Imaging patterns and prognosis of patients with gefitinib-related interstitial lung disease.

PURPOSE: We aimed to summarize the imaging findings of 25 patients with gefitinib-related interstitial lung disease (ILD), and identify the factors related to prognosis of gefitinib-related ILD in patients with non-small-cell-lung cancer. MATERIALS AND METHODS: Diagnosis of gefitinib-induced ILD by at least two chest radiologists was based on a review and analysis of the chest radiography and CT findings plus clinical data in the medical records. All patients were diagnosed with Stage III - IV non-small-cell carcinoma (adenocarcinoma (n = 24), bronchioalveolar cell carcinoma (n = 1)) and essential clinical data such as gefitinib as first-line use and survival status were recorded and analyzed to determine whether these were prognosis predictors. The imaging findings were classified into four patterns according to the previous largest study in Japan. RESULTS: The 25 chest radiographs were classified as Pattern A (n = 8), Pattern B (n = 3), Pattern C (n = 6), and pattern D (n = 8). Likewise the 23 CT images were classified as pattern A (n = 8; 34.8%), B (n = 3; 13%), C (n = 5; 21.7%), and D (n = 7; 30.4%). The mortality rate was significantly higher in patients with pattern D than in patients with the other patterns. Pattern D imaging findings were also significantly correlated with non first-line use of gefitinib (p = 0.007). CONCLUSIONS: We found an increase in mortality rate in patients with gefitinib associated ILD/pattern D compared to other radiological patterns. Familiarity with these imaging patterns can facilitate early and accurate diagnosis and help physicians gauge clinical prognosis of gefitinib-related ILD.

Adult liver abscess: characteristics of patients living in rural north-eastern Taiwan.

AIMS: This study aimed to analyse the characteristics of adult liver abscess (LA) patients living in rural townships of Taiwan. PATIENTS AND METHODS: We retrospectively screened the electronic admission records of a rural community hospital located in north-eastern Taiwan from 1 April, 2002 to 30 April, 2006. Relevant data, including subjects' basic characteristics, laboratory findings and infectious microorganisms, were extracted. RESULTS: Fifty-six subjects (mean age: 66.1 +/- 15.9 years; range: 23-94 years) were enrolled; one patient had an amoebic LA and 55 had pyogenic LA. Five subjects died in hospital. Overall, 80.5% of patients complained of having a fever, 87.5% had single abscess, 71.4% had right hepatic lobe involvement and 58.9% underwent invasive drainage. Most subjects (66.1%) did not have diabetes mellitus, 94.6% did not have a hepato-biliary tumour, 73.2% did not have gallstones, 78.6% did not have hepatitis and 87.5% did not have prior hepato-biliary surgery. Klebsiella pneumoniae was the most common infecting microorganism. Previous hepato-biliary surgery and serum creatinine >2.0 mg/dl were significantly more common in patients >or=65 years of age (p = 0.031). Diabetes mellitus was more common in female subjects (p = 0.021). Invasive drainage and single abscess were not significantly correlated to prognosis. DISCUSSION: Adult LA patients living in rural north-eastern Taiwan have different characteristics than patients living in urban areas. Geriatric LA patients should be managed cautiously because of the possibility of renal insufficiency or previous hepato-biliary surgery. Female LA patients should be evaluated for the presence of diabetes mellitus.

Alleviation of wood smoke-induced lung injury by tachykinin receptor antagonist and hydroxyl radical scavenger in guinea pigs.

We recently reported that wood smoke inhalation initially (within 5 min) causes airway injury and subsequently produces both airway and parenchymal injury after a delay (within 2 h). In this study, we investigated the mediator mechanisms of this delayed smoke-induced lung injury in 126 anesthetized and artificially ventilated guinea pigs who received challenges of either air or 40 tidal breaths of wood smoke. Two hours after inhalation, wood smoke produced various injurious responses, including increases in alveolar-capillary permeability, microvascular permeabilities, and histological injury scores, in airway and parenchymal tissues. Pre-treatment given before smoke challenge with CP-96,345 [a tachykinin NK1 receptor antagonist; (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-aza bicyclo(2.2.2.)-octan-3-amine], dimethylthiourea (a hydroxyl radical scavenger), or a combination of these two drugs largely alleviated both the airway and parenchymal responses, whereas pre-treatment with SR-48,968 [a tachykinin NK2 receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-butyl)benzamide] or a combination of CP-96,344 and SR-48,965 (inactive enantiomers) failed to do so. Post-treatment given at 5 min after smoke challenge with CP-96,345 or dimethylthiourea significantly alleviated the parenchymal responses, while having no effect on the airway responses. Pre-treatment with dimethylthiourea prevented the smoke-induced reduction in airway neutral endopeptidase activity (an enzyme for tachykinin degradation). We concluded that (1) tachykinins and hydroxyl radical play important roles in producing smoke-induced delayed lung injury in guinea pigs, and both may be involved in the spread of injury from the airways to the pulmonary parenchyma, and (2) the contribution of tachykinins is mediated via the activation of tachykinin NK1 receptors, and is associated with the hydroxyl radical-induced inactivation of airway neutral endopeptidase.

Hemodynamic response of modified fluid gelatin compared with lactated ringer's solution for volume expansion in emergency resuscitation of hypovolemic shock patients: preliminary report of a prospective, randomized trial.

The objective of this study was to compare the cardiac and hemodynamic responses to a rapid infusion of 1000 ml of modified fluid gelatin (group A) or 1000 ml of lactated Ringer's solution (group B) in emergency room patients suffering from shock. This prospective, randomized, open, noncrossover study was performed at a medical center university hospital in a surgical resuscitation room in the emergency department. The subjects were 34 patients with either hypovolemic or neurogenic shock who were admitted to the emergency room. A resuscitation protocol according to Advanced Trauma Life Support (ATLS) with an additional central venous line or Swan-Ganz catheters for hemodynamic monitoring was used. Physical parameters and hemodynamic variables were measured at baseline and 15 minutes, 30 minutes, and 1 hour after the infusion of each fluid. In both groups the mean arterial blood pressure (MAP), systolic and diastolic pressure, central venous pressure (CVP), and pulmonary artery occlusion pressure (PAOP) increased significantly. The CVP and PAOP increased significantly more in the modified fluid gelatin resuscitation group. In patients with traumatic or neurogenic shock due to acute volume deficiency, there was significantly better hemodynamic improvement, judged by CVP and PAOP measurements using the modified fluid gelatin for volume replacement than with lactated Ringer's solution during the first hour of resuscitation.

Ischaemic change of the human intestine after total portal occlusion during liver resection.

This is a clinical study of the use of several monitoring techniques to evaluate the effect of total hepatic inflow occlusion on intestinal ischaemia during liver resection. A total of 8 patients was studied. Parameters measured included intestinal oxygen extraction ratio, portal venous and arterial lactate levels and intestinal intramucosal pH (pHi), measured by an intraluminal tonometer. When venous outflow of the intestine was occluded, intestinal oxygen extraction ratio increased and portal venous lactate increased significantly, but arterial lactate did not increase significantly until after 60 minutes of occlusion. Intestinal pHi decreased significantly after 60 minutes. Following release of the occlusion, oxygen extraction and pHi returned to normal in 7 out of 8 patients. The 1 patient who had a persistent decrease in pHi died postoperatively. These findings indicate that a marked drop in pHi after total portal occlusion and persistent low pHi following the release of a portal occlusion are associated with the development of complications and mortality during liver resection.

Pseudomonas cepacia induced septic shock after propofol--a case report.

We report a healthy young female who developed septic shock and multiple organ failure soon after receiving a cosmetic surgery for augmentation of breasts under general anesthesia. Blood cultures yielded the growth of pseudomonas cepacia. We describe the clinical course and investigate the causes of the septic shock. Contamination of propofol, the intravenous anesthetic agent, was suspected.

Tumor necrosis factor gene polymorphism and septic shock in surgical infection.

OBJECTIVES: To evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-alpha polymorphism with regard to the plasma TNF-alpha concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU). DESIGN: A total of 112 postoperative critically ill infected patients were prospectively enrolled. SETTING: SICU of a tertiary university-affiliated medical center. PATIENTS: Patients who were consecutively admitted to the SICU because of surgical infection with sepsis. INTERVENTION: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Blood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-alpha level and to analyze the genotype of the biallelic polymorphism of the TNF-alpha. RESULTS: The allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%, p < .05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels. CONCLUSION: In patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-alpha level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.

Development of a new prognostic system and validation of APACHE II for surgical ICU mortality: a multicenter study in Taiwan.

BACKGROUND: To develop and to validate a new prognostic prediction system for patients admitted to the surgical intensive care unit (ICU), and to compare its performance with the Acute Physiology and Chronic Health Evaluation (APACHE) II system. METHODS: The database was derived from three surgical ICUs in three hospitals. For each patient, demographic data, diagnosis, APACHE II score and hospital survival data were collected. The accuracy in outcome prediction of the APACHE II was assessed by means of receiver operating characteristic (ROC) analysis. The new prognostic system was developed by using a multiple logistic regression in the developmental data set and validated with the validation data set. RESULTS: A total of 1,248 patients were included from three ICUs. The area under the ROC curve was 0.74 for the APACHE II score. The new prognostic system includes 18 variables. Goodness-of-fit tests indicated that the model performed well in the developmental and validation samples (p = 0.235 in the developmental data set and p = 0.297 in the validation set). The area under the ROC curve was 0.84 in the developmental sample and 0.77 in the validation sample for the new prognostic score. The area under the ROC curve was 0.71 in the validation sample for the APACHE II score. CONCLUSIONS: Although APACHE II correlates with mortality for surgical ICU patients in Taiwan, its accuracy is not as good as in the original study. Mortality prediction performance improved with the use of the new, local scoring system.

Factors affecting gentamicin pharmacokinetics in septic patients.

BACKGROUND: This prospective, comparative study was designed to estimate the volume of distribution (Vd) and elimination rate constant (K(e)) of gentamicin and to determine the clinical factors affecting the pharmacokinetics of gentamicin in different stages of sepsis. METHOD: Seventy-seven critically ill patients treated with gentamicin for gram-negative sepsis were included. These septic patients were divided into hyperdynamic septic and hypodynamic septic groups according to cardiac index. Twenty-seven patients who received postoperative prophylactic gentamicin were recruited as controls. RESULTS: Fifty-two patients in the hyperdynamic septic group had a significantly larger Vd than those in the hypodynamic septic and control groups. The Vd was correlated significantly with both Acute Physiological Score (APS) (r=0.340, P<0.01) and cardiac index (r=0.394, P<0.01). The K(e) of gentamicin correlated significantly with both blood urea nitrogen (BUN) (r= 0.565, P<0.01) and serum creatinine level (r=0.563, P<0.01). CONCLUSION: The increased Vd in the septic patients was related to the severity of illness and magnitude of cardiac output. The K(e) of gentamicin was correlated with the serum creatinine level.

Peri-anhepatic phase oxygen kinetics in porcine liver transplantation.

BACKGROUND: We applied a liver transplantation animal model to examine the relationship between oxygen delivery and consumption. The presence of pathologic flow-dependent oxygen consumption was investigated during and after the anhepatic phase. The effect of venous-to-venous bypass on oxygen kinetics was evaluated. METHODS: Twelve pigs were randomly divided into two groups. The non-bypass group consisted of six pigs that were subjected to clamping of the hepatic artery, portal vein, and the superior and inferior vena cava to produce an anhepatic phase. The bypass group consisted of six pigs that underwent vascular clamping and liver transplantation with venous bypass. Hemodynamics, oxygen delivery index (DO2) and oxygen consumption index (VO2) were recorded during the peri-anhepatic phase. Best-fit regression lines were calculated for DO2 vs VO2. RESULTS: In the pigs without venous bypass, the blood pressure, cardiac index and VO2 dropped significantly after vascular clamping and lactic acidosis developed. In pigs with venous bypass, vascular clamping induced a significant decline of cardiac output and DO2 but VO2 was maintained by a compensatory increase in oxygen extraction ratio. DO2 and VO2 after the release of vascular clamping increased significantly higher than that before vascular clamping. The O2 supply-dependent regression line was drawn from the points below critical oxygen delivery with a slope of 0.232 (95% CI = 0.110-0.354, r2 = 0.50, p = 0.010). The pathologic supply-dependent line was drawn from the points with supranormal DO2 and VO2 with a slope of 0.185 (95% CI = 0.050-0.333, r2 = 0.510, p = 0.029). The slope of the supply-independent line was 0.0089 (95% CI = -0.030-0.050, r2 < 0.009, p = 0.12). CONCLUSIONS: Oxygen delivery dropped below the critical level and flow-dependent oxygen consumption developed during the anhepatic phase without venous bypass. Venous-to-venous bypass is necessary to maintain a critical DO2 and stable hemodynamics during porcine liver transplantation. Pathologic flow-dependent oxygen consumption developed after the anhepatic phase.

Effect of transcutaneous electrical nerve stimulation for pain relief on patients undergoing hemorrhoidectomy: prospective, randomized, controlled trial.

PURPOSE: Posthemorrhoidectomy pain control remains a challenging problem. Transcutaneous electrical nerve stimulation is known to be effective in the treatment of many diseases. Our aim was to investigate the effect of transcutaneous electrical nerve stimulation on pain relief in patients undergoing hemorrhoidectomy. METHODS: Sixty patients with symptomatic hemorrhoids were randomly allocated into two groups, the acupoint group (n = 30) and the nonpoint control group (n = 30). Transcutaneous electrical nerve stimulation was applied to those patients who received hemorrhoidectomy, and patient-controlled analgesia was achieved by injection of morphine through ambulatory infusion pumps. The dependent measures in this study were pain score from 0 (no pain) to 10 (agonizing pain), analgesic doses administrated through patient-controlled analgesia, and postoperative complications. RESULTS: The subjective pain scores evaluated 8, 12, 16, and 24 hours after hemorrhoidectomy in the control group and the acupoint group were 5.9 +/- 0.5 and 4.1 +/- 0.5, 5.7 +/- 0.5 and 3.5 +/- 0.4, 4.1 +/- 0.4 and 2.3 +/- 0.3, and 3.2 +/- 0.4 and 1.9 +/- 0.2, respectively (two-way analysis of variance; P < 0.05). There was a significant difference between treatment groups in morphine use, with 11.6 +/- 2.2 mg in the control group and 6.2 +/- 1.3 mg in the acupoint group (P < 0.05). The acupoint group tended to have less postoperative acute urinary retention (Fisher's exact probability test; P = 0.145) and less need for analgesics than the control group (P = 0.112, Fisher's exact test). CONCLUSION: Transcutaneous electrical nerve stimulation is effective for pain relief in patients receiving hemorrhoidectomy. Its efficacy and safety could assist outpatient pain management after hemorrhoidectomy.

Serum albumin concentration as a prognostic indicator for acute surgical patients.

BACKGROUND: Whether or not the rapid reduction in serum albumin concentration in acute surgical patients without evidence of pre-existing energy deficit correlates with outcome has yet to be studied. In this study, we attempted to determine whether albumin infusion or nutritional supplementation can improve outcome for patients with hypoalbuminemia. METHODS: We retrospectively reviewed 80 non-calorie-deficient patients newly admitted to the surgical intensive care unit of the Veterans General Hospital-Taipei with complete data for serum albumin concentration and APACHE II score within 24 hours from August, 1998, to February, 1994. The relationships between age, sex, diagnosis, reason for intensive care, albumin infusion, hyperalimentation, APACHE II score, serum albumin concentration, days in intensive care and prognosis within three months were analyzed. RESULTS: Univariate statistical analysis showed that the serum albumin concentration and APACHE II score correlated well with patient survival (p = 0.002 and p = 0.025, respectively). Multivariate analysis showed that hypoalbuminemia was independently associated with patient outcome (p = 0.003). Simple albumin infusion or hyperalimentation for patients with hypoalbuminemia did not improve survival. CONCLUSIONS: The results suggest that serum albumin concentration appears to be a good prognostic marker for acute surgical patients. While decreased serum albumin concentration may also reflect poor nutritional status, for patients with moderate to severe hypoalbuminemia due to other causes, simple albumin infusion and/or nutritional support did not significantly improve survival. Consequently, aggressive treatment of the underlying disease is far more important.

Peripheral neural modulation of endotoxin-induced hyperventilation.

OBJECTIVE: To delineate the role of the peripheral neural reflexes involved in modulating hyperventilation during endotoxemia. DESIGN: A prospective, randomized, controlled, multigroup study. SETTING: Research animal laboratory. SUBJECTS: Adult Sprague-Dawley rats (n=43; 354+/-24 g) of either gender. INTERVENTIONS: Eight rats received a sham operation on their vagus, carotid sinus, and aortic nerves before the administration of a saline vehicle to serve as the time control. In the endotoxin group, 11 rats received a sham operation before endotoxin challenge. The remaining 24 rats received bilateral vagotomy (n=8), perivagal capsaicin treatment (n=8), or denervation of peripheral chemoreceptors (n=8) before endotoxin challenge. After the breathing pattern returned to a steady state, endotoxin (L-4130, serotype 0111, B4 lipopolysaccharide; 50 mg/kg) was injected into the vein. The rat's respiration was then monitored continuously for 5 hrs or until the animal died. MEASUREMENTS AND MAIN RESULTS: The respiratory rate and tidal volume did not change over the 5-hr observation period in the time control group. In the endotoxin group, the respiratory rate increased significantly from baseline (135.4%) 2 hrs after endotoxin challenge and increased persistently until the rats died. The tidal volume increased gradually to < or =132.8% of baseline 4 hrs after endotoxin challenge. Bilateral cervical vagotomy and perineural capsaicin treatment of the vagus nerves eliminated the tachypnea response to endotoxin injection. Denervation of the peripheral chemoreceptor accentuated the hyperventilation response to endotoxin, and resulted in the shortest survival time. CONCLUSIONS: Both lung vagal C-fiber afferents and peripheral chemoreceptors are involved in modulating the hyperventilation response after endotoxin challenge in rat models. Stimulation of vagal C-fiber afferents increased the respiratory rate. Conversely, the role of peripheral chemoreceptors was to restrain the hyperventilatory response and these receptors may play a protective role during endotoxemia.

Ultrasound-guided cannulation of the internal jugular vein for dialysis vascular access in uremic patients.

BACKGROUND: A reliable temporary vascular access is always required for hemodialysis when a permanent vascular access is not available. However, techniques for creating temporary vascular accesses remain imperfect. This study utilized the 'SiteRite' ultrasound device to improve both success and complication rates of jugular venous cannulation for temporary access. METHODS: This prospective, comparative study recruited 104 uremic patients receiving ultrasound-guided and 86 patients undergoing landmark-guided percutaneous internal jugular venous cannulation of dual-lumen dialysis catheters. Success rate, number of puncture attempts, access time, and the complication rate of the ultrasound technique, in comparison with the landmark-guided technique, were studied. RESULTS: The ultrasound-guided cannulation was superior to the external landmark-guided cannulation in overall success rate (99.0 vs. 86.0%, p < 0.01), success rate of the first puncture attempt (80.8 vs. 34.9%, p < 0.01), average puncture (access) times (15.8 vs. 43.7 s, p < 0.01), puncture trials (1.39 vs. 2.58, p < 0.01), and traumatic complication rate (1.9 vs. 1 1.6%, p = 0.015). The incidence of infective complications for the ultrasound group was not different from that of the landmark-guided groups (2.9 vs. 2.3%, p = 0.589). CONCLUSION: The ultrasound-guided technique offers both safety and convenience in inserting jugular venous dialysis catheters. It represents a valuable technique in creating temporary dialysis hemoaccesses.

Effects of high thoracic epidural anaesthesia on the peripheral airway reactivity in dogs.

BACKGROUND: It has been speculated that epidural anaesthesia may induce bronchoconstriction via the mechanism of a sympathetic blockade. However, this hypothesis has not been confirmed by any experimental evidence. Therefore, we investigated the effects of high thoracic epidural anaesthesia with neural sympathetic blockade on basal airway resistance and airway reactivity in response to bronchoconstrictive stimuli in a canine periphery lung model. METHODS: Acetylcholine (Ach, 8 microg kg[-1] i.v.) or histamine (His, 3 microg kg[-1] i.v.) was administered to 7 anaesthetized mongrel dogs before and after thoracic epidural anaesthesia. Successful neuronal sympathectomy was confirmed by nitroglycerin test. The changes of peripheral airway resistance (Rp), haemodynamics, cardiac output (CO), and the recovery time for Rp from peak returning to baseline in each challenge were studied. RESULTS: Thoracic epidural anaesthesia altered neither the baseline Rp nor the peak Rp evoked by Ach or His. However, the recovery time of the Rp was prolonged significantly after epidural anaesthesia (P<0.01) and correlated inversely with the CO in response to Ach or His challenge (Ach, r=0.542; His, r=0.651). CONCLUSIONS: Our results suggest that epidural anaesthesia with neural sympathetic blockade has no influence on the basal peripheral airway resistance; however, it prolongs the airway reactivity to Ach or His challenge, probably by the mechanism of reducing CO.

Anatomical variation of the internal jugular vein and its impact on temporary haemodialysis vascular access: an ultrasonographic survey in uraemic patients.

BACKGROUND: Creation of a reliable haemoaccess is a critical problem for practicing nephrologists once haemodialysis has been considered. A double-lumen internal jugular-vein catheter is favoured in most cases requiring temporary haemoaccess. However, numerous complications, even lethal ones, may occur with the cannulating procedure. Using ultrasound, we attempted to describe the occult anatomical variations of vessels which may be responsible for complications. METHODS: A 'SiteRite' ultrasonographic device was used to inspect the anatomical structure of the internal jugular veins (IJV) in 104 consecutive uraemic patients undergoing creation of internal jugular vein temporary angioaccess. Images of the vessels and demographic data of patients were recorded and analysed. RESULTS: Anatomical variations of the right and left IJVs were found in 19 (18.3%) and 17 (16.4%) uraemic patients respectively. Unilateral IJV variations were found in 18 patients (17.3%) and bilateral variations were discovered in nine patients (8.7%). A total of 27 patients (26.0%) had IJV anatomical variations that might contribute to difficulty in external landmark-guided IJV cannulation. CONCLUSIONS: The external anatomical landmarks for cannulating the IJV are not reliable in about one-quarter of uraemic patients. An ultrasound survey on the IJV anatomy is recommended for selecting proper puncture site and reducing risks of insertion complications for IJV dialysis catheters.

Magnetic resonance imaging contrast media in the subarachnoid space. A comparison between gadodiamide injection and gadopentetate dimeglumine in an experimental study in pigs.

RATIONALE AND OBJECTIVES: The authors studied the neural tolerance and contrast enhancement of a nonionic, gadodiamide injection (gadolinium [Gd]-DTPA-BMA), and an ionic, gadopentetate dimeglumine (Gd-DTPA), contrast medium in the subarachnoid space of the pig. METHODS: Sixteen experiments were performed in eight pigs. Lumbar and lateral C1-C2 punctures were performed. Ten milliliters of Gd-DTPA-BMA or Gd-DTPA with Gd concentrations varying from of 500 mmol/L to 0.625 mmol/L were injected, in four experiments via the lumbar route and in 12 experiments via the C1-C2 puncture. RESULTS: Four pigs injected via the C1-C2 puncture with a Gd concentration of 500 mmol/L had signs of somatomotor irritation and all were paretic after 24 hours. No somatomotor effects were observed in the other experiments, where lower concentrations of Gd were used. Marked enhancement of the cerebrospinal fluid with no visible signal differences was obtained with concentrations from 10 to 0.625 mmol/L. CONCLUSIONS: Both Gd-DTPA-BMA and Gd-DTPA are remarkably well tolerated in the subarachnoid space. In doses relevant for imaging purposes no adverse effects were seen.

[Similarity and synergy of trauma and sepsis: role of tumor necrosis factor-alpha and interleukin-6].

Both trauma and infection cause a rise in body temperature, white blood cell count, acute phase proteins, fluid and sodium retention and negative nitrogen balance. This phenomenon is often described as "acute phase response" or "systemic inflammatory response syndrome" to denote a coordinated systemic response to significant tissue injury and/or microbial invasion. It is generally agreed that the acute phase response is mediated through the interaction of cytokine and neuroendocrine pathways. Tumor Necrosis Factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are two of the major key cytokines involved in the generation of acute phase response. Interleukin-6 are consistently found in septic, trauma and post-operative patients and correlated well with the severity of sepsis or injury. IL-6 is responsible for the fever and metabolic changes in the acute phase. In addition to IL-6, TNF-alpha was proved to be the mediator that orchestrates the hemodynamic and tissue injury in septic shock. TNF-alpha destroys endothelial cells and induces disseminated intravascular coagulation, fluid shift, shock, multiple organ system failure and death. On many clinical occasions, both infection and trauma may happen simultaneously on the same patient. Our study demonstrated that operation on the infected patients would cause a synergistic effect on both TNF-alpha and IL-6 levels. The pulse increase in TNF-alpha and the persistent elevation of IL-6 were responsible for the post-operative unstable clinical condition in the infected patients. Should we block the cytokine signal and inflammatory response that appear to be harmful? Animal studies have shown that the septic shock to endotoxin challenge can be prevented by pretreatment with monoclonal antibody against TNF-alpha. The transcription of TNF-alpha can be blocked with corticosteroid in vivo. The post-operative increase in IL-6 and its related inflammation can be attenuated with corticosteroid, epidural anesthesia and narcotics. However, although blocking the inflammatory response has a beneficial effect of stress free it also eliminates our ability to fight with bacterial infection by lowering our immune response. How to manipulate these cytokines is a question of art more than science.

Perioperative plasma concentrations of tumor necrosis factor-alpha and interleukin-6 in infected patients.

OBJECTIVE: To characterize the sequential plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and their relationship with the clinical outcome in patients with intra-abdominal infection who underwent surgical intervention. DESIGN: A prospective, comparative study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Fifteen patients with surgically proved intra-abdominal infection were included as the infected group. The comparative noninfected group consisted of ten patients who underwent major abdominal surgery without infection. INTERVENTIONS: Blood samples were obtained from the indwelling arterial catheter before induction of general anesthesia, and 1, 1.5, 2, 3, 4, 6, and 24 hrs after skin incision. MEASUREMENTS AND MAIN RESULTS: Plasma cytokine concentrations were measured using radioimmunoassay. The hemodynamic and physiologic parameters were recorded for comparison with cytokine concentrations. In the noninfected group, the TNF-alpha concentration was very low throughout the observation period, and the IL-6 concentration increased 4 hrs after skin incision. The infected group had significantly higher TNF-alpha and IL-6 concentrations than the noninfected group. The TNF-alpha concentration increased from 129.2 +/- 46.4 to 1196.0 +/- 445.8 pg/mL and the IL-6 concentration increased from 54.2 +/- 24.3 to 560.3 +/- 187.5 pg/mL 2 hrs after skin incision in the infected group. The postoperative APACHE II score correlated significantly with both peak IL-6 (r2=.39) and peak TNF-alpha (r2=.32) concentrations. CONCLUSIONS: Both TNF-alpha and IL-6 concentrations increased significantly after surgical intervention in patients with intra-abdominal infection. The pulse increase in TNF-alpha concentration and the persistent increase in IL-6 concentration were related to the poor postoperative clinical condition in infected patients.