Evaluation of limb compartments with increased interstitial pressure. An improved noninvasive method for determining quantitative hardness

The purpose of this project was to study a noninvasive method of evaluating limbs at risk of compartment syndrome. Untreated limb compartment syndrome may lead to irreversible dysfunction, chronic pain and contracture. An improved means of obtaining quantitative hardness measurements is reported. The handheld noninvasive compartment syndrome evaluator (NCSE) device formulates a quantitative hardness curve of force verse depth of indentation by applying a 5.0 mm diameter indenter to a limb muscle compartment. Eighteen volunteers (9 men, 9 women) had elevated intracompartmental interstitial pressures by application of custom-made tourniquets. Comparison of interstitial pressure to quantitative hardness measurements in 71 compartments tested showed a statistically significant strong linear relationship with an average Pearson correlation coefficient of .84 (range .78-.9 P<.0001). In addition, for all compartments tested, the mean hardness value for the group with interstitial pressure greater than 50 mmHg (considered compartment syndrome) was close to 2x greater and was statistically different than the mean hardness for the group with interstitial pressure less than 30 mmHg (no compartment syndrome, t-test: P<.0001). This study utilizes a device that has improved upon previous quantitative hardness measurement techniques. In addition, by utilizing a tourniquet model to create elevated interstitial intracompartmental pressure in volunteers, data collection was easier and faster. In the future, quantitative hardness measurements may accurately predict interstitial intracompartmental pressure for most patients. This technique may greatly enhance the medical community's ability to diagnose compartment syndrome with a noninvasive means.     

Abdominal compartment syndrome in polytrauma

Authors inform about the group of 8 patients with abdominal compartment syndrome (ACS) occurred as a complication in large blunt injury of abdominal cavity. To the ACS diagnose, the measurement of intracystic pressure is used routinely, whose values correlate fully with values of intraabdominal pressure (IAP). In case of increasing values of IAP over 25 mm Hg with positive clinical signs of ACS, authors indicate decompression laparotomy with temporary closing of abdominal cavity by sterile plastic foil or Ethizip. This preventive temporary laparostomy is recommended also in serious injuries of abdominal cavity in patients with fatal haemorrhage, treated by the method of staged laparotomy with tamponade of abdominal cavity and with massive blood and volume resuscitation.     

Intracompartmental pressure of the anterior tibial compartment as a function of body and joint position

We measured the intracompartmental pressure in the anterior tibial compartment of 27 volunteers under different experimental conditions. First we recorded the pressure in the proximal, middle, and distal third of the compartment as well as at different depths of the muscle. Thereafter the pressure was measured in the lying, sitting and standing positions, and at different positions of the knee and ankle joint. There was no difference in pressure in the various parts of the muscle. However, there was a significant difference between the lying, sitting and standing positions. Dorsal flexion of the ankle resulted in an increase in the intracompartmental pressure in dorsiflexion and plantarflexion of the ankle.     

Split flexor carpi radialis muscle

A detailed anatomic and intramuscular neural staining study in 22 human and 5 monkey upper limbs revealed that the flexor carpi radialis can be raised on its proximal neurovascular pedicle and that the muscle can be split along its tendon into two independently functioning neuromuscular compartments, each with its own nerve and blood supply. A study of the muscle architecture in the human specimens found the radial compartment to have significantly longer fiber length and a larger physiologic cross-sectional area than the ulnar compartment. Independence of function of each compartment was demonstrated in electrical stimulation studies in six monkeys (Macaca fascicularis), but no significant difference was noted in the peak isometric load between the two compartments (p = 0.68) in the monkey. The extra functioning muscle units become important in local transfers for restoring function in multiple nerve palsies as in Hansen's disease, severe traumatic loss of muscle in crush injuries and compartment syndromes, and after wide resection in infective and neoplastic conditions in the forearm and hand.     

International symposium on peripheral nerve repair and regeneration and 2nd club Brunelli meeting

Recent findings on the antioxidant effects of pretreatment with α-lipoic acid (α-LA) on the crush injury of rat sciatic nerve confirm the possible usefulness of α-LA administration in humans with peripheral nerve injuries. We discussed this issue in relation with our recent results in which the combined employment of α-LA and γ-linolenic acid with a rehabilitation program for six weeks reduced sensory symptoms and neuropathic pain in patients with compressive radiculopathy syndrome from disc-nerve root conflict in comparison with patients submitted to rehabilitation program alone for six weeks.     

Initiation and duration of muscle precursor replication after mild and severe injury to skeletal muscle of mice

Summary We test the proposal (McGeachie and Grounds 1985) that myogenesis following severe (crush) injury is prolonged compared with minor (cut) injury. Forty-four mice were injured with a cut and a crush lesion on different legs, and tritiated thymidine was injected at various times after injury (0 to 120 h), samples of regenerated muscle were taken 9d after injury and autoradiography was used to determine the initiation of muscle precursor replication, and duration of proliferation after the two different injuries.In both lesions replication of potential myoblasts was initiated 30 h after injury. Myogenesis was essentially completed in cut lesions by 96 h after injury, although the peak was finished by 60 h. In contrast, significant muscle precursor replication in crush lesions was still occurring 96 h after injury, and myogenesis was almost finished by 120 h. The pronounced difference in duration of myogenesis in different lesions strongly supports the original proposalThe extended duration of myogenesis in crush lesions, in conjunction with tritiated thymidine reutilisation, appears to account for conflicting experimental results in support of the concept of a circulating muscle precursor cell.     

Mouse Model of Muscle Crush Injury of the Legs

Because crush injury to skeletal muscle is an important cause of morbidity in natural disaster and battlefield settings, a reproducible and refined animal model of muscle crush injury is needed. Both open and closed small-animal models of skeletal muscle crush injury are available but are limited by their need for surgical isolation of the muscle or by the adverse effect of fibular fracture, respectively. In the current study, we developed and validated a novel, noninvasive mouse model of lower-extremity muscle crush injury. Despite the closed nature of our model, gross evidence of muscle damage was evident in all mice and was verified microscopically through hematoxylin and eosin staining. The injury elicited both neutrophil and macrophage infiltration at 24 and 48 h after injury. The area percentage and mean antigen area of F4/80-positive macrophages were higher at 48 h than at 24 h after injury, and CD68-positive macrophage area percentage and mean antigen area differed significantly between injured and uninjured muscle. In addition, the incidence of fibular fracture was one third lower than that reported for an alternative noninvasive model. In conclusion, our model is a reproducible method for muscle crush injury in the mouse pelvic limb and is a refinement of previous models because of its decreased bone fractures and reduction of animal numbers.Abbreviations: AOI, area of interestSkeletal muscle crush injury is an important cause of morbidity in both civilian and military populations. During earthquakes, tornados, and other natural disasters, collapsed structures result in crush injuries in approximately 40% of victims entrapped in the rubble,¹⁴ and crush injuries sustained during these events primarily affect skeletal muscle tissue.¹³ Crush injuries to skeletal muscle received during military conflict can occur when a limb is compressed for an extended time period, and combat-related crush injuries of the extremities frequently are present in wounded troops who are transported via aeromedical evacuation.²²A muscle-crush injury is induced when pressure is applied to skeletal muscle, interrupting blood flow and damaging the cell membranes of the muscle fibers. Several animal models of skeletal muscle-crush injury are used to study the pathophysiology of acute muscle inflammation and to investigate potential therapies.^{1,2,3,5,8,9,12,17,18,21} The most common model is the application of force to a surgically isolated pelvic limb muscle by using a clamp.¹⁶ Although closed models have been investigated, these studies typically involve dropping weights onto rodents’ pelvic limbs, thereby increasing the adverse event of fractures. Although not often reported in the literature, the incidence of fibular fractures in rats as a result of the dropped weight was 27% in one study.³ An additional drawback to the dropped-weight model is that it simulates a high-force contusion injury and does not provide the ischemic effect of the continuous pressure applied by the open clamp model. The ideal crush-injury model would mimic a force-induced injury, because 40% of survivors trapped in building rubble develop ischemia-induced crush syndrome.¹⁴We chose to investigate a novel model of closed crush injury for several reasons. An animal model of skeletal muscle injury should mimic the human clinical presentation, and a closed model more closely simulates a real-world crush injury. Second, because the incision created in the open model can activate the inflammatory response, a group of sham-operated animals is needed to control for the variable of the incision-induced inflammation. By using a closed model, the contralateral limb can serve as the uninjured control, thereby reducing the number of animals needed to perform the study. Last, the closed model represents a refinement of the crush injury procedure by removing the additional tissue damage and inflammation that result from the incision and tissue dissection of the surgical procedure and by reducing the incidence of fractures.Because this model has not been described in the literature, the objective of the current study was to develop a closed, sustained-force model of lower-extremity crush injury that induces a measurable leukocyte response and minimizes damage to nearby bones. In addition, we used monoclonal antibodies to characterize the leukocyte populations associated with this skeletal muscle crush injury model.     

p53基因多态性和脑外伤预后及临床意义

目的：研究颅脑外伤患者中P53等位基因与基因型的频率分布,探讨其与脑损伤预后的关联性,为脑损伤患者预后提供部分参数依据。方法：选择各型颅脑损伤患者141例,正常对照者144人,患者按GCS格拉斯哥评分法进行分类;采用PCR基因型检测法检测P53等位基因,基因计数法计算等位基因频率;统计学分析等位基因和基因型在脑外伤组与正常对照组、预后良好组与预后不良组的频率分布的差异,并综合分析患者年龄、性别、GCS以及P53各等位基因等因素对脑外伤患者预后的影响。结果：在颅脑外伤患者和正常对照者中P53等位基因和基因型的频率分布,差异均无统计学意义（P〉0.05）;等位基因Arg相对于Pro的OR为1.140,基因型Arg/Pro、Arg/Arg相对于Pro/Pro的OR分别为0.890和1.170。在重型脑外伤患者（3≤GCS≤8分）86例中,预后良好31例,预后不良55例,基因型对预后不良的影响：非Pro/Pro相对于Pro/Pro的OR为0.417,非Arg/Pro相对于Arg/Pro的OR为0.419,非Arg/Arg相对于Arg/Arg的OR为3.667。在所有脑外伤患者中,预后良好组和预后不良组的患者年龄、性别差异均无统计学意义（P〉0.05）;GCS、P53等位基因差异具有显著统计学意义（P〈0.01）。结论：在重型颅脑患者中,基因型Arg/Arg有增加预后不良的风险;脑外伤预后与患者的年龄、性别无关联,与GCS、P53基因密切相关。     

Evaluation of Hyperventilation in Treatment of Head Injuries

Reduction of the partial pressure of carbon dioxide in the arterial blood by mechanical hyperventilation (Pco₂ 25-30 mm Hg; Po₂ 100-150 mm Hg) may be beneficial in cases of severe head injury. To evaluate its efficacy and establish prognostic guidelines intracranial pressure, radiocirculograms, and cerebrospinal fluid (C.S.F.) lactate levels were studied in 31 patients. In survivors intracranial pressure fell and cerebral blood flow improved with treatment. A C.S.F. lactate greater than 55 mg/100 ml was associated with a poor prognosis. Selection of patients was based on clinical judgement, and adults with signs of extensive brain damage were excluded. The importance of an adequate airway and resuscitation is stressed before a final decision is made. The object of treatment is to improve the quality of survival and the criteria measured may aid in the distinction between patients with a potential for good recovery and those capable only of a vegetative existence. Many associated factors as well as hypocapnia reduce intracranial pressure, and these are discussed. We believe that hyperventilation may improve some head injuries, and further study is indicated.     

Contractile Properties and Movement Behaviour in Neonatal Rats with Axotomy, treated with the NMDA Antagonist DAP5

ABSTRACT: BACKGROUND: It is well known that axotomy in the neonatal period causes massive loss of motoneurons, which is reflected in the reduction of the number of motor units and the alteration in muscle properties. This type of neuronal death is attributed to the excessive activation of the ionotropic glutamate receptors (glutamate excitotoxicity). In the present study we investigated the effect of the NMDA antagonist DAP5 [D-2-amino-5-phosphonopentanoic acid] in systemic administration, on muscle properties and on behavioural aspects following peripheral nerve injury. METHODS: Wistar rats were subjected to sciatic nerve crush on the second postnatal day. Four experimental groups were included in this study: a) controls (normal saline injection), b) crush c) DAP5 treated and d) crush and DAP5 treated. Animals were examined with isometric tension recordings of the fast extensor digitorum longus and the slow soleus muscles, as well as with locomotor tests at four time points, at P14, P21, P28 and adulthood (2 months). RESULTS: 1. Administration of DAP5 alone did not provoke any side-effects. 2. In all age groups, animals with crush developed significantly less tension than the controls in both muscles and had a worse performance in locomotor tests (p<0.01). Crush animals injected with DAP5 were definitely improved as their tension recordings and their kinetic behaviour were significantly improved compared to axotomized ones (p<0.01). 3. The time course of soleus contraction was not altered by axotomy and the muscle remained slow-contracting in all developmental stages in all experimental groups. EDL, on the other hand, became slower after the crush (p<0.05). DAP5 administration restored the contraction velocity, even up to the level of control animals 4. Following crush, EDL becomes fatigue resistant after P21 (p<0.01). Soleus, on the other hand, becomes less fatigue resistant. DAP5 restored the profile in both muscles. CONCLUSIONS: Our results confirm that contractile properties and kinetic behaviour of animals are severely affected by axotomy, with a differential impact on fast contracting muscles. Administration of DAP5 reverses these devastating effects, without any observable side-effects. This agent could possibly show a therapeutic potential in other models of excitotoxic injury as well.     

Modified separation of parts as an intervention for intraabdominal hypertension and the abdominal compartment syndrome in a swine model

Standard therapy for abdominal compartment syndrome is laparotomy. In many patients, laparotomy involves a recent incision; for others, volume of resuscitation may be the cause. The components separation technique allows difficult abdominal closure. The authors studied the effect of a modified separation of parts on abdominal compartment syndrome in an animal model. Eight pigs were instrumented for measurement of central venous pressure, mean arterial pressure, peak airway pressure, and intraabdominal pressure. Intraabdominal hypertension to 25 mmHg was established with intraperitoneal fluid infusion. Modified separation of parts was performed by sequential release of the abdominal wall layers. With increased intraabdominal pressure, mean arterial pressure (55.3 +/- 12.0 to 65.3 +/- 11.0), central venous pressure (7.7 +/- 2.4 to 13.3 +/- 6.9), and peak airway pressure (20.2 +/- 2.4 to 25.3 +/- 4.1; p < 0.05) also increased. Maximum intraabdominal pressure was 26.0 +/- 1.2 mmHg. Skin incision resulted in a decrease in intraabdominal pressure to 21.7 +/- 4.5, external oblique release to 18.3 +/- 3.9, internal oblique release to 13.2 +/- 4.0, and transversus muscle incision to 7.0 +/- 2.5 mmHg (p < 0.05). With completion of components separation, mean arterial pressure remained increased (63.2 +/- 16.9), central venous pressure decreased (6.8 +/- 3.6; p < 0.05), and peak airway pressure decreased (22.7 +/- 3.9; p < 0.05). Modified separation of parts technique effectively releases intraabdominal hypertension and reverses the physiologic derangements associated with abdominal compartment syndrome in the animal model.     

Effect of dopamine antibodies on neuropathic pain syndrome in rats

Dopaminergic brain system plays an important role in regulation of pain sensitivity. However, the data on participation of antidopamine antibodies in the development of neurogenic pain are absent. This work was aimed at the study of the role of antidopamine antibodies in the development of pain syndrome induced by the injury of nn. ischiadic and saphenous in rats. It was shown that after the nerve injury, the behavioral reaction such as autotomy (self-injury) appeared as a feature of the experimental neuropathic pain syndrome. It was originally established that the development of neuropathic pain syndrome induced by the injury of peripheral nerves was accompanied by induction of dopamine autoantibodies. It was also shown that immunization of the animals with conjugated dopamine-protein autigen resulted in aninerease of autidopamine antibody level and an amplification of the experimental neuropathic pain syndrome, i.e., decrease in the latency of the first autotomy, increase in expression of autotomies, and increase in the number of animals with late autotomies.     

Mechanisms of extraocular muscle injury in orbital fractures

The gross and microscopic events that occur after orbital blowout fractures were evaluated to assess the mechanisms of diplopia and muscle injury. Intramuscular and intraorbital pressures were evaluated in experimental animals, in cadavers, and at the time of orbital fracture explorations for repair of orbital fractures in humans. Histologic and circulatory changes, muscle pressure recordings, and operative observations were evaluated. Creation of a compartment syndrome was evaluated to include a histologic evaluation of the orbital fibrous sheath network for the extraocular muscles and the intramuscular vasculature. These experiments and observations do not support the role of a compartment syndrome in ocular motility disturbances because (1) intramuscular pressures were subcritical in both humans and animals; (2) no limiting fascial compartment could be demonstrated; and (3) microangiograms and histologic evaluations did not confirm areas of compartmental ischemic necrosis. Muscle contusion, scarring within and around the orbital fibrous sheath network, nerve contusion, and incarceration within fractures remain the probable causes of diplopia, with the most likely explanations being muscle contusion and fibrosis or incarceration involving the muscular fascial network.     

Postpolio syndrome and cardiopulmonary conditioning.

Postpolio syndrome is a group of related signs and symptoms occurring in people who had paralytic poliomyelitis years earlier. New weakness, fatigue, poor endurance, pain, reduced mobility, increased breathing difficulty, intolerance to cold, and sleep disturbance in various degrees and expressions make up the syndrome. The reported incidence is between 25% and 80%. The origins are multifactorial and can be associated with underexertion, overexertion, inactivity due to intercurrent illness or injury, hypo-oxygenation, sleep apnea, deconditioning, and the failure of sprouted, compensatory large motor units. The exercise question in postpolio syndrome is related to the experience of new weakness or loss of muscle function due to overuse, which is often associated with injudicious repeated challenges to weakened musculature. Carefully prescribed exercise can be used for increasing strength and endurance and improving cardiopulmonary conditioning.     

The timing of neovascularization in fingertip replantation by external bleeding

To overcome venous congestion in fingertip replantation with no venous anastomosis, the authors have used a salvage procedure that consists of continuous external bleeding through a stab incision on the paraungual area and dripping a heparinized saline solution at the incision site to maintain external bleeding. Because this method requires continuous bleeding for a certain period of time, it may be a great burden on the patient; therefore, it is most important to minimize the duration of bleeding. Many authors have studied the timing of the new venous channel formation of the flap. However, to our knowledge, a study on fingertip replantations has not yet been performed. From June of 1985 to November of 1999, the authors performed fingertip replantations on 144 fingers of 137 patients using our salvage procedure at Korea University Guro Hospital. Among the 144 fingers, 101 fingers of 96 patients were successfully transplanted, including those with partial necrosis. The authors reviewed the medical records of these 101 fingers retrospectively; they compared and analyzed the necessary duration of external bleeding according to sex, age, level of injury, cause of amputation, and the type of injury. The average period of the salvage procedure was 7.6 days. Regarding age, the shortest period (5.5 days) was required for patients younger than 10 years. On the basis of the types of injuries, the duration of bleeding was shortest for the guillotine injury group (5.9 days) compared with crush (8.2 days) or avulsion (8.0 days) injuries. Sex and level of injury did not make much difference in the duration of the procedure.     

The relation of abstinence analgesia to the development of cardiac disorders in the ethanol withdrawal syndrome in rats

Ethanol was administrated intragastrically (25%, w/v) to Wistar male rats. They received 7-10 g ethanol/kg b.wt. daily in 2 fractional doses for 6 days. In 20-24 hours after the last ethanol administration behavioral and neurological signs of withdrawal syndrome and pain latent period were measured. Analgesia was determined using the tail flick and hot plate tests. Two days later systolic function of the isolated perfusing heart and creatine phosphokinase outflow were examined. Rats had longer latent pain period than in control. Heart perfusion revealed a decrease of systolic pressure, dp/dt of systolic and diastolic pressure, increase of enzyme outflow. Kendall's correlation analysis revealed a positive relationship between intensity of withdrawal symptoms and analgesia index in the hot plate test (tau = +0.343, p. 0.01) and a lack of relationship in the tail flick test. There was negative relationship between the analgesia index and the indices of heart disorders. It is proposed that analgesia index can be used as a predictor of the cardiac muscle injury caused by the alcoholic abstinent syndrome.     

儿童噬血细胞综合征38例临床分析

摘要目的：探讨噬血细胞综合征患儿的临床特征、治疗及预后。方法：对38例噬血细胞综合征患儿的Il盏床症状、体征、试验检查结果、治疗及预后,进行回顾性总结与分析。结果：38例患儿主要表现为发热、肝脾淋巴结肿大、外周血细胞减少、铁蛋白升高、凝血功能异常;经针对性治疗后,治愈3例,好转20例,疗效不佳自动出院9例,死亡6例。结论：噬血细胞综合征病因复杂,临床表现多种多样,病情凶险,预后较差,旱期诊断及治疗对预后十分关键。     

The segmental rectus abdominis free flap for ankle and foot reconstruction.

The reconstruction of soft-tissue defects of the ankle and foot usually requires free-tissue transfer. Although certain local flaps have been described for the reconstruction of these injuries, their utility may be compromised by significant crush injury or the size and location of the defect. Part of the rectus abdominis muscle, the segmental rectus abdominis free flap, is ideally suited for this use because of the muscle's versatility, reliability, and negligible donor deformity when harvested through a low transverse abdominal incision. Seven patients reconstructed with this flap are presented, and the technique is discussed. All patients have been successfully reconstructed with preservation of the ankle and foot. At present, all patients are fully or partially weight-bearing. The segmental rectus abdominis free flap is recommended for the reconstruction of such wounds.     

Visualizing Peripheral Nerve Regeneration by Whole Mount Staining

Peripheral nerve trauma triggers a well characterised sequence of events both proximal and distal to the site of injury. Axons distal to the injury degenerate, Schwann cells convert to a repair supportive phenotype and macrophages enter the nerve to clear myelin and axonal debris. Following these events, axons must regrow through the distal part of the nerve, re-innervate and finally are re-myelinated by Schwann cells. For nerve crush injuries (axonotmesis), in which the integrity of the nerve is maintained, repair may be relatively effective whereas for nerve transection (neurotmesis) repair will likely be very poor as few axons may be able to cross between the two parts of the severed nerve, across the newly generated nerve bridge, to enter the distal stump and regenerate. Analysing axon growth and the cell-cell interactions that occur following both nerve crush and cut injuries has largely been carried out by staining sections of nerve tissue, but this has the obvious disadvantage that it is not possible to follow the paths of regenerating axons in three dimensions within the nerve trunk or nerve bridge. To try and solve this problem, we describe the development and use of a novel whole mount staining protocol that allows the analysis of axonal regeneration, Schwann cell-axon interaction and re-vascularisation of the repairing nerve following nerve cut and crush injuries.