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Craniofacial and orthognathic surgery are high risk procedures for surgical blood loss. Significant blood loss leads to increased rates of blood product transfusion which may be associated with increased morbidity to the patient. The use of anti-fibrinolytics such as tranexamic acid has become popular in these procedures. However, the evidence to support its use in pediatric craniofacial and orthognathic surgery is sparse. This review analyzes the current randomized control trials assessing the use of tranexamic acid in craniofacial and orthognathic surgery. The study reviewed published literature up until December 20th, 2020. Six trials were included in this analysis. Pooled data showed that patients who received tranexamic acid during craniofacial or orthognathic surgery have less blood loss compared to those in control groups (mean difference—5.47 ml/kg [CI -7.02-3.82], P value

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a “Question Mark Ear” (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations.

OBJECTIVEDespite increasing adoption of endoscopic techniques for repair of nonsagittal single-suture craniosynostosis, the efficacy and safety of the procedure relative to established open approaches are unknown. In this systematic review the authors aimed to directly compare open surgical and endoscope-assisted techniques for the treatment of metopic, unilateral coronal, and lambdoid craniosynostosis, with an emphasis on quantitative reported outcomes.METHODSA literature search was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant articles were identified from 3 electronic databases (MEDLINE, EMBASE, and CENTRAL [Cochrane Central Register of Controlled Trials]) from their inception to August 2017. The quality of methodology and bias risk were assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies.RESULTSOf 316 screened records, 7 studies were included in a qualitative synthesis of the evidence, of which none were eligible for meta-analysis. These reported on 111 unique patients with metopic, 65 with unilateral coronal, and 12 with lambdoid craniosynostosis. For all suture types, 100 (53%) children underwent endoscope-assisted craniosynostosis surgery and 32 (47%) patients underwent open repair. These studies all suggest that blood loss, transfusion rate, operating time, and length of hospital stay were superior for endoscopically treated children. Although potentially comparable or better cosmetic outcomes are reported, the paucity of evidence and considerable variability in outcomes preclude meaningful conclusions.CONCLUSIONSLimited data comparing open and endoscopic treatments for metopic, unilateral coronal, and lambdoid synostosis suggest a benefit for endoscopic techniques with respect to blood loss, transfusion, length of stay, and operating time. This report highlights shortcomings in evidence and gaps in knowledge regarding endoscopic repair of nonsagittal single-suture craniosynostosis, emphasizing the need for further matched-control studies.

Introduction: Children with single suture craniosynostosis (SSC) are at risk for neurocognitive problems. The reported magnitude of differences between children with SSC and their normative peers on standardized tests of academic and intellectual ability are small. Evaluation of real-world academic outcomes of these children and its impact on educational resources have not been conducted. Methods: A retrospective cohort study of academic outcomes of children with SSC was conducted using the data from Ontario's Education Quality and Accountability Office (EQAO) standardized provincial reading, writing and mathematics tests. The need for special education was identified by documentation of the child's need for an Identification, Placement, and Review Committee (IPRC). Results: Of 296 eligible children, 42 participated in the study. Half of the children had sagittal synostosis, while the remaining were 10 (24%) unicoronal, 9 (21%) metopic, and 2 (5%) lambdoid synostosis. Thirty-six (86%) underwent operative management. The EQAO scores of operated children with SSC met the provincial academic standards on the Grade 3 and 6 EQAO scores across the 3 academic subjects. Converted grade-matched EQAO scores decreased in reading and writing over time, while math improved. Of the 21 patients with special education data, one child required an IPRC in Grade 3, while an additional four (24%) required an IPRC in Grade 6. Conclusions: Operated children with SSC had average academic performance, however, their needs appeared to change over time. Future studies are needed to evaluate academic difficulties and special education needs as these children progress through grade school.

In syndromic craniosynostosis, the Le Fort III osteotomy is used to correct dental/skeletal imbalance, improve exorbitism, and increase the airway. The purpose of this study is to perform a cost comparison between the standard technique of single-stage rigid internal fixation and distraction osteogenesis (DO) in the Le Fort III osteotomy in this patient population.Hospital cost accounting databases were queried for patients undergoing single-stage advancement (SS) or DO from 2007 to 2016. Nominal cost data were adjusted using the Bank of Canada Consumer Price Index. Reported costs represented the full length of stay for all utilization per patient. Demographic information and cost data for single-stage osteotomy and DO were compared.Total costs for single-stage (n = 8) were higher than distraction (n = 6; mean $CAD57 825 vs $38 268,This single-institution retrospective cost analysis indicates standard SS rigid internal fixation Le Fort III is more costly than DO. Despite higher OR costs, prolonged ICU and hospital stay was the primary reason behind this difference. This information may be of benefit when advocating for new technology perceived as high cost.En cas de craniosynostose syndromique, l’ostéotomie de Le Fort III permet de corriger un déséquilibre dentaire et squelettique, d’améliorer l’exophtalmie et de mieux ouvrir les voies respiratoires. La présente étude vise à comparer les coûts de la technique standard de fixation interne rigide en une étape à la distraction osseuse (DO) au sein de la population de patients en cas d’ostéotomie de Le Fort III.Les chercheurs ont fouillé les bases de données comptables des coûts hospitaliers pour les patients qui avaient subi un avancement en une étape (AUÉ) ou une DO entre 2007 et 2016. Ils ont rajusté les données sur les coûts nominaux à l’aide de l’indice des prix à la consommation de la Banque du Canada. Les coûts déclarés représentaient la durée totale de tous les séjours hospitaliers par patient. Ils ont comparé l’information démographique et les données sur les coûts de l’ostéotomie en une étape à la DO.Les coûts totaux de l'AUÉ (n = 8) étaient plus élevés que ceux de la DO (n = 6) (moyenne de 57 825 $ CA par rapport à 38 268 $,D’après la présente analyse rétrospective des coûts dans un seul établissement, la fixation interne rigide de l’AUÉ standard de Le Fort III est plus coûteuse que la DO. Malgré des coûts plus élevés en salle opératoire, un séjour prolongé à l’USI et à l’hôpital est la principale raison de cette différence. Cette information peut être utile pour défendre les nouvelles technologies qui sont perçues comme coûteuses.

Oxygen’s presence during thermal desorption of volatile organic compounds from activated carbon can promote heel build-up and loss of adsorption capacity. This study investigated the simultaneous effect of desorption temperature (200 °C and 288 °C) and oxygen concentration (≤5, 10,000, and 21,000 ppmv) on heel build-up. For this purpose, 5-cycle adsorption/desorption tests of 1,2,4-trimethylbenzene on a microporous activated carbon were completed. At low oxygen concentration (≤5 ppmv), desorption at 288 °C resulted in lower cumulative heel compared to at 200 °C; however, at high oxygen concentration (10,000 and 21,000 ppmv), desorption at 288 °C resulted in higher cumulative heel compared to 200 °C. Thermal gravimetric analysis (TGA) was used to assess the thermal stability of the heels formed on the samples. At high oxygen concentrations, the heel associated with desorption at 288 °C was more thermally stable than the heel formed at 200 °C, which can be attributed to thermal oxidation reactions of the adsorbate in the activated carbon pores.

This study elucidates the different mechanisms contributing to heel formation during cyclic adsorption–desorption of volatile organic compounds (VOCs) from a painting process in a full-scale adsorber-desorber. Two batches of beaded activated carbon (BAC), one subjected to normal operation and the other inadvertently exposed to oxygen during desorption, were investigated. Both batches displayed sharp increases in apparent density during early cycles, which indicate high heel formation due to occupation/blockage of high-energy adsorption sites. Thermogravimetric analysis and gas chromatography-mass spectrometry results identified non-desorbed adsorbates, adsorbate reaction by-products and char from adsorbate decomposition. The main heel formation mechanisms include physisorption and chemisorption followed by thermal oxidation, pyrolysis and eventually char formation. We hypothesize that non-ideal heat and purge gas distribution across the desorber is the reason for the accumulation of non-desorbed species and heel formation, shortening the lifetime of the adsorbent. In addition to pyrolysis reactions that partially contributed to heel formation in the absence of oxygen, accumulation of thermal oxidation products also contributed to the deterioration of adsorbent performance in the presence of oxygen during desorption. Moreover, extended exposure of the non-desorbed physisorbed and chemisorbed heel species to repetitive desorption cycles ultimately transformed them to permanent (non-desorbable) heel via polymerization and char formation. Therefore, to reduce heel buildup and maximize long-term adsorber performance, it is recommended to (i) ensure effective desorption conditions to prevent or minimize the accumulation of non-desorbed physisorbed species, and (ii) maintain sufficiently low oxygen levels in the desorption purge gas to minimize the detrimental effects of any species that do accumulate.

The adsorption of 1,2,4-trimethylbenzene (TMB) on beaded activated carbon (BAC) in a six-stage countercurrent fluidized bed adsorber was simulated employing a two-phase model, assuming the gas in particulate phase to be either in plug flow (EGPF model) or in perfectly mixed flow (EGPM model). A rather simple model considering equilibrium state on each stage (Equilibrium model) was also used for comparison. Simulation results were compared with experimental data obtained at different values of adsorbent feed rate, superficial gas velocity, TMB initial concentration and weir height (which influences the effective bed height). The results demonstrate that the Equilibrium model overpredicts the overall removal efficiencies when the adsorbate-adsorbent system is far from equilibrium condition. On the other hand, both EGPF and EGPM show good agreement with the experimental results over industrially relevant operating conditions. Stage-wise removal efficiencies show that the EGPF model tends to predict removal efficiency better than EGPM when the weir height is high. The sensitivity analysis of the EGPM model indicates that internal diffusion within the BAC is rate-limiting for adsorption, while BAC diameter strongly influences the overall removal efficiency and can be optimized for different conditions. The effect of changes in BAC adsorption capacity on overall removal efficiency depends on the number of available adsorption sites, as well as proximity to equilibrium condition. The model developed in this study is also able to predict the effect of the number of stages on overall removal efficiency of the adsorber. The results of this study could pave the way for optimizing the design and operation of fluidized bed adsorbers, leading to cost savings and performance improvements.

OBJECTIVEIn this systematic review and meta-analysis the authors aimed to directly compare open surgical and endoscope-assisted techniques for the treatment of sagittal craniosynostosis, focusing on the outcomes of blood loss, transfusion rate, length of stay, operating time, complication rate, cost, and cosmetic outcome.METHODSA literature search was performed in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant articles were identified from 3 electronic databases (MEDLINE, EMBASE, and CENTRAL [Cochrane Central Register of Controlled Trials]) from their inception to August 2017. The quality of methodology and bias risk were assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Effect estimates between groups were calculated as standardized mean differences with 95% CIs. Random and fixed effects models were used to estimate the overall effect.RESULTSOf 316 screened records, 10 met the inclusion criteria, of which 3 were included in the meta-analysis. These studies reported on 303 patients treated endoscopically and 385 patients treated with open surgery. Endoscopic surgery was associated with lower estimated blood loss (p < 0.001), shorter length of stay (p < 0.001), and shorter operating time (p < 0.001). From the literature review of the 10 studies, transfusion rates for endoscopic procedures were consistently lower, with significant differences in 4 of 6 studies; the cost was lower, with differences ranging from $11,603 to $31,744 in 3 of 3 studies; and the cosmetic outcomes were equivocal (p > 0.05) in 3 of 3 studies. Finally, endoscopic techniques demonstrated complication rates similar to or lower than those of open surgery in 8 of 8 studies.CONCLUSIONSEndoscopic procedures are associated with lower estimated blood loss, operating time, and days in hospital. Future long-term prospective registries may establish advantages with respect to complications and cost, with equivalent cosmetic outcomes. Larger studies evaluating patient- or parent-reported satisfaction and optimal timing of intervention as well as heterogeneity in outcomes are indicated.

Objective To investigate the stability of major versus minor Le Fort I maxillary advancements in unilateral cleft lip and palate (UCLP) patients. Design A retrospective longitudinal study was undertaken on 30 nonsyndromic UCLP patients treated with the same protocol at The Hospital for Sick Children, Toronto, Canada. Patients were grouped into major and minor movement groups based on planned surgical advancement. Standard lateral cephalometric radiographs were taken preoperatively (T1), immediately postoperatively (T2), and at least 1 year postoperatively (T3). Skeletal and dental variables were measured using cephalometric analysis. Stability was compared between groups using repeated-measures analysis of variance. Linear regression analysis was used to assess the relationship between advancement and relapse for the entire study population. Results A mean maxillary advancement of 9.8 mm and 4.9 mm was seen for the major (n = 10) and minor (n = 20) movement groups, respectively. The mean skeletal horizontal relapse was 1.8 mm (18%) for the major advancement group and 1.5 mm (31%) for the minor advancement group. There was no significant difference in skeletal horizontal relapse between the groups ( P > .05). The correlation coefficient ( r) between linear horizontal advancement and relapse was calculated to be .31 ( P > .05). Dental horizontal relapse was not significant for either the major or minor groups, and no significant difference was found between the groups ( P > .05) Conclusion Skeletal and dental relapse was found to be unrelated to the amount of maxillary linear advancement using conventional Le Fort I osteotomies in UCLP.

Lateral canthopexy is a commonly performed procedure in craniofacial and cosmetic surgery. In craniofacial surgery, lateral canthal fixation is performed in conjunction with a wide range of transcranial or subcranial procedures during the process of soft tissue re-suspension. A number of fixation materials have gained popular use. A case of craniofrontonasal dysplasia is reported in which a wire loop canthopexy fixation has become disengaged 3 months after a history of trauma and rotated to present a sharp surface against the sclera. Urgent surgical exploration prevented the apparently imminent complication of globe penetration with associated threat to vision.

Due to the rarity of arteriovenous malformations (AVMs), there is a paucity of information on the outcomes of various treatments. Presently, the mainstays of treatment of an AVM are embolization, surgical excision or a combination of both. A retrospective study of 26 patients with AVMs treated at The Hospital for Sick Children, Toronto, Ontario between 1985 and 1995 was performed. The treatment strategies and patient outcomes were compared in terms of efficacy, complications and the response of patients and their families to their overall treatment. The overall findings showed that embolization alone was effective in controlling symptoms, but may be associated with an increased AVM size. A partial excision of an AVM does not appear to exacerbate recurrence, as has been previously reported. In fact, even after what appears to be a complete excision of the AVM, recurrence may still occur. Complications from a surgical excision of the AVM are more frequent but less devastating than complications from embolization of the lesion. The overall patient or parent satisfaction with treatment was high with respect to improvement in outcome. It is expected that with an increasing understanding of vascular malformations, and the evolution of interventional radiological techniques, complications will decrease and results as a whole will improve.Compte tenu de leur rareté, on dispose de peu d’informations sur le résultat des divers traitements appliqués aux malformations artérioveineuses (MAV). À l’heure actuelle, le traitement d’une MAV repose sur l’embolisation, l’excision chirurgicale ou sur les deux approches combinées.Les auteurs ont procédé à une étude rétrospective de 26 cas de MAV traités au

Phillips John H. Victims of Crime, not Forgotten but Sufficiently Remembered ?. In: Revue internationale de droit comparé. Vol. 55 N°1, Janvier-mars 2003. pp. 47-55.

Progress toward the cyclobutane core of bielshowskysin is reported. The core was thought to arise from a cyclopropane intermediate via a furan-mediated cyclopropane fragmentation, followed by a 1,4-Michael addition. The synthesis of the cyclopropane intermediate utilizes a Suzuki coupling reaction, an esterification with 2-diazoacetoacetic acid, and a copper catalyzed cyclopropanation. An alcohol intermediate within the synthetic route was obtained in high enantiopurity via a highly selective palladium(II)-catalyzed oxidative kinetic resolution (OKR).

The bovine homologue of p65, a calmodulin-binding protein located in the membranes of synaptic vesicles and endocrine secretory granules, has been studied by the use of monoclonal antibodies directed against this antigen and against dopamine beta-mono-oxygenase. The protein (apparent molecular mass 67 kDa; pI = 5.5-6.2) is partially degraded by treatment with neuraminidase or endoglycosidase F. Trypsin treatment of intact adrenal chromaffin granules or of granule membranes releases a soluble 39 kDa fragment of p65 which corresponds to the whole of its cytoplasmic domain. This domain contains both the epitope for the monoclonal antibody cgm67 and the calmodulin-binding site. The 20 amino acids at the N-terminus of this fragment are identical to part of the rat p65 sequence.

A significant release of catecholamines within the heart has been observed during myocardial ischemia. Because this can be markedly inhibited by amine-uptake-blocking agents, it has been suggested that its mechanism is a carrier-mediated efflux from neurons, which is not operative under normal conditions. The present work examined this release process in chromaffin cells isolated from the bovine adrenal medulla, a model system for studying the sympathetic nervous system. Chromaffin cells in primary culture retained normal secretory responses for up to 7 days. Conditions designed to mimic ischemia, that is, anoxia or metabolic inhibition, resulted in a significant release of catecholamines. This release was shown to be independent of extracellular calcium but, in contrast to the release observed in ischemic hearts, was not inhibited by amine-uptake blockers. Electrophoresis with immunoblotting demonstrated that significant levels of the chromaffin granule protein, chromogranin A, were released during metabolic inhibition, indicative of an exocytotic mechanism. However, there was no release of the cytosolic protein, lactate dehydrogenase, indicating that there was no concomitant breakdown of the cell membrane. These results provide evidence for an exocytotic release of catecholamines mediated by the direct action of conditions of metabolic inhibition.

Pertussis toxin stimulates both basal and nicotine-evoked catecholamine secretion from intact bovine adrenal chromaffin cells, as well as Ca2+-evoked release from permeabilized cells. Tetanus toxin inhibits all these effects; it reduces the secretion of intact cells treated with pertussis toxin to the basal level, and decreases by about 50% Ca2+-evoked release from permeabilized cells whether or not previously stimulated by pertussis toxin.

Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment was continued for > or = 10 days and for as long as there was a response. The majority of subjects (91%), had previously failed paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril. The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril. Microbiologic response is variable and relapse high. Rash is a major limiting side effect of the drug.

Chromaffin granules, the secretory vesicles of the adrenal medulla, have a Na+/H+ exchange activity in their membranes which brings their proton gradient into equilibrium with a Na+ gradient. This explains why Na+ is mildly inhibitory to amine transport (which is driven by the H+ gradient) The activity can be demonstrated by using accumulation of 22Na+ in response to a pH gradient that is either imposed by diluting membrane ‘ghosts’ into alkaline media, or generated by ATP hydrolysis. It can also be monitored indirectly by fluorescence measurements in which the pH inside ‘ghost’ is monitored by quenching of a fluorescent weak base. This method has been used to monitor Na+ entry into acid-loaded Șghosts’ of H+ entry into methylamine accumulation. The exchanger appears to be reversible and non-electrogenic, with a stoichiometry of 1:1. Using an indirect assay we measured an apparent Km for Na+ of 4.7 mM, and a Ki for amiloride, a competitive inhibitor, of 0.26 mM. Direct assays using 22Na+ suggested a higher Km. Ethylisopropylamiloride was not inhibitory.

In August 1983, a study on parasites, diseases, and health status was conducted on sympatric populations of fallow deer (Dama dama) and white-tailed deer (Odocoileus virginianus) from Land Between The Lakes, Lyon and Trigg counties, Kentucky. Five adult deer of each species were studied. White-tailed deer had antibodies to epizootic hemorrhagic disease (EHD) virus and Leptospira interogans serovariety icterohemorrhagiae, and fallow deer had antibodies to bluetongue and EHD viruses. Serologic tests for bovine virus diarrhea virus, infectious bovine rhinotracheitis virus, parainfluenza3 virus, and Brucella spp. were negative. One white-tailed deer had an infectious cutaneous fibroma, and one fallow deer had pulmonary mucormycosis. White-tailed deer harbored 16 species of parasites, all of which are considered typical of the parasite fauna of this host in the southeastern United States. Fallow deer harbored nine species of parasites, including eight species known to occur in white-tailed deer on the area and one species (Spiculopteragia assymmetrica) that is not. All fallow deer had inflammatory lesions in the spinal cord and/or brain that were attributed to prior infection with meningeal worm (Parelaphostrongylus tenuis), indicating that P. tenuis infections are not always fatal for this species. The apparent high rate of exposure of Land Between The Lakes fallow deer to P. tenuis without a resultant high rate of clinical cerebrospinal parelaphostrongylosis is hypothesized to be due to a low prevalence and intensity of P. tenuis, partial innate resistance of fallow deer, and acquired immunity.

The neurosurgeon and plastic surgeon are increasingly called upon to manage the care of patients with combined injuries of the cranium and face. The authors briefly review the pathogenesis and classification of craniofacial fractures and outline historical approaches to them. Current principles of management are then discussed. Experience with 167 patients is presented with emphasis on surgical technique, the sequence of repair and early primary reconstruction. The controversial issue of fontal sinus fracture repair is addressed. The authors favour preservation of the frontal sinus cavity, where possible, and do not obliterate the nasofrontal duct. With injuries to the floor of the sinus, the base of the sinus and frontonasal duct are sealed with bone graft and a vascularised soft tissue flap and the sinus is cranialised. Immediate bone grafts, using split skull or rib, are used to reconstruct areas of bony destruction or loss. Ninety-eight patients required 402 grafts. Immediate bone grafting resulted in few complications and low incidence of secondary deformities needing correction.

We have measured the contents of Na+ and K+ in isolated chromaffin granules. Total contents varied between 227 and 283 nmol/mg of protein, equivalent to matrix concentrations of 53-66 mM. The value found depended on the isolation buffer used, and the ratio of the two ions reflected the composition of the buffer. We then measured the free concentration of each of these ions, and of Ca2+, in the matrix, by using a null-point method with acridine-fluorescence quenching. This monitored H+ fluxes induced by an ionophore in the presence of known concentrations of the ion in the supporting medium. In contrast with organic constituents of the matrix, which have low activity coefficients, Na+ and K+ were found to have activity coefficients around 0.8 Ca2+, however, was strongly bound: its free concentration was only 0.03% of the total.

Isolated chromaffin granules aggregate reversibly in the presence of Ca 2+ and Mg 2+ . The adhering membranes maximise their areas of contact, leading to distortions of the granules and, in many cases, to membrane rupture. The adhesion is accompanied by changes in the structure of the core: it is seen to withdraw from regions of the membrane that are involved in adhesion to other granules, although it remains in contact with the membrane at other places. At the same time the osmotic pressure within the granules increases and their soluble components are released to the medium. These processes can occur at 0 °C, and at low pH, as well as at room temperature and pH 7. Similar reorganisation of membranes and cores may occur during the process of Ca 2+ -dependent exocytosis in secretion.

Two experiments are described, which involved the investigation of interactions between the nature of the conditioned stimulus (CS) and the nature of the unconditioned stimulus (UCS) in producing signal-centered behavior. In Experiment 1, rats received response-independent heat reinforcement in a cold environment. For some groups, this heat UCS was signaled by presentations of a standard aluminum retractable lever; for other groups, it was signaled by a retractable lever covered in acrylic fur (furry lever CS). Only the subjects that received the furry lever CS paired with heat exhibited differential CS-contact behavior, when compared with unpaired, aluminum lever, and warm control subjects. In Experiment 2, hungry rats received pairings of either an aluminum or a furry lever with food (UCS). When compared with unpaired controls, only the subjects that received the aluminum lever paired with food showed differential signal-directed behavior; the subjects receiving the furry lever CS did not show differential contact with the CS, but instead exhibited differential food tray entry behavior during CS presentation. In the two studies, the signal-directed behavior exhibited by subjects resembled either thermoregulatory or feeding behaviors characteristic of rats. The results suggest that signal-directed behavior is determined by a complex interaction between the ecological relevance of the CS and the nature of the UCS—an interaction that can best be described in terms of a behavior systems model of conditioned responding.

The organisation of the protein components of bovine chromaffin granules has been investigated by labelling or digesting intact granules or broken membranes with the following reagents: lactoperoxidase/Na125I as a reagent for tyrosine residues, N- (iodoacetylaminoethyl)-5-naphthylamine-1-sulphonic acid as a reagent for cysteine residues, pronase, and galactose oxidase/KB3H4. Following treatment, membranes were purified and washed and proteins were examined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Rather more than 60 bands were resolved, of which about 40 were relatively intense and reproducible. The bands were classified according to their molecular weights and sensitivity to reagents. Penetration of the membranes by the reagents was assessed by examination of intragranular proteins. The majority of chromaffin granule membrane polypeptides became labelled when intact granules were treated with impermeant reagents. Eleven were probably protected in the intact granules, reactive sites becoming exposed only on membrane lysis. By contrast, carbohydrate moieties of glycoproteins appear to be exposed only on the matrix side of the membrane. Two proteins were shown to span the membrane, although this is probably an underestimate.

A method is described for the preparation of resealed chromaffin-granule ghosts'.Thelysisandraπdpurificationproceduresprovghosts′.Thelysisandraπdpurificationproceduresprovghosts' in approximately 70% yield from crude granules; the preparation contains 0.1μmol of catecholamine/mg of protein (as compared with 2.8μmol/mg in unlysed granules), of which about one third is inside the ghosts'.Theghosts′.Theghosts' retain their ability to accumulate catecholamines, a process dependent on Mg-ATP and inhibited by reserpine, and a simple assay for this transport is described.

Tissue mast cells have been a source of great curiosity since their conclusive description by Ehrlich over 80 years ago. They have been implicated in a vast majority of connective tissue reactions both of physiologic and pathologic nature. In some species at least, mast cells have been implicated in the production, storage and release of potent cardiovascular substances including heparin, serotonin and histamine. The present report is directed particularly toward man. Evidence is presented suggesting that human tissue cells previously lumped into one large group on the basis of granular metachromasia and termed tissue mast cells, represent at least two morphologically distinct cellular types. Difference in function of these cells may be great. There is evidence that one type may be a local tissue source for epinephrine, norepinephrine, or both. It is suggested that mast cells as a whole may represent a spectrum of cell types having numerous differences in ultrastructure and function. It is believed that their continued study in various physiologic and pathologic states should prove fruitful.

1. In the purple sea urchin the digestion and absorption of the C14-labelled constituents of the alga, Iridaea, occur mainly in the esophagus and adjacent festoons of the stomach.2. The fauna and flora of the sea urchin gut do not appear to he involved in this digestive process.3. The absorbed materials arc stored mainly in the wall of the gut.4. During absorption there is a diffusion of labelled material into the plasma of the perivisceral fluid. A peak level is reached around the sixth hour after the start of feeding. Galactose accounts for 90% of this material and must have been liberated enzymatically from galactose-containing compounds such as galactosyiglycerol.5. The peak level of activity is replaced by a prolonged interval in which the level of activity is reduced hut quite constant. The radioactivity is distributed over a variety of compounds including both amino acid and carbohydrates.6. Translocation of nutrients is accomplished by the perivisceral fluid. No evidence for the participation of e...

Four patients with idiopathic enlargement of the right atrium are described. All patients were evaluated carefully by clinical means and two were subjected to extensive investigation including cardiac catheterization, angiocardiography, and intracavitary electrocardiography. The diagnosis of idiopathic enlargement of the right atrium is based primarily on radiographic examination with exclusion of other causes of right atrial enlargement by appropriate clinical and laboratory means. In the patients studied no cause for the right atrial abnormality could be established. Nonetheless, it is concluded that this disease is a distinct clinical entity that deserves further recognition and investigation.

Electrocardiographic analysis of the P wave occurring in a series of 36 patients with benign atrial fibrillation compared with similar analysis in a control group of normal subjects is reviewed. No statistically significant differences were noted in the Macruz index, height of the P wave in lead II, or P initial force V 1 when compared to controls. However, the values obtained for P terminal force V 1 , P total force V 1 (algebraic product of the total duration and total amplitude of the P wave in lead V 1 ), and the ratio of both these values in the patient group were significantly different from the control group. The existence of a minor intra-atrial conduction block in patients with benign atrial fibrillation is suggested.

Certain interesting gross pathologic features of the heart and aorta as seen in routine autopsy specimens of patients who die from malignancy and other cachectic states have been correlated with clinical, electrocardiographic and roentgenologic features and collectively described under the term “cachetic heart.” The pathogenesis of this entity remains obscure at the present time. A few postulates are discussed in light of certain observations made in experimental animals in which cancer was induced. At present, the entity is usually diagnosed in retrospect. However, with better recognition of certain diagnostic criteria outlined in this report, it should not be difficult to establish the diagnosis during life.

Transfer ribonucleic acid (tRNA) that is deficient in methyl groups may be detected in logarithmically growing Saccharomyces cerevisiae . The amount of methyl-deficient tRNA is not constant throughout the logarithmic phase, but is maximal about one generation before the onset of the late growth phase. During this latter phase, the tRNA is fully methylated. The methyl-deficient tRNA is present during a period of high metabolic activity of the cell, characterized by increased RNA and protein content.

1. Brief exposure to tritiated thymidine in vivo or in vitro labels some of the bladder-filiform amebocytes, colorless spherule amebocytes and eleocytes circulating in the perivisceral coelomic fluid of the purple sea urchin; circulating vibratile cells are not labeled. Some colorless spherule amebocytes and eleocytes are also labeled while wandering in the body wall and gut wall.2. Some, and presumably all, of the circulating coelomocytes which synthesize DNA subsequently divide in the circulation. It is not known if this proliferation constitutes all or only a part of production of new bladder-filiform amebocytes, colorless spherule amebocytes and eleocytes in the sea urchin.3. The tritium indices of the circulating bladder-filiform amebocytes, colorless spherule amebocytes and eleocytes within each inidividual urchin are significantly correlated. This suggests that DNA synthesis in these circulating cells is under the control of one or more common factors.4. Brief exposure to tritiated thymidine labels...

Phosphorylation of bovine chromaffin granules by ATP leads to the formation of diphosphoinositide in the granule membrane. Both phosphatidylinositol kinase and its substrate are components of this membrane, and triphosphoinositide is not formed under the conditions of the assay. The reaction is Mg(2+)-dependent and is stimulated by Mn(2+) and F(-) ions. The initial reaction is rapid, with a broad pH profile and a ;transition' temperature for its activation energy at 27 degrees C. The apparent K(m) for ATP is 5mum. ATP, N-ethylmaleimide, Cu(2+) ions and NaIO(4) are inhibitory. The phospholipids of chromaffin-granule membranes have been analysed: 6.8% of the lipid P is found in phosphatidylinositol, and only 2-3% in phosphatidylserine. Comparison of the rate of phosphorylation of intact and lysed granules suggests that the sites for phosphorylation are on the outer (cytoplasmic) surface of the granules, and diphosphoinositide may therefore make an important contribution to the charge of the chromaffin granule in vivo.

These studies demonstrated the existence of chromaffin-reacting granules in the human skin. The chromaffin reaction was provided by bichromate fixation. Subsequent special staining by the modified Sevki procedure revealed these granules to be localized usually to characteristic long, eel-like cells with distinctive tinctorial features. Although the true significance of these cells is not certain, they are believed to represent the local source of a vasopressor material for the peripheral tissues. Much indirect physiologic evidence supports this belief.

Methyl-deficient transfer ribonucleic acid (tRNA) is found in certain methionine auxotrophs of Saccharomyces cerevisiae during logarithmic growth (at one generation time before the late growth phase) and during residual growth in the absence of exogenous methionine. The former effect seems to be accounted for by the general increase in RNA synthesis that occurs at the time; there is no specific synthesis of tRNA in the absence of ribosomal RNA synthesis, nor is the methyl group deficiency limited to a single tRNA species. During methionine starvation, all species of tRNA are methyl-deficient, but this occurs only in strains with certain blocks in the methionine pathway. The kinetics of disappearance of the methyl group donor, S -adenosylmethionine, during starvation of D73 (which accumulates methyl-deficient tRNA), do not differ from other strains, but D73 loses the methylase inhibitor, S -adenosylhomocysteine, much more slowly.

The use of electrocardiographic leads taken during inspiration has long been advocated to aid in evaluation of possible P wave, QRS, and T wave abnormalities. Their use in the uncovering of rhythm abnormalities has not been emphasized. Careful observation of leads III and AVF taken during the act of ispiration for a period of one month revealed that the greatest value of these leads (III-2 and AVF-2) was in the provocation and clarification of cardiac arrhythmias. The clinical implications of these findings are discussed.

V A R I A T I O N IN THE TIME INTERVALS OF waves of atrial activity (P-P interval) has been observed to occur frequently in both complete and incompkte atrioventricular block and also in interference diisociation.'" The w a l observation is that those P-P intervals containing QRS complexes are shorter in duration than those not containing a ventricular deflection. Rarely the relationship is revelsed so that the P-P intervals without QRS complexes are the shorter ones. This phenomenon has been termed ventriculophasic sinus arrhythmia.'"' The mechanism of such alternating lengths of the sinus cycles is not known, although the rule of arterial vagal presoreceptors, mechanical traction on the atrium, and alternating changes in sinus

1. A method of obtaining purified suspensions of nematocysts has been developed, and a method of obtaining the toxin they contain has been described.2. A method of assay, using inhibition of the righting response of Littorina planaxis, has been shown to be applicable for toxicity titrations.3. Further work on the chemical and immunochemical characterization of the toxin is planned, as well as the use of the toxin for studies of antitoxic immunity in marine invertebrates.

Information about the in vitro effects on chromaffin granule structure of agents such as Ca’+ ions which are implicated in the release of the granule contents in vivo [l] may help to elucidate the processes involved. In this communication the changes observed in the light scattering intensity and dissymmetry ratio of isolated, purified chromaffin granules are examined as a function of time in relation to possible changes in the size and structure of the granules. The chromaffin granules of the adrenal medulla cells store catecholamines and ATP in high concentrations and release these into the blood stream in response to stimulation of the cells by sympathetic nerves. The release most probably occurs by exocytosis [2], a process in which the granule and plasma membranes become confluent such that the granule contents, but not its membrane constituents, come to lie in the extracellular space (fig. 1). Size and shape changes in subcellular particles can be studied by electron microscopy, but since the