Endothelin-1 levels in severe burn injuries.

HYPOTHESIS: Most investigators have reported high levels of endothelin (ET)-1 in patients with thermal injury. We attempted to examine the hypothesis that ET-1 levels increase in patients with severe burn injury. PATIENTS AND METHODS: Plasma from 28 adult subjects, 14 of whom had thermal injuries with a median (range) percentage of total burn surface area of 22% (20%-76%), was assessed for ET-1 and tumor necrosis factor (TNF) alpha. Samples from closely age-matched patients were obtained on admission (day 1) and 24 hours postinjury (day 2). Samples were obtained before blood transfusion or surgical treatment occurred. Enzyme immunoassay techniques suitable for the measurements of the cytokines were used. RESULTS: Median (range) of TNF-alpha was higher in patients (day 1, 10.0 ng/L [1.2-35.0 ng/L]; day 2, 12.0 ng/L [0.4-39.0 ng/L]) than controls (0. 8 ng/L [0.3-3.2 ng/L]) (P<.005) while ET-1 levels remained significantly unchanged in patients (mean [SD], day 1, 183.0 [42.2] ng/L; day 2, 204.7 [41.7] ng/L) compared with controls (170.0 [59.8] ng/L) (P>.05). CONCLUSIONS: We observed no significantly raised levels of ET-1 in patients with thermal injury within 24 hours after burn injury. We found no significant correlation between the plasma levels of TNF-alpha and ET-1. Endothelin-1 levels did not seem to reflect severity of illness. The actual evaluation of ET-1 release in patients with thermal injury could enhance the pathophysiological study of human thermal injury.

Plasma-circulating levels of natriuretic peptides in patients with bone and soft tissue injuries.

To evaluate the release and possible role of N-terminal end of atrial natriuretic factor (ANF) prohormone (proANF-1-30) and C-terminal end of ANF prohormone (aANP-1-28) in patients with soft tissue and bone injuries, 20 patients with soft tissue injuries, 18 bone-fractured patients, and 21 healthy controls were examined. Samples were collected from patients within 24 h after injury. Plasma level of proANF-1-30 and aANP-1-28 were higher in orthopedic patients than the soft tissue injury patients compared to controls (P < 0.005, P<0.05, respectively). proANF-1-30 was over 15-fold greater than aANP-1-28 in the healthy control samples. These data hypothesized that the concentration of proANF-1-30 may be related to tissue damages in man.

Plasma levels of N-terminal peptide of pro-atrial natriuretic peptides in myoskeletal injuries.

To determine whether concentrations of the N-terminal peptide of pro-atrial natriuretic peptide (proANP) and of alpha atrial natriuretic peptide 1-28 (aANP) releases are affected by myoskeletal injuries, samples from 24 patients with muscle injuries were therefore collected within 48 h of injury. The mean age of patients was 65; range: 17-90 years. These were compared with 18 non-injured subjects with a mean age of 40; range: 17-80 years. A specific enzyme immunoassay (EIA) method suitable for the determination of proANP and aANP was used. aANP required plasma extraction and no extraction was needed for proANP determination.ProANP level was significantly higher in patients on admission and this level was maintained 24 h after admission (p < 0.05) compared to controls. However, aANP 1-28 level remained statistically unchanged in the patients samples. The level of proANP was over 10 times greater than the levels obtained with aANP. N-terminal peptide of proANP may be a supplementary tool in the study of early phase of myoskeletal injuries in human.

Elevation of plasma CGRP and SP levels in orthopedic patients with fracture neck of femur.

Calcitonin gene-related peptides (CGRP) is a 37 amino acids peptide that has a proliferative effect on human endothelial cells, and is therefore important for the formation of new vessels and wound healing. As indicated by in vitro and animal studies, CGRP is also a potent vasodilator for cutaneous, cerebral, coronary vessels, a bronchoconstrictor and endocrine regulator. Systemic CGRP increase in patients with soft tissue injuries, chronic illness and sepsis, indicates that CGRP may yet be an important peptides in chronic illness. Although CGRP is a potent vasodilator, systemic vascular resistance does not increase in some patients with high CGRP levels. We questioned whether any changes occur in systemic CGRP levels in patients with one of the most common types of bone fractures especially in the elderly. In order to evaluate further the role of this peptide in these patients, a vasoconstictor (Endothelin-1 [ET]) and another sensory neuropeptide (Substance P [SP]) were measured within 24 h of injury. A sample was obtained on admission (day 1) and within 24 h post admission (day 2) in patients with fracture neck of femur (mean age 77.6, +/- 10 years, n = 20) and compared with healthy controls (51, +/- 26.8 years, n = 20). Peptides and hormones were measured by ELISA techniques. Mean (ng/l) CGRP was elevated in patients (day 1 [314 +/- 195] and day2 [209.2 +/- 150]); compared to controls (68.2 +/-31) P<0.005. Endothelin was non-significantly higher in day-2 (day 1 [28.5 +/-31], day2 [37.4 +/-38], controls [24.2 +/-21]) P = NS. SP maintained higher levels within 24 h after injury (day 1 [85.7 +/- 94], and day2 [80.9 +/- 91.8]) compared to controls, P< 0.05. Furthermore, Elastase (a decisive marker for inflammation and infectious complications) was found to be higher in patients being pronounced in day 2 than in day 1 (day 1 [200 +/-136], day2 [139 +/-118]). Creatine kinase and myoglobin were measured and found to be notably higher in patients. These peptides may be yet another group of cytokines playing significant role in immunologic, inflammatory complications or wound healing in this group of patients.

Distributions of VIP, substance P, neurokinin A and neurotensin in rat heart: an immunocytochemical study.

Vasoactive intestinal peptide (VIP) is a peptide amide containing 28 amino acids which was first isolated from the intestine and is distributed over the entire body but primarily in the nervous system. It is released in response to the electrical stimulation of nerve fibres, stimulation of the vagus, prostaglandin E1, oxytocin, operation stress, corticosterone. In the cardiovascular system, VIP has a vasodilation, hypotension, positive chronotropic and inotropic effects.

Regulatory peptides in the heart and major vessels of man and mammals.

Studies on the distribution of peptides in human tissues have been made either by measuring responses to localized stimuli or by subjecting extracts of different regions to radioimmunoassay (RIA). Attempts at isolating regulatory peptides from the mammalian tissues have resulted in the isolation of many bioactive fragments. Later, modification of initial isolation methods led to the identification of the native molecules in various tissues and body fluids. The present study examined atrial natriuretic peptide (ANP) and several other peptides in cardiac tissues of several species of laboratory mammal and human beings; using a sensitive and highly specific radioimmunoassays. In all the species studied, ANP-like immunoreactivity appeared to be highest in the heart tissue of rat. The peptide was highest in the right atrium (RA) of rat and lowest in the RA of guinea pig (P< 0.002). Neuropeptide Y (NPY) another abundant cardiac peptide was present in the cardiac tissues of all species but was more in the left atrium (LA) than the RA of all species (P<0.05). Calcitonin gene-related peptide (CGRP) was present throughout the cardiovascular system of the rat and guinea pig. Small but detectable amount of Neurotensin (NT) immunoreactivity was found in the rat but was consistently negative in the guinea pig cardiac tissues (P< 0.05). Substance P (SP) immunoreactivity was detected in the rat and higher quantities being in the Aorta but no trace of the peptide was detected in the left ventricle, aorta nor the pulmonary vein of post mortem human. Though the structure of most of the species studied has been elucidated, the primary structure of guinea pig ANP has not been fully generated. Thus the data obtained may suggest that in keeping with these mammalian peptides, the primary structures may be variant. With most of the peptides studied (e.g. ANP, Neuropepdide Y), immunoreactivity occurs predominantly in the atrial tissues, but is also present in vessels outside the heart, a finding which may be of functional significance.

Calcitonin gene-related peptide and other neuropeptides in the plasma of patients with soft tissue injury.

Calcitonin gene-related peptide [CGRP]--a powerful vasodilator, is a 37 amino acid peptide that is find primarily in the central and peripheral nervous system. It affects the regulation of local blood flow, smooth muscle tone and glandular secretion. It is an endocrine regulator and in the lungs it also exerts a bronchoconstricting effect. CGRP has a proliferative effect on human endothelial cells. Therefore, it is important for the formation of new vessels, example, in ischemia, inflammations, and in the healing of wounds. Plasma levels of CGRP are increase in patients with chronic cardiac failure and sepsis, indicating that CGRP may be another important peptide in chronic illness. We have therefore measured the release of this peptide and another sensory peptide [Substance P (SP)]; a vasoconstrictor peptide [Endothelin (ET)]; and a perivascular peptide [Neuropeptide Y (NPY)], within 24 hours of injury, in the plasma of patients with soft tissue injury. Neuropeptides were measure by enzyme immunoassay technique. Median: (lower quartile-upper quartile) in pmol/L CGRP level was elevated in patients [50.37: (12.4-110.9)] compared to controls [13.9: (10.9-36.96)] p<0.05; Endothelin and NPY did not vary much between groups p=NS; ET: patients [8.7: (1.7-87.1), controls 8.8: (1.7-32.9)]; NPY: Patients [11.7: (10.5-14.99), controls 11: (10.3-12.8)]. SP was increase in patients [302.3: (79.9-707.3)], than controls [5.6: (3.2-36.6)] p<0.05. Furthermore, Elastase (a decisive marker for inflammation and infectious complications), was measure (ng/L), and found to be slightly higher in patients (102: 25.5-223), than controls (91.8: 45.9-127). In summary, plasma levels of sensory peptides increased significantly, in patients with soft tissue injury, in contrast to vasocostrictor peptides that remained unchanged. These sensory peptides may yet be another group of neuromodulators playing a significant role in immune, pain, inflammatory and wound healing in soft tissue injury patients.

Levels of myosin heavy chain fragment in patients with tissue damage.

BACKGROUND: Myosin heavy chain fragments (MHC) levels are observed to be higher in myoskeletal injuries after surgery. MHC could be a helpful supplementary tool in the study of myoskeletal injuries. METHODS: Serum levels of myosin heavy chain fragments (MHC) were assessed in orthopedic patients before operation (OBO) and after operative (OAO) repairs and in the early phase of soft tissue injury (STI) using a radioimmunoassay involving monoclonal antibodies to the human beta-type MHC. RESULTS: Mean (SD) microU/L of MHC in comparison with the control subjects (75.3 +/- 47.1) was higher in OAO (305.8 +/- 38.1) p <0.0001, and no significant changes in MHC were found in STI (67 +/- 77.5). Myoglobin was notably higher in OBO (81.9 +/- 95.0) compared to STI (43.9 +/- 55.9) or controls p <0.05, but there was no further change in the protein after surgery. The mean proportional raised level of myoglobin in OBO was >twofold, and MHC increased by 27%. Neither myoglobin nor MHC increased in the plasma of the STI within 24 h of injury. CONCLUSIONS: These data suggest that the release of MHC could be a helpful supplementary tool in the study of tissue damage in humans.

Plasma levels of atrial natriuretic peptide in severe burn injury.

Atrial natriuretic peptide (ANP) plays a part in the regulation of volume homeostasis and possibly, in the pathophysiology of water and electrolyte disorder. Patients with serious burn injuries risk huge body fluids losses, which are compensated for by perfusion. Blood volume and the renin and aldosterone system are also disturbed. This study measured plasma ANP and vasoactive intestinal polypeptide (VIP) in patients with >20% total burned surface area (TBSA), at admission and 24 h post-admission.Eleven patients (mean age 46.5 years, 8 males) with a mean TBSA of 34.5% were sampled. Standard treatment was given. Eleven closely age-matched volunteers were used as controls. A specific ELISA method suitable for the measurement of ANP and VIP was used.ANP was higher (p<0.0001), while VIP was lower (p=NS) in patients' samples compared to controls. While the level of VIP was higher at 24 h post-admission, mean ANP level remained about the same. The increased levels of plasma ANP may result from volaemic disturbances during resuscitation, low VIP levels, the increase in pulmonary resistance or post-burn stress.

Early prediction of outcome following head injury in children.

A retrospective survey of 166 children aged 15 years or less was made in an attempt to identify which clinical features presenting in the first 24 hours after a head injury might be helpful in predicting the eventual outcome as defined by the Glasgow Outcome Scale. In 88% of the children, the trend of Glasgow Coma Scale score over the first 24 hours was useful. This included children admitted with a score of 3 or 4 and those with a score of 5 or more who did not deteriorate within 24 hours of injury. In this group only 2% of the predictions would have been inaccurate and in only 0.7% would the outcome have been worse than the prediction. The presence of both abnormal plantar and pupillary light reflexes predicted death or significant disability in 99% of cases.

Outcome of supracondylar fractures of the humerus in children.

Seventy patients who had sustained supracondylar fractures of the humerus as children were examined. Loss of carrying angle of the elbow occurred if the fracture was immobilized in a varus position during healing. Varus malalignment could have been obviated if comparative radiographs of the other elbow had been taken and the Baumann angles compared. Rotation and posterior displacement at the fracture had little bearing on the outcome. Immobilization of the fracture in a collar and cuff sling was as effective as more elaborate methods.

Cephradine and flucloxacillin in the prophylaxis of infection in patients with open fractures.

A comparison of prophylactic antibiotic cover of cephradine or flucloxacillin in sixty patients with open fractures is reported. There were more infections in the flucloxacillin than in the cephradine group and gastrointestinal side-effects were more common. The overall incidence of infection in the whole group, two out of 60 or 3.3%, was acceptably low.

Late stability of the cervical spine.

Radiological criteria, laid down to detect instability of the cervical spine after cadaveric biomechanical studies, were applied to 52 cases of cervical spine injury. Only one case of instability was detected, and late neurological signs resolved after posterior cervical fusion. Three other cases which fulfilled the radiological criteria of instability clinically were symptom free. It is concluded that these criteria alone cannot establish the indications for surgical intervention.

Intraspinal spur and scoliosis.

An unusual case of scoliosis, associated with an osteocartilaginous spur producing narrowing of the spinal canal, is reported. Routine physical examination and radiography revealed no abnormality apart form an absent left-ankle reflex. The defect was discovered at autopsy following death during operation. In order to discover this rare associated defect in scoliotic patients, myelography is recommended whenever a minor neurological defect is present.

Levels of vasodilators (SP, CGRP) and vasoconstrictor (NPY) peptides in early human burns.

An intact nociceptor system of primary afferent sensory nerves is important for the initiation of the inflammatory process and successful tissue repair. Dysfunction of this system could be a contributing factor for delayed wound healing in humans. We examined the levels of vasodilators [substance P (SP), calcitonin gene-related peptide (CGRP)] and a vasoconstrictor peptide [neuropeptide Y (NPY)] in the peripheral blood samples of patients with burns covering from 20 to 75% of body surface area. Thirteen patient samples were obtained immediately on admission (OA), which was within 12 h of the thermal injury, and 24 h post-admission (PA). Enzyme immunoassay techniques were used for the measurement of the neuropeptides. In addition, an inflammatory marker, tumour necrosis factor-alpha (TNF-alpha), and a myofibrillar protein, creatine kinase (CK), were examined and compared with levels in 13 control subjects. CGRP was high OA and the levels were maintained PA (P < 0.05). SP was also significantly high at both sampling times (P < 0.05). Although TNF-alpha and NPY were somewhat higher in the patients' samples than in the control samples, these levels were not statistically significant (P = NS). CK was higher OA (P < 0.01) than PA (P < 0.04), compared to controls. Plasma levels of SP and CGRP increased significantly in patients with thermal injuries. These peptides may yet be another group of neuromodulators playing a significant role in immune, pain, inflammatory and wound healing in burns.