Dyspnoeic dysphasia: a series of unfortunate events.

We describe a case of a 56 year old man with no previous medical history who presented with sudden onset dyspnoea, expressive dysphasia, and right arm sensory loss and paresis. A diagnosis of bilateral pulmonary embolism and transient cerebral ischaemic attack was confirmed by CT pulmonary angiogram and MRI. Paradoxical embolism through an occult patent foramen ovale (PFO) was subsequently proven by contrast echocardiography. This case highlights a number of short and long-term management conundrums, that to date are incompletely addressed by clinical trials. These include timing of anticoagulation in patients with both venous thromboembolism and cerebral infarction, and the risk:benefit ratio of surgical closure of patent foramen ovale.

Adverse events to antituberculosis therapy: influence of HIV and antiretroviral drugs.

This study investigated whether serious adverse events (SAEs) during antituberculosis therapy occur more frequently in HIV co-infected patients in a South African population. A retrospective analysis examined incidences of hepatotoxicity, peripheral neuropathy, severe arthralgia, persistent vomiting and severe rash in 400 patients treated for tuberculosis in a community clinic. A total of 141 patients were co-infected with HIV, among whom only 16.3% were receiving antiretrovirals. Details of SAEs were ascertainable in 331/400 patients, and occurred in 26.7% of HIV-infected and 13.3% of HIV-uninfected individuals (P = 0.003). The excess was attributable to increased peripheral neuropathy (8.3% and 1.9%, respectively, P = 0.009) and persistent vomiting (13.3% and 3.3%, P = 0.001). SAE occurrence was not related to antiretroviral use, although median CD4 counts were lower in those experiencing side-effects (130 and 259 cells/microL, P = 0.008). The treatment completion did not differ significantly between the two groups (76.6% and 84.2%, P = 0.08).

Ileal MALT lymphoma causing massive gastrointestinal haemorrhage revealed on computed tomography angiography.

Primary MALT lymphomas affecting the ileum are rare, and their presentation with massive haemorrhage exceptional. This report describes such a case. The patient presented with melaena and haemodynamic instability, but normal upper gastrointestinal endoscopy. Subsequent imaging with multi-detector row computed tomography angiography both localised the bleeding source to the ileum and identified the underlying tumour, resulting in considerably earlier introduction of appropriate management. The patient made an excellent recovery and remains in remission.

Can unresolved infection precipitate autoimmune disease?

Autoimmune diseases are frequently postulated to arise as post-infectious phenomena. Here we survey the evidence supporting these theories, with particular emphasis on Crohn's disease and ankylosing spondylitis. Direct proof that infection establishes persistent autoimmunity remains lacking, although it may provoke a prolonged inflammatory response when occurring on a susceptible immunological background. The argument of infective causality is by no means trivial, since it carries important consequences for the safety of vaccine development.

Impaired neutrophil chemotaxis in Crohn's disease relates to reduced production of chemokines and can be augmented by granulocyte-colony stimulating factor.

BACKGROUND: Defective neutrophil recruitment has been described as a primary pathogenic abnormality in Crohn's disease. Cantharidin-induced blisters provide a novel investigative tool to assess cellular influx and inflammatory mediator production during acute inflammation and allows the effects of therapy on these parameters to be measured. AIMS: To determine whether reduced neutrophil tissue penetration in Crohn's disease relates to impaired production of inflammatory mediators, and whether it can be reversed by granulocyte-colony stimulating factor (G-CSF). METHODS: Neutrophil and monocyte/macrophage populations and inflammatory mediators were measured in cantharidin blisters at 24 h. Neutrophil chemotaxis was assessed in vitro using blister fluid as the chemoattractant. The effect of s.c. G-CSF on blister phenotype was determined. RESULTS: Significantly fewer neutrophils migrated into blisters in Crohn's patients. The production of neutrophil chemokines, but not other inflammatory mediators, was reduced. This significantly correlated with reduced chemotaxis in vitro. Differences were unrelated to caspase-recruitment domain 15 genotype. G-CSF significantly increased blister neutrophil concentrations in control subjects and Crohn's patients. CONCLUSIONS: Reduced neutrophil migration during acute inflammation in Crohn's disease is associated with impaired production of appropriate chemoattractants. G-CSF therapy increases neutrophil tissue migration, which may partially account for its observed therapeutic effect.

Clinical features, microbiology and surgical outcomes of infective endocarditis: a 13-year study from a UK tertiary cardiothoracic referral centre.

BACKGROUND: Infective endocarditis (IE) causes substantial morbidity and mortality. Patient and pathogen profiles, as well as microbiological and operative strategies, continue to evolve. The impact of these changes requires evaluation to inform optimum management and identify individuals at high risk of early mortality. AIM: Identification of clinical and microbiological features, and surgical outcomes, among patients presenting to a UK tertiary cardiothoracic centre for surgical management of IE between 1998 and 2010. DESIGN: Retrospective observational cohort study. METHODS: Clinical, biochemical, microbiological and echocardiographic data were identified from clinical records. Principal outcomes were all-cause 28-day mortality and duration of post-operative admission. RESULTS: Patients (n = 336) were predominantly male (75.0%); median age 52 years (IQR = 41-67). Most cases involved the aortic (56.0%) or mitral (53.9%) valves. Microbiological diagnoses, obtained in 288 (85.7%) patients, included streptococci (45.2%); staphylococci (34.5%); Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella (HACEK) organisms (3.0%); and fungi (1.8%); 11.3% had polymicrobial infection. Valve replacement in 308 (91.7%) patients included mechanical prostheses (69.8%), xenografts (24.0%) and homografts (6.2%). Early mortality was 12.2%, but fell progressively during the study (P = 0.02), as did median duration of post-operative admission (33.5 to 10.5 days; P = 0.0003). Multivariable analysis showed previous cardiothoracic surgery (OR = 3.85, P = 0.03), neutrophil count (OR = 2.27, P = 0.05), albumin (OR = 0.94, P = 0.04) and urea (OR = 2.63, P < 0.001) predicted early mortality. CONCLUSIONS: This study demonstrates reduced post-operative early mortality and duration of hospital admission for IE patients over the past 13 years. Biomarkers (previous cardiothoracic surgery, neutrophil count, albumin and urea), predictive of early post-operative mortality, require prospective evaluation to refine algorithms, further improve outcomes and reduce healthcare costs associated with IE.

Innate immunity in inflammatory bowel disease: a disease hypothesis.

Crohn's disease arises from a defective interaction between the highly concentrated mass of bacteria in the gastrointestinal tract and the underlying tissues. It has generally been believed to result from an excessively exuberant inflammatory response or from 'autoimmunity'. Recent evidence has emerged that the problem is instead a failure of the way in which the body responds to the penetration of bacteria and other bowel contents through the intestinal mucosal barrier. Rather than Crohn's disease being caused by excessive inflammation, the primary mechanism is actually that of an immunodeficiency. Failure of inflammatory mediator production leads to insufficient recruitment of neutrophils, resulting in inadequate removal of bacteria and other debris. This impairment of acute inflammation can be compensated in some circumstances by signalling through NOD2. If not cleared, the foreign material in the bowel wall is taken up within macrophages, eliciting a granulomatous reaction and the local and systemic sequelae so characteristic of Crohn's disease.

Modified skin window technique for the extended characterisation of acute inflammation in humans.

OBJECTIVE: To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease. SUBJECTS: 15 healthy subjects and 5 Crohn's patients. TREATMENT: Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide (MDP) or 10 microg/ml interleukin-8 (IL-8). METHODS: Exuded leukocytes were analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT-PCR. Inflammatory mediators were quantified by ELISA. RESULTS: Infiltrating leukocytes were predominantly neutrophils. Numerous secreted mediators were detectable. MDP and IL-8 enhanced responses. Many signalling proteins were phosphorylated with differential patterns in Crohn's patients, notably PKC alpha/beta hyperphosphorylation (11.3 +/- 3.1 vs 1.2 +/- 0.9 units, P < 0.02). Activities of 44 transcription factors were detectable, and sufficient RNA isolated for expression analysis of over 400 genes. CONCLUSIONS: The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators.