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.     

Model-based inversion of speckle interferometer fringe patterns

Micrometer-scale rigid-body translations are determined fromelectronic speckle interferometric fringe patterns. An iterativeminimum error procedure employs the relative fringe order of pickedpositions of fringe maxima and minima within a single interferogram tocalculate the displacement field directly. The method does notcalculate the displacement at a single point but relies on theassumption that the character, but not the magnitudes or directions, ofthe displacements over the viewing area of the interferogram isknown. That is, a model of the displacements exists. Onperfect, noise-free forward modeled fringe patterns calculated for an 8.0-mum displacement, the phase error is less than 2 x10(-6) fringe orders (1.3 x 10(-5) rad)and probably results only from numerical noise in the inversion. Onreal fringe patterns obtained in electronic speckle interferometricexperiments, mean phase errors are generally less than 5 x10(-5) fringe orders (3.2 x 10(-4)rad), suggesting that the technique is robust despite errorsresulting from speckle noise, lack of accuracy in positioning ofexperimental components, and image-distortion corrections.     

Adrenal chromaffin cells on microcarriers exhibit enhanced long-term functional effects when implanted into the mammalian brain

Rat adrenal chromaffin cells attached to either collagen-coated dextran (Cytodex 3) or glass bead microcarriers, both of 90-200 microns diameter, were used as dopamine-secreting implants in the caudate-putamen of rats with 6-hydroxydopamine-induced unilateral lesions of the substantia nigra. As controls, beads without cells and cells in suspension alone were implanted. Chromaffin cells adhered to microcarriers reduced apomorphine-induced rotation by 75% in lesioned animals. Animals that were lesioned but not receiving cell implants or receiving beads alone showed no reduction. Animals implanted with cells not attached to beads also showed a reduction in rotation but this effect lasted less than three months. Microcarrier-attached cells, however, maintained their effect in reducing rotation for at least eight months (rotations were reduced from a control mean of 10.9 +/- 1.4 to 3.6 +/- 1.1 turns/min) without any "drop-off" of the effect. Histological examination showed that eight months post-implant the cells pre-adhered to beads were still present and could be stained by anti-tyrosine hydroxylase antibody. Sections stained with hematoxylin-eosin showed no signs of an inflammatory response. In contrast to beads implanted into the striatum, Cytodex bead implants injected into the lateral ventricle induced a histopathological response appearing to involve the ependyma and choroid plexus. Results suggest that the striatal parenchyma but not the ventricle is amenable to studies using the microcarrier approach to transplantation.     

Isolation, characterization, and partial purification of a novel ubiquitin-protein ligase, E3. Targeting of protein substrates via multiple and distinct recognition signals and conjugating enzymes

Degradation of a protein via the ubiquitin system involves two discrete steps, conjugation of ubiquitin to the substrate and degradation of the adduct. Conjugation follows a three-step mechanism. First, ubiquitin is activated by the ubiquitin-activating enzyme, E1. Following activation, one of several E2 enzymes (ubiquitin-carrier proteins or ubiquitin-conjugating enzymes, UBCs) transfers ubiquitin from E1 to the protein substrate that is bound to one of several ubiquitin-protein ligases, E3s. These enzymes catalyze the last step in the process, covalent attachment of ubiquitin to the protein substrate. The binding of the substrate to E3 is specific and implies that E3s play a major role in recognition and selection of proteins for conjugation and subsequent degradation. So far, only a few ligases have been identified, and it is clear that many more have not been discovered yet. Here, we describe a novel ligase that is involved in the conjugation and degradation of non "N-end rule" protein substrates such as actin, troponin T, and MyoD. This substrate specificity suggests that the enzyme may be involved in degradation of muscle proteins. The ligase acts in concert with E2-F1, a previously described non N-end rule UBC. Interestingly, it is also involved in targeting lysozyme, a bona fide N-end substrate that is recognized by E3 alpha and E2-14 kDa. The novel ligase recognizes lysozyme via a signal(s) that is distinct from the N-terminal residue of the protein. Thus, it appears that certain proteins can be targeted via multiple recognition motifs and distinct pairs of conjugating enzymes. We have purified the ligase approximately 200-fold and demonstrated that it is different from other known E3s, including E3 alpha/UBR1, E3 beta, and E6-AP. The native enzyme has an apparent molecular mass of approximately 550 kDa and appears to be a homodimer. Because of its unusual size, we designated this novel ligase E3L (large). E3L contains an -SH group that is essential for its activity. Like several recently described E3 enzymes, including E6-AP and the ligase involved in the processing of p105, the NF-kappa B precursor, the novel ligase is found in mammalian tissues but not in wheat germ.     

Helicobacter pylori does not migrate from the antrum to the corpus in response to omeprazole

BACKGROUND: Omeprazole is known to have an effect on Helicobacter pylori in vivo. One opinion is that H. pylori "migrates" from the antrum to the corpus in response to omeprazole therapy. METHODS: To determine whether H. pylori migrates in response to omeprazole, we assessed the presence of H. pylori in the antrum and corpus in duodenal ulcer patients receiving omeprazole for 4 wk. Culture and histological examination of antral biopsies (Genta stain) were performed before patients received omeprazole, at the end of therapy, and 4-6 wk later. The end points were presence or absence of H. pylori and the number of H. pylori colonies per biopsy. RESULTS: Seventy-two patients had H. pylori in both the antrum and corpus at entry and 4-6 wk after ending therapy. Three general patterns were prevalent at the end of omeprazole therapy: antrum- and corpus-positive (54%), antrum-negative and corpus-positive (24%), both antrum- and corpus-negative (21%), and one patient had antrum-positive with corpus-negative (1%). Evaluation of the number of colonies per biopsy in those who remained H. pylori-positive in both the antrum and corpus throughout showed that the number of H. pylori decreased in both the antrum and corpus during therapy (507 +/- 60 vs. 225 +/- 51, p < 0.01 and 415 +/- 58 vs. 290 +/- 46 0.1) for antrum and corpus, respectively, and tended to return to pre-therapy levels 4-6 wk later. The number of H. pylori in the corpus also decreased in the antrum-negative and corpus-positive group during therapy with omeprazole (433 +/- 87 vs. 185 +/- 61, p < 0.05). In most of the patients studied, the number of H. pylori in the corpus was less posttreatment than it was pretreatment. The decrease in H. pylori load was also reflected in the development of false-negative urea breath tests. CONCLUSIONS: Omeprazole is detrimental to H. pylori in both the antrum and the corpus; migration from the antrum to the corpus in response to omeprazole is a myth.     

Some sexological characteristics of stress incontinent women

The goal of stress incontinence surgery is to prevent opening of the urethra during increases in intra-abdominal pressure. Greater refinements in the understanding of the pathophysiology of incontinence and experience with newer treatments have extended surgical thinking beyond the familiar paradigm "to place the urethra in a high retropubic position." When incontinence is associated with vaginal hypermobility, vaginal support may be sufficient to restore continence if the suburethral vaginal wall is sufficiently strong, an evaluation which must often be made by physical examination alone. However, when the vaginal wall is weak, the urethra will require an alternative form of support, usually a sling. If the urethra is intrinsically deficient, vaginal support may not be sufficient to prevent opening during increased intra-abdominal pressure, and coaptation by sling obstruction or periurethral bulking injection may be required. Most laparoscopic approaches to stress incontinence use Burch's method, which offers excellent urethral stability provided the suburethral vaginal wall is strong. Newer insights into the relation between vaginal mobility and urethral closure are discussed, as well as anatomic aspects of the Burch suspension relevant to laparoscopic repair.     

QQL: A DB&;IR Query Language

Traditional database query languages are based on set theory and crisp first order logic. However, many applications require retrieval-like queries which return result objects associated with a degree of being relevant to the query. Historically, retrieval systems estimate relevance by exploiting hidden object semantics whereas query processing in database systems relies on matching select-conditions with attribute values. Thus, different mechanisms were developed for database and information retrieval systems. In consequence, there is a lack of support for queries involving both retrieval and database search terms. In this work, we introduce the quantum query language (QQL). Its underlying unifying theory is based on the mathematical formalism of quantum mechanics and quantum logic. Van Rijsbergen already discussed the strong relation between the formalism of quantum mechanics and information retrieval. In this work, we interrelate concepts from database query processing to concepts from quantum mechanics and logic. As result, we obtain a common theory which allows us to incorporate seamlessly retrieval search into traditional database query processing.     

Three-dimensional analysis of contrast-filled microvessel diameters

Organ blood flow is controlled, in part, by changes in diameter of resistance vessels. In thick tissue, vessels can be imaged with a microscope using contrast-enhancing methods (e.g., fluorescence) and image analysis techniques can be used for quantitative diameter estimations. However, a change in the position of a vessel with respect to the plane of focus can be misinterpreted as a diameter change. In order to address this problem, a 3D image in a light microscope is obtained by serial optical sectioning, and a 3D deconvolution procedure (Avinash et al., 1991, "Fourteenth Association for Research in Otolaryngology Midwinter Meeting, St. Petersberg, FL," Abstract 156) is used to deblur 3D image data. Deblurred sections are computationally projected onto a 2D plane to give an extended-focus image, from which diameter estimates of microvessels are made using a quantitative, 2D diameter-tracking algorithm (Miles, 1987, "Semiautomatic Quantitative Image Analysis of Dynamic in Vivo Cochlear Microvessel Diameters." Ph.D. dissertation, Univ. Michigan; Miles and Nuttall, 1992, IEEE Trans. Biomed. Eng.). Justification for 3D preprocessing before diameter analysis is provided by absolute and relative error analyses using computer-generated synthetic vessels. The 3D diameter analysis technique is validated using a capillary tube of known diameter, filled with fluorescent solution. Demonstration of its applicability is shown in diameter measurements from the vessels of guinea pig cochlea. Our approach, using extended-focus images, minimizes overestimation of microvascular diameters and underestimation of relative diameter changes. Therefore, unambiguous diameter measurements are possible with extended-focus images.     

Natural Borna disease in domestic animals others than horses and sheep

In 24 cats (Uppsala, Sweden) with neurological signs of "staggering disease" and typical neuropathology, 44% had Borna disease virus (BDV)-specific antibodies. In 173 cat sera (Berlin, Germany) of animals with unknown record, 7% were BDV positive. Out of 24 cats with undefined neurological disorders, 13% were BDV positive. Similarities in staggering disease of cats and Borna disease of horses and sheep suggest related etiological agents.     

After-hours telephone coverage: the application of an area-wide telephone triage and advice system for pediatric practices

BACKGROUND: After-hours telephone calls are a stressful and frustrating aspect of pediatric practice. At the request of private practice pediatricians in Denver, a metropolitan area-wide system was created to manage after-hours pediatric telephone calls and after-hours patient care. This system, the After-Hours Program (AHP), uses specially trained pediatric nurses with standardized protocols to provide after-hours telephone triage and advice for the patients of 92 Denver pediatricians, representing 56 practices. OBJECTIVES: This report describes the AHP, presents data from 4 years' experience with the program, and describes results of our evaluation of the following aspects of the program: subscribing physician satisfaction, parent satisfaction, the accuracy and appropriateness of telephone triage, and program costs. METHODS: After-Hours Program records (including quality assurance data) for all 4 years of operation were retrospectively reviewed, tabulated, and analyzed. The results of two subscribing physician surveys and one parent caller satisfaction survey are presented. A retrospective review of after-hours patient care encounter forms assessed the necessity for after-hours visits triaged by the AHP. An analysis of the total cost of this program to 10 randomly selected subscribing physicians was conducted using current AHP data and a survey of the 10 physicians. RESULTS: In 4 years, 107,938 calls have been successfully managed without an adverse clinical outcome. Minor errors in using protocols occurred in one call out of 1450 after-hours calls. After-hours phoen calls necessitated an after-hours patient visit 20% of the time and generated one after-hours hospital admission out of every 88 calls. Just over half of the patients were managed with home care advice only, and 28% were given home care advice after-hours and seen the next day in the primary physician's office. Of all patients directed by the telephone triage nurses to be seen after hours, 78% were determined to have a condition necessitating after-hours care. Data are presented regarding call volumes by time of day, day of week, patient age, and patient's initial complaint. The 6 most common complaints accounted for more than one half of the calls, and 38 complaints accounted for more than 95% of all after-hours calls. Utilization by subscribing physicians is described. Satisfaction among subscribing pediatricians was 100%, and among parents was 96% to 99% on a variety of issues. The total cost to participating Denver pediatricians (which includes revenues "given up" as a result of not seeing patients after hours) ranged from 1% to 12% of their annual net income, depending on a variety of factors. CONCLUSIONS: Large-scale after-hours telephone coverage systems can be effective and well-received by patients, parents, and primary physicians. Data presented in this report can assist in planning the training of personnel who provide after-hours telephone advice and triage. Controversies associated with this type of program are discussed. Suggestions are made regarding the direction of future programs and research.