Biomedical subjects
J B Cone
Publications and source records attributed to J B Cone.
Intraperitoneal blood exacerbates the remote inflammatory response to murine peritonitis.
BACKGROUND: This study investigated the effects of intra-abdominal blood on the systemic response to peritonitis using a murine model of hemorrhage, peritonitis, and multiple organ dysfunction syndrome. METHODS: The model used male ICR mice subjected to hemorrhage and intraperitoneal zymosan. Half of the mice received intraperitoneal blood. Outcome measures included lung myeloperoxidase, lung edema, lung injury score, and plasma and lung tissue chemokine production. RESULTS: Peritoneal blood (in association with peritoneal inflammation) increased lung neutrophil sequestration (myeloperoxidase) (2.56 +/- 1.42 vs. 1.45 +/- 0.49 U/left lung, p = 0.04) and lung weight (0.11 +/- 0.04 vs. 0.07 +/- 0.02 g/left lung, p = 0.02), and was associated with significantly higher chemokine levels in plasma (KC and MCP-1) and lung tissue (KC, MIP-2, and MCP-1). Both plasma and lung tissue neutrophil chemoattractants KC and MIP-2 were significantly linearly correlated with myeloperoxidase (p < 0.009), and lung tissue KC (a neutrophil chemokine) and MCP-1 and MIP-1alpha (mononuclear cell chemokines) correlated with lung injury score (p < 0.003). CONCLUSION: Although blood alone in the peritoneal cavity was well tolerated, in conjunction with inflammation, it was synergistic in amplifying the systemic inflammatory response. The amplified lung injury in this model was associated with significant increases in circulating and lung tissue chemokine concentrations.
Contribution of age and gender to outcome of blunt splenic injury in adults: multicenter study of the eastern association for the surgery of trauma.
BACKGROUND: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. METHODS: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. RESULTS: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients > or = 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients > or = 55 was significantly greater than patients < 55 (43% vs. 23%). Patients > or = 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women > or = 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). CONCLUSION: Patients > or = 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women > or = 55 had significantly greater mortality and failure of NOM than women < 55.
Interleukin-10 reduces morbidity and mortality in murine multiple organ dysfunction syndrome (MODS).
HYPOTHESIS: IL-10 will reduce morbidity and mortality in murine MODS. Introduction. Intraperitoneal (ip) zymosan causes a triphasic inflammatory process leading to MODS. Phase I is an acute systemic inflammatory response to sterile peritonitis. Phase II is the recovery phase. Phase III is characterized by recurrent illness, progressive organ dysfunction, and elevated proinflammatory cytokines. METHODS: Male ICR mice were randomized (on Experiment Day 0, time = 0 h) into four initial groups (A-D): Control Group A received no zymosan and no IL-10. Group B received zymosan (1 mg/g mouse BW, t = 0) and no IL-10. Group C received no zymosan and IL-10 at t = 2 h. Group D received zymosan and IL-10 at t = 2 h. On Experiment Day 4, mice in Groups B-D were randomized into six further treatment groups (B1 and B2, C1 and C2, D1 and D2). Group B1 received no treatment. Group B2 received IL-10 when clinical signs of recurrent illness developed (Phase III, 12-18 days after zymosan treatment). Mice were sacrificed when they were preterminal (clinical signs of shaking, shivering, or paralysis) or on Experiment Day 28 (survivors). Plasma total bilirubin and creatinine levels were measures of organ function. Terminal pulmonary compliance was measured in situ through a physiologic range of tidal volumes. RESULTS: Mice entering Phase III consistently progressed to MODS characterized by elevated bilirubin and hemorrhagic lungs which, if left untreated, was lethal. Mice treated with IL-10 (Group B2) when they entered Phase III had lower mortality (28.6% vs 100%, P < 0.02), longer survival (25 vs 18 days, P < 0.05), and improved lung pulmonary compliance (slope beta1 = 0.082 ml/mm Hg vs 0.059 ml/mm Hg, P < 0.001) compared to untreated (Group B1) mice in Phase III. CONCLUSIONS: IL-10 improves survival even when given after clinical signs of illness are present.
Prospective study of blunt aortic injury: Multicenter Trial of the American Association for the Surgery of Trauma.
BACKGROUND: Blunt aortic injury is a major cause of death from blunt trauma. Evolution of diagnostic techniques and methods of operative repair have altered the management and posed new questions in recent years. METHODS: This study was a prospectively conducted multi-center trial involving 50 trauma centers in North America under the direction of the Multi-institutional Trial Committee of the American Association for the Surgery of Trauma. RESULTS: There were 274 blunt aortic injury cases studied over 2.5 years, of which 81% were caused by automobile crashes. Chest computed tomography and transesophageal echocardiography were applied in 88 and 30 cases, respectively, and were 75 and 80% diagnostic, respectively. Two hundred seven stable patients underwent planned thoracotomy and repair. Clamp and sew technique was used in 73 (35%) and bypass techniques in 134 (65%). Overall mortality was 31%, with 63% of deaths being attributable to aortic rupture; mortality was not affected by method of repair. Paraplegia occurred postoperatively in 8.7%. Logistic regression analysis demonstrated clamp and sew (p = 0.002) and aortic cross clamp time of > or = 30 minutes (p = 0.01) to be associated with development of postoperative paraplegia. CONCLUSIONS: Rupture after hospital admission remains a major problem. Although newer diagnostic techniques are being applied, at this time aortography remains the diagnostic standard. Aortic cross clamp time beyond 30 minutes was associated with paraplegia; bypass techniques, which provide distal aortic perfusion, produced significantly lower paraplegia rates than the clamp and sew approach.
Manipulation of the inflammatory response to burn injury.
BACKGROUND: Burn injury is characterized by hypermetabolism and protein catabolism. Endotoxin, derived from either wound or gut, may participate in this response. METHODS: Eleven seriously burned patients were treated with the endotoxin-binding agent polymyxin B and underwent partitional calorimetry and nitrogen balance studies. The data from theses patients were compared with data from 28 contemporary, similarly burned patients who did not receive polymyxin B. RESULTS: Elevated levels of circulating endotoxin were not consistently detected in either group. Interleukin-6 was elevated and correlated with rectal temperature and nitrogen excretion in both groups. Administration of polymyxin B produced no change in metabolic rate but produced a significantly more positive nitrogen balance and was associated with a prompt reduction in interleukin-6 levels. CONCLUSIONS: These data support the hypothesis that endotoxin plays a role in the postburn protein catabolism but not in the hypermetabolic response. This protein catabolic response is statistically associated with circulating interleukin-6 levels, suggesting a possible role for interleukin-6 in postinjury protein wasting.
Retrospective evaluation of admission criteria for paediatric electrical injuries.
In the medical community, the practice of admitting all electrical burns for 24-48 h of observation, monitoring and laboratory evaluation is widespread. This retrospective review of paediatric electrical burns was conducted to determine which patients may safely be treated as outpatients. Retrospective analysis of all paediatric burns admitted between 1980 and 1991 identified 35 patients with electrical injuries. Patients were divided into two groups for analysis: those burned by exposure to household voltages (120-240 V; n = 26) and those exposed to high voltages, in excess of 1000 V (n = 9). The majority of household electrical injuries occurred secondary to contact with the household 120 V (21/26). Contact with an extremity accounted for the largest number of these injuries (18/26). The mouth was the second most frequent site of injury (7/26). Most of these patients (20/26) had < 1 per cent BSA burn. No patient in the household-voltage group had an arrythmia that required treatment, nor were there any identified examples of compartment syndrome or other vascular complications. Seven patients did require minimal skin grafting. No deaths occurred in either group. The patients in the household-voltage group were significantly younger. High-voltage electrical injuries occurred in an older patient population and required more aggressive care and surgical intervention. This was evident at the time of initial evaluation. Based on these data, healthy children with small partial-thickness electrical burns and no initial evidence of cardiac or neurovascular injury do not appear to need hospital admission.
Proximity penetrating extremity trauma: the role of duplex ultrasound in the detection of occult venous injuries.
The diagnosis and management of occult vascular injuries caused by penetrating proximity extremity trauma (PPET) remains controversial. Over 18 months, we prospectively screened 37 patients (43 lower extremities) with PPET for occult arterial and venous injuries using noninvasive studies (physical examination, ankle-brachial indices, color-flow duplex ultrasonography (CFD)) and angiography (arteriography, venography). Eight isolated, occult venous injuries were detected (incidence, 22%). CFD detected seven of eight (88%) venous injuries. Venography was technically difficult to perform in this patient population and failed to detect four femoral-popliteal vein injuries. Major thromboembolic complications (pulmonary embolism, symptomatic deep vein thrombosis, venous claudication) occurred in 50% of the patients identified with femoral-popliteal vein injuries. Arterial injuries were detected in 4 of 42 (10%) extremities (arteriography, n = 3; CFD, n = 1) and were clinically benign. We conclude that following PPET, (1) isolated, occult venous injuries are common and are associated with significant complications and (2) CFD is useful for screening for occult venous injuries.
Delayed diagnosis of duodenal rupture.
BACKGROUND: Although duodenal rupture is usually diagnosed during the course of surgery for other injuries, a small portion of such injuries occur in isolation. In such cases, the significance of the clinical and diagnostic findings may not be appreciated for an extended period. The primary determinant of mortality in duodenal rupture is the presence of associated injuries, but delay in diagnosis is often a secondary factor. METHODS: A retrospective case review of 8 patients with isolated duodenal rupture that was diagnosed more than 24 hours following the injury. RESULTS: In 5 cases, physicians did not look for the occult injury. In 3, patients did not seek medical attention. Two patients were initially treated with primary duodenal repair and drainage with poor results. All patients were eventually treated with pyloric exclusion that resulted in no deaths and no duodenal fistulas. Three patients developed abscesses after pyloric exclusion. They were drained without difficulty. CONCLUSION: Pyloric exclusion appears to offer a satisfactory option for dealing with the inflammation and contamination that result from prolonged soilage by duodenal contents.
Control of the hypermetabolic response to burn injury using environmental factors.
This study was performed to establish the relative efficiency of occlusive dressings and variable ambient temperature (group I) versus no dressings and variable ambient temperature (group II) versus no dressings and electromagnetic heaters (group III) for controlling the postburn hypermetabolic response. Fifteen burn patients and five normal controls (group IV) were studied when subjectively comfortable using partitional calorimetry, after which each patient was cold stressed by sequentially decreasing external energy support, and repeating calorimetry studies and serial plasma catecholamine assays. The percentage increase in heat production above predicted normal values was significantly increased for all groups when cold (C) versus neutral (N) (group I: [N] 24 +/- 24 versus [C] 49 +/- 25%; group II: [N] 46 +/- 35 versus [C] 74 +/- 47%; group III: [N] 21 +/- 20 versus [C] 78 +/- 25%; group IV: [N] -9 +/- 12 versus [C] 16 +/- 10%, p less than 0.05 all comparisons). Plasma catecholamine values did not increase significantly when patients were subjectively cold. These studies do not support the role of catecholamines as the primary mediator in the cause of the postburn hypermetabolic response. Using the patients' subjective comfort status as a guide for external energy support, it is possible to greatly reduce but not to eliminate the hypermetabolic response to burn injury.
Ibuprofen lowers body temperature and metabolic rate of humans with burn injury.
A group of 15 burned children and young adults with large burns (mean, 41% +/- 15% BSA) were administered ibuprofen (40 mg/kg for 3 days). Each patient served as his or her own control in this crossover study (with and without ibuprofen). Paired calorimetric and temperature studies and urinary nitrogen measurements were performed. No nitrogen-sparing effect was identified for this dose of ibuprofen. However, patients demonstrated a statistically significant reduction in average rectal temperature (0.67 degrees C decreases) (p less than 0.01) and in metabolic rate (11.4% decreases) (p less than 0.01) while taking ibuprofen. Linear regression analysis of the reduction in temperature versus the reduction in metabolic rate yielded a statistically significant correlation (p less than 0.01) with a slope of 13.6% reduction in metabolic rate per degree centigrade reduction in the 72-hour average rectal temperature. These results support the hypothesis that ibuprofen attenuates the hypermetabolic response to thermal injury by blunting the temperature elevation that is usually seen.
Percutaneous cholecystostomy in critically ill patients.
Sixteen critically ill patients underwent percutaneous cholecystostomy because of suspected acute cholecystitis. The procedure was technically successful, although 11 of 16 patients died subsequently because of various complications of their underlying primary disorders. We reviewed this series to reassess the value of percutaneous cholecystostomy. Four of 11 patients with definite acute cholecystitis (group 1) were cured by this technique, but three required surgery because of gallbladder wall necrosis. Two of these were among four cases which had demonstrated pericholecystic fluid collections on computed tomography (CT) or ultrasound of the abdomen. There were also five patients (group 2) in whom acute cholecystitis or its relationship to patients' symptoms were not fully determined, and four of them did not improve after percutaneous cholecystostomy. We conclude that this technique has a lower success rate in critically ill patients than reported previously.
Adult respiratory distress syndrome.
Basic scientists and clinicians have written numerous articles on the diverse causes of adult respiratory distress syndrome (ARDS). There is no specific diagnostic test for ARDS; the condition is characterized by interstitial lung edema, reduction in lung compliance, alveolar and small airway closure, decrease in functional residual capacity, and persistent hypoxia with increasing amounts of pulmonary blood flow coursing through nonventilated or poorly ventilated alveoli. Recent studies have emphasized the roles of macrophages and polymorphonuclear neutrophils in lung defense and injury. Advances in understanding the pathophysiology of ARDS have produced little significant change in the clinical management of the syndrome. There is no specific treatment for ARDS. The cornerstone of therapy is the early recognition and elimination of initiating factors such as sepsis. ARDS is not a single disease process, but appears to represent a final common pathway for the manifestation of a variety of lung injuries. The goal of therapy is to eliminate the predisposing condition and support the patient. New modes of ventilatory and pharmacologic therapy are presented.
Tertiary trauma care in a rural state.
Trauma patients in rural areas usually have no access to regional trauma systems or designated trauma centers. Efforts to provide quality trauma care in small hospitals may seriously overextend local capabilities. The urban trauma center retains an important role in trauma care even when the initial care must be provided at the local level. Twenty-five trauma patients were transferred to University Hospital between 1985 and 1988 after definitive care was initiated in community hospitals. During the same time period, a total of 147 trauma patients were transferred to the trauma service. No information was available on the total incidence of trauma. Medical records were reviewed to determine the reasons for transfer. Major reasons included the need for further complex surgery, better critical care support, and inadequate blood banks. Trauma centers serving rural areas provide a valuable resource well beyond the initial 24 hours.
Economics of trauma in a small academic medical center.
The recent changes in the mechanisms of health care funding have complicated trauma care and trauma center development. Hard data are needed on the current financial position of trauma care to plan for the future. To reduce the cost of trauma care without sacrificing the quality, we must know how the trauma dollar is spent. We reviewed the records of 100 random admissions to the trauma service of our institution in 1985. The records were examined for length of stay (LOS), intensive care unit length of stay (ICU-LOS), total hospital bill, types of third-party coverage, and overall collection rate. The hospital bill was broken down to identify the origins of trauma costs. To provide a control group, 100 patients admitted to the general surgical service and 100 other admissions were also analyzed. Trauma patients had greater LOS, ICU-LOS, total bills, and costs per day. Blunt trauma resulted in a greater LOS than penetrating trauma, but similar total bills. The collection rate from the blunt trauma patients was significantly greater. The greatest differences between trauma patients and others in resource utilization are the result of longer ICU-LOS and greater use of blood products. We did not identify any sites of potentially significant cost cutting that would not compromise patient care.
Acute gastric necrosis in the postoperative period.
In this report we have described three patients with upper GI bleeding who were found to have acute gastric necrosis. We have demonstrated the usefulness of esophago-gastroduodenoscopy and CT scan in further evaluation of such cases.
Vascular injury associated with fracture-dislocations of the lower extremity.
Vascular damage occurring in conjunction with orthopedic injury of the lower extremity is uncommon. This relative rarity is further complicated by the potentially subtle nature of vascular injury. Doppler signals and even palpable pulses do not exclude vascular damage. Missed or delayed diagnosis with a subsequent avoidable amputation is a too-frequent result. Displaced fractures of the distal femur and proximal tibia and particularly dislocation of the knee are associated with the highest risk of concomitant vascular injury and the poorest collateral circulation to support the distal limb. Optimal management of such injuries requires a high index of suspicion, aggressive use of angiography, and close cooperation among all members of the trauma team. With proper care, few extremities will be lost to ischemia alone. Limb loss should result only when the extremity has been too badly damaged to justify salvage efforts.
Atypical surgical infections.
The management of infections requiring surgical drainage or debridement is a significant component of surgical education and practice. Standard Gram's stain and culture techniques usually allow ready identification and adjunctive therapy of the offending organism; however, the surgical patient population is changing. More patients who require surgery are elderly, critically ill, have been exposed to broad-spectrum antibiotics, or are otherwise immunosuppressed. We identified 33 infections in this group of 32 patients. The majority of the etiologic agents were not identified using traditional microbiologic techniques, often leading to a delay in diagnosis. In this high-risk group of patients, we recommend histologic study of tissue with special stains such as methenamine silver. When the patient's condition warrants, frozen sections can be used. Optimal outcome requires early recognition of the specific etiologic agent.