Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997.
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Biomedical subjects
Publications and source records attributed to J Baum.
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OBJECTIVES: Due to its low solubility and negligible metabolism, desflurane is assumed to be especially suitable for application by low-flow anaesthetic techniques. The aim of this clinical investigation was the development of a standardised dosing scheme for low-flow and minimal-flow desflurane anaesthesia. METHODS: One hundred six ASA status I-II patient were assigned to six groups according to the duration of the initial high-flow phase, fresh gas flow, and fresh-gas desflurane concentration. The median age, height, body weight, and constitution of the groups was comparable. After an initial high-flow phase using 4.4 l/min, the fresh gas flow was reduced to 0.5 l/min (minimal-flow anaesthesia) or 1.0 1/min (low-flow anaesthesia). Inspired nitrous oxide concentrations were maintained at 60% to 70%. Using different standardised schemes of vaporizer settings, inspired desflurane concentrations were applied in the range from 3.4% to 8.7%, i.e., between 1 and 1.5 MAC. Inspired and expired desflurane concentrations were measured continuously by the side-stream technique and recorded on-line. Venous blood samples were taken immediately prior to induction and 45 min after flow reduction for measurement of carboxyhaemoglobin (COHb) concentration). RESULTS: In the 10- to 15-min initial phase during which a high fresh gas flow of 4.4 l/min was used, the inspired desflurane concentration reached values in the range of 90%-95% of the fresh gas concentration. In low-flow anaesthesia this concentration could be maintained without any alteration of the vaporizer setting, whereas in minimal-flow anaesthesia with flow reduction the fresh gas concentration had to be increased by 1% to 2%: The quotient calculated by division of the inspired desflurane concentration by its fresh gas concentration (Q = CI/CF) ranges between 0.65 and 0.75 in animal-flow and between 0.80 and 0.85 in low-flow anaesthesia. If use was made of the wide output range of the desflurane vaporizer, the inspired concentration could be increased rapidly by about 5% in 8 min, although the flow was kept constant at 0.5 l/min. Compared with its value prior to induction (2.13 +/- 1.05%), the COHb concentration decreased statistically significantly by about 0.7% during the 1st hour of minimal-flow anaesthesia (1.42 +/- 1.01%). In no case was a COHb concentration observed that exceeded threatening or even toxic values, although the soda lime was changed routinely only once a week. CONCLUSIONS: The pharmacokinetic properties of desflurane, resulting in especially low individual uptake, and the wide output range of the vaporizer facilitate the use of low-flow anesthetic techniques in routine clinical practice. Even in minimal-flow anesthesia, the duration of the initial high-flow phase can be shortened to min. If the flow is reduced to 1 l/min, the inspired desflurane concentration achieved in the initial high-flow phase can be maintained without any alteration of the vaporizer setting. In minimal-flow anesthesia, however, with flow reduction to 0.5 l/min, the fresh gas concentration has to be increased to a value 1%-2% higher than the inspired nominal value. Due to the wide dialing range of the desflurane vaporizer, the amount of vapour delivered into the breathing system can be increased to about 110 ml/min even at a flow of 0.5 l/min. The large amount of agent that can be delivered into the system even under low-flow conditions, together with the very low individual uptake, results in a time-constant that is sufficient short for the clinically required rapid increase in inspired desflurane concentrations. The short time-constant of low-flow desflurane anaesthesia improves the control of the anaesthetic concentration. If all measures are taken to safely avoid inadvertent drying out of the soda lime, there is no evidence that low-flow anaesthesia with desflurane is liable to increase the risk of accidental carbon monoxide poisoning. (ABSTRACT TRUNCATED)
OBJECTIVE: The purpose of the study is to evaluate the efficacy and risks of topical mitomycin C (MMC) for conjunctival-corneal intraepithelial neoplasia (CCIN). DESIGN: The study design was a clinical case series of CCIN. PARTICIPANTS: Seventeen patients, 16 with biopsy-confirmed CCIN and 1 with invasive squamous cell carcinoma (SCC), were included in the study. INTERVENTION: Patients received topical drops of MMC 0.02% to 0.04% four times daily from 7 to 28 days. Retreatment was done in cases of lesion recurrence. MAIN OUTCOME MEASURES: The size of the CCIN before and after the treatment and ocular complications post-MMC application were evaluated. RESULTS: Ten patients remained disease-free after one course of MMC application. In one case, residual CCIN remained very small without regrowth. In the one patient with invasive SCC and in five patients with CCIN, regrowth occurred within 6 months of the first treatment. After retreatment, invasive SCC and CCIN in an additional two patients were eradicated. In two cases, although the size of the lesions decreased after two and three applications of MMC, regrowth occurred, and the CCIN returned to its original size. In the final case, limited recurrence has occurred and no retreatment has been done. The complications of MMC use included mild-to-moderate conjunctival hyperemia and mild allergy, which resolved after discontinuation of the treatment. Severe pain manifested when treatment was longer than 14 days. CONCLUSIONS: Application of topical MMC is an efficient treatment for most but not all cases of CCIN.
Folding of the collagen triple helix provides an opportunity to look at multichain molecular assembly. This triple helix also offers unique advantages for the study of folding because the process is very slow compared to globular proteins, and the kinetics of folding can be obtained in real time by NMR. Studies on triple-helical peptides illustrate the ability to observe kinetic folding intermediates directly and the ability to propose detailed mechanisms of folding through the use of real-time NMR methods. Defective collagen folding has been implicated in various connective tissue diseases and the capacity of NMR to look at the folding of specific sites provides a tool for obtaining information about altered folding mechanisms. Comparison of folding in peptides that model normal and diseased collagens could shed light on the molecular perturbation and the etiology of disease.
A 46-year-old Caucasian man with no other known risk factors developed bilateral posterior subcapsular cataracts soon after intense exposure to ultraviolet radiation. This case report supports experimental and epidemiological evidence implicating ultraviolet radiation as a risk factor for cataract formation.
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The M90V mutant of guinea pig alpha-lactalbumin (gpLA) was expressed intracellularly in Escherichia coli using a gpLA gene fusion to the IgG-binding ('Z') domain coding sequences of staphylococcal protein A. The fusion protein was expressed as an inclusion body, then purified and refolded in vitro; CNBr cleavage of the fusion polypeptide yielded native alpha-lactalbumin. The recombinant M90V gpLA was virtually identical with natural gpLA with respect to its ability to stimulate lactose synthesis by galactosyl transferase and the recombinant and natural molecules also exhibited similar circular dichroism spectra, thermal melting profiles and NMR spectra. However, modest perturbations in the chemical shifts of amide protons in the C-helix residues, attributable to the Met-->Val mutation, were observed. In defined media, this expression system enabled the production of highly-enriched 15N- and 13C, 15N-labeled gpLA. Use of this material will allow the solution conformations of the native and molten globule states of gpLA to be characterized by high-resolution multidimensional NMR.
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PURPOSE: Selection of an appropriate animal model is crucial for the investigation of the pathogenesis of Acanthamoeba keratitis. To this end, it has been reported that fluorescein isothiocyanate (FITC)-labeled Acanthamoeba castellanii bind to human, pig, and hamster corneas, but not to rabbit corneas in organ culture. However, 35S-labeled A. polyphaga and A. culbertsoni have been found to bind to rabbit corneal epithelium grown in tissue culture. The purpose of the current study was to establish whether A. castellanii bind to rabbit corneal epithelium in organ culture. METHODS: Two different adhesion assays were used to determine whether 35S-labeled and FITC-labeled A. castellanii bind to epithelium of corneal buttons in vitro and, if so, whether the binding is temperature-dependent, enhanced by injury, and inhibited by specific saccharides. Ameba binding to rabbit corneal epithelium was also evaluated by scanning electron microscopy. The binding of A. castellanii to corneal epithelium of three different species (human, pig, and rabbit) was compared. RESULTS: Both 35S-labeled as well as FITC-labeled parasites were found to bind to epithelium of rabbit corneal buttons in vitro. Although the parasites bound avidly to the corneas at 25 degrees C and 35 degrees C, little binding was observed at 4 degrees C. Injury enhanced the binding. Methyl alpha-D-mannopyranoside, but not other saccharides (alpha-L-fucose and beta-galactose), inhibited binding of the parasites to the epithelium of rabbit corneas. By scanning EM, A. castellanii were found to adhere, invade, and penetrate the epithelium of rabbit corneas. Compared with rabbit corneas, ameba binding to pig, and human corneas was only 1.2 and 1.4 times higher, respectively. CONCLUSIONS: Rabbit animal model may prove useful for investigation of the molecular mechanisms that mediate adhesion of Acanthamoeba to corneal epithelium.
Direct NMR measurements of the folding kinetics are performed on a collagen-like triple helical peptide. The triple helical peptide was designed to model a biologically important region of collagen and has the sequence (POG)3ITGARGLAG(POG)4. Triple helical peptides were synthesized with specifically labeled 15N amino acid residues in key positions, and the kinetics of folding of the individual residues were monitored directly by measuring the loss of monomer intensity and the increase in trimer intensity. The residues at the terminal ends and central region could be followed independently and quantitated directly. Residues located at the terminal ends have rates and kinetics of folding that are distinct from residues in the central region of the peptide. This allows the monitoring of different steps in the folding mechanism and the postulation of the existence of a kinetic intermediate. The NMR data are consistent with a mechanism of association/nucleation and propagation. Hereditary connective tissue diseases are associated with mutations that result in abnormal folding of collagen, and the NMR folding experiments on a collagen-like peptide provide a basis for characterizing the molecular defect in folding mutations.
In the presence of completely dry soda lime volatile anaesthetics will decompose to carbon monoxide (CO). In an in vitro study, the absorbent (soda lime, ICI) was dried with a constant gas flow of 11/min oxygen for 120 h. The weight loss during the drying was 17.1%. Two vol% of halothane, enflurane or isoflurane in oxygen was administered with a constant flow of 0.51/min oxygen through the completely dry absorbent. Concentrations of gases were measured before and after the absorbent using mass spectrometry (MGA 1100, Perkin-Elmer) and an electrochemical NO monitor (Mini PAC CO, Dräger). The temperature inside the soda lime was monitored continuously. Shortly after adding the anaesthetic to the oxygen passing through the absorbent, carbon monoxide appeared in the outlet of the soda lime container. The measured peak concentrations varied around 450 ppm (halothane), 3500 ppm (enflurane) and 3800 ppm (isoflurane). The temperature inside the absorbent rose from the ambient temperature (19.8 degrees C) to a maximum of 52.1 degrees C during CO production and decreased when the CO production lowered after approximately 1 h (all anaesthetics). During CO production no measurable concentration of halothane left the absorber. After passing through the absorbent the concentrations of isoflurane and enflurane were slightly lower than the corresponding concentrations in the fresh gas measured before absorption.
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Electrostatic interactions were studied in a triple-helical peptide, (POG)3PKGQKGEKG(POG)4, which contains a lysine-rich 9 residue sequence from the collagen-like domain of the macrophage scavenger receptor (MSR). This peptide adopts a stable triple-helical conformation only when the pH is higher than 4.5, corresponding to ionization of the Glu side chain. Modeling shows Glu forms ion pairs with one of the Lys residues, stabilizing the structure. Previously studied collagen-like peptides show relatively small contributions of electrostatic interactions to stability. The large magnitude of the pH mediated structural changes seen for this peptide suggests that specific placement of charged residues in the triple-helix conformation can generate strong electrostatic interactions.
Cell migration is a fundamental process of wound repair in biological systems. In an attempt to identify plasma membrane glycoconjugates which mediate cell migration, migrating and nonmigrating rabbit corneal epithelia were analyzed for reactivity with monoclonal antibodies (mAbs) specific for unsubstituted N-acetyl-lactosamine (mAb 1B2), Le(x) (mAbs 7A and MMA), and sialyl Le(x) (mAb CSLEX1) carbohydrate chains of neolactoglycoconjugates. Immunohistochemical analysis indicated that regardless of whether the epithelia analyzed were from corneas of animals in vivo, corneas in organ culture, or cells in tissue culture, migrating cells stained intensely with mAb 1B2, whereas nonmigrating cells either did not stain or stained only weakly. mAbs MMA and 7A stained migrating epithelium as well as basal and middle cell layers of normal, nonmigrating epithelium. mAb CSLEX1 did not stain wounded corneas but stained the superficial cell layer of normal corneal epithelium. Biochemical analyses by TLC immunostaining revealed the presence of three mAb 1B2-reactive glycosphingolipids (GSL), neolactotetraosyl-(nLc4, paragloboside), neolactohexaosyl- (nLc6), and neolacto-octaosylceramide (nLc8) in migrating epithelia. In contrast, nonmigrating epithelia contained only trace amounts of these glycolipids. Exogenous addition of nLc4, but not various other GSLs including a Le(x)-GSL (SSEA-1), stimulated re-epithelialization of wounds in an experimental model of corneal epithelial wound healing. Moreover, re-epithelialization of wounds was significantly inhibited by mAb 1B2 but not by mAb MMA. The data suggest that neolacto-GSLs of corneal epithelium may be among the molecules which mediate healing of corneal epithelial wounds by influencing cell migration.
PURPOSE/METHODS: Corneal specialists may assess the intraocular pressure by palpation although this technique has never been validated. We explored the reliability of a tactile assessment of the intraocular pressure in comparison to Goldmann tonometry. RESULTS/CONCLUSION: There was little correlation between tactile assessment of the intraocular pressure and tonometry. However, palpation was moderately successful in identifying most eyes (five of seven eyes) with an intraocular pressure greater than 30 mm Hg. Although palpation was generally inaccurate, it may serve as a warning for marked increases in intraocular pressure exceeding 30 mm Hg.
PURPOSE: Bacterial contamination of previously worn soft contact lenses, especially at sites of lens deposits, might play a role in the pathogenesis of lens-associated bacterial keratitis. We studied the effects of three commercial contact lens cleaners and disinfectants in a rabbit model to determine whether cleaning and disinfection reduced infectivity. METHODS: Duragel 75 soft contact lenses, designed to fit the eyes of rabbits, were worn by rabbits under tarsorrhaphies, then were removed and cleaned in one of three cleaner and disinfectant solutions according to the manufacturers' instructions. The lenses were contaminated by overnight incubation in a suspension of 10(8) Pseudomonas aeruginosa/ml and were placed under tarsorrhaphies on the eyes of fresh rabbits. The rabbits were observed for two weeks for signs of infection. Control rabbits wore new, uncleaned but contaminated lenses or worn, uncleaned but contaminated lenses. RESULTS: The rates of infection with the three commercial cleaner and disinfectant solutions ranged from 18% (two of 11) to 31% (four of 13); these incidences were not significantly different from one another or from the 19% (three of 16) incidence with new, contaminated but uncleaned lenses. By contrast, when worn, uncleaned but contaminated lenses were placed in rabbits' eyes, seven of eight were infected, a rate that is significantly higher than that of the other four groups (P = .0003). CONCLUSIONS: These data indicate that the three commercial lens cleaner and disinfectant solutions were of similar efficacy in reducing the infectivity of contaminated contact lenses to a level similar to that of new, unworn lenses.(ABSTRACT TRUNCATED AT 250 WORDS)
As early as in 1850 (only 4 years after the first clinical performance of ether anaesthesia by W. T. G. Morton on 16 October 1846) John Snow recognised that ether and chloroform were exhaled unchanged with the expired air. To reuse these unchanged vapours in the following inspiration and thereby prolonging the narcotic effect of a given amount of anaesthetic vapour, he converted his ether inhaler into a To-and-Fro Rebreathing System: The apparatus was equipped with a facemask without an expiratory valve and a large reservoir bag containing pure oxygen; an aqueous solution of caustic potash was used as CO2 absorbent. In several experiments, performed on himself, Snow succeeded to demonstrate that rebreathing of the exhaled vapours was possible following carbon dioxide absorption, and that it resulted in a pronounced prolongation of the narcotic effects of the volatile anaesthetics. Furthermore, Snow performed experiments on animals using a closed system for evaluating the carbon dioxide production during anaesthesia. It is all the more worthwhile to introduce Snow's publications on these topics, as, despite their extraordinary theoretical and practical significance, they remained nearly unnoticed. Even in the fundamental articles by D. Jackson and R. Waters, both being the respected protagonists of the rebreathing technique in anaesthesia, the Snow papers remained uncited.