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Biomedical subjects

D J Castro

Publications and source records attributed to D J Castro.

At least 55 records · Page 3Linked to original sources
PubMed1992

Laser dyes for experimental phototherapy of human cancer: comparison of three rhodamines.

The mitochondrial dye Rhodamine 123 (Rh-123) has been shown to be an effective photosensitizer for argon-laser irradiation of some types of human cancer cells in vitro. We reported that 514.5-nm laser illumination of Rh-123 sensitized human melanoma, and squamous carcinoma cells strongly inhibited tumor-cell proliferation as measured by decreased 3H-thymidine (3H-T) uptake in vitro and may eradicate some tumors when grown as transplants in nude mice. However, several other human tumors were resistant to Rh-123 laser therapy in vitro and in vivo. In the current study, it was possible to obtain 100- to 1000-fold increased sensitivity to 514.5-nm laser illumination by replacement of Rh-123 with the cationic rhodamine dyes Rh-3G and Rh-6G. Cell viability was decreased over 95% and 3H-T incorporation reduced at least 80% by laser phototherapy after sensitizing tumor cells with 1 micrograms/mL Rh-123, 0.01 microgram/mL Rh-3G, or 0.001 microgram/mL Rh-6G. However, Rh-123 alone did not decrease 3H-T uptake significantly unless present at over 10- to 100-fold higher levels than Rh-3G, respectively. The tumor cell dye uptake level was measured by N-butanol extraction and absorption scans at 400 to 600 nm. The results revealed that dye uptake was more rapid, and retention of Rh-3G and Rh-6G was 5- to 10-fold higher than for Rh-123 in the human tumor cells. The data suggest that Rh-3G and Rh-6G may be highly sensitive chromophores for laser phototherapy of human cancer cells.

Adenocarcinoma↗
PubMed1992

Biodistribution of rhodamine-123 in nude mice heterotransplanted with human squamous cell carcinomas.

Rhodamine-123 uptake and release was determined in nu/nu mice heterotransplanted with P3 human squamous carcinomas to assess its value as an in vivo laser photosensitizer for treatment of solid tumors. Following intraperitoneal injection of Rh-123 (1 micrograms/g of body weight), mice were killed at 2, 4, 6 and 24 hours, and 3 and 7 days postinjection. The peak concentrations of Rh-123 per milligram of tissue measured by fluorescence spectrophotometry was distributed as follows: kidneys greater than spleen greater than intestine greater than stomach greater than liver greater than tumor greater than skin greater than skeletal muscles greater than lung greater than heart greater than blood greater than brain. No preferential uptake or retention of Rh-123 by tumors was observed. However, a longer retention with higher concentrations of the dye was seen in normal skin as opposed to P3 tumors from 4 hours to 7 days postinjection with Rh-123. The elimination of Rh-123 was rapid, with the dye falling to less than 2% of peak concentration at 7 days postinjection. Knowledge of Rh-123 biodistribution in tumors and other tissues suggests that optimal timing after injection of this dye may allow selective photodiagnosis and photodynamic therapy of tumors with the argon laser.

Animals↗
PubMed1991

Photodynamic therapy using rhodamine-123 as a new laser dye: biodistribution, metabolism and histology in New Zealand rabbits.

Rhodamine-123 (Rh-123) has been tested recently as a new laser dye for photodynamic therapy of human tumors in vitro and in vivo. Prior to initiation of clinical studies of this technique, we evaluated the biodistribution, metabolism, and pathological changes of Rh-123 in rabbits after systemic, repetitive injections of the dye in escalating doses. At doses between 0.1 to 1 mg/kg of Rh-123 injected intramuscularly (IM) daily for 5 days, no local or systemic toxicity was observed during the 4 weeks of follow-up. The peak concentrations of Rh-123 in micrograms/g of tissue was distributed as follows: kidney (3.24) greater than heart (2.24) greater than spleen (1.77) greater than lung (0.61) greater than liver (0.38) greater than skin (0.30) greater than skeletal muscle (0.17) greater than genitals (0.13) greater than brain (0.04). The elimination of Rh-123 was very rapid, with the dye falling to 2.7% of peak concentration at 72 hours in the kidneys, and to undetectable levels at 240 hours postinjection in all organs, except the skin, which retained 3% of the peak level at 240 hours. The low toxicity and rapid metabolism of Rh-123 in this preclinical model suggests that the dye and Argon laser may represent an effective combination for treatment of superficial malignancies.

Animals↗
PubMed1991

Nd: YAG interstitial laser phototherapy guided by magnetic resonance imaging in an ex vivo model: dosimetry of laser-MR-tissue interaction.

Interstitial laser phototherapy (ILP) is a promising technique in which laser energy is delivered percutaneously to various depths of tumors. This technique will become clinically useful only when efficient, sensitive, and noninvasive monitoring systems are developed. In this study, the spatial distribution of ILP in bovine liver tissue, induced by a Nd: YAG laser with an interstitial sapphire-frosted contact probe, was evaluated by magnetic resonance imaging (MRI). Tissue was exposed to three energy densities of the Nd:YAG laser by a reproducible method of dosimetry. Thermal profiles were measured with a probe inserted 5 mm from the laser tip. T1-weighted magnetic resonance images were taken after the laser exposure. Tissue specimens were then evaluated for standard quantification of laser-induced damages. A linear correlation between the level of laser energy, induced temperature change, lesion size on T1 magnetic resonance image, and volume of histological damage was observed. Further improvement of this technique of dosimetry in an in vivo model should allow the development of software for MRI which will correlate the above parameters and render this technique of ILP clinically useful.

Animals↗
PubMed1991

Future directions of laser phototherapy for diagnosis and treatment of malignancies: fantasy, fallacy, or reality?

A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current "fantasies and fallacies" regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described.

Coloring Agents↗
PubMed1990

Importance of iron repletion in the management of Plummer-Vinson syndrome.

Plummer-Vinson syndrome (PVS) is characterized by iron deficiency anemia, upper esophageal stricture, cervical dysphagia, and glossitis. The precise role of iron deficiency in PVS has yet to be defined and remains a subject of much debate. A 29-year-old woman with PVS is presented. The patient had a 4-year history of severe iron deficiency anemia, a 2-year history of progressive dysphagia and weight loss, and a greater than 90% benign upper esophageal stricture. Iron therapy alone resolved her dysphagia and anemia, and a follow-up esophagram 1 year later showed a residual stenosis of less than 30%. The development of severe iron deficiency anemia in this patient 2 years before the onset of dysphagia, as well as the response of the stricture to iron repletion, supports the theory that iron deficiency can cause dysphagia and upper esophageal strictures. The occurrence of glossitis, gastritis, and esophagitis in iron deficiency demonstrates the adverse effects of iron depletion on the rapidly proliferating cells of the upper alimentary tract.

Adult↗
PubMed1990

Interstitial laser phototherapy assisted by magnetic resonance imaging: a new technique for monitoring laser-tissue interaction.

The rapid technological advances of magnetic resonance imaging, laser fiberoptics, and compatible probes may allow treatment of deep and sometimes surgically unreachable tumors of the head and neck with minimal morbidity through interstitial laser phototherapy. In this study, a new application of magnetic resonance imaging was developed to monitor and quantify laser-induced tissue damages. Pig skin was exposed to increased levels of argon laser (514.5 nm) at energy densities between 62.5 and 375 J/cm2 as determined by an accurate and reproducible method of dosimetry. Thermal profiles were recorded using an infrared sensor and T1- and T2-weighted magnetic resonance images were taken; afterward, biopsies were performed to quantitate the level of tissue damage. Our results demonstrate that above a certain threshold of laser energy, the magnetic resonance imaging findings are temperature dependent. Appropriate development of a scale matching laser energies, temperature profiles, T1- and T2-weighted magnetic resonance images, and histological quantitation of tissue destruction will allow us to optimize the three-dimensional control and monitoring of laser-tissue interactions.

Animals↗
PubMed1990

Argon laser phototherapy of human malignancies using rhodamine-123 as a new laser dye: the intracellular role of oxygen.

Recent studies demonstrated that the cationic, mitochondrial-specific dye Rhodamine-123 (Rh-123), is an efficient tumor photosensitizer for Argon laser treatment of human cancer cells both in vitro and in tumors grown as xenografts in athymic mice. To demonstrate the photodynamic mechanism of action of this reaction, the intracellular role of oxygen and temperature changes in treated cells have to be defined. In the current study, a large panel of human tumor cell lines of diverse histologic origin were tested for in vitro sensitivity to Rh-123 and the Argon laser (514.5 nm) in oxygen, deuterium oxide (D2O), and nitrogen (N2) environment. Tumor cells in suspension were first sensitized to Rh-123 (1 or 20 micrograms/ml for 1 hour), cooled on ice to 4 degrees C, and then exposed to the Argon laser (delta T = 14 +/- 1 degree C). Cell proliferation measured by [3H]-thymidine uptake 24 hours after sensitization with Rh-123 and laser treatment was significantly decreased in tumor cells kept in oxygen and D2O atmospheres. No decrease in DNA synthesis was seen in Rh-123 and laser treated cells kept in an N2 environment. Control tumor cells treated with Rh-123 or the Argon laser separately did not show any decreased [3H]-thymidine uptake in oxygen, D2O or N2 environment. These results provide evidence of a photodynamic process since Rh-123 sensitization and Argon laser activation occur at nonthermal levels of energy and are oxygen dependent. The high effectiveness of this technique of photodynamic therapy with the Argon laser, and low toxicity of Rh-123 could make its clinical use very attractive for the treatment of superficial malignancies.

Deuterium↗
PubMed1990

Flexible Nd:YAG laser palliation of obstructive tracheal metastatic malignancies.

Flexible Nd:YAG endoscopic laser surgery may become an effective new modality for palliation in patients with obstructive endotracheal metastatic malignancies. We report the results of the treatment of two patients with severely obstructing intraluminal tracheal metastatic melanoma and medullary thyroid carcinoma, using the neodymium-YAG laser via the flexible fiberoptic bronchoscope. Both patients complained of significant dyspnea, orthopnea, cough, and hemoptysis and were not candidates for rigid bronchoscopy because of underlying medical contraindications and anatomical problems. Multiple treatment sessions were used with treatment intervals of 1 to 2 weeks. All treatments were performed in the operating room under sedation, without intubation, with topical lidocaine and standard superior laryngeal nerve block. Successful relief of airway obstruction with complete regression of the endotracheal masses was achieved and no recurrences were seen after 9 months' follow-up. Flexible Nd:YAG laser bronchoscopy offered an alternative for the relief of obstructing endotracheal or bronchial malignancies in patients in whom the rigid bronchoscope could not be passed. it seemed to prolong survival in selected cases, and provided definite improvement in quality of life.

Aged↗
PubMed1990

Interventional magnetic resonance imaging in the head and neck.

Interventional MRI is clearly in its early stages of development. While the value of MR-guided aspiration cytology and MR evaluation of deep electrode implantation in the brain has already been confirmed with human clinical studies, the future of MR-guided interstitial laser therapy remains to be proven. Despite this, as we look ahead into the 1990s and the millennium, it is possible to imagine dedicated MR laser therapy units for combined radiological and surgical outpatient approaches in what may become the operating rooms of the 21st century.

Biopsy, Needle↗
PubMed1990

"Sensible" flap coverage of pressure sores in patients with meningomyelocele.

Restoration of sensibility in the paraplegic patient is the optimal therapy for the management and prevention of debilitating pressure sores. In patients with an absence of sensibility below the L3 spinal level, a locally transposed arterialized neuromyocutaneous gracilis flap may be uniquely utilized for ischial restoration of sensibility. Two patients with meningomyelocele-induced ischial pressure sores underwent local innervated neuromyocutaneous gracilis flap transposition to insensate areas from below the anatomic level of recipient insensibility. A 10-year follow-up revealed maintenance of sensibility in the flap and spread of sensibility to adjacent insensate areas with no evidence of pressure sore recurrence. Cadaver dissection and clinical Xylocaine injection demonstrated that the cutaneous sensory innervation to this flap is by means of a consistent sensory branch from the deep neurovascular pedicle, which coincides with the L1-L3 dermatome.

Adolescent↗
PubMed1989

A significant new contribution to radical head and neck surgery. The argon beam coagulator as an effective means of limiting blood loss.

A new argon beam coagulator system promises a radically different form of electrocoagulation. Rarely does a tool make such an important contribution to the surgical armamentarium. This instrument reduces blood loss by up to half via rapid superficial coagulation, even when severe bleeding occurs. It causes minimal tissue damage, coagulates large vessels (2 to 3 mm in diameter), reduces the risk of postoperative hemorrhage, and markedly reduces operative time. Since the coagulation is superficial, healing appears to be unimpaired. We describe our experience with this new instrument (video tape recordings demonstrating its use in surgical procedures are available).

Argon↗
PubMed1989

Rhodamine-123 as a new laser dye: in vivo study of dye effects on murine metabolism, histology and ultrastructure.

Rhodamine-123 (Rh-123) is a mitochondrial-specific dye that has recently proven to be an effective fluorochrome for photo-dynamic therapy of squamous carcinoma cells and melanomas with the Argon laser. Complete eradication of heterotransplanted human tumors in nude mice was possible if tumors were first "sensitized" to Rh-123 and then treated with the Argon laser. Prior to initiation of human testing of this technique, the toxicity and pathological changes in BALB/c mice were tested by an escalating dose schedule after systemic injection of Rh-123. Animals' body weight, blood chemistry, enzymes and organ evaluation for histology, and ultrastructural changes were analyzed for 3 weeks after injection with Rh-123. The results of this study demonstrate that Rh-123 has significant systemic toxicity in BALB/c mice injected at doses of 10 micrograms/g of body weight and above, manifested by chronic weight loss and elevation of muscle enzymes with death of the animals injected at doses higher than 50 micrograms/g of body weight. At doses of 1 micrograms/g of Rh-123, no local or systemic toxicity was observed even after a 3-week follow-up, suggesting that safe and effective tumor sensitization might be possible in humans at this concentration. The high effectiveness of this new technique of photodynamic therapy and the low toxicity of this dye in this preclinical model system suggests that Rh-123 and the Argon laser may represent a powerful new method for treatment of superficial malignancies.

Animals↗
PubMed1989

Bioinhibition of human fibroblast cultures sensitized to Q-switch II dye and treated with the Nd: YAG laser: a new technique of photodynamic therapy with lasers.

Kodak Q-switch II dye has recently proven to be an effective biostimulative agent on normal human fibroblast cultures. The potential for this dye as a new chemosensitizing agent for the treatment of connective tissue diseases and wound healing with the Nd:YAG laser was examined. Two normal fibroblast cell lines were first sensitized to a nontoxic dose of Q-switch II dye, then subjected to treatment with an Nd:YAG laser at 1,060 nm, with varying levels of energy and temperatures determined by a reproducible method of dosimetry. The results indicate that Q-switch II dye at nontoxic doses of 0.1 micrograms/ml enhances the cytotoxic effects of the Nd:YAG laser at temperatures as low as 36 degrees C. Furthermore, at physiological temperature ranges as low as 24 degrees C to 34 degrees C, cell duplication was inhibited, but cell viability was not affected. Similar results were not observed when fibroblast cultures were treated with the laser alone. These observations suggest that Q-switch II dye is an effective chemosensitizing agent for the Nd:YAG laser and could potentially be used to reduce collagen deposits in conditions such as keloids and hypertrophic scars.

Benzopyrans↗
PubMed1988

Phototherapy with argon lasers and Rhodamine-123 for tumor eradication.

The effectiveness of Rhodamine-123 (Rh-123) as a new photochemosensitizing agent for the argon laser treatment of human melanoma and squamous carcinoma cells in vitro was recently demonstrated. In this study, a new technique of "rosette" treatment with the argon laser was developed to completely eradicate human squamous carcinoma (P3) tumor transplants in nude mice after chemosensitization with Rh-123. Each group included four nu/nu mice injected subcutaneously with 10(7) P3 carcinoma cells/site for a total of 48 sites. Tumor take was greater than 95% at one week, with greater than 10 mm3 tumor volume at each site. Test groups were sensitized with Rh-123 (1 microgram/ml for 1 hour) by intratumor or intraperitoneal injection at 1 week and then treated with the argon laser at 514.5 nm. To allow uniform delivery of energies to the tumor and its edges, a new "rosette" technique was developed. The tumors were then exposed to nonthermal levels of 700 J/cm2 (36 degrees C) or 950 J/cm2 (40 degrees C) as determined by a new and reproducible method of dosimetry. All 16 tumors in this test group showed complete regression with excellent wound healing at 2 weeks and no recurrences, even after an 8 week followup. These results demonstrate that effective eradication of tumors can be achieved in vivo only after sensitization with Rh-123 and specific argon laser treatment ("rosette"), even at nonthermal levels of energies. The high effectiveness of this technique and low toxicity of Rh-123 may render its clinical use very attractive for the treatment of superficial malignancies.

Animals↗
PubMed1988

Biostimulation of human carcinoma cells with the argon laser: a previously unreported potential iatrogenic effect of lasers.

The human squamous carcinoma cell line P3 was subjected to treatment with a single mode argon laser at 514.5 nm. The temperature and energy levels delivered to the target cells were determined by a reproducible method of dosimetry. At energy levels between 860 to 990 J/cm2 and a corresponding temperature of 39 +/- 1 degrees C, a significant delayed stimulation in DNA synthesis was noted after 24 hours, but the cells remained viable. However, at energy levels and temperatures higher or equal to 1100 J/cm2 (41 degrees C), an immediate suppression of DNA synthesis was accompanied by nonviability of the P3 carcinoma cells. These results indicate that the argon laser has potential for selective biostimulation on carcinoma cell duplication at the specific "non-thermal" range of 39 +/- 1 degrees C. Similar effects were not observed when the P3 carcinoma cells were heated to this same temperature using a standard heat bath. This phenomenon appears to represent a previously undescribed potential iatrogenic effect of the monochromatic laser beam in the treatment of cancer.

Carcinoma, Squamous Cell↗
PubMed1988

Phototherapy with the argon laser on human melanoma cells "sensitized" with rhodamine-123: a new method for tumor growth inhibition.

Laser photodynamic therapy of superficial malignancies is a promising new approach that will become clinically useful when fluorochromes with high tumor specificity and low toxicity to normal tissues are identified. We recently reported that the mitochondrial dye, Rhodamine-123 (Rh-123), at nontoxic doses, is an effective sensitizing agent for argon laser treatment of human squamous carcinoma and melanoma cells in vitro. We now report the complete inhibition of in vivo tumor development by human M24 melanoma cells transplanted subcutaneously into nu/nu mice after exposure to 1 microgram/ml of Rh-123 for 1 hour and treatment with an argon laser at nonthermal temperatures of 36 to 40 degrees C. Significant in vivo growth was observed for all control tumors. These results demonstrate that Rh-123 enhances the tumoricidal effects of the argon laser at nonthermal temperatures and provides evidence that effective photodynamic therapy may be possible in vivo with the new fluorochrome Rhodamine-123.

Animals↗