Lyme disease and preventive behaviors in residents of Nantucket Island, Massachusetts

BACKGROUND: To determine the age-specific prevalence of Lyme disease and whether preventive behaviors on Nantucket Island correlate with Lyme disease, we surveyed island residents. METHODS: A survey with questions on Lyme disease symptoms, history, and preventive behaviors was mailed to all residents. Respondents were stratified by likelihood of having had Lyme disease. A subsample was selected for examination, and then classified according to the Lyme disease national surveillance case definition. RESULTS: The overall lifetime prevalence of Lyme disease for Nantucket residents was 15% (CI, 10%-19.8%): 19% among females, and 11% among males. The prevalence was highest among age groups 0-16 and 30-49 years. Overall, 86% of the population practiced at least one behavior. The most frequently reported preventive behavior was checking oneself for ticks (80%), followed by wearing protective clothing (53%), avoiding tick areas (34%), and using tick repellent (11%). Younger individuals practiced fewer preventive behaviors than older individuals (p=0.001). Although males reported greater tick exposure than females, females uniformly practiced preventive behaviors more frequently (p=0.001). The practice of preventive behaviors was not associated with a history of Lyme disease, but finding more than 5 ticks per year on oneself was (p=0.001). CONCLUSION: Lyme disease is highly prevalent on Nantucket Island. Young people are particularly at risk and health education should emphasize preventive behaviors less frequently practiced: using tick repellent, avoiding tick areas, and wearing protective clothing.     

Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer

The revolution in individualized therapy for patients with advanced non-small cell lung cancer (NSCLC) has seen the emergence of a number of molecularly targeted therapies for distinct patient molecular subgroups. Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3–7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event. However, resistance to ALK-targeted therapies is a ubiquitous problem in the management of advanced ALK-positive NSCLC and can be mediated by secondary kinase mutations or the activation of compensatory alternative oncogenic drivers. New, more potent ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802), and AP26113 are now emerging, together with an increased knowledge of the molecular basis of resistance. There is a need to evaluate the optimal clinical application of these new agents, either as sequential therapies or in combination with other targeted agents, to combat resistance and prolong survival in patients with ALK-positive NSCLC. The remarkable clinical activity of ALK inhibitors also emphasizes the importance of optimal diagnostic testing algorithms, to ensure that all eligible patients receive these breakthrough therapies.     

Lack of prostate cancer radiosensitization by androgen deprivation.

PURPOSE: The majority of clinical trials have shown that high-grade prostate cancer patients treated with androgen deprivation (AD) plus radiation (RT) have a survival advantage over those treated with RT alone. One possible mechanism for such a favorable interaction is that AD sensitizes cells to radiation. Animal model studies have provided suggestive evidence that AD sensitizes cells to radiation, but this mechanism is difficult to confirm conclusively in vivo. This question was investigated in LNCaP cells grown in vitro. METHODS AND MATERIALS: LNCaP cells were cultured in vitro in Dulbecco's modified Eagle's medium (DMEM)-F12 medium, containing 10% fetal bovine serum (complete medium [CM]). AD was achieved by culture in charcoal-stripped serum (SS)-containing medium. Replacement of androgen was done by adding the synthetic androgen R1881 at 1 x 10(-10) M to SS. Apoptosis was measured with a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Clonogenic survival was used to determine overall cell death, and the results were corrected for differences in plating efficiency from the various growth conditions. RESULTS: LNCaP cells were grown in CM, SS, or SS + R1881 medium, and cell counts obtained at 3, 4, and 5 days. Cell number increased exponentially in CM, whereas no increase in cell number was observed in SS medium. Cell counts from growth in SS + R1881 were intermediate between these extremes. Apoptosis was measured to determine if the combination of AD + RT in vitro resulted in supra-additive cell death, as has been previously described in an in vivo model system. The cells were cultured for 3 days before RT and apoptosis quantified 24 h after RT. There was a consistent supra-additive increase in apoptosis in cells exposed to AD + RT (2 or 8 Gy), as compared to either treatment given individually. In contrast, significant radiosensitization by AD was not observed by clonogenic survival even when the conditions of AD were varied. No radiosensitization was observed upon incubation in SS medium for 3, 4, or 5 days before RT, or extending AD after RT for 6 h before plating or 24 h after plating. CONCLUSION: The results show that in LNCaP prostate tumor cells supra-additive apoptosis does not translate into radiosensitization by clonogenic survival. Because clonogenic survival is a measure of overall cell death, either the level of apoptosis is too small a component of overall cell death or the increases in apoptosis occurred in a subpopulation that would have been killed by other mechanisms. Although the findings indicate that AD does not act by sensitizing prostate cancer cells to RT, the additive cell death and growth inhibitory effects of AD + RT are clinically meaningful.     

Assessment of perceived difficulties by residents in performing routine steps in phacoemulsification surgery and in managing complications

Objective: To analyze the perceived difficulties of residents in performing the routine steps of phacoemulsification surgery and in managing complications.Design: Cross-sectional questionnaire-based study.Participants: Thirty-six residents performing phacoemulsification during their learning curve.Methods: On an 8-point Likert scale, residents noted comfort levels with various steps of cataract surgery and with managing complications.Results: The respondents were grouped into Group 1 (second-year residents, n = 19) and Group 2 (third-year residents, n = 17). Residents in Group 2 had greater surgical experience than residents in Group 1 (p = 0.001). The most difficult step in cases of phacoemulsification for Group 1 was loading a foldable intraocular lens (IOL) (mean score 6.05, SD 1.57), and for Group 2 it was nuclear emulsification (mean score 3.59, SD 1.42). Both second- and third-year residents found capsular bag dialysis the most difficult complication (mean scores 6.0 [SD 1.9] and 5.75 [SD 2.14], respectively). The second-year residents had significantly more difficulty with errant capsulorrhexis, anterior chamber IOL placement, and repeated iris prolapse as compared with third-year residents. Group 2 residents reported that mature, senile cataracts were the most difficult cases for them to manage (mean score 6.23, SD 1.56).Conclusions: This study identifies perceived difficulties that residents experience in routine cases of cataract surgery, highlighting specific areas in which they may benefit from additional training and practice.     

Factors Related to Successful Transcatheter Closure of Atrial Septal Defects Using the Amplatzer Septal Occluder

The Amplatzer septal occluder (ASO) is used for transcatheter closure of atrial septal defects (ASDs). This study aimed to determine the factors influencing successful closure with the ASO. A retrospective analysis of 69 patients who underwent transcatheter ASD occlusion between 2003 and 2007 was performed. The ASO was successfully implanted during 67 (97%) of 69 procedures. A major adverse event occurred for 6 patients (9%), and 13 patients (19%) experienced a minor adverse event. The outcome for 53 cases (77%) was a composite clinical success. Patient age (p = 0.191) and consultant experience (p = 0.270) were not important factors in successful ASD occlusion. However, patient weight (p = 0.031), diameter of the defect (p = 0.030), device size (p = 0.044), aortic rim size (p = 0.002), and device/defect ratio (p < 0.001) all were significant factors. Complications were significantly more likely for patients whose device/defect ratio was <1.125 (loose) or ≥1.333 (tight) (p < 0.001). The device/defect ratio may provide a clinically useful tool with the potential to predict patients likely to experience an adverse event as a result of transcatheter ASD occlusion. A larger sample would enable refinement of the device/defect ratio and provide a more robust prediction of success.     

Management of tunnel fungal infection with voriconazole

A 59-year-old woman presented 1 month after cataract surgery in the right eye with a stromal infiltrate at the site of the cataract surgery wound. The visual acuity was perception of light with accurate projection. Corneal scraping of the infiltrate revealed septate hyphae. There was no response to 6 weeks of therapy with topical fortified antibiotic agents and topical antifungal therapy in the form of natamycin 5%, amphotericin B 0.15%, and intracameral amphotericin B. The patient was started on oral voriconazole 200 mg twice daily and topical voriconazole 1% every hour, and resolution of the ulcer was noted within 3 days. At the 4-month follow-up, a visual acuity of 20/60 was achieved, with the formation of a vascularized corneal opacity superiorly. This case illustrates that topical and oral voriconazole may be used in the treatment of recalcitrant cases of fungal tunnel infections not responding to conventional antifungal therapy.     

Infectious keratitis following keratoplasty

Infectious keratitis following corneal transplantation is one of the leading causes of failure of a corneal graft. The incidence of graft infection is variable, with developing countries having a higher incidence. The majority of the graft infections occur within 1 year of the corneal transplantation. Suture-related problems and persistent epithelial defect are the most common risk factors predisposing to graft infection. Pneumococcus species and Staphylococcus aureus have been found to be the commonest microorganisms in the developed world, whereas Staphylococcus epidermidis is the most often detected microorganism in corneal graft infection in the developing world. The early identification of predisposing risk factors in patients and their appropriate management at the earliest may prevent the occurrence of graft infection and might improve graft survival. Visual prognosis in eyes with post-keratoplasty graft infection is poor even after optimal therapy and there is a high rate of graft decompensation.