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Biomedical subjects

N A Martin

Publications and source records attributed to N A Martin.

At least 37 records · Page 2Linked to original sources
PubMed2000

Treatment of a patient by vaccination with autologous dendritic cells pulsed with allogeneic major histocompatibility complex class I-matched tumor peptides. Case Report.

Dendritic cells (DCs) are antigen-presenting cells that play a central role in the initiation and modulation of antitumor immune responses. In this pilot study, we investigated the ability of autologous DCs pulsed ex vivo with allogeneic major histocompatibility complex class I-matched glioblastoma peptides to stimulate host antitumor immune responses when injected as a vaccine. A patient with recurrent brainstem glioblastoma multiforme (GBM) received a series of three intradermal immunizations of antigen-pulsed DCs on an outpatient basis following surgical debulking of her posterior fossa tumor. Dendritic cell vaccination was well tolerated, and no clinical signs of autoimmunity or experimental allergic encephalomyelitis were detected. She developed a measurable cellular immune response against the allogeneic glioblastoma peptides used in her vaccine preparation, as demonstrated by in vitro T-cell proliferation assays. In addition, increased T-cell infiltration was noted within the intracranial tumor site in the biopsy sample obtained following DC vaccination. An objective clinical response, however, was not evident, and this patient eventually died 21 months after her disease was diagnosed. To our knowledge, this is the first patient with brain cancer ever to be treated with DC-based immunotherapy. This case illustrates that vaccination with DCs pulsed with acid-eluted glioblastoma peptides is feasible and can induce systemic antigen-specific immunity in a patient with recurrent GBM. Additional studies are necessary to determine the optimum DC doses and antigen loading conditions that may translate into clinical effectiveness and survival benefit for patients with brain tumors. Phase I trials for malignant glioma are currently underway.

Antigens, Neoplasm↗
PubMed2000

Temporal and topographical characterization of language cortices using intraoperative optical intrinsic signals.

We used intraoperative optical imaging of intrinsic signals (iOIS) and electrocortical stimulation mapping (ESM) to compare functionally active brain regions in 10 awake patients undergoing neurosurgical resection. Patients performed two to four tasks, including visual and auditory naming, word discrimination, and/or orofacial movements. All iOIS maps included areas identified by ESM mapping. However, iOIS also revealed topographical specificity dependent on language task. In Broca's area, naming paradigms activated both anterior and posterior inferior frontal gyrus (IFG), while the word discrimination paradigm activated only posterior IFG. In Wernicke's area, object naming produced activations localizing over the inferior and anterior/posterior regions, while the word discrimination task activated superior and anterior cortices. These results may suggest more posterior phonological activation and more anterior semantic activations in Broca's area, and more anterior/superior phonological activation and more posterior/inferior semantic activations in Wernicke's area. Although similar response onset was observed in Broca's and Wernicke's areas, temporal differences were revealed during block paradigm (20-s) activations. In Broca's area, block paradigms yielded a boxcar temporal activation profile (in all tasks) that resembled response profiles observed in motor cortex (with orofacial movements). In contrast, activations in Wernicke's area responded with a more dynamic profile (including early and late peaks) which varied with paradigm performance. Wernicke's area profiles were very similar to response profiles observed in sensory and visual cortex. The differing temporal patterns may therefore reflect unique processing performed by receptive (Wernicke's) and productive (Broca's) language centers. This study is consistent with task-specific semantic and phonologic regions within Broca's and Wernicke's areas and also is the first report of response profile differences dependent on cortical region and language task.

Brain↗
PubMed2000

Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury.

Utilizing [18F]fluorodeoxyglucose positron emission tomography (FDG-PET), we studied the correlation between CMRglc and the level of consciousness within the first month following human traumatic brain injury. Forty-three FDG-PET scans obtained on 42 mild to severely head-injured patients were quantitatively analyzed for the determination of regional cerebral metabolic rate of glucose (CMRglc). Reduction of cerebral glucose utilization, defined as a CMRglc of < or =4.9 mg/100 g/min, was present regionally in 88% of the studies. The prevalence of global cortical CMRglc reduction was higher in severely head-injured patients (86% versus 67% mild-moderate), although the absolute magnitude was similar across the injury severity spectrum (mean CMRglc 3.9 +/- 0.6 mg/100 g/min). The level of consciousness, as measured by the Glasgow Coma Scale, correlated poorly with the global cortical CMRglc value (r = 0.08; p = 0.63). With regards to severity of head injury, this correlation was worst for the severely injured (r = -0.11; p = 0.58) and better for the mildly injured patients (r = 0.50; p = 0.07). In most cases, intraparenchymal hemorrhagic lesions were associated with either focal CMRglc reduction or elevation. It is concluded that the etiologies of CMRglc reduction are likely multifactorial given the complex nature of traumatic brain injury and that the reduction of CMRglc represents a fundamental pathobiologic state following head injury that is not tightly coupled to level of consciousness.

Adult↗
PubMed2000

A meningioma-mimicking tumor caused by Mycobacterium avium complex in an immunocompromised patient.

Intracranial tuberculomas manifesting radiologically as typical dural-based "meningiomas" have been reported, most frequently in immunosuppressed patients. Their incidence is high in developing countries; they are only sporadically observed in Western Europe and North America, usually in patients with acquired immunodeficiency syndrome (AIDS). According to published reports, intracranial tuberculomas are always due to infection by Mycobacterium tuberculosis. We report a case of a 50-year-old woman with systemic lupus erythematosus (SLE) who presented with a dural based, meningioma-like mass in the right frontal region, resulting from a localized infection by Mycobacterium avium complex. Histologically, the mass resembled a meningioma in being composed of spindly cells arranged in a fascicular pattern. Immunohistochemical stains showed this tumor to consist of a large aggregate of AFB-laden histiocytes without caseating necrosis or multinucleated giant cells.

Anti-Inflammatory Agents↗
PubMed2000

A new pocket-sized transcranial ultrasound device (NeuroDop): comparison with standard TCD.

The NeuroDop is a new bedside assessment tool consisting of a continuous wave ultrasound probe attached to a stethoscope earpiece. This study was designed to compare middle cerebral artery (MCA) velocity assessment obtained with the NeuroDop versus standard transcranial Doppler (TCD). TCD technologists performed continuous wave NeuroDop studies followed by standard TCD studies on 60 subjects. Technologists recorded presence of MCA signal and estimated velocity based on NeuroDop auditory characteristics. Signal was obtained in 108 MCA vessels with the portable unit and in 112 vessels using standard TCD. For detection of patency, sensitivity was 96%, specificity 88%, positive predictive value 99%, and negative predictive value 58%. Auditorially estimated velocities from the NeuroDop strongly correlated with TCD velocity measures (r = 0.71). Categorical estimates of velocity as decreased (< 37 cm/sec), normal (37-81 cm/sec), or increased (> 81 cm/sec) demonstrated an accuracy rate of 85%. This novel stethoscope-continuous wave unit has excellent sensitivity in detecting presence of MCA patency. Moreover, MCA velocities can be characterized to a reasonable degree of accuracy based on NeuroDop auditory characteristics. The NeuroDop shows promise as a tool to rapidly assess and serially monitor presence and amplitude of MCA velocity and may help guide thrombolytic and other emergency management decisions in stroke patients.

Blood Flow Velocity↗
PubMed2000

Activation of cannabinoid receptors in rat brain by WIN 55212-2 produces coupling to multiple G protein alpha-subunits with different potencies.

Previous studies had shown that the amplification factors for cannabinoid receptors, defined as the number of total G proteins activated per occupied receptor, differs between several rat brain regions. In this study, we sought to determine which specific Gi/Go(alpha) subunits were activated by CB1 receptors in several rat brain regions and if this coupling might explain the regional differences in receptor/G protein amplification factors. Furthermore, we examined whether cannabinoid agonists might activate different subtypes of G(alpha) subunits with varying degrees of efficacy and/or potency. Activation of specific G proteins by cannabinoid receptors was evaluated by the ability of the agonist WIN 55212-2 to stimulate incorporation of [alpha-(32)P]azidoanilido-GTP into G(alpha) subunits in membranes. Photolabeled G proteins were either directly resolved using urea/SDS-polyacrylamide gel electrophoresis or first immunoprecipitated with specific antisera for different G(alpha) subunits before electrophoresis. Individual G(alpha) subunits were separated into distinct bands on a single gel and the amount of agonist-induced increase in radioactivity was quantified by densitometry. Stimulation of CB1 receptors by WIN 55212-2 resulted in the activation of a distinct pattern of at least five different G(ialpha)/G(oalpha) subunits in several brain regions. Furthermore, although the pattern of G proteins activated by WIN 55212-2 appeared to be similar across brain regions, slight differences were observed in both the percentage of increase and the amount of the individual G(alpha) subunits activated. Most importantly, the amount of WIN 55212-2 required to half-maximally activate individual G proteins in the cerebellum varied over a 30-fold range for different G(alpha) subunits. These results suggest that cannabinoid receptors activate multiple G proteins simultaneously in several brain regions and both the efficacy and potency of cannabinoid agonists to activate individual G(alpha) subunits may vary considerably.

Animals↗
PubMed2000

Therapeutic embolization of arteriovenous malformations: the case for and against.

The field of endovascular therapy has demonstrated stunning technical achievements in AVM embolization. Embolization has the potential to enhance the safety and efficacy of AVM treatment when applied in carefully considered cases. The utility of embolization, at the present time, is limited by the fact that the procedure may be associated with disabling or fatal complications, and because complete or near-complete AVM nidus occlusion can be achieved only in a minority of cases. Because of these factors, embolization should not be considered a "standard-of-care" for the management of all cerebral AVMs, and careful case selection for embolization, with well-defined treatment goals in mind, is essential. Finally, not all AVMs that can be embolized should be embolized.

Cerebral Hemorrhage↗
PubMed1999

Ballonn-assisted Guglielmi detachable coiling of wide-necked aneurysma: Part II--clinical results.

OBJECTIVE: To demonstrate the indications and efficacy of balloon-assisted Guglielmi detachable coiling (BAGDC). METHODS: BAGDC was used for 23 patients (19 women and 4 men; mean age, 55 yr) (17%) of a series of 136 consecutive patients who underwent Guglielmi detachable coiling of aneurysms. Every aneurysm had a wide neck, and 57% were large (11-25 mm in diameter). In each case, a nondetachable silicone balloon was advanced in the parent artery and inflated to occlude the neck of the aneurysm and stabilize the Guglielmi detachable coil delivery microcatheter at the aneurysm neck. Guglielmi detachable coils were then deposited. The balloon was then deflated to verify appropriate coil placement and stability, and finally, the Guglielmi detachable coils were detached. This process was repeated until the aneurysm was suitably embolized. RESULTS: One hundred percent aneurysm embolization was achieved in 19 patients (83%), and 95 to 100% embolization was achieved in 4 patients (17%). Twenty-two patients (96%) were at their preprocedure neurological baseline after the procedure. There were three complications in the study. One patient died after sustaining subarachnoid hemorrhage-induced vasospasm followed by a hemorrhagic infarction. She had undergone an unsuccessful clip ligation of her aneurysm. A second patient developed an intra-arterial thrombus at the site of balloon deployment. She sustained ischemic events that were treated with thrombolysis and anticoagulation. She made a complete recovery. A third patient developed an intra-arterial thrombus that was noted during the procedure. She was treated with intra-arterial thrombolysis and experienced no clinical sequelae. No permanent complications could be attributed to the BAGDC technique. The median clinical follow-up time was 10 months. No patient required additional treatment or developed a recurrent aneurysm neck or lumen. CONCLUSION: BAGDC is a promising adjunct to the treatment of wide-necked aneurysms. The balloon serves two purposes: it stabilizes the microcatheter in the aneurysm during coil delivery, and it forces the coil to assume the three-dimensional shape of the aneurysm without impinging on the parent artery.

Adult↗
PubMed1999

Endovascular treatment of multiple intracranial aneurysms by using Guglielmi detachable coils.

OBJECT: The purpose of this paper is to present the authors' experience with Guglielmi detachable coil (GDC) embolization of multiple intracranial aneurysms and to evaluate the results of this therapy in single-stage procedures. METHODS: Clinical and angiographic evaluations were performed in 38 consecutive patients with multiple intracranial aneurysms treated by GDC embolization between March 1990 and October 1997. Twenty-nine patients presented with subarachnoid hemorrhage (SAH), four with mass effect, and five were asymptomatic. These 38 patients harbored 101 aneurysms, 79 of which were treated with GDCs, 14 by surgical clipping, and eight were left untreated. Of the GDC-treated lesions, a complete endovascular occlusion was achieved in 55 aneurysms (70%), and 24 (30%) presented neck remnants. Twenty-five patients (66%) underwent GDC embolization of more than one aneurysm in the first session. Eighteen (86%) of 21 patients with acute SAH underwent treatment for all aneurysms within 3 days after admission (15 of 21 in one session). Follow-up angiographic studies in 30 patients demonstrated an unchanged or improved result in 94% of the aneurysms (59 lesions) and coil compaction in 6% (four lesions). The overall clinical outcome was excellent in 34 patients (89%), good in one (3%), fair in one (3%), and death in two (5%). CONCLUSIONS: Endovascular treatment of multiple intracranial aneurysms, regardless of their location, with GDCs was performed safely in one session, even during the acute phase of SAH. Treatment of all aneurysms in one session protected the patient from rebleeding and eliminated the risk of mistakenly treating only the unruptured aneurysms.

Adolescent↗
PubMed1999

Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring.

OBJECT: The early pathophysiological features of traumatic brain injury observed in the intensive care unit (ICU) have been described in terms of altered cerebral blood flow, altered brain metabolism, and neurochemical excitotoxicity. Seizures occur in animal models of brain injury and in human brain injury. Previous studies of posttraumatic seizures in humans have been based principally on clinical observations without a systematic approach to electroencephalographic (EEG) recording of seizures. The purpose of this study was to determine prospectively the incidence of convulsive and nonconvulsive seizures by using continuous EEG monitoring in patients in the ICU during the initial 14 days post-injury. METHODS: Ninety-four patients with moderate-to-severe brain injuries underwent continuous EEG monitoring begin-ning at admission to the ICU (mean delay 9.6+/-5.4 hours) and extending up to 14 days postinjury. Convulsive and nonconvulsive seizures occurred in 21 (22%) of the 94 patients, with six of them displaying status epilepticus. In more than half of the patients (52%) the seizures were nonconvulsive and were diagnosed on the basis of EEG studies alone. All six patients with status epilepticus died, compared with a mortality rate of 24% (18 of 73) in the nonseizure group (p<0.001). The patients with status epilepticus had a shorter mean length of stay (9.14+/-5.9 days compared with 14+/-9 days [t-test, p<0.031). Seizures occurred despite initiation of prophylactic phenytoin on admission to the emergency room, with maintenance at mean levels of 16.6+/-2.8 mg/dl. No differences in key prognostic factors (such as the Glasgow Coma Scale score, early hypoxemia, early hypotension, or 1-month Glasgow Outcome Scale score) were found between the patients with seizures and those without. CONCLUSIONS: Seizures occur in more than one in five patients during the 1st week after moderate-to-severe brain injury and may play a role in the pathobiological conditions associated with brain injury.

Adolescent↗
PubMed1998

Topographical and temporal specificity of human intraoperative optical intrinsic signals.

The goal of this study was to determine the topographical and temporal specificity of neuronal and vascular responses using an intraoperative optical technique (iOIS). The face, thumb, index, and middle fingers were stimulated individually to obtain separate maps of cortical activation. Peak optical responses provided unique, non-overlapping cortical brain maps. Non-peak signals were more dispersed and produced overlapping responses from different digits. Peak iOIS responses colocalized with electrocortical stimulation mapping and evoked potentials. Temporally, we observed statistically significant specificity corresponding to sequential cortical activation during early optical signals (500-1750 ms), but later perfusion responses were non-specific. To our knowledge, this is the first report of either topographical specificity in overlapping spatial patterns, and/or temporal specificity in early perfusion profiles. These results therefore may have significant implications for other perfusion dependent functional imaging techniques.

Anesthesia, General↗
PubMed1998

Unruptured aneurysms presenting with mass effect symptoms: response to endosaccular treatment with Guglielmi detachable coils. Part I. Symptoms of cranial nerve dysfunction.

OBJECT: Embolization of intracranial aneurysms by using Guglielmi detachable coils (GDCs) is proving to be a safe method of protecting aneurysms from rupture. Occasionally, patients with unruptured intracranial aneurysms present with symptoms related to the aneurysm's mass effect on either the brain parenchyma or cranial nerves. In the present study, the authors conducted a retrospective review to evaluate the response to GDC embolization in a series of 19 patients presenting with cranial nerve dysfunction due to mass effect. METHODS: Aneurysms were classified by size, shape, wall calcification, and amount of intraluminal thrombus. Patients were classified by duration of symptoms prior to GDC treatment (range < 1 month to > 10 years). Clinical assessment was performed within days of the GDC procedure and at later follow-up appointments (range 1-70 months, mean 24 months). In the immediate post-GDC period, four patients experienced worsening of cranial nerve deficits. Two of the four patients had transient worsening of visual acuity, which later improved to better than baseline status. Another patient who had presented with headache and seventh and eighth cranial nerve deficits from a vertebrobasilar junction aneurysm had improvement in these symptoms, but developed a new diplopia. The fourth patient had worsening of her visual acuity, which had not resolved at the 1-month follow-up examination; this patient later underwent surgical decompression. CONCLUSIONS: On late follow-up review, the response was classified as complete resolution of symptoms in six patients (32%), improvement in eight patients (42%), no significant change in four patients (21%), and symptom worsening in one patient (5%). Patients with smaller aneurysms and those with shorter pretreatment duration of symptoms were more likely to experience an improvement in their symptoms following GDC treatment, although statistical significance was not reached in this series (p=0.603 and p=0.111, respectively). The presence of aneurysmal wall calcification (six patients) or intraluminal thrombus (12 patients) showed no correlation with the response of mass effect symptoms in these patients.

Adult↗
PubMed1998

Increase in extracellular glutamate caused by reduced cerebral perfusion pressure and seizures after human traumatic brain injury: a microdialysis study.

OBJECT: To determine the extent and duration of change in extracellular glutamate levels after human traumatic brain injury (TBI), 17 severely brain injured adults underwent implantation of a cerebral microdialysis probe and systematic sampling was conducted for 1 to 9 days postinjury. METHODS: A total of 772 hourly microdialysis samples were obtained in 17 patients (median Glasgow Coma Scale score 5+/-2.5, mean age 39.4+/-20.4 years). The mean (+/-standard deviation) glutamate levels in the dialysate were evaluated for 9 days, during which the mean peak concentration reached 25.4+/-13.7 microM on postinjury Day 3. In each patient transient elevations in glutamate were seen each day. However, these elevations were most commonly seen on Day 3. In all patients there was a mean of 4.5+/-2.5 transient elevations in glutamate lasting a mean duration of 4.4+/-4.9 hours. These increases were seen in conjunction with seizure activity. However, in many seizure-free patients the increase in extracellular glutamate occurred when cerebral perfusion pressure was less than 70 mm Hg (p < 0.001). Given the potential injury-induced uncoupling of cerebral blood flow and metabolism after TBI, these increases in extracellular glutamate may reflect a degree of enhanced cellular crisis, which in severe head injury in humans appears to last up to 9 days. CONCLUSIONS: Extracellular neurochemical measurements of excitatory amino acids may provide a marker for secondary insults that can compound human TBI.

Adult↗
PubMed1998

The comparative effects of sports massage, active recovery, and rest in promoting blood lactate clearance after supramaximal leg exercise.

OBJECTIVE: To determine the comparative effect of sports massage, active recovery, and rest on promoting blood lactate clearance after maximal anaerobic (supramaximal) leg exercise. DESIGN AND SETTING: A counterbalanced experimental design with repeated measures was used. The repeated measures were the three treatment conditions. The order of the conditions was determined by random assignment to a counterbalanced test sequence. All data were collected in the Human Energy Research Laboratory at the University of Pittsburgh. SUBJECTS: Ten male competitive cyclists volunteered for this investigation. MEASUREMENTS: Serial venous blood samples were drawn and analyzed for blood lactate concentration for each test condition. RESULTS: There were significant main effects for both absolute and relative values of blood lactate concentration between the three treatment groups and across time within groups. CONCLUSIONS: After supramaximal leg exercise, active recovery produced significant decreases in both absolute and relative measures of blood lactate concentration when compared with the sports massage and rest conditions. No significant difference was found between sports massage and rest for either absolute or relative changes in blood lactate concentration.

Journal Article↗
PubMed1998

The combination of endovascular and surgical techniques for the treatment of intracranial aneurysms.

Endovascular technique, primarily employing electrolytically detachable platinum coils--the Guglielmi Detachable Coil system--is a viable therapeutic option for the management of many intracranial aneurysms. Inclusion of endovascular techniques into a comprehensive intracranial aneurysm treatment program beneficially extends the options for treatment, and enhances safety and efficacy of aneurysm treatment. Endovascular therapy should be considered not a replacement for surgical clipping, but a welcome addition to the various techniques available for aneurysm treatment. The selection of surgical or endovascular treatment for ruptured and unruptured intracranial aneurysms requires an understanding of the relative physical, anatomical, and physiological characteristics of both endovascular and surgical treatment. This article discusses the selection of endovascular or surgical treatment for an individual patient, which requires a careful consideration of aneurysm-specific and patient-specific characteristics. This article also describes the combination of endovascular and surgical techniques for the management of complex aneurysms. The availability of high quality neurosurgical and endovascular treatment for intracranial aneurysms is expected to provide clinical outcomes superior to those achieved by using either method in isolation.

Cerebral Angiography↗