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Biomedical subjects

C Reed

Publications and source records attributed to C Reed.

At least 55 records · Page 3Linked to original sources

Contact lens base curve prediction from videokeratography.

PURPOSE: To assess whether the contact lens to cornea-bearing relationship, as determined from the fluorescein pattern, can be predicted from videokeratography. METHODS: Nineteen non-rigid gas permeable (RGP) lens wearers were each tested for fluorescein patterns with a series of seven RGP contact lenses of different base curves, and compared to a theoretical estimate of the fitting relationship from videokeratography. The experimentally determined alignment lens was then compared to the theoretical alignment (TA) value as determined from the central curvature and eccentricity. RESULTS: The mean difference in lens choice between the TA and experimental alignment (EA) values was -0.01 +/- 0.04 mm and between the simulated keratometric (KA) readings and the EA choice was 0.11 +/- 0.05 mm. CONCLUSION: A knowledge of the eccentricity value from videokeratography allowed a better prediction of the base curve to cornea relationship than was provided by only a central corneal measurement.

Adult↗

Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus.

PURPOSE: We have previously identified paclitaxel as an active single agent in the treatment of esophageal cancer. We performed a phase II trial of paclitaxel in combination with cisplatin and fluorouracil (5-FU), conventionally used chemotherapy for esophageal cancer. The antitumor response, toxicity, and survival of patients treated with the three-drug regimen were evaluated. PATIENTS AND METHODS: Sixty-one patients with advanced, surgically unresectable, or metastatic squamous cell or adenocarcinoma of the esophagus were treated. No prior chemotherapy was allowed. Thirty patients had adenocarcinoma and 31 patients had squamous cell carcinoma. The majority (47 patients; 77%) had metastatic disease and 14 patients (23%) had an unresectable primary or locally recurrent tumor. Patients received paclitaxel 175 mg/m2 by 3-hour infusion day 1; cisplatin 20 mg/m2 daily days 1 through 5, and 5-FU by continuous infusion at a dose of 1,000 mg/m2 daily days 1 through 5. Because of toxicity observed in the first 10 patients treated, the starting dose of 5-FU was subsequently reduced to 750 mg/m2 daily in the remaining patients. A planned attenuation of cisplatin to 15 mg/m2 daily was made after the first three cycles. Granulocyte colony-stimulating factor (G-CSF) was not routinely administered unless the patient had an episode of febrile neutropenia or prolonged grade 4 neutropenia. Treatment was recycled every 28 days. RESULTS: Sixty-one patients completed a median of five cycles, and 60 patients were assessable for response. Major responses were seen in 29 patients (48%; 95% confidence intervals, 35 to 61), which included seven complete responses (12%). Comparable response rates were seen for patients with adenocarcinoma (46%) and those with squamous carcinoma (50%), and for patients with metastatic disease (22 of 46 patients; 48%) and those with locally advanced disease (seven of 14 patients; 50%). A significantly higher complete response rate was observed in patients with squamous carcinoma (20%) compared with those with adenocarcinoma (3%; chi2 P=.04). The median duration of response was 5.7 months (range, 1 to 18.6 months). Median survival was 10.8 months (range, 1.5 to 25 months). Toxicity was severe but manageable with dose attenuation, and included 18% of patients with grade 3 neurologic toxicity. Twenty-eight patients (46%) required a dose attenuation for toxicity, and 42 of 275 treatment cycles (15%) required a dose attenuation. Twenty-nine patients (48%) required hospitalization for toxicity, which included 11 patients for neutropenic fever (18%). There were no treatment-related deaths. CONCLUSION: The combination of paclitaxel, cisplatin, and 5-FU has substantial antitumor activity in metastatic esophageal carcinoma, with a remarkable complete response rate noted in patients with squamous carcinoma. Paclitaxel is an important new agent in the treatment of esophageal carcinoma, and further evaluation of this agent in combination chemotherapy is warranted. Given the toxicity associated with the current regimen, the optimal dose and schedule of paclitaxel in combination chemotherapy remain to be established.

Adenocarcinoma↗

Mapping of conformational B cell epitopes within alpha-helical coiled coil proteins.

An approach to mapping antigenic B cell epitopes within alpha-helical coiled coil proteins has been developed and applied to two proteins: Streptococcal M protein and C. elegans paramyosin protein UNC-15. Overlapping peptides derived from an alpha-helical coiled coil conformational epitope were embedded between helical flanking peptides derived from the completely unrelated GCN4 leucine zipper peptide. The resulting chimeric peptides exhibited helical propensity. Chimeric peptides were tested for antigenicity (recognition by antibody) or immunogenicity (production of appropriate antibody response). A conformational epitope within the Streptococcal M protein recognised by three mAbs spanned 12 residues. Analysis of chimeric peptides based on C. elegans UNC-15 has enabled fine mapping of the minimal B cell epitope recognised by monoclonal antibody NE1-6B2 to seven non-contiguous residues (spanning 15 residues); the footprint of contact residues involved in antibody recognition being restricted to the hydrophilic face of the helix and covering five helical turns. This chimeric peptide epitope when coupled to diphtheria toxoid was highly immunogenic in mice and antisera recognised the conformationally dependent native peptide epitope. This approach has the potential to map conformational epitopes and design minimal epitopes for use as vaccine candidates.

Amino Acid Sequence↗

Prospective, randomized vector analysis of astigmatism after three-, one-, and no-suture phacoemulsification.

PURPOSE: To compare surgically induced astigmatism and visual outcomes after three-, one-, and no-suture phacoemulsification. SETTING: Johns Hopkins Hospital, Baltimore, Maryland and Manhattan Eye, Ear, and Throat Hospital, New York, New York, USA. METHODS: This prospective, randomized study followed 131 patients treated with phacoemulsification with a 5.5 mm self-sealing scleral tunnel and implantation of a 5.5 mm poly(methyl methacrylate) posterior chamber lens. Radial 10-0 nylon sutures were used in the three- and one-suture groups. RESULTS: Mean astigmatism was greatest in the first postoperative week in all groups and stabilized after 8 weeks. The percentage of patients with with-the-rule (WTR) astigmatism increased from baseline in the one- and three-suture groups and decreased in the sutureless group. Mean uncorrected Snellen acuity was significantly better in the no- and one-suture groups than in the three-suture group at 1 week. There were no significant differences in uncorrected acuity at other times. No statistically significant differences in the surgically induced spherical equivalent were noted among the three groups during the 1 year follow-up. There was significantly less surgically induced keratometric astigmatism in the one-suture group at 4 (P = .03) and 8 (P = .007) weeks postoperatively. At all follow-ups, the sutureless group had the greatest proportion of patients, with significant ATR astigmatic shift (1 week, 17%; 4 weeks, 32%); and the lowest proportion of patients with significant WTR astigmatic shift (10% after 1 week). At 4 weeks, the percentage of patients with significant WTR shift in the one-suture group dropped to that in the sutureless group (10%); however, those in the one-suture group had less ATR astigmatic shift (16%). CONCLUSION: Sutureless and one-suture surgery resulted in a low percentage of WTR induced astigmatism 4 weeks postoperatively. Compared with sutureless surgery, the one-suture surgery resulted in less ATR shift.

Adult↗

Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2.

Crystal structures have been determined of recombinant human tumor necrosis factor-alpha (TNF-alpha) and its R31D mutant that preferentially binds to TNF receptor R1 with more than seven times the relative affinity of binding to receptor R2. Crystals of the wild-type TNF were of space group P4(1)2(1)2 and had unit cell dimensions of a = b = 94.7 and c = 117.4 A. Refinement of the structure gave an R-factor of 22.3% at 2.5 A resolution. The crystals of TNF R31D mutant diffracted to 2.3 A resolution, and were of identical space group to the wild type with unit cell dimensions of a = b = 95.4 and c = 116.2 A, and the structure was refined to an R-factor of 21.8%. The trimer structures of the wild-type and mutant TNF were similar with a root mean square (r.m.s.) deviation of 0.56 A for Calpha atoms; however, the subunits within each trimer were more variable with an average r.m.s. deviation of 1.00 A on Calpha atoms for pairwise comparison of subunits. Model complexes of TNF with receptors R1 and R2 have been used to predict TNF-receptor interactions. Arg31 in all three subunits of wild-type TNF is predicted to form an ionic interaction with the equivalent glutamic acid in both receptors R1 and R2. Asp31 of the TNF R31D mutant is predicted to interact differently with the two receptors. The side chain of Asp31 in two subunits of the TNF mutant is predicted to form hydrogen bond interactions with Ser59 or Cys70 of R1, while it has no predicted interactions with R2. The loss of three strong ionic interactions of Arg31 and the electrostatic repulsion of Asp31 with Glu in the receptors is consistent with the reduced binding of the R31D mutant to both receptors relative to wild-type TNF. The replacement of these ionic interactions by two weaker hydrogen bond interactions between Asp31 of the R31D mutant and R1, compared with no interactions with R2, is in agreement with the observed preferential binding of the R31D mutant to R1 over R2. Analysis of the structure and function of receptor-discriminating mutants of TNF will help understand the biological role of TNF and facilitate its use as an antitumor agent.

Binding Sites↗

Comparative evaluation of patient information leaflets by pharmacists, doctors and the general public.

This study was undertaken to compare and contrast the views of pharmacists, general practitioners (GPs) and the general public on the value or otherwise of pharmacy-generated patient information leaflets. All three groups perceived these leaflets to be useful and an aid to improving compliance. Concerning the information included in leaflets, GPs rated the inclusion of a section on side-effects as being the least important, whilst pharmacists and the general public rated information on the storage of medicines as being least important. Pharmacists' estimates on what percentage of patients actually read leaflets were significantly lower than estimates by the general public. General practitioners and pharmacists generally concurred on the types of patients for whom leaflets are considered unsuitable, although a significantly higher percentage of pharmacists than GPs identified unsuitable patients. There were reservations by the pharmacists concerning the cost-effectiveness of leaflet facilities and on the value of leaflets compared with verbal counselling. The general public expressed the view that a leaflet facility would affect their choice of pharmacy and that they would be prepared to wait an additional short time to receive such a leaflet. Almost all GPs thought that it was in the patient's best interest to receive an information leaflet.

Adolescent↗

L-Glutamate and serotonin are endogenous in squid chromatophore nerves

Colour changes in cephalopods are controlled by complex organs termed chromatophores whose radial muscles are directly innervated from the brain. In the squids Alloteuthis subulata and Loligo vulgaris, light microscopy of silver- or Methylene-Blue-stained preparations shows that each muscle is innervated by 2-6 nerves running along its length. An electron microscope (EM) study shows that most of these nerves contain 50 nm diameter electron-lucent vesicles organised into numerous synapses along the muscle. Their size and appearance is consistent with their containing l-glutamate (l-Glu). Usually there is one nerve on each muscle containing 95 nm diameter electron-dense vesicles that are not organised into synapses. Such vesicles, whose appearance is consistent with their containing serotonin (5-HT), are never found co-localised with the small, clear vesicles. Topically applied l-Glu causes the radial muscles to contract (and the chromatophore to expand), even after chronic denervation; this effect is blocked by the glutamate antagonists CNQX and DNQX. In contrast, topically applied 5-HT (or its agonists 8-OH-DOPAT and -methyl 5-HT) induces relaxation of precontracted muscle. Incubation with antibodies to l-Glu (Lg-A), using peroxidase anti-peroxidase/diaminobenzidine visualisation, produces specific staining along the radial muscles like that seen with silver. Antibodies to 5-HT produce similar specific staining. When sections of skin that had stained positively with Lg-A in the light microscope are examined at the EM level, it is seen that such staining is confined to nerve axons. These results, showing that l-Glu and 5-HT are endogenous in the nerves innervating squid chromatophores and that the radial muscles contain receptors for both substances, suggest that l-Glu is an excitatory transmitter at squid chromatophore muscles. The way in which 5-HT acts to relax the muscles, however, remains to be established.

Journal Article↗

Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines.

Several prototype vaccines against the asexual blood stage of malaria are undergoing preclinical and phase I testing. Although these vaccines have been chosen for their ability to elicit an anti-parasite response, no practical and sensitive clinical trial procedure has been available for measuring their impact on parasite growth. We describe a system that allows parasite growth rates to be measured in volunteers through the incubation period. Two necessary elements of this system are developed: suitable blood-stage Plasmodium falciparum inocula, and a highly sensitive and quantitative assay to measure parasite growth during the incubation period. We infected five nonimmune volunteers with an inoculum as small as 300 parasites and demonstrated that the resultant in vivo asexual parasite growth rates were reproducible at 12-15-fold per cycle. The system allowed the infection to be followed for eight days before treatment without symptoms developing. These findings suggest that it is feasible to directly measure the anti-parasite efficacy of a prototype malaria vaccine in human volunteers without subjecting them to the risk of disease.

Adult↗

Care of postoperative patients with pulmonary edema.

Postanesthesia nursing requires advanced assessment skills and prompt intervention by the nurse. This article discusses the cause, pathology, diagnosis, and management of postanesthesia cardiogenic and noncardiogenic pulmonary edema. An annotated bibliography is included as an additional clinical reference.

Humans↗

Endosonographic diagnosis of an esophageal duplication cyst.

A patient with an esophageal duplication cyst who presented with dysphagia is described here. The diagnosis was accurately made preoperatively by endosonography due to the demonstration of contiguity of the muscularis propria of the esophagus with the muscle layer of the cyst wall. Endoscopic ultrasound is the most reliable nonsurgical method for the diagnosis of this lesion, assisting in surgical planning in symptomatic patients and observation in asymptomatic ones.

Adult↗

Resistance trained athletes using or not using anabolic steroids compared to runners: effects on cardiorespiratory variables, body composition, and plasma lipids.

OBJECTIVE: To determine whether there is a difference in cardiac size and function as well as in body composition, aerobic capacity, and blood lipids between resistance trained athletes who use anabolic steroids and those who do not, and to compare them to university cross country athletes. METHODS: Four groups of men were evaluated: recreational lifters, n = 11, lifting < 10 h.week-1; heavy lifters, n = 16, lifting > 10 h.week-1; steroid users, n = 8, same as heavy lifters and used steroids; runners, n = 8, university track members. Echocardiograms, body composition (hydrostatic weighing), maximum oxygen consumption (Vo2), and lipids were studied. RESULTS: As expected, Vo2 (ml.kg-1.min-1), was greatest in the runners, with no difference among the lifting groups. High density lipoprotein cholesterol in the steroid user group was lower than in heavy lifters or runners. Left ventricular internal diastolic dimension was similar among the groups. The left ventricular mass index of the steroid user group was significantly greater than recreational lifters, at 161 v 103. There was no difference among heavy lifters (127), runners (124), and steroid users. There was no compromise in diastolic function in any group. There were no differences among groups in resting or exercise blood pressure. CONCLUSIONS: Resistance training in the absence of steroid use results in the same positive effects on cardiac dimensions, diastolic function, and blood lipids as aerobic training.

Adolescent↗

Model complexes of tumor necrosis factor-alpha with receptors R1 and R2.

The biological activities of tumor necrosis factor-alpha (TNF-alpha) are mediated by two different receptors, TNFR1 and TNFR2. To analyze the receptor binding site(s) of TNF-alpha, molecular models have been built of the complexes of TNF-alpha with the extracellular regions of receptors R1 and R2, based on the known crystal structures of TNF-alpha and lymphotoxin bound to R1. The model structure of R2 from residues 18-160 was built by analogy to the crystal structure of R1 in complex with lymphotoxin. The amino acid sequences of R1 and R2 show 27.5% identity over this region and were aligned with five insertions and three deletions. There are 18 conserved cysteines that form disulfides. R2 has lost one pair of cysteines compared with R1, but two new cysteines were modeled as forming a new disulfide bond. Both symmetric and asymmetric trimers of TNF-alpha were used to model the complexes with TNFR1 and R2. An analysis of differences in the model complexes showed good agreement with data on the differential binding of TNF mutants to its two receptors.

Amino Acid Sequence↗

Making history: the Bloomsbury group's construction of aesthetic and sexual identity.

This essay examines the way England's well-known Bloomsbury group in the first decades of this century negotiated the legacy of prominent figures of the generation before in order to create its own identity. Looking at the group's ideas about both aesthetics and sexuality, the author shows how the group privileged Leo Tolstoy over J. A. M. Whistler, and Oscar Wilde over Walter Pater. The introduction and conclusion seek to set this study in the context of current issues in gay and lesbian studies.

Art↗