A theory of pitch for the hydrodynamic properties of molecules, helices, and achiral swimmers at low Reynolds number.

We present a theory for pitch, a matrix property that is linked to the coupling of rotational and translational motion of rigid bodies at low Reynolds numbers. The pitch matrix is a geometric property of objects in contact with a surrounding fluid, and it can be decomposed into three principal axes of pitch and their associated moments of pitch. The moments of pitch predict the translational motion in a direction parallel to each pitch axis when the object is rotated around that axis and can be used to explain translational drift, particularly for rotating helices. We also provide a symmetrized boundary element model for blocks of the resistance tensor, allowing calculation of the pitch matrix for arbitrary rigid bodies. We analyze a range of chiral objects, including chiral molecules and helices. Chiral objects with a Cn symmetry axis with n > 2 show additional symmetries in their pitch matrices. We also show that some achiral objects have non-vanishing pitch matrices, and we use this result to explain recent observations of achiral microswimmers. We also discuss the small but non-zero pitch of Lord Kelvin's isotropic helicoid.

Separation of Enantiomers through Local Vorticity: A Screw Model Mechanism.

We present a model to explain the mechanism behind enantiomeric separation under either shear flow or local rotational motion in a fluid. Local vorticity of the fluid imparts molecular rotation that couples to translational motion, sending enantiomers in opposite directions. Translation-rotation coupling of enantiomers is explored using the molecular hydrodynamic resistance tensor, and a molecular equivalent of the pitch of a screw is introduced to describe the degree of translation-rotation coupling. Molecular pitch is a structural feature of the molecules and can be easily computed, allowing rapid estimation of the pitch of 85 druglike molecules. Simulations of model enantiomers in a range of fluids such as Λ- and Δ-[Ru(bpy)3]Cl2 in water and (R, R)- and (S, S)-atorvastatin in methanol support predictions made using molecular pitch values. A competition model and continuum drift-diffusion equations are developed to predict separation of realistic racemic mixtures. We find that enantiomeric separation on a centimeter length scale can be achieved in hours, using experimentally achievable vorticities. Additionally, we find that certain achiral objects can also exhibit a nonzero molecular pitch.

Prospective controlled cohort study of Troponin I levels in patients undergoing elective spine surgery for degenerative conditions: Prone versus supine position.

Prior studies have suggested that elevated serum Troponin-I (TnI) levels immediately after non-cardiac surgical procedures (8-40%) represent subclinical cardiac stress which independently predicts increased 30-day mortality. Routine post-operative TnI monitoring has therefore been suggested as a standard of care. However, no prior studies have focussed on elective degenerative spine surgery, whilst few have measured pre-op TnI. Further, prolonged prone positioning could represent an additional, independent, cardiac stress. We planned a prospective controlled cohort study of consecutive TnI levels in routine elective spine surgery for degenerative spine conditions, incorporating 3 groups: 'prone<2h', 'prone>2h' and 'supine' positioning. TnI levels (>0.04µg/L) were recorded immediately pre-/post-surgery, and by 24h of surgery. N=120 patients were recruited. Complete results were obtained in 92 (39 supine, 53 prone). No significant between-groups differences were observed in demographic or cardiovascular risk factors. Validated TnI-elevation by 24h was not observed in any group. Spurious elevations were recorded in one 'prone<2h' and one 'prone>2h'. One non-ST segment myocardial infarction (STEMI) occurred on day 7 without TnI elevation by 24h (prone>2h). There was no 30-day mortality. CONCLUSIONS: Despite a lower cut-off, no validated TnI elevation was observed in any group by 24h after surgery. One non-STEMI had not been associated with TnI-elevation by 24h. Immediately peri-operative cardiac stress therefore appeared comparatively rare in patients undergoing routine elective spine surgery. Further, prone positioning did not represent an additional, independent, risk. Routine immediately post-operative TnI monitoring in elective spine surgery therefore appears unjustified. Our study highlighted several caveats regarding consecutive TnI testing.

Resistance training and hormone replacement increase MMP-2 activity, quality and quantity of bone in ovariectomized rats

AIMS: The aim of the present study was to investigate the influence of resistance training (RT) and hormone replacement (HR) on MMP-2 activity, biomechanical and physical properties bone of ovariectomized (OVX) rats. METHODS: Sprague-Dawley female rats were grouped into six experimental groups (n = 11 per group): sham-operated sedentary (SHAM Sed), ovariectomized sedentary (OVX Sed), sham-operated resistance training (SHAM RT), ovariectomized resistance training (OVX RT), ovariectomized sedentary hormone replacement (OVX Sed-HR), and ovariectomized resistance training hormone replacement (OVX RT-HR). HR groups received implanted silastic capsules with a 5% solution of 17ß-estradiol (50 mg 17ß-estradiol/ml of sunflower oil). In a 12-week RT period (27 sessions; 4-9 climbs) the animals climbed a 1.1 m vertical ladder with weights attached to their tails. Biomechanical and physical bone analyses were performed using a universal testing machine, and MMP-2 activity analysis was done by zymography. RESULTS: Bone density and bone mineral content was higher in the RT and HR groups. The MMP-2 activity was higher in the RT and HR groups. The biomechanical analysis (stiffness, fracture load and maximum load) demonstrated better bone tissue quality in the RT associated with HR. CONCLUSION: The RT alone as well as when it is associated with HR was efficient in increasing MMP-2 activity, biomechanical and biophysical properties bone of ovariectomized rats.(AU)

Crystallographic and biochemical analyses of the metal-free Haemophilus influenzae Fe3+-binding protein.

The crystal structure of the iron-free (apo) form of the Haemophilus influenzae Fe(3+)-binding protein (hFbp) has been determined to 1.75 A resolution. Information from this structure complements that derived from the holo structure with respect to the delineation of the process of iron binding and release. A 21 degrees rotation separates the two structural domains when the apo form is compared with the holo conformer, indicating that upon release of iron, the protein undergoes a change in conformation by bending about the central beta-sheet hinge. A surprising finding in the apo-hFbp structure was that the ternary binding site anion, observed in the crystals as phosphate, remained bound. In solution, apo-hFbp bound phosphate with an affinity K(d) of 2.3 x 10(-3) M. The presence of this ternary binding site anion appears to arrange the C-terminal iron-binding residues conducive to complementary binding to Fe(3+), while residues in the N-terminal binding domain must undergo induced fit to accommodate the Fe(3+) ligand. These observations suggest a binding process, the first step of which is the binding of a synergistic anion such as phosphate to the C-terminal domain. Next, iron binds to the preordered half-site on the C-terminal domain. Finally, the presence of iron organizes the N-terminal half-site and closes the interdomain hinge. The use of the synergistic anion and this iron binding process results in an extremely high affinity of the Fe(3+)-binding proteins for Fe(3+) (nFbp K'(eff) = 2.4 x 10(18) M(-1)). This high-affinity ligand binding process is unique among the family of bacterial periplasmic binding proteins and has interesting implications in the mechanism of iron removal from the Fe(3+)-binding proteins during FbpABC-mediated iron transport across the cytoplasmic membrane.

Residency program director evaluations do not correlate with performance on a required 4th-year objective structured clinical examination.

BACKGROUND: Assessment of resident performance is a complex task. PURPOSE: To correlate performance on a 4th-year objective structured clinical examination (OSCE) with residency program director assessment, class rank, and U.S. Medical Licensing Examination (USMLE) scores. METHODS: We surveyed program directors about the performance of 50 graduates from our medical school chosen to represent the highest (OSCEHI) and lowest (OSCELO) 25 performers on our required 4th-year OSCE. Program directors were unaware of the OSCE scores of the graduates. RESULTS: OSCE scores did not correlate with Likert scores for any survey parameter studied (r < .23, p > .13 for all comparisons). Similarly, program director evaluations did not correlate with class rank or USMLE scores (r < .26, p > .09 for all comparisons). CONCLUSIONS: We concluded that program director evaluations of resident performance do not appear to correlate with objective tests of either clinical skills or knowledge taken during medical school. These findings suggest that more structured and objective evaluative tools might improve postgraduate training program assessment of trainees.

Abnormal duodenal bile composition in patients with acalculous chronic cholecystitis.

OBJECTIVE: Our goal was to characterize biliary lipid composition in patients with the syndrome of chronic biliary pain, absence of gallstones, and inflammation of the gallbladder mucosa (acalculous chronic cholecystitis). METHODS: Duodenal bile, obtained from 27 patients with a history of right upper quadrant pain and with negative imaging studies of the biliary tract, was analyzed enzymatically for bile acids, phospholipids, and cholesterol. Fifteen patients were found to have inflammation and/or fibrosis of the gallbladder at cholecystectomy. RESULTS: The 15 patients with abnormal gallbladder histology had more dilute duodenal bile, as indicated by a low bile acid concentration and a lower proportion of phospholipids (p < 0.01) when values were compared with those of duodenal bile samples from postmenopausal women without gallbladder disease or from radiolucent gallstone subjects participating in the National Cooperative Gallstone Study. Cholecystectomy relieved pain in 9 of 14 patients. CONCLUSIONS: Some patients with acalculous chronic cholecystitis have duodenal bile samples characterized by a decreased bile acid concentration and a decreased proportion of biliary phospholipids. The low biliary bile acid concentration may result from impaired gallbladder contraction and/or secretion by the biliary tract epithelium. The low proportion of phospholipid may result from posthepatic hydrolysis of luminal phosphatidylcholine followed by absorption of the hydrolysis products. The latter process could be caused by and/or contribute to mucosal inflammation and would also elevate the cholesterol saturation of bile, increasing the risk for cholesterol gallstone formation.

Proteome studies of Saccharomyces cerevisiae: identification and characterization of abundant proteins.

Two-dimensional (2-D) gel electrophoresis can now be coupled with protein identification techniques and genome sequence information for direct detection, identification, and characterization of large numbers of proteins from microbial organisms. 2-D electrophoresis, and new protein identification techniques such as amino acid composition, are proteome research techniques in that they allow direct characterization of many proteins at the same time. Another new tool important for yeast proteome research is the Yeast Protein Database (YPD), which provides the sequence-derived protein properties needed for spot identification and tabulations of the currently known properties of the yeast proteins. Studies presented here extend the yeast 2-D protein map to 169 identified spots based upon the recent completion of the yeast genome sequence, and they show that methods of spot identification based on predicted isoelectric point, predicted molecular mass, and determination of partial amino acid composition from radiolabeled gels are powerful enough for the identification of at least 80% of the spots representing abundant proteins. Comparison of proteins predicted by YPD to be detectable on 2-D gels based on calculated molecular mass, isoelectric point and codon bias (a predictor of abundance) with proteins identified in this study suggests that many glycoproteins and integral membrane proteins are missing from the 2-D gel patterns. Using the 2-D gel map and the information available in YDP, 2-D gel experiments were analyzed to characterize the yeast proteins associated with: (i) an environmental change (heat shock), (ii) a temperature-sensitive mutation (the prp2 mRNA splicing mutant), (iii) a mutation affecting post-translational modification (N-terminal acetylation), and (iv) a purified subcellular fraction (the ribosomal proteins). The methods used here should allow future extension of these studies to many more proteins of the yeast proteome.

Cycloserine-induced Stevens-Johnson syndrome in an AIDS patient with multidrug-resistant tuberculosis.

We report a case of cycloserine-induced Stevens-Johnson syndrome (SJS) in a 38-year-old male with the acquired immune deficiency syndrome (AIDS) and multidrug resistant tuberculosis (MDR-TB). The patient developed a cutaneous reaction after 60 days of therapy with ofloxacin, streptomycin (SM), pyrazinamide (PZA), ethambutol (EMB), and cycloserine (CSN). All drugs were stopped and the rash improved. Due to the severity of his disease, anti-tuberculosis drugs were resumed, one at a time. The patient developed a recurrent rash consistent with SJS, which began when CSN was restarted. CSN was stopped and the SJS began to gradually resolve with palliative treatment despite continuation of the other anti-tuberculosis drugs. However, the patient's overall condition gradually deteriorated and he died. To our knowledge, this is the first case of probable CSN-related SJS.

Neurofilament-like immunoreactivity in the sea anemone Condylactis gigantea (Cnidaria: Anthozoa).

The neuronal cytoskeleton contains neurofilament proteins that serve as markers for nervous tissue in many species across phyla. Antiserum generated to mammalian neurofilaments was used for immunocytochemical staining of tissues in the sea anemone Condylactis gigantea (Cnidaria: Anthozoa). Specific staining, visible at the light and electron microscope levels, was found in the tissues of the tentacle. Proteins were extracted from the tissues and solubilized. SDS-polyacrylamide gel electrophoresis and Western blotting revealed two bands of MWr 156 kD and 74 kD that reacted with antiserum generated to neurofilaments. The protein bands also bound a monoclonal antibody shown to react with a highly conserved epitope in many classes of intermediate filaments. These data suggest that the neurons of this anthozoan contain neurofilament-like proteins with molecular properties similar to those of mammalian neurons.

Analysis of the costs and benefits of using standardized patients to help teach physical diagnosis.

BACKGROUND: Although a majority of medical schools use standardized patients (SPs) for teaching or evaluating students, the costs and benefits of such programs have not been examined in depth. In 1992-93 the Tulane University School of Medicine reduced by 40% the faculty-precepted sessions in its physical diagnosis program in order to incorporate seven focused examinations using SPs to teach basic examination skills. METHOD: Costs for the revised program included costs for SPs, staff, supplies, and faculty. Faculty cost was estimated at a minimum to equal hourly salary and at a maximum to equal this salary plus potential collectible billings. An objective structured clinical examination (OSCE) was used to assess the skill acquisitions of 150 second-year students in 1991-92, before SPs were used, and in 1992-93, when SPs were used. An unpaired t-test was then used to compare the OSCE performances of the two groups of students. Chi-square analysis was used to compare the evaluations of the physical diagnosis program by the 1992-93 and 1991-92 students. RESULTS: The cost of incorporating SPs into the program was $43,800. The amount of time spent teaching by faculty was reduced by 608 hours, costing between $33 (salary) and $108 (salary plus potential revenue) per hour. Thus, the total savings in the cost of faculty time was between $20,064 and $65,664. Despite the reduction in faculty involvement, the students' performance on the OSCE did not change, and the students' evaluations of the course became significantly more favorable. CONCLUSION: The incorporation of SPs as instructors in the physical diagnosis program was accomplished at a minimal cost and resulted in an increase in students' enthusiasm for the purpose, with no loss of skill acquisition as measured by the OSCE.

Assessing the consistency and educational benefits of students' clinical experiences during an ambulatory care internal medicine rotation.

BACKGROUND: Although ambulatory care settings are being used increasingly in undergraduate clinical education, variability in the depth and breadth of students' contacts with basic medical problems may compromise the educational benefits of this teaching modality. The present study examines the nature of such variation and the educational effectiveness of ambulatory care education. METHOD: During the one-month ambulatory care component of the third-year internal medicine rotation at the University of Michigan Medical School, 43 students in 1989-90 and 1990-91 recorded the patient problems they saw at a hospital and satellite clinics. In addition, the students' diagnostic-recognition abilities were assessed before and after the component. The extents of the students' experiences in various categories of patient problems were quantified and correlated with their diagnostic abilities in relevant content areas. RESULTS: The students saw many categories of problems but few instances in any given category. There were numerous and potentially worrisome gaps in their exposure to several typical ambulatory care problems. Although the students showed significant increases in diagnostic-recognition abilities, these increases were not correlated with the students' levels of experience in any of the relevant problem categories. CONCLUSION: The variability and potentially worrisome gaps in the students' experiences in the ambulatory care settings studied are probably representative of students' experiences in such settings, and should be considered in the implementation and evaluation of educational experiences in ambulatory care.

Blunt bile duct injuries in children.

Three of 87 children with blunt liver injuries initially managed without operation required late intervention for bile leakage. Abdominal computed tomography scans in these patients showed liver injuries extending into the porta hepatis. Clinical courses were characterized by persistent abdominal pain, low-grade fever, and prolonged ileus. Radionucleide scan confirmed the suspicion of bile leakage. One patient had complete transection of the common bile duct, which was repaired surgically. Another had partial transection of the left hepatic duct, managed successfully with transampullary biliary decompression. The third patient with an intrahepatic injury was managed with a drain placed at celiotomy. Nonoperative management of blunt pediatric liver injuries carries a risk of persistent bile leakage. Radionucleide scan and endoscopic retrograde cholangiopancreatography are reliable modes of diagnosis and localization. Transampullary biliary decompression is a newer, effective modality for management of the proximal and/or partial bile duct injuries. Treatment must be individualized according to the site and extent of injury.

Vigabatrin--plasma enantiomer concentrations and clinical effects.

Plasma concentrations of the [R]- and [S]- enantiomers of the new anticonvulsant vigabatrin were measured by an enantiospecific gas-liquid chromatographic assay in a group of therapy-resistant epileptic patients in whom racemic vigabatrin was added to their existing antiepileptic drug regimens. The peak plasma concentrations of the biologically active [S]-enantiomer of vigabatrin were correlated with those of the [R]-enantiomer, with drug dose, seizure frequency and change in score on various tests of psychological function administered prior to and when the subjects were under steady-state conditions following vigabatrin therapy. Plasma [S]-vigabatrin concentrations correlated with drug dose, [R]-vigabatrin concentration and change in score of certain psychological tests reflecting verbal memory, recall and speed of information processing. No definite pharmacokinetic interactions were detected, though plasma phenobarbitone concentrations tended to fall during vigabatrin administration. There were too few data to assess the relation between [S]-vigabatrin concentrations and seizure frequency.

Optical metrology for two large highly aspheric telescope mirrors.

We describe a relatively simple, but highly effective, approach to the system design and alignment of an all-refractive Offner null corrector and phase-measuring Shack cube interferometer. In addition we outline procedures for fabricating and testing the optical components. Allowable errors for all parameters are determined by a tolerance analysis that separates axisymmetric and residual figure errors. An open construction optics frame provides a high degree of metering flexibility by incorporating simple kinematic mounts that provide adjustment of each lens while also allowing the lens to be removed and replaced with <2microm absolute repeatability. Nonaxisymmetric alignment errors are removed by rotating the optics on a high-precision bearing. Axial spacings are measured with contact transducers attached to both ends of an Invar metering rod. Two completed systems have guided the stressed-lap polishing of 1.8-m f/ 1.0 and 3.5-m f/ 1.5 aspheric mirrors.

A case of Rh isoimmunization: should threatened first-trimester abortion be an indication for Rh immune globulin prophylaxis?

Despite the recommended 28 weeks' gestation antenatal, postnatal, and postabortion prophylaxis with Rh immune globulin, residual Rh immunization still occurs in Rh-negative women. We describe a patient whose history suggests development of an anti-D antibody after first-trimester bleeding. To our knowledge, this is the first such case reported in the English literature.

Career preferences and career outcomes of Australian medical students.

Students entering three Australian medical schools were followed over a 15-year period to trace both movement into the profession and the longer-term outcomes of early career aspirations. A variety of student entry characteristics are examined together with aspirations, attainments and self-images. The results indicate that women, rather than men, are more likely to enter medical school with aspirations that involve specialty training. As they proceed through medical school, both groups move away from the idea of pursuing specialty training, although women tend to decide earlier than men that specialty practice is not for them. Women students are more likely than men to attain career goals if these involve general practice and less likely to if these involve specialization. The results indicate that although at graduation women medical practitioners have the same career goals and desires as men, if additional training is required women are unlikely to have their aspirations fulfilled.