p38 MAPK phosphorylation and NF-kappa B activation in human crescentic glomerulonephritis.

BACKGROUND: p38 mitogen-activated protein kinase (p38 MAPK) followed by the activation of NF-kappa B participates in the intracellular signal transduction and production of cytokines and chemokines. The pathophysiological roles of p38 MAPK and NF-kappa B in human glomerulonephritis, however, remain to be investigated. METHODS: We investigated the phosphorylated p38 MAPK (p-p38 MAPK) and activated NF-kappa B immunohistochemically in the kidneys of 34 patients with crescentic glomerulonephritis and 26 control patients with thin basement membrane disease and minimal change nephrotic syndrome. We also explored the co-localization of p-p38 MAPK with CCR5, the signal of which leads to p38 MAPK activation. Furthermore, urinary levels of MIP-1 alpha, the cognate ligand for CCR5, were determined by enzyme-linked immunosorbent assay. RESULTS: p-p38 MAPK-positive cells and activated NF-kappa B-positive cells were mainly detected in crescentic lesions, tubular epithelial cells, and interstitial mononuclear infiltrates. The number of p-p38 MAPK-positive cells in patients with crescentic glomerulonephritis was higher than that in control patients. The number of p-p38 MAPK-positive cells in glomeruli was well correlated with the percentage of cellular crescents, the number of CD68-positive cells, and urinary MIP-1 alpha levels. In addition, the number of activated NF-kappa B-positive cells was well correlated with the number of p-p38 MAPK-positive cells in glomeruli. Dual staining revealed that most of CCR5-positive cells were positive for p-p38 MAPK. Finally, p-p38 MAPK-positive cells and activated NF-kappa B-positive cells decreased during glucocorticoid therapy-induced convalescence. CONCLUSIONS: We conclude that the phosphorylation of p38 MAPK associated with the activation of NF-kappa B may be involved in the upregulation of intrarenal MIP-1 alpha and the utilization of CCR5 signalling, which may result in human crescentic glomerulonephritis.     

Role of vitamin C on adrenocortical effects of etomidate]

This study was carried out to assess whether the adrenal inhibition induced by etomidate could be prevented by associating ascorbic acid with etomidate, as a protective effect of ascorbic acid administered three hours after etomidate has been described. Sixteen ASA 1 or 2 patients, less than 65 years old, free of endocrine disease, were included. At induction of anaesthesia, eight of them (group B) were given an infusion of ascorbic acid 1 g, in 500 ml of 5% glucose. Group A patients (n = 8) were given 500 ml of 5% glucose. Anaesthesia was induced with etomidate 0.3 mg.kg-1, fentanyl 0.005 mg.kg-1 and vecuronium 0.1 mg.kg-1. Maintenance was carried out using a continuous infusion of etomidate (0.1 mg.kg-1.h-1 for 10 min, followed by 0.01 to 0.02 mg.kg-1.h-1). Additional boluses of fentanyl or diazepam (10 mg) were administered when arterial blood pressure or heart rate were 20% greater than preanaesthetic values. The number of injections required was the same in both groups. Plasma cortisol concentrations were measured by radioimmunoassay (RIA) before anaesthesia (T0), 4 h (T4) and 24 h (T24) after the end of surgery. Blood ACTH levels were also assessed by RIA at T0 and T4. The adrenal insufficiency at T4 had completely ended at T24. In fact, the relative decrease in cortisol levels was greater in patients treated with ascorbic acid (T4/T0: 47.6 +/- 9% in group A vs 76.5 +/- 33% in group B, p less than 0.05); this was suggestive of a higher degree of adrenal inhibition in patients receiving ascorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

ABO-incompatible kidney transplantation using antigen-specific immunoadsorption and rituximab: a single center experience

BACKGROUND: For years ABO-incompatible kidney transplantations were preferentially performed in Japanese centers. In order to overcome the increased risk of humoral rejections, patients were treated with multiple sessions of plasmapheresis, intensified immunosuppressive therapy and splenectomy before transplantation. Despite good long-term results regarding patient and organ survival rates, increased morbidity during the early post-transplant period prevented a broad application of this method. Recently, a new protocol including the anti-CD20-antibody (Ab) rituximab and blood group-specific immunoadsorption instead of splenectomy and plasmapheresis was published with excellent short-term results. METHODS: From April 2004 to September 2005, 11 patients were prepared for ABO-incompatible transplantation. All patients received 375 mg/m2 rituximab intravenous 3 to 4 weeks before transplantation. Immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil and prednisone and was started at least 7 days before transplantation. Intravenous immunoglobulins (0.5 g/kg) were administered the day before transplantation. Immunoglobulin G (IgG)-anti-A or -B Ab titers before starting immunoadsorption treatment ranged between 1 : 4 and 1 : 1024. Immunoadsorption treatment was started in parallel with immunosuppressive medication and was continued until the anti-A or anti -B Ab titers (IgG and IgM) were lowered to the aimed pre-transplant threshold of <1 : 8. During the early postoperative period, additional immunoadsorption treatments were performed, if the titers increased again above 1 : 8 (days 0 to 7) or 1 : 16 (days 8 to 14), respectively. RESULTS: Transplantation could be conducted in eight of 11 patients (two females, six males, mean recipient age 52+/-11 yr). The mean follow-up was 7.0 months (range 4 to 17). The blood group constellation was A1 to 0 in four cases, A2 to 0 in two cases, B to A in one case, and A1 to B in another case, respectively. On average, each patient received seven immunoadsorption treatments. All transplants showed primary function and no humoral rejections occurred. Three of our 11 patients showed rapid increases of isoagglutinin titers after each immunoadsorption treatment and thus could not be transplanted. One patient died 4 months after transplantation with a functioning graft due to sepsis secondary to pseudomembranous enterocolitis. The mean creatinine value of the remaining seven patients now is 1.6 mg/dl. SUMMARY: The use of antigen-specific immunoadsorption and an immunosuppressive regimen consisting of a conventional triple immunosuppressive therapy has shown excellent short-term results. The immunoadsorption treatment using antigen-specific columns is highly effective and even patients with high isoagglutinin titers can be transplanted. This protocol is an option for end-stage renal disease patients who have no blood group-compatible donor.     

FOLFOX方案化疗对晚期结直肠癌患者免疫功能的影响

目的 研究FOLFOX方案化疗对晚期结直肠癌患者免疫功能的影响.方法 43例晚期结直肠癌患者中22例接受了FOLFOX方案化疗（化疗组）,21例未接受化疗（对照组）.分别于化疗前、化疗结束时和化疗结束3个月后,取患者外周静脉血,采用抗体标记流式细胞仪检测外周血CD4＋T细胞中CD4＋CD25＋Foxp3＋T细胞所占比例;并通过ELISA法检测外周血中Th1/Th2细胞因子（IL-2、IFN-γ、IL-4和IL-10）水平.结果 化疗结束时,相对于化疗前和对照组,化疗组CD4＋CD25＋Foxp3＋T细胞比例显著降低 [（4.15±0.56）%比（5.60±0.88）%和（5.38±0.92）%,均P＜0.01];外周血IL-4和IL-10水平亦显著降低,IFN-γ和IL-2水平则明显升高（均P＜0.01）.化疗结束后3个月,CD4＋CD25＋Foxp3＋T细胞比例略微升高 [（4.53±0.58）%],但仍低于化疗前和对照组（P＜0.01）;而IFN-γ、IL-2、IL-4和IL-10则恢复到化疗前和对照组同期水平（均P＜0.01）.结论 FOLFOX化疗可降低晚期结直肠癌患者的调节性T细胞的比例,引起Th1/Th2细胞因子平衡向Th1漂移,从而有利于患者肿瘤免疫抑制的解除.     

Intraoperative effects of combined versus general anesthesia during major liver surgery

AIM: The study compares the intraoperative effects of combined versus general anesthesia during major liver surgery. METHODS: In this prospective randomized study, 70 patients were divided into 2 group of 35 subjects. Group A received general anesthesia (thiopentone, fentanyl, vecuronium, sevoflurane in a closed circuit) 15 minutes after placement of an epidural catheter (D9-D10) and induction of epidural anesthesia (6 ml 2% naropine). Continuous epidural infusion was initiated before surgical incision and continued with 0.2% naropine (7 ml/h) until the end of the operation. Group B received combined intraoperative anesthesia wit fentanyl doses according to hemodynamic parameters and 0.1 mg/kg morphine 30-4 minutes before cutaneous suture. Hemodynamic values were measured at base line (T0), and then at 15, 30, 60, 120 and 180 minutes after induction of general anesthesia (T1, T2, T3, T4 and T5, respectively). On recovery, patients were assessed for pain at rest and on movement reported on a visual analog scale; degree of motor blockade according to the Bromage scale; appearance of side effects; use af analgesic. RESULTS: A statistically significant decrease in the mean arterial blood pressure (ABP) and heart rate (HR) was noted within each group at 15 minutes after induction of general anesthesia. Significant differences in ABP were found between the 2 groups at T1 to T5, whereas HR values were substantially similar. The mean intraoperative use of fentanyl was significantly higher in Group B than in Group A, as was that of vecuronium. Pain intensity on recovery in patients who received epidural anesthesia was lower both at rest and on movement; only the patients in Group B required additional analgesics. No motor blockade was observed in either group. Nausea and vomiting were more frequent in Group B; hypotension was more frequent in Group A. CONCLUSION: The study confirms the safety of locoregional anesthesia in liver surgery, with good hemodynamic stability and absence of major side effects. The lower intraoperative use of opioids and muscle relaxants in patients who received epidural anesthesia confirms the neurovegetative protection this method provides. The data support the hypothesis that greater intraoperative use of opioids may be responsible for the higher incidence of side effects. Therefore, the intraoperative use of combined low-concentration anesthetic agents alone appears to offer a reasonable treatment option that provides adequate pain control at recovery from general anesthesia, with only minor side effects typically associated with analgesic (motor blockade) and opioids (nausea and vomiting). Given the complications associated with the technique, it should be performed by an expert anesthetist.     

Interpleural bupivacaine infusion compared with intravenous pethidine infusion after cholecystectomy.

Twenty-six cholecystectomy patients received either an interpleural infusion of bupivacaine (Group B, n = 12) or an intravenous infusion of pethidine (Group P, n = 14) for management of postoperative pain over a three-day period. Patients in Group P experienced a significantly (P less than 0.05) greater incidence of total side-effects (146) than patients in Group B (66). Pain scores (VAS) and responses to a pain questionnaire were similar for both groups; however, within Group B improvement in mean VAS scores at rest with time were more sustained. Similar reductions in FEV1 and FVC from preoperative values occurred for both groups, while for Group P there were significant (P less than 0.05) changes in arterial blood gases (increase in PCO2, decrease in PO2) over two days postoperatively. Patients in Group P recorded longer times to passing flatus and unaided mobilisation (P less than 0.05), and required a significantly greater number of additional medications (anti-emetics and analgesics) over the postoperative period (41 vs 29, P less than 0.05).     

Treatment of thoracolumbar burst fractures with polymethyl methacrylate vertebroplasty and short-segment pedicle screw fixation

OBJECTIVES: We aimed to evaluate the efficacy of reinforcing short-segment pedicle screw fixation with polymethyl methacrylate (PMMA) vertebroplasty in patients with thoracolumbar burst fractures. METHODS: We enrolled 70 patients with thoracolumbar burst fractures for treatment with short-segment pedicle screw fixation. Fractures in Group A (n = 20) were reinforced with PMMA vertebroplasty during surgery. Group B patients (n = 50) were not treated with PMMA vertebroplasty. Kyphotic deformity, anterior vertebral height, instrument failure rates, and neurological function outcomes were compared between the two groups. RESULTS: Kyphosis correction was achieved in Group A (PMMA vertebroplasty) and Group B (Group A, 6.4 degrees; Group B, 5.4 degrees). At the end of the follow-up period, kyphosis correction was maintained in Group A but lost in Group B (Group A, 0.33-degree loss; Group B, 6.20-degree loss) (P = 0.0001). After surgery, greater anterior vertebral height was achieved in Group A than in Group B (Group A, 12.9%; Group B, 2.3%) (P < 0.001). During follow-up, anterior vertebral height was maintained only in Group A (Group A, 0.13 +/- 4.06%; Group B, -6.17 +/- 1.21%) (P < 0.001). Patients in both Groups A and B demonstrated good postoperative Denis Pain Scale grades (P1 and P2), but Group A had better results than Group B in terms of the control of severe and constant pain (P4 and P5) (P < 0.001). The Frankel Performance Scale scores increased by nearly 1 in both Groups A and B. Group B was subdivided into Group B1 and B2. Group B1 consisted of patients who experienced instrument failure, including screw pullout, breakage, disconnection, and dislodgement (n = 11). Group B2 comprised patients from Group B who did not experience instrument failure (n = 39). There were no instrument failures among patients in Group A. Preoperative kyphotic deformity was greater in Group B1 (23.5 +/- 7.9 degrees) than in Group B2 (16.8 +/- 8.40 degrees), P < 0.05. Severe and constant pain (P4 and P5) was noted in 36% of Group B1 patients (P < 0.001), and three of these patients required removal of their implants. CONCLUSION: Reinforcement of short-segment pedicle fixation with PMMA vertebroplasty for the treatment of patients with thoracolumbar burst fracture may achieve and maintain kyphosis correction, and it may also increase and maintain anterior vertebral height. Good Denis Pain Scale grades and improvement in Frankel Performance Scale scores were found in patients without instrument failure (Groups A and B2). Patients with greater preoperative kyphotic deformity had a higher risk of instrument failure if they did not undergo reinforcement with vertebroplasty. PMMA vertebroplasty offers immediate spinal stability in patients with thoracolumbar burst fractures, decreases the instrument failure rate, and provides better postoperative pain control than without vertebroplasty.     

Cellular immunoregulatory aspects of IgA nephropathy

Polyclonal activation of IgA-producing B cells has been observed in the majority of patients with IgA nephropathy (IgAN) and some of their family members. The precise mechanism of such activation is presently unknown. However, abnormalities of T and B cell interactions have recently been observed in this disease. These abnormalities include the decrease of IgA-specific suppressor T cell activity and the increase of IgA-specific helper T cell activity. A T cell subpopulation with receptors for the Fc portion of IgA and with CD4 antigens (ie, T alpha 4 cells) has been proposed as a candidate of IgA-specific switch T cells that convert IgM-producing B cells to IgA-producing B cells. Further analysis of the immunogenetic mechanism and the clinical correlates of the cellular immunoregulatory aspects of IgAN is necessary to elucidate the pathogenesis of this disease.     

Resection for solitary brain metastasis. Role of adjuvant radiation and prognostic variables in 229 patients.

The authors reviewed 229 consecutive patients treated intramurally by resection of solitary cerebral metastasis. Patients were classified into four groups on the basis of whether a gross total resection or subtotal resection was performed and whether systemic disease was present or absent at the time of craniotomy. Group 1 had gross total resection and no systemic disease; Group 2 had subtotal resection and no systemic disease; Group 3 had subtotal resection and systemic disease; and Group 4 had gross total resection and systemic disease. All four groups were further subdivided into Subgroup A (adjuvant whole-brain radiation therapy) or Subgroup B (no adjuvant radiation). Data were collected regarding multiple patient and tumor variables for multivariate analysis. Survival data for the 46 patients in Group 1A (median 1.3 years, 2-year survival rate 41%, 5-year survival rate 21%) were markedly better than those for the 75 in Group 1B (median 0.7 year, 2-year survival rate 19%, 5-year survival rate 4%). The 20 patients in Group 2A also had superior survival data (median 1.1 years, 2-year survival rate 30%, 3-year survival rate 30%) when compared with the eight patients in Group 2B (median 3 months, 1-year survival rate 0%). However, the 16 and 22 patients in Groups 3A and 4A, respectively, had no discernible differences compared to the seven and 35 patients in their Group 3B and 4B counterparts. Multivariate analyses were performed to assess the association of survival with multiple patient, disease, and treatment variables. Poor neurological status and systemic disease were significantly associated with inferior survival, while longer (greater than 36 months) intervals between primary diagnosis and craniotomy were significantly associated with improved survival. After adjusting for the effects of other patient, disease, and treatment characteristics, adjuvant whole-brain radiotherapy was significantly associated with improved survival times. These data support the continued use of craniotomy followed by adjuvant whole-brain radiation therapy for treatment of solitary brain metastasis. However, this aggressive therapy appears relatively contraindicated in the face of either systemic disease or substantial neurological deficit.     

Surgical treatment of iatrogenic perforations of the distal third of the esophagus. Personal experience

AIM: The esophageal perforations are associated with a high mortality and morbidity when they are not diagnosed and treated quickly. The aim of our study is to analyze the treatment and prognosis of the distal iatrogenic esophageal perforations on the basis of time of onset, concomitant disease and size of perforations. METHODS: The retrospective review was performed on 10 patients treated for distal iatrogenic esophageal perforations at our Institution from 1994 to 2003. The cause of perforations was: pneumatic dilation (7 patients) and esophageal endoprosthesis placing (3 patients). Seven patients presented within 24 h (Group A), and 3 patients presented after 24 h (Group B). In Group A, 4 patients underwent primary repair, 2 patients required esophagectomy and 1 patient was treated conservatively. In Group B, 2 patients were treated conservatively and 1 patient required an esophagectomy. RESULTS: Hospital morbidity was 20% and mortality was 30%. In Group A no patients died. In Group B hospital mortality was 100%. The most common cause of death was multiorgan failure resulting from sepsis. CONCLUSIONS: The prognosis for esophageal perforations is influenced by the time elapsed between diagnosis and treatment. Esophagectomy is indicated for patients with extensive perforation and necrosis of the esophagus when primary repair cannot be carried out. It is indicated also as treatment for the concomitant disease.     

Analysis of T cell subsets and beta chemokines in patients with pulmonary sarcoidosis

BACKGROUND: Sarcoidosis is a systemic granulomatous disorder of unknown origin characterised by accumulation of T lymphocytes and macrophages in multiple organs. Several cytokines and adhesion molecules may contribute to the accumulation of T lymphocytes in pulmonary sarcoidosis. The distribution of T lymphocyte subsets, T cell bearing CD11a and beta chemokines such as regulated on activation normal T expressed and secreted (RANTES), macrophage inflammatory peptide 1 alpha (MIP-1 alpha), and macrophage chemoattractant protein 1 (MCP-1) in bronchoalveolar lavage (BAL) fluid and peripheral blood were compared in untreated patients with sarcoidosis and normal subjects. METHODS: Flow cytometric analysis with monoclonal antibodies to cell surface antigens was used to identify T lymphocyte subsets in the BAL fluid of untreated patients with sarcoidosis (n = 40)--either without (group A, n = 12) or with (group B, n = 28) radiological evidence of pulmonary involvement--and in 22 normal subjects. The level of different beta chemokines was estimated by enzyme linked immunosorbent assay (ELISA). RESULTS: A high percentage of CD3+ cells, CD4+ cells expressing HLA-DR antigen, and a high CD4/CD8 ratio were detected in the BAL fluid of patients compared with normal subjects. In particular, CD4+ CD29+ memory T cells were significantly increased in patients with sarcoidosis. Furthermore, these cells were higher in those in group B than group A. The level of RANTES in the BAL fluid of patients was significantly higher than in normal subjects and correlated well with the percentage, number, and expression of CD29 on CD4 cells. The expression of CD11a (alpha chain of lymphocyte function associated antigen-1, LFA-1) on CD3+ cells in the BAL fluid of patients with sarcoidosis was not different from that of normal subjects. However, the expression of CD11a on CD3+ cells in the BAL fluid of patients in group A was significantly lower than that of patients in group B and normal subjects. CONCLUSIONS: These results suggest a possible interaction between activated memory T cells bearing CD11a and RANTES which may contribute to the pulmonary involvement in patients with sarcoidosis.


     

Presentation of the Goodpasture autoantigen requires proteolytic unlocking steps that destroy prominent T cell epitopes

The most abundant autoreactive T cells in patients with Goodpasture's disease are specific for peptides in the autoantigen that have high affinity for the disease-associated HLA class II molecule, DR15. How can such T cells escape self-tolerance mechanisms? This study showed that these peptides are highly susceptible to destruction in the earliest stages of antigen processing, and some must be cleaved for antigen digestion to be possible ("unlocking"). Goodpasture autoantigen [collagen alpha3(IV)NC1; approximately 31 kD] that was incubated with B cell lysosomes was cleaved within a few minutes to form approximately 9- and approximately 22-kD fragments, then increasing quantities of smaller peptides. The processing was completely abrogated by pepstatin A, a specific inhibitor of cathepsin D/E, even though lysosomal extracts contain a rich array of proteases. Purified cathepsin D generated the same major alpha3(IV)NC1 fragments as entire lysosomes, suggesting that cathepsin D cleavages are required to initiate alpha3(IV)NC1 processing. The initial unlocking cleavages destroyed two major self-epitopes, and subsequent preferred cleavages destroyed all of the other T cell epitopes that are recognized by most patients' autoreactive T cells. The responses of T cell clones that are specific for a major disease-associated peptide to antigen-pulsed intact antigen-presenting cells were substantially enhanced by pepstatin A treatment. Therefore, cathepsin D activity significantly diminishes presentation of alpha3(IV)NC1 peptides that are recognized by patients' T cells by destroying the peptides in early processing. These observations can explain why the mature T cell repertoire includes reactivity toward these self-peptides and suggests that a key factor in disease initiation is likely to be a shift in antigen processing.     

Postoperative change of serum protease inhibitor and C-reactive protein level--with special reference to surgical resection of liver cirrhosis]

Changes in the activities of blood protease inhibitors and acute-phase reactive substances during surgical resection of liver cirrhosis were investigated by measuring the pre- and postoperative blood concentrations of alpha 1-antitrypsin (alpha 1AT), alpha 2-macroglobulin (alpha 2MG), pancreatic secretory trypsin inhibitor (PSTI), urinary trypsin inhibitor (UTI) and C-reactive protein (CRP), in patients with liver cirrhosis who underwent hepatectomy (Group A, n = 19), those without liver cirrhosis who underwent hepatectomy (Group B, n = 6) and those without liver cirrhosis who underwent surgeries other than hepatectomy (Group C, n = 5). On examining the preoperative blood levels of protease inhibitors, Group A had an increased level of alpha 2MG and a decreased level of UTI compared to Groups B and C. alpha 1AT and CRP began to increase on the first day following hepatectomy and formed peaks on the third postoperative day. The increases were significantly higher in Group B than Group A (p less than 0.01). To investigate factors causative of these differences, alpha 1AT and CRP on the third postoperative day were compared in relation to the time of operation, amount of intraoperative bleeding, weight of the resected liver and preoperative ICGR15. alpha 1AT and CRP were significantly correlated to only preoperative ICGR15. PSTI was increased postoperatively but showed no difference between Groups A and B.     

Removal of lymphocytotoxic antibodies by pretransplant immunoadsorption therapy in highly sensitized renal transplant recipients

A high level of panel-reactive antibodies (PRA) in potential renal transplant recipients is associated with a long waiting time until transplantation and correlates inversely with graft outcome. We report our experience with the employment of immunoadsorption (IA) using a column composed to sepharose-bound staphylococcal protein A (which has a relatively selective affinity for binding IgG compared with other immunoglobulins) to decrease the PRA levels and expedite transplantation in 6 highly sensitized potential renal transplant recipients (1 primary and 5 awaiting second transplants). All patients had PRA levels of greater than or equal to 70% for a duration of 1 year prior to IA. Only patients with antibody specificity localized to 1 or 2 HLA A or B antigens were accepted for the study. IA procedures were performed on alternate days until a twofold decrease in antibody titer had occurred (maximum: 6 procedures). Repeat procedures were initiated if the HLA antibody titer returned to its baseline value. Intravenous cyclophosphamide (CY) (10 mg/kg/day every 3 weeks) and methylprednisolone (MP) (0.5 mg/kg/day) were provided as adjunctive immunosuppression until transplantation. A total of 44 immunoadsorption procedures were performed (27 primary and 17 repeat) with treatment of 2.49 +/- 0.02 plasma volumes per session. Serum IgG concentration decreased 95 +/- 3% and PRA activity decreased 75 +/- 16% after the primary treatment course. Four patients received cadaveric grafts within 3.7 +/- 1.2 months following the last IA procedure. Three grafts are functioning at 1 year, 8 months, and 8 weeks posttransplant. The remaining graft demonstrated primary nonfunction. All four patients had a past positive crossmatch using pre-IA sera with their respective donors. Patients not transplanted exhibited rapid resynthesis of IgG and a return of the PRA towards baseline levels within a few weeks after IA. We conclude that IA can effectively remove HLA antibodies and expedite graft availability in highly sensitized patients.     

Multimodal therapy in locally advanced breast carcinoma

Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.     

T1G3 bladder cancer--indications for early cystectomy

OBJECTIVES: To review our experience with early radical cystectomy in patients with T1G3 Transitional Cell Carcinoma of bladder (TCC). PATIENTS AND METHODS: Thirty patients, who underwent early radical cystectomy over a 10-year period for clinical stage T1G3 TCC bladder, were studied. Of these 21 (70%) had radical cystectomy without treatment with intravesical chemo/immunotherapy. The number of tumours, presence or absence of Carcinoma In-Situ (CIS) and the pathological stage of the cystectomy specimen were recorded in each patient. Disease specific survival was determined in the subgroups using Kaplan-Meier estimates. RESULTS: Seventeen patients underwent radical surgery for a single tumour without concomitant CIS (Group A). The other 13 had multiple tumours with or without concomitant CIS or a single tumour with CIS (Group B). The disease was upstaged after cystectomy in 1 (6%) patient in Group A compared to 7 (55%) in Group B, (p = 0.009). Nine (53%) had pT0 disease in Group A compared to 0% in Group B, (p = 0.0017). The 5-year cancer specific survival rates were 92% in Group A and 82% in Group B. CONCLUSIONS: In patients with multiple T1G3 tumours with or without associated CIS, or in those with single T1G3 tumour with associated CIS the incidence of the disease being already muscle invasive at the time of clinical diagnosis is 55%. Early radical cystectomy should be advocated in this group. Conversely, for a single T1G3 tumour without associated CIS, conservative bladder preserving strategy with immuno-chemotherapy and close surveillance is justified.     

Effect of preoperative chemotherapy for bulky N2 non-small-cell lung cancer]

The effect of chemotherapy as the adjuvant therapy to bulky N2 disease (stage IIIA) non-small-cell lung cancer was examined. From January 1992 to December 1996, 464 patients with non-small-cell lung cancer underwent surgery. Seven patients (1.5%) with N2 disease (stage IIIA) received two cycles of preresectional cisplatin and vindesin chemotherapy, followed by standardized surgical resection (Group A). 46 patients (9.9%) had pathological N2 disease (T1-3, M0) after surgery (Group B). In Group A a complete resection was accomplished in two patients (28.6%), and five patients had incomplete resection with a deseased margin, followed thoracic irradiation 60 to 75 Gy. In three patients in Group A the N2 disease was pathologically downstaged to N1 or N0 disease. Overall survival at five years in Group A and in Group B was 48% and 39%, and median survival time was 49 months and 38 months. Although complete resection rate was lower in Group A (28.6%) than in Group B (78.2%), there was no significant difference between five year survival and median survival time in Group A and Group B. These data may be thought to suggest that induction chemotherapy in Group A was effective on occult micrometastatic disease.     

Bone marrow purging for multiple myeloma by avidin-biotin immunoadsorption

Avidin-biotin immunoadsorption, a technique based on the high affinity between the protein avidin and the vitamin biotin, has been used to remove neoplastic plasma cells from the bone marrow of patients with multiple myeloma. Buffy coat cells obtained from 25 patients were first incubated with monoclonal antibodies (MoAb) capable of recognizing plasma cell-associated antigens (i.e., 8A, 8F6, 62B1, and cocktails of 8A plus 8F6 or 62B1), then with biotinylated goat antimouse immunoglobulin, and passed over a column containing avidin conjugated to Sepharose GMB. Both non-linked and linked cells were analyzed by immunofluorescence and morphological staining. The results showed that over 98% of plasma cells were removed by using 8A or 8F6 alone, while 99.5% +/- 0.4 SD of plasma cell purging was achieved with 2 associated MoAb. In addition, the overall recovery of committed granulocyte-macrophage (CFU-GM),* erythroid (BFU-e), and multilineage (CFU-GEMM) progenitors after column treatment ranged from 39% +/- 15 SD to 50% +/- 6 SD, from 15% +/- 2 SD to 39% +/- 7 SD, and from 16 +/- 4 SD to 64% +/- 10 SD, according to the MoAb employed. On this basis avidin-biotin immunoadsorption appears to be a suitable technique for ex-vivo manipulation of bone marrow infiltrated by neoplastic plasma cells.     

不同年龄发绀型先心病患儿围体外循环期凝血功能的比较

Objective To investigate the changes in blood coagulation during cardiopulmonary bypass (CPB) in children of different ages undergoing open heart surgery for cyanotic congenital heart disease.Methods Sixty children with cyanotic congenital heart disease undergoing open heart surgery under CPB were divided into 3 age groups: Group A(age≤12 mort, n=25), Group B (12mon＜age≤24 mon, n= 17) and Group C (24 mon＜ age＜4 yr, n=18). Venous blood samples were taken immediately after induction of anesthesia(T1) and at 10 min after protamine administration (T2)for determination of activated coagulation time (SonACT), clot rate and platelet function (PF) using Sonoclot coagulation and platelet function analyzer-type DP2951 (Sieuco Co., USA).Results There was significant difference in SonACT, clot rate and PF at T1 among the 3 groups: the SonACT was significantly shorter in Groups B and C than in Group A, the clot rate was significantly higher in Group B than in Group C, and the PF was significantly lower in Group C than in Group A. At T2 , the SonACT was significantly prolonged in all 3 groups, the clot rate was significantly decreased in Groups A and B, and the PF was significantly decreased in Group A.Conclusion There are significant differences in blood coagulation and PF among the 3 different age groups of children with cyanotic congenital heart disease after induction of anesthesia and CPB has different effects on their blood coagulation and PF.     

Is crystalloid preloading useful in spinal anaesthesia in the elderly?

Sixty ASA grade 1 or 2 patients, aged 60 years or over, scheduled for surgery to the lower abdomen or lower limbs under spinal anaesthesia were allocated randomly to one of three treatment groups. Group A received 16 ml/kg of Ringer's acetate solution immediately before spinal anaesthesia, group B received 8 ml/kg and group C received no volume preload. Heart rate, arterial pressure and anaesthetic level were recorded by an independent observer. The overall incidence of systemic arterial hypotension (defined as a decrease of 25% or more in systolic arterial pressure) was 27%; there were no significant differences among groups. The overall incidence of hypotension was 60%, when temperature sensation was blocked to T7 and above (n = 25). The number of patients with hypotension which required treatment increased as block height increased above T7; at a level of T4 or higher, all patients required ephedrine. Crystalloid preloading had no effect on the incidence of hypotension after spinal anaesthesia in fit, elderly patients.