Quantitative Analysis of Conebeam CT for Delineating Stents in Stent-Assisted Coil Embolization.

BACKGROUND AND PURPOSE: Innovative techniques and device-related advances have improved the outcomes of neuroendovascular treatment. 3D imaging has previously used 2 × 2 binning, but 1 × 1 binning has recently been made available. The aim of this study was to evaluate the quantitative ability of conebeam CT for stent delineation and to investigate its effectiveness in the clinical environment. MATERIALS AND METHODS: Four acquisition groups of 3D MIP images acquired using conebeam CT with varying conditions (acquisition time, 10 or 20 seconds and binning, 1 × 1 or 2 × 2) were compared. Two methods of analysis were performed, a phantom study and an analysis of 28 randomly selected patients. The phantom study assessed the contrast-to-noise ratio and full width at half maximum values in conebeam CT images of intracranial stent struts. In the clinical subjects, we assessed contrast-to-noise ratio, full width at half maximum, and dose-area product. RESULTS: In the phantom study, the contrast-to-noise ratio was not considerably different between 10- and 20-second acquisition times at equivalent binning settings. Additionally, the contrast-to-noise ratio at equivalent acquisition times did not differ considerably by binning setting. For the full width at half maximum results, equivalent acquisition times differed significantly by binning setting. In the clinical analyses, the 10-second/1 × 1 group (versus 20 second/2 × 2) showed a higher contrast-to-noise ratio (P < .05) and a dose-area product reduced by approximately 70% (P < .05), but the difference in full width at half maximum was not significant (P = .20). CONCLUSIONS: For stent-assisted coil embolization, quantitative assessment of conebeam CT showed that 10 second/1 × 1 was equivalent to 20 second/2 × 2 for imaging deployed intracranial stents. Furthermore, the 10-second/1 × 1 settings resulted in a much smaller DAP.

Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation.

BACKGROUND: There is synteny in the CC-type chemokine gene clusters between humans (CCL2/MCP-1, CCL7MCP-3, CCL11/eotaxin, CCL8/MCP-2, CCL13/MCP-4, and CCL1/I-309) and mice (CCL2, CCL7, CCL11, CCL12/MCP-5, CCL8, and CCL1). OBJECTIVE: As many putative Bcl6/STAT-binding sequences are observed in the clusters, we examined the roles of a transcriptional repressor Bcl6 and the regional histone modification in the expression of these chemokine genes in pulmonary epithelium. METHODS: We generated transgenic (Tg) mice carrying the Bcl6 or the dominant-negative (DN)-Bcl6 gene under the control of the surfactant protein C (SPC) promoter that induces the exogenous gene expression in the distal lung epithelium. For in vitro studies, A549, alveolar type II-like epithelial cell line transfected with the SPC-DN-Bcl6 gene were stimulated with IL-4+TNF-α, and Bcl6 or STAT6 binding to and histone modification of the cluster in the transfectants were analysed by chromatin immunoprecipitation assays. Tg mice sensitized with ovalbumin (OVA) were challenged with OVA inhalation. The amounts of mRNAs in each sample were analysed by quantitative RT-PCR. RESULTS: The amount of Bcl6 bound to the cluster decreased in A549 cells stimulated with IL-4 and TNF-α, whereas STAT6 binding increased in association with regional histone H3-K9/14 acetylation and H3-K4 methylation. The expression of all chemokine genes in the gene cluster was augmented in activated A549 cells transfected with the DN-Bcl6 gene. We also induced allergic airway inflammation in Tg mice. Expression of the chemokine genes and infiltrated cell numbers in the lungs of these Tg mice with allergic airway inflammation were inversely correlated with the amount of Bcl6 in the lungs. CONCLUSION AND CLINICAL RELEVANCE: Expression of the pulmonary epithelium-derived CC-type chemokine genes in the cluster is orchestrated by the conserved machinery related to Bcl6. Thus, Bcl6 in pulmonary epithelium may be a critical regulator for pathogenesis of various pulmonary inflammatory diseases.

Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia.

AIMS: Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known to overlap with respiratory bronchiolitis-interstitial lung disease (RB-ILD). The aim was to review biopsy-proven cases of DIP to investigate further the clinical, imaging and histological features of this disease. METHODS AND RESULTS: Twenty patients fulfilled the pathological criteria: 19 men and one woman with a mean age of 54 years. Clinical features, bronchoalveolar lavage (BAL) data, radiological findings, pathological findings other than criteria, effect of therapy and outcome were examined. The BAL data for 17 cases revealed marked eosinophilia (mean 18%) and moderate neutrophilia (mean 11%). Computed tomography in 17 patients showed peripheral involvement in all cases with a clear margin in 64% and thin-walled cysts in 35% of cases. Additional pathological features were a distinct lobular distribution (70%) and architectural destruction (70%) with cyst formation (55%). Eighteen of the 19 patients (95%) improved under steroid pulse and/or oral therapy. Sixteen subjects (80%) are alive, three died of other diseases and one died of DIP 74 months after the diagnosis. Percent vital capacity increased significantly and new thin-walled cysts appeared in one case. CONCLUSIONS: BAL eosinophilia, lobular distribution and architectural destruction with cyst formation are characteristic features of DIP.

Mechanism of the ropivacaine-induced increase in intracellular Ca2+ concentration in rat aortic smooth muscle.

BACKGROUND: Ropivacaine is a long-acting local anesthetic with low cardiac toxicity that induces vasoconstriction in vitro and in vivo. Vascular smooth muscle tone is regulated by changes in both intracellular Ca(2+) concentration ([Ca(2+)](i)) and myofilament Ca(2+) sensitivity. Therefore, the aim of this study was to examine the mechanism underlying the increase in [Ca(2+)](i) in ropivacaine-induced vascular contraction. METHODS: Ropivacaine-induced contractile responses and changes in [Ca(2+)](i) were examined using an isometric force transducer and a fluorometer, respectively. RESULTS: Ropivacaine induced a biphasic, concentration-dependent change in [Ca(2+)](i) and contractile response in rat aortic smooth muscles: an increase in [Ca(2+)](i) occurred at lower ropivacaine concentrations (3 x 10(-5) to 3 x 10(-4) M) and a decrease was observed at higher concentrations (10(-3) to 3 x 10(-3) M). Contraction and the [Ca(2+)](i) increase induced by ropivacaine were attenuated significantly by a voltage-dependent Ca(2+) channel antagonist, an inositol 1,4,5-triphosphate receptor antagonist and Ca(2+)-free solution (P < 0.01, n = 6). CONCLUSION: Ropivacaine-induced contraction of rat aortic smooth muscle is, in part, regulated by Ca(2+) influx from the extracellular space and Ca(2+) release from the sarcoplasmic reticulum.

Antifungal susceptibility of Candida species using the Clinical and Laboratory Standards Institute disk diffusion and broth microdilution methods.

There are conflicting reports on the agreement between the Clinical and Laboratory Standards Institute disk diffusion (M44-A) and reference broth microdilution (M27-A) methods for determination of antifungal susceptibility of yeasts. The antifungal susceptibility of 541 yeasts, the majority of which were from the oral cavity, was determined using these two methods and the accuracy of the disk diffusion method assessed for clinical testing of various Candida species. Of the strains tested, Candida albicans predominated (390 out of 541). The classification of susceptibility determined by the disk diffusion method was largely in concordance with that obtained using the broth dilution method, regardless of species within Candida genus. The overall observed agreement between these two methods was 94.7% for fluconazole and 96.7% for voriconazole was with a 'very major' discrepancy level of 1.5% and 1.7% respectively. This study demonstrates a strong agreement of the simple disk diffusion method with the more labour intensive 'gold standard' broth microdilution method. These findings would support the use of the disk diffusion method in a routine mycology service.

Antimicrobial susceptibility of 800 anaerobic isolates from patients with dentoalveolar infection to 13 oral antibiotics.

INTRODUCTION: The aim of this study was to determine the current antimicrobial susceptibility of the principle anaerobic pathogens involved in dentoalveolar infection, to 13 oral antibiotics, and to assess the value of each antibiotic in the management of the infection. METHODS: A total of 800 isolates from patients with dentoalveolar infection (Prevotella species, Fusobacterium species, Porphyromonas species and Peptostreptococcus micros) were tested for their susceptibility to amoxicillin, amoxicillin/clavulanate, cefaclor, cefuroxime, cefcapene, cefdinir, erythromycin, azithromycin, telithromycin, minocycline, levofloxacin, clindamycin, and metronidazole using an agar dilution method. RESULTS: Although the majority of Fusobacterium strains were resistant to erythromycin, azithromycin, and telithromycin, the remaining antibiotics demonstrated a high level of antimicrobial activity. P. micros and Porphyromonas species exhibited high susceptibility to all antibiotics tested in this study. In the case of Prevotella species, resistance to amoxicillin occurred in 34% of isolates and all of these resistant strains were found to produce beta-lactamase. Susceptibility of Prevotella strains to cefaclor, cefuroxime, cefcapene, cefdinir, erythromycin, azithromycin, and minocycline was found to correlate with amoxicillin susceptibility. Amoxicillin/clavulanate, telithromycin, clindamycin, and metronidazole exhibited high antimicrobial activity even against amoxicillin-resistant strains of Prevotella species. CONCLUSION: Amoxicillin would still be advocated therefore as being a suitable first-line agent, while reduced susceptibility of Prevotella strains remains a matter of concern with penicillins. Amoxicillin/clavulanate, clindamycin, and metronidazole are useful alternatives in combating the anaerobic bacteria involved in dentoalveolar infection.

The effects of FasL on inflammation and tumor survival are dependent on its expression levels.

The apoptosis-inducing Fas ligand (FasL) is expressed in a variety of human cancers and has been implicated in tumor immune evasion. Paradoxically, ectopic expression of FasL in experimental tumors triggers a neutrophil-mediated inflammatory response and tumor rejection. To resolve these conflicting findings, we have established B16 melanoma and P29 Lewis lung carcinoma lines expressing different levels of FasL and examined their tumorigenicity in vivo. While tumors with a high level of FasL were rapidly rejected as previously reported, those expressing a low level of FasL were not rejected but grew faster than did FasL-negative parental cells. The growth enhancement of FasL(low) tumors was not observed in T-cell-deficient nude mice, suggesting that FasL expressed in tumors at low levels counteracted against T-cell-dependent antitumor responses. In support of this notion, FasL(low) tumors were found to grow faster than parental cells in mice that had acquired tumor-specific immunity. Furthermore, histological examinations revealed apoptosis of lymphocytes in tissue sections of FasL(low) tumors. These results collectively suggest that FasL on tumors is a double-edged sword: at high levels it triggers tumor rejection whereas at low levels it facilitates tumor growth possibly by suppressing antitumor immune responses.

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae isolated from patients with community-acquired pneumonia and molecular analysis of multidrug-resistant serotype 19F and 23F strains in Japan.

A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42.1%) were susceptible, 40 (35.1%) showed intermediate resistance (MIC, 0.12-1.0 microg/ml) and 26 (22.8%) were resistant (MIC, >or=2.0 microg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 microg/ml), imipenem (4 microg/ml) and vancomycin (4 microg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified.

In vitro susceptibility of oral Candida to seven antifungal agents.

The in vitro susceptibility of 618 Candida isolates to fluconazole, itraconazole, voriconazole, ketoconazole, miconazole, amphotericin B, and nystatin was determined. The isolates were obtained from 559 patients who had attended the UK dental hospital departments in Cardiff, Belfast, Glasgow or London. Antifungal susceptibility was assessed using a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS) M27-A guidelines. The majority of the test strains were C. albicans (n = 521) with few of these being resistant to fluconazole (0.3%). A low incidence of fluconazole resistance (0-6.8%) was similarly evident with all non albicans species (Candida glabrata, 5 of 59 resistant; Candida krusei, 0 of 7 resistant; Candida tropicalis, 0 of 13 resistant; Candida parapsilosis, 0 of 12 resistant; other Candida species, 0 of 6 resistant). Voriconazole, ketoconazole, and miconazole also revealed high activity against both C. albicans and non albicans isolates, and 23.7% of C. glabrata isolates were found to be resistant to itraconazole. There was little difference in the antifungal susceptibilities of Candida isolated from patients who had a history of previous antifungal therapy compared with those who had not received antifungal treatment. In summary, this surveillance study of antifungal susceptibility of oral candidal isolates in the UK, through the collaboration of four dental hospitals, demonstrates that oral Candida species have a high level of susceptibilities to a range of antifungal agents.

An outcome audit of the treatment of acute dentoalveolar infection: impact of penicillin resistance.

OBJECTIVES: The aim of this audit was to measure the outcome of treatment of acute dentoalveolar infection and to determine if this was influenced by choice of antibiotic therapy or the presence of penicillin-resistance. SUBJECTS AND METHODS: A total of 112 patients with dentoalveolar infection were included in the audit. All patients underwent drainage, either incisional (n=105) or opening of the pulp chamber (n=7) supplemented with antibiotic therapy. A pus specimen was obtained from each patient for culture and susceptibility. Clinical signs and symptoms were recorded at the time of first presentation and re-evaluated after 48 or 72 h. RESULTS: A total of 104 (99%) of the patients who underwent incisional drainage exhibited improvement after 72 h. Signs and symptoms also improved in five of the seven patients who underwent drainage by opening of the root canal although the degree of improvement was less than that achieved by incisional drainage. Penicillin-resistant bacteria were found in 42 (38%) of the 112 patients in this study. Of the 65 patients who were given penicillin, 28 had penicillin-resistant bacteria. There was no statistical difference in the clinical outcome with regard to the antibiotic prescribed and the presence of penicillin-resistant bacteria. Strains of penicillin-resistant bacteria were isolated more frequently in patients who had previously received penicillin (p<0.05). CONCLUSION: Incisional drainage appeared to produce a more rapid improvement compared to drainage by opening of the root canal. The presence of penicillin-resistant bacteria did not adversely affect the outcome of treatment. The observations made support surgical drainage as the first principle of management and question the value of prescribing penicillin as part of treatment.

Experimental study on the morphological and functional recovery following partial glossectomy in rabbits: a comparison between CO2 laser and electrocautery.

OBJECTIVE: The aim of the present study was to evaluate and compare the morphological and functional recovery following partial glossectomy in rabbits with the CO(2) laser and electrocautery. METHODS: Partial glossectomy with the CO(2) laser or electrocautery in rabbits was performed to investigate changes in the body weight and tongue width after surgery. The study models were classified into three groups. In group 1, the excised edges of the wound were left unsutured after partial glossectomy with the CO(2) laser. In group 2, the wound was closed after CO(2) laser surgery. In group 3, as a control group, the wound was closed after partial glossectomy with electrocautery. The specimens of the tongues obtained from the rabbit were microscopically assessed. RESULTS: No significant differences were found in the percent change in the body weight among the three groups. There was a significant difference in the tongue width between groups 1 and 3 at each time point: 2 weeks (p < 0.05), 4 weeks (p < 0.01), and 8 weeks (p < 0.001) postoperatively. Furthermore, there was a significant difference in the tongue width between groups 2 and 3 at 8 weeks (p < 0.02) postoperatively. Histologically, the scar tissue of the wound was extensive in the control group, although it was localized in the laser group. CONCLUSION: Postoperative dysfunction was reduced when excised edges were left unsutured after partial glossectomy with the CO(2) laser.

Association of clinical features with HLA in chronic pulmonary thromboembolism.

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH. HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied. The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients. These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.

Expression of interleukin-22 in murine carcinoma cells did not influence tumour growth in vivo but did improve survival of the inoculated hosts.

Interleukin (IL)-22, a novel cytokine belonging to the IL-10 family, is secreted from activated T and natural killer cells and is possibly involved in inflammatory responses. We examined whether expression of the IL-22 gene in murine colon carcinoma Colon 26 cells (Colon 26/IL-22) could produce any antitumour effects in the inoculated mice. Although growth of Colon 26/IL-22 tumours in syngeneic mice was not different from that of parent tumours, survival of the mice that were subcutaneously or intraperitoneally inoculated with Colon 26/IL-22 tumours was significantly prolonged compared with the mice inoculated with parent tumours. Metastasis was not influenced by IL-22 expressed in tumours. Expression of the IL-22 receptor-specific gene, IL-22R, was not induced in spleen cells stimulated with concanavalin A, anti-CD3 or anti-CD40 antibody, despite constitutive expression of the IL-10R2 gene, which encodes another component of the heterodimeric IL-22 receptor complex. IL-22 thereby does not directly act on immunocompetent cells, and IL-22 expressed in tumours can favour apothanasia of inoculated hosts.

The microbial synergy of Peptostreptococcus micros and Prevotella intermedia in a murine abscess model.

This study characterized the microbial interaction of Peptostreptococcus micros and Prevotella intermedia, the major pathogens of dentoalveolar infection, using a murine model. Subcutaneous injection of P. micros cells in the dorsum of the mouse together with living cells of P. intermedia resulted in a significantly larger abscess when compared with single injection of the organisms (P < 0.02). The abscess size was also significantly increased (P < 0.05) when the plate-cultured cell suspension of P. micros was injected into mouse with the culture filtrate of P. intermedia. The heat-treated culture filtrate of P. intermedia also enhanced the virulence of P. micros. P. micros culture filtrate did not affect the virulence of P. intermedia. Interestingly, the virulence of P. micros appeared to be enhanced even when the culture filtrate of P. intermedia was injected at separate sites in the mouse. These results suggest that a heat-stable product or products of P. intermedia increase the virulence of P. micros indirectly by altering the host condition, whereas living cells of P. micros can directly enhance virulence of P. intermedia.

In vitro secreted aspartyl proteinase activity of Candida albicans isolated from oral diseases and healthy oral cavities.

The in vitro secreted aspartyl proteinase (SAP) activity of Candida albicans isolated from a variety of oral conditions, including healthy oral cavities, was determined. SAP activity (units/10(6) cells/ml, +/-SD) was 0.28 +/- 0.33 for pseudomembranous candidosis isolates (n = 18), 0.35 +/- 0.46 for chronic erythematous candidosis isolates (n = 21) and 0.30 +/- 0.32 for chronic hyperplastic candidosis isolates (n = 50). SAP activity of 0.19 +/- 0.22 was recorded for isolates from squamous cell carcinoma (n = 18), 0.26 +/- 0.37 for burning mouth syndrome isolates (n = 29), 0.25 +/- 0.38 for isolates from xerostomia (n = 15) and 0.39 +/- 0.50 for isolates from lichen planus (n = 13). The SAP activity of isolates from oral disease states was significantly (P < 0.05) higher than that recorded for 28 isolates from healthy mouths (activity of 0.04 +/- 0.03). However, there was no significant difference in the SAP activity between the three forms of clinical oral candidosis (P > 0.05). SAP activity was inhibited in control samples containing the SAP inhibitor, pepstatin A. These results indicate that C. albicans strains associated with oral disease have inherently higher SAP activity.

Feasibility of combination chemotherapy with cisplatin and etoposide for haemodialysis patients with lung cancer.

Cancer chemotherapy for haemodialysis patients has never been established. To elucidate the feasibility of cisplatin-based combination chemotherapy for haemodialysis patients with lung cancer, a dose escalation study was conducted. Five haemodialysis patients with lung cancer were treated with cisplatin and etoposide. A starting dose of 40 mg m(-2) of cisplatin on day 1 and 50 mg m(-2) of etoposide on days 1, 3 and 5 were administered as the first course for the first patient. Membrane haemodialysis was regularly performed three times a week and soon after the completion of therapy. By monitoring toxicity and pharmacokinetics data, the dose was escalated course by course and patient by patient. Dose escalation was completed for the first two patients resulting in full-dose chemotherapy consisting of 80 mg m(-2) of cisplatin on day 1 and 100 mg m(-2) of etoposide on days 1, 3 and 5. Multiple courses of the full-dose chemotherapy were administered to the other three patients. Toxicity was manageable and tolerable for all. Pharmacokinetics data were comparable to those from patients with normal renal function, except for potential long-lasting higher levels of free platinum in the renal insufficiency group. In conclusion, this standard-dose combination chemotherapy was feasible even for haemodialysis patients.

Antimicrobial susceptibility of major pathogens of orofacial odontogenic infections to 11 beta-lactam antibiotics.

In this study, we evaluated the current effectiveness of 11 beta-lactam antibiotics for treatment of orofacial odontogenic infections by determining the antimicrobial susceptibility of the major pathogens. The antimicrobial susceptibilities of viridans streptococci (n = 47), Peptostreptococcus (n = 67), Porphyromonas (n = 18), Fusobacterium (n = 57), black-pigmented Prevotella (n = 59) and non-pigmented Prevotella (n = 47) isolated from pus specimens of 93 orofacial odontogenic infections to penicillin G, cefmetazole, flomoxef, cefoperazone, cefoperazone/sulbactam, ceftazidime, cefpirome, cefepime, cefoselis, imipenem and faropenem were determined using the agar dilution method. Penicillin G, most cephalosporins, imipenem and faropenem worked well against viridans streptococci, Peptostreptococcus, Porphyromonas and Fusobacterium. Penicillin G and most cephalosporins, including fourth-generation agents, were not effective against beta-lactamase-positive Prevotella, though they were effective against beta-lactamase-negative strains. Cefmetazole, cefoperazone/sulbactam, imipenem and faropenem expressed powerful antimicrobial activity against beta-lactamase-positive Prevotella. In conclusion, penicillins have the potential to be first-line agents in the treatment of orofacial odontogenic infections. Most of the other beta-lactam antibiotics, including fourth-generation cephalosporins, were not found to have greater effectiveness than penicillins. In contrast, cefmetazole, cefoperazone/sulbactam, imipenem and faropenem were found to have greater effectiveness than penicillins.

Effects of insulin-like growth factor on nitrogen balance during hypoxic exposure.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) accompanied with hypoxaemia may induce net protein catabolism and hypoxaemia could be an important trigger of a systemic catabolic response. The aim of this study was to examine the anabolic effects of recombinant human insulin-like growth factor-I (IGF-1) in rats exposed to hypoxia. Although acute hypoxia is usually accompanied with a decrease in dietary intake, the usual nitrogen intake was maintained in this study. Sprague-Dawley rats were maintained by continuous infusion of solution for total parenteral nutrition for 6 days. The animals were then randomly assigned to a normoxic (N) or a hypoxic (H) group. During the last 3 days of the experiment N and H rats were randomised to receive either IGF-I or vehicle. Exposure to hypoxia caused a decrease in body-weight gain accompanied by a negative nitrogen balance, which was mainly due to increased urinary nitrogen excretion. No effect of recombinant human IGF-I treatment on body weight was observed during exposure to hypoxia, although nitrogen balance normalised. The co-infusion of recombinant human insulin-like growth factor-1 and total parenteral nutrition has a significant net anabolic effect, as demonstrated by nitrogen retention and reduction in urine protein excretion observed in rats. Insulin-like growth factor-1 may help to ameliorate the protein catabolism observed under hypoxic conditions.

Activation of pulmonary T cells in corticosteroid-resistant and -sensitive interstitial pneumonitis in dermatomyositis/polymyositis.

To study the activation states and cytokine profiles of pulmonary T cells in corticosteroid-resistant and corticosteroid-sensitive interstitial pneumonitis (IP) in dermatomyositis (DM)/polymyositis (PM), we examined the activation markers and cytokine profiles of T cells in bronchoalveolar lavage fluids (BALF) from patients with IP in DM/PM before prednisolone therapy and then compared the activation states of T cells according to the therapeutic response of IP to prednisolone therapy. CD25+ CD4+ T cells in BALF were significantly increased in both corticosteroid-resistant and corticosteroid-sensitive IP in DM/PM as compared with those in controls without IP. Furthermore, CD25+ CD4+ T cells in BALF were significantly more increased in corticosteroid-resistant IP than those in cortico teroid- sensitive IP. Moreover, CD25+ CD8+ T cells in BALF were significantly increased only in corticosteroid-resistant IP, but not in corticosteroid-sensitive IP or controls without IP. IFN-gamma mRNA was detected in BALF T cells in corticosteroid-resistant and corticosteroid-sensitive IP but not in controls without IP, whereas IL-4 mRNA was virtually undetected in BALF T cells in both the IP groups. However, there were no significant differences in CD4/CD8 ratio of BALF T cells, HLA-DR+ BALF T cells or CD25+ and HLA-DR+ peripheral blood T cells between the two IP groups. These results indicate that activated Th1-type pulmonary T cells play an important role in the development of corticosteroid- resistant IP in DM/PM and that the increase in CD25+ CD8+ T cells in BALF is a useful indicator for corticosteroid-resistant IP in DM/PM and hence may be an indicator for early use of cyclosporin.