Ocular biocompatibility and structural integrity of micro- and nanostructured poly(caprolactone) films.

The identification of biomaterials that are well tolerated in the eye is important for the development of new ocular drug delivery devices and implants, and the application of micro- and nanoengineered devices to biomedical treatments is predicated on the long-term preservation within the target organ or tissue of the very small functional design elements. This study assesses the ocular tolerance and durability of micro- and nanostructured biopolymer thin films injected or implanted into the rabbit eye. Structured poly(caprolactone) (PCL) thin films were placed in adult rabbit eyes for survival studies, with serial ophthalmic examinations over 6 months. Morphologic abnormalities and device/tissue reactions were evaluated by histologic studies, and scanning electron microscopy (SEM) of films was used to determine the structural integrity. Structured PCL thin films (20- to 40-µm thick) were constructed to design specifications with 50-µm linear microgrooves or arrays of nanopores with ~30-nm diameters. After up to 9 months of ocular residency, SEM on devices retrieved from the eye showed preservation of micro- and nanostructural features. In ocular safety evaluations carried out over 6 months, serial examinations in 18 implanted eyes showed no evidence of chronic inflammation, cataractogenesis, or retinal toxicity. Postoperative ocular inflammation was seen in 67% of eyes for 1 week, and persistent corneal edema occurred in 1 eye. Histology revealed no ocular inflammation or morphologic abnormalities of ocular tissues. Thin-film/tissue responses such as cellular reaction, fibrosis, or surface biodeposits were not seen. Micro- and nanostructured PCL thin films exhibited acceptable ocular tolerance and maintained the structural integrity of design features while residing in the eye. Thin-film micro- and nanostructured PCL appears to be a feasible biomaterial for intraocular therapeutic applications.

Management of a recalcitrant candidal chorioretinal abscess.

PURPOSE: To describe a case of endogenously acquired Candida albicans chorioretinitis that was unresponsive to aggressive local and systemic therapy. METHOD: Single retrospective case report and review of pertinent literature. A 42-year-old woman with metastatic colon cancer acquired endogenous C. albicans chorioretinitis secondary to total parenteral nutrition after a small-bowel resection. RESULTS: A lesion involving the left fovea progressed despite systemic antifungal therapy with intravenous anidulafungin followed by oral fluconazole, intravenous Ambisome, and 11 total intravitreal injections of either Amphotericin B (5 mg each) or voriconazole (50-100 mg each). The patient underwent pars plana vitrectomy with subfoveal aspiration and removal of infectious material using submacular surgery, resulting in resolution of the infection. Postoperatively the patient's visual acuity was the same as before surgery (20/200 in the left eye). CONCLUSION: When treating endogenous fungal chorioretinitis, attention should be paid to both systemic treatment that has good intraocular penetration and early local therapy with intravitreal antifungals for sight-threatening lesions. Surgical intervention may also be warranted.

Referential delusions of communication and reality discrimination deficits in psychosis.

BACKGROUND: There appear to be two kinds of delusion of reference, which vary independently: delusions of observation and delusions of communication. It has been suggested that delusions of communication might derive from an impairment in reality discrimination, though the impairment would be centred on non-verbal channels in delusions of communication as opposed to verbal channels in auditory hallucinations. METHOD: Patients (N=64) with acute psychotic symptoms were recruited according to a 2 x 2 design: presence versus absence of delusions of communication crossed with presence versus absence of auditory hallucinations. They were presented with 100 brief video clips in which an actor either made a well-known gesture or an incidental movement, with the clips being obscured by visual noise. For each clip, the patients indicated how confident they were that a gesture was portrayed. RESULTS: According to a signal detection analysis, all groups showed adequate sensitivity and the groups did not differ in sensitivity, but patients with delusions of communication showed a bias to report gestures which was not shown by patients with hallucinations. A control group of healthy volunteers (N=57) showed significantly greater sensitivity than the patients and a more conservative bias than patients with delusions of communication. CONCLUSIONS: A bias to report gestures is not part of a general tendency to externalize one's own thoughts but may be the result of a reality discrimination deficit that is specific to delusions of communication. A possible theoretical explanation for such a deficit is discussed.

Referential delusions of communication and interpretations of gestures.

Gestures are an important aspect of non-verbal communication, but people with schizophrenia have poor comprehension of them. However, the tests of gesture comprehension that have been used present only scenes in which interpersonal meaning is communicated, though there is evidence that people with psychotic disorders tend to perceive communications where none were intended. Such mistakes about non-verbal behaviour are the hallmark of a subtype of delusions of reference identified as delusions of communication. Thus we hypothesised that patients with delusions of communication would tend to misinterpret incidental movements as gestures and, since delusions are often derogatory to the self, they would also tend to misinterpret gestures as insulting. Patients with acute psychotic symptoms (n=64) were recruited according to a 2 x 2 design (presence vs. absence of delusions of communication by presence vs. absence of auditory hallucinations). They, and 57 healthy controls, were presented with 20 brief video clips in which an actor either made a well-known gesture or an incidental movement. After each clip, they selected one of four interpretations: a correct interpretation if a gesture had been presented; the interpretation of a different gesture; an insulting interpretation; no gesture intended (correct for incidental movements). The patients made significantly more errors of all kinds than the controls, perceived significantly more of the incidental movements as gestures, and selected significantly more insulting interpretations of the clips. These differences between patients and controls were almost wholly due to patients with delusions of communication. These results suggest that the difficulties that people with delusions of communication experience in understanding gestures can be explained, at least in part, by the misattribution of self-generated internal events to external sources.

Salvage esophagectomy for recurrent tumors after definitive chemotherapy and radiotherapy.

OBJECTIVES: Some patients and oncologists choose to treat localized esophageal cancer with definitive chemotherapy and radiation therapy rather than surgery. A subset of these patients have local relapse without distant metastases and therefore have no other curative intent treatment option but salvage esophagectomy. METHODS: We reviewed our experience with salvage esophagectomy from 1987 to 2000 at M.D. Anderson Cancer Center (n = 13, salvage after chemotherapy and radiotherapy group) and compared the data with those of patients receiving esophagectomy in a planned fashion 4 to 6 weeks after preoperative chemotherapy and radiation therapy (n = 99, preoperative chemotherapy and radiotherapy group). RESULTS: Increases in morbidity were seen after resection in the salvage after chemotherapy and radiotherapy group relative to the preoperative chemotherapy and radiotherapy group: mechanical ventilation (9.0 days vs 3.3 days, P =.08), intensive care unit stay (11.2 days vs 5.1 days, P =.07), hospital stay (29.4 days vs 18.4 days, P =.03), and anastomotic leak rates (5/13 [39%] vs 7/99 [7%], P =.005). Operative mortality (within 30 days) also tended to be increased statistically nonsignificantly (2/13 [15%] vs 6/99 [6%], P =.2). Salvage esophagectomy resulted in long-term survival (25% 5-year survival) in a subset of patients. Improved survival after salvage esophagectomy was associated with early pathologic stage (T1 N0, T2 N0), prolonged time to relapse, and R0 surgical resection. CONCLUSION: Patients who undergo salvage esophagectomy for relapse of tumor after definitive chemoradiation therapy have increased morbidity, mortality, and hospital use relative to patients undergoing planned esophagectomy after preoperative chemoradiation. Nevertheless, long-term survival can be achieved in this group, and such treatment should be considered for carefully selected patients at an experienced center.