Biomedical subjects

Adam N Mamelak

Publications and source records attributed to Adam N Mamelak.

12 recordsLinked to original sources

PubMed2006

Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma.

PURPOSE: TM-601 binds to malignant brain tumor cells with high affinity and does not seem to bind to normal brain tissue. Preclinical studies suggest that iodine-131 (131I) -TM-601 may be an effective targeted therapy for the treatment of glioma. We evaluated the safety, biodistribution, and dosimetry of intracavitary-administered 131I-TM-601 in patients with recurrent glioma. PATIENTS AND METHODS: Eighteen adult patients (17 with glioblastoma multiforme and one with anaplastic astrocytoma) with histologically documented recurrent glioma and a Karnofsky performance status of > or = 60% who were eligible for cytoreductive craniotomy were enrolled. An intracavitary catheter with subcutaneous reservoir was placed in the tumor cavity during surgery. Two weeks after surgery, patients received a single dose of 131I-TM-601 from one of three dosing panels (0.25, 0.50, or 1.0 mg of TM-601), each labeled with 10 mCi of 131I. RESULTS: Intracavitary administration was well tolerated, with no dose-limiting toxicities observed. 131I-TM-601 bound to the tumor periphery and demonstrated long-term retention at the tumor with minimal uptake in any other organ system. Nonbound peptide was eliminated from the body within 24 to 48 hours. Only minor adverse events were reported during the 22 days after administration. At day 180, four patients had radiographic stable disease, and one had a partial response. Two of these patients further improved and were without evidence of disease for more than 30 months. CONCLUSION: A single dose of 10 mCi 131I-TM-601 was well tolerated for 0.25 to 1.0 mg TM-601 and may have an antitumoral effect. Dosimetry and biodistribution from this first trial suggest that phase II studies of 131I-TM-601 are indicated.

Adult↗

PubMed2006

Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex.

The ability to distinguish novel from familiar stimuli allows nervous systems to rapidly encode significant events following even a single exposure to a stimulus. This detection of novelty is necessary for many types of learning. Neurons in the medial temporal lobe (MTL) are critically involved in the acquisition of long-term declarative memories. During a learning task, we recorded from individual MTL neurons in vivo using microwire electrodes implanted in human epilepsy surgery patients. We report here the discovery of two classes of neurons in the hippocampus and amygdala that exhibit single-trial learning: novelty and familiarity detectors, which show a selective increase in firing for new and old stimuli, respectively. The neurons retain memory for the stimulus for 24 hr. Thus, neurons in the MTL contain information sufficient for reliable novelty-familiarity discrimination and also show rapid plasticity as a result of single-trial learning.

Action Potentials↗

PubMed2006

Online detection and sorting of extracellularly recorded action potentials in human medial temporal lobe recordings, in vivo.

Understanding the function of complex cortical circuits requires the simultaneous recording of action potentials from many neurons in awake and behaving animals. Practically, this can be achieved by extracellularly recording from multiple brain sites using single wire electrodes. However, in densely packed neural structures such as the human hippocampus, a single electrode can record the activity of multiple neurons. Thus, analytic techniques that differentiate action potentials of different neurons are required. Offline spike sorting approaches are currently used to detect and sort action potentials after finishing the experiment. Because the opportunities to record from the human brain are relatively rare, it is desirable to analyze large numbers of simultaneous recordings quickly using online sorting and detection algorithms. In this way, the experiment can be optimized for the particular response properties of the recorded neurons. Here we present and evaluate a method that is capable of detecting and sorting extracellular single-wire recordings in realtime. We demonstrate the utility of the method by applying it to an extensive data set we acquired from chronically implanted depth electrodes in the hippocampus of human epilepsy patients. This dataset is particularly challenging because it was recorded in a noisy clinical environment. This method will allow the development of "closed-loop" experiments, which immediately adapt the experimental stimuli and/or tasks to the neural response observed.

Action Potentials↗

PubMed2005

Spatial selectivity in human ventrolateral prefrontal cortex.

The functional organization of lateral prefrontal cortex is not well understood, and there is debate as to whether the dorsal and ventral aspects mediate distinct spatial and non-spatial functions, respectively. We show for the first time that recordings from human ventrolateral prefrontal cortex show spatial selectivity, supporting the idea that ventrolateral prefrontal cortex is involved in spatial processing. Our results also indicate that prefrontal cortex may be a source of control signals for neuroprosthetic applications.

Brain Mapping↗

PubMed2005

Lack of association of cytomegalovirus with human brain tumors.

Cytomegalovirus (CMV) is thought to possess oncogenic properties and has been linked with a number of human malignancies. CMV infection was recently described in association with malignant gliomas. The intent of the present study was to further investigate the reported association between CMV and malignant gliomas. Tissue from 22 brain tumors of various histologic types and grades, four normal brains, six breast carcinomas, six colon carcinomas, six lung carcinomas, and six sarcomas were evaluated for the presence of CMV by polymerase chain reaction (PCR), in situ hybridization, and immunohistochemical methods. None of the brain tumors or normal brain tissue tested demonstrated evidence of CMV pp65 or early nuclear proteins by immunohistochemistry. In addition, no CMV RNA or DNA was detected in these cases by in situ hybridization and PCR. None of the carcinomas or sarcomas evaluated were positive for CMV by immunohistochemistry, in situ hybridization, or PCR. The findings of the present study suggest that CMV is not significantly associated with brain tumors in humans.

Brain Neoplasms↗

PubMed2005

Imaging glioma extent with 131I-TM-601.

UNLABELLED: TM-601, a 36-amino-acid peptide, selectively binds to glioma cells but not normal brain parenchyma. A phase I/II clinical trial of intracavitary 131I-TM-601 in adult patients with recurrent high-grade glioma was performed to determine the biodistribution and toxicity of this potential therapy. We evaluated imaging and biodistribution data from this trial to assess whether 131I-TM-601 might be useful in determining tumor extent. METHODS: Adult patients with recurrent high-grade gliomas underwent tumor resection, implantation of an intracavitary reservoir, and a single-dose injection of 370 MBq (10 mCi) 131I-TM-601 (0.25-1.0 mg of 131I-TM-601) 2-4 wks after surgery. Total-body planar scans and whole-brain SPECT scans were obtained on days 0, 1, 2, 3, and 6-8 after injection. Postresection MR images were coregistered to the SPECT scans using image analysis software. Analysis of the rate of radioactive decay and biologic elimination from the body and at the cavity site was performed. T1-weighted with gadolinium contrast (T1-Wc), T2-weighted (T2), and SPECT volumes were estimated by stereological Cavalieri sections and compared for overlap. RESULTS: Nonbound 131I-TM-601 was eliminated by 48 h after injection with the remaining radiolabeled peptide bound to tumor for at least 6-8 d. Biologic decay rates from 24 to 168 h after injection were only slightly shorter than the physical decay of 131I (6.3 vs. 8.0 d). A comparison of tumor volume estimates using all 3 imaging parameters indicated that 131I-TM-601-determined tumor volumes more closely paralleled T2 volumes than T1-Wc volumes. Overlap between coregistered MRI and SPECT scans corroborated the presence of radiolabeled peptide in the vicinity of infiltrating tumor up to 168 h after injection. CONCLUSION: 131I-TM-601 provides a reliable estimate for primary tumor extent. Further modification of this radiopeptide with other better imaging isotopes may provide an important tool for determining tumor extent and differentiating regions of viable tumor from necrosis.

Adult↗

PubMed2005

Locoregional therapies for glioma.

Glioma is the most common form of primary brain tumor, as well as the most lethal. Primary treatment strategies for glioma, including cytoreductive surgery, external-beam irradiation, and systemic chemotherapy have had generally disappointing results for these tumors. Limitations of these approaches include tumor invasion into functional brain tissue, lack of chemosensitivity, and shortcomings of systemic delivery. Recent attention has focused on locoregional strategies for treatment, as well as new methods for delivering therapy. Identification of tumor-specific surface targets, biologic agents, and more sophisticated means to deliver macromolecules to the brain is offering new promise in the treatment of these tumors. This paper will review the current state of the art of available locoregional therapies for glioma, with a particular focus on convection-enhanced delivery, targeted toxin, and other biologic strategies.

Antineoplastic Agents↗

PubMed2002

Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task.

For nonhumans, it has been shown that the hippocampus (HPC) is critical for spatial memory. We tested patients with unilateral HPC resections on a virtual analogue of a classic spatial task to assess HPC functioning in nonhumans: the Morris water task. We found that when humans are required to use spatial cues to navigate to a hidden escape platform in a pool, patients with HPC resections display severe impairments in spatial navigation relative to age-matched controls and age-matched patients who have had extra-HPC resections. This effect occurred for every patient tested and was evident regardless of side of surgery. Hence, it is apparent across species and irrespective of which hemisphere is damaged that the human HPC is critical for spatial/relational memory.

Brain Damage, Chronic↗

PubMed2002

Quantification of B0 homogeneity variation with head pitch by registered three-dimensional field mapping.

In this study, we quantify the extent to which B(0) homogeneity in adult humans is dependent on head pitch relative to the B(0) vector. Three-dimensional, whole-brain B(0) field maps were acquired in five normal subjects for three generalized head pitch angles. Optimal first- and second-order shimming of the experimental B(0) maps were simulated numerically. The spatial B(0) distribution within the brain was analyzed following automated volumetric co-registration of all data. Increasing head pitch improves both the resonance offset and local homogeneity in the inferior frontal lobes, but introduces inhomogeneities in other regions of the brain which cannot be compensated by first-order shimming but are further improved by second-order shimming.

Adult↗

PubMed2002

Choriocarcinoma brain metastasis in a patient with viable intrauterine pregnancy. Case report.

The authors report the case of a woman who presented during her 30th week of pregnancy with a large brain metastasis from a previously undetected metastatic choriocarcinoma. The metastasis caused significant neurological deficit due to mass effect, necessitating rapid intervention. Medical management included a regimen of high-dose corticosteroid medications for 36 hours, followed by cesarean delivery of the fetus and craniotomy to remove the metastatic tumor, chemotherapy and radiation therapy were begun within 1 week postsurgery. Both the baby and mother survived, and as of the 1-year follow-up examination, there was no evidence of disease in the mother. This is only the second report of a metastatic choriocarcinoma associated with a simultaneous viable intrauterine pregnancy, and the only case in which surgical removal of a brain metastasis was required. Coordinated multidisciplinary treatment of mother and fetus by members of the neurosurgery, medical oncology, neonatology, and obstetrics services facilitated a good outcome in this case.

Adult↗

PubMed2002

Magnetoencephalography-directed surgery in patients with neocortical epilepsy.

OBJECT: Magnetoencephalography (MEG) and magnetic source (MS) imaging are techniques that have been increasingly used for preoperative localization of epileptic foci and areas of eloquent cortex. The use of MEG examinations must be carefully balanced against the high cost and technological investments required to perform these studies, particularly when less expensive alternative localization methods are available. To help elucidate the value of MEG, the authors have critically reviewed their experience with whole-head MEG in the case management of patients undergoing epilepsy surgery. METHODS: The authors identified 23 patients with suspected focal epilepsy who underwent whole-head MEG and MS imaging at Huntington Memorial Hospital and, subsequently, underwent invasive intracranial electrode monitoring and electrocorticography (ECoG) to localize the zone of seizure origin for surgical resection. The results of the MS imaging were retrospectively stratified into three groups by the number of interictal spikes recorded during a 4-hour recording session: Class I (no spikes), Class II (< or = five spikes), and Class III (> or = six spikes). Class III was further subdivided according to the clustering density of the interictal spikes: Class IIIA represents a mean distance between interictal spikes of 4 mm or greater (that is, diffusely clustered) and Class IIIB represents a mean distance between interictal spikes of less than 4 mm (that is, densely clustered). The authors analyzed these groups to determine to what extent the results of MS imaging correlated with the ECoG-determined zone of seizure origin. In addition, they assessed whether the MS imaging study provided critical localization data and correlated with surgical outcome following resection. A statistical analysis of these correlations was also performed. Of the 40 patients studied, 23 underwent invasive monitoring, including 13 with neocortical epilepsy, four with mesial temporal lobe epilepsy, and six with suspected neocortical epilepsy that could not be clearly localized by ECoG. Depth electrodes were used in nine cases, subdural grids in nine cases, depth electrodes followed by subdural grids and strips in four cases, and intraoperative ECoG in one case. Electrocorticography was able to localize the zone of seizure origin in 16 (70%) of 23 cases. In 11 (69%) of the 16 cases in which ECoG was able to localize the zone of seizure origin, the interictal spikes on the MS images were classified as Class IIIB (densely clustered) and regionally correlated to the MS imaging-determined localization in all cases (that is, the same lobe). In contrast, no Class IIIB cases were identified when ECoG was unable to localize the zone of seizure origin. This difference showed a trend toward, but did not achieve, statistical significance (p < 0.23), presumably because of the relatively small number of cases available for analysis. In three cases (all Class IIIB), MS imaging was used to guide invasive electrodes to locations that otherwise would not have been targeted and provided unique localization data, not evident from other imaging modalities, that strongly influenced the surgical management of the patient. The classification of findings on MS images into subgroups and subsequent statistical analysis generated a model that predicted that Class IIIB MS imaging data are likely to provide reliable information to guide surgical placement of electrodes, but all other data groups do not provide localization information that is reliable enough to guide surgical decision making. CONCLUSIONS: Magnetic source imaging can provide unique localization information that is not available when other noninvasive methods are used. Magnetic source imaging appears most useful for cases of neocortical epilepsy. In particular, when an MS imaging study revealed six or more interictal spikes that were densely clustered in a single anatomical location, the MS image was highly correlated with the zone of seizure origin identified by ECoG. In these cases the MS imaging data may be useful to guide placement of intracranial electrodes.

Adult↗

PubMedDate not supplied

Current surgical options in the control of cancer pain.

PURPOSE: Pain syndromes resulting from recurrent or metastatic cancer require careful evaluation to determine the cause of the pain and the appropriate and judicious use of antitumor treatment. The choice of therapy must integrate the type of pain, its function, the overall disease burden of the patient, and psychological aspects of the cancer. As a general rule, opioid analgesics are the mainstay of treatment in patients with cancer-related pain. When pharmacologic pain control is insufficient or is associated with intolerable side effects, the surgical management of pain can be considered. OVERVIEW: In this article, we review the options, indications, and side effects of the interventional and surgical methods available for the treatment of cancer-related pain. CLINICAL IMPLICATIONS: Planning surgical treatment for cancer-related pain after a patient's lack of response to therapy with opioid analgesics requires an understanding of sensory innervation as well as a realistic expectation of survival, anesthetic risk, or possibility of incomplete pain relief. As such, surgical interventions must be tailored to the individual patient. Clinicians should keep in mind the surgical alternatives for the effective control of pain when it becomes apparent that medical therapy is ineffective.

Humans↗