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Biomedical subjects

R Kahn

Publications and source records attributed to R Kahn.

At least 55 records · Page 3Linked to original sources

Lower-pole caliceal stone clearance after shockwave lithotripsy, percutaneous nephrolithotomy, and flexible ureteroscopy: impact of radiographic spatial anatomy.

Spatial anatomy of the lower renal pole, as defined by the infundibulopelvic angle (LIP angle), infundibular length (IL), and infundibular width (IW), plays a significant role in the stone-free rate after shockwave lithotripsy. A wide LIP angle, a short IL, and a broad IW, individually or in combination, favor stone clearance, whereas a LIP <70 degrees, an IL >3 cm, or an IW < or =5 mm are individually unfavorable. When all three unfavorable factors or an unfavorable LIP and IL coexist, the post-SWL stone-free rate falls to 50% or less. Using these criteria, more than one fourth of our patients with a lower-pole calculus might have been better served by an initial percutaneous or perhaps ureteroscopic procedure, neither of which is significantly affected by the lower-pole spatial anatomy.

Adolescent↗

Acute vasoconstriction after subarachnoid hemorrhage.

OBJECTIVE: Decreased cerebral blood flow (CBF) and cerebral ischemia occurring immediately after subarachnoid hemorrhage (SAH) may be caused by acute microvascular constriction. However, CBF can also be influenced by changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The goal of these experiments was to assess the significance of acute vasoconstriction after SAH and its relationship to changes in CBF, ICP, CPP, and extracellular glutamate concentrations. METHODS: Three experiments were performed using the endovascular filament technique to produce SAH. In the first experiment, CBF, ICP, and CPP were measured for 60 minutes after SAH (n = 21) and were correlated with the 24-hour mortality rate. In the second experiment, rats undergoing SAH (n = 23) or a sham procedure (n = 7) were perfused 60 minutes after SAH for measurement of the circumference and wall thickness of the internal carotid and anterior cerebral arteries and correlation with CBF, ICP, and CPP. In the third experiment (n = 11), extracellular glutamate concentrations determined by hippocampal and cortical microdialysis and high performance liquid chromatography were correlated with physiological changes. RESULTS: CBF reductions to less than 40% of baseline for 60 minutes after SAH predicted 24-hour mortality with 100% accuracy and were used to define "lethal" SAH. In contrast, ICP and CPP 60 minutes after SAH were not correlated with the mortality rate. The vascular circumference was significantly smaller in lethal than in sublethal SAH or sham-operated rats (P < 0.001). Vessel measurements were correlated with both CBF and hemorrhage size (P < 0.01). Extracellular glutamate concentration increased to 600% of baseline after lethal SAH in both hippocampus and cortex and was inversely correlated with CBF (r = 0.9, P < 0.001) but did not increase after sublethal SAH. CONCLUSION: Acute vasoconstriction after SAH occurs independently of changes in ICP and CPP and is associated with decreased CBF, larger hemorrhage size, persistent elevations of extracellular glutamate, and poor outcome. Acute vasoconstriction seems to contribute directly to ischemic brain injury after SAH. Further evaluations of pharmacological agents with the potential to reverse acute vasoconstriction may increase CBF and improve outcome.

Animals↗

[Cervical extraosseous Ewing sarcoma].

A case of extraosseous Ewing's sarcoma is presented. The clinical, morphological and imaging characteristics of this rare neoplasm are briefly discussed.

Adult↗

Protein Crystallography at Ultra-Short Wavelengths: Feasibility Study of Anomalous-Dispersion Experiments at the Xenon K-edge.

A protein crystallography experiment at the xenon K-edge (lambda = 0.358 A) has been successfully carried out at the materials science beamline (BL2/ID11) of the ESRF. The samples used in this methodological study were crystals of porcine pancreatic elastase, a 26 kDa protein of known structure. The diffraction data are of excellent quality. The combination of isomorphous replacement and anomalous dispersion of a single xenon heavy-atom derivative allowed accurate phase determination and the computation of a high-quality electron density map of the protein molecule. This is the first fully documented report on a complete protein crystallography experiment, from data collection up to phase determination and calculation of an electron density map, carried out with data obtained at ultra-short wavelengths. Experimental considerations as well as possible advantages and drawbacks of protein crystallography at very short and ultra-short wavelengths are discussed.

Journal Article↗

Lung mechanical behavior during one-lung ventilation.

OBJECTIVE: Switching from two-lung to one-lung ventilation would be expected to have large effects on lung mechanical properties, and these effects may depend on tidal volume and respiratory frequency. These changes in lung mechanics with one-lung ventilation may be similar to pulmonary edema. Deteriorating lung mechanics during pulmonary edema have been attributed to a loss of ventilated lung units. Therefore, changes in lung mechanics caused by one-lung ventilation were measured and compared with those previously seen during pulmonary edema. DESIGN: Prospective study. SETTING: Research laboratory. INTERVENTIONS: After induction of anesthesia, beagle dogs' tracheas were intubated with an endotracheal tube with a bronchial blocker (Univent System Corp, Tokyo, Japan) to apply one-lung ventilation. The proper position of the bronchial blocker during one-lung ventilation was confirmed with a fiberoptic bronchoscope. MEASUREMENTS AND MAIN RESULTS: Lung elastance (EL) and resistance (RL) were calculated from measurements of airway pressure, esophageal pressure, and airway flow in five anesthetized, paralyzed dogs during sinusoidal forcing at a constant mean airway pressure of 10 cmH2O in a wide range of breathing frequencies (0.2 to 1.0 Hz in intervals of 0.2) and tidal volumes (50, 100, 200, and to 300 mL). Measurements were made before and after the left mainstem bronchus was occluded with the bronchial blocker. During ventilation of both lungs, EL and RL depended relatively little on frequency, and both EL and RL were independent of tidal volume. During one-lung ventilation, EL doubled and, at most frequencies, RL increased; frequency dependences were not increased, and no dependence on tidal volume was observed. CONCLUSIONS: The lack of tidal volume dependence in EL and lack of large-frequency dependence in RL during one-lung ventilation are inconsistent with changes induced by severe pulmonary edema. Although decreases in ventilatable lung volume may contribute to increases in lung elastance, other characteristics of mechanical behavior during one-lung ventilation differ from those of pulmonary edema; therefore, other additional mechanisms must be involved in determining lung mechanical properties during severe pulmonary edema.

Airway Resistance↗

Respiratory impedances and acinar gas transfer in a canine model for emphysema.

We examined how the changes in the acini caused by emphysema affected gas transfer out of the acinus (Taci) and lung and chest wall mechanical properties. Measurements were taken from five dogs before and 3 mo after induction of severe bilateral emphysema by exposure to papain aerosol (170-350 mg/dose) for 4 consecutive wk. With the dogs anesthetized, paralyzed, and mechanically ventilated at 0.2 Hz and 20 ml/kg, we measured Taci by the rate of washout of 133Xe from an area of the lung with occluded blood flow. Measurements were repeated at positive end-expiratory pressures (PEEP) of 10, 5, 15, 0, and 20 cmH2O. We also measured dynamic elastances and resistances of the lungs (EL and RL, respectively) and chest wall at the different PEEP and during sinusoidal forcing in the normal range of breathing frequency and tidal volume. After final measurements, tissue sections from five randomly selected areas of the lung each showed indications of emphysema. Taci during emphysema was similar to that in control dogs. EL decreased by approximately 50% during emphysema (P < 0.05) but did not change its dependence on frequency or tidal volume. RL did not change (P > 0.05) at the lowest frequency studied (0.2 Hz), but in some dogs it increased compared with control at the higher frequencies. Chest wall properties were not changed by emphysema (P > 0.05). We suggest that although large changes in acinar structure and EL occur during uncomplicated bilateral emphysema, secondary complications must be present to cause several of the characteristic dysfunctions seen in patients with emphysema.

Aerosols↗

Crystal structure of a fungal elicitor secreted by Phytophthora cryptogea, a member of a novel class of plant necrotic proteins.

BACKGROUND: Elicitins form a novel class of plant necrotic proteins which are secreted by Phytophthora and Pythium fungi, parasites of many economically important crops. These proteins induce leaf necrosis in infected plants and elicit an incompatible hypersensitive-like reaction, leading to the development of a systemic acquired resistance against a range of fungal and bacterial plant pathogens. No crystal structures of this class of protein are available. The crystal structure determination of beta-cryptogein (CRY), secreted by Phytophthora cryptogea, was undertaken to identify structural features important for the necrotic activity of elicitins. RESULTS: The structure of CRY was determined using the multiwavelength anomalous diffraction technique and refined to 2.2 A resolution. The overall structure has a novel fold consisting of six alpha helices and a beak-like motif, whose sequence is highly conserved within the family, composed of an antiparallel two-stranded beta sheet and an omega loop. This motif is assumed to be a major recognition site for a putative receptor and/or ligand. Two other distinct binding sites seem to be correlated to the level of necrotic activity of elicitins. CONCLUSIONS: The determination of the crystal structure of a member of the elicitin family may make it possible to separate the activity that causes leaf necrosis from that inducing systemic acquired resistance to pathogens, making it feasible to engineer a non-toxic elicitin that only elicits plant defences. Such studies should aid the development of non-toxic agricultural pest control.

Algal Proteins↗

The Multiwavelength Anomalous Solvent Contrast (MASC) Method in Macromolecular Crystallography.

The wavelength dependence of anomalous scattering of X-rays, due to atoms randomly dispersed in the solvent phase of a macromolecular crystal, is a way of producing solvent-density contrast variation with perfect isomorphism. The largest contrast variations are obtained by tuning the X-ray wavelength near an absorption edge of the anomalous-scattering species. In this method, which we call MASC, the anomalous partial structure is an extended uniform electron density, in contrast to the few punctual ordered scatterers in the multiwavelength anomalous-dispersion (MAD) method. MASC is, in principle, applicable to the determination of the molecular envelope and of low-resolution structure-factor phases. Structure factors (lambda)F(+/-h) leads to a set of equations which can be solved to give |G(h)| and |(0)F(h)|, the modulus of the envelope and of the total ;normal' structure factors, respectively, and Deltavarphi = (varphi(0)(F)-varphi(G)). The moduli {|G|} behave like structure-factor amplitudes from small-molecule crystals, and the estimation of their phases can be carried out by statistical direct methods. Then, the phase of (0)F(h) and finally the conventional (e.g. in vacuum) protein structure factor F(p)(h) can be determined. As in the MAD method, the strength of MASC signals can be quantified by Bijvoet and dispensive ratios, for which practical expressions are derived in the case of zero contrast. The behaviour of these ratios at increasing resolution is discussed, using approximations for |G(h)| and |Delta(h)| , respectively, derived from Porod's law and assuming a random distribution of atoms in the solvent excluding volume. Expected values of anomalous ratios are calculated for a hypothetical MASC experiment based on the known three-dimensional structure of kallikrein A, using a solvent with 3.5 M ammonium selenate to ensure zero contrast, and wavelength tuning near the Se K-absorption edge. The main steps of a MASC experiment are discussed in the context of a MAD-like data collection optimized for accurate measurements of intensities of anomalous pairs at low resolution. Finally, the results of preliminary experiments on two protein crystals are reported. The first, a partial single-wavelength data collection, used anomalous scattering of selenium at the K edge and gave anomalous ratios with the expected behaviour. The second one, at three wavelengths, used anomalous scattering of ytterbium at the L(III) edge. In this case, effects from solvent as well as from ordered lanthanide ions were demonstrated.

Journal Article↗

In vitro oxyhaemoglobin saturation measurements in haemoglobin solutions using fibreoptic pulmonary artery catheters.

We compared in vitro oxyhaemoglobin saturations using two pulmonary artery catheters (catheter SO2), with oxyhaemoglobin saturations (SO2) measured by the IL282 co-oximeter and derived partial oxyhaemoglobin saturations (partial SO2) at different oxygen tensions (PO2) in six solutions: whole blood, 50:50 mixture of whole blood and Plasmalyte A (haemodiluted blood), 50:50 mixture of whole blood and 8% pyridoxylated haemoglobin-polyoxyethylene (PHP) conjugate (WB-PHP), 75:25 mixture of 8% PHP and Plasmalyte A solution (PHP66), 50:50 mixture of 8% PHP and Plasmalyte A solution (PHP44) and stroma-free haemoglobin solution (SFH). Calculated P50 values (PO2 vs SO2) were 3.79, 3.58, 3.49, 3.15, 3.04 and 2.07 kPa, respectively. However, if partial SO2 was used the curves were shifted to the left, reducing P50. Catheter SO2 correlated well with SO2 in whole blood (r2 > 0.99 for both catheters), haemodiluted blood (r2 > 0.98 for both catheters) and WB-PHP solution (r2 = 0.94 for both catheters). In PHP44 (r2 = 0.64 and r2 = 0.57), PHP66 (r2 = 0.40 for the Oximetrix and r2 = 0.25 for the Edwards catheter) and SFH solutions (r2 = 0.33 for the Oximetrix and r2 = 0.22 for the Edwards catheter) both catheters performed poorly. We conclude that mixed venous oxyhaemoglobin saturations measured by oximetric pulmonary artery catheters are inaccurate in the presence of haemoglobin solutions. For accuracy a multi-wavelength co-oximeter should be used if blood containing PHP or SFH is to be analysed.

Catheterization, Peripheral↗

Change in productive activity in late adulthood: MacArthur studies of successful aging.

Both cross-sectional comparisons and patterns of change in productive activities among members of the MacArthur Successful Aging cohort were examined. The data came from a three-site longitudinal study of community-dwelling adults aged 70-79. The highest functioning cohort (n = 1,192) was found to be significantly more productive than a comparison group of medium- and low-functioning respondents at baseline in four of five domains examined. In longitudinal models, we tested several hypotheses regarding the determinants of change in levels of productive activity over a three-year period. Overall, 15.1 percent (n = 162) of the cohort became less productive, while another 12.7 percent (n = 136) became more productive. Risk factors for decline in productivity included hospital admission and stroke. Age, functional disability, marriage, and increased mastery were protective against declines. Conversely, Blacks, those who were more satisfied with life at baseline, and those reporting increased mastery were more likely to increase their productivity.

Activities of Daily Living↗

Transesophageal echocardiography can be used to screen for ascending aortic atherosclerosis.

Atherosclerosis of the ascending aorta may be associated with a higher perioperative stroke risk in cardiac surgery. This study investigated the use of biplane transesophageal echocardiography (TEE) scanning of the entire thoracic aorta to predict the presence of plaque in the ascending aorta. Eighty-one patients (57 male, 24 female; aged 32-88 yr, mean age 64 yr) scheduled for elective cardiac surgery participated in an institutional review board-approved protocol. A comprehensive examination of the entire thoracic aorta in both the longitudinal and transverse planes was performed. After pericardiotomy, a sterilely draped 7-MHz probe was used to scan the entire ascending aorta in both long and short axis views. In both echocardiographic examinations, the presence and location of protruding plaques and intimal thickening > 3 mm were recorded. Using epiaortic (EPI) scanning as the "gold standard," the sensitivity, specificity, positive predictive value, and negative predictive value of TEE for detecting ascending aortic atherosclerosis were calculated. Fourteen (17%) of the 81 patients had significant atherosclerotic disease of the ascending aorta as diagnosed by EPI echocardiography. The sensitivity of TEE was 100%, the specificity was 60%, the positive predictive value was 34%, and the negative predictive value was 100%. These data show that, if the complete biplane TEE examination is negative for plaque, it is highly unlikely that there is significant plaque in the ascending aorta. If the TEE examination is positive for plaque, there is a 34% chance that there is significant disease of the ascending aorta, and EPI scanning should be considered. Thus, TEE is a very sensitive but only mildly specific method of determining whether ascending aortic atherosclerosis is present.

Adult↗

Lung tissue and airway impedances during pulmonary edema in normal range of breathing.

How pulmonary edema affects lung tissue and airway properties is not clear. From measurements of airway pressure and flow, we measured lung elastance (EL) and resistance (RL) in 5 anesthetized-paralyzed open-chested dogs during sinusoidal forcing in the frequency (f) and tidal volume (VT) ranges of normal breathing. RL was divided into its tissue (Rti) and airway (Raw) components from measurements of alveolar pressure through capsules glued to the lung surface. After induction of severe pulmonary edema by injection of oleic acid into the right atrium, forcing was repeated at the same mean airway pressure (Paw) as in control animals (11 cmH2O) and at a higher Paw (14 cmH2O), as would occur in closed-chested dogs during edema (G. M. Barnas, D. Stamenovic, and K. R. Lutchen. J. Appl. Physiol. 73: 1040-1046, 1992). Edema increased EL, and this increase was greater at Paw = 14 cmH2O (P < 0.05). The f dependences of EL and Rti were increased by edema (P < 0.05), and there was a large negative dependence of EL on VT at Paw = 14 cmH2O. Edema increased RL (P < 0.05), but this increase depended on f, VT, and Paw. The increase in RL was due largely to increases in Rti at Paw = 14 cmH2O and to increases in Raw at Paw = 11 cmH2O. We conclude that the functional effects of oleic acid-induced pulmonary edema on RL are due mostly to changes in lung tissue.

Airway Resistance↗

Refined three-dimensional structure of the Fab fragment of a murine IgGl,lambda antibody.

We report the cDNA sequence determination and the crystal structure of the Fab fragment of a murine IgG1,lambda antibody (HC19), specific for an influenza virus hemagglutinin. The HC19 Fab-fragment structure has been refined; the crystallographic R-factor is 19.5% at 2.3 A resolution. We have compared the conformation of HC19 complementarity determining regions (CDRs) with those of CDR loops of Fab structures available from the Protein Data Bank. These loops were chosen based on the identity of key residues, following the canonical-structure approach; four CDRs have a main-chain conformation very similar to the canonical structure that had been identified. HC19 L1 CDR adopts a conformation clearly distinct from all L1 CDRs that belong to a chain of a different class or origin; this is determined by the nature of a few residues at positions in the sequence different from those of key residues in other light chains. This canonical structure should be representative of most murine lambda-class light chains, as inferred from the very high sequence homologies of these polypeptides.

Journal Article↗

Medical education about substance abuse: changes in curriculum and faculty between 1976 and 1992.

PURPOSE: To examine changes in substance abuse education in U.S. medical schools between 1976 and 1992. METHODS: In 1991-92 the authors conducted a 16-year follow-up survey of six clinical departments in each of the 126 U.S. medical schools. Two previous surveys by scholars and surveys conducted by the Liaison Committee on Medical Education, Association of American Medical Colleges, and the National Center for Medical Fellowships in the Addictions provided baseline data for comparison. The statistical methods used in the comparisons were paired t-tests, one-way analyses of variance, and tests of differences between proportions. RESULTS: Significant increases were found in the numbers of required and elective curriculum units for medical students between 1986-87 and 1991-92. The number of medical schools requiring courses in substance abuse treatment increased from five to eight between 1986-87 and 1991-92. For residents, there were significant increases in the numbers of curriculum units for residents in family medicine and pediatrics. The average number of faculty in the 116 medical schools that reported units on substance abuse was 4.1. There were 45 fellowships in addiction medicine identified in 1991-92, with a total of 61 fellows in training. CONCLUSION: While the findings confirm positive changes, the amount of curricula time and the number of faculty having expertise in substance abuse education do not compare well with the amounts of time and numbers of faculty involved in clinical problems of similar prevalence, such as cancer and heart disease.

Curriculum↗