Biomedical subjects

W T Couldwell

Publications and source records attributed to W T Couldwell.

At least 37 records · Page 2Linked to original sources

PubMed2001

No ordinary time, no ordinary men: the relationship between Harvey Cushing and Franklin D. Roosevelt, 1928-1939.

The authors elucidate the strong personal relationship that developed between Dr. Harvey Cushing and Franklin Delano Roosevelt (FDR) from 1928 to 1939, as manifested in their frequent letters to each other. The relationship was initiated by the marriage of their children. Through his correspondence with FDR, Cushing was able to affect several medical issues of the period. The relationship of these two individuals is set within the historical, social, and political contexts of the times.

Correspondence as Topic↗

PubMed2001

Glioma invasion.

Explore the source record for details and available documents.

Brain↗

PubMed2001

Effect of absorbable topical hemostatic agents on the relaxation time of blood: an in vitro study with implications for postoperative magnetic resonance imaging.

OBJECT: Absorbable topical hemostatic agents are commonly used in neurosurgery. In this study the authors examine the longitudinal relaxation time (T1) of blood in contact with these agents over time, measured in vitro, to determine if their presence could affect the interpretation of postoperative magnetic resonance (MR) images. METHODS: Coagulated and anticoagulated blood were used, both oxygenated and deoxygenated. The effects of a collagen-based agent (Collastat) and a cellulose-based agent (Surgicel) on the pH and T1 values of blood and on those of saline (used as a control) were investigated. The T1 was measured as a function of magnetic field strength and time by using a field-cycling relaxometer. This instrument measures 1/T1, the rate of T1, from which the T, value is computed. The T1 values of blood were compared with those of hemostat-induced blood clots and with those of both gray and white matter of the brain. Signal changes on T1-weighted MR images were predicted on the basis of altered T, values in vitro. Postoperative images were visually examined for the predicted changes. With the addition of Surgicel, blood had decreased pH and significantly shortened T1 at all fields, essentially within minutes, although it affected the T1 of saline only minimally. The effect of Surgicel increasingly shortened the T1 for 4 days in oxygenated blood. Collastat had no significant effect. The presence of some paramagnetic methemoglobin in Surgicel-induced clots was demonstrated using the relaxometer at a time when diamagnetic oxyhemoglobin would be present in naturally occurring blood clots. A bright signal that could mimic residual tumor on contrast-enhanced images was predicted and confirmed on postoperative T1-weighted MR images obtained in patients in whom Surgicel lined the tumor bed. It was not present in cases in which Surgicel was not used. CONCLUSIONS: Surgicel alters the appearance of early postoperative MR images. To avoid misinterpretation, clinicians should be aware of this phenomenon.

Absorption↗

PubMed2001

The history and evolution of transsphenoidal surgery.

Initial attempts at transcranial approaches to the pituitary gland in the late 1800s and early 1900s resulted in a mortality rate that was generally considered prohibitive. Schloffer suggested the use of a transsphenoidal route as a safer, alternative approach to the sella turcica. He reported the first successful removal of a pituitary tumor via the transsphenoidal approach in 1906. His procedure underwent a number of modifications by interested surgeons, the culmination of which was A. E. Halstead's description in 1910 of a sublabial gingival incision for the initial stage of exposure. From 1910 to 1925, Cushing, combining a number of suggestions made by previous authors, refined the transsphenoidal approach and used it to operate on 231 pituitary tumors, with a mortality rate of 5.6%. As he developed increasing expertise with transcranial surgery, however, Cushing reduced his mortality rate to 4.5%. With the transcranial approach, he was able to verify suprasellar tumors and achieve better decompression of the optic apparatus, resulting in better recovery of vision and a lower recurrence rate. As a result he and most other neurosurgeons at the time abandoned the transnasal in favor of the transcranial approaches. Norman Dott, a visiting scholar who studied with Cushing in 1923, returned to Edinburgh, Scotland, and continued to use the transsphenoidal procedure while others pursued transcranial approaches. Dott introduced the procedure to Gerard Guiot, who published excellent results with the transsphenoidal approach and revived the interest of many physicians throughout Europe in the early 1960s. Jules Hardy, who used intraoperative fluoroscopy while learning the transsphenoidal approach from Guiot, then introduced the operating microscope to further refine the procedure; he thereby significantly improved its efficacy and decreased surgical morbidity. With the development of antibiotic drugs and modern microinstrumentation, the transsphenoidal approach became the preferred route for the removal of lesions that were confined to the sella turcica. The evolution of the transsphenoidal approaches and their current applications and modifications are discussed.

History, 19th Century↗

PubMed2001

Use of cylindrical titanium mesh and locking plates in anterior cervical fusion. Technical note.

After performing anterior cervical corpectomy or discectomy for cervical spondolytic myelopathy or radiculopathy, iliac crest bone graft and fibular auto- or allograft is often used to achieve arthrodesis in the cervical spine. The purpose of this study was to evaluate the use of a cylindrical titanium mesh and locking plate system as an alternative technique in achieving anterior cervical fusion and maintaining lordosis. Hospital records and radiographs of 38 patients who underwent anterior cervical discectomies (28 patients) or corpectomies (10 patients) from 1995 to 1997 were reviewed retrospectively. All patients had undergone arthrodesis in which autograft and a cylindrical titanium mesh and anterior locking plate fixation were used after discectomy or corpectomy. There were 20 men and 18 women (mean age 46.1 years; range 34-72 years). Presenting symptoms included radiculopathy (61%), myelopathy (37%), and neck pain (2%). Preoperative and postoperative radiographs were studied, and data were obtained on the following: overall lordosis or kyphosis of the cervical spine, segmental lordosis or kyphosis at each surgically treated level, and evidence of fusion. In all of the patients in whom lordosis was present preoperatively, lordosis was maintained during the follow-up period. The overall fusion rate was 100%. The average change in overall lordosis or kyphosis related to the fixation devices was 1.2 degrees (range 1-5 degrees) the average segmental change was 2.3 degrees (range 0-5 degrees); and the mean follow up was 16 months (range 12-36 months). Anterior cervical fusion with cylindrical titanium mesh and cervical locking plate system is an effective method of achieving arthrodesis and maintaining alignment in the cervical spine. The construct may provide additional load-sharing function, and it avoids the use of cadaveric bone or the need for harvesting tricortical iliac crest autograft.

Adult↗

PubMed2000

Tamoxifen-induced enhancement of calcium signaling in glioma and MCF-7 breast cancer cells.

The antiestrogen tamoxifen is commonly used to treat breast cancer, but it also has therapeutic activity in several other types of cancer. Many of these tumors, including malignant gliomas, are estrogen receptor negative. Nonetheless, high concentrations of tamoxifen can directly reduce cell proliferation in some of these tumors and induce apoptosis. In this study, the role of tamoxifen in calcium signaling and calcium-induced cell death was studied in both malignant glioma cell lines and MCF-7 breast cancer cells. Tamoxifen potently increased the spatial expansion of calcium waves by 30-150% while significantly enhancing and prolonging agonist-induced calcium elevations. Furthermore, tamoxifen pretreatment accelerated calcium ionophore-induced death by more than 20 min, suggesting that tamoxifen lowered cellular resistance to calcium loads. In contrast to its potentiating of calcium signaling in tumors, tamoxifen had no significant effect on calcium signaling in cultures of primary astrocytes from either human or rat brain. This study demonstrates the existence of calcium signaling in breast cancer and glioma cells and identifies tamoxifen as a potential modulator of tumor-associated calcium signaling.

Adenosine Triphosphate↗

PubMed2000

Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone.

Adult humans, like their nonhuman mammalian counterparts, harbor persistent neural progenitor cells in the forebrain ventricular lining. In the absence of adequate surface markers, however, these cells have proven difficult to isolate for study. We have previously identified and selected neural progenitor cells from both the fetal and adult rodent ventricular zone (VZ), by sorting forebrain cells transfected with plasmid DNA encoding the gene for green fluorescent protein driven by the early neuronal promoter for Talpha1 tubulin (P/Talpha1:hGFP). We have now extended this approach by purifying both P/Talpha1:hGFP tubulin-defined neuronal progenitors, as well as potentially less committed E/nestin:hGFP-defined neural progenitor cells, from the adult human VZ. The ventricular wall of the temporal horn of the lateral ventricle was dissected from temporal lobes obtained from four adult patients undergoing therapeutic lobectomy. These samples were dissociated, and the cultured cells transduced with either P/Talpha1:hGFP or E/nestin:EGFP plasmid DNA. A week later, the cells were redissociated, selected via fluorescence-activated cell sorting (FACS) on the basis of neural promoter-driven GFP expression, and replated. The majority of these cells expressed the early neuronal protein betaIII-tubulin upon FACS; within the week thereafter, most matured as morphologically evident neurons that coexpressed betaIII-tubulin and microtubule-associated protein (MAP)-2. Many of these neurons had incorporated bromodeoxyuridine in vitro in the days before FACS, indicating their mitogenesis in vitro. Thus, the use of fluorescent transgenes under the control of early neural promoters permits the enrichment of neuronal progenitor cells from the adult human ventricular zone. The specific acquisition, in both purity and number, of residual neural progenitor cells from the adult human brain may now permit hitherto unfeasible studies of both their biology and practical application.

Adult↗

PubMed2000

Approaches to the sellar and parasellar region: a retrospective comparison of the endonasal-transsphenoidal and sublabial-transsphenoidal approaches.

Tumors of the hypophysis are often managed surgically by the neurosurgeon and the otolaryngologist. Three widely used anterior routes to the sella are the endonasal (transcolumellar) transsphenoidal, sublabial transsphenoidal, and transethmoidal approaches. We reviewed the charts of 60 patients who underwent surgery, 42 transcolumellar and 18 sublabial, for sellar and parasellar adenomas and compared the two transsphenoidal approaches. None of the patients in our study underwent the transethmoidal approach. Furthermore, 26 of the patients underwent an extensive interview to assess postoperative progress. Clinically, neither approach had any significant complications, and none of the patients in either group reported significant postoperative morbidity. On the basis of these results, we believe there is minimal difference in patient subjective reports and objective morbidity when comparing the sublabial and transcolumellar approaches.

Adenoma↗

PubMed2000

In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus.

Neurogenesis persists in the adult mammalian hippocampus. To identify and isolate neuronal progenitor cells of the adult human hippocampus, we transfected ventricular zone-free dissociates of surgically-excised dentate gyrus with DNA encoding humanized green fluorescent protein (hGFP), placed under the control of either the nestin enhancer (E/nestin) or the Talpha1 tubulin promoter (P/Talpha1), two regulatory regions that direct transcription in neural progenitor cells. The resultant P/Talpha1:hGFP+ and E/nestin:enhanced (E)GFP+ cells expressed betaIII-tubulin or microtubule-associated protein-2; many incorporated bromodeoxyuridine, indicating their genesis in vitro. Using fluorescence-activated cell sorting, the E/nestin:EGFP+ and P/Talpha1:hGFP+ cells were isolated to near purity, and matured antigenically and physiologically as neurons. Thus, the adult human hippocampus contains mitotically competent neuronal progenitors that can be selectively extracted. The isolation of these cells may provide a cellular substrate for re-populating the damaged or degenerated adult hippocampus.

Adult↗

PubMed2000

Extradural extranasal combined transmaxillary transsphenoidal approach to the cavernous sinus: a minimally invasive microsurgical model.

UNLABELLED: The authors have previously described an extradural transmaxillary approach to the anterior compartment of the cavernous sinus. In an effort to expand the surgical access to that area without necessitating a craniotomy or wide transfacial dissection, they present a modification of the transmaxillary approach to the sellar region and cavernous sinus. METHODS: The approach was developed on 12 fresh and 12 embalmed cadaveric specimen, and 2 dry skulls. The initial sublabial incision is followed by a maxillotomy to expose the course of the infraorbital nerve (terminal branch of maxillary branch of the trigeminal nerve) on the roof of the maxillary sinus. The route of the infraorbital nerve is traced to the pterygopalatine fossa as a guide to the foramen rotundum. Superomedial drilling of the foramen rotundum is then performed to reveal the contents of the superior orbital fissure. After the nerves are safely identified in the superior orbital fissure, medial enlargement of the window into the cavernous sinus is made possible by drilling the lateral and posterior wall and septum of the sphenoid sinus. RESULTS: The combined transmaxillary transsphenoidal approach offers an excellent exposure of the sellar and infrasellar region. The approach offers clear visualization of the ipsilateral loop of the carotid artery, the pituitary fossa, and the cranial nerves of the ipsilateral cavernous sinus. Mean operative reach is 38 mm from the posterior wall of the maxillary sinus to the ipsilateral carotid loop and 56 mm to the contralateral loop. The width of the operative window is 26 mm at the base within the cavernous sinus. CONCLUSION: The model offers a minimally invasive approach that avoids the need for craniotomy or violating the nasal cavity. It may be safely employed to access vascular as well as invasive lesions of the sellar and infrasellar region. The approach offers excellent visualization of the ipsilateral intracavernous carotid artery with both proximal and distal control, as well as cranial nerves III, IV, VI, V2, the hypophyseal region, and the medial aspect of the contralateral cavernous sinus.

Cavernous Sinus↗

PubMed2000

Type IV spinal arteriovenous malformation in association with familial pulmonary vascular malformations: case report.

OBJECTIVE AND IMPORTANCE: Type IVc arteriovenous malformations (AVMs) of the spinal cord consist of multiple high-flow feeding vessels, and they often present a challenging management situation. Their location is intradural and extramedullary, and they are rare malformations that are difficult to treat owing to the risk of thrombosis of the anterior spinal artery. The authors report a case of Type IVc spinal AVM in a patient with a family history of three siblings with pulmonary AVMs. Spinal AVMs have been reported to be associated with inherited syndromes such as familial cutaneous hemangiomas and Kartagener's syndrome, but an association with pulmonary AVMs has not previously been described. CLINICAL PRESENTATION: A 27-year-old man presented with sudden onset of occipital headache with cervical radiation while weightlifting. Results of computed tomography of the brain were normal, but lumbar puncture revealed a subarachnoid hemorrhage. The patient had a 1-year history of a neurogenic bladder and exhibited marked left calf muscle wasting. INTERVENTION: The patient underwent spinal magnetic resonance imaging, which revealed the AVM in the conus region. Selective spinal angiography was performed for diagnostic purposes. A laminectomy was performed, and the vessels feeding the AVM were clipped, as was the fistula. CONCLUSION: The patient remained neurologically stable, and angiography confirmed obliteration of the AVM. This is the first case report of a patient with a spinal AVM who had multiple siblings with pulmonary malformations or AVMs.

Adult↗

PubMed2000

Rupture of a large ophthalmic segment saccular aneurysm associated with closed head injury: case report.

OBJECTIVE AND IMPORTANCE: Although each year approximately 30,000 to 50,000 cases of subarachnoid hemorrhage in the United States are caused by the rupture of intracranial saccular aneurysms, there is little information in the literature documenting the association of aneurysmal rupture with closed head injury. CLINICAL PRESENTATION: A 61-year-old woman presented after a motor vehicle accident with multiple injuries, including a severe closed head injury. Computed tomography revealed a diffuse basal subarachnoid hemorrhage. Angiography revealed the source as a large aneurysm arising from the ophthalmic segment of the left carotid artery. INTERVENTION: After the patient was stabilized for her multiple injuries, she underwent craniotomy and clipping of the aneurysm. She recovered without developing new neurological deficits. CONCLUSION: Although the association of head trauma and aneurysmal subarachnoid hemorrhage is rare, the presence of significant basal subarachnoid blood on a computed tomographic scan should alert the physician to the possibility of a ruptured aneurysm.

Aneurysm, Ruptured↗

PubMed1999

Direct gap junction communication between malignant glioma cells and astrocytes.

Gap junctions are intercellular channels that connect the interiors of coupled cells. We sought to determine the extent to which malignant glioma cells form gap junction channels with astrocytes from either adult human brain or rat forebrain. The astrocytic gap junction protein, connexin 43 (Cx43), was identified in immunoreactive plaques at areas of cell-to-cell contact between cocultured glioma cells and astrocytes. These gap junction plaques were composed of functional channels, because extensive dye coupling was evident between the glioma cells and astrocytes from both human and rat brain. Calcium signaling was also readily transmitted from glioma cells to astrocytes and vice versa. In live rat brain, injection of glioma cells prelabeled with the gap junction tracer, dicarboxy-dichlorofluorescein, revealed extensive dye transfer to host cells, demonstrating that malignant glioma cells directly couple with normal brain cells. These observations suggest that intercellular communication via gap junctions may play a role in regulating cellular interactions during tumor invasion. In fact, the presence of gap junctions between astrocytes and glioma cells was sufficient to induce a transformation of astrocytic phenotype. Astrocytes cocultured with C6 glioma cells overexpressing Cx43 were significantly smaller and expressed a lower level of glial fibrillary acidic protein than astrocytes cocultured with otherwise identical mock-transfected, gap junction-deficient C6 cells. Thus, direct cellular coupling with glioma cells result in a phenotypic transformation of astrocytes that may contribute to the susceptibility of surrounding tissue to glioma invasion.

Adult↗

PubMed1999

Glucocorticoids-potent modulators of astrocytic calcium signaling.

Glucocorticoids are the first line of choice in the treatment of cerebral edema associated with brain tumors. High-dose glucocorticoids reduce the extent of edema within hours, often relieving critical increases in intracranial pressure, but the mechanisms by which glucocorticoids modulate brain water content are not well-understood. A possible target of action may be glucocorticoid receptor-expressing astrocytes, which are the primary regulators of interstitial ion homeostasis in brain. In this study, we demonstrate that two glucocorticoids, methylprednisolone and dexamethasone, potentiate astrocytic signaling, via long-range calcium waves. Glucocorticoid treatment increased both resting cytosolic calcium (Ca2+i) level and the extent and amplitude of Ca2+ wave propagation two-fold, compared to matched controls. RU-486, a potent steroid receptor antagonist, inhibited the effects of methylprednisolone. The glucocorticoid-associated potentiation of Ca2+ signaling may result from upregulation of the cellular ability to mobilize Ca2+ and release ATP, because both agonist-induced Ca2+i increments (via ATP and bradykinin) and ATP release were proportionally enhanced by glucocorticoids. In contrast, neither gap junction expression (as manifested connexin 43 immunoreactivity) nor functional coupling was significantly affected by methylprednisolone. Confocal microscopy revealed both the expression of glucocorticoid receptors and nuclear translocation of these receptors when exposed to methylprednisolone. We postulate that the edemolytic effects of glucocorticoids may result from enhanced astrocytic calcium signaling.

Adenosine Triphosphate↗

PubMed1999

Approaches to the sellar and parasellar region: anatomic comparison of the microscope versus endoscope.

OBJECTIVE: Traditionally, surgical approaches to the sellar region require the use of the operating microscope. Over the past decade endoscopic surgery has gained much popularity because of advances in optics and illumination. Endoscopic surgery of the sellar region has been performed successfully. The goal of the present study was to quantify the amount of exposure to the sellar and suprasellar region that the endoscope provides versus the microscope, with three different anterior approaches to the sellar region. METHODS: The transethmoidal, endonasal-transsphenoidal, and sublabial-transsphenoidal approaches were performed on 14 formalin-fixed cadaver heads with a 0 degrees endoscope and repeated with the operative microscope. The distances of relevant surgical landmarks and the amount of exposure superior and anterior to the dorsum sella, as well as the lateral exposure, were measured. The mean distances were then used to calculate the volume of exposure for each of the approaches. RESULTS: It was found that the endoscope provided greater view than the operating microscope in all three approaches. The difference was statistically significant using a paired Student t test and a signed-rank test (P<.001). CONCLUSION: The authors believe that endoscopic surgery of the sellar region can be performed safely and effectively, while providing the surgeon with a view that is superior to that afforded by the operating microscope.

Cadaver↗

PubMed1998

Loss of Rb expression in an ACTH-secreting pituitary carcinoma.

Little is known about the molecular mechanisms of tumor progression in the pituitary. However, animal studies suggest that the Rb gene may be involved in the development of pituitary carcinoma. Pathologic examination of a pituitary tumor that included both benign and malignant components provided insight into this mechanism. Both benign and malignant tumors were immunoreactive for ACTH. The benign adenoma showed strong nuclear immunoreactivity for Rb, however, both the adjacent sellar carcinoma and its metastases were Rb-negative. This study suggests that loss of Rb may in some cases be important in the progression of pituitary adenoma to carcinoma.

Adrenocorticotropic Hormone↗

PubMed1998

Posterolateral approach for decompression with anterior and posterior fusion: a less invasive surgical technique for stabilization of the thoracic spine. Case report.

The goals of surgery in unstable thoracic fractures or tumors involving the thoracic spine are neural decompression, correction of deformity, and stabilization. Several different approaches can be used to achieve these goals. The anterior, combined anterior and posterior, and more recently thoracoscopic approaches are well described in the literature and are extremely effective in achieving the goals mentioned. However, they do carry with them significant morbidity and mortality rates in patients who are elderly, who have associated medical problems, or for whom there are contraindications to thoracic surgery. The authors believe the posterolateral approach is a viable alternative that is reasonably well tolerated in this select patient population. One can achieve circumferential neural decompression as well as anterior and posterior arthrodesis through a single incision. Most neurosurgeons are familiar with the anatomical landmarks and technical steps in the posterolateral approach, and the authors believe it is a less invasive method that can be especially useful and should not be overlooked in this subgroup of patients.

Journal Article↗

PubMed1998

Tamoxifen and carboplatin combinational treatment of high-grade gliomas. Results of a clinical trial on newly diagnosed patients.

Between April, 1992 and December, 1995, forty consecutive patients with a cerebral malignant glioma (WHO Grade III and IV) were enrolled in a trial consisting in surgery and post-operative administration of radiotherapy (4500-6000 cGy), carboplatin (CBDCA; dose of 450-600 mg/m2), and oral tamoxifen (TAM; at doses of 40, 80 or 120 mg/day). Two patients of the TAM group died in the postoperative period from a pulmonary embolism and myocardial infarction, respectively. The patients (all dosages combined) had a median survival time of 13 months from the time of diagnosis. The 12-month and 24-month survival rates were 52% and 32%, respectively. The median relapse-free survival time was 7 months. Patients treated with higher doses of TAM (80-120 mg/day) demonstrated a longer median survival rate (13 months both) and a longer 12-month survival result (58% and 76%, respectively). Patients who assumed TAM for a period longer than 3 months (group +3) have a higher median survival rate (16 months) and better 12-month and 24-month results (62% and 40%, respectively). Moreover, the median relapse-free survival time was 10 months (versus 6 months in group -3; p = 0.0038). However, it is not possible to exclude that patients of group +3 had a slower growing or a stable tumor and were well enough to assume TAM for a longer period. The results observed in the TAM-group have been compared with those of 40 matched controls treated with surgery, radiotherapy and CBDCA. These patients had a median survival time of 9 months (p = 0.04) and the 12-month and 24-month survival rates were 30% and 0%, respectively. The median relapse-free survival time was 4 months (p = 0.0014). These data suggest a potential role for combinational TAM-CBDCA therapy in the post-operative treatment of cerebral malignant gliomas; further clinical phase III trials, especially those with higher dosages of TAM are warranted.

Administration, Oral↗