Biomedical subjects

I Han

Publications and source records attributed to I Han.

At least 37 records · Page 2Linked to original sources

PubMed2000

Neutron radiation enhances cisplatin cytotoxicity independently of apoptosis in human head and neck carcinoma cells.

Recent advances in combined modality treatment of locally advanced head and neck cancer have improved local and regional disease control and survival with better functional outcome. However, the local and regional failure rate after radiation therapy is still high for tumors that respond poorly to cisplatin-based neoadjuvant chemotherapy. This clinical observation suggests a common biological mechanism for resistance to cisplatin and photon irradiation. In this report, we investigated the molecular basis underlying cisplatin resistance in head and neck squamous carcinoma (HNSCC) cells and asked if fast neutron radiation enhances cisplatin cytotoxicity in cisplatin-resistant cells. We found that cisplatin sensitivity correlates with caspase induction, a cysteine proteinase family known to initiate the apoptotic cell death pathway, suggesting that apoptosis may be a critical determinant for cisplatin cytotoxicity. Neutron radiation effectively enhanced cisplatin cytotoxicity in HNSCCs including cisplatin-resistant cells, whereas photon radiation had little effect on cisplatin cytotoxicity. Interestingly, neutron-enhanced cisplatin cytotoxicity was associated neither with apoptosis nor with cell cycle regulation, as determined by caspase activity assay, annexin V staining, and flow cytometric analysis. Taken together, the present study provides a molecular insight into cisplatin resistance and may also provide a basis for more effective multimodality protocols involving neutron radiation for patients with locally advanced head and neck cancer.

Annexin A5↗

PubMed1999

Development and clinical implementation of an enhanced display algorithm for use in networked electronic portal imaging.

PURPOSE: To introduce and clinically validate a preprocessing algorithm that allows clinical images from an electronic portal imaging device (EPID) to be displayed on any computer monitor, without loss of clinical usability. The introduction of such a system frees EPI systems from the constraints of fixed viewing workstations and increases mobility of the images in a department. METHODS AND MATERIALS: The preprocessing algorithm, together with its variable parameters is introduced. Clinically, the algorithm is tested using an observer study of 316 EPID images of the pelvic region in the framework of treatment of carcinoma of the cervix and endometrium. Both anterior-posterior (AP/PA) and latero-lateral (LAT) images were used. The images scored were taken from six different patients, five of whom were obese, female, and postmenopausal. The result is tentatively compared with results from other groups. The scoring system, based on the number of visible landmarks in the port, is proposed and validated. Validation was performed by having the observer panel score images with artificially induced noise levels. A comparative study was undertaken with a standard automatic window and leveling display technique. Finally, some case studies using different image sites and EPI detectors are presented. RESULTS: The image quality for all images in this study was deemed to be clinically useful (mean score >1). Most of the images received a score which was second highest (AP/PA landmarks > or =6 and LAT landmarks > or =5). Obesity, which has been an important factor determining the image quality, was not seen to be a factor here. Compared to standard techniques a highly significant improvement was determined with regard to clinical usefulness. The algorithm performs fast (less than 9 seconds) and needs no additional user interaction in most of the cases. The algorithm works well on both direct detection portal imagers and camera-based imagers whether analog or digital cameras. CONCLUSIONS: We have demonstrated that it is possible to preprocess EPIs in such a way that the clinically relevant landmarks are easily detected on a generic computer screen. The algorithm is system-independent and fast. This allows for the encoding of EPIs in more generalized commercial formats so that distribution of images is facilitated.

Algorithms↗

PubMed1999

An N-terminal region of Sp1 targets its proteasome-dependent degradation in vitro.

The transcription factor Sp1 is important for the expression of many cellular genes. Previously, it was shown that reduced O-glycosylation of Sp1 is associated with increased proteasome susceptibility. Sp1 undergoes proteasome-dependent degradation in cells stressed with glucose deprivation and adenylate cyclase activation, and this process is blocked in cells treated with glucosamine. In this study, using a reconstituted in vitro system, we identified the principal structural determinant in Sp1 that targets Sp1 for proteasome-dependent degradation. We found by using deletion analysis that the N-terminal 54 amino acids of Sp1 is required for Sp1 degradation. This element can act as an independent processing signal by directing degradation of an unrelated protein. Recognition of this Sp1 element by the proteasome-dependent system is saturable, and ubiquitination of this element is not required for recognition. Time course experiments revealed that Sp1 degradation is a two-step process. First, a discrete endoproteolytic cleavage occurs downstream of the target region immediately C-terminal to Leu56. The Sp1 sequence C-terminal to the cleavage site is subsequently degraded, whereas the N-terminal peptide remains intact. The identification of this Sp1 degradation-targeting signal will facilitate the identification of the critical proteins involved in the control of Sp1 proteasome-dependent degradation and the role of OGlcNAc in this process.

Amino Acid Sequence↗

PubMed1999

Combined low-dose-rate brachytherapy and external beam radiation for cervical cancer: experience over ten years.

Cervical cancer was treated with a combination of external beam and intracavitary radiation during a 10-year period at Wayne State University. Data were collected for 216 patients treated radically with external beam radiation (EBRT) and low-dose-rate brachytherapy for cervical cancer between 1980 and 1991 at Wayne State University. Patient distribution by stage was IB, 20.8%; IIA, 7.4%; IIB, 26.9%; IIIA, 1.8%; IIIB, 40.7%; and IVA, 2.3 %. Survival curves were constructed using Kaplan-Meier methods and differences between groups were tested for significance using the log-rank test. Multivariate analysis was done using the Cox proportional hazards model. With a median follow-up of 114 months, actuarial disease-free survival for all patients was 60% at 5 years and 55% at 10 years. Actuarial 5-year survival for Stage IB was 79%; for Stage II, 59%; and for Stage III, 53%. There were 14/216 (6%) of patients with severe late complications. On univariate analysis, race was found to be statistically significant, with Caucasian patients having better survival than African American (P = 0.03). The survival for patients treated in shorter overall times was significantly higher (P<0.001), especially with treatment completion in under 58 days. The stepwise Cox multivariate analysis provided the following significant results: race (African American vs. Caucasian; P = 0.04, RR = 1.6), Stage (II vs. I, P = 0.004, RR = 2.6), Stage (III vs. I; P = 0.004, RR = 2.5), and overall treatment time (P = 0.006, RR = 1.62). Rates of local control, survival, and complications among women treated with combined external beam and intracavitary radiation for cervix cancer were similar to those of prior retrospective studies.

Actuarial Analysis↗

PubMed1999

Concomitant increase in neutrophil adhesion to inflammatory peritoneum and remote organs during peritonitis.

BACKGROUND: Neutrophils contribute to the host defense mechanism, but they can cause remote organ injury in peritonitis. The purpose of this study was to examine neutrophil adhesion to the peritoneum and remote organs simultaneously in peritonitis using a fluorescence microscopic method. STUDY DESIGN: Experiment 1: Sprague-Dawley rats (n = 16) were injected intraperitoneally (ip) with saline solution or 10(5), 10(7), or 10(9) Escherichia coli. Five hours after challenge, 1 x 10(6) fluorescein-labeled neutrophils were infused. Two minutes after neutrophil injection, five peritoneal samples (the greater omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Lung myeloperoxidase (MPO) activity was also determined. Experiment 2: Rats (n = 23) were given 10(9) E. coli ip. Before challenge (0 h) or at 1, 5, or 10 h after challenge, labeled neutrophils were infused. Then, the labeled neutrophil numbers in organs and lung MPO activities were assessed as described for Experiment 1. Hemodynamic and arterial blood gas data were also obtained in another set of rats before and at 1, 5, 8 and 10 h after 10(9) E. coli ip challenge. RESULTS: Experiment 1: The labeled neutrophil numbers in the peritoneum, lungs, and kidney showed significant positive correlations with the injected bacterial numbers. Lung MPO also positively correlated with E. coli number and labeled neutrophil number in the lungs. Experiment 2: Labeled neutrophil numbers in the peritoneum and kidney peaked at 5 h. The pulmonary labeled neutrophil number rose, reaching a plateau at 5 h. No remarkable change was observed in the hepatic labeled neutrophil number. There was a positive correlation between lung MPO activity and pulmonary labeled neutrophil number. Hemodynamic and blood gas data reflected a hyperdynamic state. CONCLUSIONS: Concomitant dose-dependent increases in neutrophil adhesion in the peritoneum, lungs, and kidney were observed in this peritonitis model. Increased neutrophil adhesion was transient in the peritoneum and kidney but persistent in the lungs. Strategies modulating neutrophil adhesion in organs are anticipated to be useful for the treatment of peritonitis.

Animals↗

PubMed1999

Giant solid cystic tumor of the pancreas with a fibrous septum caused by extracapsular growth in middle-aged woman: report of a case.

We report herein the case of a 57-year-old female who was admitted to our hospital for treatment of rectal carcinoma and incidentally found to have a giant cystic tumor, 20 cm in diameter, in the body and tail of the pancreas. Several imaging procedures, including ultrasonography, computed tomography, and magnetic resonance imaging, showed that this tumor was round and hypovascular, and had a septum with protuberant lesions. The capsule was 3-4 mm thick with partial calcification. A preoperative diagnosis of a solid cystic tumor (SCT) of the pancreas was made, even though these tumors are rarely found in females in their fifties. Moreover, few reports of SCT with a septum have been described. Distal pancreatectomy and splenectomy were performed, and the tumor was found to be filled with massive necrotic tissue. Microscopically, the tumor was confirmed to be a SCT with a fibrous septum. We present this case due to the atypical findings, including the age of the patient and the existence of a septum caused by extracapsular growth.

Biopsy, Needle↗

PubMed1999

Non-association of estrogen receptor genotypes with bone mineral density and bone turnover in Korean pre-, peri-, and postmenopausal women.

Estrogen is known to play a critical role in both skeletal maturity and the rate of bone loss. This suggests the possibility that the estrogen receptor (ER) gene is one of the candidate genes that determines peak bone density and/or bone turnover rate. We investigated two established restriction fragment length polymorphisms (RFLPs) in intron 1 at the ER gene, represented as PvuII and XbaI. In 598 healthy Korean women aged 20-74 years, we examined the association of these ER genotypes with bone mineral density (BMD) and bone turnover status. The distribution of the PvuII and XbaI RFLPs was as follows: pp 205 (34.3%), Pp 308 (51.5%), PP 85 (14.2%) and xx 384 (64.2%), Xx 180 (30.1%), XX 34 (5.7%), respectively (where capital letters signify the absence of, and lower-case letters signify the presence of, the restriction site of each RFLP). No significant genotypic differences were found in BMD and bone markers. We grouped the subjects into three categories according to their menstrual status: 104 premenopausal women with regular menstruation, 182 perimenopausal women who had amenorrhea of not less than 3 months and not more than 12 months' duration, and 312 postmenopausal women whose last menstruation was at least 12 months previously. No significant genotypic difference in either BMD or bone markers was found in any of these three groups. Furthermore we categorized women in peri- and postmenopause into a high loser group and a normal loser group according to the level of bone resorption markers. There was no difference in genotypic proportions between the high and normal loser groups. Our data suggest that these ER polymorphisms are not associated with BMD or bone turnover in Korean women.

Absorptiometry, Photon↗

PubMed1999

Growth hormone/insulin-like growth factor 1 axis alterations contribute to disturbed protein metabolism in cirrhosis patients after hepatectomy.

BACKGROUND/AIM: Liver cirrhosis is accompanied by a fall in whole-body protein turnover and alterations of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. However, the influence of liver cirrhosis on the GH/IGF-1 axis in the perioperative period, and the contribution of the GH/IGF-1 axis alteration in cirrhosis to postoperative nitrogen metabolism are not known. METHODS: Plasma GH, IGF-1 and IGF binding protein 3 (IGF-BP3) levels were measured sequentially in patients undergoing hepatectomy with or without cirrhosis. Postoperative nitrogen excretion and whole-body protein turnover rate were also determined. RESULTS: Preoperative plasma IGF-1 level showed a negative correlation with indocyanine green retention rate. Cirrhosis patients undergoing hepatectomy had low IGF-1 and IGF-BP3 levels, despite extremely high GH levels in the perioperative period. Perioperative IGF-1 levels were lower in patients with postoperative complications than in those without complications. Postoperative nitrogen excretion was higher and whole-body protein turnover rate was lower in patients with cirrhosis than in those without cirrhosis. The post-operative IGF-1 level showed a positive correlation with whole-body protein turnover rate. CONCLUSIONS: Postoperative hepatic IGF-1 production may be severely disturbed in patients with cirrhosis, and the impaired IGF-1 production contributes to the suppressed postoperative protein metabolism in cirrhosis. It may be appropriate to increase plasma IGF-1 level in patients with cirrhosis to enhance postoperative protein metabolism and improve the postoperative outcome.

Aged↗

PubMed1999

Prophylactic treatment with growth hormone and insulin-like growth factor I improve systemic bacterial clearance and survival in a murine model of burn-induced gut-derived sepsis.

The purpose of this investigation was to evaluate the effects of GH and IGF-I administration in a murine model of burn-induced gut-derived sepsis. BALB/C mice were treated with 4.8 mg/kg/day of GH, 24 mg/kg/day of IGF-I or saline for 4 days. They were then administered 10(10) E. coli by gavage and subjected to 20% full thickness flame burn. All mice received allogeneic blood transfusion 5 days before burn injury to induce mild immunosuppression. Seventy-three mice were observed for survival and 51 mice were sacrificed at 4 and 20 h postburn. Blood, mesenteric lymph nodes (MLN), spleen and liver were harvested aseptically, and viable bacterial counts in the organs were determined. The small intestine was harvested for the evaluation of villus height and mitoses in the crypts. GH and IGF-I groups showed a significantly better survival than the control group. GH and IGF-I groups had significantly greater villus height and mitoses/crypt than the control group. Translocation of bacteria was not significantly different among groups, however, the relation between the numbers of viable bacteria in MLN and blood suggests that both GH and IGF-I reduced systemic spread of translocated bacteria. It is concluded that GH and IGF-I had positive effects on outcome in this model of burn-induced gut-derived sepsis. It appears that GH and IGF-I may have immune-enhancing effects and that administration of these agents may be useful for burn injury.

Animals↗

PubMed1999

Ratio of bacteria to polymorphonuclear neutrophils (PMNs) determines PMN fate.

This study was designed to investigate how live Escherichia coli influence the fate of polymorphonuclear neutrophils (PMNs) in vitro. PMNs from 10 healthy volunteers were cocultured with or without live E. coli at different ratios. Heat-killed E. coli (Hk) were also added to PMNs at a ratio of 1:10. The PMNs were then analyzed by flow cytometry for cell death, reactive oxygen intermediates (ROI) production, and CD16 expression. Morphologic features were also assessed. PMN apoptosis was confirmed by DNA gel electrophoresis. Low doses of E. coli (PMN:E. coli ratios of 1:0.01 and 1:0.1) inhibited PMN apoptosis. In contrast, a high dose of E. coli (PMN:E. coli ratio of 1:10) increased PMN necrosis. ROI production was significantly greater at PMN:E. coli ratios of 1:10 and 1:10 (Hk) than at ratios of 1:0.01 and 1:0.1, or in PMNs cultured alone after a 15 or 30 minute coculture. CD16 expressions were significantly lower in PMNs cocultured with E. coli than in those cultured alone after a 4 or 12-h coculture. Tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 levels in cell-free supernatants were also measured. The mean percentages of apoptosis at PMN:E. coli ratios of 1:0.01 and 1:10 (Hk), and in PMNs cultured alone after a 12-h coculture showed significant inverse correlations with these cytokine levels in cell-free supernatants at 12 h. Our results demonstrate that low doses of live E. coli inhibits predominantly PMN apoptosis, whereas a high dose of E. coli increases necrosis. Augmented PMN bactericidal function, via inhibition of PMN cell death, may be beneficial for host defense against bacterial infection and/or sepsis.

Apoptosis↗

PubMed1998

Radiation therapy for endometrial cancer in patients treated for postoperative recurrence.

PURPOSE: To retrospectively evaluate the outcome and risk factors in patients treated with radiation for endometrial cancer at time of recurrence. MATERIALS AND METHODS: Three hundred ninety-nine women were treated with radiation therapy for endometrial cancer at KCI/WSU from January 1980 to December 1994. Of these, 26 patients treated primarily with surgery received radiation therapy at the time of recurrence. Median time to recurrence after surgery was 8 months, with all recurrences occurring within 24 months. Twenty-four patients had recurrences in the vaginal cuff, vagina, or pelvis. These patients received external-beam radiation to the pelvis (45.00-50.40 Gy) and periaortic lymph nodes (45.00-50.00 Gy), along with a boost given by external-beam radiation or brachytherapy (16.00-30.00 Gy). Mean follow-up was 15 months (range 1-85 months). RESULTS: The 2-year survival was 50% and median survival was 16 months (survival range 1-85 months). Of 26 patients, 54% (14) failed locally following radiation therapy. Factors indicative of poor survival included histology (sarcoma, poorly differentiated adenocarcinoma), grade, and lymph node positivity. Histological differentiation influenced local control; lymphovascular space invasion was of borderline significance with regard to local control. CONCLUSION: Local control and survival for surgically treated endometrial cancer patients who receive radiation at the time of recurrence are poor, with the exception of those patients with recurrent disease limited to the vagina. Early detection of recurrence may improve outcome. Pathologic risk factors may identify those patients at risk for extrapelvic recurrence. Alternative treatment modalities need to be developed for this high-risk group of patients.

Adult↗

PubMed1998

Nitric oxide donor decreases neutrophil adhesion in both lung and peritoneum during peritonitis.

BACKGROUND: As nitric oxide (NO) is an antiadhesive molecule, exogenous NO may modulate neutrophil adhesion in organs. This study was designed to examine the effects of the NO donor SNAP (S-nitroso-acetyl penicillamine) on neutrophil adhesion at the inflammatory site and in remote organs, in peritonitis using a fluorescent microscopic method. MATERIALS AND METHODS: In experiment 1, rats (n = 12) were given saline or 10 micrograms/kg of SNAP intravenously followed by continuous infusion of saline, or of 2, 20, or 200 micrograms/kg/h SNAP until sacrifice. Ten minutes after injection of saline or SNAP, 10(7) Escherichia coli were injected into the peritoneal cavity. Five hours after challenge, 10(6) fluorescein-labeled neutrophils were infused. Peritoneal samples, lungs, liver, and kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. In experiment 2, rats (n = 25) were treated with saline or 10 micrograms/kg of SNAP intravenously and infused with saline or 20 micrograms/kg/h SNAP; E. coli was injected as in experiment 1. Before or 5 h after challenge, hemodynamic data were obtained. Then, labeled neutrophils were infused for counting of neutrophil numbers in organs. Arterial blood gas data and the circulating neutrophil number were also determined. RESULTS: Experiment 1. Twenty and 200 micrograms/kg/h SNAP infusions tended to reduce labeled neutrophil numbers in lungs, while all three SNAP doses decreased the peritoneal labeled neutrophil numbers. RESULTS: Experiment 2. Five hours after bacterial injection, SNAP infusion simultaneously decreased both pulmonary and peritoneal labeled neutrophil numbers. SNAP had no effect on hemodynamic and blood gas data, or on circulating neutrophil numbers. CONCLUSION: NO donors may be useful for preventing neutrophil-associated lung injury, but should be used with caution in light of the possible adverse effects on host defense in the peritoneal cavity.

Animals↗

PubMed1998

Interaction of the transcription factor Sp1 with the nuclear pore protein p62 requires the C-terminal domain of p62.

The transcription factor Sp1 plays an important role in the expression of many cellular genes. In studies of proteins that associate with Sp1, a 62-kDa glycoprotein was found in immunoprecipitates of Sp1. This protein was detected in these immunoprecipitates by the monoclonal antibody, RL2, which was originally raised against nuclear pore proteins but was subsequently found to recognize an epitope that contains O-linked N-acetylglucosamine (O-GlcNAc). The association of this protein with Sp1 could be blocked by SDS denaturation of the protein complex. Western blot analysis of the Sp1 immunoprecipitate using antibodies to p62 nucleoporin indicated that this nuclear pore protein associates with Sp1. Furthermore, immunoprecipitation of p62 nucleoporin resulted in the coprecipitation of Sp1. Recombinant p62, expressed as a GST-fusion protein using a vaccinia virus system, also interacted with both recombinant and native Sp1. This interaction between p62 and Sp1 required the C-terminus of p62 and the C-terminus was able to bind Sp1, albeit less efficiently than native p62. A mammalian two-hybrid interaction assay was devised in which p62 was fused to the Gal4 DNA-binding domain. This system also indicated that p62, through its C-terminus, interacts with Sp1 in the living cell. We propose that this interaction of a nuclear pore protein with Sp1 may reflect the nuclear organization required to bring transcribable DNA in contact with the transcription factors.

Animals↗

PubMed1998

Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic phagocytes in a lethal peritonitis model.

OBJECTIVE: To investigate the effects of pretreatment with growth hormone (GH) and insulin-like growth factor I (IGF-I) on phagocyte exudation and bacterial clearance, focusing on CD11b and CD32/CD16 expression on local and systemic phagocytes, in a lethal peritonitis model. DESIGN: Prospective randomized experimental study. SETTING: Research laboratory in a university hospital. SUBJECTS: Balb/c mice (n = 21). INTERVENTIONS: Mice were challenged intraperitoneally with 1 x 10(8) Escherichia coli, after 6 days of pretreatment with saline (control), GH (4.8 mg/kg/day), or IGF-I (24 mg/kg/day). Samples were harvested at 4 hrs after the challenge. MEASUREMENTS AND MAIN RESULTS: Viable bacterial counts in peritoneal lavage fluid (PLF) and blood were determined. Peritoneal exudative cells and peripheral blood leukocytes were counted and analyzed for receptor expressions by flow cytometry. GH reduced viable bacterial counts in PLF, as compared with the saline control. GH (three-fold) and IGF-I (two-fold) increased the number of peritoneal exudative neutrophils (PENs), as compared with the saline control. The number of PENs showed an inverse correlation with PLF viable bacterial counts. By contrast, there were no differences in peripheral blood neutrophil (PN) counts among the three groups, nor was there a correlation between PN and PEN counts. CD11b expression was greater on PENs than on PNs in all three groups. CD11b expression on PNs did not differ among the three groups. However, GH increased CD11b expression on PENs, as compared with saline and IGF-I, and this expression showed a positive correlation with PEN numbers and an inverse correlation with PLF viable bacterial counts. CD11b expression on peritoneal macrophages and peripheral blood monocytes did not differ among the three groups. There were no differences in phagocyte CD32/CD16 expression among the three groups. CONCLUSIONS: GH pretreatment enhanced CD11b expression on PENs, but not PNs, possibly in association with enhanced neutrophil recruitment, phagocytosis, and bacterial elimination by PENs, without activation of PNs. GH prophylaxis may be useful for reducing the frequency rate and severity of septic complications, via modulation of CD11b expression on local and systemic neutrophils.

Animals↗

PubMed1998

Growth hormone and insulin-like growth factor I augment bactericidal capacity of human polymorphonuclear neutrophils.

Effects of growth hormone (GH) and insulin-like growth factor (IGF)-I on bactericidal capacity of human polymorphonuclear neutrophils (PMNs) were investigated. Venous blood was collected from healthy volunteers. In Experiment 1, PMNs were isolated, incubated with GH or IGF-I, and cocultured with Escherichia coli. E. coli-killing capacity, viability, and CD11b and CD16 expressions of PMNs were then assessed. Both GH and IGF-I enhanced E. coli killing by PMNs. GH preserved PMN viability during E. coli killing, whereas IGF-I enhanced PMN CD11b expression before coculture with E. coli. In Experiment 2, whole blood was washed and incubated with GH or IGF-I. PMNs in washed whole blood were then analyzed for phorbol myristate acetate (PMA)-stimulated CD11b, CD35, and CD16 expressions and production of reactive oxygen intermediates (ROI), as well as phagocytosis with/without anti-CD11b antibody. IGF-I enhanced PMN expressions of CD11b and CD35, but not CD16, stimulated with PMA. Both hormones enhanced phagocytosis, which was abrogated by anti-CD11b antibody, and intracellular ROI production by PMNs. These results indicate that both GH and IGF-I augment human PMN bactericidal capacity, via increased phagocytosis and intracellular ROI production. Preservation of PMN viability by GH and enhanced complement receptor expression by IGF-I may also be associated with augmented PMN bactericidal capacity. Although PMN activation has potentially harmful aspects, these results encourage additional studies to confirm the clinical relevance of exogenous GH or IGF-I for the prevention or management of septic complications in perioperative or critically ill patients especially with low circulating GH and/or IGF-I levels.

Cell Survival↗

PubMed1997

Postoperative radiation for cervical cancer with pathologic risk factors.

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.

Adult↗

PubMed1997

Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while increasing adhesion in remote organs in peritonitis.

Nitric oxide (NO) is a regulator of leukocyte adhesion in the microcirculation. This study was designed to examine the effects of a NO synthase inhibitor on neutrophil adhesion in the peritoneum, lung, liver, and kidney in a rat peritonitis model using a fluorescence microscopic method. Sprague-Dawley rats were given normal saline (control) or N omega-nitro-L-arginine methyl ester (L-NAME) at dosages of 10 mg/kg (N10) or 100 mg/kg (N100) (n = 66) intraperitoneally. One hour after pretreatment fluorescein-labeled neutrophils were infused without bacterial challenge (0 hr). Other rats received an injection of 10(7) Escherichia coli into the peritoneal cavity 1 hr after pretreatment. Labeled neutrophils were infused 1 and 5 hr after bacterial challenge. Just 2 min after neutrophil injection, blood samples were obtained and the animals were killed. Five peritoneal samples (omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Combined plasma nitrite/nitrate levels were determined. In another set of rats (n = 36), an arterial catheter was inserted after L-NAME treatment and bacterial challenge. At 0, 1, 5, and 12 hr after challenge, blood pressure, heart rate, and arterial blood gas data were measured. One hour after E. coli challenge, the number of neutrophils in the peritoneum was significantly lower in both L-NAME-treated groups than in the control group. In contrast, the number of labeled neutrophils in the lungs was significantly higher in the N100 group than in the control group. Neutrophil accumulation in the lungs and peritoneum at 0 and 5 hr and in the liver and kidney at 0, 1, and 5 hr did not differ among groups, nor did combined plasma nitrite/nitrate levels. L-NAME treatment had no influence on either hemodynamic or blood gas data. In conclusion, administration of L-NAME increases neutrophil adhesion in the lung, while decreasing that in the peritoneum. NO plays an important role in neutrophil adhesion at the inflammatory site, as well as in remote organs, during peritonitis. NO inhibition may be detrimental, due to neutrophil sequestration, in this peritonitis model.

Animals↗

PubMed1997

Glutamine-enhanced bacterial killing by neutrophils from postoperative patients.

Neutrophils play an important role in host defense by phagocytosing and destroying invading bacteria. A recent investigation revealed that glutamine (Gln) augmented the in vitro bactericidal activity of neutrophils from burn patients. However, it is unclear whether Gln enhances the function of neutrophils in postoperative patients. This study was designed to investigate the effect of Gln on the in vitro Escherichia coli-killing activity of neutrophils from postoperative patients. Nine randomly selected patients were included in this study. On the morning of the first postoperative day, blood was drawn and neutrophils were isolated. Eight healthy volunteers served as controls. E. coli was opsonized with pooled normal serum. Neutrophils (5 x 10(6)), together with opsonized E. coli (5 x 10(5)), were incubated for 2 h at 37 degrees C in Hanks' balanced salt solution supplemented with 0, 100, 500, or 1000 nmol/mL of Gln. The bactericidal function of neutrophils was determined by counting the number of viable bacteria. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, and granulocyte elastase levels in the cell culture supernatant were measured. Plasma C-reactive protein (CRP), cortisol, and amino acids were also analyzed. The plasma concentration of Gln was significantly lower in the postoperative patients than in the controls. Following culture with patient neutrophils, the number of viable E. coli decreased by 26% as the in vitro Gln concentration was increased from 500 to 1000 nmol/mL (P < 0.01). We defined the Gln 1000/Gln 500 ratio of the number of viable bacteria as the number of viable E. coli at an in vitro Gln concentration of 1000 nmol/mL divided by the number of viable E. coli at an in vitro Gln concentration of 500 nmol/mL. A positive correlation was thus demonstrated between the plasma Gln level and the Gln 1000/Gln 500 ratio of the number of viable bacteria in the patients (r = 0.69, P = 0.04). This finding indicated that as plasma Gln fell, there was an enhancement of neutrophil E. coli-killing activity by neutrophils in in vitro tests when the Gln concentration was increased from 500 to 1000 nmol/mL. Gln supplementation caused no appreciable changes in TNF-alpha, IL-1 beta, IL-8, or granulocyte elastase levels in cell culture supernatants. A negative correlation was recognized between the patient plasma Gln level and the Gln 1000/Gln 500 ratio of the cell culture supernatant IL-8 level (r = -0.73, P = 0.025). In conclusion, Gln supplementation enhanced the in vitro bactericidal function of neutrophils from postoperative patients.

Adult↗