The causative pathogen determines the inflammatory profile in cerebrospinal fluid and outcome in patients with bacterial meningitis

BACKGROUND The brain's inflammatory response to the infecting pathogen determines the outcome of bacterial meningitis (BM), for example, the associated mortality and the extent of brain injury. The inflammatory cascade is initiated by the presence of bacteria in the cerebrospinal fluid (CSF) activating resident immune cells and leading to the influx of blood derived leukocytes. To elucidate the pathomechanisms behind the observed difference in outcome between different pathogens, we compared the inflammatory profile in the CSF of patients with BM caused by Streptococcus pneumonia (n = 14), Neisseria meningitidis (n = 22), and Haemophilus influenza (n = 9). METHODS CSF inflammatory parameters, including cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were assessed in a cohort of patients with BM from Burkina Faso. RESULTS Pneumococcal meningitis was associated with significantly higher CSF concentrations of IFN-γ , MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a fatal outcome, levels of TNF-α, IL-1 β, IL-1RA, IL-6, and TGF-α were significantly higher. CONCLUSION The signature of pro- and anti-inflammatory mediators and the intensity of inflammatory processes in CSF are determined by the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis being associated with a higher case fatality rate than meningitis caused by N. meningitidis or H. influenzae.

Two variants in the KIT gene as candidate causative mutations for a dominant white and a white spotting phenotype in the donkey.

White spotting phenotypes have been intensively studied in horses, and although similar phenotypes occur in the donkey, little is known about the molecular genetics underlying these patterns in donkeys. White spotting in donkeys can range from only a few white areas to almost complete depigmentation and is characterised by a loss of pigmentation usually progressing from a white spot in the hip area. Completely white-born donkeys are rare, and the phenotype is characterised by the complete absence of pigment resulting in pink skin and a white coat. A dominant mode of inheritance has been demonstrated for spotting in donkeys. Although the mode of inheritance for the completely white phenotype in donkeys is not clear, the phenotype shows similarities to dominant white in horses. As variants in the KIT gene are known to cause a range of white phenotypes in the horse, we investigated the KIT gene as a potential candidate gene for two phenotypes in the donkey, white spotting and white. A mutation analysis of all 21 KIT exons identified a missense variant in exon 4 (c.662A>C; p.Tyr221Ser) present only in a white-born donkey. A second variant affecting a splice donor site (c.1978+2T>A) was found exclusively in donkeys with white spotting. Both variants were absent in 24 solid-coloured controls. To the authors' knowledge, this is the first study investigating genetic mechanisms underlying white phenotypes in donkeys. Our results suggest that two independent KIT alleles are probably responsible for white spotting and white in donkeys.

Incidence and causative agents of chemical eye injuries in Switzerland

CONTEXT Chemical eye injuries are ophthalmological emergencies with a high risk of secondary complications and severe visual loss. Only limited epidemiological data for such injuries are available for many countries. PATIENTS AND METHODS We performed two independent studies. The cause of chemical eye injuries was assessed with a prospective questionnaire study. Questionnaires were sent to all ophthalmologists in Switzerland. A total of 163 patients (205 eyes) were included, between December 2012 and October 2014. Independent of the questionnaire study, the incidence of chemical eye injuries was assessed with a retrospective cohort study design using the database of the mandatory accident insurance. RESULTS Ophthalmological questionnaires revealed that plaster/cement (20.5%), alkaline (12.2%) and acid (10.2%) solutions caused the highest number of chemical injuries. Only 2% of all injuries were classified as grade III and none as grade IV (Roper-Hall classification). The official toxicological information phone-hotline was contacted in 4.3% of cases. Using data from the accident insurance, an incidence of chemical eye injuries of about 50/100 000/year was found in the working population. CONCLUSION Here, we present data on the involved agents of chemical eye injuries in Switzerland, and also the incidence of such injuries in the working population. This may also help to assess the need for further education programs and to improve and direct preventive measures.

ABCA4 and ROM1: Implications for modification of the PRPH2-associated macular dystrophy phenotype

To identify the causative mutation leading to autosomal dominant macular dystrophy, cone dystrophy, and cone-rod dystrophy in a five-generation family and to explain the high intrafamilial phenotypic variation by identifying possible modifier genes.

Endocarditis due to Tropheryma whipplei: rapid detection, limited genetic diversity, and long-term clinical outcome in a local experience

The characteristic features of Whipple's disease include abdominal pain, diarrhoea, wasting, and arthralgias, with the causative agent, Tropheryma whipplei, being detected mainly in intestinal biopsies. PCR technology has led to the identification of T. whipplei in specimens from various other locations, including the central nervous system and the heart. T. whipplei is now recognized as one of the causes of culture-negative endocarditis, and endocarditis can be the only manifestation of the infection with T. whipplei. Although it is considered a rare disease, the true incidence of endocarditis due to T. whipplei is not clearly established. With the increasing use of molecular methods, it is likely that T. whipplei will be more frequently identified. Questions also remain about the genetic variability of T. whipplei strains, optimal diagnostic procedures and therapeutic options. In the present study, we provide clinical data on four new patients with documented endocarditis due to T. whipplei in the context of the available published literature. There was no clinical involvement of the gastrointestinal tract. Genetic analysis of the T. whipplei strains with DNA isolated from the excised heart valves revealed little to no genetic variability. In a selected case, we describe acridine orange staining for early detection of the disease, prompting early adaptation of the antibiotic therapy. We provide long-term follow-up data on the patients. In our hands, an initial 2-week course of intravenous antibiotics followed by cotrimoxazole for at least 1 year was a suitable treatment option for T. whipplei endocarditis.

Pulse or hyaline ring granuloma. Review of the literature on etiopathogenesis of oral and extraoral lesions

Since the late 1950s, reports on an unusual giant-cell granulomatous lesion affecting the jaws, lungs, stomach and intestines have been published. Histopathologically, the lesions showed the presence of structureless hyaline rings with multinucleated giant cells. The aim of this review was to summarize the literature on the etiopathogenesis of the so-called oral and extraoral pulse or hyaline ring granuloma. Literature was searched using PubMed and Medline. In addition, hand search was performed. Search words were oral and extraoral hyaline ring granuloma, giant-cell hyaline angiopathy, pulse granuloma and chronic periostitis. Numerous terms for hyaline ring granuloma have been introduced over time (1971-2008). One hundred seventy-three cases of oral hyaline ring granuloma have been retrieved from the literature. In the mandible, 72.3% occurred . Two theories for etiopathogenesis have been proposed: (1) the origin of the hyaline rings is due to a foreign material (pulse and legumes) having penetrated the oral mucosa or gastrointestinal tract and lungs (exogenous theory) and (2) the rings are due to hyaline degenerative changes in walls of blood vessels (endogenous theory). Experimental production of oral and extraoral hyaline ring granulomas is consistent with the exogenous origin. Particles or remains of leguminous cells having been implanted or aspirated into human tissues whether located to the oral cavity or throughout the entire digestive tract and respiratory system are thought to be causative. Pulse or hyaline ring granulomas are rare but are well-defined oral and extraoral lesions due to implantation of the cellulose moiety of plant foods in contrast to the starch components.

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer.

Adverse effects of drugs on the esophagus

Given the function of the esophagus to transport orally ingested solids and liquids into the stomach there are several medications with adverse effect on esophageal structures and function. Various pharmacologic agents can induce esophageal injury, promote gastroesophageal reflux by decreasing lower esophageal sphincter tone or affect esophageal perception and motility. The risks of bisphosphonates, doxycycline, ferrous sulfate, ascorbic acid, aspirin/NSAIDs and chemotherapeutic agents to induce esophageal lesions have been documented in case reports and short series. In addition to direct mucosal injury, many commonly used medications including nitroglycerins, anticholinergics, beta-adrenergic agonists, aminophyllines, and benzodiazepines promote/facilitate gastroesophageal reflux by reducing lower esophageal sphincter pressure. Additional evidence accumulates on the adverse effects of various medications on esophageal motility and perception. The treatment of medication-induced esophageal lesions includes (1) identifying and discontinuing the causative medication, (2) promoting healing of esophageal injury by decreasing esophageal acid exposure or coating already existing esophageal lesions, (3) eventual use of protective compounds.

Approach to the patient with drug allergy

Clinicians commonly encounter patients who report to have drug allergy. In a large part, such allergy corresponds to adverse drug reactions, which are not immune mediated. The incriminated drug need not always be avoided for further therapy. On the other hand, drug allergy may manifest in many unexpected clinical pictures and thus not be recognized. There is no single standardized diagnostic test to confirm the immune-mediated mechanism and to identify the causative drug. Therefore, immune-mediated drug hypersensitivity reactions and their causative drugs have to be considered by the constellation of exposure, timing, and clinical features, including the pattern of organ manifestation. Prior experience with the drug is also an important feature. An allergologic workup with additional investigation may provide some help. Patients should be informed carefully about their drug allergy, whereby symptoms, drug that elicits reaction, modes of diagnosis of drug allergy, and possibly alternatives should be indicated in their allergy passport.

Postpartal recurrent non-ST elevation myocardial infarction in essential thrombocythaemia: case report and review of the literature

ABSTRACT: Normal pregnancy corresponds to a procoagulant state. Acute myocardial infarction during pregnancy is rare, yet considering the low non-pregnant risk score of childbearing women it is still surprisingly frequent. We report a case of postpartum recurrent non-ST elevation myocardial infarction in a 40-year-old caucasian woman with essential thrombocythaemia in the presence of a positive JAK-2 mutation and an elevated anti-cardiolipin IgM antibody titer. In the majority of cases of myocardial infarction in pregnancy or in the peripartal period, atherosclerosis, a thrombus or coronary artery dissection is observed. The combination of essential thrombocythaemia and elevated anti-cardiolipin IgM antibody titer in the presence of several cardiovascular risk factors seems to be causative in our case. In conclusion, with the continuing trend of childbearing at older ages, rare or unlikely conditions leading to severe events such as myocardial infarction must be considered in pregnant women.

Predicting the pathogen of diabetic toe osteomyelitis by two consecutive ulcer cultures with bone contact

In this study, we investigate the accuracy of two consecutive ulcer cultures with bone contact compared to bone biopsy for the diagnosis of diabetic toe osteomyelitis. The same nurse and orthopaedic surgeon obtained all samples: sample A-1: bone contact swabbing through the ulcer; sample A-2: a second culture swabbing from the bone surface within 24 h; sample B: surgical bone biopsy in the operating theatre. The kappa statistic measure between samples A-1 and A-2 (bone contact swabs) indicated 82.35% agreement. The sensitivity, specificity, positive and negative predictive values of the two samples A compared to B were 96%, 79%, 92% and 88%, respectively, for the causative pathogen. These results were similar with prior antibiotic treatment, discordant bone surface swabs or with monomicrobial infections. As a conclusion, two consecutive diabetic toe cultures with bone contact accurately predict the pathogen of diabetic toe osteomyelitis in 90% of cases.

Incidence, aetiology and pattern of mandibular fractures in central Switzerland

The two major causative factors for mandibular fractures, as stated in the literature, are either interpersonal violence or motor vehicle accidents. The purpose of this study was to describe epidemiological trends of mandibular fractures in Switzerland. A special emphasis was directed towards the potential impact of socio-economic standards on the mechanism and pattern of mandible fractures.

[Periprosthetic joint infections - a review for general practitioners]

The number of prosthetic joint implantation is continuously increasing. Periprosthetic joint infection is a rare but serious complication. The correct diagnosis is essential for successful treatment. It requires the close collaboration between general practitioners, orthopaedic surgeons and infectious disease specialists. A delayed diagnosis sets hurdles to the medical and surgical treatment. Also, antimicrobial treatment without proper microbiological sampling must be avoided. Swabs from wounds are not helpful, because the results represent the skin flora, but not the causative pathogen of infection. The general practitioner is the first physician that patients contact and has, therefore, a central role in diagnosing and managing periprosthetic joint infections. In this review, classification, diagnostic means and treatment concepts of periprosthetic joint infections are presented.

In vitro diagnosis of T cell-mediated drug allergy

Diagnosis of drug hypersensitivity relies on history, skin tests, in vitro tests and provocation tests. In vitro tests are of great interest, due to possible reduction of drug provocation tests. In this review we focus on best investigated in vitro techniques for the diagnosis of T cell-mediated drug hypersensitivity reactions. As drug hypersensitivity relies on different pathomechanisms and as a single diagnostic test usually does not cover all possible reactions, it is advisable to combine different tests to increase the overall sensitivity. Recently, proliferation-based assays have been supplemented by a panel of novel in vitro tests including analysis of cytotoxic potential of effector cells (granzyme B, granulysin, CD107a), evaluation of cytokine secretion (IL-2, IL-5, IL-13, and IFN-γ) and up-regulation of cell surface activation markers (CD69). We discuss the latest findings and readout systems to identify causative drugs by detecting functional and phenotypic markers of drug-reacting cells, and their ability to enable a more conclusive diagnosis of drug allergy.