Early mobilization programme improves functional capacity after major abdominal cancer surgery: a randomized controlled trial.

Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and safety of a supervised postoperative exercise programme. Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncology surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary outcome was inability to walk without human assistance at postoperative day 5 or hospital discharge. Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilitation care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P=0.01), with an absolute risk reduction of 22.2% [95% confidence interval (CI) 5.9-38.6] and a number needed to treat of 5 (95% CI 3-17). All patients in the intervention group were able to follow at least partially the exercise programme, although the performance among them was rather heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises. Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact on clinical outcomes is still unclear. Clinical trial registration: NCT01693172.

Safe and rapid contouring of fibro-osseous lesions in the orbital area using navigation with minimally invasive cranial bone registration.

BACKGROUND: Bone contouring is currently the best treatment for fibro-osseous lesions after bone growth arrest. Navigation systems available for this surgery allow intra-operative visualisation with improved cosmetic outcomes. However, conventional navigation systems using superficial skin registration cannot prevent subtle discrepancies. METHOD: To address this problem, we used a non-invasive cranial bone registration that uses patient-specific dental templates to maintain exact registration. We created the preset goal using the mirror image of the unaffected side for unilateral lesions, and using images obtained before the onset of symptoms for bilateral lesions. This system achieved precise pre-operative simulation. A sound aid in the navigation system provided information regarding proximity to critical structures and to the preset goal. RESULTS: We used this system to contour fibro-osseous lesions in three patients. All patients achieved good facial contours and improvement in symptoms. CONCLUSIONS: This method offers a safe, rapid surgical aid in treating orbital fibro-osseous lesions.

Well-differentiated liposarcoma arising in the parapharyngeal space: a case report and review of the literature.

BACKGROUND: Liposarcomas rarely occur in the parapharyngeal space and only a few case reports exist. For curative therapy of liposarcoma, surgical excision remains the dominant modality. Although a wide surgical margin is important to prevent local recurrence, wide excision is often difficult in the head and neck region. CASE REPORT: We report a case of a 19-year-old female with a well-differentiated liposarcoma arising in the parapharyngeal space. We removed the tumour surgically utilising a cervical-parotid approach. The histological diagnosis was well-differentiated sclerosing liposarcoma. There is no recurrence after five years and nine months of follow up. CONCLUSION: The patient's age and the tumour site made it difficult for us to make a quantitative diagnosis before the operation. Well-differentiated liposarcoma rarely develop distant metastasis, but often recur locally. The benefit of adjuvant radiotherapy for well-differentiated liposarcoma is still not clear and careful and long-term follow up is necessary.

Positive fluid balance is associated with reduced survival in critically ill patients with cancer.

BACKGROUND: There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. METHOD: One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. RESULTS: The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104-557), P = 0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100 ml/24 h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P = 0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P = 0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95% CI (1.45-18.24), P = 0.011]. CONCLUSION: A cumulative positive fluid balance higher than 1100 ml/24 h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.

Use of pulse pressure variation to estimate changes in preload during experimental acute normovolemic hemodilution.

BACKGROUND: Acute normovolemic hemodilution (ANH) is an alternative to blood transfusion in surgeries involving blood loss. This experimental study was designed to evaluate whether pulse pressure variation (PPV) would be an adequate tool for monitoring changes in preload during ANH, as assessed by transesophageal echocardiography. METHODS: Twenty-one anesthetized and mechanically ventilated pigs were randomized into three groups: CTL (control), HES (hemodilution with 6% hydroxyethyl starch at a 1:1 ratio) or NS (hemodilution with saline 0.9% at a 3:1 ratio). Hemodilution was performed in animals of groups NS and HES in two stages, with target hematocrits 22% and 15%, achieved at 30-minute intervals. After two hours, 50% of the blood volume withdrawn was transfused and animals were monitored for another hour. Statistical analysis was based on ANOVA for repeated measures followed by multiple comparison test (P<0.05). Pearson's correlations were performed between changes in left ventricular end-diastolic volume (LVEDV) and PPV, central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP). RESULTS: Group NS received a significantly greater amount of fluids during ANH (NS, 900 ± 168 mL vs. HES, 200 ± 50 mL, P<0.05) and presented greater urine output (NS, 2643 ± 1097 mL vs. HES, 641 ± 338 mL, P<0.001). Significant decreases in LVEDV were observed in group NS from completion of ANH until transfusion. In group HES, only increases in LVEDV were observed, at the end of ANH and at transfusion. Such changes in LVEDV (∆LVEDV) were better reflected by changes in PPV (∆PPV, R=-0.62) than changes in CVP (∆CVP, R=0.32) or in PAOP (∆PAOP, R=0.42, respectively). CONCLUSION: Changes in preload during ANH were detected by changes in PPV. ∆PPV was superior to ∆PAOP and ∆CVP to this end.

Aging transition of the bacterial community structure in the chick ceca.

The transition of the bacterial community structure and predominant bacteria in the ceca of chicks from hatching to 2 wk of age was investigated using denaturing gradient gel electrophoresis with the 16S ribosomal RNA gene, followed by phylogenetic analysis. The results demonstrated that most of the cecal bacterial flora from hatching to a few days old consisted of Escherichia coli (sequence similarity: 100%), and the floral diversity was still low 2 wk posthatch. These findings will help contribute to the development of a novel competitive exclusion product.

Imaging of early pancreatic cancer on multidetector row helical computed tomography.

Early pancreatic cancer is small and limited to the pancreas. In contrast, small pancreatic cancer may include peripancreatic vasculature or metastasis involvement. This study evaluates images of early pancreatic cancer on multidetector CT (MDCT) using contrast-enhanced multiphasic imaging, and post-processed pancreatic duct images. CT findings and pathological features were analysed in eight patients with early pancreatic cancer. Pathological evaluation included location, size and histological grading of the tumour. MDCT evaluation covered the maximum diameter of the main pancreatic duct (MPD), stenosis or obstruction of the MPD, loss of normal lobar texture and associated pancreatitis. Attenuation differences between normal pancreatic parenchyma and the tumour (AD-PT) were also measured. Focal stenosis or obstruction of the MPD with dilatation of the distal MPD was demonstrated in all patients. Associated pancreatitis occurred in six patients with tumours measuring 12 mm or greater. Loss of normal lobar texture was recognised in four cases with the tumour measuring 14 mm or greater. Statistically, low-attenuated lesions and high-attenuated lesions differed with respect to the tumour size (p<0.01), and a positive relationship was demonstrated between the tumour size and AD-PT (r = 0.84). In seven cases, AD-PT is higher during the arterial phase than the pancreatic phase. Early pancreatic cancer appears as low attenuation on early phase, and as high- to iso-attenuation during the pancreatic and delayed phases in respect to the tumour size. Focal stenosis or obstruction of the MPD with dilatation of the distal MPD observed on curved reformation imaging seems important in the diagnosis of early pancreatic cancer.

Celsior versus Wisconsin solution in pancreas transplantation.

Celsior solution (CS), which has recently become available, that might theoretically offer a new means for improving graft preservation quality. The present prospective, randomized study was designed to evaluate the efficacy of CS compared with University of Wisconsin (UW) for pancreas allografts. Between January 2001 and January 2007, 88 patients underwent pancreatic transplantation, including the last 30 consecutive simultaneous pancreas kidney patients who were randomly assigned to either CS or UW. There was no case of graft thrombosis in either group. There were 2 cases of pancreatitis in the UW group compared with 1 in the CS group. No case of primary nonfunction occurred in either group. There were 2 cases of early duodenal stump fistulae in the CS group that required transplantectomy, whereas this complication was not observed in the UW group. Relaparotomy in the UW group was required in 3 cases due to infection and treated by close drainage that which, progressed to fatal sepsis in 1 patient. In the UW group with 6 months of follow-up, there were 12 patients insulin free. In the CS group, 6 patients underwent relaparotomy, 3 for transplantectomy and the others for intra-abdominal infection, which was fatal in 2 cases. In the CS group with 6 months of follow-up, there were 10 patients insulin free. Two patients died with functioning grafts. These results provided indirect evidence that CS solution is at least as safe as UW to mitigate postreperfusion graft edema and pancreatitis, as well as graft thrombosis.

Postural changes during eye-head movements.

We investigated postural sway in young subjects during eye-head movements. Subjects stood on the force plate wearing a helmet on which a laser spot was attached. Visual targets were presented stepwise at 60 degrees to right and left or 50 degrees to upward and downward of the straight-ahead position. Subjects were asked to look at the targets quickly by directing the laser spot to the target. The anterior-posterior component of centre of pressures (COPs) exhibited the largest changes and shortest latencies during downward movements. Most of the subjects showed COP changes preceding the onset of downward head movements, and these changes were associated with EMG activity of biceps femoris and gastrocnemius. When subjects were asked to look at the target only by eyes, no consistent change was detected in ground reaction forces. These results indicate that the eye-head movements elicited the COP changes that preceded the onset of head movements.

Predictive signals in the pursuit area of the monkey frontal eye fields.

In order to pursue a moving target with our eyes, visual motion-signals are converted into eye movement commands. Because of delays in processing visual information, prediction is necessary to compensate for those response-delays and maintain target images on the foveae. Previous studies showed that the majority of FEF pursuit neurons receive visual signals related to actual and predicted target motion. However, in those studies, discharge related to the memory of visual motion could not be separated from that related to prediction. To distinguish the two, while fixating a stationary spot, monkeys were required to memorize the direction of random dot motion (cue-1). After a delay (delay-1), a second cue (cue-2) instructed the monkeys to prepare either pursuit in the memorized direction or to maintain fixation. After a second delay (delay-2), the monkeys selected the correct response. In virtually all tested neurons that showed a visual motion-response to cue-1, the response was not maintained during the delay-1. The majority of responsive neurons were modulated during cue-2 and delay-2. Changing the delay-2 duration also changed the duration of discharge modulation, suggesting that delay-2 modulation was predictive. These results suggest that activity related to visual motion-memory was not conveyed by the discharge of caudal FEF pursuit neurons.

Unusual imaging appearances of pancreatic serous cystadenoma: correlation with surgery and pathologic analysis.

BACKGROUND: We describe imaging and pathologic features of serous cystadenoma of the pancreas on multislice helical computed tomography CT (MS-CT) and surgical resection. METHODS: Radiologic and pathologic features were analyzed in five patients. All patients underwent MS-CT and digital subtraction angiography (DSA), and four patients underwent magnetic resonance (MR) imaging. Preoperatively, three cases showed radiologic evidence of mainly solid appearance on MS-CT, and the suspected diagnoses were solid pancreatic tumors (patients 1-3). The other two cases showed radiologic evidence of macrocystic tumor of the pancreas, and the suspected diagnoses were mucinous cystic tumors (cases 4 and 5). All patients underwent surgery, and the diagnosis of serous cystadenoma was confirmed on pathologic examination. RESULTS: In three cases that showed a solid appearance on MS-CT, a microcystic appearance was identified on microscopic examination, and the tumors were found to be hypervascular lesions on multiphasic contrast-enhanced CT and DSA. In cases 1 and 2, the lesions showed high intensity with internal septation on T2-weighted MR images. In two cases, the tumors were classified as a macrocystic variant of serous cystadenoma, and no mural nodules, papillary projections, or calcifications were seen in the tumors. CONCLUSION: Imaging appearance of serous cystadenoma on MS-CT is various and sometimes indistinguishable from that of solid tumor or mucinous cystic tumors of the pancreas. Imaging findings of hypervascularity and a well-marginated high-intensity lesion with internal septation on T2-weighted MR imaging may be crucial to identify serous cystadenoma that contains no visible cystic compartments on MS-CT.

Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs).

AIMS: To determine the prevalence of CD99 expression in pancreatic endocrine tumours (PETs). We evaluated CD99 expression and analysed Ki67 labelling by immunohistochemistry in PETs. METHODS AND RESULTS: Thirty-eight PETs from 33 patients were analysed. CD99 immunoreactivity was consistently observed in normal islets of the pancreas, regardless of the cell type. Tumours comprising more than 30% CD99+ cells were defined as positively immunoreactive for CD99. CD99 expression was observed in 20 of the 38 PETs examined, but not in any of the pancreatic tumours of other histological subtypes (10 ductal adenocarcinomas, five intraductal papillary-mucinous tumours, and two acinar cell tumours). Loss of CD99 expression was related to markers of worse prognosis for PET, including gross local invasion, metastasis to the lymph nodes or other organs, lymphatic or blood vessel invasion, and neuroendocrine carcinoma (NEC). Thus, CD99 expression may have an efficiency comparable to that of high Ki67 labelling index (5% or more) for prognostication. CONCLUSIONS: CD99 expression was observed frequently and exclusively in PETs, and loss of CD99 expression in PETs was found to be associated with ominous prognostic indicators.

EBAG9/RCAS1 expression in hepatocellular carcinoma: correlation with tumour dedifferentiation and proliferation.

The oestrogen-responsive gene, EBAG9, whose product is identical to the cancer cell surface antigen RCAS1, is reported to be associated with tumour progression and invasiveness in various carcinomas. In this study, we examined the expression of EBAG9/RCAS1 in hepatocellular carcinoma (HCC), with special reference to its relationship with the stepwise evolution of HCC. Expression was examined by immunohistochemistry and western blotting analysis in 143 HCCs, as well as in non-cancerous liver tissues. After which, the association between enhanced EBAG9/RCAS1 expression and various clinicopathological parameters including Ki-67 labelling index (LI), a marker of proliferative activity, was evaluated. There was a constant low level of EBAG9/RCAS1 expression in non-cancerous liver tissues, with a regular cytoplasmic distribution. Positive immunoreactivity for EBAG9/RCAS1 was detected on the surface and in the cytoplasm of 84 HCC tumours, with an irregular staining pattern. Enhanced EBAG9/RCAS1 expression was correlated with a lower degree of differentiation and Ki-67 LI. Interestingly, expression was enhanced specifically in the less differentiated lesions within 'nodule-in-nodule' tumours. In conclusion, EBAG9/RCAS1 was associated with HCC tumour dedifferentiation and increased proliferative activity. Its exact functional role remains to be established.

Directional asymmetry in smooth ocular tracking in the presence of visual background in young and adult primates.

The smooth pursuit system moves the eyes in space accurately while compensating for visual inputs from the moving background and/or vestibular inputs during head movements. To understand the mechanisms underlying such interactions, we examined the influence of a stationary textured visual background on smooth pursuit tracking and compared the results in young and adult humans and monkeys. Six humans (three children, three adults) and six macaque monkeys (five young, one adult) were used. Human eye movements were recorded using infrared oculography and evoked by a sinusoidally moving target presented on a computer monitor. Scleral search coils were used for monkeys while they tracked a target presented on a tangent screen. The target moved in a sinusoidal or trapezoidal fashion with or without whole body rotation in the same plane. Two kinds of backgrounds, homogeneous and stationary textured, were used. Eye velocity gains (eye velocity/target velocity) were calculated in each condition to compare the influence of the textured background. Children showed asymmetric eye movements during vertical pursuit across the textured (but not the homogeneous) background; upward pursuit was severely impaired, and consisted mostly of catch-up saccades. In contrast, adults showed no asymmetry during pursuit across the different backgrounds. Monkeys behaved similarly; only slight effects were observed with the textured background in a mature monkey, whereas upward pursuit was severely impaired in young monkeys. In addition, VOR cancellation was severely impaired during upward eye and head movements, resulting in residual downward VOR in young monkeys. From these results, we conclude that the directional asymmetry observed in young primates may reflect a different neural organization of the vertical, particularly upward, pursuit system in the face of conflicting visual and vestibular inputs that can be associated with pursuit eye movements. Apparently, proper compensation matures later.

Iron-Mediated regulation of alkaline proteinase production in Pseudomonas aeruginosa.

We analyzed the regulation by iron of alkaline proteinase (AP) production in Pseudomonas aeruginosa. Extracellular AP production was detected from the mid-logarithmic to the stationary phase by an antibody-based assay system, and was strongly repressed by iron in the medium. This repression was shown by Northern hybridization and primer extension to occur at the level of transcription. The primer extension analysis revealed that the start point of transcription of AP gene was the nucleotide position -84 from the start point of translation. Furthermore, we investigated whether this transcriptional repression involved PvdS protein. Using the mutant strain of pvdS, the alternative sigma factor gene revealed that the PvdS protein is required for the full expression of AP, and a previous study showed that expression of pvdS is also repressed by iron. Therefore, we thought that one mechanism of repression of AP production operated through reduction of the PvdS protein level. Purified AP decomposed the transferrin, and released iron from it. Purified AP added to the medium containing transferrin as the only iron source enhanced the growth of P. aeruginosa. Moreover, mutation in the AP gene decreased the growth rate in the medium containing the transferrin as the only iron source. These results clearly indicated that AP expression should occur in a free-iron-deficient environment and emphasized the importance of AP to iron acquisition in the infection site.

Adaptive eye movements induced by cross-axis pursuit--vestibular interactions in trained monkeys.

We showed previously that smooth pursuit training combined with whole-body rotation in the orthogonal plane induces adaptive cross-axis vestibulo-ocular reflex (VOR). To gain an insight into the possible pathways and the nature of error signals for cross-axis VOR adaptation, we examined further properties of adaptive responses. In the first series, we trained monkeys for vertical pursuit during sinusoidal yaw rotation at 0.5 Hz (+/- 10 degrees) by presenting a target spot either in phase with, or with phase shifts (lead or lag) of 90 degrees to, the chair for 1 h. After training, sinusoidal or trapezoidal yaw rotation was tested in complete darkness without a target. Different training conditions resulted in different amounts of phase shift in cross-axis VOR. Trapezoidal yaw rotation (peak acceleration approximately 780 degrees/s2) revealed further differences in the direction, latency and time course of the adaptive responses depending on the conditions of the pursuit task. At least two (fast and slow) components with different latencies were induced in the cross-axis VOR by trapezoidal rotation after in-phase and phase-shift training. Adaptive responses were accurately simulated by the weighted sum of these two components. In the second series, we examined the effects of sequentially flashed (10 microseconds) targets in the horizontal plane during pitch rotation. The monkeys learned to track such targets by smooth pursuit, and cross-axis VOR was also induced after such apparent motion stimuli without retinal slip of the target image. These results indicate the importance of eye velocity for cross-axis VOR and suggest that this adaptation occurs most probably in the smooth pursuit pathways.

Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit-vestibular interaction training in monkeys.

The smooth pursuit system interacts with the vestibular system to maintain the accuracy of eye movements in space. To understand neural mechanisms of short-term modifications of the vestibulo-ocular reflex (VOR) induced by pursuit-vestibular interactions, we used a cross-axis procedure in trained monkeys. We showed earlier that pursuit training in the plane orthogonal to the rotation plane induces adaptive cross-axis VOR in complete darkness. To further study the properties of adaptive responses, we examined here the initial eye movements during tracking of a target while being rotated with a trapezoidal waveform (peak velocity 30 or 40 degrees/s). Subjects were head-stabilized Japanese monkeys that were rewarded for accurate pursuit. Whole body rotation was applied either in the yaw or pitch plane while presenting a target moving in-phase with the chair with the same trajectory but in the orthogonal plane. Eye movements induced by equivalent chair rotation with or without the target were examined before and after training. Before training, chair rotation alone resulted only in the collinear VOR, and smooth eye movement-tracking of orthogonal target motion during rotation had a normal smooth pursuit latency (ca 100 ms). With training, the latency of orthogonal smooth tracking eye movements shortened, and the mean latency after 1 h of training was 42 ms with a mean gain, at 100 ms after stimulus onset, of 0.4. The cross-axis VOR induced by chair rotation in complete darkness had identical latencies with the orthogonal smooth tracking eye movements, but its gains were <0.2. After cross-axis pursuit training, target movement alone without chair rotation induced smooth pursuit eye movements with latencies ca 100 ms. Pursuit training alone for 1 h using the same trajectory but without chair rotation did not result in any clear change in pursuit latency (ca 100 ms) or initial eye velocity. When a new target velocity was presented during identical chair rotation after training, eye velocity was correspondingly modulated by just 80 ms after rotation onset, which was shorter than the expected latency of pursuit (ca 100 ms). These results indicate that adaptive changes were induced in the smooth pursuit system by pursuit-vestibular interaction training. We suggest that this training facilitates the response of pursuit-related neurons in the cortical smooth pursuit pathways to vestibular inputs in the orthogonal plane, thus enabling smooth eye movements to be executed with shorter latencies and larger eye velocities than in normal smooth pursuit driven only by visual feedback.

Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.

System L is a major nutrient transport system responsible for the transport of large neutral amino acids including several essential amino acids. We previously identified a transporter (L-type amino acid transporter 1: LAT1) subserving system L in C6 rat glioma cells and demonstrated that LAT1 requires 4F2 heavy chain (4F2hc) for its functional expression. Since its oncofetal expression was suggested in the rat liver, it has been proposed that LAT1 plays a critical role in cell growth and proliferation. In the present study, we have examined the function of human LAT1 (hLAT1) and its expression in human tissues and tumor cell lines. When expressed in Xenopus oocytes with human 4F2hc (h4F2hc), hLAT1 transports large neutral amino acids with high affinity (K(m)= approximately 15- approximately 50 microM) and L-glutamine and L-asparagine with low affinity (K(m)= approximately 1.5- approximately 2 mM). hLAT1 also transports D-amino acids such as D-leucine and D-phenylalanine. In addition, we show that hLAT1 accepts an amino acid-related anti-cancer agent melphalan. When loaded intracellularly, L-leucine and L-glutamine but not L-alanine are effluxed by extracellular substrates, confirming that hLAT1 mediates an amino acid exchange. hLAT1 mRNA is highly expressed in the human fetal liver, bone marrow, placenta, testis and brain. We have found that, while all the tumor cell lines examined express hLAT1 messages, the expression of h4F2hc is varied particularly in leukemia cell lines. In Western blot analysis, hLAT1 and h4F2hc have been confirmed to be linked to each other via a disulfide bond in T24 human bladder carcinoma cells. Finally, in in vitro translation, we show that hLAT1 is not a glycosylated protein even though an N-glycosylation site has been predicted in its extracellular loop, consistent with the property of the classical 4F2 light chain. The properties of the hLAT1/h4F2hc complex would support the roles of this transporter in providing cells with essential amino acids for cell growth and cellular responses, and in distributing amino acid-related compounds.

Activation of alveolar macrophages in acid-injured lung in rats: different effects of pentoxifylline on tumor necrosis factor-alpha and nitric oxide production.

OBJECTIVE: To determine whether acid instillation augments tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages in rats, and to study the effects of treatment with pentoxifylline before acid instillation on the production of these inflammatory mediators. DESIGN: Controlled laboratory investigation on tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury. SETTING: University research laboratory. SUBJECT: Alveolar macrophages of rats. INTERVENTIONS: Alveolar macrophages were recovered by bronchoalveolar lavage at 4, 10, 16, 24, and 72 hrs after unilateral hydrochloric acid (pH, 1.0; volume, 0.1 mL) instillation into the lungs of rats. Alveolar macrophages then were cultured with or without lipopolysaccharide. One group of rats was pretreated with pentoxifylline before acid instillation. MEASUREMENTS AND MAIN RESULTS: Alveolar macrophages from both acid-instilled and contralateral lungs, which had recovered 24 hrs after acid instillation, produced significantly greater tumor necrosis factor-alpha and nitric oxide. Subsequent exposure to lipopolysaccharide, as a surrogate for bacterial infection, further promoted tumor necrosis factor-alpha and nitric oxide release. Alveolar macrophages from rats pretreated with pentoxifylline before acid instillation produced significantly less tumor necrosis factor-alpha and did not overproduce tumor necrosis factor-alpha when exposed to lipopolysaccharide. In contrast, pretreatment with pentoxifylline had no effect on nitric oxide production by alveolar macrophages. CONCLUSIONS: Acid instillation stimulates alveolar macrophages to produce tumor necrosis factor-alpha and nitric oxide. Pentoxifylline preserved innate production of tumor necrosis factor-alpha to lipopolysaccharide and did not inhibit the production of bactericidal nitric oxide. This may partly explain why pentoxifylline reduces acid aspiration-induced lung injury while maintaining the host's ability to combat bacterial infection after acid aspiration.

Activation of HIV-1-specific immune responses to an HIV-1 vaccine constructed from a replication-defective adenovirus vector using various combinations of immunization protocols.

We constructed a recombinant replication defective adenovirus vector containing the env gene (Ad-Bal) derived from macrophage-trophic HIV-1 (HIV-1 Bal). We then immunized mice with this vector using several administration routes and protocols, and examined the immune response. When the Ad-Bal viral vector (over 1 x 10(7) pfu) was injected subcutaneously, both humoral and cell-mediated immunities were induced. However, immune response induced by the Ad-Bal vector alone was weaker than that induced by the recombinant vaccinia viral vector. We then employed the following three immunization protocols: (l) DNA vaccination followed by immunization with the Ad-Bal; (2) vaccination using the Ad-Bal vector followed by DNA vaccination; and (3) DNA vaccination followed by Ad-Bal infection and passive transfer of dendritic cells (DCs) infected with the Ad-Bal. Among the three protocols, the last gave the strongest humoral and cell-mediated immunity. These results suggest that the combination of DNA vaccination, Ad-Bal vector infection and passive transfer of Ad-Bal-infected DCs can induce strong immunity against HIV-1 Bal.