[Neuroendocrine neoplasia of the stomach : What is new?] / Neuroendokrine Neoplasien des Magens : Was ist neu?

INTRODUCTION: Neuroendocrine Neoplasms are classified according to the new WHO classification in (1.) well differentiated neuroendocrine tumors G1 (NET G1, Ki67 ≤ 2 or mitosis count <2) and (2.) well differentiated neuroendocrine tumors G2 (NET G2, Ki67 3-20 or mitosis count 2-20) and (3.) poorly differentiated neuroendocrine carcinomas G3 (NEC G3, Ki67 > 20 or mitosis count >20). MATERIAL AND METHODS: In this study 310 NENs of the Ludwig-Maximilians-University in Munich were reevaluated according to the new WHO classification. RESULTS: 7% of the analyzed NENs were presented as neoplasias of the stomach. In NENs of the stomach three distinct subtypes are recognized: (1) type 1 associated with autoimmune chronic atrophic gastritis (2) type 2, associated with multiple endocrine neoplasia (MEN1) and Zollinger-Ellison Syndrom; and (3) type 3, sporadic tumors. DISCUSSION: Precursor lesions (i. e. hyperplasia of the ECL cells) are found in patients with hypergastrinaemia (type 1 and 2). This article should provide insights into the diagnosis of NENs of the stomach with emphasis on the new international standard.

In-stent restenosis after interventional treatment of carotid artery stenoses: a long-term follow-up of a single center cohort.

BACKGROUND: Whereas in-stent restenosis (ISR) is widely discussed after coronary stenting procedures, this phenomenon is a considerable problem after interventional treatment of carotid artery stenosis as well. We sought to quantify ISR rate and to identify important respective risk factors in our cohort. METHODS: We retrospectively analyzed data of our carotid artery stenting database comprising 1165 angiographically successful interventional procedures during the last 19 years. Significant ISR was assessed by Doppler ultrasound and defined as a flow velocity exceeding 300 cm/s representing a lumen narrowing >70%. Examinations were performed the day after intervention, at follow-up visits 1, 6 and 12 months after index hospitalization and once a year afterwards. RESULTS: Thirty-nine patients (3.4%) developed a significant ISR > 70% during the follow-up period (median 19.6 months, IQR 5.1-49.6 months). In 13 of them, restenosis was caused by a mechanical collapse (stent crush) of the implanted stent. All patients with significant ISR were free of neurological events during follow-up and 31 patients underwent a stent-in-stent implantation. We found a shorter stent length, a narrower stent diameter, performance of post-dilatation as well as stent type to significantly influence development of ISR. CONCLUSION: ISR > 70% after carotid artery stenting is a rare finding also during long-term follow-up. Especially in patients treated with balloon-expandable stents, post-dilatation reduced ISR significantly. As ISR was rare and clinically benign, this technique seems to remain a good therapy option in patients with significant carotid artery stenosis.

[Exposure of Pupils to Recreational Noise from Portable Listening Devices and Possible Preventive Measures]. / Freizeitlärmbelastung durch tragbare Musikabspielgeräte bei Schülern und Präventionsmöglichkeiten.

Background and Objectives: Exposure to recreational noise is becoming increasingly important due to a change in leisure behavior amongst children and adolescents. The aim of this pilot study was to assess exposure of 6th grade pupils to recreational noise from portable listening devices (PLD). Furthermore, preventive measures to reduce recreational noise exposure should be identified. Methods: In "Ohrkan Kids", 38 Bavarian pupils aged 11 to 14 were interviewed regarding their music listening behavior using a standardized questionnaire. In addition, measurements of commonly used volume settings on the children's portable listening devices were carried out. Furthermore, the German Social Accident Insurance (DGUV), health insurance companies as well as health and education ministries of the German federal states were surveyed regarding their activities in the prevention of recreational noise exposure. Results: Based on the questionnaire data for weekly usage, 10 out of 31 children (32.3%) exceeded the upper exposure value of 85 dB recommended by labor protection law. Taking actually measured values, 9 out of 31 children (29%) exceeded this level. The DGUV and some federal states carry out specific projects for the prevention of recreational noise exposure. Conclusion: The large number of children with hazardous music consumption indicates that measures for the prevention of noise-induced hearing loss are already required for 11 to 14 year olds. To maximize the number of children addressed, age-appropriate and target-group-specific preventive measures are needed. As there are only few studies which examined the effectiveness of awareness campaigns for the prevention of recreational noise, any future prevention projects should be evaluated with an increased focus on estimating their effectiveness.

An association and haplotype analysis of porcine maternal infanticide: a model for human puerperal psychosis?

An association analysis using the Illumina porcine SNP60 beadchip was performed to identify SNPs significantly associated with porcine maternal infanticide. We previously hypothesised that this was a good animal model for human puerperal psychosis, an extreme form of postnatal mood disorder. Animals were selected from carefully phenotyped unrelated infanticide and control groups (representing extremes of the phenotypic spectrum), from four different lines. Permutation and sliding window analyses and an analysis to see which haplotypes were in linkage disequilibrium (LD) were compared to identify concordant regions. Across all analyses, intervals on SSCs 1, 3, 4, 10, and 13 were constant, contained genes associated with psychiatric or neurological disorders and were significant in multiple lines. The strongest (near GWS) consistent candidate region across all analyses and all breeds was the one located on SSC3 with one peak at 23.4 Mb, syntenic to a candidate region for bipolar disorder and another at 31.9 Mb, syntenic to a candidate region for human puerperal psychosis (16p13). From the haplotype/LD analysis, two regions reached genome wide significance (GWS): the first on SSC4 (KHDRBS3 to FAM135B), which was significant (-logP 5.57) in one Duroc based breed and is syntenic to a region in humans associated with cognition and neurotism; the second on SSC15, which was significant (-log10P 5.68) in two breeds and contained PAX3, which is expressed in the brain.

[Pseudoexfoliation syndrome: no central zone of pseudoexfoliation material in patients with pseudophakia - a clinical study]. / Pseudoexfoliationssyndrom: Fehlen der zentralen Zone des Pseudoexfoliations-Materials bei Patienten mit Pseudophakie - eine klinische Studie.

BACKGROUND, MATERIAL AND METHODS: 1. An evaluation of medical findings and photodocumentation of 6 patients with pseudoexfoliation (PEX) material on the anterior surface of posterior chamber intraocular lenses was undertaken. Molecular genetic analysis of mutations in LOX-L1 was performed in order to confirm the association with pseudoexfoliation syndrome or glaucoma. Age of patients, the maximal intraocular pressure and perimetry with Octopus and Goldmann perimeters were documented as well as the time between implantation of the posterior chamber lens and diagnosis of pseudoexfoliation material on the anterior surface of posterior chamber lens. 2. Consecutive examinations of 35 patients with pseudoexfoliation syndrome or -glaucoma and pseudophakia were made to evaluate the frequency of patients with pseudoexfoliation material on the anterior surface of posterior chamber lenses. RESULTS: 1. The characteristic formation of stripe-shaped peripheral pseudoexfoliation material is seen in all examined patients on the anterior surface of posterior chamber lenses, but there is no central homogeneous round zone of pseudoexfoliation material in all patients. 2. the mean observation time of patients with pseudophakia and pseudoexfoliation syndrome or glaucoma is 4.4 ± 3.9 years. 5.7 % of the patients show pseudoexfoliation material in the periphery of posterior chamber lenses. The mean time between implantation of the intraocular lens and diagnosis of pseudoexfoliation material on the lenses is 3 years. CONCLUSIONS: The lack of a central homogeneous round zone of pseudoexfoliation material deposits on the anterior surface of posterior chamber lenses seems to be characteristic. The change in topography of PEX material on intraocular lenses is described here for the first time. A knowledge of this change in the topography of pseudoexfoliation material in pseudophakia is important for glaucoma screening, because pseudoexfoliation deposits can only be detected in mydriasis due to the peripheral location on the intraocular lens. Due to the old age of patients at the onset of pseudoexfoliation deposits, a pseudoexfoliation syndrome frequently is likely to develop after cataract surgery in many patients.

Usefulness of post mortem determination of serum tryptase, histamine and diamine oxidase in the diagnosis of fatal anaphylaxis.

The diagnosis of fatal anaphylaxis can be difficult for clinical features may not always be evident in necropsy. Therefore post mortem determination of tryptase and other blood parameters can be helpful in verifying the diagnosis. We compared post mortem tryptase, histamine and diamine oxidase (DAO) serum levels of two patients who had died after a Hymenoptera sting and one patient who died of bronchospasm during anaesthesia with data obtained from 55 control subjects who had died from other causes than anaphylaxis. In the three anaphylactic cases, serum tryptase level was 880, 68 and 200 µg/l (normal range in living subjects: <11.4 µg/l), histamine was 37.5, 8.5 and 23.2 ng/ml (normal range: <0.3 ng/ml) and DAO was 1, 30 and 4 U/ml (normal range 10-30 U/ml), respectively. Values in the control group were as follows: tryptase 1-340 µg/l (mean 24.2 ± 58.2), histamine 5.0-22.0 ng/ml (mean 14.7 ± 3.9) and DAO 0-114 U/ml (mean 21.1 ± 27.8). 19/55 (34.5%) of the controls had elevated tryptase levels >11.4 µg/l, with four of them showing values >45 µg/ml. Significantly higher histamine levels were seen in blood samples taken more than 24h post mortem (p<0.05), whereas the timing of blood collection had no effect on tryptase and DAO levels. While moderately elevated tryptase levels are common in post mortem sera, values above 45 µg/l may support the diagnosis of fatal anaphylaxis. Strongly elevated histamine levels might give an additional clue on fatal anaphylaxis, whereas DAO does not seem to be helpful.

[Corneal epitheliopathy following trabeculectomy with postoperative adjunctive 5-fluorouracil]. / Korneale Epitheliopathie nach Trabekulektomie mit postoperativer subkonjunktivaler 5-Fluorouracil-Injektion.

PURPOSE: The success of trabeculectomy in glaucoma not sufficiently controlled by maximal medical therapy substantially depends on postoperative scarring of the filtering bleb. This process of scarring can be inhibited by antimetabolites like mitomycin C (MMC) and 5-fluorouracil (5-FU). The aim of this study is the evaluation of incidence and long-term outcome of corneal surface defects and intraocular pressure following MMC- or 5FU-trabeculectomy using different doses of postoperative 5FU. METHODS: A retrospective, non-randomised comparative study of 381 patients undergoing trabeculectomy with intraoperative application of either 5FU (group A, n = 169) or MMC (group B, n = 212) was performed. Based on the Wuerzburg bleb classification score (WBCS) for postoperative wound healing evaluation, 30 of these operations of group A (group B: n = 26) did not receive 5 FU postoperatively (controls), 67 (93) received up to 7 postoperative injections of 5 mg 5 FU (normal dosage group), and 72 (93) received more than 7 injections (high dosage group). Surface epithelial defects were routinely assessed by slit-lamp microscopy and fluorescein staining. Intraocular pressure (IOP) was measured by Goldmann applanation tonometry. RESULTS: In the normal dosage group the mean total dose of 5 FU was 25.8 ± 9.1 mg in group A (group B: 28.4 ± 7.5 mg) and in the high dosage group 54.2 ± 10.9 mg 5 FU (51.7 ± 11.8 mg), respectively. Increased doses of postoperative 5 FU induced more frequent corneal erosions in both groups. Corneal erosions were seen in controls in 16.7 % (26.9 %), in the normal dosage group in 55.2 % (47.3 %) and in the high dosage group in 77.8 % (59.1 %) in group A and group B, respectively. The incidence of a corneal erosion between group A and group B did not differ significantly (p = 0.074). The mean reduction of intraocular pressure in mmHg did not show a significant difference 12 months after trabeculectomy between controls and postoperative 5-FU operations. CONCLUSION: In eyes with beginning scarring of the filtering bleb after trabeculectomy the subconjunctival injection of 5-FU allows a similar reduction of intraocular pressure as in eyes without scarring. Corneal epitheliopathy following trabeculectomy and postoperative 5 FU is dose-dependent with higher doses leading to a higher incidence of corneal erosions. As serious corneal long-term complications are rare, risk-benefit analysis justifies the application of 5-FU after filtrating glaucoma surgery.

Adult hippocampal neurogenesis is involved in anxiety-related behaviors.

Adult hippocampal neurogenesis is a unique example of structural plasticity, the functional role of which has been a matter of intense debate. New transgenic models have recently shown that neurogenesis participates in hippocampus-mediated learning. Here, we show that transgenic animals, in which adult hippocampal neurogenesis has been specifically impaired, exhibit a striking increase in anxiety-related behaviors. Our results indicate that neurogenesis plays an important role in the regulation of affective states and could be the target of new treatments for anxiety disorders.

[Anticipation in patients with iridescent multicoloured posterior capsular lens opacities ("Christmas tree cataract") : The Role in the diagnosis of myotonic dystrophy]. / Antizipation bei Patienten mit Christbaumschmuckkatarakt : Ihre Bedeutung für die Diagnose der myotonen Dystrophie.

BACKGROUND: Myotonic dystrophy (DM type 1) is the most common type of muscular dystrophy in adults, accompanied by myotonia, iridescent multicoloured posterior capsular lens opacities ("Christmas tree cataract", CTC), and, for example, cardiac arrhythmias and respiratory failure. A further feature is anticipation, which is the occurrence of increasing disease severity and decreasing age of onset in successive generations, depending on inherited unstable DNA sequences that become larger with each generation. AIM: To evaluate the frequency of clinically manifest DM in patients with CTC and the age at diagnosis of CTC. METHODS: Retrospective analysis of ophthalmologic, neurologic, and internal findings in 18 consecutively diagnosed patients with CTC. RESULTS: Three of 18 CTC patients showed clinical signs of DM. The mean age at diagnosis was 72,8+/-16,5 years (range 36-94 years). DISCUSSION: A relationship existed between CTC and manifest DM in 16.7% of the patients with CTC. A hypothesis states that the other 83.3% might have premutations in the DMPK gene, which might lead to a complete mutation after transmission through subsequent generations. In the meantime, molecular genetic DM tests are available. Because of clinical heterogeneity and the anticipation phenomenon in DM, confirmation with such molecular genetic DM tests should be obtained.

Anaesthetic management of a parturient with the postural orthostatic tachycardia syndrome: a case report.

Postural orthostatic tachycardia syndrome encompasses a group of disorders characterized by orthostatic intolerance. We describe the anaesthetic management of analgesia for labour and of Caesarean section in a parturient suffering from this disorder. Worsening of her symptoms during pregnancy was managed with an increase in the dose of beta-blockers taken by the patient. Epidural analgesia was instigated early to attenuate the stress of labour and avoid consequent triggering of a tachycardic response. Slow titration of epidural analgesia and anaesthesia after an adequate fluid preload was undertaken to minimize hypotension and subsequent tachycardia. Neuraxial opioid, combined with non-steroidal anti-inflammatory drugs and bilateral iliohypogastric and ilioinguinal nerve blocks were used to optimize postoperative analgesia.

A novel technique to measure position-dependent resistance changes in the vertebral arteries postmortem: new insights into the aetiology of SIDS?

AIM: A central respiratory regulation disturbance--triggered by impaired oxygen supply to the brainstem--is being discussed as an aetiological factor in sudden infant death syndrome. In this experimental study, further insight was sought into how far cervical spine movements may induce critical narrowing of the vertebral arteries. METHODS: In 10 infant bodies, the vertebral arteries were cannulated close to their origin and perfused with a fluid bolus of 5 ml in 2 s. The intravascular peak pressure created was memorized. Individual resistance indices were computed for every vertebral artery by relating the average pressure maximum from 10 measurements each with maximal rotation of the neck to either side alone and then with additional hyperextension of the cervical spine to the average peak pressure in neutral head position. RESULTS: Alterations of position-induced pressure changes occurred in the vertebral arteries of all children. Considering exclusively the combined movements of rotation plus extension, resistance increased ipsi- and contralaterally--no matter which side the head was turned--in three infants. A further three reacted with resistance surges only contralateral to the direction of rotation, and one only ipsilateral. Double contralateral associated with only one-directional ipsilateral rise was observed twice, and vice versa once. CONCLUSION: The presented method enables crude quantification of postmortem dynamic resistance alterations in the vertebral arteries. How far such measurements reflect authentic circulatory conditions during life remains to be assessed.

Platinum determination by inductively coupled plasma-sector field mass spectrometry (ICP-SFMS) in different matrices relevant to human biomonitoring.

The analytical challenges of Pt determination by ICP-SFMS posed by different human tissues and fluids have been critically assessed. Investigated samples were (1) urine, (2) serum of cancer patients sampled during chemotherapy with carboplatin, (3) microdialysates (20 micro L sample volume) collected from tumor and non-tumor tissue, and, finally-for the first time-(4) human lung tissue to study background concentrations of inhaled platinum. Sample preparation involved microwave digestion and open vessel treatment or simple dilution (microdialysates). Depending on the sample preparation and introduction systems used (microconcentric nebulization, ultrasonic nebulization with and without membrane desolvation) excellent procedural detection limits (3s criterion) of 0.35 pg g(-1) for urine, 420 pg g(-1) for serum, 400 pg g(-1) for lung tissue and 13 pg g(-1) for microdialysates could be obtained. Ultratrace concentrations of 1-40 pg g(-1), and 1000-3000 pg g(-1) were measured in urine and human lung tissue, respectively, as typical for samples in environmental studies. Quantification was carried out by IDMS and standard addition in the case of urine samples. Internal standardization could not correct for non-spectral interferences in external calibration. In the serum and microdialysates of patients during chemotherapy with carboplatin, elevated Pt levels ranging between 0.01 and 10 micro g g(-1) were determined by external calibration ((195)Pt isotope). For all investigated samples spectral interferences could be excluded by following different strategies. High-resolution control measurements ((194)Pt, (195)Pt) were performed in the case of elevated Pt levels, i.e. for microdialysates and serum samples. An Hf/Pt ratio of 0.4 was determined in human lung samples. An HfO formation ratio of 0.2% was assessed for standard solutions at the present experimental conditions, revealing that the contribution of (179)Hf(16)O, (178)Hf(17)O, (177)Hf(18)O to the (195)Pt isotope signal used for quantification was not significant.

Insulin rescues retinal neurons from apoptosis by a phosphatidylinositol 3-kinase/Akt-mediated mechanism that reduces the activation of caspase-3.

The ability of insulin to protect neurons from apoptosis was examined in differentiated R28 cells, a neural cell line derived from the neonatal rat retina. Apoptosis was induced by serum deprivation, and the number of pyknotic cells was counted. p53 and Akt were examined by immunoblotting after serum deprivation and insulin treatment, and caspase-3 activation was examined by immunocytochemistry. Serum deprivation for 24 h caused approximately 20% of R28 cells to undergo apoptosis, detected by both pyknosis and activation of caspase-3. 10 nm insulin maximally reduced the amount of apoptosis with a similar potency as 1.3 nm (10 ng/ml) insulin-like growth factor 1, which acted as a positive control. Insulin induced serine phosphorylation of Akt, through the phosphatidylinositol (PI) 3-kinase pathway. Inhibition of PI 3-kinase with wortmannin or LY294002 blocked the ability of insulin to rescue the cells from apoptosis. SN50, a peptide inhibitor of NF-kappaB nuclear translocation, blocked the rescue effect of insulin, but neither insulin or serum deprivation induced phosphorylation of IkappaB. These results suggest that insulin is a survival factor for retinal neurons by activating the PI 3-kinase/Akt pathway and by reducing caspase-3 activation. The rescue effect of insulin does not appear to be mediated by NF-kappaB or p53. These data suggest that insulin provides trophic support for retinal neurons through a PI 3-kinase/Akt-dependent pathway.

Effect of temperature on Lucilia sericata (Diptera: Calliphoridae) development with special reference to the isomegalen- and isomorphen-diagram.

Developmental behavior of eggs, larva and pupa of the blowfly species Lucilia sericata (Meigen) were studied under 10 different temperature regimes. Data from these studies were used to construct the isomegalen-diagram. In this diagram, time from hatching to peakfeeding is plotted against temperature, each line representing identical larval length at various temperatures. If the temperature is roughly constant, as is the case with corpses found indoors, the age of the maggot can be read off instantly from its length, provided that the maggot has not entered the migratory phase. Where temperature is variable, an age range can be estimated between the points where the measured larval length cuts the graph at the maximum and minimum temperatures recorded. Equally, the isomorphen-diagram representing all morphological stages from oviposition to eclosion should be used, if maggots in the migratory phase or pupae or puparia are recovered from the scene. The isomegalen- and the isomorphen-diagrams could facilitate a quick and more precise estimate of the postmortem interval even for the inexperienced investigator. In addition, our results vary from those of other investigators, suggesting a different thermal behavior of the holarctic blowfly L. sericata in various zoogeographic regions.

L-arginine chlorination products inhibit endothelial nitric oxide production.

The myeloperoxidase-derived oxidant hypochlorous acid (HOCl) is thought to contribute to endothelial dysfunction, but the mechanisms underlying this inhibitory effect are unknown. The present study tested the hypothesis that HOCl and L-arginine (L-Arg) react to form novel compounds that adversely affect endothelial function by inhibiting nitric oxide (NO) formation. Using spectrophotometric techniques, we found that HOCl and L-Arg react rapidly (k = 7.1 x 10(5) m(-1) s(-1)) to form two major products that were identified by mass spectrometry as monochlorinated and dichlorinated adducts of L-Arg. Pretreatment of bovine aortic endothelial cells with the chlorinated L-Arg metabolites (Cl-l-Arg) inhibited the -induced formation of the NO metabolites nitrate (NO(3)(-)) and nitrite (NO(2)(-)) in a concentration-dependent manner. Preincubation of rat aortic ring segments with Cl-L-Arg resulted in concentration-dependent inhibition of acetylcholine-induced relaxation. In contrast, blood vessels relaxed normally to the endothelium-independent vasodilator sodium nitroprusside. In vivo administration of Cl-L-Arg to anesthetized rats increased carotid artery vascular resistance. A greater than 10-fold excess of L-Arg was required to reverse the inhibitory effects of Cl-L-Arg in vivo and in vitro. Reaction of HOCl with D-arginine (D-Arg) did not result in the formation of inhibitory products. These results suggest that HOCl reacts with L-Arg to form chlorinated products that act as nitric-oxide synthase inhibitors.

[Drugs for young Mozart. Medical treatment of Wolfgang as a child by his father Leopold Mozart]. / Medikamente für den jungen Mozart. Die medizinische Behandlung des Kindes Wolfgang durch seinen Vater Leopold Mozart.

Leopold Mozart (1719-1787), father of Wolfgang Amadé, had profound medical knowledge and was a passionate medical dilettante. As long as the young Mozart lived with his father and travelled on his concert tours with him, Leopold cared for his son in medical matters. Doctors were only consulted occasionally. In the extensive correspondence of Mozart's father drugs and treatments used for Wolfgang Amadé are reported in detail. This represents a reliable description of the pharmacological therapies of the late 18th century. The mentioned drugs are, as far as possible, viewed from todays medical perspective.

Interlibrary loan in primary access libraries: challenging the traditional view.

INTRODUCTION: Primary access libraries serve as the foundation of the National Network of Libraries of Medicine (NN/LM) interlibrary loan (ILL) hierarchy, yet few published reports directly address the important role these libraries play in the ILL system. This may reflect the traditional view that small, primary access libraries are largely users of ILL, rather than important contributors to the effectiveness and efficiency of the national ILL system. OBJECTIVE: This study was undertaken to test several commonly held beliefs regarding ILL system use by primary access libraries. HYPOTHESES: Three hypotheses were developed. HI: Colorado and Wyoming primary access libraries comply with the recommended ILL guideline of adhering to a hierarchical structure, emphasizing local borrowing. H2: The closures of two Colorado Council of Medical Librarians (CCML) primary access libraries in 1996 resulted in twenty-three Colorado primary access libraries' borrowing more from their state resource library in 1997. H3: The number of subscriptions held by Colorado and Wyoming primary access libraries is positively correlated with the number of items they loan and negatively correlated with the number of items they borrow. METHODS: The hypotheses were tested using the 1992 and 1997 DOCLINE and OCLC data of fifty-four health sciences libraries, including fifty primary access libraries, two state resource libraries, and two general academic libraries in Colorado and Wyoming. The ILL data were obtained electronically and analyzed using Microsoft Word 98, Microsoft Excel 98, and JMP 3.2.2. RESULTS: CCML primary access libraries comply with the recommended guideline to emphasize local borrowing by supplying each other with the majority of their ILLs, instead of overburdening libraries located at higher levels in the ILL hierarchy (H1). The closures of two CCML primary access libraries appear to have affected the entire ILL system, resulting in a greater volume of ILL activity for the state resource library and other DOCLINE libraries higher up in the ILL hierarchy and highlighting the contribution made by CCML primary access libraries (H2). CCML primary access libraries borrow and lend in amounts that are proportional to their collection size, rather than overtaxing libraries at higher levels in the ILL hierarchy with large numbers of requests (H3). LIMITATIONS: The main limitations of this study were the small sample size and the use of data collected for another purpose, the CCML ILL survey. CONCLUSIONS: The findings suggest that there is little evidence to support several commonly held beliefs regarding ILL system use by primary access libraries. In addition to validating the important contributions made by primary access libraries to the national ILL system, baseline data that can be used to benchmark current practice performance are provided.

Superoxide reacts with nitric oxide to nitrate tyrosine at physiological pH via peroxynitrite.

Tyrosine nitration is a widely used marker of peroxynitrite (ONOO(-)) produced from the reaction of nitric oxide with superoxide. Pfeiffer and Mayer (Pfeiffer, S., and Mayer, B. (1998) J. Biol. Chem. 273, 27280-27285) reported that superoxide produced from hypoxanthine plus xanthine oxidase in combination with nitric oxide produced from spermine NONOate did not nitrate tyrosine at neutral pH. They suggested that nitric oxide and superoxide at neutral pH form a less reactive intermediate distinct from preformed alkaline peroxynitrite that does not nitrate tyrosine. Using a stopped-flow spectrophotometer to rapidly mix potassium superoxide with nitric oxide at pH 7.4, we report that an intermediate spectrally and kinetically identical to preformed alkaline cis-peroxynitrite was formed in 100% yield. Furthermore, this intermediate nitrated tyrosine in the same yield and at the same rate as preformed peroxynitrite. Equivalent concentrations of nitric oxide under aerobic conditions in the absence of superoxide did not produce detectable concentrations of nitrotyrosine. Carbon dioxide increased the efficiency of nitration by nitric oxide plus superoxide to the same extent as peroxynitrite. In experiments using xanthine oxidase as a source of superoxide, tyrosine nitration was substantially inhibited by urate formed from hypoxanthine oxidation, which was sufficient to account for the lack of tyrosine nitration previously reported. We conclude that peroxynitrite formed from the reaction of nitric oxide with superoxide at physiological pH remains an important species responsible for tyrosine nitration in vivo.