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.

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.

Animal experimental myelography in the pig. A comparison between iohexol and iotrolan.

RATIONALE AND OBJECTIVES: The authors compared the effects of a nonionic monomeric, iohexol (Omnipaque, 300 mg I/ml), and a nonionic dimeric, iotrolan (Isovist, 300 mg I/ml), contrast medium in the spinal subarachnoid space of the pig. METHODS: Lumbar and lateral C1-C2 punctures were performed in 10 pigs. Ten milliliters iohexol or iotrolan were injected via the lumbar needle. Blood pressure, electrocardiogram, intravesical pressure, and cerebrospinal fluid pressure were recorded during the injections and at intervals for 4 to 5 hours after the injections. Blood samples were taken at 30, 60, 120, 180, 240, and 300 minutes after the injections and analyzed for iodine concentration. RESULTS: No changes were seen during the injections, and there were no differences in the blood pressure, cerebrospinal fluid pressure, electrocardiographic recordings, or in the plasma iodine concentrations during the first 4 to 5 hours after the injections. Short-lasting, rhythmic bladder contractions were seen during some injections with both iohexol and iotrolan. CONCLUSION: Both iohexol and iotrolan were well tolerated, and there was no significant difference between them. and there was no significant difference between them.

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.

The role of flow cytometry in non-resected cervical carcinoma.

Flow cytometry (FCM) has a prognostic value for many malignant neoplasms in terms of treatment response rate and survival. However, its role in non-resected cervical carcinoma remains uncertain. We have collected 96 paraffin-embedded specimens taken from non-resected cervical cancer patients treated by radiotherapy (RT) alone between 1984 and 1986. Our data revealed that FCM has little correlation with patients' age, pathological grade and clinical stage. Ploidy pattern and clinical stage correlate significantly with complete remission (CR) rate (p = 0.001 and 0.03). Most diploid or low-stage tumours (IB to IIA) obtained CR after RT alone. The application of an intravaginal extension electron cone (IVEC) (p = 0.019) and CR status (p = 0.0001) yield significant better overall survival (OS) rates than their alternative groups. The Cox regression model has confirmed these two variables as having an independent influence on OS. We thus conclude that both ploidy pattern and S-phase fraction (SPF) predict neither pre-treatment biological behaviour of the tumours nor overall survival. However, ploidy pattern has an independent influence on CR rate.

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.

[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.

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.

[Protrusion of thoracic intervertebral disk: report of 11 cases].

The authors reported 11 cases of thoracic intervertebral disk protrusion examined with plane film, myelography, CT and CT-myelography in 11 cases and MR imaging in 3. All of the 11, cases were confirmed by operation. There were 13 protrusions in the 11 cases with the locations of T10-11 in 4, T11-12 in 5 cases and T12-L1 in 4. 9 protrusions fell into central type, 1 into paracentral type and 1 into lateral type. The clinical symptoms were prominent with all 11 cases, however, most primary clinical diagnoses were erroneously given as lumber intervertebral disk protrusions and even the disorders of heart, lung, alimentary tract and urinary system. It was concluded that the main causes of the misdiagnosis included: (1) not easily to think of this entity for the clinic physicians due to its low incidence, (2) the untypical clinical manifestations. The authors considered that the exam method with the highest accuracy is CT-myelography.

The role of submucosal oedema in increased peripheral airway resistance by intravenous volume loading in dogs.

Pulmonary congestion leads to an increase in airway resistance. It is still unknown whether this is due to vascular engorgement or to submucosal oedema. The present study was designed to determine the relative contribution of these two potential mechanisms. We examined the effect of intravenous volume loading on canine peripheral airway resistance (Rp). Bronchoscopes were wedged in contralateral sublobar segments and used to record Rp during rapid infusion of normal saline. Volume loading with normal saline increased pulmonary capillary wedge pressure (PCWP) and Rp. Unlike normal saline, dextran 70 did not increase Rp when infused at a rate that produced similar changes in PCWP. During infusion of normal saline, delta Rp was significantly enhanced in lung segments previously challenged with dry air when compared to contralateral control lungs, unexposed to dry air, and the use of dextran 70 significantly reduced this effect. Vasoconstriction with phenylephrine significantly decreased baseline Rp, but did not completely reverse the effect of fluid infusion. In addition, in lung segments exposed to dry air, delta Rp was significantly greater after volume loading and treatment with phenylephrine when compared to contralateral control lung. Finally, muscarinic receptor blockade was ineffective in preventing Rp from increasing during infusion of normal saline. Our results suggest that volume loading-induced increases in Rp are not caused by either vascular engorgement or the stimulation of muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

The autonomic nervous system modulates dry air-induced constriction in the canine lung periphery.

To determine the modulatory role of the autonomic nervous system on dry air-induced bronchoconstriction (AIB) in the canine lung periphery, we examined the effect of cholinergic, alpha- and beta-adrenergic, and total autonomic ganglionic blockade on AIB. Pretreatment with atropine significantly attenuated AIB by approximately 30%, indicating that AIB is partially mediated via a vagal reflex. Pretreatment with either phentolamine or propranolol did not affect AIB, indicating that alpha- and beta-adrenoceptors, respectively, were not activated in response to dry air challenge. In contrast, pretreatment with hexamethonium significantly potentiated AIB. In addition, exogenous vasoactive intestinal peptide (VIP), a potential neurotransmitter for the nonadrenergic-noncholinergic (NANC) inhibitory system, significantly inhibited AIB. We conclude that (1) neither alpha- or beta-adrenergic efferents are activated during dry air challenge, (2) total autonomic blockade potentiates the response to dry air, and (3) VIP attenuates AIB. Based on these observations, we speculate that NANC inhibitory activity may be stimulated during dry air challenge and antagonizes AIB.

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.

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.

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.

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.

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.