response or stable disease). Log-rank tests showed that rCBV exhibited a significant negative association with disease-free survival (P = 0.0015), such that low rCBV values were associated with longer time to progression. Kaplan-Meier curves demonstrated that lesions with rCBV less than 1.75 (n = 16) had a median time to progression of 4620 +/- 433 days, and lesions with rCBV more than 1.75 (n = 19) had a median time to progression of 245 +/- 62 days (P < 0.005). Lesions with low baseline rCBV (< 1.75) demonstrated stable tumor volumes when followed up over time, and lesions with high baseline rCBV (> 1.75) demonstrated progressively increasing tumor volumes over time. CONCLUSION: Dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging may be used to identify LGGs that are either high-grade gliomas, misdiagnosed because of sampling error at pathological examination or that have undergone angiogenesis in the progression toward malignant transformation. This suggests that rCBV measurements may be used as a second reference standard to determine the surgical management/risk-benefit equation and postsurgical adjuvant therapy for LGGs.

Adolescent↗
PubMed2006

History of the cushing reflex.

Increasing systolic and pulse pressure with bradycardia and respiratory irregularity are signs of increased intracranial pressure, leading to cerebral herniation and fatal brainstem compression. This phenomenon, the vasopressor response, is generally known as the Cushing reflex based on Harvey Cushing's experimental work in Europe in 1901 and 1902. However, similar experiments had been carried out decades earlier by others, notably Paul Cramer, Ernst von Bergmann, Ernst von Leyden, Georg Althann, Friedrich Jolly, Friedrich Pagenstecher, Henri Duret, Bernard Naunyn, and Julius Schreiber. Cushing initially failed to give credit to the work of these predecessors. Nonetheless, he studied the brain's reaction to compression more carefully than previous researchers and offered an improved explanation of the pathophysiology of the phenomenon named after him.

Animals↗
PubMed2006

Rickettsia africae in the West Indies.

Rickettsia africae is the agent of African tick-bite fever, a mild but common disease of local persons and tourists in Africa. The major vector of this spotted fever group rickettsia is most likely Amblyomma variegatum, the tropical bont tick, which has become widely distributed through the West Indies in the last 30 years. This report reviews all available information on R. africae in the West Indies.

Animals↗
PubMed2005

Statistical design and analysis of pharmacogenetic trials.

Pharmacogenetic trials investigate the effect of genotype on treatment response. When there are two or more treatment groups and two or more genetic groups, investigation of gene-treatment interactions is of key interest. However, calculation of the power to detect such interactions is complicated because this depends not only on the treatment effect size within each genetic group, but also on the number of genetic groups, the size of each genetic group, and the type of genetic effect that is both present and tested for. The scale chosen to measure the magnitude of an interaction can also be problematic, especially for the binary case. Elston et al. proposed a test for detecting the presence of gene-treatment interactions for binary responses, and gave appropriate power calculations. This paper shows how the same approach can also be used for normally distributed responses. We also propose a method for analysing and performing sample size calculations based on a generalized linear model (GLM) approach. The power of the Elston et al. and GLM approaches are compared for the binary and normal case using several illustrative examples. While more sensitive to errors in model specification than the Elston et al. approach, the GLM approach is much more flexible and in many cases more powerful.

Clinical Trials as Topic↗
PubMed2005

An adaptive group sequential design for phase II/III clinical trials that select a single treatment from several.

There is increasing interest in combining Phases II and III of clinical development into a single trial in which one of a small number of competing experimental treatments is ultimately selected and where a valid comparison is made between this treatment and the control treatment. Such a trial usually proceeds in stages, with the least promising experimental treatments dropped as soon as possible. In this paper we present a highly flexible design that uses adaptive group sequential methodology to monitor an order statistic. By using this approach, it is possible to design a trial which can have any number of stages, begins with any number of experimental treatments, and permits any number of these to continue at any stage. The test statistic used is based upon efficient scores, so the method can be easily applied to binary, ordinal, failure time, or normally distributed outcomes. The method is illustrated with an example, and simulations are conducted to investigate its type I error rate and power under a range of scenarios.

Clinical Trials, Phase II as Topic↗
PubMed2005

A practical comparison of group-sequential and adaptive designs.

Sequential methods provide a formal framework by which clinical trial data can be monitored as they accumulate. The results from interim analyses can be used either to modify the design of the remainder of the trial or to stop the trial as soon as sufficient evidence of either the presence or absence of a treatment effect is available. The circumstances under which the trial will be stopped with a claim of superiority for the experimental treatment, must, however, be determined in advance so as to control the overall type I error rate. One approach to calculating the stopping rule is the group-sequential method. A relatively recent alternative to group-sequential approaches is the adaptive design method. This latter approach provides considerable flexibility in changes to the design of a clinical trial at an interim point. However, a criticism is that the method by which evidence from different parts of the trial is combined means that a final comparison of treatments is not based on a sufficient statistic for the treatment difference, suggesting that the method may lack power. The aim of this paper is to compare two adaptive design approaches with the group-sequential approach. We first compare the form of the stopping boundaries obtained using the different methods. We then focus on a comparison of the power of the different trials when they are designed so as to be as similar as possible. We conclude that all methods acceptably control type I error rate and power when the sample size is modified based on a variance estimate, provided no interim analysis is so small that the asymptotic properties of the test statistic no longer hold. In the latter case, the group-sequential approach is to be preferred. Provided that asymptotic assumptions hold, the adaptive design approaches control the type I error rate even if the sample size is adjusted on the basis of an estimate of the treatment effect, showing that the adaptive designs allow more modifications than the group-sequential method.

Algorithms↗
PubMed2005

Naming of Rickettsiae and rickettsial diseases.

Over the last 20 years, advances in molecular techniques have greatly facilitated the identification of the members of the Rickettsiales, and numerous new species and diseases have been described. In this paper, we review taxonomic rules and appropriate approaches to valid naming of rickettsial species and the diseases they cause.

Animals↗
PubMed2005

Resection of parietal lobe gliomas: incidence and evolution of neurological deficits in 28 consecutive patients correlated to the location and morphological characteristics of the tumor.

OBJECT: The goal of this study is to report the incidence and clinical evolution of neurological deficits in patients who underwent resection of gliomas confined to the parietal lobe. METHODS: Patient demographics, findings of serial neurological examinations, tumor location and neuroimaging characteristics, extent of resection, and surgical outcomes were tabulated by reviewing inpatient and office records, as well as all pre- and postoperative magnetic resonance (MR) images obtained in 28 consecutive patients who underwent resection of a glial neoplasm found on imaging studies to be confined to the parietal lobe. Neurological deficits were correlated with hemispheric dominance, location of the lesion within the superior or inferior parietal lobules, subcortical extension, and involvement of the postcentral gyrus. The tumors were located in the dominant hemisphere in 18 patients (64%); had a mean diameter of 39 mm (range 14-69 mm); were isolated to the superior parietal lobule in six patients (21%) and to the inferior parietal lobule in eight patients (29%); and involved both lobules in 14 patients (50%). Gross-total resection, documented by MR imaging, was achieved in 24 patients (86%). Postoperatively, nine patients (32%) experienced new neurological deficits, whereas seven (25%) had an improvement in their preoperative deficit. A correlation was noted between larger tumors and the presence of neurological deficits both before and after resection. Postoperatively higher-level (association) parietal deficits were noted only in patients with tumors involving both the superior and inferior parietal lobules in the dominant hemisphere. At the 3-month follow-up examination, five of nine new postoperative deficits had resolved. CONCLUSIONS: Neurological deterioration and improvement occur after resection of parietal lobe gliomas. Parietal lobe association deficits, specifically the components of Gerstmann syndrome, are mostly associated with large tumors that involve both the superior and inferior parietal lobules of the dominant hemisphere. New hemineglect or sensory extinction was not noted in any patient following resection of lesions located in the nondominant hemisphere. Nevertheless, primary parietal lobe deficits (for example, a visual field loss or cortical sensory syndrome) occurred in patients regardless of hemispheric dominance.

Adult↗
PubMed2004

Location of the active contact within the subthalamic nucleus (STN) in the treatment of idiopathic Parkinson's disease.

BACKGROUND: Chronic electrical stimulation of the subthalamic nucleus (STN) has been shown to be safe and effective in the treatment of medically refractory idiopathic Parkinson's disease. The clinically most relevant location of stimulation within the physiologically defined STN has not been confirmed. We reviewed the locations of active electrical contacts in 33 patients who underwent simultaneous bilateral STN deep brain stimulator (DBS) implantation. METHODS: The location of the microelectrode-defined dorsal STN border was compared to the location of the center of the active contact(s) employed in achieving optimal clinical results 6 to 18 months postoperatively. Furthermore, the location of this optimal contact was determined with respect to each individual patient's midcommissural point. Bilateral monopolar stimulation was employed in 30 patients using quadripolar DBS electrodes. RESULTS: After a minimum follow-up period of 6 months, the motor subscores (UPDRS Part III) in the postoperative on-stimulation/off-medication state were 64 +/- 18% (mean +/- SD) improved as compared to the preoperative off-medication state (p < 0.01). Additionally, an improvement of 53 +/- 38% was noted when comparing the postoperative on-stimulation/on-medication state to the preoperative on-medication state (p < 0.01). On average, the center of the optimal contact was 13.3 mm lateral, 0.5 mm posterior, 0.1 mm inferior to the mid-commissural point and was 0.1 +/- 2.1 mm dorsal to the physiologically defined dorsal STN border. CONCLUSIONS: While the achieved clinical results are comparable to those published in the literature, it appears that monopolar electrical stimulation at the anterior dorsolateral border of the STN yields optimal clinical results. Further studies are crucial in determining the precise mechanism of various modes of DBS in an effort to maximize clinical outcome.

Adult↗
PubMed2004

Advanced MRI for brain tumors: a neurosurgical perspective.

This paper discusses the modern neurosurgeon's use of advanced magnetic resonance imaging in pre-operative and perioperative planning. The effect of advanced imaging on the risk and benefit analysis of surgery is discussed in particular.

Brain Neoplasms↗
PubMed2004

Stereotactic navigation, Jean Talairach, and I.

This is not meant to be a comprehensive review of the work of Jean Talairach and his associates at the Centre Hospitalier Ste. Anne in Paris. Much more space than is available here would be required for that purpose. Talairach's contributions in the development of stereotactic instrumentation and methods, cerebral anatomy, neurophysiology, epilepsy, stereotactic biopsy and interstitial irradiation of tumors, radionuclide ablation of the pituitary gland, and surgical treatment of pain, movement disorders, and psychiatric illnesses are legend. Talairach is a creative pioneer who, from the time he arrived at Ste. Anne in 1937 at 28 years of age, has remained productive throughout his life and, even in his late eighties, continued to contribute to his field. His legacy is enormous. This work is simply meant to relate some of my personal anecdotes about Talairach and the people around him and to describe how the experience influenced my own career.

History, 20th Century↗
PubMed2003

Incidence and clinical evolution of postoperative deficits after volumetric stereotactic resection of glial neoplasms involving the supplementary motor area.

OBJECTIVE: We report the incidence and clinical evolution of postoperative deficits and supplementary motor area (SMA) syndrome after volumetric stereotactic resection of glial neoplasms involving the posterior one-third of the superior frontal convolution. We investigated variables that may be associated with the occurrence of SMA syndrome. METHODS: The postoperative clinical status of 27 consecutive patients who underwent resection of SMA gliomas was retrospectively reviewed. Neurological examination results were recorded 1 day, 1 week, 1 month, and 6 months postoperatively. The extent of tumor resection, the percentage of SMA resection, violation of the cingulate gyrus, and operative complications were tabulated. RESULTS: The overall incidence of SMA-related deficits was 26% (7 of 27 patients), with 3 patients having complete SMA syndrome and 4 patients having partial SMA syndrome. Two additional patients (7.5%) had other postoperative deficits, including one with mild facial weakness and one with transient aphasia. The resection of low-grade gliomas was associated with a higher incidence of SMA syndrome, an outcome that likely reflects more complete removal of functional SMA cortex in this subset of patients. Intraoperative monitoring localized the precentral sulcus within the preoperatively defined tumor volume in 6 (22%) of 27 patients, thereby precluding gross total resection. All 27 patients had excellent outcomes at the 6-month follow-up examination. CONCLUSION: When the resection of SMA gliomas is limited to the radiographic tumor boundaries, the incidence and severity of SMA syndrome may be minimized. With the use of these resection parameters, patients with high-grade SMA gliomas are unlikely to experience SMA syndrome. These findings are helpful in the preoperative counseling of patients who are to undergo cytoreductive resection of SMA gliomas.

Adolescent↗
PubMed2003

Vietnam, 1968-1969: a place and a year like no other.

THE VIETNAM WAR touched a generation of Americans with its human tragedy, sacrifice, and strife. In terms of casualties, it was the fourth most costly war in American history. However, despite a monumental military effort and modern technology, the war was lost as support from the American public and its elected officials waned. Now, in the aftermath of September 11, 2001, as we embark on what might well be another protracted war, lessons from the Vietnam experience become relevant. On a positive note, a refined system for the triage, management, and evacuation of wounded military personnel evolved in Vietnam. A wounded soldier could actually be at a well-equipped base hospital within minutes after injury. At those facilities, casualties had a more than 90% chance of survival, despite some of the most horrific wounds in the history of warfare.

Air Ambulances↗