Use of the patient at risk scores in the emergency department: a preliminary study

Objectives: To assess the feasibility of using a modified patient at risk (PAR) scoring system in the emergency department.

Methods: Modified PAR scores were calculated for 30 triage category 1 and 2 patients on arrival in the department and at 15 minutes after the initial resuscitation was underway using observation datasheets designed for this project.

Results: Three patients (10%) were admitted to the intensive care unit (ICU). Twenty six patients (88%) were admitted to a general ward and one was discharged. Fifty per cent of the patients had a PAR score of 3 or more on arrival. Eighty seven per cent of the general ward patients had a PAR score that was stable or improved during the first 15 minutes of resuscitation. The other three ward patients, whose scores deteriorated, were assessed in the emergency department by the appropriate teams and deemed appropriate for ward beds. Two of the three ICU patients deteriorated in the resuscitation room. The third ICU patient maintained a PAR score of 2 but had such overwhelming injuries that ICU was the only option.

Discussion: Serial PAR scores are far more informative than isolated scores. This study suggests that serial PAR scores could be used in three ways in the emergency department. Firstly, in the assessment of individual patients and their response to initial resuscitation. Secondly, as a guide to the need further specialist assessment before leaving the emergency department. Finally, as an audit tool to measure the effectiveness of initial treatments in large numbers of patients during the initial resuscitation.

     

Introduction of H-2Dd determinants into the H-2Ld antigen by site-directed mutagenesis

We used site-directed mutagenesis to localize serologically defined (s) and CTL (c)-defined alloantigenic determinants to discrete amino acid sequences of a murine MHC class I antigen. Based on the prediction that amino acid position 63-73 of the H-2Dd antigen forms s-allodeterminants, the H-2Ld gene was mutated in a sequential fashion to replace codons for amino acid positions 63, 65, 66, 70, and 73 with those of the H-2Dd amino acids. Epitopes of the mutant antigens expressed in L-cells were examined by the binding of a series of mAbs specific for the H-2Dd antigen. The mutant antigen M66 had substitutions at residues 63, 65, and 66, and resulted in the acquisition of a number of H-2Dd-specific s-epitopes. Mutant M70 had an additional substitution at residue 70, which led to the gain of multiple additional H-2Dd s-epitopes. Together, more than half of all the relevant H-2Dd s-epitopes were mapped into amino acid position 63-70 of the H-2Dd molecule, which was expressed in the mutant H-2Ld gene. The final mutation at residue 73 (M73) caused no new epitope gains, rather, a few Dd s-epitopes acquired by the preceding mutations were lost. All of the H-2Ld-specific s-determinants were retained in the mutant molecules, as were H-2Dd s-determinants specific for the alpha-2 or alpha-3 domains. Changes of these residues affected c-determinants defined by CTL. Anti-H-2Dd CTL cultures and an anti-H-2Dd CTL clone recognized the mutant H-2Ld molecules, M66 and M70. Some CTL clones generated against the Q10d molecule, which has an identical sequence to H-2Dd between residues 61 and 73, failed to recognize native H-2Dd or Ld but did crossreact with mutant Ld. While bulk-cultured anti-H-2Ld CTL cultures reacted strongly against M73, bulk-cultured H-2Ld restricted anti-vesicular stomatitis virus CTL did not. Finally, at the clonal level two of three anti-H-2Ld CTL clones lost reactivity with some or all of these mutant molecules. From these results we conclude that a stretch of amino acids from position 63 to 70 of the alpha-1 domain controls major s- and c-antigenic sites on the H-2Dd antigen and c-sites on H-2Ld antigen.     

Sonographic changes of the pancreas in chronic renal failure

Several abnormalities regarding pancreatic morphology and function have been reported in patients with chronic renal failure (CRF) with an incidence as high as 72%. In a prospective study we investigated 96 outpatients from our chronic ambulatory hemodialysis program by abdominal ultrasound. Of the patients with CRF, 20.6% were found to have morphologic alterations of the pancreas compared to 4.7% of controls. Although pathologic sonograms of the pancreas correlated with biliary disease, hyperparathyroidism and years of hemodialysis, the most obvious etiologic factor appeared to be the duration of CRF. Possible pathogenetic mechanisms are discussed and screening abdominal ultrasound examinations in patients with long-standing CRF are recommended.     

The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins

A primary pathologic component of Alzheimer's disease (AD) is the formation of neurofibrillary tangles composed of hyperphosphorylated tau (p-tau). Expediting the removal of these p-tau species may be a relevant therapeutic strategy. Here we report that inhibition of Hsp90 led to decreases in p-tau levels independent of heat shock factor 1 (HSF1) activation. A critical mediator of this mechanism was carboxy terminus of Hsp70-interacting protein (CHIP), a tau ubiquitin ligase. Cochaperones were also involved in Hsp90-mediated removal of p-tau, while those of the mature Hsp90 refolding complex prevented this effect. This is the first demonstration to our knowledge that blockade of the refolding pathway promotes p-tau turnover through degradation. We also show that peripheral administration of a novel Hsp90 inhibitor promoted selective decreases in p-tau species in a mouse model of tauopathy, further suggesting a central role for the Hsp90 complex in the pathogenesis of tauopathies. When taken in the context of known high-affinity Hsp90 complexes in affected regions of the AD brain, these data implicate a central role for Hsp90 in the development of AD and other tauopathies and may provide a rationale for the development of novel Hsp90-based therapeutic strategies.     

Developing research criteria to define medical necessity in emergency medical services

“The Neely Conference: Developing Research Criteria to Define Medical Necessity in EMS” convened emergency medical services (EMS) physicians, researchers, administrators, providers, and federal agency representatives to begin the development of a set of uniform triage criteria and outcome measures that could be used to study and evaluate medical necessity among EMS patients. These standardized criteria might be used in research studies examining EMS dispatch and response (e.g., dispatch triage protocols, alternative response configurations), and EMS treatment and transport (e.g., field triage protocols, alternative care destinations). The conference process included review and analysis of the literature, expert judgment, and consensus building. There was general agreement on the following: 1. Any dispatch triage or field triage system that is developed must be designed to offer patients alternatives to EMS, not to refuse care to patients. 2. It is theoretically possible to develop a set of clinical criteria for need. Some groups of patients will clearly need a traditional EMS response and other groups will not, but this has yet to be defined. 3. In addition to clinical criteria, certain social and other nonclinical criteria such as pain or potential abuse may be used to justify a response. 4. Communication barriers, patient age, special needs, and other conditions complicate patient assessment but should not exclude patients from consideration for alternate triage or transport. 5. These research questions are important, and standard sets of outcome measures are needed so that different studies and innovative programs can be compared.     

Cell cycle inhibition preserves endothelial function in genetically engineered rabbit vein grafts.

We have recently shown that ex vivo gene therapy of rabbit autologous vein grafts with antisense oligodeoxynucleotides (AS ODN) blocking cell cycle regulatory gene expression inhibits not only neointimal hyperplasia, but also diet-induced, accelerated graft atherosclerosis. We observed that these grafts remained free of macrophage invasion and foam cell deposition. Since endothelial dysfunction plays an important role in vascular disease, the current study examined the effect of this genetic engineering strategy on graft endothelial function and its potential relationship to the engineered vessels' resistance to atherosclerosis. Rabbit vein grafts transfected with AS ODN against proliferating cell nuclear antigen (PCNA) and cell division cycle 2 (cdc2) kinase elaborated significantly more nitric oxide and exhibited greater vasorelaxation to both calcium ionophore and acetylcholine than did untreated or control ODN-treated grafts. This preservation of endothelial function was associated with a reduction in superoxide radical generation, vascular cell adhesion molecule-1 (VCAM-1) expression, and monocyte binding activity in grafts in both normal and hypercholesterolemic rabbits. Our data demonstrate that AS ODN arrest of vascular cell cycle progression results in the preservation of normal endothelial phenotype and function, thereby influencing the biology of the vessel wall towards a reduction of its susceptibility to occlusive disease.     

Some lifestyle habits of female Belgrade university students with migraine and non-migraine primary headache

Abstract We performed a prevalence study to compare some lifestyle habits between subjects with migraine and those with nonmigraine primary headaches. We surveyed female students in randomly selected classes of the School of Medicine and the School of Pharmacy, Belgrade University. Among all observed students (1943 subjects), 245 had migraine and 1053 had non-migraine primary headache. According to multivariate logistic regression analysis, the following factors were associated with migraine: irregular eating (odds ratio (OR)=1.99; 95% confidence interval (95% CI), 1.69 to 2.34; p<0.01), sleep duration shorter than usual (OR=1.18; 95% CI 1.00 to 1.38; p=0.0449) and smoking >10 cigarettes per day (OR=1.18; 95% CI=1.00 to 1.39; p=0.0433). The results of the present study are in line with some other investigations suggesting that some lifestyle habits probably play a role as migraine precipitants.     

Influence of pigments and pH of urine on the determination of N-acetyl-beta-D-glucosaminidase activity with 2-methoxy-4-(2'-nitrovinyl)-phenyl-N-acetyl-beta-D-glucosaminide

The influence of urinary pigments and urine pH on the spectrophotometric determination of N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30) activity with 2-methoxy-4-(2'-nitrovinyl)-phenyl-N-acetyl-beta-D-glucosaminide as a substrate was studied. The investigation was performed with human and rabbit urine samples. It was found that alkaline urine pH values influenced NAG activity in two ways: 1) NAG activity decreased due to enzyme instability with pH increase, and 2) NAG activity increased because of the contribution of urinary pigments to absorbance of 2-methoxy-4-(2'-nitrovinyl)-phenol (MNP) at 505 nm. It was shown that besides the maximum (I) in the range of 350-360 nm of the absorption spectra of alkaline urine, there was a maximum (II) in the range of 380-460 nm. With the increase of pH, maximum II was shifted toward higher wavelengths and contributed to MNP absorption (5-90%). On the other hand, the maximum of MNP absorption was shifted toward lower wavelengths (495-400 nm) with increasing pH. Two procedures to eliminate the influence of urinary pigments are presented. The justification of applying a correction to the values of NAG activity in human and rabbit urine (a model system for studying the toxic effects of cadmium) was discussed.     

Systematic review of the efficacy of fat grafting and platelet‐rich plasma for wound healing

Adipose‐derived stem cells found in fat grafts may have significant healing properties. When fat is combined with autologous platelet‐rich plasma (PRP), there may be enhanced healing effects due to the pro‐angiogenic and anti‐inflammatory effects of PRP. This study aimed to evaluate the current evidence on fat grafting in combination with PRP for wound healing to establish the efficacy of this technique. A comprehensive search in the MEDLINE, EMBASE, CENTRAL, Science Citation Index, and Google Scholar databases (to March 2017) was conducted to identify studies on fat grafting and PRP for wound healing. Case series of less than 3 cases and studies only describing harvest technique were excluded. The database identified 571 articles, of which 3 articles that used a combination of fat and PRP for wound healing (1 RCT and 2 case series) were included in this review. A total of 69 wounds in 64 patients were treated with an average wound size of 36.32cm². Of these, 67% of wounds achieved complete healing. When reported, the mean time to healing was 7.5 weeks for those who underwent a single treatment. There were no significant complications in any patients. The combination of fat grafting and PRP may achieve adequate wound healing with relatively quick wound healing time compared with standard wound management options. However, evidence is extremely limited, and further studies are required to evaluate its efficacy for wound healing.