Identifying the sick: can biochemical measurements be used to aid decision making on presentation to the accident and emergency department.

BACKGROUND: Early and accurate identification of patients who may benefit from aggressive optimal medical intervention is essential if improved outcomes in terms of survival are to be achieved. We studied the usefulness of routine clinical measurements and/or markers of metabolic abnormality in the early identification of those patients at greatest risk of deterioration on presentation to the accident and emergency department. METHODS: We conducted a prospective observational study in the accident and emergency department of a 602-bed district general hospital. Routine clinical measurements (heart rate, systolic blood pressure, temperature, oxygen saturation in room air, level of consciousness and ventilatory frequency) and venous blood analysis for metabolic markers (pH, bicarbonate, standard base excess, lactate, anion gap, strong ion difference, and strong ion gap) and biochemical markers (Na+, K+, Ca2+, Cl-, PO4- albumin, urea and creatinine) were recorded from unselected consecutive hospital admissions over two 3-month periods (September-November 2002 and February-April 2003). RESULTS: Logistic regression analysis showed that neither conventional clinical measurements upon presentation to the accident and emergency department nor venous biochemical and metabolic indices have good discriminatory ability when used as single predictors of either hospital mortality or length of hospital stay. Selecting variables from all the clinical and venous blood measurements gave a parsimonious model containing only age, heart rate, phosphate and albumin (area under the receiver operating characteristic curve, 0.82 [95% CI 0.76, 0.87]). CONCLUSIONS: A combination of clinical and venous biochemical measurements in the accident and emergency department proved the best predictors of hospital mortality. Consequently, they may be helpful as a triage tool in the accident and emergency department to help identify patients at risk of deterioration.

Proteomic analysis reveals a novel set of cell wall proteins in a transformed tobacco cell culture that synthesises secondary walls as determined by biochemical and morphological parameters.

A cell suspension culture of a tobacco (Nicotiana tabacum L. cv. Petit Havana) cell line derived from a cultivar transformed with the Tcyt gene from Agrobacterium, which leads to high endogenous levels of cytokinin, has been established. This cell line shows increased cell aggregation, elongated cells and a 5-fold increase in wall thickness. If allowed to carry on growing it can form a single mass without shedding cells into the medium. When analysed at an earlier growth stage, these cultures were found to produce improved levels of vascular nodule formation than in other systems that employ exogenous cytokinin. This differentiation was optimised with respect to sucrose and auxin signals in order to induce maximum production of cells with thickened walls and a morphology characteristic of fibre cells and tracheids, in addition to cells that remain meristematic. In order to establish the validity of this system for studying secondary wall formation, the walls and associated biosynthetic changes were analysed in these cells by chemical analysis of the walls, changes in activities of enzymes of xylan and monolignol synthesis, and expression of mRNAs coding for enzymes of lignin biosynthesis. The wall composition of the transformed cells was compared with that determined for primary walls from a typical untransformed tobacco cell line. Recovery of wall material was 50% greater in the transformed culture. In this material a major difference was found in the pectin fraction where there was a distinct difference in size distribution together with a lower level of methylation for the transformed line, which may be related to increased adhesiveness. There were increased amounts of xylan, although the ratio of xyloglucan to xylan content was not substantially different due to the mixture of cell types. There was also an increase in cellulose and phenolic components. Increased activity of enzymes involved in the synthesis of xylan as a marker for the secondary wall occurred around the time of tracheid differentiation and coincided with a broad peak of cinnamyl alcohol dehydrogenase activity. The expression of mRNAs coding for enzymes of the general phenylpropanoid pathway, phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, catechol O-methyl transferase was relatively constitutive in the cultures while transcripts of ferulate 5-hydroxylase, cinnamoyl CoA-reductase, cinnamyl alcohol dehydrogenase and lignin peroxidase were induced. The walls of the transformed cells also showed considerable differences in the subset of extractable proteins from that found in primary walls of tobacco when these were subjected to proteomic analysis. Many of these proteins appear to be novel and not present in primary walls. However an Mr-32,000 chitinase, an Mr-34,000 peroxidase, an Mr-65,000 polyphenoloxidase/laccase and possibly an Mr-68,000 xylanase could be identified as well as structural proteins.

Differential extraction and protein sequencing reveals major differences in patterns of primary cell wall proteins from plants.

The proteins of the primary cell walls of suspension cultured cells of five plant species, Arabidopsis, carrot, French bean, tomato, and tobacco, have been compared. The approach that has been adopted is differential extraction followed by SDS-polyacrylamide gel electrophoresis (PAGE), rather than two-dimensional gel analysis, to facilitate protein sequencing. Whole cells were washed sequentially with the following aqueous solutions, CaCl2, CDTA (cyclohexane diaminotetraacetic acid, DTT (dithiothreitol), NaCl, and borate. SDS-PAGE analysis showed consistent differences between species. From the 233 proteins that were selected for sequencing, 63% gave N-terminal data. This analysis shows that (i) patterns of proteins revealed by SDS-PAGE are strikingly different for all five species, (ii) a large number of these proteins cannot be identified by data base searches indicating that a significant proportion of wall proteins have not been previously described, (iii) the major proteins that can be identified belong to very different classes of proteins, (iv) the majority of proteins found in the extracellular growth media are absent from their respective cell wall extracts, and (v) the results of the extraction process are indicative of higher order structure. It appears that aspects of speciation reside in the complement of extracellular wall proteins. The data represent a protein resource for cell wall studies complementary to EST (expressed sequence tag) and DNA sequencing strategies.

Radiographic features of neonatal congenital dislocation of the hip.

Over the 10-year period 1969 to 1978, 271 consecutive cases of congenital dislocation of the hip were diagnosed at birth. Standard anteroposterior radiographs of the pelvis were obtained routinely and were analysed retrospectively. The medial gap, a measure of the separation between the proximal femur and the pelvic wall, was found to be significantly increased in cases with unilateral or bilateral dislocation when compared to normal. A medial greater than five millimetres is indicative of femoral head displacement and is of value where the clinical diagnosis is uncertain. The rate of missed dislocation at birth was 0.6 cases per thousand. Treatment with the Malmo splint was the normal routine. The Pavlik harness was applied if splintage was poorly tolerated by the infant, or in the rare instance of limited hip abduction. Failure to maintain reduction by splintage occurred in 3.3 per cent. The incidence of pressure deformities of the femoral head was 2.95 per cent and there was a residual deformity in later childhood of 1.1 per cent. It is presumed that this lesion can be attributed to the effect of splintage and it was notably avoided in the later period of the review when greater mobility of the abducted hips was encouraged.

Exercise testing after the Chiari pelvic osteotomy.

The work capacity of 26 women after a Chiari pelvic osteotomy for symptomatic unilateral subluxation of the hip was assessed using two simple exercise tests: the maximal walking speed during a 12-minute test and the time taken to climb stairs. A significant linear decline in walking speed occurred with increasing age, despite the operation, and only one patient over the age of 25 years was able to walk at a normal rate. Compared to the results in a control group of women of similar age the stair climbing time was increased in 54 per cent of the patients and showed a significant negative correlation with the maximal walking speed. Age-adjusted walking speed was closely associated with the degree of pain experienced but there was no relationship between observed function and conventional clinical assessment based on the range of movement and the radiographic appearances of the hip.

Late congenital dislocation of the hip.

Congenital dislocation of the hip in a child over the age of 4 may be discovered as a late untreated displacement, presenting with subluxation or dislocation, or as a late treated displacement presenting as a subluxating or subluxated hip. Conservative treatment is inadequate in untreated dislocations. Surgical reduction is the only possible procedure, associated with shortening femoral. The procedure may be used up to the age of 7 in bilateral cases, and up to the age of 12 in unilateral cases. Subluxating hips are recognised on the anteroposterior radiograph by a break in Shenton's line. A delayed Trendelenburg sign may also been seen. In such cases, innominate osteotomy or femoral derotation osteotomy should be performed, according to the anatomical defects present. Femoral shortening may be indicated in cases of increased length of the lower limb, associated with residual coxa valga or over growth following a previous rotation osteotomy to avoid the mechanical effects on the opposite hip. In cases of subluxated hip, varus upper femoral osteotomy may be indicated, or a Chiari osteotomy in painful hips. It is concluded that routine follow-up radiography is necessary, surgery being indicated as soon as a loss of acetabularcover of the femoral head is detected.

Abductor hallucis release in congenital metatarsus varus.

Adduction of the forefoot diagnosed in the young child generally corrects spontaneously. Resistant forefoot adduction is usually combined with a degree of supination of the forefoot and described as congenital metatarsus varus. In true congenital metatarsus varus there is a contraction or shortening of the abductor hallucis muscle and tendon which is considered to be the primary deforming factor. In the early severe or resistant deformity correction can be achieved by either division of the tendon with release of its capsular attachment, or, in the more severe deformity, by complete release of the abductor hallucis muscle from its extensive attachment to bone and soft tissues.

Posterior displacement osteotomy of the calcaneus.

In cases of established calcaneus after anterior poliomyelitis the deformity can be greatly reduced by combining an extensive plantar release with an oblique transverse osteotomy of the calcaneus that permits displacement upwards and backwards of the posterior weight-bearing part of the bone. The procedure greatly improves the mechanical advantage of subsequent tendon transplantations to the heel. Between 1956 and 1969 fifteen such osteotomies were carried out and the long-term results have been reviewed.