Combined use of cryotherapy and diode laser photocoagulation for the treatment of threshold retinopathy of prematurity.

PURPOSE: Cryotherapy and indirect laser retinal photoablation are both effective in the treatment of retinopathy of prematurity (ROP). We describe the safety, efficiency, and effectiveness of combined cryotherapy and diode laser photocoagulation to treat threshold ROP. METHODS: Records of patients developing threshold ROP from January 1, 1996 through December 31, 1998, were retrospectively reviewed to identify those treated with combined cryotherapy and photocoagulation and followed up for at least 45 days postoperatively. Diode laser was used to ablate posterior avascular retina, and cryotherapy was used for anterior retina. Data reviewed included ocular and systemic complication rates, treatment duration, number of laser burns, most recent fundus examination, visual acuity, and refraction. RESULTS: In 13 patients, 23 eyes received combined treatment. No intraoperative complications occurred. Mean duration of anesthesia and treatment was 35 +/- 8 minutes/eye. A mean of 117 +/- 84 laser burns/eye were applied. In 20 of 23 eyes (87.0%), anatomic outcome was favorable at last examination. In 13 of 16 eyes (81.3%), functional (visual acuity) outcome was favorable (visual acuity better than 20/200) at 1 year. At 6 months or later, 14 of 16 eyes (87.5%) measured were myopic, of which 5 (31.3%) were highly myopic (> 6 diopters). CONCLUSIONS: The effectiveness of treating ROP with combined cryotherapy and diode laser photocoagulation compares with that of either modality alone. By decreasing the number of laser applications, combined therapy may be faster and technically easier for eyes with very posterior ROP. This may decrease the number of complications seen when either excessive cryotherapy or laser retinal photoablation is used.     

Novel quinuclidine-based ligands for the muscarinic cholinergic receptor

Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.     

A novel series of non-quaternary oxadiazoles acting as full agonists at muscarinic receptors

1 A novel series of non-quaternary oxadiazole-based muscarinic agonists demonstrated high affinity for muscarinic receptors. 2. These agonists possessed high efficacy in the nanomolar range at muscarinic receptors in the superior cervical ganglion, atrium and ileum but did not show selectivity across the tissue preparations. 3. Two amino oxadiazoles, one from a quinuclidine series (L-660,863) and one from a 1-azanorbornane series (L-670,207) possessed a high ratio of potency for displacing the binding of [3H]-N-methyl-scopolamine ([3H]-NMS) to potency for displacing the agonist [3H]-oxotremorine-M cortex. 4. The two azanorbornane derivatives L-670,548 and L-670,207 stimulated the turnover of phosphatidylinositol in the cortex with a potency higher than that obtained with any other known muscarinic agonist (ED50 0.26 and 0.18 microM respectively). 5. The maximum response obtained with L-670,207 was greater than that observed for carbachol but was comparable to that of the natural ligand acetylcholine. 6. These oxadiazole muscarinic agonists are among the most potent and efficacious non-quaternary muscarinic agonists ever described.     

The '2-week rule' for suspected breast carcinoma: a qualitative study of the views of patients and professionals.

BACKGROUND: The '2-week rule' for the referral of patients with potential cancers is an important but controversial development. AIMS: To investigate the 2-week rule for women with breast problems from the perspective of the patients and of healthcare professionals. DESIGN OF STUDY: Qualitative study using semi-structured interviews. SETTING: Patients referred to two breast care units and professionals from primary and secondary care in Teesside and Hartlepool. METHOD: Semi-structured interviews with a purposive sample of 12 patients referred under the 2-week rule and 20 professionals. RESULTS: All women experienced considerable worries in the time leading up to diagnosis. This affected relationships with others, and they used selective telling to help maintain control over their own anxiety and prevent anxiety in others. They were not aware of the 2-week rule as a new initiative, but wanted quick referral to assure them that they did not have cancer. Patients felt they needed more information about breast symptoms and the referral process. Comments about communication with professionals, both good and poor, were frequent in their accounts, which contrasted with the absence of such concerns in the accounts of the professionals. The professionals thought that the 2-week rule was advantageous in reducing anxiety, but thought that disadvantages included longer waits for patients referred outside the rule and increased pressure on hospital services. Cultural changes, including increased patient assertiveness and 'breast awareness', were considered important contextual factors. General practitioners (GPs) were concerned about missing diagnoses in patients statistically unlikely to have carcinomas. CONCLUSION: Differences in emphasis were apparent, with patients wanting to be assured that they did not have cancer, specialists concerned both about increased workload and the impact on patients with cancers, and GPs anxious about missing diagnoses. The 2-week rule compromises professional autonomy, which partially accounts for the anger directed against it. There is a need for patients to have more information, and they place great value on good communication. All patient responders experienced significant distress while waiting to be seen.     

Effectiveness of a brief workshop designed to improve teaching performance at the University of Alberta.

PURPOSE: To determine whether a two-day teaching enhancement workshop at the University of Alberta improved participants' teaching performance as rated by students. METHOD: Workshop participants (academic staff or residents) were asked to assess the value of the workshop. In addition, students were asked to rate instructors' teaching abilities before and after the instructors participated in the workshops, by completing a five-statement questionnaire routinely used to assess instruction at the University of Alberta. For control purposes, ratings were also obtained for a group of instructors who had not taken the workshop, over a similar time period. The authors used data from 1993-2002. RESULTS: The participants uniformly regarded the workshops as helpful. Both faculty and residents regarded the short teaching exercise as the most important component of the program. Of the instructional sections, the presentations on objectives and on structure (set, body, closure) were rated most highly by both groups. The students' mean ratings for the instructors after the workshop were significantly increased, while ratings for those who had not taken the workshop were unchanged CONCLUSION: Short teaching-enhancement workshops are regarded by the participants as helpful in improving their instructional skills. This view is supported by a significant increase in students' ratings of the instructors after they had taken the workshop.     

The immune response of healthy adults to a reduced dose of hepatitis B vaccine

Three hundred thirty-six medical personnel from hemodialysis centers were treated with three doses, 20 μg each, of the Merck hepatitis B vaccine (at 0, 1, and 6 months). Within 1 month after the first injection, 41% converted to anti-HBs positivity; after the second injection the conversion rate rose to 80–90%; and after the booster, to 96–98%. The later rate remained unchanged during the 18-month follow-up period. Only 2.8% of those vaccinated did not respond to the vaccine. The patterns of immune responses to 20-μg doses were found to be exactly the same as to 40-μg doses. It is suggested that reduced doses of vaccine should be as efficacious as the larger ones.