On the history of Cinchona bark in the treatment of Malaria.

How and when the medical value of Cinchona bark was discovered is obscure, but it is said that the powder was given to a European for malaria for the first time in the 1630s. The bark was brought to Europe by Spanish missionaries and it was recommended by the cardinal Juan de Lugo. In the 1660s, the use of Cinchona bark became known in England - and in Denmark by Thomas Bartholin. It was used for the treatment of malaria, but several debates on its value continued up to the 1730s. However, successful treatment of malaria was obtained by Thomas Sydenham, Robert Tabor and Francesco Torti. Sydenham emphasized a modern view that Cinchona bark was a unique specific drug for the treatment of malaria, and the treatment was fully accepted when Torti's Therapeutice specialis appeared. In the early 18th century, botanical expeditions were arranged in search of the most valuable Cinchona species for cultivation. The content of quinine was impor- tant, and determination of quinine was realized when Pierre Pelletier and Joseph Caventou isolated the alkaloid from the bark in 1820. Dutch plantations and quinine industry dominated the market, but the supply of quinine came to an end when the Japanese occupied Indonesia in 1942, cutting off the rest of the world from the main supplies of Cinchona. Synthetic antimalarials were developed and chloroquine became the drug of choice, but the intensive use of these drugs caused drug resistance. Chloroquine-resistant strains of P. falciparum are now treated with other drugs as artemisinin and artemether.

The stethoscope - A 200th anniversary.

René T.H. Laënnec was the man who designed the first monaural instrument for mediate auscultation. The invention became a medical breakthrough. An instrument capable of enhancing the subtle sounds created by the human heart and lungs. This evolutionary instrument also had the benefit of decreasing the oftentim s too direct bodily contact between the doctor and the patient. Laënnec carefully described the different sounds created by the human organs and attempted to link them to the post mortem findings. Even though many doctors were enthusiastic regarding this new medical breakthrough, the stethoscope also had its opponents, but John Forbes' English translation of Laënnec's De l'auscultation midiate as well as William Stokes' treatise on the use of the stethoscope spread the news to the medical world. In Denmark the stethoscope was introduced by Oluf Lundt Bang, S.M. Trier and E. Hornemann. The next step forward was the develop- ment of the binaural stethoscope by G.P. Camman in New York. The Littmann Electronic Stethoscope (3M Health Care) created by David Littmann is considered the leading product globally in this medical field. Digitization, ultrasound and Doppler effect, as well as 2D and 3D printing, are evidence of an on-going evolution within this field of medical equipment as we get ready to celebrate the stethoscopes 200th anniversary.

[On the history of barbiturates]. / Pionerer bag barbituraterne.

Throughout the history of humanity, numerous therapeutic agents have been employed for their sedative and hypnotic properties such as opium, henbane (Hyoscyamus niger) and deadly nightshade (Atropa belladonna), but also alcohol and wine. In the 19th century potassium bromide was introduced as a sedative - and antiepileptic drug and chloral hydrate as sedative-hypnotics. A new era was reached by the introduction of barbiturates. The story started with the chemist Adolf von Baeyer. His breakthrough in the synthesis of new agents as barbituric acid and indigo and his education of young chemists was of great importance for the science of organic chemistry and the development of the dye and medicine industry in the late 19th century. The next important step was the development of barbiturates. The pioneers were Josef von Mering and Emil Fischer. Using the Grimaux-method they synthesized various barbiturates. It was von Mering who got the idea of introducing ethyl groups in the inactive barbituric acid to obtain sedatives, but the synthesis was succeeded by the chemist Emil Fischer. Experiments with dogs clearly showed sedative and hypnotic effect of the barbiturates and the oral administration of barbital (Veronal) confirmed the effect in humans. Barbital was commercialized in 1903 and in 1911 phenobarbital (Luminal) was introduced in the clinic, and this drug showed hypnotic and antiepileptic effects. Thereafter a lot of new barbiturates appeared. Dangerous properties of the drugs were recognized as abuse, addiction, and poisoning. An optimum treatment of acute barbiturate intoxication was obtained by the "Scandinavian method", which was developed in the Poison Centre of the Bispebjerg Hospital in Copenhagen. The centre was established by Carl Clemmesen in 1949 and the intensive care treatment reduced the mortality of the admitted persons from 20% to less than 2%. To-day only a few barbiturates are used in connection with anaesthesia and for the treatment of epilepsy, and chemists are focusing on drugs with more selective effects.

[On the history of vitamin K, dicoumarol and warfarin]. / Pionerer bag vitamin K, dikumarol og warfarin.

The history of the discovery and development of vitamin K and its antagonists, the oral anticoagulants dicoumarol and warfarin, are fascinating, triumphant landmarks in the annals of medicine. Vitamin K was found by Carl Peter Henrik Dam and Fritz Schønheyder from the University of Copenhagen. The discovery was initiated by Dam, by a lucky choice of chicks in the dissertation of sterol metabolism, since the vitamin is not formed by intestinal bacteria in these animals. In these experiments the lack of an unknown factor in the synthetic diet caused internal bleeding similar to that found in scurvy, but the bleeding was not reversed by vitamin C and it could not be explained by the lack of classical vitamins. In 1935 the unknown antihaemorrhagic factor was named vitamin K and a few months later the phenomenon was also observed by H.J. Almquist and E.L.R. Stokstad in Berkeley. The activity of the factor was determined by bioassay in different extracts of green vegetables and alfalfa by Dam and Schønheyder. Vitamin K was isolated in 1939 by Dam and Paul Karrer in Zurich and the structure was determined by Edward Adelbert Doisy. Dam and Doisy were awarded the Nobel Prize in 1943. A dramatic story starts the discovery of dicoumarol. In the 1920s cattle in Canada began dying of internal bleeding with no obvious precipitating cause. Frank W. Schofield, a veterinary pathologist in Alberta, found that the mysterious disease was connected to the consumption of spoiled sweet clover hay and noted a prolonged clotting time. Ten years after a farmer traveled in a blizzard with his dead cow and a milk can of the unclotted blood to the University of Wisconsin. Only the door to the biochemical department of Karl Paul Link was open. This event started the isolation of the anticoagulant agent dicou- marol which was formed by microbial induced oxidation of coumarin in the mouldy sweet clover hay. More than hundred dicoumarol-like anticoagulants were synthesized by Link and his co-workers. A potent hemorrhagic agent named warfarin was first used as an effective rat poison. However, warfarin became the drug of choice and the break- through in the treatment of thromboembolic diseases. Today new oral anticoagulants are competing with warfarin.

[History of gold--with danish contribution to tuberculosis and rheumatoid arthritis]. / Guld i medicinens tjeneste--Med traek af dansk indsats ved tuberkulose og reumatoid artrit.

Gold has a long history as a therapeutic agent, first as gold particles and colloidal gold, then as a soluble salt made by the alchemists, and potable gold was recommended almost as a panacea against different diseases. Gold compounds were introduced in the treatment of tuberculosis, based initially on the reputation of Robert Koch, who found gold cyanide effective against Mycobacterium tuberculosis in cultures. Although several investigations of gold salts showed no convincing effect in experimental tuberculosis in guinea pigs, the idea of using gold compounds as chemotherapy was furthermore encouraged from the work of Paul Ehrlich with arsenicals. The enthusiasm and the craving desperately for a remedy for tuberculosis forced Danish physicians, in the mid-1920s to treat tuberculosis with Sanocrysin (gold sodium thiosulfate). Professor Holger Møllgaard, in collaboration with the clinicians the professors Knud Secher and Knud Faber, was the theoretical promoter of the project. He recommended sanocrysin-antiserum therapy, since sanocrysin caused serious reactions in tuberculosis animals, possible by releasing toxins from tubercle bacilli "killed" by sanocrysin. However the enthusiastic response to sanocrysin in Europe declined along by controlled trials and reports on toxicity in the 1930s. The belief that rheumatoid arthritis was a form of tuberculosis caused a renaissance in chrysotherapy. In France Jacques Forestier obtained encouraging results in the treatment of rheumatoid arthritis with myochrysine and other gold salts, and he pointed out the disease modifying effect of chrysotherapy. In Denmark Knud Secher, who was the clinical initiator of Sanocrysin therapy in tuberculosis, now became the founder of chrysotherapy in rheumatoid arthritis. Although new potential agents are now taking over in the treatment of arthritis, it is still believed, that there is a place for the chrysotherapy. However a new future for gold, in the form of nanoparticles, appears on the horizon, especially in the imaging, diagnostics and therapies of cancer.

[Ambroise Paré (1510-90)--and features of the history of surgery]. / Ambroise Paré (1510-1590)--Traek af kirurgfagets historie og dets medi- kamentelle aspekter.

For six centuries the barbers of Europe practiced surgery. In 1215 a papal edict forbade members of the clergy (physicians) from performing surgical procedures as contact with blood was felt to be contaminating to men of the church. Bloodletting and minor surgery was now turned over to the barber-surgeons and this was in agreement with the medical doctors who felt that these procedures were beneath their dignity. The barber-surgeons were sometimes called "doctors of the short robe" to distinguish them from the medical doctors and surgeons who were called "doctors of the long robe", although university status was hardly given to the surgeons. Ambroise Paré started as a barber-surgeon and his eminence was honoured by the long robe. It was his experience at the Hôtel Dieu that permitted him to serve as a surgeon to the French army and through his open mind Paré made many innovations during his career. Paré abolished the painful practise of cautery to stop bleeding and used ligatures and dressings instead. A multitude of subjects were included in his writings such as military surgery, aneurysm, hernia, obstetrics and plague, and through his techniques he guided the development of the gentle art of surgery. Paré became the founder of modern surgery, a restorative process that heals the body with minimal suffering.

[From willow bark to acetylsalicylic acid]. / Fra pilebark til acetylsalicylsyre.

Acetylsalicylic acid is one of the most widely used drugs in the world. Its ancestry the salicylates, including salicin and salicylic acid, are found in the bark and leaves of the willow and poplar trees. The ancient Sumerians and Egyptians, as well as Hippocrates, Celsus, Pliny the Elder, Dioscorides and Galen used these natural products as remedies for pain, fever and inflammation. In the Middle Ages these remedies were used for fever and rheumatism by Hildegard of Bingen and Henrik Harpestreng. The first "clinical trial" was reported by Edward Stone in 1763 with a successful treatment of malarial fever with the willow bark. In 1876 the antirheumatic effect of salicin was described by T. MacLagan, and that of salicylic acid by S. Stricker and L. Riess. Acetylsalicylic acid was synthesized by Charles Gerhardt in 1853 and in 1897 by Felix Hoffmann in the Bayer Company. The beneficial effect of acetylsalicylic acid (Aspirin) on pain and rheumatic fever was recognized by K. Witthauer and J. Wohlgemuth, and the mechanism of action was explained in 1971 by John Vane. Today the antithrombotic effect of acetylsalicylic acid and new aspects of ongoing research demonstrates a still living drug.

[Mercury--a major agent in the history of medicine and alchemy]. / Kviksølv--et centralt stof i medicinens og alkymiens historie.

From ancient time the history of mercury has been connected with that of the medicine and chemistry. Mercury therefore contributes to the history of science throughout times. Knowledge of cinnabar (HgS) is traced back to ancient Assyria and Egypt, but also to China. The Greek philosophers were the initiators of theoretical science. The idea of the four elements, earth, air, water and fire, was introduced mainly by Empedocles and Aristotle in the 5th and 4th century BC. The theory encouraged the hope of transmuting metal to gold. The early development of practical alchemy is obscure, but some hints are given in the encyclopedia compiled by Zosimos about 300 A.D. in Alexandria. It also includes the invention of equipment such as stills, furnaces and heating baths. Medical treatment is described by Pliny and Celsus, e.g. the use of cinnabar in trachoma and venereal diseases. When the Arabs learned Greek alchemy by the Nestorians, they introduced or improved chemical equipments and new chemicals were obtained such as sublimate (HgCl2), different salts, acids, alkaline carbonates and metal oxides. The first recorded account of animal experimentation on the toxicity of mercury comes from Rhazes (al-Razi) in the 9th century and in the 11th century Avicenna (Ibn Sina) had the foresight to recommend the use of mercury only as an external remedy, and quicksilver ointments were used by the Arabs in the treating of skin diseases. In the medieval west scientific experiments were forbidden since the interpretation of the world order should not be changed. Greek and Arabic medicine and alchemy were therefore authoritative and the breakthrough in scientific inventions first appeared after the introduction of the Renaissance. The Renaissance medicine included ancient medicine as well as "modern medicine", based on iatrochemistry, and this chemical approach was introduced by Paracelsus. The medicine included sulphur and salts or oxides of for instance mercury, copper, iron, antimony, bismuth and lead. Most important was mercury when the outbreak of syphilis appeared in Europe at the end of the 15th century. The Arabian quicksilver ointment was remembered and used for the treatment of syphilis, but the treatment also included pills and ointments of sublimate and calomel (Hg2Cl2). The breakthrough in science was the discovery of oxygen by Priestley in the late 18th century. Priestley heated the oxide of mercury and examined the gas and thereafter Lavoisier recognized that combustion involves oxidation. All this led to a new understanding of respiration and furthermore established the basis of modern chemistry. The apothecaries of the 19th and 20th century showed many colourful mercurials as calomel, sublimate, cinnober, oxides of mercury and mercury. Calomel pills were used in acute and chronic diseases and furthermore as a diuretic drug before the organomercurials appeared in the 1920s. Skin diseases were treated with ointments or plasters of the mercurials or quicksilver. Antiseptics were introduced by Semmelweis hand-washing with chlorinated water before deliveries in obstetrics and by Lister's antiseptic ritual with carbolic acid during surgical operations. Also organomercurial "antiseptics" were used but unfortunately these agents were bacteriostatic rather than bacteriocidal and allergic contact dermatitis has been observed. Today the problems are solved by sterilization and aseptic conditions. Penicillin appeared in the 1940s and chlorothiazide in 1957 and new effective agents have taken over in the treatment of diseases with mercurials.

Potentiation of histamine release by Microfungal (1-->3)- and (1-->6)-beta-D-glucans.

(1-->3)-beta-D-Glucans, a cell wall component in most microfungi, are suggested to play a role in the development of respiratory and general symptoms in organic dust-related diseases. The mechanisms by which they induce these effects are, however, not clear. In the present study, mediator release and its potentiation by the (1-->3)-beta-D-glucan as well as by the (1-->6)-beta-D-glucan found in yeast and other fungi were therefore examined. Blood leucocytes from healthy volunteers and from patients allergic to house dust mite were incubated with (1-->3)-beta-D-glucans with increasing 1,6-branchings: curdlan [a linear (1-->3)-beta-D-glucan], laminarin and scleroglucan, and furthermore with pustulan, a linear (1-->6)-beta-D-glucan. Histamine release was not observed on exposure to the glucans only, but in the presence of anti-immunoglobulin E (IgE) antibody or specific antigens, all the glucans investigated led to an enhancement of the IgE-mediated histamine release. The glucans induced a significant potentiation of the mediator release when present at concentrations in the range of 2-5 x 10(-5) M. These results suggest that (1-->3)-beta-D-glucan as well as (1-->6)-beta-D-glucan aggravates IgE-mediated histamine release. Knowledge concerning the effects of glucans on immune responses may be of importance for understanding and treating inflammatory and allergic diseases.

Epithelial cell kinetics of the gastric mucosa during Helicobacter pylori infection.

Helicobacter pylori is an important pathogen in major gastroduodenal diseases, including inflammation with ulceration and gastric malignancies. Alterations in H. pylori associated cell turnover in gastric epithelial cells are examined in relation to inflammatory activity, bacteria load and cytokines which may improve knowledge concerning the outcome of gastric diseases caused by H. pylori. Antral biopsies from 42 dyspeptic patients including 27 H. pylori-positive and 15 H. pylori-negative patients were tested for apoptotic activity by the TUNEL assay, and immuno-histochemically for p53 and the proliferative marker Ki-67. H. pylori infection, bacteria load and inflammatory activity were associated with increased cell turnover as judged by enhanced activities of TUNEL, p53 and Ki-67. Only p53 was significantly correlated to IFN-gamma, IL-8 and IL-10. The H. pylori-positive state was furthermore accompanied by varying degrees of altered distribution pattern of the markers studied, with occasional presence of apoptosis in the deeper pit zones, upward extension of Ki-67 and to a lesser degree of p53. Given a similar pattern of change in proliferation and apoptosis in some neoplastic lesions in other parts of the gastrointestinal tract, such studies in cell turnover may provide insights valuable in the investigations of potential precursors of gastric malignancies.

[Pictures from the Dolphin Pharmacy in Copenhagen]. / Billeder fra Delfin Apoteket i København.

The development of the pharmacy in the 19th and 20th centuries is illustrated by education and activity in the Dolphin Pharmacy in Copenhagen. The career within chemistry and pharmacy started with an apprenticeship of 4 year in the pharmacies. The Dolphin Pharmacy was responsible for part of the examination, i.e. the examination of the preparation of medicine. Passing the examination the chemist's assistant was free to prepare and to dispense medicine. Graduation as a pharmaceutical candidate was necessary to obtain license. Lectures in chemistry, physics, pharmacy, botany and pharmacognosy were obtained at the University of Copenhagen and the Polytechnic, but no curriculum was available. A rational education was obtained later on by the establishment of the School of Pharmacy in 1892. The proprietor pharmacists of the Dolphin Pharmacy were excellent scientists who contributed to the development of pharmacy. Pictures of the pharmacy from about the 1930s show the manufacture of medicines on the basis of a prescription and a pharmacopoeia. Ointments containing zinc white, sulphur and tar were used for various skin diseases and for the tiresome cough; cough mixtures containing codeine or extract of ipecacuanha root were used. In the 1930s the medicine for injection was sterilized and the tablet machine was the breakthrough for a rational production in the pharmacy. However, at the end of the 1900s it was no more possible to compete with the pharmaceutical industry and all the production of medicine was taken over by the industry.

[On the history of injection]. / Traek af injektionens historie.

Although the effect of snake bites and poisoned arrows was known from ancient time, the development of the syringe and the needle lasted several centuries. Forms of intravenous injection and infusion are clearly documented in the 1650s. Sir Christopher Wren used a syringe made of animal bladder fixed to a goose quill to inject wine and opium into the veins of dogs. J.D. Major from Kiel and J.S. Elsholtz from Berlin probably were the first to deliberately administer intravenous injections to people in the 1660s. However, these early injections were not successful and injections did not come into fashion again until the latter part of the 1800s. Forerunners of subcutaneous administration were either the introduction of the drug under the epidermis by means of a vaccination-lancet or the application of a vesicant to remove the epidermis, after which the drug was applied to the denuded cutis. Lafargue, Lembert and Lesieur described these methods in the first half of the 1800s, and the methods continued to be of use in the second part of the century until the advent of subcutaneous injection. Alexander Wood of Edinburgh and Charles-Gabriel Pravaz from Lyon are known commonly as the inventors of the syringe for subcutaneous injection, but other pioneers such as Taylor, Washington and Rynd had already begun this form of administration. Increased use, safety and accuracy were accomplished by the progressive steps introduced by Wood, Pravaz and Luer. Thus, the syringe of Luer was fitted for aseptic heating, and a sharp needle readily perforated the skin. Sterilization by heating in an autoclave was developed by Pasteur, Chamberland and Koch, after managing aseptic conditions by the addition of preservatives such as carbolic acid. A safe method for the storage of sterile injectates was provided by Limousin's ampoule from 1886, and later by the introduction of multi-dose containers. The evolution of the syringe and its needle continues with the introduction of transdermal drug delivery by micron-scale needles and monitored drug delivery.

Gastric inflammatory markers and interleukins in patients with functional dyspepsia, with and without Helicobacter pylori infection.

Helicobacter pylori is the most important cause of gastritis, peptic ulcers and the development of gastric cancer. The chronic active inflammation is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins (IL-8, IL-10 and IFN-gamma) are involved in the inflammatory process in the gastric mucosa. The aim of this study was to investigate the gastric inflammation in patients with functional dyspepsia. Fifty-three consecutive patients were included and antral biopsies were obtained for histology, culture and immunohistochemistry. The sections were examined for the interleukins IL-4, IL-6, IL-8, IL-10 and IFN-gamma as well as for the cell markers CD4, CD8, CD14, Cd19, CD25 and CD30. Only CD4 and CD19 were significantly increased in patients with increased gastric inflammation and increased density of H. pylori. However, several of the examined markers (IFN-gamma, IL-8, IL-10 and CD14) showed a non-significant trend to be increased in patients with extensive gastric inflammation and high density of H. pylori. Therefore, an arbitrary index (IM11) for all the 11 immunological markers was made as an average value for each of the four morphological groups. For the four morphologically different groups of patients the values were 0.49, 0.77, 0.86 and 1.25, respectively. Significant increases in the index from none to moderate antral inflammation as well as the density of H. pylori were found (p<0.001). By using an index of inflammatory markers trends can be summarized and thereby significant which may be of importance when gastric inflammation is investigated in children and patients with functional dyspepsia.

[History of opium poppy and morphine]. / Opiumsvalmuen og morfin gennem tiderne.

Opium has been known for millennia to relieve pain and its use for surgical analgesia has been recorded for several centuries. The Sumerian clay tablet (about 2100 BC) is considered to be the world's oldest recorded list of medical prescriptions. It is believed by some scholars that the opium poppy is referred to on the tablet. Some objects from the ancient Greek Minoan culture may also suggest the knowledge of the poppy. A goddess from about 1500 BC shows her hair adorned probably with poppy-capsules and her closed eyes disclose sedation. Also juglets probably imitating the poppy-capsules were found in that period in both Cyprus and Egypt. The first authentic reference to the milky juice of the poppy we find by Theophrastus at the beginning of the third century BC. In the first century the opium poppy and opium was known by Dioscorides, Pliny and Celsus and later on by Galen. Celsus suggests the use of opium before surgery and Dioscorides recommended patients should take mandrake (contains scopolamine and atropine) mixed with wine, before limb amputation. The Arabic physicians used opium very extensively and about 1000 AD it was recommended by Avicenna especially in diarrhoea and diseases of the eye. Polypharmacy, including a mixture of nonsensical medications were often used. Fortunately for both patients and physicians many of the preparations contained opium. The goal was a panacea for all diseases. A famous and expensive panacea was theriaca containing up to sixty drugs including opium. Simplified preparations of opium such as tinctura opii were used up to about 2000 in Denmark. In the early 1800s sciences developed and Sertürner isolated morphine from opium and was the founder of alkaloid research. A more safe and standardized effect was obtained by the pure opium. Several morphine-like drugs have been synthesized to minimize adverse effects and abuse potential. Opioid receptors were identified and characterized in binding assays and their localization examined. However, the complexity of the system including interaction with several neurons and transmitters indicate the goal of nonaddictive opiates to be elusive. Combination therapy, innovative delivery systems and long-acting formulations may improve clinical utility.

[Cardiac glycosides: From ancient history through Withering's foxglove to endogeneous cardiac glycosides]. / Hjerteglykosider: Fra oldtiden over Witherings digitalis til endogen glykosider.

For centuries, drugs that increase the power of contraction of the failing heart have been used for the treatment of congestive heart failure (dropsy). The cardiac effect is due to the content of cardiac glycosides. Squill or sea onion, Urginea (Scilla) maritima, a seashore plant, was known by the ancient Romans and Syrians and possibly also by the ancient Egyptians. Squills were used erratically, but some prescriptions indicate that they may have been used for the treatment of oedematous states. The toxic effect of strophanthus species was known from poisoned arrows used by the natives in Africa. Digitalis, derived form the foxglove plant, Digitalis purpurea, is mentioned in writings as early as 1250; a Welsh family, known as the Physicians of Myddvai, collected different herbs and digitalis was included in their prescriptions. However, the druge was used erratically until the 18th century, when William Withering, an English physician and botanist, published a monograph describing the clinical effects of an extract of the foxglove plant. Later, in 1785, the indication and the toxicity of digitalis were reported in his book, "An account of the Foxglove and some of its medical uses with practical remarks on dropsy, and other diseases". In Denmark, the leaves of Digitalis purpurea or Digitalis lanata were tested for cardiac glycoside activity. The standardized digitalis powder was used in tinctures, infusions, and tablets. The preparations were included in successive editions of the Danish pharmacopoeia, some of the tinctures already in 1828, i.e. before the standardization of the drug. Isolation of cardiac glycosides from digitalis, strophanthus and squill and determination of their chemical structures initiated biochemical and pharmacological studies. The scientific advances led to an understanding of cardiac muscle contractility and the Na,K pump as the cellular receptor for the inotropic action of digitalis. Examination of putative endogenous ligands to the receptor revealed some endogenous cardiac glycosides of similar or identical structures as those found in digitalis, strophanthus and squill. Increased concentrations of these glycosides are found in patients with heart failure. Further investigations are needed to determine whether the secretion of glycosides might be a physiologic response to a diminished cardiac output.

Chlamydia pneumoniae infection and its role in asthma and chronic obstructive pulmonary disease.

Chlamydia pneumoniae (CP) is a common cause of respiratory tract infections, and several studies have asked whether it may play a pathogenic role in connection with bronchial asthma and chronic obstructive pulmonary disease (COPD). Evidence that CP infection is associated with these diseases is a cardinal item. However, evaluation of CP infection is hampered by difficulties in obtaining agreement on the definition of a gold standard. In the literature, serology is based on different cutoff points of antibody titres, which complicates the definition of CP seropositive findings and the classification of acute infection, chronic and past infection. In connection with acute and chronic infection, it is important to demonstrate the presence of CP by culture or polymerase chain reaction (PCR) in the respiratory tract, especially in the lower airways. Often, the results of serology is not associated with the findings by culture or PCR testing, which may involve the risk of inconclusive evidence. Evaluation of a possible presence of CP by clinical improvement after treatment with antibiotics is difficult since uncontrolled studies have been used and other microorganisms are also affected by antibiotics. Furthermore, many patients improve without antibiotics, and improvement has also been observed in patients remaining culture positive after treatment with antibiotics. It should also be noted that the antiinflammatory effects of antibiotics may improve the clinical status of patients. Despite these obstacles, studies point to the possibility that in some patients acute CP infections may lead to acute exacerbations of bronchial asthma. Whether a persistent CP infection contributes to chronic asthma or severe COPD, or whether it incites the diseases in previously healthy individuals is a question for further studies. Whether a causal relationship exists between CP infection and obstructive pulmonary disease or whether these patients are more susceptible to CP infection is unknown. Nevertheless, a cooperative role of CP in the proinflammatory mechanisms involved in these diseases remains to be examined since cellular studies show that CP stimulates the production and expression of cytokines, chemokines and adhesion molecules, actions that may amplify and prolong the inflammation.