Biomedical subjects
J Baum
Publications and source records attributed to J Baum.
Carbon monoxide generation in carbon dioxide absorbents.
Several cases of unexpected high carboxyhemoglobin (COHb) levels in patients undergoing general anesthesia were observed. To avoid carbon monoxide (CO) intoxication, the use of high fresh gas flows and frequent changes of the absorbent were recommended. However, due to economic and ecologic considerations, low-flow anesthetic techniques have advantages. Thus, the subject urgently needed to be reexamined. In 1001 patients undergoing enflurane or isoflurane anesthesia, blood samples were taken 30 min after fresh gas flow reduction to 0.5 L/min and analyzed for COHb. The absorbent canisters, containing soda lime, were used for several days. The statistical mean and SD of COHb was 1.17% +/- 0.97% in the range of 0%-7.6%. There was no statistical difference between the COHb values when broken down by the duration of use of the absorbent canisters. In no case were dangerously high COHb levels observed. As recently revealed, only dry absorbents produce CO if exposed to volatile anesthetics containing a CHF2-moiety. Thus, all measures must be avoided that dry out the absorbent. Low-flow anesthesia preserves the moisture content of the absorbent and, thus, seems to be a factor protecting from CO generation.
Benefits and liabilities of hypermobility in the back pain disorders of industrial workers.
OBJECTIVES: Back pain disorders, sometimes called 'the nemesis of medicine and the albatross of industry', are ubiquitous, but have stubbornly defied diagnosis and treatment. Hypermobility syndrome, which is also very common, has been called 'an enigma of human physiology'. Both conditions have attracted wide attention and interest only recently. In an earlier study, we considered the benefits and liabilities of joint hypermobility by studying 660 musicians in the USA. In a parallel manner, the present study analysed the back pain disorders of 606 workers in a Swedish high-technology industrial plant in the context of spinal hypermobility. SUBJECTS AND METHODS: The 606 industrial workers were examined for spinal hypermobility using a standard protocol, and interviewed for work-related body-posture requirements and the low back, shoulder and neck pain disorders experienced by them. The data were analysed for associations between hypermobility and physical complaints as a whole, and by taking into account gender and body-postures at work. RESULTS: Twenty-six per cent (37) of 144 workers with hypermobility but only 14% (64) of 453 without hypermobility experienced back pain (P < 0.002). Among the 326 workers with sitting or standing jobs, 40% (29) of 71 with hypermobility had back pain, whereas only 12% (30) of the 255 without hypermobility experienced back pain (P < 0.001). The corresponding numbers with back pain for 235 in jobs with changing body-postures were 4.5% (3) of 66 with hypermobility and 14% (14) of 169 without hypermobility (P = 0.04). CONCLUSIONS: Hypermobility of the spine is an asset if the work requires change of body-posture, but a liability for those in a standing or sitting assignment. It reinforces a similar hypothesis proposed by Larsson et al.
George Wise and subretinal neovascularization.
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Performing arts rheumatology.
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On the location of the cone and the etiology of keratoconus.
I suggest that the location of the cone in keratoconus is most often located in the paracentral inferonasal quadrant of the cornea due to the presence of the most senile epithelial cells in this location. These cells may be more vulnerable than younger epithelial cells to the chronic subtle trauma of eyelid rubbing and may be more prone to release enzymes that thin the cornea.
The outcome of children referred to a pediatric rheumatology clinic with a positive antinuclear antibody test but without an autoimmune disease.
OBJECTIVE: To assess the diagnostic value of positive antinuclear antibody (ANA) test results in children with musculoskeletal or dermatologic problems but without autoimmune disease at presentation. DESIGN: Retrospective chart review. SETTING: Pediatric rheumatology clinic in a tertiary care center. PATIENTS: Five hundred charts reviewed, comprising all new patients seen, 1978 to 1993. RESULTS: Of 500 children seen, 113 had positive ANA test results available at referral. Of those 113 patients, 72 (64%) had an autoimmune condition diagnosed at initial clinic visit; another 10 (9%) were lost to follow-up. Thirty-one children (27%) had no autoimmune condition diagnosed at initial clinic visit and had clinical follow-up over a mean of 37 months. Nonspecific musculoskeletal complaints and hypermobility accounted for the majority of presentations. Routine hematology data were usually normal. Median ANA titer was 1:160; ANA patterns varied. On follow-up, 25 patients (81%) cleared their symptoms; five (16%) had significant improvement. One patient developed an autoimmune disease (autoimmune hepatitis). CONCLUSIONS: Based on our findings, the vast majority of children who have positive ANA test results but do not have autoimmune conditions at initial diagnosis will not develop an autoimmune condition. ANA testing of children who have musculoskeletal or dermatologic problems in the absence of autoimmune conditions does not reveal new diagnoses, and represents unnecessary laboratory time and expense. The prognosis of children who have positive ANA test results in the absence of autoimmune conditions is usually excellent.
Crystal structure and NMR conformation of a cyclic pseudotetrapeptide containing urethane backbone linkages.
Urethane bonds, derived from the hydroxyl group of the tyrosine side chain, have been investigated as a new type of amide bond mimetic in the design of pseudopeptides. The structure of a representative cyclic pseudotetrapeptide that consists of an -Ala-Tyr(urethane)Ala-Tyr(urethane) sequence fused into a rigid ring has been studied in the solid state by x-ray crystallography and in solution by two-dimensional nmr techniques. The cyclic pseudotetrapeptide has an oblong shape. The backbone urethane bonds assume a trans-trans conformation. The carbonyl groups in the ring have an alternating pattern of down, up, down, up with respect to the average ring plane. Solution nmr studies give observed nuclear Overhauser effects and coupling constants largely in agreement with the crystal structure. However, in solution the observed structure is likely to be conformationally averaged, and in the averaged structure, the urethane bond is perpendicular to the plane of the aromatic ring of the tyrosine, while in the crystal it is close to this plane. These differences may be explained by intermolecular hydrogen-bonding interactions. Four aspects of the conformation of the cyclic pseudotetrapeptide were investigated in detail: the tyrosine residue with the attached side-chain urethane bond (the tyrosine-urethane unit), the conformation of the two urethane backbone linkages, the conformation of the two conventional peptide bonds within this unusual ring structure, and the tight turns within the cyclic pseudotetrapeptide. The conformation of the tight turns present in the cyclic pseudotetrapeptide is very similar to that of a beta-bend of type II. Intermolecular hydrogen bonding, joining adjacent layers of the cyclic pseudotetrapeptide in the solid state, resemble a parallel beta-pleated sheet. The presence of these structural motifs in the cyclic pseudotetrapeptide indicates that the tyrosine urethane unit may find applications in peptide and protein engineering.
Three-dimensional structure of echistatin and dynamics of the active site.
The snake venom protein echistatin contains the cell recognition sequence Arg-Gly-Asp and is a potent inhibitor of platelet aggregation. The three-dimensional structure of echistatin and the dynamics of the active RGD site are presented. A set of structures was determined using the Distance Geometry method and subsequently refined by Molecular Dynamics and energy minimization. Disulfide pairings are suggested, based on violations of experimental constraints. The structures satisfy 230 interresidue distance constraints, derived from nuclear Overhauser effect measurements, five hydrogen-bonding constraints, and 21 torsional constraints from vicinal spin-spin coupling constants. The segment from Gly5 to Cys20 and from Asp30 to Asn42 has a well-defined conformation and the Arg-Gly-Asp sequence, which adopts a turn-like structure, is located at the apex of a nine-residue loop connecting the two strands of a distorted beta-sheet. The mobility of the Arg-Gly-Asp site has been quantitatively characterized by 15N relaxation measurements. The overall correlation time of echistatin was determined from fluorescence measurements, and was used in a model-free analysis to determine internal motional parameters. The active site has order parameters of 0.3-0.5, i.e., among the smallest values ever observed at the active site of a protein. Correlation of the flexible region of the protein as characterized by relaxation experiments and the NMR solution structures was made by calculating generalized order parameters from the ensemble of three-dimensional structures. The motion of the RGD site detected experimentally is more extensive than a simple RGD loop 'wagging' motional model, suggested by an examination of superposed solution structures.
[Low flow anesthesia].
It is a strange contradiction that increasingly sophisticated anaesthesia machines are developed meeting all requirements for rebreathing techniques and the highest safety standards, but the usual anaesthetic management is still based on the use of fresh gas flows that preclude substantial rebreathing. The advantages of rebreathing can only be realised if low-flow anesthesia techniques are adopted. Increasing acceptance of these methods is due to the availability of comprehensive anaesthetic gas monitoring. Different techniques of low-flow anaesthesia, the characteristic features, technical requirements, and considerations concerning their performance and contraindications are discussed. This paper presents a topic that is left unmentioned by most anaesthesia textbooks. The use of new inhalational anaesthetics such as desflurane that require comparatively high concentrations, or even xenon, will motivate to sparing use. Increasingly stringent health and safety regulations as well as sharpened ecological awareness will prompt anaesthetists to minimise all anaesthetic gas emission according to the possibilities of available equipment. Last but not least, the demand for economical working methods will be an argument for applying low-flow anaesthesia techniques.
[A simple bite protector for the laryngeal mask].
A new simple gag is presented securing the width of the tube of the laryngeal mask. The device is a 45 degrees-angled, u-shaped, synthetic-coated aluminium rod. This gag, while being additionally an aid to ensure the proper position of the laryngeal mask, is easy to handle and can be re-used after disinfection. Due to its rounded shape and the soft synthetic coating, accidental damage of the teeth seems to be nearly impossible.
[General anesthesia with high fresh gas flow is safer than "minimal flow"--fact or fiction?].
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Management and motivational factors in the control of noise induced hearing loss (NIHL).
This paper describes a study investigating attitudes to noise as an occupational hazard. The objectives of the study were to understand the individual and organizational factors which affect attitudes towards noise induced hearing loss (NIHL) and to relate these to the standards of hearing conservation achieved in industry as demonstrated by compliance with the Noise at Work Regulations. The study comprised a survey of 48 organizations across Britain, and a more detailed examination of 10 of these as case studies. Methods used included desk research, audits of hearing conservation programmes, questionnaires and interviews. Whilst there is widespread acceptance that industrial noise is a hazard, it is one that is frequently taken for granted, and measures to deal with it are often inadequate. Most organizations place the onus on the workforce to protect their own hearing through the use of personal hearing protectors. Workers reactions to noise tended however to be passive and much of the time neither managers nor the workforce are concious of the noise hazard. This is the case even where some managers are committed to good industrial housekeeping and accident prevention. As effective hearing conservation programme requires three management attributes: leadership from senior management, the ability of middle management (particularly in production and engineering) to put hearing conservation measures into practice, and specialist technical knowledge of noise and of the legislation. The study points to the need for more education and motivation of senior managers as the priority in improving standards of hearing conservation and noise control.
Backbone dynamics of (Pro-Hyp-Gly)10 and a designed collagen-like triple-helical peptide by 15N NMR relaxation and hydrogen-exchange measurements.
The backbone dynamics of specific residues in two collagen-like triple-helical peptides with (X-Y-Gly)n sequences have been investigated using two-dimensional inverse-detected 15N NMR relaxation measurements and hydrogen-exchange experiments. One peptide, (POG)10, has the highest possible imino acid content and is considered to be a very stable prototype of a triple helix. The second peptide, (POG)3ITGARGLAGPOG(POG)3 (denoted T3-785), models an imino acid poor region of type III collagen and contains 12 residues from near the unique collagenase cleavage site. 15N relaxation parameters and hydrogen-exchange data were obtained for a glycine residue in the center of (POG)10 and for the tripeptide unit Gly-Leu-Ala in the middle of T3-785. Analysis of the relaxation data of the rodlike triple-helical peptides required the assumption of anisotropic overall motion, and the model-free approach of Lipari and Szabo (1982) was used to derive overall motional parameters and the order parameter, S2, that describes the amplitudes of the internal motion. First the mobilities of the Gly, Leu, and Ala residues in peptide T3-785 were compared. Both hydrogen-exchange methods and relaxation measurements indicated that the residue in the Y position (Ala) is more mobile than residues in the Gly and X positions (Leu). The slower exchange rates of Gly and Leu compared to that of Ala are consistent with the two-hydrogen-bonded model for the triple helix. Then the backbone mobilities of the central Gly residue were compared for the two peptides (POG)10 and T3-785. In this case, 15N relaxation measurements give different results from hydrogen exchange. The glycine residues in the trimer form of both T3-785 and (POG)10 have high values for the order parameter (near 0.85), suggesting similar small-amplitude internal motions and rigid backbones in both peptides. In contrast to the similar values of the order parameters, hydrogen-exchange data indicate that the central Gly exchanges at a faster rate in the trimer form of T3-785 than in (POG)10. These results suggest that a Gly in the imino acid rich environment of (POG)10 is dynamically different from a Gly in the imino acid poor environment of T3-785 and that the difference lies in the slower motion related to stability, rather than the faster motion on the picosecond time scale. This sequence-dependent difference in dynamical properties may have important consequences for recognition processes in collagen.
Characterization of collagen-like peptides containing interruptions in the repeating Gly-X-Y sequence.
Glycine is found as every third residue along the entire length of triple helices in fibrillar collagens, but the triple-helix regions of nonfibrillar collagens and other proteins usually contain one or more interruptions in this repeating pattern. A set of four peptides was designed to model the effect of interruptions in the (Gly-X-Y)n repeating pattern on triple-helix formation, stability, and folding. Into the middle of the stable triple-helical peptide (Pro-Hyp-Gly)10, an interruption was introduced representing one of the four possible categories: a glycine deletion, a deletion of a hydroxyproline (Y position), an alanine insertion, or a glycine to alanine substitution. As shown by sedimentation equilibrium, NMR, and CD studies, the introduction of an interruption still allowed formation of trimers in solution, but with marked decrease in stability. The degree of destabilization and the thermodynamic basis for the loss of stability depended on the type of interruption. The glycine substitution and alanine insertion were the least disruptive, followed by the hydroxyproline deletion, with the glycine deletion being the most destabilizing. Our results suggest that the breaks in these peptides affect both the triple-helical conformation and the monomer conformation. These studies provide a basis for considering the structural and functional consequences of different kinds of interruptions in collagen.
Benefits and disadvantages of joint hypermobility among musicians.
BACKGROUND: Joint hypermobility is considered to be both an advantage and a disadvantage. However, the degree of hypermobility in members of particular occupations requiring intense physical activity and the nature of the association between symptoms referable to specific joints and their hypermobility are unknown. METHODS: We interviewed 660 musicians (300 women and 360 men) about work-related symptoms such as joint pain and swelling and examined them for joint hypermobility according to a standard protocol. We then determined the relation between the mobility of their fingers, thumbs, elbows, knees, and spine and any symptoms referable to these regions. RESULTS: Five of the 96 musicians (5 percent) with hypermobility of the wrists, mostly instrumentalists who played the flute, violin, or piano, had pain and stiffness in this region, whereas 100 of the 564 musicians (18 percent) without such hypermobility had symptoms (P = 0.001). Hypermobility of the elbow was associated with symptoms in only 1 of 208 musicians (< 1 percent), whereas 7 of 452 (2 percent) without this hypermobility had symptoms (P = 0.45). Among the 132 musicians who had hypermobile knees, 6 (5 percent) had symptoms, whereas only 1 of 528 (< 1 percent) with normal knees had symptoms (P < 0.001). Of the 462 musicians who had normal mobility of the spine, 50 (11 percent) had symptoms involving the back, as compared with 46 of the 198 musicians (23 percent) who had hypermobility of the spine (P < 0.001). CONCLUSIONS: Among musicians who play instruments requiring repetitive motion, hypermobility of joints such as the wrists and elbows may be an asset, whereas hypermobility of less frequently moved joints such as the knees and spine may be a liability.
Two-dimensional NMR assignments and conformation of (Pro-Hyp-Gly)10 and a designed collagen triple-helical peptide.
Homonuclear and heteronuclear 2D NMR methods are used to study two triple-helical peptides. One peptide, (POG)10, is considered to be the most stable prototype of a triple helix. The second peptide, (POG)3ITGARGLAGPOG(POG)3 (denoted T3-785), was designed to model an imino acid poor region of collagen and contains 12 residues from near the unique collagenase cleavage site in type III collagen. Both peptides associated as trimers, with melting temperatures of 60 degrees C for (POG)10 and 25 degrees C for the T3-785 peptide. Sequence-specific assignments were made for a tripeptide unit POG in (POG)10, and 80% of the POG triplets are found to be in an equivalent environment. In T3-785, with nonrepeating X-Y-Gly units incorporated in the sequence, the three chains of the homotrimer can be distinguished from one another by NMR. The solution conformation of (POG)10 is very similar to the model derived from X-ray fiber diffraction data, although the peptide contains less ordered regions at the peptide ends. In the trimer from of T3-785, the central residues of the three chains are closely packed, and the data are consistent with a triple-helical model with a one-residue stagger of three parallel chains. For T3-785, in contrast to (POG)10, there are also resonances from a less ordered form, which are probably due to the presence of a small amount of monomer. The similarity of the backbone conformations of T3-785 and (POG)10 suggests that an alternative conformation is not present in the imino acid poor region.
Structure and stability of the molten globule state of guinea-pig alpha-lactalbumin: a hydrogen exchange study.
A partially folded state of guinea pig alpha-lactalbumin (the A-state or molten globule state), formed by denaturation at low pH, has been studied using hydrogen exchange methods. The overall distribution of exchange kinetics, measured by 1-D NMR, suggests that fewer than 20 amides in the structure are involved in highly persistent residual structure, although CD results suggest that many other parts of the chain are folded, for a significant proportion of the time, into less stable structural elements. The pH-jump experiments show that some amides that are strongly protected from exchange in the native state become freely accessible in the A-state but that conversely a majority, at least, of those that are slow to exchange in the A-state retain that protection in the native state. This suggests that the persistent structure in the A-state is native-like although the possibility that nonnative like structural elements persist cannot be eliminated. Resonance assignments for key residues in the NMR spectrum of the native state have enabled us to use the pH-jump method also to identify the majority of the most protected amides in the A-state: they are located in two hydrophobic segments, corresponding to the B- and C-helices of the native structure. This strongly suggests that the most persistent structure of the A-state includes these regions. A variety of lines of evidence, including fluorescence quenching data and, most remarkably, very effective protection from exchange of an indole NH in a tryptophan side chain, suggest that some form of hydrophobic core in the helical domain of the native structure persists in the A-state, although without the stereochemical rigidity of the native tertiary structure. The other domain of the native structure, including the beta-sheet, appears not to contain structural elements which persist to the same extent in the A-state, emphasizing that the molten globule is highly heterogeneous, in terms of the stability and specificity of both backbone and side chain interactions.