Treatment of syphilis by arylarsonates

(1) The chief points about ATOXYL are its varying composition, its liability to contamination during the process of manufacture, its relative toxicity and its liability to decomposition under various physical and chemical conditions. Besides, there is its injurious action on the neuro-retinal visual apparatus. There is a conflict of opinion regarding its value. Although it is able to modify primary, secondary and various tertiary specific lesions, it fails in hereditary and parasyphilitic conditions. The fact that it sometimes succeeds where Mercury and the Iodides have failed, is no reason why it should be adopted as a routine mode of treatment in human Syphilis in view of the better results obtained by some of the newer arsenical preparations. The only conditions where it is likely to replace Mercury are in the various cases - already mentioned -- where that drug is contra-indicated or cannot be tolerated.(2) SOAMIN recommends itself to us on account of its definite chemical composition, its purity and relative non -toxicity. There is a unanimity of opinion as to its beneficial effects in primary, secondary and tertiary specific lesions. Authorities are also agreed as to its failure in hereditary and parasyphilitic conditions. It certainly succeeds where Mercury and the Iodides sometimes fail or are contra-indicated. Very seldom does it give rise to toxic effects or to visual disturbances. In conditions where Mercury is contra-indicated or useless, it is likely to replace it, and again in the Tropics where on account of the debility caused by climatic and malarial conditions it cannot be given. It certainly causes an increase in weight in almost every case and acts as a tonic in tropical debility. Its advantage over Mercury is that it causes no salivation, stomatitis or spongy gums. Likewise, in moderate remedial doses, it does not cause diarrhoea, a point of great value, as compared with Mercury, in the tropics where diarrhoea is such a prevalent disease or symptom.(3) ARSACETIN recommends itself to us on account of its purity, marked stability and the rapid manner in which it modifies all forms of the disease except hereditary and parasyphilitic ones. Compared with Soamin and Atoxyl, the weight of clinical evidence is 108. in its favour. It does not cause neuro-retinal ocular disturbances (like Atoxyl), is relatively nontoxic, well borne and certainly indicated where Mercury is useless or contra-indicated. When possible, it should be followed by a mercurial course, and is indicated in tropical conditions. Under its action, patients rapidly increase in weight and it acts indirectly as a tonic.Colonel Lambkin, in speaking of this drug and. Soamin, said that the good results he obtained in his cases strengthened his conviction that we had in them, a secondary specific for Syphilis, at least from a preventive and remedial point of view. As regards the former, he had then under his care cases with undoubted primary specific lesions which were treated with Soamin and which were closely observed every week for ten months without developing any further sign of the disease. From the remedial point of view the good results he obtained speak for it. But as a curative agent, it is beyond us all at present to give a positive answer to this all -important question; time and clinical experience alone would enable us to do so. This could not be done until it was proved beyond doubt that arylarsonates were capable of permanently expelling the spirochaetae pallida from the system, as indicated by the patient being rendored capable of re- infection. Neisser's successful experiments on apes from this point of view justified us in hoping for this end. Until the question as to the capability of arylarsonates bringing about a permanent cure was fully established, he would give Mercury after a course of treatment by arylarsonates. Later on, the same author(2)in speaking of the arylarsonates, said that our present knowledge of the power of these arsenical salts over Syphilis was in a very elementary stage, but he looked forward to further experience of them and improved technique leading us to that goal in the treatment of Syphilis which had already been attained with dourine. Regarding Arsacetin, Neisser(3)says that he has hitherto applied the mercurial and arsacetin treatment simultaneously, but perhaps they could be carried out alternately.(4) ARSENO-PHENYL-GLYCIN has been fully dealt with elsewhere and it only remains for me to say that, despite the brilliant results which follow its administration, there is no likelihood, on account of its instability and the inconvenient form in which it is supplied, of it ever replacing Mercury, and even other arylarsonates like Soamin, Arsacetin, Atoxylate of Mercury and Salvarsan in the treatment of human Syphilis.In reviewing the arylarsonates hitherto discussed and used before the introduction of Salvarsan and Mercury Atoxylate, Colonel Lambkin said that it was far too soon to express an opinion as to whether they were likely to prove of permanent benefit in Syphilis or whether they were likely to replace Mercury in the disease, but the results were encouraging. Whether they had any abortive or prophylactic effect on the future development of the disease after inoculation, he was unable to speak except to note that when given at an early date they delayed and modified considerably the secondary signs of the disease and that they had very beneficial effects on all specific mucous ulcerations. It was well established, he thought, that in the arylarsonates we had a second specific for Syphilis, the importance of which could not well be exaggerated.(5) In MERCURY ATOXYLATE we have a very potent drug exerting both the specific actions of Atoxyl and Mercury on the spirochaetae, both in vitro and in corpore. It is far more potent than Calomel injections alone. If applied to suitable cases and care taken in its administration, it is a safe drug. Lambkin and others who have used it, prefer it to Mercury over which it has a decided advantage in the rapidity with which it controls the symptoms of the disease. I am of opinion that this drug will certainly displace the mercurial treatment of Syphilis.(6) SALVARSAN or Ehrlich Hata's "606" is the most potent drug hitherto discovered and applied to the treatment of human Syphilis in its protean aspects. Its stability, non -toxicity, ease of administration, rapidity of action, the fact that it does not affect the neuro-retinal visual apparatus, all speak in its favour. It is indicated in all forms of the disease viz. primary, secondary, tertiary and hereditary lues, while it has a marked effect in combating some of the symptoms occurrinm_ in parasyphilis. It has yielded marvellous results in alleviating the various crises of locomotor ataxia of specific origin. With the doses at present used, cases have been said to recur, but Professor Herxheimer, Dr H. Isaac and others have never seen them. Dr Leonor Michaelis found that the recovery was absolute in a few days in most of his cases, while Dr Gourwitsch and S. Bormann selected cases which had been treated with the most powerful of mercurial methods and found that the comparison of these with Arseno-benzol proved the over-whelming value of the latter.By way.of conclusion, I may say that from a personal experience of the effects produced by Salvarsan and the reports of eminent authorities, that the drug is absolutely superior in Syphilis to any other known drug, and. that a single injection, in a suitable case, will produce results obtained only after years of_ treatment with Mercury. This latter drug, however, is not to be discarded because it seems to have been proved that there are strains of spiroçhaetaç that are arsenic-proof. In the same way, there are strains that are Mercury-proof. Perhaps by using one drug after the other we may be able to destroy all these various strains and so bring about a permanent cure of the disease.In spite of the pre-eminence of Salvarsan as the best curative and prophylactic agent hitherto discovered for Syphilis, I venture to state that the last word has not yet been spoken on the treatment of. Syphilis

Correspondence: Reply to ‘Numerical modelling of the PERM anomaly and the Emeishan large igneous province’

Tectonic plates and plate boundaries migrate substantially through time and mantle plumes are generally accepted to be mobile within the convecting mantle, but it has been proposed that large low shear velocity provinces (LLSVPs) could have been fixed and rigid for as much as 540 million years (Myr). The hypotheses of fixed and rigid LLSVPs cannot be easily tested in the absence of constraints on the past location of lowermost mantle structures. We evaluated the hypothesis9of lower mantle thermochemical structure fixity with numerical experiments. As in earlier studies, we argue that the location of lower mantle thermochemical structures has changed through time

Origin and evolution of the deep thermochemical structure beneath Eurasia

A unique structure in the Earth’s lowermost mantle, the Perm Anomaly, was recently identified beneath Eurasia. It seismologically resembles the large low-shear velocity provinces (LLSVPs) under Africa and the Pacific, but is much smaller. This challenges the current understanding of the evolution of the plate–mantle system in which plumes rise from the edges of the two LLSVPs, spatially fixed in time. New models of mantle flow over the last 230 million years reproduce the present-day structure of the lower mantle, and show a Perm-like anomaly. The anomaly formed in isolation within a closed subduction network ∼22,000 km in circumference prior to 150 million years ago before migrating ∼1,500 km westward at an average rate of 1 cm year^(−1), indicating a greater mobility of deep mantle structures than previously recognized. We hypothesize that the mobile Perm Anomaly could be linked to the Emeishan volcanics, in contrast to the previously proposed Siberian Traps

Propagation of social representations

Based on a minimal formalism of social representations as a set of associated cognems, a simple model of propagation of representations is presented. Assuming that subjects share the constitutive cognems, the model proposes that mere focused attention on the set of cognems in the field of common conscience may replicate the pattern of representation from context into subjects, or, from subject to subject, through actualization by language, where cognems are represented by verbal signs. Limits of the model are discussed, and evolutionist perspectives are presented with the support of field data

Elongation of confined ferrofluid droplets under applied fields

Ferrofluids are strongly paramagnetic liquids. We study the behavior of ferrofluid droplets confined between two parallel plates with a weak applied field parallel to the plates. The droplets elongate under the applied field to reduce their demagnetizing energy and reach an equilibrium shape where the magnetic forces balance against the surface tension. This elongation varies logarithmically with aspect ratio of droplet thickness to its original radius, in contrast to the behavior of unconfined droplets. Experimental studies of a ferrofluid/water/surfactant emulsion confirm this prediction.Comment: 12 pages, 7 figures. Submitted to Phys. Rev.

Altimeter processing tools for analyzing mesoscale ocean features

Satellite altimeters provide many opportunities for oceanographers to supplement their research with a valuable new data set. The recent GEOSAT exact repeat mission is the first of several altimeter missions proposed during the next decade. To utilize this new data, a software package was developed at the Woods Hole Oceanographic Institution and the University of Hawaii to facilitate the extraction of useful information from the NODC distributed GEOSAT data tapes. This software package was written with portability and modularity in mind. It should be possible to use this package with little or no modifications on data from future altimeters. The code was written in C and tested on Sun workstations and is oriented toward UNIX operating systems. However, since standard code was used, the programs should port easily to other computer systems. The modularity of the code should enable users to create additional programs. Additional programs designed to handle collocated water vapor corrections are also included for comparison.Funding was provided by the Office of Naval Research through Grant No. N00014-86-K-0751

Molecular Characteristics of Extraintestinal Pathogenic E. coli (ExPEC), Uropathogenic E. coli (UPEC), and Multidrug Resistant E. coli Isolated from Healthy Dogs in Spain. Whole Genome Sequencing of Canine ST372 Isolates and Comparison with Human Isolates Causing Extraintestinal Infections

Under a one health perspective and the worldwide antimicrobial resistance concern, we investigated extraintestinal pathogenic Escherichia coli (ExPEC), uropathogenic E. coli (UPEC), and multidrug resistant (MDR) E. coli from 197 isolates recovered from healthy dogs in Spain between 2013 and 2017. A total of 91 (46.2%) isolates were molecularly classified as ExPEC and/or UPEC, including 50 clones, among which (i) four clones were dominant (B2-CH14-180-ST127, B2-CH52-14-ST141, B2-CH103-9-ST372 and F-CH4-58-ST648) and (ii) 15 had been identified among isolates causing extraintestinal infections in Spanish and French humans in 2015 and 2016. A total of 28 (14.2%) isolates were classified as MDR, associated with B1, D, and E phylogroups, and included 24 clones, of which eight had also been identified among the human clinical isolates. We selected 23 ST372 strains, 21 from healthy dogs, and two from human clinical isolates for whole genome sequencing and built an SNP-tree with these 23 genomes and 174 genomes (128 from canine strains and 46 from human strains) obtained from public databases. These 197 genomes were segregated into six clusters. Cluster 1 comprised 74.6% of the strain genomes, mostly composed of canine strain genomes (p < 0.00001). Clusters 4 and 6 also included canine strain genomes, while clusters 2, 3, and 5 were significantly associated with human strain genomes. Finding several common clones and clone-related serotypes in dogs and humans suggests a potentially bidirectional clone transfer that argues for the one health perspective

An Extended Network of Genomic Maintenance in the Archaeon Pyrococcus abyssi Highlights Unexpected Associations between Eucaryotic Homologs.

In Archaea, the proteins involved in the genetic information processing pathways, including DNA replication, transcription, and translation, share strong similarities with those of eukaryotes. Characterizations of components of the eukaryotic-type replication machinery complex provided many interesting insights into DNA replication in both domains. In contrast, DNA repair processes of hyperthermophilic archaea are less well understood and very little is known about the intertwining between DNA synthesis, repair and recombination pathways. The development of genetic system in hyperthermophilic archaea is still at a modest stage hampering the use of complementary approaches of reverse genetics and biochemistry to elucidate the function of new candidate DNA repair gene. To gain insights into genomic maintenance processes in hyperthermophilic archaea, a protein-interaction network centred on informational processes of Pyrococcus abyssi was generated by affinity purification coupled with mass spectrometry. The network consists of 132 interactions linking 87 proteins. These interactions give insights into the connections of DNA replication with recombination and repair, leading to the discovery of new archaeal components and of associations between eucaryotic homologs. Although this approach did not allow us to clearly delineate new DNA pathways, it provided numerous clues towards the function of new molecular complexes with the potential to better understand genomic maintenance processes in hyperthermophilic archaea. Among others, we found new potential partners of the replication clamp and demonstrated that the single strand DNA binding protein, Replication Protein A, enhances the transcription rate, in vitro, of RNA polymerase. This interaction map provides a valuable tool to explore new aspects of genome integrity in Archaea and also potentially in Eucaryotes

Phase transitions in a ferrofluid at magnetic field induced microphase separation

In the presence of a magnetic field applied perpendicular to a thin sample layer, a suspension of magnetic colloidal particles (ferrofluid) can form spatially modulated phases with a characteristic length determined by the competition between dipolar forces and short-range forces opposing density variations. We introduce models for thin-film ferrofluids in which magnetization and particle density are viewed as independent variables and in which the non-magnetic properties of the colloidal particles are described either by a lattice-gas entropy or by the Carnahan-Starling free energy. Our description is particularly well suited to the low-particle density regions studied in many experiments. Within mean-field theory, we find isotropic, hexagonal and stripe phases, separated in general by first-order phase boundaries.Comment: 12 pages, RevTex, to appear in PR