Livres sur le sujet « Multiple disease resistance »

Airflow disruption can be triggered through multiple mechanisms. The obstruction can stem from within the airway lumen, airway walls, or the tissues surrounding it. This section focuses on airflow disruption initiated by bronchospasm, obstructive lung disease, asthma and status asthmaticus. Bronchospasm presents with increased airway resistance secondary to airway hyperreactivity or anaphylaxis. Asthma and chronic obstructive pulmonary disease (COPD) are obstructive and inflammatory lung pathologies. Airflow disruption in asthma is reversible between exacerbations. The airway obstruction in COPD is not fully reversible. Status asthmaticus is the most severe presentation of asthma and can be life threatening. Poorly controlled obstructive lung disease can result in perioperative complications. Patients should therefore be medically optimized before undergoing operative procedures.

Antibiotic selection is a crucial drug choice in critically-ill patients. Optimization of empiric antibiotic choice can be gained by knowledge of the site of infection and the probable causative organisms at that site. This should be linked with knowledge of the local epidemiology of antibiotic resistance in the actual intensive care unit housing the patient. Initial empiric antimicrobial choice may need to be broad in order to cover potential antibiotic-resistant pathogens. However, it is important to be prudent in antibiotic strategy since the selection of multiple-resistant organisms by excessively broad or prolonged antibiotic therapy may affect not just the patient undergoing antibiotic therapy, but also other future patients. Selection of appropriate antibiotic regimens can be facilitated by the use of technology such as MALDI-TOF for rapid bacterial identification. Consultation with infectious disease physicians or specialist pharmacists may also be warranted in order to optimize antibiotic dosing, duration of infusion and frequency of administration, so as to meet pharmacodynamics targets linked to improved patient outcome.

Resistant hypertension is defined as a blood pressure above target despite adherence to at least three different antihypertensive agents. The term can be used to identify patients with difficult-to-treat hypertension, who might benefit from specialist investigation and/or treatment. It likely affects 10–15% of patients with hypertension. ‘White coat’ hypertension should be excluded first by the use of out-of-office blood pressure monitoring. Risk factors include obesity, older age, chronic kidney disease, and diabetes.Treatment is based on identifying and treating any underlying cause and through the use of multiple antihypertensive medications, in particular ensuring adequate diuretic therapy.

Hypertension affects multiple groups of patients characterized by different clinical presentations and a spectrum of potential causes. The pathophysiology is complex and multifactorial. Although most patients are labelled ‘essential hypertension’, multiple mechanisms are involved in blood pressure regulation. Factors that influence blood pressure homeostasis include endothelial function, the renin-angiotensin system, and the sympathetic nervous system. In elderly patients, hypertension is common as the vascular system and arterial stiffness also contribute. Other important factors include inflammatory processes as part of systemic diseases, including atherosclerosis,which may contribute to renal and vascular injury. Hypertension is also associated with metabolic disturbances including dyslipidaemia that manifests in obese patients who also have insulin resistance. These different pathways all represent potential targets for treatment, but also increase the challenge of multimodal pathophysiology.

Mutations in the Wilms tumour suppressor gene, WT1, are associated with Wilms tumour in childhood. However, in addition WT1 has a key role in renal development, emerging roles in podocyte function, and a potential role in tissue regeneration. An understanding of WT1 is of increasing importance to clinical practice. WT1 is a complex gene with multiple isoforms. It is crucial for normal embryonic development, especially kidney development, where it is necessary for mesenchymal-to-epithelial transition to form the nephron. WT1 mutations lead to abnormalities in renal and genitourinary development, causing diseases such as Denys–Drash syndrome and Frasier syndrome as well as Wilms tumour. Recently, WT1 mutations have been recognized as a significant cause of isolated steroid-resistant nephrotic syndrome in children and young adults, without other associated syndromic features. WT1 continues to be expressed in adult podocytes, where it acts as a transcriptional activator of many podocyte genes. However, the specific role of WT1 in adult podocyte function remains poorly understood.

Weaning failure has been defined as failure to discontinue mechanical ventilation, as assessed by the spontaneous breathing trial, or need for re-intubation after extubation, so-called extubation failure. Both events represent major clinical and economic burdens, and are associated with high morbidity and mortality. The most important mechanism leading to discontinuation failure is an unfavourable balance between respiratory muscle capacity and the load they must face. Beyond specific diseases leading to loss of muscle force-generating capacity, other factors may impair respiratory muscle function, including prolonged mechanical ventilation, sedation, and ICU-acquired neuromuscular dysfunction, potentially consequent to multiple factors. The load depends on the mechanical properties of the respiratory system. An increased load is consequent to any condition leading to increased resistance, reduced compliance, and/or occurrence of intrinsic positive-end-expiratory pressure. Noteworthy, the load can significantly increase throughout the spontaneous breathing trial. Cardiac, cerebral, and neuropsychiatric disorders are also causes of discontinuation failure. Extubation failure may depend, on the one hand, on a deteriorated force-load balance occurring after removal of the endotracheal tube and, on the other hand, on specific problems. Careful patient evaluation, avoidance and treatment of all the potential determinants of failure are crucial to achieve successful discontinuation and extubation.

Verocytotoxin (VT)-producing Escherichia coli (VTEC), also known as Shiga toxin producing E. coli (STEC), are zoonotic agents, which cause a potentially fatal illness whose clinical spectrum includes diarrhoea, haemorrhagic colitis, and the haemolytic uraemic syndrome (HUS). VTEC are of serious public health concern because of their association with large outbreaks and with HUS, which is the leading cause of acute renal failure in children. Although over 200 different OH serotypes of VTEC have been associated with human illness, the vast majority of reported outbreaks and sporadic cases of VTEC-infection in humans have been associated with serotype O157:H7.VTs constitute a family of related protein subunit exotoxins, the major ones implicated in human disease being VT1, VT2, and VT2c. Following their translocation into the circulation, VTs bind to endothelial cells of the renal glomeruli, and of other organs and tissues via a specific receptor globotriosylceramide (Gb 3), are internalized by a process of receptor-mediated endocytosis, and cause subcellular damage that results in the characteristic microangiopathic disease observed in HUS.The incubation period of VTEC-associated illness is about 3–5 days. After ingestion VTEC (especially of serotype O157:H7) multiply in the bowel and colonize the mucosa of probably the large bowel with a characteristic attaching and effacing (AE) cytopathology. Colonization is followed by the translocation of VTs into the circulation and the subsequent manifestation of disease.The majority of patients with uncomplicated VTEC infection recover fully with general supportive measures. Historically, the case-fatality rate was high for HUS. However, improvement in the treatment of renal failure and the attendant biochemical disturbances has substantially improved the outlook, although long-term sequelae may develop.Ruminants, especially cattle, are the main reservoirs of VTEC. Infection is acquired through the ingestion of contaminated food, especially under-cooked hamburger, through direct contact with animals, via contaminated water or environments, or via personto-person transmission.The occurrence of large outbreaks of food-borne VTEC-associated illness has promoted close scrutiny of this zoonoses at all levels in the chain of transmission, including the farm, abattoir, food processing, packaging and distribution plants, the wholesaler, the retailer and the consumer. While eradication of VTEC O157 at the farm may not be an option, interventions to increase animal resistance or to decrease animal exposure are being developed and validated. Hazard Analysis and Critical Control Programmes are being implemented in the processing sector and appear to be associated with temporal decreases in VTEC serotype O157 illness in humans. Education programmes targeting food handling procedures and hygiene practices are being advocated at the retail and consumer level. Continued efforts at all stages from the farm to the consumer will be necessary to reduce the risk of VTEC-associated illness in humans.