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Twenty-eight rhodium, iridium or ruthenium complexes were evaluated for their in vitro antifungal activities against Candida albicans and Candida tropicalis. Fourteen compounds showed an antifungal activity against C. albicans and C. tropicalis with a range of the minimum inhibitor concentrations (MICs) between 16 and 250 micrograms/mL.
Since the evolution of prostate-specific antigen testing for prostate cancer, men have been diagnosed with earlier staged disease. Earlier staged cancer is amenable to local therapy. Over the last decade, new technology has evolved in the treatment of localized prostate cancer. High dose rate afterloading 192 Iridium prostate brachytherapy is a new innovative technique utilizing state of the art equipment and highly specialized computers to achieve precise treatment of prostate cancer with radiation. We present our initial experience with this innovative technique.
While the surgical and chemotherapeutic therapy is an established procedure for the treatment of ovarian cancer, the role of radiotherapy is not quite clear. We investigated whether the recurrence rate concerning the vaginal cuff and pelvis in ovarian cancer patients can be reduced by postoperative irradiation with afterloading technique. In retrospective analysis 20 patients with ovarian cancer, stage I-IV, received radiological contact therapy with 192-Iridium 2 x 7.5 Gy in 0.5 cm tissue depth after surgical and chemotherapeutic treatment. A control group of 20 patients with similar oncological parameters was formed. In both groups a local recurrence occurred in 6 women, which was confirmed clinically, histologically and by diagnostic devices. After 2 years, 6 of the irradiated patients survived and 11 of the control group. The results show, that the irradiation of the vaginal cuff, as applied in endometrial carcinoma, will not reduce local recurrence rate of ovarian cancer.
A 2 1/2-year-old girl with a history of bilateral retinoblastoma underwent primary enucleation of the right eye and was referred for further management of persistent tumor in the fellow eye. Previous treatment of the left eye included external beam radiotherapy, systemic chemotherapy, laser photocoagulation, cryotherapy, and direct scleral application of a bare iridium-192 radioactive seed. Examination revealed focal full-thickness necrosis of the left upper and lower eyelid and a large inferonasal viable retinoblastoma tumor with overlying retinal detachment. Systemic chemotherapy and direct laser photocoagulation were administered. Four months after presentation, the patient developed focal scleral necrosis with 360 degrees hemorrhagic choroidal detachment. Enucleation was performed and histopathologic examination demonstrated full-thickness scleral necrosis with adjacent viable retinoblastoma tumor cells. Follow-up examinations showed no evidence of recurrent or metastatic tumor. This case is the first report of scleral necrosis following combined modality treatment of retinoblastoma.
BACKGROUND: Post-stenting restenosis is a significant clinical problem, involving vascular smooth muscle cells (VSMCs) proliferation and apoptosis. It is reported that c-myc antisense oligodeoxynucleotides (ASODNs) local delivered by catheter can inhibit VSMCs proliferation. This study was designed to assess tissue distribution of c-myc ASODN local delivered using gelatin-coated platinum-iridium (Pt-Ir) stents, and its effect on apoptosis of VSMCs. METHODS: Gelatin-coated Pt-Ir stents that had absorbed caroboxyfluorescein-5-succimidyl ester (FAM) labeled c-myc ASODNs (550 microg per stent) were implanted into the right carotid arteries of 6 rabbits. Tissue samples were obtained at 45 minutes, 2 hours, and 6 hours. Tissue distribution of c-myc ASODNs was assessed by fluorescence microscopy. In addition, 32 rabbits were randomly divided into two groups. Rabbits in the control group (n = 16) were implanted with gelatin-coated Pt-Ir stents, and those in the treatment group (n = 16) were implanted with gelatin-coated stents that had absorbed c-myc ASODNs. 7, 14, 30, or 90 days (n = 4, respectively, for each group) after the stenting procedure, the stented segments were harvested, and histopathological examinations were performed to calculate neointimal area and mean neointimal thickness. The expression of c-myc was assessed using in situ hybridization (ISH) and immunohistochemical methods. Apoptotic VSMCs were detected using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM). RESULTS: According to fluorescence microscopic results, FAM-labeled c-myc ASODNs were concentrated in the target vessel media at the 45 minutes time point, and then dispersed to the adventitia. Morphometric analysis showed that neointimal area and mean neointimal thickness increased continuously up to 90 days after stent implantation, but that total neointimal area and mean neointimal thickness were less in the treatment group than in the control group at all time points (P < 0.0001). At day 7 and day 14 after stenting, there were no detectable apoptotic cells in either group. However, apoptotic cells were present in the neointima 30 and 90 days after stenting, and the number of apoptotic cells was less at 30 days than at 90 days. Meanwhile, c-myc ASODNs appeared to induce apoptosis in more cells in the treatment group than that in the control group. Typical apoptotic VSMCs were observable under TEM. The expression of c-myc was positive in the control group and negative or weakly positive in the c-myc ASODN treatment group, according to both ISH and immunohistochemical examination. CONCLUSION: Gelatin-coated Pt-Ir stent mediated local delivery of c-myc ASODNs is feasible. The localization of c-myc ASODN is primarily in the target vessel walls. c-myc ASODNs can inhibit VSMCs proliferation and induce its apoptosis after local delivery in vivo.
Iridium (Ir) is one of the six elements collectively known as the platinum group metals. For its excellent catalytic properties, Ir was recently introduced into DeNOx, a new generation of automotive catalysts. The aim of our study was to evaluate urinary Ir levels in an urban population. A total of 122 healthy male subjects of Rome (Italy) were studied. Ir quantification in the urine samples of these subjects was carried out by sector field inductively coupled plasma mass spectrometry. The mean urinary Ir level was 10.41 ng/g creatinine (standard deviation: 9.67; 25th-75th percentile: 3,62-12,74 ng/g creatinine). The scientific community should respond to a potential increase in environmental exposure to Ir, due to its growing use as a catalyst, with very careful evaluation of the biological levels of this metal and monitoring of airborne particulate present in the life environment. Further investigation will enable researchers to confirm and integrate the findings of our present study undertaken in the context of surveillance.
The authors, after recalling the technique of Iridium 192* brachytherapy in the treatment of keloid scars, report a series of 46 cases operated at Rothschild Hospital (Department of Professor Baux) and irradiated at Tenon Hospital (Department of Professor Laugier), between 1981 and 1987. 87% of results were considered to be satisfactory.
In the therapy of localized prostatic cancer the radical prostatectomy shows good results within a five-year interval with no evidence of disease in nearly 90%. An important alternative is the radiotherapy by external beam or interstitial technique with iodine, gold or iridium. We use the high dose rate technique with Ir-192. In this technique five to seven hollow needles are placed in the prostate from perineal punctures under transrectal sonographic control. The three-dimensional brachytherapy planning is done according the actual needle position. A computer program calculates the radiation dose and distribution for each needle by adjustment of time and stops of the Ir-implants. The Ir-192 is temporary loaded twice with 9 Gy supplemented with external beam radiation (18 x 2 Gy). Since 1985 29 patients with localized tumor (T1-T3, N0, M0) have been irradiated. 21/29 had a pelvic lymphadenectomy before. In 85% of the patients were seen no side effects. Only one patient had a serious complication through a recto-vesical fistula. Out of the 21 followed-up patients 16 were in full remission, three had an androgen deprivation because of progression. A local tumor control could be demonstrated by cytology in 70% of the patients. This rational technique seems to be an alternative for patients not eligible for a radical prostatectomy.
Extremely high precision is needed to place radiation sources in the after-loading technique, but localisation techniques so far described do not offer the required accuracy. We used the computer-assisted surgery (CAS) localising system for the placement of after-loading probes in patients with head and neck carcinoma. Surgical instruments can be positioned without visual control using the CAS system. Since 1989 after-loading tubes have been placed using the CAS method. We evaluated the accuracy to be better than 1 mm. Ten after-loading treatments with iridium 192 of head and neck carcinomas were carried out between August 1989 and February 1991 with exact placement of the after-loading tubes in the nasopharynx. It seems feasible to treat cerebral tumours as well as tumours of the pelvic region by computer-assisted after-loading brachytherapy.
A simple experimental technique for interstitial iridium-192 high dose-rate afterloading is described which allows to perform experimental brachytherapy on a rat tumor model. To illustrate the possibilities and limitations of the technique, rhabdomyosarcoma R1H of the rat were subjected to a combined brachy- and teletherapy treatment applying a total dose of 60 Gy in fractions of 2 Gy. The results show that the surgical procedure had no influence on tumor response. However, would healing was considerably disturbed in animals which received afterloading treatment.
Optimization of brachytherapy means first of all a physical adaptation of isodoses to shape and tolerances of radiosensitive tissues surrounding the target volume, and also to shape and dosage requirements of the tumor to be treated. Dose computation algorithms for optimizing afterloading therapy postulate the discontinuous movement of the iridium source. A new method for the application of the discontinuous movement to our afterloading equipment was worked out. It combines the abilities of the source movements and the demands of the clinical optimization of the isodoses used for the brachytherapy of cervix carcinoma.
Cosmetic results of 80 patients with axillary lymph node negative or unknown T1 and T2 carcinoma of the breast who were treated with wide local excision, external beam radiotherapy and iridium-192 boost, were evaluated by the patient and the radiotherapist at 18-36 months. Their overall cosmetic results were assessed as good, very good or excellent by 80% of the patients. The radiotherapist's assessment was similar but in general the patients score was more favourable. After a follow-up of 24-72 months recurrence was found in only one patient at 40 months. This approach offers good cosmesis with low local recurrence rates in early breast carcinoma patients with negative axillary lymph nodes.
In order to compare the local efficiency of two different therapy modalities, 37 patients with advanced inoperable tumors of esophagus and cardia were evaluated hitherto in a prospective randomized study. Twenty patients received an exclusive laser treatment, 17 were additionally submitted to three high-dose-rate iridium-192 afterloading irradiations (single dose at the reference point 1 cm radially to the source: 7 Gy). In both groups, 15 patients died whose survival times were not different (125 versus 130 days), however, a beneficial influence was exerted by the afterloading therapy with respect to the duration of the palliative effect (67 versus 28 days) and the hospitalization time (25 versus 48 days).
Recent results on the antitumor activity of organometallic compounds of rhodium, iridium, copper and gold are reviewed. Coordination compounds of some organic ligands are also briefly mentioned. The most promising seem to be copper and gold complexes which exhibited remarkable activity against several tumor systems.
Iridium-191m would appear to be a highly useful agent for first-pass radionuclide angiocardiography (FPNA), with its very short half-life (4.96 sec), dual photopeaks (65 and 129 keV), and high injectable activity levels (greater than 100 mc). In order to compare 191mIr FPNA to current methods used to define cardiac function, 20 patients referred for cardiac catheterization were studied. Count rate data, right ventricular (RV), and left ventricular ejection fraction (LVEF), LV and diastolic volume (EDV), and end diastolic long axis (AXIS) were evaluated. Count rate data using 191mIr FPNA was consistently better than similar data obtained by 99mTc FPNA. There were acceptable correlations between 191mIr and 99mTc FPNA RVEF (r = 0.848), 191mIr FPNA and contrast angiography LVEF (r = 0.944), LVEDV (r = 0.917), and LV AXIS (r = 0.866). The data thus suggests that 191mIr FPNA has great potential in the evaluation of cardiac function.
Ultrashort-lived 191mIr (4.96 sec; 63-74 and 129 keV photons) is potentially advantageous for first-pass radionuclide angiocardiography, offering the opportunity to perform repeat studies with very low absorbed radiation dose to the patient. Left ventricular (LV) first-pass studies were performed in 72 patients with 191mIr from a new bedside 1.3 Ci (48.1 GBq) 191Os/191mIr generator system using an activated carbon support that offers high 191mIr yields (15-18%) and consistent low 191Os breakthrough (2-4 x 10(-4)%/bolus). Using a single crystal digital gamma camera, uncorrected end-diastolic counts in the left ventricular representative cycle ranged from 10 up to 30 k counts. The reproducibility of repeated LV ejection fraction (LVEF) determination at 2-min intervals in 50 patients was r = 0.97, mean diff. = 2.08 +/- 1.55 EF units. Comparison between 191mIr (80-120 mCi; 2,960-4,400 MBq) and 99mTc (20-25 mCi; 750-925 MBq) LV count rates indicates a 3 wk useful shelf life of this new generator system for cardiac studies. Iridium-191m determined LVEF correlated closely with 99mTc determined LVEF in 32 patients (r = 0.96, mean diff. = 1.87 +/- 1.23 EF units). Parametric images for LV wall motion analysis were comparable with both isotopes. We conclude that rapid, repeat, and reproducible high count rate first-pass left ventricular studies can be obtained with 191mIr from this new 191Os/191mIr generator system using a single crystal digital gamma camera.
Following the experience of the German authors, the treatment of choroidal melanoma with ruthenium 106 disk was introduced in Lyon. Between 1983 and 1988, 127 patients were treated. Results are analysed on a group of 84 patients followed 18 months and more. In 72 cases a reduction of thickness was noted. It was complete in 33 cases. Enucleation was performed in 10 patients due to no response or regrowth. In 3 cases the tumor was sterilized. Five patients died of metastases, and 73 are alive, 3 of them with liver metastases. An afterloading iridium template disk was used in 8 patients. 4 of them with a tumor thickness between 6.5 and 8 mm had a good response. Edema of the fovea was observed in 21% of cases, while cataracts were very unusual with Ru 106. An enucleation was performed in 6 patients because of a complication. A useful vision may be preserved in 60% of cases. The scleral tolerance dose is close to 1,500 Gy. These results are in agreement with those of the literature and are considered to be satisfactory for tumors not exceeding 5 to 6 mm in thickness. If the tumor is located close to the fovea or the papilla, and/or if the thickness is 8 mm or more, proton beam could be a good alternative.
Between January 1985 and January 1988, 56 patients received radioactive implant therapy of the Eustachian tube with Iridium 192 in the context of tympanoplasty for chronic otitis with tubal dysfunction. After reviewing the method used, we present the results by category of chronic otitis and attempt to propose its indications. Tubal dysfunction was assessed on clinical and otoscopic data and tubal manometry in each patient. A randomised study would appear to be necessary to confirm the interesting results obtained in chronic mucous otitis, in the sequelae of chronic otitis, in evolving retraction pockets and finally for certain manifestly discharging cavities.