With the growing number of fatalities resulting from the 100 or so cancer-related diseases, new enabling tools are required to provide extensive molecular profiles of patients to guide the clinician ...in making viable diagnosis and prognosis. Unfortunately with cancer-related diseases, there is not one molecular marker that can provide sufficient information to assist the clinician in making effective prognoses or even diagnoses. Indeed, large panels of markers must typically be evaluated that cut across several different classes (mutations in certain gene fragments—DNA; over/under-expression of gene activity as monitored by messenger RNAs; the amount of proteins present in serum or circulating tumor cells). The classical biosensor format (dipstick approach for monitoring the presence of a single element) is viewed as a valuable tool in many bioassays, but possesses numerous limitations in cancer due primarily to the single element nature of these sensing platforms. As such, if biosensors are to become valuable tools in the arsenal of the clinician to manage cancer patients, new formats are required. This review seeks to provide an overview of the current thinking on molecular profiling for diagnosis and prognosis of cancers and also, provide insight into the current state-of-the-art in the biosensor field and new strategies that must be considered to bring this important technology into the cancer field.
Summary
The dissemination of Enterobacteriaceae expressing resistance to extended‐spectrum cephalosporins, which are therapeutically used in both human and veterinary medicine, is of critical ...concern. The normal commensal flora of food animals may serve as an important reservoir for the zoonotic food‐borne transmission of Enterobacteriaceae harbouring β‐lactam resistance. We hypothesized that the predominant AmpC and ESBL genes reported in US livestock and fresh retail meat products, blaCMY‐2 and blaCTX‐M, would also be predominant in human enteric flora. We recovered enteric flora from a convenience sample of patients included in a large tertiary medical centre's Clostridium difficile surveillance programme to screen for and estimate the frequency of carriage of AmpC and ESBL resistance genes. In‐ and outpatient diarrhoeic submissions (n = 692) received for C. difficile testing at the medical centre's clinical diagnostic laboratory from July to December, 2013, were included. Aliquoted to a transport swab, each submission was inoculated to MacConkey broth with cefotaxime, incubated at 37°C and then inoculated to MacConkey agars supplemented with cefoxitin and cefepime to select for the AmpC and ESBL phenotypes, with blaCMY and blaCTX‐M genotypes confirmed by PCR and sequencing. From the 692 diarrhoeic submissions, our selective culture yielded 184 isolates (26.6%) with reduced susceptibility to cefotaxime. Of these, 46 (6.7%) samples harboured commensal isolates carrying the AmpC blaCMY. Another 21 (3.0%) samples produced isolates harbouring the ESBL blaCTX‐M: 19 carrying CTX‐M‐15 and 2 with CTX‐M‐27. Our results indicate that β‐lactam resistance genes likely acquired through zoonotic food‐borne transmission are present in the enteric flora of this hospital‐associated population at lower levels than reported in livestock and fresh food products.
Preeclampsia is associated with a risk of abnormal hemostasis that occurs most commonly secondary to thrombocytopenia. Thromboelastography measures whole blood coagulation and has been used to manage ...coagulation defects in obstetric patients. The authors conducted this investigation in a large number of preeclamptic women to assess changes in coagulation using thromboelastography.
Thromboelastography and platelet counts were performed in 52 healthy pregnant women, 140 mild preeclamptic women, and 114 severe preeclamptic women in active labor using disposable plastic cups and pins and native whole blood. In preeclamptic patients with a platelet count <100,000/mm3, conventional coagulation tests were also performed. Epidural analgesia was provided in some women when they requested pain relief.
Fifteen percent of all preeclamptic women (38 of 254) and 2% (1 of 52) of healthy pregnant women had a platelet count <100,000/mm3. The incidence of thrombocytopenia <100,000/mm3 was 3% (4 of 140) and 30% (34 of 114) in mild preeclamptic patients and severe preeclamptic patients, respectively. Severe preeclamptic patients with a platelet count <100,000/mm3 were significantly hypocoagulable when compared to the other study groups. Ten severe preeclamptic women with a platelet count <100,000/mm3 had a maximum amplitude <54 mm (the lower limit of maximum amplitude in healthy pregnant women enrolled in this investigation). None of the mild preeclamptic women had a maximum amplitude <54 mm. Five severe preeclamptic women with a platelet count <100,000/mm3 had an abnormal coagulation profile, whereas all four mild preeclamptic women with a platelet count <100,000/mm3 had a normal coagulation profile.
This study shows that severe preeclamptic women with a platelet count <100,000/mm3 are hypocoagulable when compared to healthy pregnant women and other preeclamptic women.
Cardiopulmonary bypass (CPB) is characterized by systemic endotoxemia immediately after its onset as well as the systemic release of proinflammatory cytokines, including tumor necrosis factor-α and ...the interleukins 1 and 6. Recent studies document that increased morbidity and mortality rates correlate with elevated systemic concentrations of these proinflammatory cytokines during adult and neonatal sepsis, following thoracoabdominal aortic aneurysm repair, as well as following CPB. These proinflammatory cytokines induce increased neutrophil and endothelial surface adhesive molecule expression, thereby promoting enhanced neutrophil-endothelial adherence. Increased neutrophil-endothelial adherence and subsequent neutrophil organ binding are thought to be a “final common pathway” of organ injury during clinical inflammatory conditions. Proinflammatory cytokines also increase cellular expression of inducible nitric oxide synthase, thus increasing cellular production of nitric oxide, a known inflammatory mediator. This review discusses recent evidence of the adverse effects of proinflammatory cytokine release during CPB and therapeutic modalities that can reduce the systemic concentrations of these mediators of inflammation.
There is an increasing trend toward performing craniotomy for primary brain tumor excision with local anesthesia. We report the use of the laryngeal mask airway as a part of an anesthetic technique ...designed for patients requiring awake cortical mapping during brain tumor excision.
A shell disease epizootic is described for the American clawed lobster (Homarus americanus) populations in southern New England. This paper presents a conceptual model for examination of shell ...disease and presents evidence to support three hypotheses. Hypothesis one proposes that epizootic shell disease prevalence has increased in wild lobster populations; hypothesis two proposes that there are population-level effects of shell disease and hypothesis three explores the relationship between shell disease, and environmental and anthropogenic disturbances. This conceptual model links environmental stressors to physiological upsets and disease to population level impacts and can serve as a general model of disease in the marine environment.
In 1994, the American Society of Anesthesiologists established the Task Force on Blood Component Therapy to develop evidence-based indications for transfusing red blood cells, platelets, fresh-frozen ...plasma, and cryoprecipitate in perioperative and peripartum settings. The guidelines were developed according to an explicit methodology. The principal conclusions of the task force are that red blood cell transfusions should not be dictated by a single hemoglobin "trigger" but instead should be based on the patient's risks of developing complications of inadequate oxygenation. Red blood cell transfusion is rarely indicated when the hemoglobin concentration is greater than 10 g/dL and is almost always indicated when it is less than 6 g/dL. The indications for autologous transfusion may be more liberal than for allogeneic (homologous) transfusion. The risks of bleeding in surgical and obstetric patients are determined by the extent and type of surgery, the ability to control bleeding, the actual and anticipated rate of bleeding and the consequences of uncontrolled bleeding. Prophylactic platelet transfusion is ineffective when thrombocytopenia is due to increased platelet destruction. Surgical and obstetric patients with microvascular bleeding usually require platelet transfusion if the platelet count is less than 50 times 10(9)/l and rarely therapy if it is greater than 100 times 10(9)/l. Fresh-frozen plasma is indicated for urgent reversal of warfarin therapy, correction of known coagulation factor deficiencies for which specific concentrates are unavailable, and correction of microvascular bleeding when prothrombin and partial thromboplastin times are >1.5 times normal. It is contraindicated for augmentation of plasma volume or albumin concentration. Cryoprecipitate should be considered for patients with von Willebrand's disease unresponsive to desmopressin, bleeding patients with von Willebrand's disease, and bleeding patients with fibrinogen levels below 80-100 mg/dL. The task force recommends careful adherence to proper indications for blood component therapy to reduce the risks of transfusion. (Key words:Practice guide-lines: anemia: blood component therapy; coagulopathy; cryoprecipitate; fresh-frozen plasma; red blood cells; transfusion.)
Summary The dissemination of Enterobacteriaceae expressing resistance to extended-spectrum cephalosporins, which are therapeutically used in both human and veterinary medicine, is of critical ...concern. The normal commensal flora of food animals may serve as an important reservoir for the zoonotic food-borne transmission of Enterobacteriaceae harbouring beta-lactam resistance. We hypothesized that the predominant AmpC and ESBL genes reported in US livestock and fresh retail meat products, blaCMY-2 and blaCTX-M, would also be predominant in human enteric flora. We recovered enteric flora from a convenience sample of patients included in a large tertiary medical centre's Clostridium difficile surveillance programme to screen for and estimate the frequency of carriage of AmpC and ESBL resistance genes. In- and outpatient diarrhoeic submissions (n = 692) received for C. difficile testing at the medical centre's clinical diagnostic laboratory from July to December, 2013, were included. Aliquoted to a transport swab, each submission was inoculated to MacConkey broth with cefotaxime, incubated at 37°C and then inoculated to MacConkey agars supplemented with cefoxitin and cefepime to select for the AmpC and ESBL phenotypes, with blaCMY and blaCTX-M genotypes confirmed by PCR and sequencing. From the 692 diarrhoeic submissions, our selective culture yielded 184 isolates (26.6%) with reduced susceptibility to cefotaxime. Of these, 46 (6.7%) samples harboured commensal isolates carrying the AmpC blaCMY. Another 21 (3.0%) samples produced isolates harbouring the ESBL blaCTX-M: 19 carrying CTX-M-15 and 2 with CTX-M-27. Our results indicate that beta-lactam resistance genes likely acquired through zoonotic food-borne transmission are present in the enteric flora of this hospital-associated population at lower levels than reported in livestock and fresh food products.
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