Biomedical subjects

N G Baldwin

Publications and source records attributed to N G Baldwin.

16 recordsLinked to original sources

PubMed1997

Ex vivo expansion of tumor-draining lymph node cells using compounds which activate intracellular signal transduction. I. Characterization and in vivo anti-tumor activity of glioma-sensitized lymphocytes.

It has been shown that adoptive immunotherapy can be curative for established malignant tumors. The key to this treatment lies in obtaining sufficient numbers of lymphocytes which are sensitized to recognize tumor antigens and carry out immunological reactions to destroy tumor cells. Reported here are the results of experiments to: 1) sensitize lymphocytes to the antigens of rat glioma cells and expand them ex vivo for use in adoptive immunotherapy, 2) characterize the cells of the expanded population, and 3) evaluate antitumor activity in a cohort of rats with well-established intracranial gliomas. Viable RT-2 glioma cells were injected into the hind foot pads of syngeneic Fischer 344 rats. After 10 days, the tumor draining lymph nodes (DLN) were harvested from the injected limbs and mechanically dissociated. The cells of the DLN were then suspended in culture medium supplemented with low dose interleukin-2 (IL-2) and incubated for 18 hours with Bryostatin-1 and ionomycin (Bryo/Io) to stimulate expansion. The cells were next washed to remove the Bryo/Io and resuspended in culture medium and IL-2. Population expansions of 40- to 100-fold were seen after 8 days. Flow cytometric analysis showed these cells to be a nearly pure population of T lymphocytes of the CD3+CD8+ phenotype. Intravenous injection of the ex vivo expanded DLN cells did not significantly improve survival of rats with a seven-day intracerebral RT-2 glioma, although, compared to untreated controls, the tumors of the treated animals were smaller, showed no necrosis, and appeared to be less infiltrative. Furthermore, the treated animals had a pronounced lymphocytic infiltration of their tumors with greater associated degrees of hemorrhagic change and peritumoral edema. When the ex vivo expanded DLN cells were intravenously injected into three-day intracerebral RT-2 glioma models, tumors were almost always eliminated and the animals survived their tumor challenge. We conclude that successful expansion of glioma-sensitized DLN lymphocytes is possible and that adoptive immunotherapy using these cells is capable of effectively limiting the progression of large gliomas, while totally eradicating small ones.

Animals↗

PubMed1997

Ex vivo expansion of tumor-draining lymph node cells using compounds which activate intracellular signal transduction. II. Cytokine production and in vivo efficacy of glioma-sensitized lymphocytes.

We have investigated the anti-tumor activity of ex vivo activated and expanded T cells which had been sensitized in vivo to one of two different syngeneic rat glioma cell lines; D74 or RT-2. Rats were sensitized by inoculation of irradiated tumor cells into each hind foot pad. After 10 days, the tumor-draining lymph node (DLN) from each popliteal region was excised and prepared as a single cell suspension. Tumor-DLN lymphocytes were next activated overnight in RPMI-1640 medium containing 10% fetal bovine serum (FBS), Bryostatin-1 (5 nM), ionomycin (1 microM), and 20 U human recombinant interleukin-2 (IL-2) per ml. Culture for seven days in RPMI-1640 supplemented with FBS and IL-2 resulted in approximately 100-fold expansion of the lymphocyte population. Both D74- and RT-2-sensitized T cells constitutively secreted tumor necrosis factor-alpha, and both lymphocyte populations produced comparable amounts of the cytokine when co-cultured with either glioma cell line. Neither D74- and RT-2-sensitized effectors constitutively secreted gamma-interferon (gamma-IFN), but both populations produced gamma-IFN when exposed to either glioma cell line in vitro. D74-sensitized T cells released significantly more gamma-IFN than the RT-2 DLN lymphocytes. In vitro Chromium-release assays indicated that RT-2-sensitized T cells were more cytotoxic for RT-2 targets than for the D74 line and that D74-sensitized effectors were also more cytotoxic for RT-2 targets. To assess in vivo therapeutic efficacy, rats who had been inoculated intradermally with RT-2 cells three days earlier received an intravenous injection of RT-2- or D74-sensitized DLN cells (10(6) cells/gram body weight) expanded after activation with Bryostatin-1 and ionomycin or an equal number of lymphokine-activated killer (LAK) cells. Tumor diameters were measured daily and revealed that injection of glioma-sensitized lymphocytes led to the elimination of tumor while treatment with LAK cells had no therapeutic benefit. These results indicate, that at least for these two glioma lines, gamma-IFN release, rather than in vitro cytotoxicity, was a better predictor for in vivo immunotherapeutic efficacy of the glioma-sensitized, expanded T cells.

Animals↗

PubMed1997

Adoptive immunotherapy of malignant glioma using tumor-sensitized T lymphocytes.

Malignant glioma remains one disease for which there is no curative therapy. Clearly there is a need to explore new and innovative approaches for their treatment. In this report, we review our preclinical trial of a new adoptive immunotherapy protocol using cytotoxic T lymphocytes (CTL) which had been sensitized to glioma in vivo and then activated and their number expanded ex vivo using compounds which enhance signal transduction. These glioma-sensitized lymphocytes, when introduced systemically into rats with either an intracerebral or intradermal glioma, eradicated or slowed the progression of their tumor. These results indicate for the first time that a reproducible and sustained eradication of a malignant glioma could be achieved by the adoptive transfer of tumor-sensitized, ex vivo expanded CTL. A Phase I clinical trial is now underway to test the safety and potential efficacy of this immunotherapy in patients with recurrent malignant glioma.

Animals↗

PubMed1996

A comparison of the pathophysiologic effects of carbon dioxide, nitrous oxide, and helium pneumoperitoneum on intracranial pressure.

BACKGROUND: Previous studies have suggested that diagnostic laparoscopy may be contraindicated in multiple trauma patients with closed head injuries because of the detrimental effects of carbon dioxide (CO2) pneumoperitoneum on intracranial pressure (ICP). In this study we compared the effects of two alternative inflation gases, helium (He) and nitrous oxide (N2O), against the standard agent used in most hospitals, CO2. ICP was monitored in experimental animals both with and without a space occupying intracranial lesion designed to simulate a closed head injury. METHODS: Twenty-four domestic pigs (mean, 30 kg) were divided into four groups (6 CO2, 6 He, 6 N2O, and 6 control animals without insufflation). All animals were monitored for ICP, intraabdominal pressure, mean arterial pressure, end-tidal CO2 (ETCO2), and arterial blood gases. These parameters were measured for 30 minutes prior to introducing a pneumoperitoneum and then for 80 minutes thereafter. The measurements were repeated after artificially elevating the ICP with a balloon placed in the epidural space. RESULTS: The mean ICP increased significantly in all groups during peritoneal insufflation compared with the control group (P < 0.005). The CO2-insufflated animals also showed a significant increase in PaCO2 (P < 0.05) and ETCO2 (P < 0.05), as well as a decrease in pH (P < 0.05). After inflating the epidural balloon the ICP remained significantly higher in animals inflated with CO2 as compared with the He and N2O groups (P < 0.05). CONCLUSIONS: Peritoneal insufflation with He and N2O resulted in a significantly less increase in ICP as compared with CO2. That difference was most likely due to a metabolically mediated increase in cerebral perfusion (PaCO2) in the CO2 group. Further studies need to be conducted to determine the safety and efficacy of using He and N2O as inflation agents prior to attempting diagnostic or therapeutic laparoscopy in patients with potential closed head injuries.

Animals↗

PubMed1996

Magnetic resonance imaging for the evaluation of patients with occult cervical spine injury.

Because it is often difficult to diagnose accurately the structurally intact cervical spine after acute trauma, a series of patients was evaluated with magnetic resonance (MR) imaging to assess its efficacy for the evaluation and clearance of the cervical spine in a trauma victim in the early posttrauma period. Ultralow-field MR imaging was used to evaluate 174 posttraumatic patients in whom physical findings indicated the potential for spine injury or minor radiographic findings indicated injury. This series includes only those patients who did not appear to harbor disruption of spinal integrity on the basis of a routine x-ray film. None had clinically obvious injury. Of the 174 patients, 62 (36%) had soft-tissue abnormalities identified by MR imaging, including disc interspace disruption in 27 patients (four with ventral and dorsal ligamentous injury, three with ventral ligamentous injury alone, 18 with dorsal ligamentous injury alone, and two without ventral or dorsal ligamentous injury). Isolated ligamentous injury was observed in 35 patients (eight with ventral and dorsal ligamentous injury, five with ventral ligamentous injury alone, and 22 with dorsal ligamentous injury alone). One patient underwent a surgical fusion procedure, 35 patients (including the one treated surgically) were placed in a cervical collar for at least 1 month, and 27 patients were placed in a thermoplastic Minerva jacket for at least 2 months. All had a satisfactory outcome without evidence of instability. The T2-weighted sagittal images were most useful in defining acute soft-tissue injury; axial images were of minimal assistance. Posttraumatic soft-tissue cervical spine injuries and disc herniations (most likely proexisting the trauma) are more common than expected. A negative MR image should be considered as confirmation of a negative or "cleared" subaxial cervical spine. Diagnostic and patient management algorithms may be appropriately tailored by this information. Thus, MR imaging is useful for early acute posttrauma assessment in a very select group of patients.

Adolescent↗

PubMed1995

Anatomy of the thoracic pedicle.

Thoracic pedicle anatomy (interpedicular distance, transverse and sagittal pedicle widths, transverse and sagittal pedicle angles, and the distance from the axis of the pedicle to the axis of the transverse process) was assessed in 11 cadavers of elderly people. The cadaveric spines were extensively dissected to augment the accuracy of the measurements via caliper and goniometer. The results were compared with those of previous studies that assessed pedicle anatomy with computed tomography, direct measurement, and three-dimensional morphometry. Between the studies, significant differences were found in transverse pedicle width and transverse and sagittal pedicle angles. These morphometric differences may reflect either the diversity of the techniques used to measure the pedicle anatomy or sampling variation. This article presents a previously unreported morphometric finding, the rostral-caudal distance from the thoracic pedicle to the midpoint of the base of the transverse process. At T1, the transverse process is 5.45 +/- 1.2 mm rostral to the pedicle. This relationship gradually changes as the thoracic spine is descended, so that at T12, the transverse process is 6.6 +/- 2.4 mm caudal to the pedicle. Crossover consistently occurs at the T6-T7 region. Although the transverse process is a reliable external landmark for the location of the pedicle in the lumbar spine, this relationship in the thoracic spine is variable and only moderately predictable.

Aged↗

PubMed1995

Resection of giant invasive pituitary tumors through a transfacial approach: technical case report.

Giant invasive pituitary adenomas are rare tumors that have been reported to extensively involve the cranial base, as well as other intra- and extra-cranial structures, making surgical resection by traditional approaches impossible. We report two cases, each of a giant invasive adenoma involving the entire length of the clivus and adjacent structures that was resected via a transfacial approach with excellent results. Both tumors were in middle-aged men; one was nonsecreting, and the other secreted follicle-stimulating hormone alpha-subunit. Most previously reported giant invasive adenomas have been prolactinomas. Both tumors were resected via a transfacial approach that incorporated an osteoplastic maxillotomy with palatal division and a posterior pharyngeal incision that provided exposure from the suprasellar region to C2. Both of the patients received postoperative radiation and have done very well. Their cosmetic results were excellent. The complications included postoperative meningitis in one patient and a nasal voice in the other. The transfacial approach provides excellent access for this type of extensive midline tumor requiring resection from the suprasellar region down to the foramen magnum.

Adenoma↗

PubMed1995

A comparison of fluoroscopy and computed tomography-derived volumetric multiple exposure transmission holography for the guidance of lumbar pedicle screw insertion.

Holographic technology has recently been modified in such a manner that it may now provide clinical use. It allows the visualization of complex structures in three dimensions and permits clinician interaction with the image, which, in turn, provides significant additional geometric and anatomic information. To objectively assess the potential clinical applicability of holography in pedicle screw placement, we studied 11 elderly human cadavers. All of the cadavers, each of which showed significant degenerative disease of the lumbar spine, underwent thin-section computed tomographic scans of the lumbar spine. The acquired digital information was processed, and volumetric multiple exposure transmission holographic images were rendered. Pedicle screws were passed into anatomically acceptable and radiographically visualized L3-L5 pedicles in each cadaver, half using fluoroscopic guidance and half using holographic guidance alone. The accuracy of screw placement was objectively assessed by a three-point grading scale. The total score for the placement of each pedicle screw was determined by both trajectory (location within the pedicle) and accuracy (containment within the vertebral body) of screw tip placement parameters. Three points were possible for each screw placed. Screw placement in the last six cadavers was individually timed for each technique, and fluoroscopic time was also recorded. Each technique was used on 27 pedicles. The total score for fluoroscopic screw placement was 71 (71 of a possible 81; 88%) and for holographic screw placement was 74 (74 of a possible 81; 91%). In the last six cadavers, the screw placement time (per cadaver) was 8 minutes for fluoroscopic placement and 3.6 minutes for holographic placement. Fluoroscopic time averaged 1.9 minutes per cadaver.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Crossed-screw fixation of the unstable thoracic and lumbar spine.

An ideal spinal construct should immobilize only the unstable spinal segments, and thus only the segments fused. Pedicle fixation techniques have provided operative stabilization with the instrumentation of a minimal number of spinal segments; however, some failures have been observed with pedicle instrumentation. These failures are primarily related to excessive preload forces and limitations caused by the size and orientation of the pedicles. To circumvent these problems, a new technique, the crossed-screw fixation method, was developed and is described in this report. This technique facilitates short-segment spinal fixation and uses a lateral extracavitary approach, which provides generous exposure for spinal decompression and interbody fusion. The technique employs two large transverse vertebral body screws (6.5 to 8.5 mm in diameter) to bear axial loads, and two unilateral pedicle screws (placed on the side of the exposure) to restrict flexion and extension deformation around the transverse screws and to provide three-dimensional deformity correction. The horizontal vertebral body and the pedicle screws are connected to rods and then to each other via rigid crosslinking. The transverse vertebral body screws are unloaded during insertion by placing the construct in a compression mode after the interbody bone graft is placed, thus optimizing the advantage gained by the significant "toe-in" configuration provided and further decreasing the chance for instrumentation failure. The initial results of this technique are reported in a series of 10 consecutively treated patients, in whom correction of the deformity was facilitated. Follow-up examination (average 10.1 months after surgery) demonstrated negligible angulation. Chronic pain was minimal. The crossed-screw fixation technique is biomechanically sound and offers a rapid and safe form of short-segment three-dimensional deformity correction and solid fixation when utilized in conjunction with the lateral extracavitary approach to the unstable thoracic and lumbar spine. This approach also facilitates the secure placement of an interbody bone graft.

Adolescent↗

PubMed1995

Failure of a titanium anterior cervical plate implant: microstructural analysis of failure. Case report.

The authors present the case of a failed titanium anterior cervical spine plate. The plate was contoured during implantation. Analysis of the failed implant with electron microscopy showed no metallurgical flaw to have caused the plate fracture. A crack was apparently initiated with the contouring of the plate. It was located at the weakest point in the plate (the position of the intermediate screw hole), and with subsequent stress, it propagated and led to fracture. Techniques for avoiding failure of this type are discussed.

Bone Plates↗

PubMed1994

A simple method to ensure proper screw position and plate size selection using the Morscher cervical spine locking plate. Technical note.

The use of bone plate instrumentation with screw fixation has proved to be a useful adjunctive measure in anterior cervical spine fusion surgery. Proper fitting, positioning, and attachment of this instrumentation have been shown to be frequently suboptimal if done without radiographic guidance. The most commonly used method of radiographic assistance for placement of this instrumentation is fluoroscopy. While this gives satisfactory technical results, it is expensive and time-consuming, and exposes the patient and the operating room personnel to ionizing radiation. The authors present a simple technique to ensure screw placement and plate fitting using Kirschner wires and a single lateral radiograph. This technique saves time, reduces exposure to radiation, and has led to satisfactory results in over 20 operative cases.

Bone Plates↗

PubMed1994

Fractures of the C-2 vertebral body.

Vertical C-2 body fractures are presented in 15 patients with clinical and imaging correlations that suggest the existence of a variety of mechanisms of injury. In these patients, clinical and imaging correlations were derived by: 1) defining the point of impact by clinical examination; 2) defining the point of impact by soft-tissue changes on cranial magnetic resonance (MR) imaging or computerized tomography (CT); 3) obtaining an accurate history of the mechanism of injury; and 4) spine imaging (x-ray studies, CT, and MR imaging) of the C-2 body fracture and surrounding bone and soft tissue. The cases presented involve the region located between the dens and the pars interarticularis of the axis. Although these fractures are rarely reported, they are not uncommon. An elucidation of their pathological anatomy helps to further the understanding of the mechanistic etiology of upper cervical spine trauma. A spectrum of mechanisms of injury causing upper cervical spine fractures was observed. The type of injury incurred is determined predominantly by the force vector applied during impact and the intrinsic strength and anatomy of C-2 and its surrounding spinal elements. From this clinical experience, two types of vertical C-2 body fractures are defined and presented: coronally oriented (Type 1) and sagittally oriented (Type 2). A third type of C-2 body fracture, the horizontal rostral C-2 fracture (Type 3), is added for completeness; this Type 3 fracture is the previously described Type III odontoid process fracture described by Anderson and D'Alonzo.

Adult↗

PubMed1994

Sacral fixation using iliac instrumentation and a variable-angle screw device. Technical note.

Secure fixation of the sacrum is technically challenging. The bone of the dorsal sacral surface is often thin, making hook fixation tenuous. The use of bone screws in the sacral pedicles has gained popularity, but rigidity is often not achieved and screw pullout is common. Solid constructs have been achieved using angled rods to stabilize the ilium, but these methods are technically difficult and time-consuming to perform. A technique is described that achieves rigid sacral fixation by adding a bone screw placed through both cortical surfaces of the ilium. This bone screw is a new type that allows attachment to a rod at variable angles. It permits easy attachment to an appropriately contoured rod, which is affixed to sacral hooks or screws. The resulting configuration of the bone-metal interface creates a tripod for load distribution. Additionally, the splayed geometry of these purchase sites provides a significant biomechanical advantage preventing the instrument from being pulled out. The technique for this fixation method, particularly for patients with complex spinal disorders, is described. Use of this new technique provides significant advantages to the spine surgeon in situations in which substantial sacral fixation integrity is necessary.

Biomechanical Phenomena↗

PubMed1993

The sequential hook insertion technique for universal spine instrumentation application. Technical note.

A new technique of universal spine instrumentation insertion for the management of thoracic and lumbar spine instability is presented and the results in 10 patients are described. The technique involves the sequential insertion of Texas Scottish Rite Hospital (TSRH) central-post hooks, followed by hook fixation to the rod; force is then applied with correction of deformity, if needed. This allows for methodical, safe, and rapid instrumentation insertion. The new TSRH central-post hook configuration permits manipulation of the hook/rod relationships to the advantage of the surgeon (and patient) by providing more room for both hook insertion and hook/rod fixation. This technique has reduced operative time, facilitated ease of deformity correction, and provided uniformly acceptable early postsurgical results.

Equipment Design↗

PubMed1991

Association of vascular compression in trigeminal neuralgia versus other "facial pain syndromes" by magnetic resonance imaging.

Magnetic resonance imaging was performed in 13 patients with trigeminal neuralgia and 18 control patients with facial pain of other types. Among trigeminal neuralgia patients, eight (62%) had vessels seen abutting, or immediately adjacent to, the trigeminal nerve on the side of their symptoms. Only three control patients (17%) had such vessels. The proportion of patients having a trigeminal region vessel associated with their symptoms was significantly higher in patients with trigeminal neuralgia than in controls (p = 0.0086). These findings provide evidence supporting the theory that trigeminal neuralgia is associated with vascular compression of the fifth cranial nerve.

Constriction, Pathologic↗

PubMed1990

Relation of hypesthesia to the outcome of glycerol rhizolysis for trigeminal neuralgia.

The effects of percutaneous retrogasserian glycerol rhizolysis were observed in a population of 58 cases of classical trigeminal neuralgia. The follow-up period ranged from 7 to 52 months postoperatively. It was noted that 84% of the patients had immediate relief of pain. The overall recurrence rate was 29%. Based on Kaplan-Meier survival curves, the overall half-life (T1/2) of this procedure was 16 months. Although none of the patients developed anesthesia dolorosa or corneal ulceration, one group of patients developed either a clinical or subclinical persistent "minimal hypesthesia." In these there was a statistically significant difference in the T1/2 associated with this procedure (p = 0.01). This finding suggests that, contrary to the general belief, persistent hypesthesia after glycerol rhizolysis is a negative indicator of long-term success.

Adult↗