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Energy spectra of the ocean's internal wave field: theory and observations.
The high-frequency limit of the Garrett and Munk spectrum of internal waves in the ocean and the observed deviations from it are shown to form a pattern consistent with the predictions of wave turbulence theory. In particular, the high-frequency limit of the Garrett and Munk spectrum constitutes an exact steady-state solution of the corresponding kinetic equation.
The health manpower gap re-examined.
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The pathogenic human sulfite oxidase mutants G473D and A208D are defective in intramolecular electron transfer.
Mutations G473D and A208D were identified in patients with isolated sulfite oxidase (SO) deficiency, and the equivalent amino acids (G451 and A186, respectively) have been localized to the vicinity of the molybdopterin active site in the X-ray structure of chicken SO [Kisker, C., Schindelin, H., Pacheco, A., Wehbi, W., Garrett, R. M., Rajagopalan, K. V., Enemark, J. H., and Rees, D. C. (1997) Cell 91, 973-983]. To assess the effects of these mutations in human SO, steady-state kinetic studies of enzyme turnover and laser flash photolysis measurements of intramolecular electron transfer (IET) rate constants between the reduced heme [Fe(II)] and Mo(VI) centers were carried out in the recombinant G473D, G473A, G473W, G473D/R212A, and A208D human SO mutants. In the G473D and A208D mutants, the IET rate constants at pH 6.0 are decreased by 3 orders of magnitude relative to that of the wild type. Steady-state kinetic measurements indicate that the IET process is the rate-limiting step in the catalytic cycle of these two mutants. Thus, the large decreases in the IET rate constants and the kcat values, and the large increases in the Km(sulfite) values, rationalize the fatal impact of these mutations. Far-UV CD spectra of G473D indicate that the protein backbone conformation is remarkably changed, and the sedimentation equilibrium indicates that the protein is monomeric. Furthermore, EPR studies also suggest that the active site structure of the Mo(V) form of A208D is different from that of the wild type. In contrast, similar studies on G473A show that it is dimeric, that its Mo(V) active site structure is similar to that of the wild type, and that its IET rate constant is only 2.6-fold smaller than that of the wild type. IET in G473W is severely impaired, and no IET is observed for G473D/R212A. In chicken SO, the equivalent residues (G451 and A186) are both buried inside the protein. Thus, for human SO, the mutations to charged residues at the equivalent sites most likely cause crucial global or localized structural changes, and expose an alternative docking site that may compete with the Mo domain for docking of the heme, thereby retarding IET and efficient catalytic turnover of the sulfite oxidation reaction.
A coordinated teaching program for future dairy practitioners at the university of Wisconsin-Madison, School of Veterinary Medicine.
The University of Wisconsin School of Veterinary Medicine (UW-SVM) has implemented a variety of strategies to optimize teaching in dairy herd medicine. These include the provision of opportunities for dairy cow handling and management using a dairy teaching herd for veterinary students throughout the four-year curriculum, exposure for all students in their final year to a substantial first-opinion dairy case load using a private practice-based ambulatory clinic rotation, and, finally, the teaching of dairy herd health management and problem solving in a group of four final-year elective production medicine clinical rotations. On average, since 1986, 32.6% of each graduating class attended at least one elective production medicine rotation, with a range from 19.0% to 43.4%. For those University of Wisconsin students who could be traced, 65% were still actively involved in some aspect of dairy practice, representing a range of between seven and 17 students per year since the start of the program. The advantages and disadvantages of operating a "regional center of excellence" for training students from out-of-state institutions are discussed.
Essential role of conserved arginine 160 in intramolecular electron transfer in human sulfite oxidase.
Arginine 160 in human sulfite oxidase (SO) is conserved in all SO species sequenced to date. Previous steady-state kinetic studies of the R160Q human SO mutant showed a remarkable decrease in k(cat)/K(m)(sulfite) of nearly 1000-fold, which suggests that Arg 160 in human SO makes an important contribution to the binding of sulfite near the molybdenum cofactor [Garrett, R. M., Johnson, J. L., Graf, T. N., Feigenbaum, A., Rajagopalan, K. V. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 6394-6398]. In the crystal structure of chicken SO, Arg 138, the equivalent of Arg 160 in human SO, is involved in the formation of a positively charged sulfite binding site [Kisker, C., Schindelin, H., Pacheco, A., Wehbi, W., Garnett, R. M., Rajagopalan, K. V., Enemark, J. H., Rees, D. C. (1997) Cell 91, 973-983]. To further assess the role of Arg 160 in human SO, intramolecular electron transfer (IET) rates between the reduced heme [Fe(II)] and oxidized molybdenum [Mo(VI)] centers in the wild type, R160Q, and R160K human SO forms were investigated by laser flash photolysis. In the R160Q mutant, the IET rate constant at pH 6.0 was decreased by nearly 3 orders of magnitude relative to wild type, which indicates that the positive charge of Arg 160 is essential for efficient IET in human SO. Furthermore, the IET rate constant for the R160K mutant is about one-fourth that of the wild type enzyme, which strongly indicates that it is the loss of charge of Arg 160, and not its precise location, that is responsible for the much larger decrease in IET rates in the R160Q mutant. Steady-state kinetic measurements indicate that IET is rate-limiting in the catalytic cycle of the R160Q mutant. Thus, the large decrease in the IET rate constant rationalizes the fatal impact of this mutation in patients with this genetic disorder.
A comparison of standardized and narrative letters of recommendation.
OBJECTIVE: To compare the Council of Emergency Medicine Residency Directors' (CORD's) standardized letters of recommendation (SLORs) with traditional narrative letters of recommendation (NLORs) with regard to interrater reliability, consistency, and time of interpretation. METHODS: In part I of the study, four members of the residency selection committee each evaluated the same 20 SLORs and 20 NLORs from which all identifying characteristics had been deleted. Using Likert-type scales of the global assessment, each letter was assigned a numeric value from 1 to 7. The interrater reliability was calculated for both types of letters using the Kendall coefficient of concordance. Average time to interpretation of the letters was also determined. In part II, using the same numeric values as in part I, 207 single-author SLOR/NLOR pairs were evaluated to determine whether the global assessment of the SLOR was consistent with that of its partner NLOR. Interpretation of the NLOR was performed blinded to the SLOR. Statistical analysis was calculated using Spearman correlation coefficients. RESULTS: In part I of the study, the interrater reliability of the SLOR was 0.97, as compared with 0.78 for the NLOR. The average time to interpret the global assessment of the SLOR was 16 seconds, vs 90 seconds for the NLOR. In part II of the study, of the 207 SLOR/NLOR pairs, 112 (54%) were assigned the same numeric value, 80 (39%) differed by one, 13 (6%) differed by two, and two (1%) differed by three, for an overall correlation of 0.58. CONCLUSIONS: Compared with NLORs, the CORD SLOR offers better interrater reliability with less interpretation time. Single-author SLOR/NLOR pairs submitted for a single applicant do not correlate well. Residency selection committees must decide whether the added work of interpreting NLORs is beneficial.
Student Research Award 1990. Catecholaminergic innervation of the inner ear.
Cochlear blood flow has been shown to be controlled, in part, by the sympathetic nervous system. We have used immunocytochemical staining for tyrosine hydroxylase (TH) to further demonstrate the extent of catecholaminergic innervation of the cochlea. Deeply anesthetized Mongolian gerbils were systemically perfused with phosphate-buffered saline, followed by 4% paraformaldehyde. The cochleae were dissected out and post-fixed for 3 hours in 4% paraformaldehyde. They were then incubated in anti-TH antibody and subsequently processed using the avidin-biotin immunoperoxidase method. Microscopic examination of whole-mounted tissue revealed many immunoreactive fibers on the spiral modiolar artery. TH-positive fibers have also been found on both radiating arterioles and radial collecting venules, which has not been previously reported. With innervation of these small vessels, blood flow in the cochlea may be segmentally controlled. We also further describe the organization of TH-positive fibers in the osseous spiral lamina.
Multistate outbreak of Norwalk-like virus gastroenteritis associated with a common caterer.
In February 2000, an outbreak of gastroenteritis occurred among employees of a car dealership in New York. The same meal was also supplied to 52 dealerships nationwide, and 13 states reported illness at dealerships where the banquet was served. A retrospective cohort study was conducted to identify risk factors associated with the illness. Stool samples were collected to detect Norwalk-like virus, and sera were drawn and tested for immunoglobulin A antibodies to the outbreak strain. By univariate analysis, illness was significantly associated with consumption of any of four salads served at the banquet (relative risk = 3.8, 95% confidence interval: 2.5, 5.6). Norwalk-like virus was detected by reverse transcription-polymerase chain reaction assay in 32 of 59 stool samples from eight states. Nucleotide sequences of a 213-base pair fragment from 16 stool specimens collected from cases in eight states were identical, confirming a common source outbreak. Two of 15 workers at caterer A had elevated immunoglobulin A titers to an antigenically related Norwalk-like virus strain. This study highlights the value of molecular techniques to complement classic epidemiologic methods in outbreak investigations and underscores the critical role of food handlers in the spread of foodborne disease associated with Norwalk-like virus.
Isospin symmetry of odd-odd mirror nuclei: identification of excited states in N=Z-2 48Mn.
Excited states have been observed in the N=Z-2 odd-odd nucleus 48Mn for the first time. Through comparison with the structure of 48V, a first high-spin study of an odd-odd mirror pair has been achieved. Differences between the T=1 analogue states in this pair have been interpreted in terms of Coulomb effects, with the aid of shell-model calculations in the full pf valence space. Unlike other mirror pairs, the energy differences have been interpreted almost entirely as due to a monopole effect associated with smooth changes in radius (or deformation) as a function of angular momentum. In addition, the large energy shift between analogue negative-parity states is interpreted in terms of the electromagnetic spin-orbit interaction in nuclei.
Near-hanging as presenting to hospitals in Queensland: recommendations for practice.
Near-hanging is an increasing presentation to hospitals in Australasia. We reviewed the clinical management and outcome of these patients as they presented to public hospitals in Queensland. A retrospective clinical record audit was made at five public hospitals between 1991 and 2000. Of 161 patients enrolled, 82% were male, 8% were indigenous and 10% had made a previous hanging attempt. Chronic medical illnesses were documented in 11% and previous psychiatric disorders in 42%. Of the 38 patients with a Glasgow Coma Scale score (GCS) of 3 on arrival at hospital, 32% returned to independent living and 63% died. Fifty-two patients received CPR, of whom 46% had an independent functional outcome. Independent predictors of mortality were a GCS on hospital arrival of 3 (AOR 150, CI 95% 12.4-1818, P<0.001), taking plain X-rays of the cervical spine (AOR 0.06, CI 95% 0.004-0.97, P=0.047) and contact with the ground (AOR 0.03, CI 95% 0.002-0.62, P=0.02). Only 66% had imaging of the cervical spine performed with other imaging performed infrequently. There were three laryngeal, two hyoid bone and three cervical spine injuries and one carotid dissection. The number of cervical spine X-rays required to find a significant cervical spine fracture was 54. Near-hanging presenting to hospital with a poor conscious state or even cardiac arrest can have a favourable clinical outcome. Radiological investigations are infrequently performed despite a low GCS precluding early accurate assessment. Given the general favourable outcome, an aggressive approach to searching for correctable injuries is recommended.
Aortocaval fistula associated with aneurysm of the abdominal aorta: current management using autotransfusion techniques.
Two patients with aortocaval fistula associated with abdominal aortic aneurysm were managed successfully using a patient care plan which includes proper monitoring of the hemodynamic state, careful dissection of the aneurysm, and return of blood loss by autotransfusion while the patient is fully anticoagulated with heparin. This unusual and serious problem in vascular surgery can be managed in an orderly and controlled fashion using these techniques.
The emergence of decreased susceptibility to vancomycin in Staphylococcus epidermidis.
BACKGROUND: Coagulase-negative staphylococci (CNS) are the major cause of nosocomial bloodstream infection. Emergence of vancomycin resistance among CNS is a serious public health concern, because CNS usually are multidrug-resistant, and glycopeptide antibiotics, among which only vancomycin is available in the United States, are the only remaining effective therapy. In this report, we describe the first bloodstream infection in the United States associated with a Staphylococcus epidermidis strain with decreased susceptibility to vancomycin. METHODS: We reviewed the hospital's microbiology records for all CNS strains, reviewed the patient's medical and laboratory records, and obtained all available CNS isolates with decreased susceptibility to vancomycin. Blood cultures were processed and CNS isolates identified by using standard methods; antimicrobial susceptibility was determined by using minimum inhibitory concentration (MIC) and disk-diffusion methods. Nares cultures were obtained from exposed healthcare workers (HCWs) to identify possible colonization by CNS with decreased susceptibility to vancomycin. RESULTS: The bloodstream infection by an S. epidermidis strain with decreased susceptibility to vancomycin occurred in a 49-year-old woman with carcinoma. She had two blood cultures positive for CNS; both isolates were S. epidermidis. Although susceptible to vancomycin by the disk-diffusion method (16-17 mm), the isolates were intermediate by MIC (8-6 microg/mL). The patient had received an extended course of vancomycin therapy; she died of her underlying disease. No HCW was colonized by CNS with decreased susceptibility to vancomycin. CONCLUSIONS: This is the first report in the United States of bloodstream infection due to S. epidermidis with decreased susceptibility to vancomycin. Contact precautions likely played a role in preventing nosocomial transmission of this strain, and disk-diffusion methods may be inadequate to detect CNS with decreased susceptibility to vancomycin.
Medical student teaching in the preclinical years: a national family medicine survey.
We surveyed teaching by departments of family medicine at American medical schools during the preclinical period of their programs. Ninety-seven percent of departments responded to our questionnaire. Eighty-five percent participate in at least one required preclinical medical school course. The course title most frequently mentioned was "Introduction to Clinical Medicine," and the most frequent content areas with some department of family medicine responsibility were interviewing, physical diagnosis, and the physician-patient relationship. Departments from schools with a four-year enrollment of less than 300 are more likely to participate in at least one required course, but we found no other differences based on size of medical school enrollment, geographic region, or public v. private status. In conjunction with the current period of national reassessment regarding American medical education, now is a good time to evaluate department of family medicine medical student teaching, fill in gaps, and implement new programs for the next phase of our development as an academic specialty.
Asthma and the employment experience.
Previous asthma research has had a medical focus, and only one study has investigated the relationship between asthma and employment. This study describes the employment experience in relation to occupational choice and career advancement in 93 sequentially selected adult asthmatics attending a hospital based asthma clinic serving a socially disadvantaged urban population. Repeated hospital admissions and frequent asthma related sick leave from work were identified as contributing factors to employer discrimination, job dismissal, and lack of career advancement. Seventy-seven percent had not informed their employers of their asthma and 32% of those currently employed stated that getting time off work was a problem in relation to Asthma Clinic attendance. Of those not employed, 22.9% were receiving sickness or invalid benefits and 8.3% had lost their jobs because of asthma. This study illustrates how the stigma attached to the diagnosis of asthma in this community may not only impact negatively on employment opportunity, but also on asthma care.
Observation of (46)Cr and testing the isobaric multiplet mass equation at high spin.
The ground state band in (46)Cr and the isospin T = 1 band in (46)V have been delineated up to Ipi = 10(+) (tentatively 12(+)). These observations complete the highest spin T = 1 isospin triplet known. Following the isobaric multiplet mass equation, a combination of level energies in (46)Cr, (46)Ti, and (46)V are taken to highlight the angular momentum dependence of the isovector and isotensor parts of the interaction. The results are compared with full- fp-space shell model calculations. The influence of the one-body and two-body contributions to the isovector energy difference are investigated.
Thermal effects on skeletal muscle tensile behavior.
The effect of temperature on the mechanical failure properties of rabbit skeletal muscle (tibialis anterior and extensor digitorum longus) was examined. For all tests, one leg was maintained at 25 degrees C and the contralateral leg at 40 degrees C. Muscles were pulled to failure according to assignment into one of three groups: 1) passive failure at 10 cm/sec, 2) passive failure at 1 cm/sec, or 3) active (muscle is stimulated to contract as it is pulled) failure at 10 cm/sec. Load to failure was higher in the cold muscle for all groups tested. Total deformation was the same except in Group 1, when the warm muscle had a greater deformation. Energy absorbed before failure was greater in the cold muscle in Groups 2 and 3. Stiffness was higher in cold muscles for all muscles except the extensor digitorum longus in Group 1. In this study, temperature had a significant effect on the tensile properties; these thermal effects were dependent on both loading rate and contractile state. Comparing loading rates, warm muscle tested at 10 cm/sec had higher failure loads than that tested at 1 cm/sec. Comparing stimulated versus unstimulated muscle (Group 1 versus Group 3), the stimulated tibialis anterior muscle absorbed more energy than unstimulated ones. Stimulated extensor digitorum longus muscles had higher failure loads, absorbed more energy, and were stiffer than nonstimulated muscles. This study offers experimental data to support the theory that warming muscles can aid in injury prevention and improvement in athletic performance.
Isolated sulfite oxidase deficiency: identification of 12 novel SUOX mutations in 10 patients.
We report twelve novel mutations in patients with isolated sulfite oxidase deficiency. The mutations are in SUOX, the gene that encodes the molybdohemoprotein sulfite oxidase. These include two frameshift mutations, a four-basepair deletion (562del4) and a single-basepair insertion (113insC), both resulting in premature termination. Nonsense mutations predicting Y343X and Q364X substitutions were identified in a homozygous state in three patients, the latter in two sibs. The remaining eight are missense mutations generating single amino acid substitutions. From the position of the substituted residues, seven of these mutations are considered to be causative of the enzyme deficiency: I201L, R211Q, G305S, R309H, K322R, Q339R, and W393R. The eighth, a C>T transition, predicts an R319C substitution, which could affect the binding of the molybdenum cofactor and thus severely reduce sulfite oxidase activity. This mutation, however, is downstream of a frameshift mutation and is therefore not the causative mutation in this individual.