Theophylline toxicity: Successful management of a patient with distributive shock secondary to drug overdose.

Presenting a case of acute theophylline and salbutamol overdose with distributive shock. Twenty one years old lady presented with history of consumption of 3 gram of theophylline and 40 mg of salbutamol. On admission she had altered sensorium with the systolic blood pressure of 60 mmHg, unrecordable diastolic blood pressure and heart rate of 147/min. Investigations revealed severe metabolic acidosis, hypokalemia, hypocalcemia which was managed by intravenous fluids, vasopressors, infusion of injection calcium gluconate and injection potassium chloride. As her hemodynamic status did not improve, she has been initiated on 1.5 mL/kg of lipid emulsion as bolus and then 0.5 mL/kg/h as infusion. Her hemodynamic status improved gradually and she was discharged in 24 h. Lipid emulsion had been used in local anesthetics and many tablet overdoses. In this patient timely administration of lipid emulsion resulted in early recovery of shock.

Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis.

BACKGROUND: The VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions. METHODS: The mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay. RESULTS: Pegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs. CONCLUSIONS: Targeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.

Role of free space and conformational control on photoproduct selectivity of optically pure α-alkyldeoxybenzoins within a water-soluble organic capsule.

Optically pure α-alkyl deoxybenzoins resulting in products of Norrish Type I and Type II reactions upon excitation has been investigated within the octa acid (OA) capsule in water. The product distribution was different from that in an organic solvent and was also dependent on the length of the α-alkyl chain. Most importantly, a rearrangement product not formed in an organic solvent arising from the triplet radical pair generated by Norrish Type I reaction was formed, and its yield was dependent on the alkyl chain length. In an organic solvent, since the cage lifetime is shorter than the time required for intersystem crossing (ISC) of the triplet radical pair to the singlet radical pair the recombination with or without rearrangement of the primary radical pair (phenylacetyl and benzyl) does not occur. Recombination without rearrangement within the capsule as inferred from monitoring the racemization of the optically pure α-alkyl deoxybenzoins suggesting the capsule's stability for at least 10(-8) s (the time required for ISC) is consistent with our previous photophysical studies that showed partial opening and closing of the capsule in the time range of microseconds.

A sensitive and selective mercury(II) sensor based on amplified fluorescence quenching in a conjugated polyelectrolyte/spiro-cyclic rhodamine system.

A novel fluorescence-based sensor for mercury(II) ion is described consisting of a water-soluble, anionic-conjugated polyelectrolyte (CPE) and spiro-cyclic rhodamine derivative (1). A solution containing the CPE (0.1 × 10(-6) M repeat unit concentration) and 1 (1 × 10(-6) M concentration) in aqueous solution exhibits a sensitive and selective turn-off fluorescence response to Hg(II). The Stern-Volmer quenching constant for quenching of the fluorescence of the system by Hg(II) is ≈1.5 × 10(7) M(-1) , and Hg(II) can be sensed with a detection limit <10 × 10(-9) M. A mechanism for the sensor response is proposed and it consists of efficient and selective complex formation between 1 and Hg(II), along with a very high association between the 1-Hg(II) complex and the anionic CPE.

Triplet sensitization in an anionic poly(phenyleneethynylene) conjugated polyelectrolyte by cationic iridium complexes.

We describe a systematic study of triplet sensitization in a poly(phenyleneethynylene) conjugated polyelectrolyte (CPE) in methanol solution by using a series of three cationic iridium complexes with varying triplet energy. The cationic iridium complexes bind to the anionic CPE by ion-pairing, leading to singlet state quenching of the polymer, and allowing for efficient back-transfer of triplet excitation energy to the polymer. Efficient (amplified quenching) of the polymer's fluorescence is observed for each iridium complex, with Stern-Volmer quenching constants in excess of 10(5) M(-1). Triplet sensitization is confirmed for two of the iridium complexes by monitoring the relative yield of the CPE triplet state by transient absorption spectroscopy. One of the iridium complexes does not sensitize the CPE triplet, and consideration of the energies of the three complexes allows us to bracket the triplet energy of the CPE within the range 1.95-2.26 eV.

Efficacy of end-only-functionalized oligo(arylene-ethynylene)s in killing bacterial biofilms.

Cationic end-only-functionalized oligo(arylene-ethynylene)s (EO-OPEs) have recently been found to be broad-spectrum and effective antimicrobial agents because of their unique structure and optical properties. In this study, we investigated their potential use for preventing and reducing Escherichia coli (E. coli) biofilms. The Calgary biofilm device (CBD) was used to form bacterial biofilms of E. coli; in these studies, the minimum inhibitory concentration (MIC) and the minimum biofilm eradication concentration (MBEC) were determined. E. coli biofilms uniformly grow on pegs of the CBD device lid. The MIC values determined for EO-OPEs are comparable to those found for standard antibiotics such as kanamycin (MIC = 11.2 µg/mL). About 10-30 times the concentration of EO-OPEs was required to eradicate E. coli biofilms and prevent regrowth in the dark. Near-UV irradiation of EO-OPEs enhanced their efficacy in killing biofilms.

Aggregation-induced amplified quenching in conjugated polyelectrolytes with interrupted conjugation.

A pair of anionic conjugated polyelectrolytes that contain three-ring (phenylene ethynylene) units linked by a single -CH(2)- or -O- tether (P1 and P2, respectively) are studied. The linkers serve to interrupt the π conjugation along the polymer backbone. Fluorescence spectroscopy reveals that P2 forms a fluorescent aggregate in methanol and water; however, the fluorescence of P1 is much weaker in water, and P1 exhibits only weak aggregate fluorescence. Fluorescence quenching of the polymers was examined using methyl viologen (MV(2+)) as a cationic quencher. P1 shows only a weak amplified quenching effect, with a Stern-Volmer quenching constant of K(SV) ≈ 6 × 10(5) M(-1) in methanol. Interestingly, for P2 in methanol, the aggregate emission is strongly quenched with K(SV) ≈ 5 × 10(6) M(-1), which is comparable to the highest quenching efficiency observed for fully π-conjugated polyelectrolytes. By contrast, the monomer emission is quenched much less efficiently, with K(SV) ≈ 2 × 10(5) M(-1). The results are explained by a model in which -O- linked polymer P2 is able to fold into a helical conformation in solution, which facilitates the formation of extended π-stacked aggregates allowing long-distance exciton transport.

Antibacterial activity of conjugated polyelectrolytes with variable chain lengths.

Cationic poly(phenylene ethynylene)- (PPE-) based conjugated polyelectrolytes (CPEs) with six different chain lengths ranging in degree of polymerization from ∼7 to ∼49 were synthesized from organic-soluble precursor polymers. The molecular weight of the precursor polymers was controlled by the amount of a monofunctional "end-capping" agent added to the polymerization reaction. Cationic CPEs were prepared by quaternization of amine groups to tetraalkylammonium groups. Their structure-property relationships were investigated by observing their photophysical properties and antibacterial activity. The polymers were found to exhibit a chain-length dependence in their photophysical properties. It has also been observed that the polymers exhibit effective antibacterial activity against both Gram-positive and Gram-negative bacteria under UV irradiation, whereas they show little antibacterial activity in the dark. An effect of chain length on the light-activated antibacterial activity was also found: The shortest polymer (n=7) exhibited the most effective antibacterial activity against both Gram-positive and Gram-negative bacteria.

Light-induced antibacterial activity of symmetrical and asymmetrical oligophenylene ethynylenes.

The light-induced antibacterial activity of symmetric and asymmetric oligophenylene ethynylenes (OPEs) was investigated against Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Escherichia coli) bacteria. To understand the light-induced biocidal effect better, the transient absorption and triplet lifetime of OPEs were studied in methanol and water. A higher triplet lifetime was observed for OPE samples in water than in methanol. The magnitudes of the changes in optical density (ΔOD) of the S-OPE-n(H) series of symmetric oligomers are much higher than that of the asymmetric OPE-n series in water and are generally correlated with the singlet oxygen yield. It was found that the antibacterial activity against both Gram-positive and Gram-negative bacteria is size-, concentration-, and time-dependent. The light-induced antibacterial activity may result from the coordinated interactions of membrane disruption and interfacial or intracellular singlet oxygen generation, and the dominant factor is most likely the latter. The results obtained in this study will aid in the design of more efficient biocides in the future.

Role of free space and weak interactions on geometric isomerization of stilbenes held in a molecular container.

Photochemical geometric isomerization of olefins is long known to depend on the medium in which it occurs. Highest selectivity occurs in flexible biological systems as well as in inflexible crystals. We present results in this report that suggest the isomerization is selective even in an isotropic flexible aqueous medium provided it occurs within an isolated water-soluble inflexible reaction cavity. By examining the photochemistry of twelve stilbenes (trans and corresponding cis isomers) included in an organic cavitand octa acid we have been able to probe the role of 'free volume', 'weak interactions' and 'supramolecular steric effects' on the geometric isomerization process. Geometric isomerization becomes selective when the olefin's mobility is restricted by the medium through weak interactions, supramolecular steric effects and controlled free space (free volume).

Thiourea as a template for photodimerization of azastilbenes.

In this study we have explored the potential of thiourea (TU) as a template to preorient stilbazoles and bispyridylethylenes (azastilbenes) in the crystalline state. TU is able to preorient eleven azastilbenes toward dimerization in the crystalline state. While cocrystals of these eleven olefins photodimerized to a single dimer expected based on crystal packing, pure crystals of these olefins either were nonreactive or gave a mixture of dimers. The differential photobehavior of the pure crystals and cocrystals highlights the importance of TU in templating the olefins in a photoreactive orientation in the crystalline state. X-ray crystallographic and photochemical studies have identified a few azastilbenes that photodimerize in spite of not being arranged in an ideal orientation in the crystalline state. These as well as a few examples already reported in the literature suggest that it is important to recognize that molecules could experience large amplitude motions in the crystalline state, especially when energized by light. Short-term lattice instability caused by photoexcitation can be effective in driving a photochemical reaction. Thus one should view the crystalline arrangement of molecules upon light exposure as "dynamic" rather than "static" as determined from X-ray structure analysis.

Guest rotations within a capsuleplex probed by NMR and EPR techniques.

With the help of (1)H NMR and EPR techniques, we have probed the dynamics of guest molecules included within a water-soluble deep cavity cavitand known by the trivial name octa acid. All guest molecules investigated here form 2:1 (host/guest) complexes in water, and two host molecules encapsulate the guest molecule by forming a closed capsule. We have probed the dynamics of the guest molecule within this closed container through (1)H NMR and EPR techniques. The timescales offered by these two techniques are quite different, millisecond and nanosecond, respectively. For EPR studies, paramagnetic nitroxide guest molecules and for (1)H NMR studies, a wide variety of structurally diverse neutral organic guest molecules were employed. The guest molecules freely rotate along their x axis (long molecular axis and magnetic axis) on the NMR timescale; however, their rotation is slowed with respect to that in water on the EPR timescale. Rotation along the x axis is dependent on the length of the alkyl chain attached to the nitroxide probe. Overall rotation along the y or z axis was very much dependent on the structure of the guest molecule. The guests investigated could be classified into three groups: (a) those that do not rotate along the y or z axis both at room and elevated (55 degrees C) temperatures, (b) those that rotate freely at room temperature, and (c) those that do not rotate at room temperature but do so at higher temperatures. One should note that rotation here refers to the NMR timescale and it is quite possible that all molecules may rotate at much longer timescales than the one probed here. A slight variation in structure alters the rotational mobility of the guest molecules.

Outcomes of therapeutic deep lamellar keratoplasty and penetrating keratoplasty for advanced infectious keratitis: a comparative study.

PURPOSE: To compare the therapeutic success, visual outcomes, complications, and graft survival rates of therapeutic deep anterior lamellar keratoplasty (TDALK) and therapeutic penetrating keratoplasty (TPK) for advanced infectious keratitis. DESIGN: Retrospective, comparative study. PARTICIPANTS: One hundred twenty-three patients (126 eyes) with medically uncontrolled infectious keratitis of bacterial, fungal, or acanthamoeba etiologies who underwent TDALK (n = 26) or TPK (n = 100 eyes; 80 nonperforated ulcers; 20 perforated ulcers; mean follow-up in TDALK, 12.9 months; in TPK, 21.3 months). METHODS: We performed TDALK for infections confined to the corneal stroma and the technique used was either manual lamellar dissection or Anwar's big bubble technique for total stromal removal. Therapeutic penetrating keratoplasty was performed for either nonperforated or perforated ulcers. Comparison with respect to recurrence of infection, visual acuity, graft survival, and complications was made. Baseline characteristics of the patients were analyzed using the chi-square test. Kaplan-Meier survival analysis was used to evaluate graft survival. MAIN OUTCOMES MEASURES: Therapeutic success (eradication of infection) or therapeutic failure (recurrence of original infection in cornea or sclera, or as endophthalmitis), graft survival (clarity), and best-corrected visual acuity (BCVA). RESULTS: Therapeutic success rate of 84.6% was achieved in the TDALK group and 88% in the TPK group (P = 0.74); of the 12 eyes with recurrence of infection in the TPK cohort, 6 developed endophthalmitis with poor outcomes. A BCVA of > or =6/9 was achieved in 50% of patients in the TDALK group and 20.2% in the TPK group (P = 0.01). Mean improvement of acuity was 7.27 lines in the TDALK group and 4.76 lines in the TPK group (P = 0.01). Kaplan-Meier survival analysis at 1 year showed better graft survival for TDALK (90%) compared with TPK (78.4%). CONCLUSIONS: For medically unresponsive infectious keratitis, TDALK may be considered instead of TPK yielding similar graft survival, without an increased risk of disease recurrence.

Keratoprosthesis surgery for end-stage corneal blindness in asian eyes.

PURPOSE: To establish a multidisciplinary surgical program for osteo-odonto-keratoprosthesis (OOKP) surgery in Asia and to evaluate efficacy and preliminary safety of this keratoprosthesis in end-stage corneal and ocular surface disease. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Sixteen adults of Asian ethnic origin, bilaterally blind with end-stage corneal blindness from Stevens-Johnson syndrome, or severe chemical or thermal burns. METHODS: Osteo-odonto-keratoprosthesis surgery involves 2 procedures-in stage 1, an autologous canine tooth is removed, modified to receive an optical polymethyl methacrylate cylinder, and implanted into the cheek. The ocular surface is denuded and replaced with full-thickness buccal mucosa. Stage 2 surgery, performed 2 to 4 months later, involves retrieval of the tooth-cylinder complex and implanting it into the cornea, after reflection of the buccal mucosal flap, corneal trephination, iris and lens removal, and anterior vitrectomy. Concurrent glaucoma and vitreoretinal procedures are also performed at either stage, as required. MAIN OUTCOME MEASURES: Visual acuity (VA), field of vision, anatomical integrity and stability, and ocular and oral complications related or unrelated to the OOKP device. RESULTS: Osteo-odonto-keratoprosthesis surgery was performed on 15 patients, with a mean follow-up of 19.1 months (range, 5-31). Intraoperative complications included expulsive hemorrhage (keratoprosthesis device not implanted), tooth fracture (n = 1), oronasal fistula (n = 1), and mild inferior optic tilt (n = 1). Anatomical stability and keratoprosthesis retention has been maintained in all eyes, with no dislocation, extrusion, retroprosthetic membrane formation, or keratoprosthesis-related infection. Other complications not directly related to device insertion included retinal detachment (RD) related to silicone oil removal (n = 1) and endophthalmitis related to endoscopic cyclophotocoagulation performed 1 year after OOKP surgery (n = 1). Eleven patients (73.3%) attained a stable best spectacle-corrected VA of at least 20/40 or better, whereas 9 (60%) attained stable 20/20 vision. Four patients achieved their best visual potential, ranging from 20/100 to counting fingers vision, related to preexisting glaucomatous optic neuropathy or previous RD. CONCLUSIONS: Establishment of our OOKP program suggests that OOKP surgery has the potential to restore good vision to the most severe cases of corneal blindness in an Asian setting, with minimal device-related complications. Longer follow-up of these cases is currently underway.

Outcomes of femtosecond laser-assisted penetrating keratoplasty.

PURPOSE: To evaluate outcomes from the use of a femtosecond laser to trephine both donor and recipient corneas during penetrating keratoplasty (PK). DESIGN: Prospective interventional case series. METHODS: Patients were recruited from the cornea clinic of the Singapore National Eye Centre. We used a 10-kHz Femtec (20/10 Perfect Vision, Heidelberg, Germany) femtosecond laser to perform trephination of the donor cornea on an artificial anterior chamber, followed by trephination of the recipient cornea. Trephination cuts were straight and performed 90 degrees to the corneal surface. Tissue bridges were bluntly separated with a Barrett phaco chopper. The donor button was then sutured to the recipient with double continuous sutures, or interrupted sutures if significant host corneal vascularization was present. Postoperatively, visual acuity, refraction, intraocular pressures, and optical coherence tomography (Visante; Carl Zeiss, Jena, Germany) were evaluated. RESULTS: Eight eyes of eight patients underwent PK for conditions ranging from bullous keratopathy to corneal scarring from herpetic stromal keratitis. Patients were followed up for a mean of 9.5 months. Best-corrected visual acuities of patients with no ocular comorbidity ranged from 20/20 to 20/80. Mean cylindrical refractive error at last review was 2.56 diopters [D] (range, 0.50 to 4.00 D). Tissue bridges were bluntly dissected except for one case that required scissors completion of trephination. No complications were encountered related to use of the Femtec laser. CONCLUSION: The Femtec laser reliably trephines both donor and recipient corneas for PK, with good visual outcomes and relatively low degrees of astigmatism.

Corneal (lymph)angiogenesis--from bedside to bench and back: a tribute to Judah Folkman.

The normal cornea, the transparent "windscreen" of the eye, is devoid of both blood and lymphatic vessels. Nevertheless, both hem- and lymphangiogenesis can occur in response to severe corneal inflammation and can lead to blindness. Judah Folkman and co-workers exceedingly used the normally avascular cornea as the in vivo model system to study the mechanisms of angiogenesis and to test activators and inhibitors of angiogenesis in the last 3 decades. Recently, the cornea also became a successful model to study especially inflammatory lymphangiogenesis. As the last step in the circle from bedside to bench and back, we now are seeing the first (usually off-label) use of specific novel angiogenesis inhibitors in the diseased and pathologically vascularized human cornea to treat sight-threatening corneal angiogenesis and to promote graft survival after corneal transplantation by inhibiting lymphangiogenesis.

Controlling photochemical geometric isomerization of a stilbene and dimerization of a styrene using a confined reaction cavity in water.

Utility of a water-soluble deep cavity cavitand, octa acid, as a reaction medium is illustrated by carrying out photochemical reactions of a stilbene and a styrene included within the octa acid in water. Geometric isomerization of trans-4,4'-dimethyl stilbene is restricted while dimerization of 4-methyl styrene is facilitated within the octa acid cavity. The excited-state chemistry of both systems is different in this medium from that in organic solvents. The change in chemistry is attributed to the supramolecular effects provided by the host cavity.

Adjuvant radiotherapy in incompletely staged IC and II endometrioid uterine cancer.

OBJECTIVES: To estimate if adjuvant radiotherapy improves the disease-specific survival of patients with clinical stage IC and II endometrioid corpus cancer who did not undergo lymphadenectomy. METHODS: Information was obtained on patients with endometrioid corpus cancer from the National Cancer Institute database between 1988 and 2001. Data were analyzed using Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: A total of 3,664 patients (median age 70 years) with clinical stage IC to II endometrioid carcinoma did not undergo lymphadenectomy, of which 2,170 had stage IC and 1,494 stage II disease. Of these, 1,175 had grade 1, 1,637 had grade 2, 693 had grade 3, and in 159, grade was unknown. The 5-year disease-specific survival rates of clinical stage IC compared with stage II patients were 91.3% and 86.7% (P<.001). Of the 1,964 who received adjuvant radiotherapy, the 5-year disease-specific survival rate was 89.9% compared with 87.8% in those who did not undergo further treatment (P=.04). Adjuvant radiation improved the disease-specific survival rate of those with stage II disease, (86.5% compared with 81.9%; P=.02), but not in those with stage IC disease (91.7% compared with 92.6%; P=.68). The benefit of radiotherapy was significant in patients with grade 3 disease and patients 70 years or older (88.2% compared with 83.3%; P<.001). On multivariable analysis, age, stage, and grade were significant independent prognostic factors for disease-specific survival. CONCLUSION: Adjuvant radiotherapy marginally improved the survival of clinically staged IC-II endometrioid uterine cancer patients without lymphadenectomy. After excluding those without hysterectomy, radiotherapy did not significantly affect disease-specific survival. LEVEL OF EVIDENCE: II.

Infectious keratitis after laser epithelial keratomileusis.

PURPOSE: To report two cases of infectious keratitis occurring after laser epithelial keratomileusis (LASEK). METHODS: Two patients who underwent LASEK were referred to our center for the management of postoperative infectious keratitis. Infection occurred on postoperative days 2 (case 1) and 5 (case 2). Presenting visual acuity was count fingers in both cases. RESULTS: Patients were treated aggressively with hourly topical broad-spectrum fortified antibiotics after corneal scrapings were obtained. Culture was positive for Staphylococcus aureus in case 2. Both eyes responded to treatment, resulting in residual corneal scarring with reduced best spectacle-corrected visual acuity of 20/40 in case 1 and uncorrected visual acuity of 20/25 in case 2. CONCLUSIONS: Infectious keratitis can occur after LASEK surgery, and early diagnosis and aggressive therapy are required to aser ereduce visual loss.