Eikenella corrodens endocarditis and liver abscess in a previously healthy male, a case report.

BACKGROUND: Eikenella corrodens is one of the HACEK bacteria constituting part of the normal flora of the oropharynx, however, still an uncommon pathogen. We report a case of a large Eikenella corrodens liver abscess with simultaneously endocarditis in a previously healthy male. CASE PRESENTATION: A 49-year-old Danish man was admitted because of one-month malaise, fever, cough and unintentional weight loss. On admission there was elevated white blood cell count and C-reactive protein, as well as affected liver function tests. Initially pneumonia was suspected, but due to lack of improvement on pneumonia treatment, a PET-CT scan was performed, which showed a large multiloculated abscess in the liver. The abscess was drained using ultrasound guidance. Culture demonstrated Eikenella corrodens. Transesophageal echocardiography revealed aortic endocarditis. The patient was treated with antibiotics and abscess drainage, on which he slowly improved. He was discharged after 1.5 months of hospitalisation. On follow-up 2 months later, the patient was asymptomatic with normalized biochemistry and ultrasound showed complete regression of the abscess. CONCLUSIONS: This is the first case of documented Eikenella corrodens concurrent liver abscess and endocarditis. The case report highlights that Eikenella corrodens should be considered as a cause of liver abscess. Empirical treatment of pyogenic liver abscess will most often cover Eikenella corrodens, but the recommended treatment is a third generation cephalosporin or a fluoroquinolon. A multiloculated liver abscess may require drainage several times during treatment. The finding of Eikenella corrodens should elicit an echocardiography to diagnose endocarditis even in patients without clinical signs of endocarditis.

Immunodeficiency associated with FCN3 mutation and ficolin-3 deficiency.

Ficolin-3, encoded by the FCN3 gene and expressed in the lung and liver, is a recognition molecule in the lectin pathway of the complement system. Heterozygosity for an FCN3 frameshift mutation (rs28357092), leading to a distortion of the C-terminal end of the molecule, occurs in people without disease (allele frequency among whites, 0.01). We describe a patient with recurrent infections who was homozygous for this mutation, who had undetectable serum levels of ficolin-3, and who had a deficiency in ficolin-3-dependent complement activation.

First attempt to produce experimental Campylobacter concisus infection in mice.

AIM: To infect mice with atypical Campylobacter concisus (C. concisus) for the first time. METHODS: Three separate experiments were conducted in order to screen the ability of five clinical C. concisus isolates of intestinal origin and the ATCC 33237 type strain of oral origin to colonize and produce infection in immunocompetent BALB/cA mice. The majority of the BALB/cA mice were treated with cyclophosphamide prior to C. concisus inoculation to suppress immune functions. Inoculation of C. concisus was performed by the gastric route. RESULTS: C. concisus was isolated from the liver, ileum and jejunum of cyclophosphamide-treated mice in the first experiment. No C. concisus strains were isolated in the two subsequent experiments. Mice infected with C. concisus showed a significant loss of body weight from day two through to day five of infection but this decreased at the end of the first week. Histopathological examination did not consistently find signs of inflammation in the gut, but occasionally microabscesses were found in the liver of infected animals. CONCLUSION: Transient colonization with C. concisus was observed in mice with loss of body weight. Future studies should concentrate on the first few days after inoculation and in other strains of mice.

Gastric inflammatory markers and interleukins in patients with functional dyspepsia treated with astaxanthin.

The chronic active inflammation caused by Helicobacter pylori is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins are involved in the inflammatory process. The aim of this study was to investigate the effect of astaxanthin on gastric inflammation in patients with functional dyspepsia. Forty-four consecutive patients were included, and biopsies were examined for IL-4, IL-6, IL-8, IL-10, interferon-gamma, CD4, CD8, CD14, CD19, CD25 and CD30. Patients were randomized: 21 patients were treated with 40 mg of astaxanthin daily, and 23 patients were treated with a placebo. There was a significant decrease in gastric inflammation in H. pylori-positive patients from both groups. There were no significant changes in the density of H. pylori or in any of the interleukins during or after treatment. There was a significant up-regulation of CD4 and down-regulation of CD8 in patients with H. pylori treated with astaxanthin. Astaxanthin had an effect on the inflammation and on the density of H. pylori in mice in a study where the diet could be standardized without antioxidants (Bennedsen et al., 1999). These dietary conditions are impossible in studies involving humans, and may be due to the minor effect when the host have access to antioxidants in their diet.

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.

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 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.

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.

Characterization and subgrouping of Campylobacter concisus strains using protein profiles, conventional biochemical testing and antibiotic susceptibility.

OBJECTIVE: To characterize and subgroup clinical strains of Campylobacter concisus isolated from patients with gastrointestinal disease. METHODS: A total of 109 C. concisus isolates from 98 patients obtained between June 1997 and December 1998 were analysed using protein profiles, conventional biochemical tube tests, ApiCampy, and susceptibility patterns by Neosensitabs and E-test. RESULTS: Two groups were identified by using protein profiles. One resembled the ATCC 33237 type strain of oral origin, and a second group differing from it, particularly in the high molecular weight zone. Considerable diversity exists in the lower molecular range of the gels, also within assigned subgroups. Biochemical testing showed differences between the groups in the ability to reduce nitrate, ApiCampy testing also yielded differences between the two assigned groups, although reactions were highly heterogeneous. Resistance to erythromycin, ciprofloxacin, ampicillin, ceftriaxone and tetracycline occurred in 3%, 13%, 7%, 11% and 0% of the isolates when using Neosensitabs. The E-test yielded comparable results 7%, 5%, 0%, 2% and 3%, respectively. CONCLUSION: Results indicate that C. concisus can be assigned to two broad groups based on differences in protein profiles. No distinct phenotypic marker was identified. Susceptibility patterns are not suitable for discrimination between the two assigned groups. Further studies using a polyphasic approach including the application of genetic methods are needed to assess the complex taxonomy of this potential pathogen.

[A historical perspective of Ebola virus]. / Ebolavirus i et historisk perspektiv.

The 2014 Ebola fever outbreak was the first of its kind in West Africa. This epidemic, affecting multiple countries, by far exceeded any previous outbreak in case counts and geographical spread. But Ebola viruses are not new to Africa, as they have occurred in epidemic proportion in the central part of the continent since 1976. The objective of this article is to compare previous outbreaks with the ongoing epidemic in an effort to identify some of the factors which have con-tributed to the size and scope of the existing outbreak.

[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.

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.

[Tuberculous spondylitis--Pott disease--in a 33-year-old man from Greenland]. / Tuberkuløs spondylitis--Potts sygdom--hos en 33-årig grønlandsk mand.

We report a case where tuberculous spondylitis was diagnosed in a 33-year-old man from Greenland. Very typically for Pott's disease, there was back pain, weight loss, and a characteristic kyphotic deformity. Computed tomography showed destruction of the thoracic vertebrae with paraspinal abscesses. The treatment was antituberculous therapy and surgery.

[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.

Primary complement C5 deficiencies - molecular characterization and clinical review of two families.

Inherited deficiency states of the terminal complement component C5 are rare and often associated with increased risk of recurrent Neisseria infections. More than 50 cases with primary C5 deficiency have been reported. In spite of this, the molecular basis has only been documented in a few cases. In the present study we investigated two unrelated Caucasian probands with C5 deficiency originating from Norway and Denmark, respectively, and found three previously undescribed mutations. With these data, thirteen mutations associated with C5 deficiency have been described. By genetic screening of the family of the Norwegian patient, previously diagnosed as homozygous C5 deficient and suffering four Neisseria infections, an additional case of C5 deficiency was discovered, who had experienced one episode of Neisseria infections. Detailed review of the clinical history of the patients and their healthy relatives did not reveal any differences between C5 deficient and sufficient individuals with regard to clinical presentation, apart from the susceptibility to Neisseria infections. Of note, one of the patients described here, and several C5 deficient patients from the literature had Neisseria meningitidis serotype B infections, which is not covered by the current vaccines. These data support the clinical guidelines for patients treated with C5 inhibitors, who are functional C5 deficient by the treatment.

[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.