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T C Origitano

Publications and source records attributed to T C Origitano.

At least 37 records · Page 2Linked to original sources
PubMed1995

Inhibition of in vitro meningioma proliferation after growth factor stimulation by calcium channel antagonists: Part II--Additional growth factors, growth factor receptor immunohistochemistry, and intracellular calcium measurements.

We have previously reported that calcium channel antagonists can block both the growth of meningiomas in culture and the potent growth stimulation of meningioma cells by epidermal growth factor (EGF) and platelet-derived growth factor (PDGF). This study further defines the nature of this growth inhibition. Primary meningioma cultures were established, and cells were characterized. Fibroblast growth factor or insulin-like growth factor-I growth stimulation in the presence of calcium channel antagonists was examined. In addition, the effects of ethylene glycol-bis-(aminoethylether) N,N,N',N"-tetraacetic acid and Bay K 8644, a calcium channel agonist, on the growth factors were analyzed. Growth factor receptor immunohistochemistry was performed on the original tumors and the in vitro meningioma cells. Twelve of 17 (71%) meningiomas in this study were positive for the EGF receptor, and 14 of 17 (82%) were positive for the PDGF receptor. Five of six (83%) of the culture cells were positive for the EGF receptor, and four of five (80%) were positive for the PDGF receptor. Intracellular calcium changes were quantified using the intracellular calcium-chelating, fluorescent dye, Fura-2. The growth stimulation of fibroblast growth factor and insulin-like growth factor-I on meningioma cells in culture was decreased in a dose-dependent manner by calcium channel antagonists. The growth stimulation of fibroblast growth factor and insulin-like growth factor-I was not affected by a reduction of extracellular calcium, whereas the growth stimulation of EGF and PDGF was. Interestingly, intracellular calcium was not increased after exposure to growth factors but was increased after serum stimulation. This increase could be blocked by preincubation with verapamil. Calcium channel antagonists can inhibit proliferation of meningioma cells in culture after stimulation with a number of growth factors. These drugs might disrupt intracellular calcium homeostasis or interfere with key elements of the growth factor signal transduction pathways. These mechanisms as well as the potential clinical relevance of these findings are discussed.

Adult↗
PubMed1994

Vascular considerations and complications in cranial base surgery.

The technical evolution of cranial base surgery has resulted in approaches that allow more radical surgical extirpation of complex cranial base lesions. Our service has extensively applied these cranial base approaches for lesions of the cranial base. A subgroup of 100 patients who had cranial base tumors involving potential manipulation or sacrifice of carotid arteries underwent 20-minute balloon test occlusions coordinated with vascular assessments consisting of a combination of the following: 1) four-vessel cerebral angiogram with compression studies; 2) occlusion transcranial Doppler ultrasonography; 3) occlusion single-photon emission computed tomography perfusion studies; and 4) xenon-133 cerebral blood flow studies. Transient neurological deficits associated with balloon test occlusion occurred in 7 of 100 patients (7%). Subsequently, 18 patients underwent permanent carotid occlusion by endovascular detachable balloons. Delayed ischemic complications (> 72 h) occurred in 4 of 18 (22%) patients. Additionally, a number of vascular complications not predicted by the balloon occlusion tests and vascular assessments were experienced. Repeat vascular assessments defined the causes and guided treatment of ischemic patients. Ischemic complications were caused by hemodynamic insufficiency, embolization, vasospasm, radiation vasculopathy, and venous anomaly. Our experience leads us to believe that no vascular assessment exists today that can predict the occurrence of vascular complications accurately. The current enthusiasm for cranial base surgery must be tempered with the sober reality that management of cerebrovascular anatomy and physiology remain significant limitations. Consideration of potential cerebrovascular complications is paramount to successful outcome and implementation of cranial base surgery.

Adult↗
PubMed1993

Skull base approaches to complex cerebral aneurysms.

The authors used skull base approaches to improve the surgical treatment of cerebral aneurysms. These approaches facilitate aneurysm surgery by allowing early proximal and distal vascular control, shortening and widening of the operative field, increasing the range of the surgeon's operative view and motion, and alleviating brain retraction. Twenty-two patients with ruptured giant or complex aneurysms were operated upon acutely using skull base approaches appropriate for their location: (1) the orbitocranial approach for anterior circulation, ophthalmic artery, and intracavernous lesions (n = 10); (2) the orbitozygomatic approach for aneurysms of the upper third of the basilar artery (n = 6); (3) the petrosal approach for aneurysms of the middle third of the basilar artery (n = 2); and (4) the far lateral-transcondylar approach for vertebrobasilar aneurysms (n = 4). Clipping and dissection of the aneurysms was facilitated by the skull base approaches. No surgical mortality occurred in this series of patients; transient cranial nerve paresis was the only morbidity related to the approaches. We compare the three-dimensional spatial geometry of skull base and conventional approaches, and discuss the advantages and nuances of skull base approaches.

Adult↗
PubMed1993

Use of vascularized fat from the rectus abdominis myocutaneous free flap territory to seal the dura of basicranial tumor resections.

Resection of large skull base tumors may sometimes result in extirpation defects that are not amenable to local tissue closure. Patients with these tumors require free tissue transfer for closure of the intracranial space after basicranial tumor extirpation. The deep inferior epigastric artery supplies the rectus abdominis muscle and the skin and subcutaneous tissue of the lower abdomen. The closure of massive, central defects can be performed with a free flap designed from the ample rectus abdominis vascular territory. This free tissue donor site has abundant and reliable well-vascularized skin and subcutaneous tissue that can be customized to seal these tenuous areas and provide three-dimensional reconstruction. We have modified the rectus abdominis myocutaneous free flap in seven patients for reconstruction of the skull base. The subcutaneous fat was sculptured to form a soft, vascularized "cork" and was used for obliteration of the irregular deep portions of defects at the midcranial base against the repaired or unrepaired dura. All patients who had the vascularized fat used to obliterate the deep space had successful closure of the defect without cerebral spinal fluid leak. There were two wound infections and one donor-site hernia in this group. The judicious use of the vascular territory of the deep inferior epigastric vessels can accomplish secure three-dimensional reconstruction of the skull base. The flap can be reliably transferred, and the vascularized subcutaneous fat can be used to sequester and seal the dura repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1993

Photodynamic therapy for intracranial neoplasms: investigations of photosensitizer uptake and distribution using indium-111 Photofrin-II single photon emission computed tomography scans in humans with intracranial neoplasms.

Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms. The efficacy of this therapy is based on the uptake of photosensitizer by neoplastic tissue, its clearance from surrounding brain tissue, and the timing and placement of photoactivating sources. Photofrin-II is the photosensitizer most actively being investigated. We labeled Photofrin-II with Indium-111 and studied the uptake and distribution of this agent in 20 patients with intracranial neoplasms, using single photon emission computed tomography (SPECT) with volume rendering in three dimensions. Of these patients, 16 had malignant glial tumors, 2 had metastatic deposits, 1 had a chordoma, and 1 had a meningioma. Anatomical-spatial data correlated well between the SPECT images and contrast-enhanced computed tomography or magnetic resonance images. Regions of focal uptake on SPECT images correlated with the surgical histopathological findings of the neoplasm. The kinetics of photosensitizer uptake varied according to the tumor's histological findings, the patient's use of steroids, and among patients with similar types of tumor histology. Peak ratios of target-to-nontarget tissue varied from 24 to 72 hours after injection. The study data show that, to be most effective, photodynamic therapy may need to be tailored for each patient by correlating SPECT images with anatomical data produced by computed tomography or magnetic resonance images. Photoactivating sources then can be placed, using computer-assisted stereotactics, to activate a prescribed volume of photosensitized tumor at the optimal time for treatment.

Adult↗
PubMed1993

Photodynamic therapy for intracranial neoplasms: development of an image-based computer-assisted protocol for photodynamic therapy of intracranial neoplasms.

Photodynamic therapy is being studied as an adjuvant therapy for malignant gliomas. Therapeutic efficacy is based on photosensitizer uptake kinetics and the ability to deliver adequate light doses to an appropriate treatment volume at the optimal time. Our laboratory has developed an image-based, computer-assisted treatment-planning protocol to study the treatment variables leading to optimizing photodynamic therapy for intracranial neoplasms. Fifteen patients with recurrent malignant glial tumors underwent 16 treatments in the developmental phase of the project in which light treatment volume was progressively expanded. Group I (n = 4) received postresection intracavitary photoillumination only, Group II (n = 3) received limited interstitial/intracavitary photoillumination, and Group III (n = 9) received multiple interstitial/intracavitary photoillumination. Between 3 and 18 interstitial fiber probes were placed through optically lucent tumor access catheters. Computed three-dimensional image-based treatment planning provided reproducible data-based tumor volumes, treatment volumes, and stereotactic accuracy for tumor volume resection and interstitial light fiber insertion. Initial observations include: 1) treatment failures occur outside of the effective light treatment volumes; 2) effective light volumes can be expanded safely with multiple stereotactically implanted interstitial light fibers; and 3) optimal treatment involves individualized tailoring of light dose volume and geometry. This protocol allows standardized scientific study of the variables affecting the application of photodynamic therapy for intracranial neoplasms.

Adult↗
PubMed1993

Refinements using free-tissue transfer for complex cranial base reconstruction.

Resection of skull base tumors may sometimes result in massive extirpation defects that are not amenable to local tissue closure. Closure of large basicranial defects can be performed with either a myocutaneous, a deepithelialized myocutaneous, or a simple muscle free flap designed from the ample rectus abdominis vascular territory. This free-tissue donor site has abundant and reliable well-vascularized tissue that can easily be customized to seal these tenuous areas. The rectus abdominis muscle and its vascularized territory were used in 18 of 19 consecutive patients at our center to close basicranial ablation defects. Of these, 6 were rectus abdominis muscle flaps, 5 were myocutaneous rectus abdominis flaps, and 7 were deepithelialized rectus abdominis muscle flaps. All free flaps survived. The intracranial space was sealed successfully in all but one patient. This patient underwent reconstruction with a muscle free flap and had a postoperative cerebrospinal fluid leak. This complication could have been avoided by using a deepithelialized myocutaneous flap to obliterate the central dead space with the vascularized subcutaneous fat. Two patients experienced minor wound infections, and one had a subdural abscess that was fully contained by a free flap placed over the duraplasty. One patient had a donor-site hernia. There was no incidence of meningitis. Knowledge of the anatomy of the vascular territory of the deep inferior epigastric vessels can be used judiciously to secure three-dimensional reconstruction of the skull base. The donor site supplies ample tissue for reconstruction and allows individual tailoring for obliteration of geometrically complex extirpation defects in and around the cranial base without the need to reposition the patient.

Adolescent↗
PubMed1992

Complex cranial base trauma resulting from recreational fireworks injury: case reports and review of the literature.

Two patients who sustained complex skull base trauma secondary to recreational fireworks injuries are reported. Initial assessment and management included axial and coronal computerized tomography, control of hemorrhage, debridement of wound and brain, isolation of brain from external environment, and reconstruction of the cranial base floor. Secondary orbital and facial reconstruction used available bone fragments and iliac bone graft in one patient and vascularized free tissue transfer in the other. In both patients, reconstruction of both the intracranial and extracranial compartments was successful with acceptable cosmetic result. Modification of multiple conventional approaches, along with a multispecialty surgical team, was used to deal effectively with these unique cases.

Adult↗
PubMed1992

Improved cerebral blood flow and CO2 reactivity after microvascular anastomosis in patients at high risk for recurrent stroke.

The medical community has not yet identified cerebrovascular pathophysiological factors that distinguish patients at high risk for stroke or aid in selecting patients for microvascular cerebral bypass. In this study, we describe the courses of 13 patients, all of whom suffered recurrent episodes of transient cerebral ischemia after previous cerebral infarction. These patients underwent regional cerebral blood flow studies using xenon inhalation with a CO2 challenge before and at various times after extracerebral-to-intracerebral microvascular anastomosis. Collateral circulation was assessed in all patients before surgery using four-vessel cerebral angiography. Patients were followed for a mean of 30 months (range, 1-7 yr) after the anastomosis. Measurements of mean cortical cerebral blood flow, as measured using the initial Slope Index, and CO2 cerebrovascular reactivity of these 13 patients were compared with those in a group of 20 patients designed as controls. Hemispheric cortical blood flow was significantly depressed in these patients before surgery compared with those in the control group (P less than 0.05). After the bypass, the mean resting Initial Slope Index in these patients increased 14% (P = 0.0005). Cerebral blood flow both before and after CO2 inhalation improved significantly in these patients after surgery (P = 0.001). Detectors bordering computed tomographic or magnetic resonance image documented infarctions, identified as peri-infarct regions, and demonstrated significant mean increases in both cerebral blood flow (38.8-43.2 ml/min/100 g, P = 0.05) and CO2 cerebrovascular reactivity in these patients after bypass (1.71 + 1.91% to 4.00 + 2.38% change Initial Slope Index/mm Hg CO2, P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

En bloc resection of an ethmoid carcinoma involving the orbit and medial wall of the cavernous sinus.

The involvement of the cavernous sinus by malignant tumors has limited their surgical treatment. We report here a successful en bloc resection of an invasive ethmoid carcinoma involving the cavernous sinus in a 46-year-old man. To prepare for surgery on this patient, a cadaver study was performed to investigate the feasibility of en bloc cavernous sinus resection and reconstruction. The preoperative evaluation, operative approach, and postoperative management are presented.

Adenocarcinoma↗
PubMed1991

Transoral crossbow injury to the cervical spine: an unusual case of penetrating cervical spine injury.

The complexity of missile injuries to the cervical spine has increased as the technology that causes these injuries has become more sophisticated. Management requires adaptation of conventional neurosurgical approaches to the cervical spine in an effort to limit neurological deficit and establish stability. We report an unusual case of a 19-year-old man who suffered transoral penetration of the cervical spine by an arrow released by a crossbow at close range.

Adult↗
PubMed1990

Sustained increased cerebral blood flow with prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) after subarachnoid hemorrhage.

Delayed cerebral ischemia is the major cause of death and disability in patients who initially survive an aneurysmal subarachnoid hemorrhage (SAH). In the present study, a protocol for prophylactic hypertensive hypervolemic hemodilution ("triple-H" therapy) was utilized in the treatment of SAH, and the response of cerebral blood flow (CBF) was evaluated. Serial CBF measurements, f1 and CBF15, were performed using the xenon-133 inhalation technique to maximize therapy. Surgery within 24 hours of subarachnoid hemorrhage was preferred. In 43 patients with SAH, mean hemoglobin and hematocrit were lowered 3.0 +/- 0.3 g/dL and 8.9 +/- 0.5%, respectively, over the first 24 hours. Mean f1 and mean CBF15 over the same period increased 34.2 +/- 5.8% and 21.2 +/- 3.6%, respectively. The maximum mean increase in CBF was 47.2 +/- 4.7% for f1 and 30.1 +/- 3.2% for CBF15. Cerebral blood flow remained elevated during the 21 days after SAH, irrespective of neurological grade on admission, age, sex, or angiographic arterial narrowing. This is the first report of a consistent method for establishing sustained improvement in CBF after SAH. All patients managed in total compliance with the protocol remained neurologically stable or improved. Two patients developed delayed ischemia and infarction because of the inability to sustain protocol requirements. Thirty-six of the 43 patients (84%) were discharged capable of an independent lifestyle. Triple-H therapy is a safe and effective modality for elevating and sustaining CBF after SAH. In combination with early aneurysm surgery, it can minimize delayed cerebral ischemia and lead to an improved overall outcome.

Adult↗
PubMed1989

Indium-111-Photofrin-II scintillation scan.

Photodynamic therapy is under intense investigation as an adjuvant treatment for malignant glial tumors of the central nervous system. Photofrin-II (HpD-II) is currently the most actively investigated photosensitizing agent. A crucial issue regarding the safe and efficacious usage of HpD-II-based photodynamic therapy is the individual in vivo kinetics of tumor uptake and retention, compared with normal brain clearance. The optimal time for photoactivation of sensitized tumor must be known to ensure a high target-to-nontarget ratio, resulting in the maximal tumor destruction while preserving normal brain. Our laboratory developed a radionuclide scan based on 111indium (111In)-labeled HpD-II to evaluate HpD-II localization and clearance noninvasively within a canine model of intracerebral gliosarcoma. Synthesis of the 111In-HpD-II complex in greater than 90% yield is achieved by a simple, rapid labeling method. Radiochemical purity and stability were verified by high-performance liquid chromatography. Using the canine model of intracerebral gliosarcoma, we followed the uptake of 111In-HpD-II in tumors with serial scintillation scanning. Localization of the tumor by 111In-HpD-II has been verified by contrast-enhanced computed tomographic scan followed by gross and histological examination of the enhancing brain region. Total body biodistribution of 111In-HpD-II at various times after injection has been evaluated. The ratio of uptake in tumor compared with surrounding brain peaked at 72 hours after injection. The knowledge of regional distribution and concentration of a photosensitizing agent within a tumor mass and surrounding brain allows for the most efficacious timing and localization of a photoactivating source.

Animals↗
PubMed1987

Inhibition of catechol-O-methyltransferase by 6,7-dihydroxy-3,4-dihydroisoquinolines related to dopamine: demonstration using liquid chromatography and a novel substrate for O-methylation.

We report that 6,7-dihydroxy-3,4-dihydroisoquinolines related to dopamine are potent inhibitors of catechol-O-methyltransferase (COMT), but are not apparent substrates for the enzyme in vitro or in vivo. Three dihydroxy (catecholic) dihydroisoquinolines, including the 1-benzyl (DesDHP) and the 1-methyl (DSAL) analogs, were found to inhibit COMT activity in rat liver supernatant more effectively than the well-known inhibitor, tropolone. Inhibition of O-methylation was uncompetitive with substrate, and O-methylated products of the catecholic dihydroisoquinolines were undetectable. For these in vitro studies, a facile liquid chromatographic assay was developed utilizing as a site-specific substrate, 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline-1-carboxylate (salsolinol-1-carboxylate). This catechol produces only one phenolic product isomer when incubated with liver supernatant and S-adenosylmethionine. Following central injection of DSAL in rats, inhibition of brain COMT in vivo was indicated by the reduced brain levels of homovanillic acid, but not of 3,4-dihydroxyphenylacetic acid. Furthermore, O-methylated DSAL metabolites could not be detected in brain by liquid or gas chromatography. We suggest that 6,7-dihydroxy-dihydroisoquinolines are "nonmethylatable" COMT inhibitors because they exist as quinoidal tautomers resembling pyridones or tropolones rather than as catechols. Quinoid formation is supported by the fluorescence and ultraviolet spectra for DSAL and its O-methyl derivatives. The experiments reveal a new class of COMT inhibitors that may be of pharmacological and mechanistic value. Additionally, 3,4-dihydroisoquinolines could arise endogenously via oxidation of the 1,2,3,4-tetrahydroisoquinolines which are ingested or produced from cellular catecholamine condensations. However, it is unlikely that dihydroisoquinoline (e.g., DSAL) concentrations necessary to inhibit COMT significantly would be attained via endogenous pathways.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Bactericidal effects of photoradiation therapy with hematoporphyrin derivative.

Hematoporphyrin derivative (Hpd) localizes selectively in malignant and rapidly metabolizing tissues and undergoes a cytotoxic reaction when exposed to light of a specific wavelength. Hpd has been studied extensively with regard to the diagnosis and treatment of tumors but not with regard to bactericidal activity. This investigation assessed the effect of light-activated Hpd on various microorganisms, on human polymorphonuclear leukocytes, and on the interactions of polymorphonuclear leukocytes and bacteria. Light-activated Hpd was 99.9% bactericidal against Staphylococcus aureus, Streptococcus faecalis, Bacteroides fragilis, Streptococcus M-G intermedius, Streptococcus mutans, Peptostreptococcus anaerobius, Peptococcus magnus, and Clostridium perfringens, but did not affect Escherichia coli, Pseudomonas aeruginosa, or Candida albicans. Photoactivation of Hpd rendered 98% of polymorphonuclear leukocytes inviable. Combinations of light-activated Hpd and polymorphonuclear leukocytes had a 4-log (99.99%) bactericidal effect on both intra- and extracellular S. aureus. The ability of Hpd to localize in inflammatory tissues may have therapeutic applications in the treatment of abscesses.

Bacteria↗
PubMed1984

Gas chromatographic analysis of endogenous catecholamines, phenolic amines and derived isoquinolines using short glass capillary columns and electron-capture detection.

A gas chromatographic method is described for the concomitant separation and analysis of catecholamines, catecholamine or 3,4-dihydroxyphenylethylamine condensation products (tetrahydroisoquinolines), and their isomeric mono-O-methyl (phenolic) metabolites which may be present in neuronal tissues, utilizing short glass capillary columns and electron-capture detection. Isomeric phenolic amines that were not generally separable with conventional-packed gas chromatographic columns were rapidly resolved on the capillary system, and with their catecholamine or catechol isoquinoline precursors, quantitated with high sensitivity (0.25-7.0 pg) and reproducibility. Key steps in the approach with tissues include initial amine isolation with a weak cation-exchange resin (BioRex-70), fluoracyl derivative formation, and brief washing of the derivatives with ammonium phosphate buffer (pH 5.8) just prior to capillary analysis; overall recoveries of amines or alkaloids added to rat brain homogenates ranged from 79% to 89%. Application of the method is demonstrated in an assay of endogenous dopamine in rat corpus striatum and hypothalamus. This new procedure should complement and in some instances may be preferred over liquid chromatographic assays for catecholic and phenolic amines and isoquinolines, and ought to be applicable to mass spectrometric detectors as well.

Animals↗