Trauma resuscitation and the damage control approach

Trauma is a leading cause of morbidity and mortality worldwide. Developments in trauma care, from point of wounding to rehabilitation, have often been led and driven by military medical experiences in recent conflicts. Trauma mechanisms are manifold, affecting an omnifarious patient population indiscriminately, and potentially resulting in significant multisystem dysfunction or damage, sometimes permanently. The horizontal approach to trauma resuscitation, whereby a patient is assessed and treated by multiple specialists to prioritize management of life-threatening issues swiftly and concurrently, was exploited to good effect by clinicians at Camp Bastion in Afghanistan. This tactic is just one element of the dynamic and synchronous teamwork that this complex and challenging area of clinical practice demands. Similarly, the damage control approach deploys medical and surgical treatment strategies in parallel, balancing therapies in pursuit of physiological equipoise, aiming to reduce mortality and accepting the risk of morbidity. Damage control therapy embodies bold, yet nuanced, clinical care.     

Lack of transmission of neutrophil and platelet antibodies by intravenous immunoglobulin in bone marrow transplant patients

BACKGROUND: Several studies have demonstrated that the administration of intravenous immunoglobulin (IVIG) may be followed by the transient appearance of positive red cell antibody screens, positive direct antiglobulin tests, and, occasionally, frank hemolysis. However, little information is available regarding the possibility that IVIG could transmit neutrophil and/or platelet antibodies. STUDY DESIGN AND METHODS: Serum samples were obtained both immediately before and immediately after the administration of 12 separate lots of commercially available IVIG to bone marrow transplant patients. RESULTS: None of the patients were shown by standard granulocyte immunofluorescence testing to have acquired neutrophil antibodies. Four of the 12 postinfusion sera were positive for platelet antibodies in standard platelet suspension immunofluorescence testing, but in all four instances the corresponding preinfusion serum was positive as well. CONCLUSION: The risk of acquiring neutrophil and/or platelet antibodies after the administration of commercially available IVIG appears to be low.     

DIAPHRAGMATIC PARALYSIS IN MOTOR NEURONE DISEASE: USE OF NON-INVASIVE INVESTIGATIVE AND THERAPEUTIC TECHNIQUES

SUMMARY Two cases of bilateral diaphragmatic weakness are described in which the condition was the presenting feature of motor neurone disease. Inspiratory muscle strength was assessed by a non-invasive technique involving measurements of pressures generated within the mouth. One patient with severe inspiratory muscle weakness is being treated with domiciliary nasal ventilation and has returned to a good-quality life. The other patient with less severe weakness has thus far required no ventilatory support.     

The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture

OBJECTIVES: To evaluate the effects of MK-0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals. DESIGN: Placebo-controlled, randomized, double-blind trial. SETTING: Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers. PARTICIPANTS: One hundred sixty-one hip-fracture patients were enrolled. Entry criteria included consenting hip-fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity. INTERVENTION: Random assignment to 6 months of daily treatment with MK-0677 or placebo. Patients were followed for an additional 6 months after completion of therapy. MEASUREMENTS: Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP-NH), the ability to live independently, and insulin-like growth factor I (IGF-I) levels. RESULTS: MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant. CONCLUSION: Although MK-0677 treatment increased serum IGF-I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip-fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.     

The role of MAP kinase kinase in interleukin-3 stimulation of proliferation

Expression of a dominant interfering mutant of MAP kinase kinase (MAPKK) inhibits interleukin-3 (IL-3) activation of MAP kinase in the murine bone marrow-derived cell line BAF3. This results in an increase in the level of IL-3 required to stimulate cell proliferation and suppress apoptosis. When apoptosis is constitutively inhibited by coexpression of bcl-2, the dominant interfering MAPKK inhibits IL-3 driven cell cycle progression. Thus, MAPKK function is necessary for optimal IL-3 inhibition of apoptosis and optimal IL-3 stimulation of entry into S phase. Expression of a constitutively activated mutant of MAPKK does not replace IL-3, but renders cells able to proliferate in a density-dependent manner. Cell contact is required to allow cell proliferation; such contact can be supplied by cells without activated MAPKK.     

Circulating glycosaminoglycan anticoagulants associated with suramin treatment

A complex coagulopathy appeared in three women receiving suramin as treatment for metastatic adrenocortical carcinoma. Although hepatocellular dysfunction accounted for some of the abnormality, a unique feature of the coagulopathy was the presence of an inhibitor of the thrombin clotting time. The potency of this circulating anticoagulant increased markedly during exacerbations of hepatic injury. The anticoagulant was removed from plasma samples from two of the patients by passage over a column of diethylaminoethyl (DEAE)- Sephacel. It eluted from the DEAE at salt concentrations that removed "high-charge" glycosaminoglycans. Elimination of the purified anticoagulant activity in vitro required a combination of heparitinase and chondroitinase ABC, suggesting that the activity was mediated by both heparan sulfate and dermatan sulfate. Suramin is hypothesized to inhibit enzymes that normally degrade glycosaminoglycans, resulting in accumulation of these substances, which are released from the liver into the circulation during periods of hepatic injury.     

Deficiency of lubricating surfactant lining the articular surfaces of replaced hips and knees

While preceding papers have demonstrated that the active load-bearing agent in the boundary mode of joint lubrication is surface-active phospholipid (SAPL)--probably adsorbed as the outermost layer of articular cartilage--this study is designed to determine whether that layer is deficient in osteoarthritis (OA). This layer has been studied on 12 hips and 31 knees obtained from surgically replaced joints afflicted with OA. Measurement of the contact angle (theta) subtended by a droplet of saline clearly demonstrated a highly significant decrease in hydrophobicity, theta falling from 100 degrees for 13 bovine controls (78 degrees for five human controls) to 56 degrees for arthritic hips and 63 degrees and 68 degrees for the 'worn' and 'unworn' areas of arthritic knees, respectively. These changes were reflected in the quantities of SAPL (and proteolipid) recovered from the same articular surfaces by solvent rinsing, yields of SAPL being 36% lower in hips and 25% lower in 'worn' areas of knees, but not significantly different in 'unworn' areas. These results indicate that the outermost lubricating layer of SAPL deposited onto articular cartilage from SF is deficient in OA.