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PubMed1999

Phase II trial of docetaxel, cisplatin, fluorouracil, and leucovorin as induction for squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the toxicity and efficacy of a 4-day regimen of docetaxel, cisplatin, fluorouracil, and leucovorin (TPFL4) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Thirty previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status of 2 or less were treated with TPFL4. Postchemotherapy support included prophylactic growth factors and antibiotics. Patients who achieved a complete response (CR) or partial response (PR) to three cycles of TPFL4 received definitive twice-daily radiation therapy. The primary end points were toxicity and response to TPFL4. RESULTS: Eighty-five cycles were administered to 30 patients. The major acute toxicities to TPFL4 were mucositis and nausea. One patient died of neutropenic sepsis during therapy. Additional major toxicities were neutropenia, anorexia, nephropathy, neuropathy, and diarrhea. Fourteen percent of all cycles were associated with hospitalization for toxicity. The overall clinical response rate to TPFL4 was 93%, with 63% CRs and 30% PRs. Primary tumor site clinical and pathologic response rates were 93% and 68%, respectively. CONCLUSION: TPFL4 has an acceptable toxicity profile in good-performance-status patients. Modification of the 5-day TPFL regimen (TPFL5: shorter chemotherapy infusion time, earlier intervention with growth factors and antibiotics) led to fewer episodes of febrile neutropenia and hospitalization. Response rates to TPFL justify further evaluation of combinations of these agents in the context of formal clinical trials.

Adult↗

PubMed2001

Addition of oxaliplatin to continuous fluorouracil, l-folinic acid, and concomitant radiotherapy in rectal cancer: the Lyon R 97-03 phase I trial.

PURPOSE: Oxaliplatin could increase the efficacy of fluorouracil (5-FU)/folinic acid chemoradiotherapy in rectal cancer. We tested three dose levels to identify a feasible oxaliplatin dose for combination therapy. PATIENTS AND METHODS: Between February 1998 and April 2000, we included 17 rectal adenocarcinoma patients in a single-center phase I study. Patients had T4 rectal carcinoma, T1-T3 disease with colostomy refusal, or potentially operable T2/T3 M1 requiring local treatment. Pelvic radiotherapy was 45 Gy over 5 weeks, 1.8 Gy/fraction, with concomitant chemotherapy weeks 1 and 5. Chemotherapy was oxaliplatin 80, 100, or 130 mg/m2 2-hour infusion on day 1 followed by L-folinic acid 100 mg/m2/d intravenous bolus, and 5-FU 350 mg/m2/d continuous infusion on days 1 to 5 (FolfoR1). Six patients refusing surgery received additional contact radiotherapy +/- brachytherapy. Dose escalation proceeded if less than two of six patients had dose-limiting toxicity (DLT) at a given dose-level. RESULTS: All except two patients completed treatment; patients at level 1 (prolonged grade 1 thrombocytopenia) and level 3 (prolonged cold-related dysesthesia) had no second chemotherapy course. Median follow-up is 14 months (range, 2 to 28 months). One elderly patient at dose level 1 had DLT asthenia, severe diarrhea and vomiting, and more than 10% weight loss. There were no other DLTs and no severe rectitis or gastrointestinal toxicity. There were objective responses at all doses and no progressions. Eight patients underwent radical surgery after chemoradiotherapy. Two had complete pathologic responses. CONCLUSION: FolfoR1 seems feasible and effective. Dose escalation did not increase toxicity. Although the MTD was not reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies because it is the dose determined from studies in metastatic patients with no toxicity when given concurrently with radiation.

Adult↗

PubMedDate not supplied

[Multimodal treatment in locally advanced esophageal cancer: a multicenter phase II study with neoadjuvant oxaliplatin, 5-fluorouracil, leucovorin and neoadjuvant radiotherapy: preliminary results].

The aim of the study was to evaluate the feasibility and efficacy of treatment with oxaliplatin, 5-fluorouracil and leucovorin concomitant with radiation therapy in locally advanced oesophageal cancer. Fifty-eight patients with previously untreated, histologically proven oesophageal cancer were enrolled. Downstaged patients underwent either surgery or received brachytherapy. We report the results obtained in the first 54 patients. The median age was 58 years. The diagnosis was squamous cell carcinoma/adenocarcinoma/poorly differentiated: 45/8/1; clinical stage: T3N1M0 38 (70%), T4 10 (19%), M1a 6 (11%). Thirty-nine patients (72%) received the planned 8 weeks of chemotherapy and 45 completed the entire course of scheduled radiotherapy. Four (7%) toxic deaths were recorded, 2 more patients died prematurely from massive oesophageal bleeding and 1 from progression of disease. We recorded 8 (15%) complete responses and 24 (44%) partial responses. Resection was complete (R0) in 24 (80% of resected patients, 44% of treated patients). A complete pathological response was documented in 6 patients (11% of those treated). Postoperative complications were recorded in 8 (25%) patients, with 2 (6.2%) deaths. RO resection was accomplished in 44% of patients. Toxicity was moderate, but postoperative mortality was not negligible. Survival data are awaited before a phase III comparison with cisplatin-containing chemo-radiotherapy may be considered.

Adult↗

PubMed1996

Paclitaxel and carboplatin as neoadjuvant chemotherapy in operable (stage I and II) and locally advanced (stage IIIA-N2) non-small cell lung cancer.

In 1995, a randomized intergroup study of neoadjuvant chemotherapy followed by either surgery or radiotherapy in the treatment of non-small cell lung cancer was started under the auspices of the European Organization for Research and Treatment of Cancer (EORTC 08941). The objective of this study is to investigate whether surgery or radiotherapy represents superior locoregional treatment, in terms of survival and quality of life, for patients with stage IIIA(N2) non-small cell lung cancer who have achieved a response after three courses of neoadjuvant chemotherapy. A phase II side study will investigate the clinical and pathologic response rate (if applicable), as well as acute and late side effects during or after consecutive surgery and/or radiotherapy of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin. It is planned that paclitaxel 175 mg/m2 will be given as a 3-hour infusion, followed by a 30-minute infusion of carboplatin at a dose based on a target area under the concentration-time curve of 6 mg x min/mL. This phase II study was started in October 1996. Depending on the response rate and early and late side effects observed in this well-defined, prognostically favorable group of patients, it will be decided whether and how to use the same combination chemotherapy in an ongoing randomized trial currently being conducted by the Dutch Lung Cancer Study Group (DLCSG 94-2). In the latter trial, patients with stage I and II non-small cell lung cancer are randomized to immediate surgery or two courses of neoadjuvant chemotherapy. Responding patients will receive another two courses of chemotherapy before surgery; nonresponders will go directly to surgery.

Antineoplastic Agents, Phytogenic↗

PubMed1997

The aesthetic and endodontic dilemmas of calcific metamorphosis.

Traumatic injuries to dentition can initiate either a resorptive or calcific pulpal response. In the sequelae of calcific degeneration, the clinical crown frequently becomes discolored, requiring an aesthetic correction to restore the tooth to its natural color. Four potential solutions are currently available to achieve this goal. The learning objective of this article is to describe the etiology of calcific metamorphosis, discuss the four potential solutions, and present the responses of endodontists polled as to the treatment indications. While the posterior dentition may experience the identical pathologic response to trauma and crown discoloration, this article focuses on the restoration of the anterior dentition. Several cases are presented to illustrate the four treatment modalities, and recommendations for follow-up of traumatic injuries are indicated.

Bicuspid↗

PubMed2005

Gefitinib is more effective in never-smokers with non-small-cell lung cancer: experience among Asian patients.

We retrospectively analysed the results of patients with advanced non-small-cell lung cancer treated with gefitinib to derive clinical factors predictive of response and a favourable survival outcome. Patients were treated with gefitinib 250 mg per day and re-evaluated 4-8 weeks later with repeat CT scan and every 8 weeks thereafter to assess response and the duration of response. Pathology review by a histopathologist was conducted, in particular to confirm a recently published result of bronchioloalveolar carcinoma histology or its components as predictive of response to gefitinib. Logistic regression and Cox regression analytical methods were applied to determine factors that could predict for response and improved overall survival. A total of 110 patients were treated. The overall response rate was 32% partial responses (PRs). Only never-smoking status was predictive of response in the logistic regression analysis, adjusted OR=6.1, 95% CI=1.7, 21.5. The presence of a PR and good performance status were predictive of a favourable survival outcome from the Cox regression modelling. Responders had an adjusted HR of 3.0, 95% CI=1.5-5.8 compared to nonresponders, while patients with ECOG status 0-1 had an adjusted HR of 0.42, 95% CI=0.25-0.72, compared with patients with ECOG status 2-4. Bronchioloalveolar carcinoma or its components were distinctly absent on pathology review. In conclusions, Never-smoking status is an important clinical predictor of a favourable response to gefitinib.

Adult↗

PubMed1997

Neoadjuvant chemotherapy in stage IB2 squamous cell carcinoma of the cervix.

To determine the effects of neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma Stage IB2 (tumor diameter > 4 cm), we reviewed 52 surgically treated patients diagnosed between January 1987 and December 1993. There were 20 patients treated with preoperative neoadjuvant chemotherapy and 32 treated by primary radical hysterectomy. Mean tumor diameter was significantly larger in the neoadjuvant, compared with the primary surgery group (6.5 +/- 1.8 vs 5.4 +/- 0.7, P = 0.003). In the NAC group, 5 of 20 patients were treated with three courses of cisplatin, methotrexate, and bleomycin every 21 days, whereas 15 of 20 patients received three courses of cisplatin, vincristine, and bleomycin every 10 days. Postoperative adjuvant therapy consisting of either radiation or chemotherapy was employed in 13/20 patients (65%) in the NAC group and 20/32 patients (63%) in the primary surgical group. At a median follow-up of 52.5 months, 4/20 patients (20%) in the NAC group recurred vs 11/32 (34%) in the primary surgery group. The overall response rate to NAC was 90%, with 2/20 complete clinical responders and 16/20 partial responders. High-risk pathologic factors were less commonly observed in the NAC group when compared with the primary surgical group with the incidence of nodal metastases, positive vascular space involvement, undiagnosed parametrial disease, and > or = 75% depth of invasion observed in 10.0% vs 37.5%, 20.0% vs 46.9%, 0.0% vs 15.6%, and 30.0% vs 68.8%, respectively. No differences were noted in operative time or blood loss. Cox proportional-hazards analysis indicated that the most significant prognostic factor was depth of invasion. Although the patients who received neoadjuvant chemotherapy had significantly larger tumors at baseline, their 5-year survival rate was slightly higher than that of the primary surgery group (80.0% vs 68.7%, P = 0.162). Patients receiving neoadjuvant chemotherapy, despite having significantly larger pretreatment tumors, had fewer high-risk pathologic factors, postoperatively. Although this was a small, nonrandomized study, the relative improvement in pathologic response and long-term outcome associated with neoadjuvant chemotherapy was encouraging. This highlights the need for a prospective randomized clinical trial to establish whether neoadjuvant chemotherapy can significantly improve the long-term outcome of women with Stage IB2 squamous cell carcinoma of the cervix.

Adult↗

PubMed1990

Advanced ovarian cancer: long-term results following chemotherapy and second-look laparotomy.

Thirty patients who showed a complete clinical response to cis-platinum-containing combination chemotherapy underwent second-look laparotomy. Seventeen patients (56.7%) achieved a pathologically confirmed complete remission as documented by a negative second-look laparotomy. After a minimum follow-up of 60 months, 6 of 17 patients developed recurrent disease and subsequently died. Due to the occurrence of late relapse in these negative second-look patients routine second-look laparotomy to confirm pathological response cannot be justified. Ten of thirty patients underwent secondary cytoreductive surgery at second-look operation. All ten patients had suboptimal initial debulking surgery. Five of these ten patients (50%) survived 4 years. Secondary cytoreductive surgery may improve survival in patients who undergo suboptimal initial debulking surgery.

Adult↗

PubMed1988

Asbestos exposure indices.

The ability of inhaled asbestos to produce asbestosis, lung cancer, and mesothelioma in both humans and animals is well established, and asbestos exposures in the occupational and general community environment are recognized as significant hazards. However, it has not been possible to establish realistic and credible dose-response relationships, primarily because of our inability to define which constituents of the aerosols produce or initiate the pathological responses. It is generally acknowledged that the responses are associated with the fibers rather than the nonfibrous silicate mineral of the same chemical composition. Available data from experimental studies in animals exposed by injection and inhalation to fibers of defined size distributions are reviewed, alone with data from studies of fiber distributions in lungs of exposed humans in relation to the effects associated with the retained fibers. It is concluded that asbestosis is most closely related to the surface area of retained fibers, that mesothelioma is most closely associated with numbers of fibers longer than approximately 5 microns and thinner than approximately 0.1 micron, and that lung cancer is most closely associated with fibers longer than approximately 10 microns and thicker than approximately 0.15 micron. The implications of these conclusions on methods for fiber sampling and analyses are discussed.

Animals↗

PubMed1989

Neuromuscular transmission studies in human chronic Chagas' disease.

An electrophysiological investigation of the state of the neuromuscular transmission (nmt) was carried out in 58 patients with the diagnosis of chronic Chagas' disease. On repetitive supramaximal nerve stimulation it was found that some patients did not show abnormalities, others had decremental muscle responses, others developed enhancement of the muscle evoked potential amplitudes, while some other patients combined both types of pathological responses. The findings suggest that some patients with chronic Chagas' disease develop impairment of nmt, though data obtained in this study do not give information about neither the type of impairment nor the localization (pre or postsynaptic, or both) of the damage.

Adult↗

PubMed2007

Hydrogen peroxide selectively increases TREK-2 currents via myosin light chain kinases.

Two-pore domain K+ (K2P) channels play a critical role in cellular responses to various stimuli, such as stretch or changes in pH and are considered to be important in pathological responses such as apoptosis and tumorigenesis. We investigated effects of H2O2 on various K2P channels expressed in CHO cells. Application of H2O2 did not affect TASK-1, TASK-3, TRAAK currents, but specifically increased TREK-2 currents recorded using a nystatin perforated whole cell technique. The H2O2-induced activation of TREK-2 currents was also observed at single channel levels in cell-attached patches, and the effect was reversed by the reducing agent, dithiothreitol. In contrast, TREK-2 currents recorded using ruptured whole cell technique or single channel recording in inside-out patches were not affected by H2O2. Furthermore, direct application of 5,5'-dithiobis-(2-nitrobenzoic acid) inhibited TREK-2, suggesting that the H2O2-induced activation does not result from direct oxidation of TREK-2 proteins. Among the cell signaling agents, myosin light chain kinase (MLCK) inhibitors significantly inhibited the H2O2-induced activation of TREK-2 currents. These results suggest that TREK-2 channels have a potential to play a specific role in cellular responses to reactive oxygen species and that MLCK activation is involved in this process.

Animals↗

PubMed1997

A phase II trial of paclitaxel and cisplatin in patients with locally advanced metastatic esophageal cancer: a preliminary report.

We demonstrated in an earlier trial that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has substantial antineoplastic activity, with acceptable toxicity, in patients with advanced metastatic esophageal cancer. Preclinical and clinical data from studies in other tumors indicate substantial additive or even synergistic activity for paclitaxel/cisplatin combination chemotherapy. We encountered substantial toxicity with a cisplatin/paclitaxel/5-fluorouracil combination. To maximize paclitaxel dose, we initiated a phase II trial using cisplatin and paclitaxel alone. This report summarizes preliminary data from that trial. Paclitaxel 200 mg/m2 is given as a continuous, 24-hour infusion on day 1. On day 2, cisplatin 75 mg/m2 is given. Courses are repeated every 21 days. Dose adjustments are based on myelosuppression, neurotoxicity, and (for cisplatin) renal or auditory toxicity. All patients receive recombinant human granulocyte colony-stimulating factor to minimize the risk of neutropenic fever. The primary end point of the study is tumor regression. Secondary end points include duration of response and toxicity. Two groups of patients are being studied. Those with advanced metastatic disease receive chemotherapy alone as palliative treatment. The second group has locoregional disease that is potentially resectable. These patients receive combined-modality therapy involving induction paclitaxel/cisplatin chemotherapy followed by surgery. To date, 37 evaluable patients have been treated. Twenty had advanced metastatic disease and 17 were treated before planned surgery. Twenty-seven patients had adenocarcinoma and 10 had epidermoid carcinoma. Major objective responses were seen in 49% of all patients, with similar response rates for patients with metastatic and locoregional disease. The median duration of response for patients with metastases is 4+ months. Among 14 patients treated before surgery, one experienced a complete pathologic response, and the neoplasms of 43% were downstaged. Primary toxicity was neutropenia, which was tolerable. Surgical morbidity or mortality did not increase. Cisplatin plus paclitaxel is an active combination in the treatment of patients with advanced or locoregional esophageal cancer. Further studies with this combination both in metastatic and locally advanced disease are indicated.

Adult↗

PubMed1996

Teratoma in primary testis tumor reduces complete response rates in the retroperitoneum after primary chemotherapy. The case for primary retroperitoneal lymph node dissection of stage IIb germ cell tumors with teratomatous elements.

BACKGROUND: Recent advances in the therapy of advanced testicular nonseminomatous germ cell tumors (NSGCT) have resulted in increased attention to avoiding double therapy in cases where single modality therapy will suffice. METHODS: Over an 8-year period, 104 patients with Stage II and III testicular NSGCT received primary chemotherapy. Seventy-nine patients had retroperitoneal lymph nodal metastases, 33 of whom had a radiologic complete response, 43 a radiologic incomplete response, and 3 were not re-evaluated after induction chemotherapy. Thirty-nine patients underwent retroperitoneal lymph node dissection (RPLND). The radiologic and pathologic response of the nodes to primary chemotherapy was correlated with tumor burden (lymph node metastasis size < or = 2 cm, 2.1-5 cm, 5.1-10 cm, and >10 cm), primary tumor pathology, and prechemotherapy marker levels. RESULTS: Larger initial lymph node size, metastases size, the presence of teratoma in the primary tumor, and prechemotherapy alpha-fetoprotein (alpha-FP) > 80 mg/L and beta-HCG (bHCG) 10000 IU/L were found to correlate significantly with an incomplete radiologic response. Lymph node metastases size was the only independent prognostic factor on multivariable logistic regression analysis. Prechemotherapy alpha-FP > 80 mg/L and beta-HCG > 10000 IU/L were associated with the presence of teratoma or carcinoma in the retroperitoneal nodes. The presence of teratoma in the primary tumor is associated with a higher incomplete response rate and residual teratoma in the retroperitoneal lymph nodes after primary chemotherapy. CONCLUSIONS: Predictors of need for postchemotherapy RPLND include large lymph node metastasis size and presence of teratomatous elements in the primary tumor. To reduce the need for and morbidity of double therapy, patients with low volume clinical Stage II, NSGCT and teratomatous elements in the primary tumor are arguably better served by primary RPLND.

Adolescent↗

PubMed2006

Multidisciplinary therapy of locally far-advanced or inflammatory breast cancer with fixed perioperative sequence of epirubicin, vinorelbine, and Fluorouracil chemotherapy, surgery, and radiotherapy: long-term results.

BACKGROUND: Based on phase II data in advanced breast cancer (BC), the fluorouracil, epirubicin, and vinorelbine (FEN) combination was assessed as perioperative chemotherapy, integrated in a multidisciplinary treatment for locally advanced BC. PATIENTS AND METHODS: Patients with newly diagnosed inoperable (stage IIIB or inflammatory) BC. Multimodality treatment protocol consisted of four preoperative courses of fluorouracil (600 mg/m(2) day 1), epirubicin (75 mg/m(2) day 1), and vinorelbine (25 mg/m(2) day1 and day 8), all i.v. every 21 days, followed by radical or conservative surgery according to clinical response and four postoperative identical chemotherapy courses aimed to eradicate micrometastatic disease. Locoregional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonotherapy according to hormone receptor status. The primary end points of the study were: (a) clinical and pathological response, (b) downstaging and conversion to operable disease, and (c) recurrence-free survival (RFS) and overall survival (OS). RESULTS: Forty-eight women, one stage IIIA, 27 (56.2%) stage IIIB, two stage IIIC (4.1%), and 12 (25%) with inflammatory BC, aged 34-75 years (median, 52), were accrued. Thirty-eight and 34 patients completed the planned pre- and postoperative chemotherapy, respectively. Totals of 175 and 135 cycles were administered pre- and postoperatively, respectively. Toxicity of both phases, mainly hematologic, was in general acceptable without treatment-related death. Venous reactions were a frequent problem. All but three tumors were converted to operable, 31.3% with breast conservation. The clinical response rate (RR) was 77.7% (22.2% complete) and pathological RR was 73.3% (complete, 20% in both primary and axilla). After a median follow-up of 72 months, 62.5% and 16.7% of patients remain relapse free at 3 and 5 years, respectively, while 83% and 58.3% were alive 3 and 5 years, respectively, after the start of chemotherapy. Median RFS and OS have not yet been reached, and are currently 37+ and 62+ months, respectively. CONCLUSION: This fixed number of FEN perioperative courses schedule followed by radiotherapy is safe and highly active in inducing both local and distant control of locally far-advanced BC. This strategy is at least not inferior to other established regimens or strategies for locally far-advanced BC, while the integration of taxanes or new targeted agents may help show its true value for this challenging clinical entity.

Adult↗

PubMed1981

Peritoneal responses to implanted fabrics used in operating rooms.

Fibers obtained from woven and nonwoven surgical fabrics were operatively instilled into the peritoneal cavities of rats to assess pathologic responses at 2, 8, 16, and 32 weeks postoperatively. Adhesions were found in 20% of the sham-operated animals and in 22% and 29% of the animals with fibers from woven and nonwoven fabrics, respectively. These differences were not significant. The adhesions were not progressive with time and were not related to increased morbidity or mortality rates. Foreign-body granulomas were found in 8% of the sham-operated animals and in 96% and 89% of the animals with fibers from woven and nonwoven fabrics, respectively. Differences between the groups with fibers were not significant. There were no morphologic differences in the granulomas of woven and nonwoven materials; they did not increase in number of enlarge with time. We conclude that responses to cellulose fibers, whether from cotton or from nonwoven materials produced from wood fibers, are virtually identical.

Animals↗

PubMed2006

Male sex and intraventricular hemorrhage.

BACKGROUND: Neonatal mortality and morbidity are sex biased in low birth weight infants. The "Y chromosome effect" has been suggested to be responsible for these maturational differences. OBJECTIVE: To examine the association of sex and neonatal outcomes. DESIGN AND METHODS: A retrospective observational study. Data on all low birth weight infants who survived for >48 hrs were analyzed. Neonatal outcomes were compared between male and female infants. A regression model was used to detect the influence of sex on outcomes after controlling for confounders. Analysis was repeated after stratification of infants into three groups: group A (<1000 g), group B (1000-1499 g), and group C (1500-2499 g). RESULTS: A total of 833 infants were included in this study; 419 female infants and 414 male infants. Male infants had an increased rate of overall intraventricular hemorrhage (IVH) (12.2% vs. 7.2%, p = .02) and IVH grades 3-4 (4.8% vs. 2.3%, p = .04). In addition, male infants had higher bilirubin levels (10.19 +/- 3.1 mg/dL vs. 9.32 +/- 2.94 mg/dL, p = .001). In a regression model, male sex continued to have significant influence on IVH, IVH grades 3-4, death, and bilirubin. In group A, male infants had a significantly increased prevalence of death (regression coefficient, 1.82 +/- 0.65; p = .005) that could not be explained by the increased prevalence of IVH (p = .18) in regression analysis. In group B, male sex was significantly associated with a higher bilirubin level (regression coefficient, 0.94 + 0.3; p = .002). In bivariate analyses, IVH and IVH grades 3-4 were significantly higher in male compared with female infants (19.8% vs. 3.9%, p < .0001) and (8.5% vs. 0.97%, p = .02), respectively, but these differences lost significance in multiple-regression analysis. In group C, male sex positively influenced the prevalence of IVH (regression coefficient, 1.7 +/- 0.57; p = .003). Bilirubin measured higher in male infants (11.38 +/- 2.87 mg/dL vs. 10.19 +/- 3.22 mg/dL, p = .0004), but the difference lost significance in regression analysis (regression coefficient, 0.21 +/- 0.31; p = .5). CONCLUSIONS: Bilirubin, IVH, and death were significantly higher in male infants. In subgroup analysis, significance was retained in group A (<1000 g). Whether a single biological factor is responsible for these differences or perhaps a multi-causal process involving a complex interaction of physiologic, environmental, and pathologic responses needs to be further addressed in future research.

Cerebral Ventricles↗

PubMed1988

Spontaneous and polyclonal Ig secretion by circulating B cells after surgery.

Abnormalities of the immune response are commonly observed after surgery. In many cases, they are part of a physiologic rather than of a pathologic response to trauma. In this study we show that after elective surgery in otherwise healthy subjects the B cell compartment is deeply affected, as documented by the appearance, 7 days after the intervention, of circulating lymphoblastoid B cells spontaneously secreting in vitro IgG and IgA antibodies. Analogous lymphoblastoid B cells have been described after in vivo immunization and represent a sensitive marker of the B cell response against the immunizing antigen. To better understand the origin of the reaction, we have analyzed the specificity of the antibodies secreted in culture supernatants. We show that the antibody response is polyclonal, since low titers of antibodies against several different bacterial antigens--such as tetanus toxoid, pneumococcal capsular polysaccharides (PCPs), and the lipopolysaccharides (LPSs) of several enteropathogenic strains of Escherichia coli--are detected. This response seems to reflect the previous immunologic experience of the single patient and to be caused by antigens released from traumatized tissues or absorbed through breaches in skin or mucous membranes.

Adolescent↗

PubMed2002

A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma.

Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.

Adenocarcinoma↗