Power-injectable ports: safety during placement, therapeutic use, and contrast administration during computed tomography procedures.

PURPOSE: To determine the safety of power-injectable ports during placement, therapeutic use, and administration of intravenous contrast material using automated mechanical injectors. METHODS: This retrospective, single institution study examined all patients undergoing placement of a power-injectable port between May 1, 2006 and June 30, 2010, with follow-up data collected through October 31, 2010. Electronic records and PACS were searched for patient demographics, placement indication, device placed, placement site, attending operator, and complications. The number of CECT scans performed for patients with indwelling ports, rate of port access for such studies, and contrast extravasation or device failure events during power injection of contrast were recorded and compared to the results of all other methods of venous access for CECT scans. RESULTS: In total, 313 ports were placed in 307 patients. Device dwell time ranged from 3 to 1506 days with a mean of 577. A total of 20 (6.5%) complications were identified during the study period, all of which were late. There was no statistically significant difference in complication rates between five attending operators. Patients with ports underwent 676 CECT scans during which the port was injected 142 times (20.9%). Neither extravasation nor device failure occurred during any scan, yielding no statistically significant difference when compared to the results of other venous access methods. CONCLUSIONS: Power-injectable tunneled catheters with attached subcutaneous ports are safe with low rates of complication during placement and dwell time. Power injection of contrast through these ports may be as safe as power injection using other venous access methods.

Effect of a photoactivated rhodium complex in melanoma.

cis-Dichlorobis (3,4,7,8-tetramethyl-1,10-phenanthroline) rhodium(III) chloride (OCTBP) is an octahedral complex that has been shown to react with nucleic acids when irradiated with light. Earlier studies on its phototoxicity toward human esophageal, bladder, pancreas, and colon cancer cells have been extended to in-vitro and in-vivo evaluation of its effect on malignant melanoma cells using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium proliferation assay and xenograft model of melanoma. Tumor volume and the percentage of tumor growth delay were used to assess the antitumor effect of light-activated OCTBP. Terminal deoxynucleotidyl transferase dUTP nick-end labeling assays and immunohistochemistry were also performed on tumor tissue samples. Photoactivated OCTBP was found to inhibit melanoma cell growth by 40% at 100 µmol/l concentration. Phototherapy with OCTBP was most efficacious with optimal percentage treated/control values observed early in the course of the experiment. At the end of the experiment (60 days), there was a 50% tumor inhibition compared with vehicle or drug controls. OCTBP treatment resulted in a tumor growth delay of 16 days (tumor growth of 24%) compared with the untreated control, whereas cisplatin resulted in 10 days tumor growth delay. This antitumor activity was found to be closely associated with the induction of apoptosis. The use of photoactivated OCTBP as an adjuvant therapy for the treatment of melanoma may provide a new targeted therapy to prevent progression of this disease.

Effect of ring methylation on the photophysical, photochemical and photobiological properties of cis-dichlorobis(1,10-phenanthroline)rhodium(III)Chloride.

Methylated analogues of cis-dichlorobis(1,10-phenanthroline)rhodium(III)chloride (BISPHEN) have been prepared in order to increase the hydrophobicity of the parent compound, and thus create octahedral rhodium (III) complexes suitable for use as anticancer and antiviral agents that can be photoactivated. The parent complex has been shown in earlier work to be unable to cross through cell membranes. Octamethylation, as in the case of cis-dichlorobis(3,4,7,8-tetramethyl-1,10-phenanthroline)rhodium(III)chloride (OCTBP), provides enough hydrophobicity to be taken up by KB tumor cells. It also provides a higher level of ground-state association with double-stranded DNA and increases the quantum efficiency of photoaquation by greater than 10-fold, relative to BISPHEN. OCTBP forms covalent bonds to deoxyguanosine when irradiated with the nucleoside, as has been seen with the parent complex. Irradiation of OCTBP in the presence of the KB or M109 tumor cell lines using narrow-band UVB (lambda = 311 nm) irradiation initiates a considerable amount of phototoxicity. There is evidence that OCTBP acts as a prodrug (i.e. after passing through the cell membrane the metal complex is photolyzed to cis-chloro aquo OCTBP, which may be the active phototoxic agent). OCTBP and the tetramethyl analogue cis-dichlorobis(4,7-dimethyl-1,10-phenanthroline)rhodium(III)chloride (47TMBP) also show photoaquation upon excitation with visible light (lambda > 500 nm), and indeed, some phototoxicity of KB cells is observed at these wavelengths as well. This is attributed to direct population of photoactive triplet-excited states. These results, together with our earlier studies of cis-dichloro[dipyrido(3,2-a: 2',3'-c)phenazine (1,10-phenanthroline)rhodium(III)chloride (DPPZPHEN) demonstrate that such octahedral rhodium complexes are viable "photo-cisplatin" reagents.

Catheter-directed thrombolysis for acute limb ischemia.

Acute limb ischemia is a potentially life-threatening clinical event. Thrombosis in situ, bypass graft thrombosis, and embolic occlusion are the three major precipitating events leading to acute limb ischemia. Management of acute ischemia depends on the clinical status of the affected limb and patient comorbidities. Catheter-directed thrombolysis (CDT) is the treatment of choice for patients with relatively mild acute limb ischemia (Rutherford categories I and IIa) with no contraindications to thrombolytic therapy. Patients with severe acute limb ischemia (Rutherford category IIb) need emergent revascularization. CDT should be considered, nonetheless, if the relative risks compared with primary operation are favorable. CDT is a life- and limb-saving treatment for many patients despite limitations of efficacy and associated complications. This article is a review of the etiology of acute arterial occlusion; clinical triage of patients presenting with acute limb ischemia; catheter guide wire techniques, pharmacological agents, and devices in current use for CDT; as well as the outcomes of CDT.

'Photocisplatin' reagents.

Owing to the effectiveness of cisplatin in cancer chemotherapy, there is a growing interest in the development of other metal complex-based drugs. Similarly, the approval of photodynamic therapy and extracorporeal photopheresis in clinical practice, and the general advantages of temporal and spatial specificity inherent in phototherapy have generated a general interest in the development of other light-dependent treatment modalities. Over a decade ago it was demonstrated that the thermally inert octahedral bisbipyridyl complex cis-dichlorobis(1,10-phenanthroline)-rhodium(Ill) chloride (BISPHEN) could be activated by light and could then mimic the thermal chemistry between cisplatin and calf thymus-DNA. Thus, the term 'photocisplatin reagents' was coined for rhodium (and related) metal complexes that are thermally inert, but which form covalent bonds with DNA upon irradiation with ultraviolet/visible light. This review discusses recent developments in the elaboration of such photocisplatin reagents.

Photochemistry of 5-phenyl-1-pentene in the gas phase.

The photochemistry of the title compound has been studied in the gas phase using 254-nm irradiation. In addition to meta cycloadducts analogous to those observed in solution, population of S1(vib) in the gas phase gives several products, the relative amounts of which depend on quencher gas pressure but not on excitation wavelength. For example, in the absence of butane, the major photoproduct is compound 5. This product is formed by a [1,5] hydrogen shift in the primary photoproduct, compound 4. Compound 4 is an intramolecular meta cycloadduct that is generated in the gas phase with sufficient excess vibrational energy to undergo rearrangement unless quencher gas is present. Likewise, there is evidence that two other meta cycloadducts (2 and 3) are also formed with appreciable vibrational energy in the absence of a quencher gas. A unique intramolecular ortho cycloadduct is also formed from 1 but only within a narrow range of quencher gas pressures. This is a two-photon product, with the initial cycloadduct (11) ring opening to a cyclooctatriene (12) that photochemically closes to 6. The pressure dependence of this ortho cycloaddition may be due to a requirement for vibrational deactivation of 11 (Scheme 5) or a precursor species (Scheme 6). The overall chemistry is outlined in Scheme 7.

Phototoxicity against tumor cells and Sindbis virus by an octahedral rhodium bisbipyridyl complex and evidence for the genome as a target in viral photoinactivation.

An octahedral rhodium complex (cis-dichloro(dipyrido[3,2a-2',3'c]phenazine)(1,10-phenanthroline)rhodium(III) chloride; DPPZPHEN) has been prepared that can penetrate tumor cell membranes and the Sindbis viral capsid. The compound is phototoxic to these entities when irradiated with UVA light. Model studies with calf thymus and supercoiled plasmid DNA indicate that the complex can both bind with, and nick, nucleic acid. Analysis of Sindbis virus, following irradiation with the metal complex, confirmed that the viral genome was rendered noninfectious by this treatment.

Photooxidation of 2'-deoxyguanosine 5'-monophosphate in aqueous solutions.

Mass spectrometric and ultraviolet absorption spectral evidence are presented for the assignment of structures to three products detected in the reaction mixtures formed upon the photolysis of aqueous solutions of the nucleotide 2'-deoxyguanosine 5'-monophosphate (dGMP) with light of wavelengths >270 nm. The products for which structures are assigned are spiroiminodihydantoin 2'-deoxyribonucleotide (1), 2,2-diamino-4-([2-deoxy-5-monophosphate-beta-D-erythro-pentofuranosyl]amino)-5-(2H)-oxazolone (oxazolone 2'-deoxyribonucleotide, 2) and 2-amino-5-([2-deoxy-5-monophosphate-beta-D-erythro-pentofuranosyl]amino)-4H-imidazol-4-one (imidazolone 2'-deoxyribonucleotide, 3). These results, when combined with mechanistic data presented in an earlier communication, provide support for the proposal that the irradiation of dGMP with UVB light leads to the formation of singlet oxygen. The UV absorption spectral properties of the imidazolone make this product a reasonable candidate to rationalize the autosensitization of dGMP degradation reported in the earlier communication.

Photoaquation of methylated cis-dichlorobis(1,10-phenanthroline)rhodium(III)chloride compounds by direct population of a photoactive triplet excited state.

Photoaquation in compounds II and III by direct excitation into a photoactive triplet excited state is reported. The location of the singlet to triplet transition in compound III is estimated by a combination of the action spectrum for photoaquation in the region between 520 and 600 nm and the phosphorescence spectrum at 77 K. The significant increment of the reactivity (10-fold) of the triplet states in II and III as compared to that in I is explained in terms of increasing sigma-donation from the phen ligands stabilizing the pentacoordinated rhodium intermediate formed by chloride expulsion.

Reactive oxygen species formation by UV-A irradiation of urocanic acid and the role of trace metals in this chemistry.

We have extended our study of the decomposition of urocanic acid (UCA) with ultraviolet A radiation (UV-A) by the self-sensitized generation of singlet oxygen (see Photochem. Photobiol. 75, 565 [2002]). The chemistry has been found to be partially dependent on the presence of trace metal, most likely iron. Rigorous removal of metal impurities from the reaction mixture, using Chelex, retarded (but did not eliminate) the UV-A-initiated UCA degradation. The addition of small amounts of ferric chloride to the Chelex-treated solutions restored reactivity. Chelex treatment had a modest effect on the previously reported ability of UCA photoproducts to photonick supercoiled plasmid DNA. Also, photoinactivation of Sindbis virus on irradiation with the UCA photoproducts is now reported. Inactivation of the virus by a photoproduct mixture derived from a UCA solution that had been pretreated with Chelex was less rapid and gave better behaved time-course plots than was observed for photoproducts from non-Chelex treated solutions. These results are particularly noteworthy in light of the ubiquitous presence of both UCA and iron in the skin.

Formation of singlet oxygen by urocanic acid by UVA irradiation and some consequences thereof.

Singlet oxygen-initiated decomposition of urocanic acid (UCA) (3-(1H-imidazol-4(5)-yl)-2-propenoic acid) was used to successfully confirm the report that UCA generates singlet oxygen when irradiated with ultraviolet A light (UVA). The UCA-generated singlet oxygen converts UCA to one or more products that then catalyze the further destruction of the UCA with UVA light by singlet oxygen formation. Some nicking of the phiX-174 supercoiled plasmid DNA was observed when UCA was irradiated with UVA to complete destruction of the starting material, and the product mixture was then mixed with the plasmid in the dark. More extensive nicking was seen when the photoproduct mixture and the plasmid were irradiated with UVA light. An "aged" (4 days) solution of UCA photoproduct no longer caused nicking in the dark but retained the capability to nick the plasmid when irradiated. There is evidence for the presence of hydroperoxides in the UCA photolysis product mixture, and the quenching studies with 2-propanol indicate that free radicals are involved in the plasmid-nicking photochemistry. Singlet oxygen does not appear to play a role in the nicking of the plasmid.

Antenna-Initiated Photochemistry in Polyfunctional Steroids. Intramolecular Singlet and Triplet Energy Transfer between Aryl, Ketone, and Alkene Groups in 6beta-(Dimethylphenylsiloxy)-5beta-androstanes(1).

Steroids have been prepared that bear a dimethylphenylsiloxy (DPSO) group and additional C3 and/or C17 ketone functionalities. The DPSO group has been used to harvest 266 nm photons and then activate the ketone functionalities through intramolecular singlet-singlet energy transfer (intra-SSET). Thus, the monoketones 3,3-(ethylenedioxy)-6beta-(DPSO)-5beta-androstan-17-one (6) and 6beta-(DPSO)-5beta-androstan-3-one (8) both exhibit DPSO-initiated photochemistry at the carbonyl groups. Irradiation of the diketone, 6beta-(DPSO)-5beta-androstane-3,17-dione (5), gives two ring D-derived photoproducts, an epimer (19) and an enal (18), both coming from the C17 ketone excited singlet state. Here Phi(intra-SSET) from the aryl antenna to the carbonyl groups is ca. 88% efficients and occurs with a rate of ca. 6.5 x 10(9) s(-)(1), with the chemistry indicative of facile intra-SSET between the C3 and C17 ketones. The alkylidene group at C3 (i.e., as in 6beta-(DPSO)-3(E)-ethylidene-5beta-androstan-17-one (33) and its Z isomer (34)) has no effect on the rate or efficiency of aryl activation of the C17 ketone.