Quantification of in vivo Photofrin uptake by human pituitary adenoma tissue

2004 ◽  
Vol 101 (2) ◽  
pp. 272-277 ◽  
Author(s):  
Usiakimi Igbaseimokumo
Keyword(s):  
Photodynamic Therapy ◽  
Pituitary Adenoma ◽  
The Body ◽  
Human Pituitary ◽  
Human Pituitary Adenoma ◽  
Content Type ◽  
The Mean ◽  
Adenoma Tissue ◽  
Fine Print

Object. Photofrin is widely distributed in the body after intravenous injection. This study was designed to quantify the preferential uptake of Photofrin by pituitary adenoma tissue for intraoperative photodynamic therapy. Methods. Eight patients (seven men) with recurrent pituitary adenomas who had undergone previous surgery and radiation therapy were recruited for a Phase I/II feasibility study of the application of photodynamic therapy to pituitary tumors. Photofrin was administered intravenously at a dose of 2 mg/kg body weight 48 hours before repeated transsphenoidal hypophysectomy was performed. At the time of the operation, pituitary adenoma tissue, muscle, fat, skin, and plasma were obtained for measurement of Photofrin content by fluorometric assay. The mean Photofrin level in pituitary adenoma tissue was 6.87 ng/mg (95% confidence interval [CI] 3.99–9.75), which was significantly higher than the uptake by skeletal muscle (2.24 ng/mg, 95% CI 1.28–3.2; p = 0.008), or fat (2.54 ng/mg, 95% CI 0.66–4.42; p = 0.007). Nevertheless, the mean drug concentration in pituitary adenoma tissue was not significantly different from the level in plasma (7.65 µg/ml, 95% CI 5.38–9.90; p = 0.558). Skin specimens were available in four patients, and these showed a mean uptake of 2.19 ng/mg. Conclusions. Photofrin is preferentially retained by pituitary adenoma tissue to levels both adequate for intraoperative photodynamic therapy and approximately 50% higher than those reported for gliomas.

A preliminary experimental in vivo study of the effect of photodynamic therapy on human pituitary adenoma implanted in mice

1998 ◽  
Vol 12 (2) ◽  
pp. 140-145 ◽  
Author(s):  
R. W. Kirollos, ◽  
P. V. Marks, ◽  
U. Igbaseimokumo, ◽  
A. Chakrabarty
Keyword(s):  
Photodynamic Therapy ◽  
Pituitary Adenoma ◽  
In Vivo Study ◽  
Human Pituitary ◽  
Human Pituitary Adenoma

In vivo assessment of the window of barrier opening after osmotic blood—brain barrier disruption in humans

2000 ◽  
Vol 92 (4) ◽  
pp. 599-605 ◽  
Author(s):  
Tali Siegal ◽  
Rina Rubinstein ◽  
Felix Bokstein ◽  
Allan Schwartz ◽  
Alexander Lossos ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Time Course ◽  
Photon Emission ◽  
Brain Barrier ◽  
Therapeutic Window ◽  
Content Type ◽  
Blood Brain ◽  
The Mean ◽  
Fine Print

Object. Osmotic blood—brain barrier (BBB) disruption induced by intraarterial infusion of mannitol is used in conjunction with chemotherapy to treat human brain tumors. The time course to barrier closure, or the so-called therapeutic window, has been examined in animals but little information is available in humans. The authors, therefore assessed the time course to barrier closure after osmotic BBB disruption in humans.Methods. Disruption of the BBB was demonstrated using 99mTc-glucoheptonate (TcGH) single-photon emission computerized tomography (SPECT) scanning in 12 patients who were treated monthly with combination chemotherapy in conjunction with BBB disruption. The primary diagnosis was primary central nervous system lymphoma in seven patients and primitive neuroectodermal tumors in five. The TcGH (20 mCi) was injected at 1- to 480-minute intervals after osmotic BBB disruption, and patients underwent SPECT scanning after 4 hours. A total of 38 studies was performed. Good-to-excellent BBB disruption was obtained in 29 procedures and poor-to-moderate disruption was seen in the other nine studies.The TcGH indices correlated with the degree of BBB disruption as measured postprocedure on contrast-enhanced CT scans (r = 0.852). Mean baseline TcGH indices were 1.02 ± 0.07. For the group of patients with good-to-excellent disruptions the mean indices at 1 minute postdisruption measured 2.19 ± 0.18. After 40 minutes no significant change was noted (mean index 2.13 ± 0.2). Then the indices declined more steeply and at 120 minutes after the disruption the index was 1.36 ± 0.02. A very slow decline was noted between 120 and 240 minutes after mannitol infusion. At 240 minutes the barrier was still open for all good-to-excellent disruptions (index 1.33 ± 0.08) but at 480 minutes the mean indices had returned to the baseline level.Conclusions. Results of these in vivo human studies indicate that the time course to closure of the disrupted BBB for low-molecular-weight complexes is longer than previously estimated. The barrier is widely open during the first 40 minutes after osmotic BBB disruption and returns to baseline levels only after 6 to 8 hours following the induction of good or excellent disruption. These findings have important clinical implications for the design of therapeutic protocols.

In vivo model of intracranial stent implantation: a pilot study to examine the histological response of cerebral vessels after randomized implantation of heparin-coated and uncoated endoluminal stents in a blinded fashion

2003 ◽  
Vol 98 (3) ◽  
pp. 544-553 ◽  
Author(s):  
Elad I. Levy ◽  
Alan S. Boulos ◽  
Ricardo A. Hanel ◽  
Fermin O. Tio ◽  
Ronald A. Alberico ◽  
...  
Keyword(s):  
Stent Implantation ◽  
In Vivo Model ◽  
Content Type ◽  
Intracranial Stent ◽  
Neointimal Thickness ◽  
Neointimal Proliferation ◽  
The Mean ◽  
Endoluminal Stent ◽  
Fine Print

Object. No animal model currently exists for the examination of time-dependent histological changes occurring in intracranial vessels after endoluminal stent placement. The authors' goal was to develop a reproducible in vivo model of stent implantation in intracranial vessels in dogs that was capable of demonstrating stent-related vascular changes after the implantation of coated and uncoated devices. Methods. The authors implanted heparin-coated or uncoated stents in the basilar arteries (BAs) of 11 mongrel dogs. In a 12th animal, one coated stent was implanted in the BA and a second uncoated one was implanted in the distal anterior spinal artery. All the devices were oversized to induce intimal injury. Surviving animals were observed for 12 weeks, after which they underwent repeated angiography before planned death and removal of the brain. Histological studies and computer-assisted morphometric analyses were conducted on stent-treated and untreated sections of the BAs to assess the percentage of stenosis, neointimal proliferation, vessel injury, and inflammation. Perforating vessels partially covered by stent struts (“jailing”) were studied for evidence of stenosis or occlusion. The pathologist, interventionists, histopathologist, histopathology technicians, and radiologist were blinded to the stent type. Seven stents (three uncoated and four coated) were removed from the six animals that were observed during the follow-up period. The mean neointimal proliferation was 0.42 mm2 in the group treated with uncoated stents and 0.18 mm2 in the group treated with heparin-coated devices (p = 0.04). Neointimal thickness was significantly increased in the group with uncoated stents (p = 0.04). The mean percentage of occlusion was less (12%) in the group with heparin-coated stents, compared with 22% in the group with uncoated devices (p = 0.07). When comparing results between the heparin-coated and uncoated devices implanted in the five animals that received a single stent only, greater differences (indicating a benefit from heparin-coated stents) were observed in neointimal area (p = 0.009), neointima/media ratio (p = 0.001), neointimal thickness (p = 0.002), and percentage of occlusion (p = 0.009). All brainstem perforating vessels covered by stent struts remained patent. Conclusions. This in vivo intracranial stent model was developed to assess proliferative and inflammatory responses to endoluminal stent implantation in the cerebrovasculature. The results indicate that a lower percentage of occlusion occurs 12 weeks after implantation of heparin-coated compared with uncoated stents.

Computational model for the estimation of the extracranial doses received during Leksell gamma knife model C treatment

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 14-18
Author(s):  
Mustafa Majali ◽  
Josef Novotny ◽  
Josef Novotny
Keyword(s):  
Treatment Planning ◽  
Gamma Knife ◽  
Total Error ◽  
The Body ◽  
Peripheral Dose ◽  
Content Type ◽  
Thermoluminescent Dosimeter ◽  
Model C ◽  
Fine Print

Object. Extracranial doses received by patients undergoing Leksell gamma knife surgery (GKS) can be of clinical concern. Therefore, the ability to preestimate peripheral doses received outside the treatment field during the GKS would be beneficial and could be used for the optimization of treatment planning by providing a reference for practitioners to calculate the extracranial dose burden to the body before the start of treatment. Methods. A dose of 40 Gy was delivered to the Rando phantom in a single fraction to a midline hypothetical target close to the center of the skull. Treatment planning was performed for multiple isocenters with a prescription to the 50% isodose of each collimator. Treatment plans were produced for 1, 5, 10, 15, and 20 shots, keeping the same dose and dose distribution at different target volumes. An automatic positioning system was used for positioning the phantom during the treatment. The doses to different organs were measured during GKS using a thermoluminescent dosimeter. In vivo measurements were also made in 200 patients who underwent GKS with the model C unit for different diagnoses at Na Homolce Hospital. Conclusions. The peripheral dose depended on the collimator size with a logarithmic dependence on collimator size and a linear dependence on the number of shots. This model can be used for the estimation of peripheral doses with a total error less than 20%. This information can help clinicians with treatment planning optimization, especially in patients with long survival expectancy.

Computational model for the estimation of the extracranial doses received during Leksell gamma knife model C treatment

2005 ◽  
Vol 102 ◽  
pp. 14-18 ◽  
Author(s):  
Mustafa Majali ◽  
Josef Novotny ◽  
Josef Novotny
Keyword(s):  
Treatment Planning ◽  
Gamma Knife ◽  
Total Error ◽  
The Body ◽  
Peripheral Dose ◽  
Content Type ◽  
Thermoluminescent Dosimeter ◽  
Model C ◽  
Fine Print

Object. Extracranial doses received by patients undergoing Leksell gamma knife surgery (GKS) can be of clinical concern. Therefore, the ability to preestimate peripheral doses received outside the treatment field during the GKS would be beneficial and could be used for the optimization of treatment planning by providing a reference for practitioners to calculate the extracranial dose burden to the body before the start of treatment. Methods. A dose of 40 Gy was delivered to the Rando phantom in a single fraction to a midline hypothetical target close to the center of the skull. Treatment planning was performed for multiple isocenters with a prescription to the 50% isodose of each collimator. Treatment plans were produced for 1, 5, 10, 15, and 20 shots, keeping the same dose and dose distribution at different target volumes. An automatic positioning system was used for positioning the phantom during the treatment. The doses to different organs were measured during GKS using a thermoluminescent dosimeter. In vivo measurements were also made in 200 patients who underwent GKS with the model C unit for different diagnoses at Na Homolce Hospital. Conclusions. The peripheral dose depended on the collimator size with a logarithmic dependence on collimator size and a linear dependence on the number of shots. This model can be used for the estimation of peripheral doses with a total error less than 20%. This information can help clinicians with treatment planning optimization, especially in patients with long survival expectancy.

Superficial landmarks for the spinal accessory nerve within the posterior cervical triangle

2005 ◽  
Vol 3 (5) ◽  
pp. 375-378 ◽  
Author(s):  
R. Shane Tubbs ◽  
E. George Salter ◽  
John C. Wellons ◽  
Jeffrey P. Blount ◽  
W. Jerry Oakes
Keyword(s):  
The Body ◽  
Spinal Accessory Nerve ◽  
Accessory Nerve ◽  
Mastoid Process ◽  
Exit Point ◽  
Content Type ◽  
Spinal Accessory ◽  
Mean Width ◽  
The Mean ◽  
Fine Print

Object. The spinal accessory nerve (SAN) within the posterior cervical triangle (PCT) is the most commonly iatrogenically injured nerve in the body. Nevertheless, there is a paucity of published information regarding superficial landmarks for the SAN in this region. Additional identifiable landmarks of this nerve may assist the surgeon in identifying it for repair, use of it in peripheral nerve neurotization, or avoiding it as in proximal brachial plexus repair. The present study was undertaken to provide reliable superficial landmarks for the identification of the SAN within the PCT. Methods. The PCT was dissected in 30 cadaveric sides. Measurements were made between the SAN and surrounding landmarks. The mean distances between the entry site of the SAN into the trapezius and a midpoint of the clavicle, mastoid process, acromion process, and lateral aspect of the sternocleidomastoid (SCM) muscle were 6, 7, 5.5, and 3.5 cm, respectively. The mean distances between the angle of the mandible and the mastoid process and the exit point of the SAN from the posterior border of the SCM muscle were 6 and 5 cm, respectively. The mean width and length of the SAN were 3 and 3.5 cm, respectively. Conclusions. It is the authors' hope that these data will aid those who may need to locate or avoid the SAN while undertaking surgery in the PCT and thus decrease morbidity that may follow manipulation of this region.

Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice

2001 ◽  
Vol 94 (3) ◽  
pp. 487-492 ◽  
Author(s):  
Ian E. McCutcheon ◽  
Allan Flyvbjerg ◽  
Holly Hill ◽  
Jessica Li ◽  
William F. Bennett ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Receptor Antagonist ◽  
Tumor Volume ◽  
Vehicle Group ◽  
Content Type ◽  
Gh Receptor ◽  
Igf I ◽  
The Mean ◽  
Fine Print

Object. The authors have previously demonstrated that modulation of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis can significantly affect meningioma growth in vitro. These studies were performed to evaluate the efficacy of GH receptor blockade in vivo. Methods. Primary cultures from 15 meningioma tumors obtained in humans were xenografted into athymic mice. Approximately 1.5 million cells from each of the 15 tumors were implanted into the flanks of two female mice, one pair for each tumor. One animal from each of the 15 pairs was then treated with the GH receptor antagonist pegvisomant and the other with vehicle alone for 8 weeks. The tumor volume was measured using digital calipers three times per week. The mean tumor volume at the initiation of injections was 284 ± 18.8 mm3 in the vehicle group and 291.1 ± 20 mm3 in the pegvisomant group. After 8 weeks of treatment, the mean volume of tumors in the pegvisomant group was 198.3 ± 18.9 mm3 compared with 350.1 ± 23.5 mm3 for the vehicle group (p < 0.001). The serum IGF-I concentration in the vehicle group was 319 ± 12.9 µg/L compared with 257 ± 9.7 in the pegvisomant group (p < 0.02). A small but significant decrease was observed in circulating IGF binding protein (IGFBP)—3 levels, whereas slight increases occurred with respect to serum IGFBP-1 and IGFBP-4 levels. In the placebo group the tumor weight was 0.092 ± 0.01 g compared with 0.057 ± 0.01 g in the pegvisomant group (p < 0.02). The IGF-I and IGF-II concentrations were measured in the tumors by using a tissue extraction method. These human-specific immunoassays demonstrated that there was no autocrine production of IGF-I in any of the tumors, either in the pegvisomant or vehicle group. The IGF-II levels were highly variable (0–38.2 ng/g tissue) and did not differ significantly between treatment groups. Conclusions. In an in vivo tumor model, downregulation of the GH/IGF-I axis significantly reduces meningioma growth and, in some instances, causes tumor regression. Because the concentrations of IGF-II in tumor did not vary with pegvisomant treatment and there was no autocrine IGF-I production by the tumors, the mechanism of the antitumor effect is most likely a decrease of IGF-I in the circulation and/or surrounding host tissues. Because the authors have previously demonstrated that the GH receptor is ubiquitously expressed in meningiomas, direct blockade of the GH receptor on the tumors may also be contributing to inhibitory actions.

A laboratory model of shunt-dependent hydrocephalus

1987 ◽  
Vol 66 (5) ◽  
pp. 734-740 ◽  
Author(s):  
Arno Fried ◽  
Kenneth Shapiro ◽  
Futoshi Takei ◽  
Ira Kohn
Keyword(s):  
Volume Index ◽  
Laboratory Model ◽  
Content Type ◽  
Shunt Placement ◽  
Shunt Occlusion ◽  
Shunt Dependency ◽  
Biomechanical Changes ◽  
The Mean ◽  
Fine Print

✓ This study was designed to determine whether implanting shunts in hydrocephalic cats produced the same biomechanical changes as have previously been found in children with shunts. Neuraxis volume-buffering capacity (pressure-volume index: PVI) and the resistance to the absorption of cerebrospinal fluid (CSF) were determined before and 3 weeks after placing shunts in 16 hydrocephalic cats. Intracranial pressure (ICP) was monitored for at least 6 hours after the shunts were occluded. The brains were perfused in vivo and removed to assess the size of the ventricles. The mean PVI of the hydrocephalic cats was 3.6 ± 0.2 ml (± standard error of the mean) before the shunts were placed. Three weeks after adequate shunt function was first established, the mean PVI decreased to 1.1 ± 0.1 ml and was similar to values determined in control animals. Prior to shunt placement, the resistance to the absorption of CSF was 28.4 ± 4.5 mm Hg/ml/min and did not vary with ICP. This parameter changed after shunting and increased as a function of ICP (r = 0.87, p < 0.001). At ICP's below 20 mm Hg, the resistance to the absorption of CSF was 65.0 ± 18.0 mm Hg/ml/min but increased to 220.0 ± 40.5 mm Hg/ml/min when determined at ICP's above 20 mm Hg. Corroborating evidence for this linkage of resistance to the absorption of CSF to ICP was found in the inexorable rise of ICP during the 6 hours of monitoring after the shunts were occluded. After shunt placement, the ventricles were normal in size in 12 cats and slightly enlarged in four. The biomechanical profile and pressure response to shunt occlusion in this laboratory model resembles that previously described in shunt-dependent children. As in humans, shunt placement in hydrocephalic cats results in normalization of the PVI and a linkage of the resistance to the absorption of CSF to ICP. The significance of these changes as they relate to shunt dependency is discussed.

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