A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs

The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and infl ammation, but without any infl uence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs). This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and lefl unomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive ("therapeutic pyramid") or of more aggressive treatment, through the simultaneous use of two or more DMARDs ("combination therapy")

A short history of anti-rheumatic therapy. II. Aspirin

The discovery of aspirin, an antipyretic, anti-inflammatory and analgesic drug, undoubtedly represents a milestone in the history of medical therapy. Since ancient times the derivatives of willow (Salix alba) were used to treat a variety of fevers and pain syndromes, although the first report dates back to 1763 when the English Reverend Edward Stone described the effect of an extract of the bark willow in treating malaria. In the XIX century many apothecaries and chemists, including the Italian Raffaele Piria and Cesare Bertagnini, developed the biological processes of extraction and chemical synthesis of salicylates, and then analyzed their therapeutic properties and pharmacokinetic and pharmacodynamic characteristics. In 1899 the Bayer Company, where Felix Hoffmann, Heinrich Dreser and Arthur Eichengrun worked, recorded acetyl-salicylic acid under the name "Aspirin". In the XX century, besides the definition of the correct applications of aspirin in the anti-rheumatic therapy being defined, Lawrence L. Crawen identified the property of this drug as an anti-platelet agent, thus opening the way for more widespread uses in cardiovascular diseases

[Filippo Civinini (1805-1844) and the discovery of plantar neuroma].

Pathological abnormality (neuroma) related to the painful foot condition commonly called "Morton's metatarsalgia" was first observed in 1835 by Filippo Civinini (1805-1844) of Pistoia, in course of a cadaverous dissection, and clearly described in the anatomic letter entitled "Su un nervoso gangliare rigonfiamento alla pianta del piede" ("On the neural gangliar swelling of the foot sole"). In this study a brief review on the history of Morton's metatarsalgia is carried out, and the importance of Civinini in the discovery of the neuroma of the III intermetatarsal web is underlined

Wars in the history of rheumatology

Some important discoveries in the history of rheumatology happened during war periods. It is well known that arthritis associated with conjunctivitis and urethritis, following dysenteric episodes, has been described during the First World War from the German Hans Reiter and, nearly contemporarily, from the French Noel Fiessinger and Edgar Leroy. Less known is instead the fact that the first cases of sympathetic algoneurodystrophy have been reported by the American Silas Weir Mitchell in soldiers wounded by fire-arms, during the Civil War of Secession. Other war episodes have been crucial for the development of some drugs now abundantly applied to the care of rheumatic diseases. The discovery of therapeutic effects of immunosuppressive agents, in fact, happened as an indirect consequence of the use of poison gas, already during the First World War (mustard gas), but above all after an episode in the port of Bari in 1943, where an American cargo boat was sunk. It had been loaded with a quantity of cylinders containing a nitrogenous mustard, whose diffusion in the environment provoked more than 80 deaths owing to bone marrow aplasia.Moreover, the history of the cortisone shows a strict link to the Second World War, when Germany imported large quantities of bovine adrenal glands from Argentina, with the purpose of producing some gland extracts for the Luftwasse aviators, in order to increase their performance ability

A short history of anti-rheumatic therapy. I. An introduction on traditional and drug treatments

The origins of anti-rheumatic therapy are very old and mainly related to the use of traditional, sometimes extravagant, treatments, as a part of folk medicine. Spa therapy has long been used for the treatment of rheumatic diseases, as well as, in later times, physical treatments, including electrotherapy. Drug treatment has developed beginning from substances of vegetable origin, such as willow and colchicum extracts. Then it has been spread out through the chemical synthesis of compounds with specific action and therefore more effective, owing to the great development of pharmaceutical industry

The main stages in the history of systemic lupus erythematosus

Systemic lupus erythematosus can be considered the most characteristic and important among the connective tissue diseases. In this short review the main stages of its history are sketched, from the introduction of the term "lupus", traditionally attributed to Roger Frugardi, in 1230 (but in fact already documented in the 10th century) to the actual knowledge of its clinical and laboratory aspects. Initially considered exclusively of dermatological interest, the first to describe a systemic form with visceral involvement were Moriz Kohn Kaposi and William Osler. Significant contribution was also given by serological diagnosis, and in particular, by the identification of specific markers of disease, such as anti-native DNA and anti-Sm antibodies, allowing early diagnosis and the establishment of an adequate therapy

Double Channel Neural Non Invasive Blood Pressure Prediction

Cardiovascular Diseases represent the leading cause of deaths in the world. Arterial Blood Pressure (ABP) is an important physiological parameter that should be properly monitored for the purposes of prevention. This work applies the neural network output-error (NNOE) model to ABP forecasting. Three input configurations are proposed based on ECG and PPG for estimating both systolic and diastolic blood pressures. The double channel configuration is the best performing one by means of the mean absolute error w.r.t the corresponding invasive blood pressure signal (IBP); indeed, it is also proven to be compliant with the ANSI/AAMI/ISO 81060-2:2013 regulation for non invasive ABP techniques. Both ECG and PPG correlations to IBP signal are further analyzed using Spearman’s correlation coefficient. Despite it suggests PPG is more closely related to ABP, its regression performance is worse than ECG input configuration one. However, this behavior can be explained looking to human biology and ABP computation, which is based on peaks (systoles) and valleys (diastoles) extraction

Towards Uncovering Feature Extraction from Temporal Signals in Deep CNN: The ECG Case Study

Despite all the progress made in biomedical field, the Electrocardiogram (ECG) is still one of the most commonly used signal in medical examinations. Over the years, the problem of ECG classification has been approached in many different ways, most of which rely on the extraction of features from the signal in the form of temporal or morphological characteristics. Although feature engineering can led to adequately good results, it mostly relies on human ability and experience in selecting the correct feature set. In the last decade, a growing class of techniques based on Convolutional Neural Network (CNN) has been proposed in opposition to feature engineering. The efficiency and accuracy of CNN-based approaches is indisputable, however their ability in extracting and using temporal features from raw signal is poorly understood. The main objective of this work was to uncover the differences and the relationships between CNN feature maps and human-curated temporal features, towards a deeper understanding of neural-based approaches for ECG. In fact, the proposed study succeeded in finding a similarity between the output stage of the first layers of a deep 1D-CNN with several temporal features, demonstrating that not only that the engineered features effectively works in ECG classification tasks, but also that CNN can improve those features by elaborating them towards an higher level of abstraction

A Comparison of Deep Learning Techniques for Arterial Blood Pressure Prediction

Continuous vital signal monitoring is becoming more relevant in preventing diseases that afflict a large part of the world’s population; for this reason, healthcare equipment should be easy to wear and simple to use. Non-intrusive and non-invasive detection methods are a basic requirement for wearable medical devices, especially when these are used in sports applications or by the elderly for self-monitoring. Arterial blood pressure (ABP) is an essential physiological parameter for health monitoring. Most blood pressure measurement devices determine the systolic and diastolic arterial blood pressure through the inflation and the deflation of a cuff. This technique is uncomfortable for the user and may result in anxiety, and consequently affect the blood pressure and its measurement. The purpose of this paper is the continuous measurement of the ABP through a cuffless, non-intrusive approach. The approach of this paper is based on deep learning techniques where several neural networks are used to infer ABP, starting from photoplethysmogram (PPG) and electrocardiogram (ECG) signals. The ABP was predicted first by utilizing only PPG and then by using both PPG and ECG. Convolutional neural networks (ResNet and WaveNet) and recurrent neural networks (LSTM) were compared and analyzed for the regression task. Results show that the use of the ECG has resulted in improved performance for every proposed configuration. The best performing configuration was obtained with a ResNet followed by three LSTM layers: this led to a mean absolute error (MAE) of 4.118 mmHg on and 2.228 mmHg on systolic and diastolic blood pressures, respectively. The results comply with the American National Standards of the Association for the Advancement of Medical Instrumentation. ECG, PPG, and ABP measurements were extracted from the MIMIC database, which contains clinical signal data reflecting real measurements. The results were validated on a custom dataset created at Neuronica Lab, Politecnico di Torino

[A short history of anti-rheumatic therapy--V. analgesics].

The pharmacological treatment of pain has very ancient origins, when plant-derived products were used, including mandrake extracts and opium, a dried latex obtained from Papaver somniferum. In the XVI and XVII centuries opium came into the preparation of two compounds widely used for pain relief: laudanum and Dover's powder. The analgesic properties of extracts of willow bark were then recognized and later, in the second half of the XIX century, experimental studies on chemically synthesized analgesics were planned, thus promoting the marketing of some derivatives of para-amino-phenol and pyrazole, the predecessors of paracetamol and metamizol. In the XX century, nonsteroidal anti-inflammatory drugs were synthesized, such as phenylbutazone, which was initially considered primarily a pain medication. The introduction on the market of centrally acting analgesics, such as tramadol, sometimes used in the treatment of rheumatic pain. is quite recent