The effect of combined antenatal vitamin K and phenobarbital therapy on umbilical blood coagulation studies in infants less than 34 weeks' gestation

OBJECTIVE: To determine if antenatal vitamin K and phenobarbital therapy affect coagulation studies in umbilical blood at birth, and to provide 95% reference ranges for umbilical blood coagulation parameters in premature gestations. METHODS: Patients at imminent risk for spontaneous or indicated premature delivery less than 34 weeks' gestation were randomized to receive either placebo or vitamin K and phenobarbital. Prothrombin time (PT), activated partial thromboplastin time (PTT), functional coagulation factors, and decarboxylated prothrombin assays were performed on umbilical blood specimens. Decarboxylated prothrombin, also known as "protein induced by vitamin K absence-factor II" or precursor prothrombin, is a sensitive marker for vitamin K deficiency. Standardized values of PT and PTT are reported in seconds and standardized values of factor assays in percentage of normal adult functional activity (mean +/- one standard deviation). RESULTS: Newborns in the placebo and treatment groups had similar umbilical blood PT (12.6 +/- 1.2 versus 12.7 +/- 1.4 seconds), PTT (48.8 +/- 13.4 versus 49.6 +/- 13.8 seconds), and functional activity of factor II (40.3 +/- 12.5 versus 42.0 +/- 12.1%), factor VII (67.0 +/- 20.9 versus 66.8 +/- 18.9%), factor IX (27.4 +/- 12.8 versus 25.8 +/- 8.9%), and factor X (47.0 +/- 12.8 versus 49.2 +/- 11.6%). Newborns in the treatment group were about half as likely as those in the placebo group to have detectable decarboxylated prothrombin levels in umbilical blood at birth (gestational age-adjusted odds ratio 0.47, 95% confidence interval 0.22-1.01; P = .05). CONCLUSIONS: Combined maternal therapy with vitamin K and phenobarbital before premature delivery does not affect umbilical blood PT, PTT, or functional activity of vitamin K-dependent coagulation factors II, VII, IX, and X. However, it is associated with the reduced presence of decarboxylated prothrombin in umbilical blood at birth. There is significant improvement in umbilical blood coagulation tests as gestational age advances from 24 to 34 weeks.     

Arginine 206 of the C5a receptor is critical for ligand recognition and receptor activation by C-terminal hexapeptide analogs

C5a is a 74-amino-acid glycoprotein whose receptor is a member of the rhodopsin superfamily. While antagonists have been generated to many of these receptors, similar efforts directed at family members whose natural ligands are proteins have met with little success. The recent development of hexapeptide analogs of C5a has allowed us to begin elucidation of the molecular events that lead to activation by combining a structure/activity study of the ligand with receptor mutagenesis. Removal of the hexapeptide's C-terminal arginine reduces affinity by 100-fold and eliminates the ability of the ligand to activate the receptor. Both the guanidino side chain and the free carboxyl of the arginine participate in the interaction. The guanidino group makes the energy-yielding contact with the receptor, while the free carboxylate negates "electrostatic" interference with Arg-206 of the receptor. It is the apparent movement Arg-206 induced by this set of interactions that is responsible for activation, since conversion of Arg-206 to alanine eliminates the agonist activity of the hexapeptides. Surprisingly, activation is a nearly energy-neutral event and may reflect the binding process rather than the final resting site of the ligand.     

Impact of asphalt concrete fatigue endurance limit definition on pavement performance prediction

Many well-constructed Hot Mix Asphalt pavements have been in service for 40 or more years without any evidence of fatigue cracking. This field experience suggests that there exists a strain level, known as the fatigue endurance limit (FEL), below which an asphalt concrete pavement will not exhibit fatigue cracks. Several studies have been conducted to define and verify this limit. Each of these methods is associated with certain assumptions regarding the nature of the FEL and heretofore a comprehensive comparison of each has not been made using a consistent set of mixtures. Likewise, the impact of any observed differences in FEL on the predicted pavement performance has not been made. This paper investigates and compares six different methods for identifying the FEL: NCHRP 9–44A approach, simplified viscoelastic continuum damage model, smeared-healing with continuum damage model, plateau value approach, pseudo-strain analysis method, and reduced cycles method. Each method is found to yield different values ranges from approximately 30–170 microstrains at 21.1 °C. The predicted FEL from each of the six methods are then used with the mechanistic empirical design algorithm to evaluate their effects on predicted pavement performance. Simulation outputs show different pavement performance and perpetual pavement structural design thicknesses from each of the methods. The study outcomes are expected to benefit future field verification research of FEL as it provides comprehensive analyses using six different methods. This future verification research may indicate the method that best represents actual perpetual pavement design and performance.     

Communal Foraging Behavior and Recruitment Communication in Gloveria sp.

The caterpillars of Gloveria sp. mark trails with a pheromone they deposit by dragging the ventral surface of the tip of the abdomen along branch pathways as they move between their communal nest and distance feeding sites. The threshold sensitivity of the caterpillar for an extract prepared from the secretory site was approximately 0.5 × 10^–3 caterpillar equivalents/cm of trail. Bioassays show that Gloveria follows neither authentic trails of Malacosoma americanum nor artificial trails prepared from 5-cholestane-3-one, a chemical previously reported to elicit trail following from other social caterpillars. Although our observations show that fed caterpillars mark heavily as they return to their nest, we found no evidence that individual caterpillars are able to recruit hungry nestmates to new food finds. In this species, recruitment to food occurs only after many caterpillars have reinforced a trail to a newly discovered food source. In contrast, hungry caterpillars of the confamilial species M. americanum, tested under identical conditions, responded strongly to the postprandial trails of individual caterpillars and rapidly abandoned depleted sites in favor of new food finds. We postulate that the difference in the efficiency with which these two species recruit nestmates to food evolved in response to differences in the spatial distribution of their food supplies.     

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.     

Penile erection in response to remote cues from females: albino rats severely impaired relative to pigmented strains

Male rats have been observed to display erections when exposed to inaccessible estrous females, and it was suggested that these "noncontact erections" (NCEs) represent a species-typical response that may index sexual arousal. Initial efforts in other laboratories to repeat and extend this research were unsuccessful, and it appeared that differences in the rat strains being used might be responsible. To address this question NCE tests were given to rats of two albino strains, Wistar and Sprague-Dawley, and two pigmented strains, hooded Long-Evans and inbred Brown Norway. A high proportion of Long-Evans and Brown Norway rats displayed NCEs, whereas Wistar and Sprague-Dawley albino rats rarely did. Additional experiments did not reveal the reasons for the strain difference in NCE, but they provided evidence against hypotheses based on the relative erectogenic effect of albino and hooded estrous females, the attention paid to estrous females, the motor repertoire, or erectile function per se. Albinism-related neural pathology, possibly outside of the visual system, may contribute to the deficit in NCE in albino rats.     

1H-NMR resonance assignments, secondary structure, and global fold of the TR1C fragment of turkey skeletal troponin C in the calcium-free state

The TR1C fragment of turkey skeletal muscle TnC (residues 12-87) comprises the two regulatory calcium binding sites of the protein. Complete assignments of the 1H-NMR resonances of the backbone and amino acid side chains of this domain in the absence of metal ions have been obtained using 2D 1H-NMR techniques. Sequential (i,i+1) and short-range (i,i+3) NOE connectivities define two helix-loop-helix calcium binding motifs, and long-range NOE connectivities indicate a short two-stranded beta-sheet formed between the two calcium binding loops. The two calcium binding sites are different in secondary structure. In terms of helix length, site II conforms to a standard "EF-hand" motif with the first helix ending one residue before the first calcium ligand and the second helix starting one residue after the beta-sheet. In site I, the first helix ends three residues before the first calcium ligand, and the second helix starts three residues after the beta-sheet. A number of long-range NOE connectivities between the helices define their relative orientation and indicate formation of a hydrophobic core between helices A, B, and D. The secondary structure and global fold of the TR1C fragment in solution in the calcium-free state are therefore very similar to those of the corresponding region in the crystal structure of turkey skeletal TnC [Herzberg, O., & James, M.N.G. (1988) J. Mol. Biol. 203, 761-779].     

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.     

Gram-negative anaerobic bacilli: Their role in infection and patterns of susceptibility to antimicrobial agents. II. Little-known Fusobacterium species and miscellaneous genera

Twenty infrequently reported species of gram-negative anaerobic bacilli other than Fusobacterium nucleatum, Fusobacterium necrophorum, and members of the genus Bacteroides were studied with regard to their role in infection and their susceptibility to antimicrobial agents. In addition, the literature regarding the recovery of these organisms from both the normal flora and infections of humans was reviewed. During a six-year period at the Wadsworth Clinical Anaerobic Bacteriology Research Laboratory (Veterans Administration Wadsworth Medical Center, Los Angeles, Calif.), 39 (6%) of 679 specimens obtained from anaerobic infections yielded "other gram-negative anaerobic bacilli" (OGNAB). Fusobacterium naviforme, Fusobacterium gonidiaformans, Fusobacterium varium, Fusobacterium mortiferum, and Fusobacterium russii were the most commonly isolated OGNAB. Most of the OGNAB tested were resistant to erythromycin, and most strains, except for F. varium, were susceptible to beta-lactam antibiotics and clindamycin. Chloramphenicol and metronidazole were active against all strains of OGNAB tested. Certain Fusobacterium species are undoubtedly previously unrecognized members of the normal flora of the oropharynx, upper respiratory tract, or urogenital tract and may be present in infections derived from these floras.