Absolute configuration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol formed metabolically from 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone (NNK). Using the chiral derivatizing agent, (R)- (+)-alpha-methylbenzyl isocyanate [(R)-(+)-MBIC], previous work has shown that the enantiomeric ratio of metabolically formed NNAL and its glucuronide derivative may be species dependent. However, the absolute configuration of such NNAL has not been previously reported. Synthetically prepared racemic NNAL was converted to diastereomeric esters by reaction with (R)-(+)- and (S)-(-)-alpha-methoxy-alpha- (trifluoromethyl)phenylacetic acid (MTPA) chloride (Mosher's reagent) and the products were characterized by 1H-NMR. Based on chemical shift data, the absolute configuration of NNAL in each diastereomeric ester was assigned. Hydrolysis of (R)-NNAL-(R)-MTPA gave (R)-NNAL. This was converted to the corresponding carbamate by reaction with (R)-(+)-alpha- MBIC and the absolute configurations of the diastereomeric carbamates formed by reaction of (R)- and (S)-NNAL with (R)-(+)-MBIC were thereby assigned. Conversion of metabolically produced NNAL to the same carbamates allowed us to assign the NNAL formed from NNK by rat liver microsomes as (R)-NNAL. The major and minor NNAL-glucuronide diastereomers found in the urine of patas monkeys and humans exposed to NNK were similarly assigned; they were formed from (R)-NNAL and (S)- NNAL, respectively.      

Thoracic empyema: a study of 56 patients

Fifty seven children with thoracic empyema (37 boys and 20 girls) aged less than 12 years were seen at the University of Port Harcourt Teaching Hospital between January 1989 and December 1991. Staphylococcus aureus was the most common organism isolated from the pus of these patients (36 (63%) patients). Pseudomonas aeruginosa, the next most common organism, was isolated in 10 (18%) patients. The most common symptoms at presentation were acute illness with fever and cough (51 (89%) patients). All the patients were treated with closed intercostal tube drainage and appropriate antibiotics. Decortication was resorted to in only one patient. There were two deaths and the overall survival rate was 97%.     

Human myeloid precursors forming colonies in diffusion chambers expresses the Ia-like antigen.

Normal human bone marrow contains cells capable of forming myeloid colonies (CFU-DG) in fibrin clots in diffusion chambers placed in the peritoneal cavity of cyclophosphamide-treated mice. Evidence has accumulated indicating that these colony-forming cells represent an earlier stem cell than the granulocyte-monocyte precursor cell (CFU-C) assayed in soft agar. We provide data showing that these stem cells express the "Ia-like" or DR antigen. In the presence of rabbit Ia antiserum at a titer of 1:300, all CFU-DG were inhibited. Cytotoxicity was complement-dependent. Data are also presented that suggest that the megakaryocyte stem cell also expresses the Ia antigen.     

Human T lymphocyte response to Borrelia burgdorferi infection: no correlation between human leukocyte function antigen type 1 peptide response and clinical status

We tested the hypothesis that cross-reactivity between the outer surface protein A (OspA) of Borellia burgdorferi and human leukocyte function antigen (LFA) type 1 mediates chronic autoimmune sequelae of Lyme disease. T cell response was studied in subjects with Lyme disease presenting with erythema migrans alone (n=36), erythema migrans with neurological disease (n=12), and chronic Lyme disease syndrome (n=20), as well as healthy control subjects from Lyme-endemic (n=50) and -nonendemic (n=18) regions. Antigens included recombinant OspA and OspC (all strain B31) and human LFA-1 peptide (IYVIEGTSKQDLTSF). Proliferation to OspA was detected in 11 (28%) of 39 of subjects presenting with erythema migrans, which increased to 50% at 4 weeks of follow-up. Reactivity to OspA and LFA-1 was significantly correlated (P<.001) and was observed in 18 (78%) of 23 of OspA-responsive subjects. However, there was no correlation between T cell response to human LFA-1 peptide and clinical status.     

A comparison of visual analyses of intrapartum fetal heart rate tracings according to the new national institute of child health and human development guidelines with computer analyses by an automated fetal heart rate monitoring system

OBJECTIVES: The aim of this study was to compare the visual analyses of fetal heart rate tracings by observers according to recent National Institute of Child Health and Human Development interpretative guidelines both with each other and with those of a computerized fetal heart rate analysis and alerting system. STUDY DESIGN: One-hour sections of intrapartum fetal heart rate records were analyzed by a computerized monitoring system (Hewlett-Packard TraceVue; HP GmbH, B?blingen, Germany) and by 4 observers (a registered obstetric nurse, a certified nurse-midwife, an obstetrics resident physician, and a physician maternal-fetal medicine faculty member) instructed to use the new National Institute of Child Health and Human Development guidelines. We compared specific alerts, baseline rates, frequencies of accelerations and decelerations, and signal quality assessments generated by the TraceVue system and the observers. Power analysis indicated that 50 tracings were required to detect interobserver and observer-computer agreement levels of 80% +/- 10%. Statistical comparisons used kappa coefficient, chi(2) test, and analysis of variance with repeated measures as appropriate. RESULTS: Levels of agreement between observer pairs and the computer did not vary significantly across successive 10-minute intervals. Overall levels of interobserver agreement for baseline rate, tracing quality assessment, frequencies of accelerations and decelerations, and alerts ranged from 45% to 99% and were highest for baseline rate and signal loss and lowest for acceleration and deceleration counts. Interobserver agreement for alerts was relatively high (range, 72%-84%), with virtually no difference between any of the observers and the computer (range, 76.9%-79.2%; kappa = 0.25). CONCLUSION: Use of the National Institute of Child Health and Human Development guidelines for visual fetal heart rate interpretation did not increase agreements on most fetal heart rate features beyond those expected by chance or noted in previous reports. These guidelines did appear to blunt some interpretive differences, possibly as a result of observer background. Although levels of agreement on fetal heart rate features differed, agreements on clinical alerts were similar among all observers and a computerized fetal heart rate monitoring system. Computer analysis of fetal heart rate tracings could eliminate interobserver variation that results from visual analysis and could produce more consistent clinical responses to normal and abnormal fetal heart rate patterns.